SUPPLEMENT TO March 15, 2006

A J O B S O N P U B L I C AT I O N w w w. r e v o p t o m . c o m

Eyelids & Adnexa

EIGHTH EDITION

Conjunctiva & Sclera

Handbook of
Cornea

Ocular Disease
Uvea & Glaucoma

Management
Vitreous & Retina

Neuro-Ophthalmic Disease

Oculosystemic Disease

Joseph W. Sowka, O.D. Andrew S. Gurwood, O.D. Alan G. Kabat, O.D.

Sponsored by
 TABLE OF CONTENTS

EYELIDS & ADNEXA NEURO-OPHTHALMIC DISEASE

Chronic Epiphora . . . . . . . . . . . . . . . . . . . . . . . . .6A
Eyelid Laceration . . . . . . . . . . . . . . . . . . . . . . . . .7A
Phthiriasis Palpebrarum . . . . . . . . . . . . . . . . . . . .8A
Chalazion . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10A
CONJUNCTIVA & SCLERA
Conjunctival Abrasion and Laceration . . . . . . . . .12A
Toxic Conjunctivitis . . . . . . . . . . . . . . . . . . . . .13A
Ocular Cicatricial Pemphigoid . . . . . . . . . . . . . .14A
Pingueculitis . . . . . . . . . . . . . . . . . . . . . . . . . .16A
Building a Therapeutic Practice, Part 1 . . . . . . .17A
Building a Therapeutic Practice, Part 2 . . . . . . .18A
CORNEA
Fungal Keratitis . . . . . . . . . . . . . . . . . . . . . . . .19A
Granular Dystrophy . . . . . . . . . . . . . . . . . . . . . .20A
Contact Lens Acute Red Eye (CLARE) . . . . . . . .21A
Microcornea . . . . . . . . . . . . . . . . . . . . . . . . . . .23A
Corneal Laceration . . . . . . . . . . . . . . . . . . . . . .24A
Fourth Generation Fluoroquinolones and
Bacterial Keratitis . . . . . . . . . . . . . . . . . . . . . . .25A
Aberrant Regeneration of Cranial Nerve III . . . . .43A
Horner’s Syndrome . . . . . . . . . . . . . . . . . . . . . .44A
Tonic Pupils . . . . . . . . . . . . . . . . . . . . . . . . . . .46A
The Argyll Robertson Pupil . . . . . . . . . . . . . . . .48A
Migraine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .49A
Differential Diagnosis of Headache . . . . . . . . . . .52A
OCULOSYSTEMIC DISEASE
Sturge-Weber Syndrome . . . . . . . . . . . . . . . . . .53A
Lyme Disease . . . . . . . . . . . . . . . . . . . . . . . . . .55A
Neurally Mediated Syncope . . . . . . . . . . . . . . . .57A
Rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .58A
New Perspectives in Allergy . . . . . . . . . . . . . . .61A
Professional Communication . . . . . . . . . . . . . . .64A

UVEA AND GLAUCOMA A Peer-Reviewed Supplement

Choroidal Folds . . . . . . . . . . . . . . . . . . . . . . . . .27A The articles in this supplement were subjected to
Review of Optometry’s peer-review process. The
Choroidal Nevus and Choroidal Melanoma . . . . .28A magazine employs a double-blind
Pars Planitis . . . . . . . . . . . . . . . . . . . . . . . . . . .30A review system for clinical man-
Acute Angle Closure Glaucoma . . . . . . . . . . . . .32A uscripts. Two referees review
each manuscript before publi-
Contemporary Glaucoma Therapy: Lowering
cation. This supplement was
Intraocular Pressure or Controlling Intraocular edited by the editors of Review
Pressure? . . . . . . . . . . . . . . . . . . . . . . . . . . . . .35A of Optometry.
Frequency Doubling Technology
(FDT Marix™ Perimetry) . . . . . . . . . . . . . . . . . . .36A

VITREOUS AND RETINA

Idiopathic Polypoidal Choroidal Vasculopathy
(Posterior Uveal Bleeding Syndrome) . . . . . . . . .37A
Commotio Retinae . . . . . . . . . . . . . . . . . . . . . .38A
Posterior Vitreous Detachment . . . . . . . . . . . . .39A
©2006. Reproducing editorial content and photographs
Optomap Technology . . . . . . . . . . . . . . . . . . . .41A require permission from Review of Optometry.
Indocyanine Green Angiography (ICG) Primer . . .41A

4A REVIEW OF OPTOMETRY MARCH 15, 2006

 ® FROM THE AUTHORS
Dear Colleagues,

Once again, we are pleased to bring you our annual edition of the Handbook of Ocular Disease Management. This year is
a very special one for us, because it marks our 10th anniversary of working together on this project. During the SECO
meeting in 1996, a gentleman named Jack Persico from Review of Optometry approached us regarding our idea about cre-
ating a “quick & dirty” handbook of the 50 most common ocular disease entities encountered in optometry. Over the
last seven editions, our humble little project, initially conceived as a one-time-only event, has evolved into a compendi-
um of clinically useful, up-to-date evidence-based reports on a multitude of ocular and oculosystemic disorders.

It is interesting to note that the evolution of our handbook has paralleled the continued advancement of our profession.
Optometry plays a far more substantial role in the management of ocular disease today than even 10 years ago. During
that time, we’ve seen substantially greater interest and investment in our profession by pharmaceutical and technology
companies, who recognize our abilities and potential in the diagnostic and therapeutic arenas. We’ve also seen new soci-
eties arise within our own profession, solely dedicated to advancing our aptitude and interest in ocular disease.
Organizations such as the Optometric Glaucoma Society, the Optometric Retina Society and the Optometric Dry Eye
Society now exist within a profession that was once described as “drugless.” In fact, the Optometric Glaucoma Society
has been recognized by, and is a full member of the Association of International Glaucoma Societies.

This edition of The Handbook offers some timely updates on previously covered disease entities, including acute angle
closure glaucoma, choroidal melanoma and pupillary disorders. In addition, we’ve added new material on important ocu-
lar and oculosystemic conditions, such as cicatricial pemphigoid, choroidal folds and migraine. We’ve also included per-
tinent comments on professional communication, practice-building strategies and the use of some new diagnostic tech-
nologies such as the OptoMap® retinal exam and frequency doubling perimetry.

We hope that you find the eighth edition of the Handbook of Ocular Disease Management educationally beneficial and
clinically practical. Once again, we are indebted to Review of Optometry and our generous sponsor, Alcon Laboratories,
for continuing to support this effort. Most important, thanks to all of you—our colleagues—who have overwhelming-
ly endorsed this project. We hope to stay in your top desk drawer for many years to come.

Best regards,

Joe, Andy and Al

Joseph W. Sowka, O.D., F.A.A.O., Dipl., is a professor of optometry at Nova

Southeastern University College of Optometry, where he teaches Glaucoma
and Retinal Disease. He is the director of the Glaucoma Service and chief of

]
the Advanced Care Service. He is a diplomate of the Disease Section of the
American Academy of Optometry (Glaucoma Subsection) and a founding
member of the Optometric Glaucoma Society and the Optometric Retina
Society. He can be reached at (954) 262-1472 or at jsowka@nova.edu.
Andrew S. Gurwood, O.D., F.A.A.O., Dipl., is an associate professor of clinical
sciences and staff optometrist at The Eye Institute of the Pennsylvania
College of Optometry, where he teaches clinical medicine and ocular urgen- The authors do not have a
cies and emergencies. He is a diplomate of the American Academy of
Optometry’s Primary Care Section, a founding member of the Optometric financial interest in any of the
Retina Society and a member of the Optometric Glaucoma Society. He products mentioned.
serves on the American Academy of Optometry admittance committee and is
the chairperson of the fellowship candidate workshop. He can be reached at
(215) 276-6134 or at agurwood@pco.edu.

Alan G. Kabat, O.D., F.A.A.O., is an associate professor and the director of resi-
dency programs at Nova Southeastern University College of Optometry, where
he teaches courses in clinical medicine and physical diagnosis. He also
serves as an attending physician and is director of the Urgent Care Service at
the college’s Eye Institute. He is a founding member of the Optometric Dry
Eye Society. He can be reached at (954) 262-1470 or at kabat@nova.edu.

MARCH 15, 2006 REVIEW OF OPTOMETRY 5A

 EYELIDS AND ADNEXA

CHRONIC EPIPHORA canaliculus—may also be observed on patients present with complaints of

biomicroscopy.5,6 excessive tearing. Moderate-to-severe
Signs and Symptoms dry eye disease or exposure secondary
Epiphora describes the spillover of Pathophysiology to proptosis or facial nerve palsy may
tears from the eye onto the lids and Epiphora may result from a variety induce reflex tear production resulting
ocular adnexa. Rather than an absolute of conditions, but all can be ascribed to in epiphora. Finally, hypersecretion of
diagnosis, epiphora is more of a clinical one of four basic categories: lid-globe tears may occur in rare conditions
sign that is suggestive of insufficient appositional abnormalities, obstructive affecting the nervus intermedius, the
tear drainage. Numerous etiologic fac- lacrimal drainage disorders, ocular sur- collection of nerves containing, among
tors can lead to this phenomenon.1-4 A face disorders and, rarely, neurogenic other things, parasympathetic lacrimal
distinction must be made, however, lacrimal hypersecretory disorders.4 In fibers, which join the facial nerve at the
between chronic and acute epiphora. level of the cerebellopontine angle.
Chronic epiphora results from long- Compressive irritation of these
standing or unremitting disorders fibers or aberrant regeneration of
and presents a greater clinical chal- cranial nerve VII after trauma may
lenge than acute epiphora. The acute result in enhanced and inappropri-
variety most often results from irrita- ate lacrimation, sometimes called
tive ocular conditions such as corneal the gustolacrimal reflex or “crocodile
foreign bodies or allergic conjunctivi- tearing.”4 Neurogenic complications
tis, and usually resolves following must be ruled out prior to initiating
treatment of the associated disorder. therapy for a lacrimal outflow prob-
Patients with chronic epiphora lem.
report excessive lacrimation, in some
cases to the point of having tears Ectropion leading to chronic epiphora. Management
streaming down the face. Symptoms Treatment for epiphora involves
may be exacerbated by environmental conditions that alter the normal prox- alleviating the symptoms and correct-
factors such as excessive cold, wind, imity of the lacrimal puncta to the ocu- ing the underlying disorder. For lid-
pollen or other airborne particulate lar surface, elimination of tears is phys- globe appositional abnormalities such
matter, sleep deprivation, nearpoint ically impeded. The most obvious as ectropion, the only cure is to surgi-
strain or emotional stress. Patients may illustration of this situation is acquired cally reorient the punctum to be in
report that they cry very easily or that ectropion; other examples include proper alignment with the globe. Most
they are constantly wiping their eyes. entropion and floppy eyelid syndrome. often this involves modified resection
Associated signs and symptoms of Obstructive disorders of the lacrimal of the lid tissue, or what is known as
epiphora vary with the underlying eti- system are similar to appositional horizontal lid shortening proce-
ology. Often, the patient complains of abnormalities, except that in the for- dures.9,10 Entropion can be corrected
intermittently reduced acuity from the mer there is mechanical impedance of via serial eyelash epilation or by surgical
excessive tears. Irritation of the lids, in the outflow channel. This may take the repositioning as well. Obstructive dis-
particular the inner canthus, is com- form of acquired punctal stenosis, orders generally require invasive thera-
mon because of the constant wetting of canalicular stenosis or canaliculitis, peutic measures. Punctal and/or
that area as well as the continuous dacryocystitis or lacrimal sac tumors. canalicular dilation and irrigation is the
mechanical abrasion of tissues, poten- Occasionally, a large hordeolum or most common management for steno-
tially leading to fissure formation. Signs chalazion may induce punctal or sis of the lacrimal system. In cases of
may include punctate epithelial ker- canalicular stenosis. Congenital naso- chronically flaccid or stenotic puncta,
atopathy, lid-globe appositional abnor- lacrimal obstruction is quite common laser punctoplasty or ampullotomy
malities, punctal stenosis or other and results from a lack of patency at the may enlarge the outflow orifice.11,12 If
lacrimal outflow disorders (e.g., dacry- valve of Hasner. Ocular surface disor- the blockade exists more distally with-
ocystitis or canaliculitis). Conjunctivo- ders can in some instances induce in the nasolacrimal system, probing
chalasis—a condition in which redun- excessive and symptomatic reflex tear- alone may be inadequate to alleviate
dant, “sagging” conjunctiva covers the ing.2,7,8 Typically, this is not significant the problem. In these cases, dacryocys-
lacrimal punctum and impedes enough to constitute true epiphora, torhinostomy (DCR) is often required.
drainage through the nasolacrimal but it should be considered when This creates a surgical bypass of the

6A REVIEW OF OPTOMETRY MARCH 15, 2006


common canaliculus directly into the
nasal mucosa. It is performed with or
without a synthetic conduit (Lester
Jones tube).13,14 Probing procedures are
contraindicated in cases of inflamma-
tion, such as chronic dacryocystitis, or
suspected neoplasm; for these condi-
tions, DCR is utilized. When an ocular
surface disorder is the etiology of
chronic epiphora, treatment should be
aimed at removing the provocative
substance (foreign body, chemical) or
replenishing the normal basal tear vol-
ume and improving the overall quality
of the tear film. This may be achieved
by using artificial tear preparations,
immunomodulatory agents (e.g.,
Restasis), or oral secretagogues (e.g.,
Salagen, Evoxac). Neurogenic hyper-
secretory disorders, when suspected,
should be referred to a neurologist for
evaluation and management.
Clinical Pearls
• Tearing is a common complaint in
most optometric practices. For proper
management, a clear distinction needs
to be made between functional epipho-
ra and occasional symptomatic
lacrimation.
• True epiphora constitutes a chron-
ic problem warranting intervention,
whereas normal tearing does not.
Dilation and irrigation, the most com-
mon management strategy for punctal
and canalicular obstruction, is a quick
and easy in-office procedure for man-
aging appropriate cases. This procedure
is not always permanent and may need
to be repeated several times each year to
maximize patient comfort and satisfac-
tion. Surgical intervention, when nec-
essary, should be directed to an experi-
enced oculoplastic specialist.
1. Narayanan K, Barnes EA. Epiphora with eyelid lax-
ity. Orbit 2005;24(3):201-3.
2. Singh Bhinder G, Singh Bhinder H. Reflex epipho-
ra in patients with dry eye symptoms: Role of variable
time Schirmer-1 test. Eur J Ophthalmol
2005;15(4):429-33.
3. Tu AH, Chang EL. Botulinum toxin for palliative
® EYELIDS AND ADNEXA
treatment of epiphora in a patient with canalicular
There is typically a linear split in
obstruction. Ophthalmol 2005;112(8):1469-71.
the dermis, which may or may not
4. Keegan DJ, Geerling G, Lee JP, et al. Botulinum
toxin treatment for hyperlacrimation secondary to follow a lid crease. Other associated
aberrant regenerated seventh nerve palsy or salivary findings may include hyphema, con-
gland transplantation. Br J Ophthalmol
junctival or corneal laceration, globe
2002;86(1):43-6.
rupture, ecchymosis, orbital fracture
5. Liu D. Conjunctivochalasis. A cause of tearing and
its management. Ophthal Plast Reconstr Surg and uveitis. Any observation of
1986;2(1):25-8. orbital fat indicates a breach of the
6. Georgiadis NS, Terzidou CD. Epiphora caused by orbital septum with possible damage
conjunctivochalasis: Treatment with transplantation of
to the underlying levator palpebrae
preserved human amniotic membrane. Cornea
2001;20(6):619-21. superioris muscle.7,9
7. Berdy GJ, Hedqvist B. Ocular allergic disorders and
dry eye disease: Associations, diagnostic dilemmas, Pathophysiology
and management. Acta Ophthalmol Scand
Obviously, the precipitating trau-
2000;230(Suppl):32-7.
ma contributes to the formation of an
8. Bielory L. Ocular allergy and dry eye syndrome.
Curr Opin Allergy Clin Immunol 2004;4(5):421-4. eyelid laceration. Sharp objects may
9. Eliasoph I. Current techniques of entropion and cut or tear the dermis and underlying
ectropion correction. Otolaryngol Clin N Amer contents, or blunt force may split the
2005;38(5):903-19.
tissue.
10. Vick VL, Holds JB, Hartstein ME, Massry GG.
Wound healing has three distinct
Tarsal strip procedure for the correction of tearing.
Ophthal Plast Reconstr Surg 2004;20(1):37-9. phases. The inflammatory stage
11. Kashkouli MB, Beigi B, Astbury N. Acquired occurs during the first several days
external punctal stenosis: Surgical management and after the injury. Vasoconstriction
long-term follow-up. Orbit 2005;24(2):73-8.
occurs initially to limit bleeding.
12. Awan KJ. Laser punctoplasty for the treatment of
Platelets and thromboplastin allow
punctal stenosis. Am J Ophthalmol 1985;
100(2):341-2. for clot formation to further control
13. Beigi B, Westlake W, Chang B, et al. bleeding. Following this will be
Dacryocystorhinostomy in south west England. Eye vasodilation, during which blood
1998;12(Pt 3a):358-62.
components extravasate into the
14. Thompson CJ. Review of the diagnosis and man-
wound. Inflammatory polymorphonu-
agement of acquired nasolacrimal duct obstruction.
Optom 2001;72(2):103-11. clear leukocytes and mononuclear cells
will clean the wound and neutralize
EYELID LACERATION
Signs and Symptoms
Eyelid lacerations occur
more commonly in men than
women1,2 and are relatively
common in children.3,4 There
will be a history of facial or
head trauma immediately pre-
ceding laceration.2,5,6 While
sharp objects are typical causes
of a laceration of the eyelid, Superficial eyelid laceration secondary to blunt trauma.
(Photo courtesy of Dr. Lori Vollmer)
blunt trauma and bites can also
lacerate the eyelid.7 Common
etiologies include projectiles, auto- bacteria. During the proliferative stage,
mobile airbag deployment, falls, fibroblasts fill in the wound with colla-
assault and gunshot injuries, among gen in a process termed granulation.
numerous others.2,4,6,8 New blood vessels will replace vascula-
MARCH 15, 2006 REVIEW OF OPTOMETRY 7A
 ture that was lost to trauma. Epithelial
cells from the wound margins will
migrate across the laceration toward
the center of the wound. Myofibro-
blasts then cause contraction of the
wound, resulting in shrinkage and
apposition of the edges. The wound
gradually contracts maximally and is
covered by a layer of skin. In the matu-
ration and remodeling stage, further
collagen formation and remodeling
strengthen the scar, possibly changing
the shape of the original wound. Note
that scar tissue is never as strong as the
original tissue. However, it goes from
5% tensile strength to nearly 80%.
Over time, the scar will thin, shrink
and pale.7
Management
The goals in managing lacerations of
the eyelid are to stabilize the wound
and overall health of the patient (pre-
vent shock), and to set the stage for
maintaining lid cosmesis and proper
eyelid dynamics. A careful history
needs to be taken. Always try to deter-
mine the nature of the trauma, time of
occurrence, involvement of drugs or
alcohol, possible witnesses, last intake
of food or water, medication allergies
and tetanus shot status. Evaluate the
depth and location of the laceration
with care to determine whether extru-
sion of orbital fat and potential damage
to the globe have occurred. Special care
should be made to examine for poten-
tial involvement of the lacrimal system,
particularly the canaliculi if the lacera-
tion is located medially.
It should be determined whether
surgical closure is necessary. An expert
in oculoplastics may need to make this
determination. When there is only
superficial tissue loss with no exposure
of orbital fat or damage to the levator
palpebrae superioris muscle or canali-
culi, then allowing the wound to gran-
ulate naturally will likely have an excel-
lent outcome.7,10 If the wound is not
actively bleeding, it can be temporarily
8A REVIEW OF OPTOMETRY MARCH 15, 2006
dressed after irrigation and removal of
foreign bodies. If anything is impaled
in the skin, it should not be pulled out.
For small and superficial lacerations,
Betadine or a similar skin decontami-
nant can be used. Topical antibiotic
solutions and ointments should be
used in order to prevent infection.
Close follow-up is necessary to moni-
tor for infection—in some rare
instances, necrotizing fasciitis (Strepto-
coccal gangrene) can have a disastrous
effect.11 Steri-strips or butterfly band-
ages can be used along with a light cov-
ering; it is believed that increased
humidity from a covered wound
enhances re-epithelialization.7 This will
work well if the laceration is small, is
not missing much tissue, and has skin
margins in close apposition.
If the laceration is large, deep,
involves extrusion of orbital fat or
involves critical anatomy such as the
tarsus, canaliculi or levator palpebrae
superioris muscle, then surgical closure
is necessary. If the wound is fresh and
the practitioner involved in first-
response care will not be involved in
the wound closure, any dressing
already present should not be removed.
In fact, once a dressing is placed on the
wound (and around an impaled object,
if present), it should never be lifted. If
bleeding remains active, additional
bandages or pads can be added with
direct pressure. Once the patient is sta-
bilized, the patient should be trans-
ferred, in his or her current state to the
individual who can make the repair. In
such cases, avoid the temptation to get
involved and treat the wound; doing so
may interfere with a surgeon’s designs.
Simply protect the eyelid from further
manipulation with a Fox shield (or
similar dressing). Do not apply any
topical medications, and recommend
that the patient refrain from eating and
drinking to facilitate surgical repair.
Clinical Pearls
• Wound healing is often impaired
in diabetic patients, so surgical closure
may be most appropriate. Likewise, the
elderly have slower wound repair times.
• Discuss issues of scarring, particu-
larly if the patient has dark skin.
• Many scars will fade and become
smaller in six to 12 months after the
injury. Surgical revision should be
delayed until the scar is fully mature.
• Light dermabrasion can greatly
enhance cosmesis.
• Determining by history the direc-
tion from which the trauma came may
be helpful in identifying areas most at
risk of structural damage.
1. Kaimbo WK, Spileers W, Missotten L. Ocular emer-
gencies in Kinshasa (Democratic Republic of Congo).
Bull Soc Belge Ophthalmol 2002;(284):49-53.
2. Lo S, Aslam N. Mechanisms and pattern of facial
lacerations in the Accident Department. Int J Clin
Pract 2005;59(3):333-5.
3. Ng JD, Payner TD, Holck DE, et al. Orbital trauma
caused by bicycle hand brakes. Ophthalm Plast
Reconstr Surg. 2004;20(1):60-3.
4. Lueder GT. Air bag–associated ocular trauma in
children. Ophthalmol 2000;107(8):1472-5.
5. Odebode TO, Ademola-Popoola DS, Ojo TA, et al.
Ocular and visual complications of head injury. Eye
2005;19(5):561-6.
6. Moshfeghi DM, Moshfeghi AA, Belafsky PC, et al.
Mardi Gras eye injury survey, 1998-1999. South Med
J 2000;93(11):1083-6.
7. Chang EL, Rubin PAD. Management of complex
eyelid lacerations. Int Ophthalmol Clin 2002;
42(3):187-201.
8. Lehto KS, Sulander PO, Tervo TM. Do motor vehi-
cle airbags increase risk of ocular injuries in adults?
Ophthalmol 2003;110(6):1082-8.
9. Kushima H, Yuzuriha S, Kondo S, et al.
Reconstruction of an inner layer defect of the upper
eyelid with avulsion of the superior levator palpebrae
muscle and orbital fat. Ann Plast Surg
2003;51(3):321-4.
10. Mehta HK. Spontaneous reformation of the
upper eyelid. Br J Ophthalmol 1988:72(11):856-62.
11. Balaggan KS, Goolamali SI. Periorbital necrotis-
ing fasciitis after minor trauma. Graefes Arch Clin Exp
Ophthalmol 2005;Jul 23:1-3.
PHTHIRIASIS PALPEBRARUM
Signs and Symptoms
Patients who manifest this particular
form of blepharoconjunctivitis typical-
ly are sexually active.1 There is often
 ® EYELIDS AND ADNEXA
concurrent genital involvement.2 The Phthirus is 2 mm long with a broad- cein (as used in angiography), 2.5%
patient will frequently report eyelid shaped, crablike body. Its thick, clawed permethrin cream or 3% ammoniated
irritation and itching; pruritic lid mar- legs make it less mobile than the mercuric oxide BID for 1 to 2
gins will be grossly apparent. Biomicro- Pediculus species and allow it to infest weeks.4,6,11,12 Alternate treatments
scopically, there will be visible organ- areas where the adjacent hairs are with- include a cholinesterase inhibitor such
in its grasp (eyelashes, beard, as physostigmine, or even Pilopine
chest, axillary region, pubic gel.6,13 Typically, the nits will survive a
region).5,7 Both organisms single application of these agents
suck the blood of the host, and because the egg is totally encased by a
Pediculus humanus may serve proteinaceous sheath and must hatch
as a vector of diseases such as before becoming susceptible to topical
typhus and trench fever. therpy.14
Pediculus and Phthirus look Oral ivermectin (Stromectol), an
alike and interbreed freely. agent for the treatment of scabies
Both types of lice lay eggs on infection as well as onchocerciasis, has
the hair shafts which remain had some anecdotal success in the
Nits and ruptured egg sacs in Phthiriasis palpebrarum. firmly adherent and resist management of phthiriasis palpe-
mechanical and chemical brarum.15
removal.5,9 Pediculus possesses When phthiriasis palpebrarum is
isms and egg sacs (nits)—which may good mobility and can pass from per- diagnosed, genital involvement must
be ruptured or intact—within the son to person either by close contact be suspected. Infested patients should
scalp, hair, eyebrows, eyelashes or with an infested individual or by con- be instructed to obtain and use a
beard; visible blue skin lesions (louse tact with contaminated bedding. pediculocidal medicated shampoo.
bites); reddish brown deposits (louse Conversely, Phthirus is a slow-moving These include but are not limited to:
feces); secondary blepharitis with organism that cannot typically pass lindane 1%, permethrin 1% (market-
preauricular adenopathy; follicular unless cilia are brought into close prox- ed as Nix cream rinse by Warner-
conjunctivitis and, in severe cases, mar- imity with infested cilia. Both species Lambert, Alimite cream by Allergan,
ginal keratitis.3-6 Superinfection of bites are associated with crowded conditions or Acticin cream by Bertek), A-200
may lead to preauricular gland or poor personal hygiene. Pyrinate (pyrethrins, piperonyl
swelling.
Management
Pathophysiology Management begins
Pediculosis refers to eyelid infesta- with forceps removal of all
tion by Pediculus humanus corporis visible organisms and
(body louse) or capitus (head louse). nits.2,3,5,6,9,10 The removed
These organisms rarely infect the eye- organisms and nits should
lids, however. Phthiriasis palpebrarum be killed by placing them
refers to eyelid infestation by Phthirus onto an alcohol wipe or
pubis (pubic louse, sometimes referred dipping in alcohol and
to as crab louse). Eyelid infestation is then discarding. Adjunc-
almost always by Phthirus pubis. tive topical therapy may
However, this organism will occasion- be employed to ensure Living Phthirus pubis organism
ally infect the scalp.7 It appears that eradication following
outbreaks of Pediculus capitis are more physical removal. If physical removal butoxide and kerosene ) and Kwell or
frequent during warmer months, is not possible or practical, topical Rid, which are safe, effective, nonpre-
whereas Phthirus pubis is more domi- therapy will suffice. The lice and nits scription pediculocides. However,
nant in cooler months.8 can be smothered with petroleum jelly due to toxicity, these agents cannot
Pediculus is an organism 2 to 4 mm or other bland ophthalmic antibiotic be used on the eyelids. Medical test-
long that typically infests the hair of the ointments TID for 1 to 2 weeks. ing for other sexually transmitted
patient. Infestation of the cilia is rare Other topical therapies include 1% diseases, including HIV infection,
and only occurs in the worst cases. yellow mercuric oxide, 20% fluores- should be recommended.1 In chil-

MARCH 15, 2006 REVIEW OF OPTOMETRY 9A

 dren, abuse must be considered.
Instruct patients to thoroughly
wash all clothing and linens that may
have been exposed. Have them disin-
Living Phthirus pubis organism
fect clothing, linen and personal
items in 50°C (125°F) heat for 30
minutes.
Clinical Pearls
• Follow up is required through 7
to 10 days; nits hatch within that
period.
• Educate patients about how the
organisms are transmitted and advise
them to refrain from contact with
others until the disease is 100%
resolved. Counsel patients to inform
exposed partners to report for exam-
ination and evaluation.
• Mechanical removal at the bio-
the treating doctor or office staff
members will contract the infestation
through the examination or removal
process.
1. Beltrami C, Manfredi R, D’Antuono
A, et al. Sexually-transmitted infec-
tions in adolescents and young adults
in a large city of Northern Italy: A nine-
year prospective survey. New Microbiol
2003;26(3):233-41.
2. Lopex Garcia JS, Garcia Lozano I,
Martinez Garchitorena J. Phthiriasis
palpebrarum: Diagnosis and treatment.
Arch Soc Esp Oftalmol 2003;
78(7):365-74.
3. Ikeda N, Nomoto H, Hayasaka S, et
al. Phthirus pubis infestation of the
eyelashes and scalp hairs in a girl.
Pediatr Dermatol 2003;20(4):356-7.
4. Morsy TA, El-Ghazali SM. A four years
old girl with Phthiriasis pubis infestation. J Egypt Soc
Parasitol 1999;29(3):893-6.
5. Lin YC, Kao SC, Kau HC, et al. Phthiriasis palpe-
brarum: an unusual blepharoconjunctivitis. Zhonghua
Yi Xue Za Zhi (Taipei) 2002;65(10):498-500.
6. Couch JM, Green WR, Hirst LW, et al. Diagnosing
and treating Phthirus pubis palpebrarum. Surv
Ophthalmol 1982;26(4):219-25.
7. Hernandez Contreras N, Isla Garcia M, Vega Correa
E. Hair infestation by Phthirus pubis (Anoplura: Pedi-
culidae). Rev Cubana Med Trop 2001;53(1):63-5.
8. Mimouni D, Ankol OE, Gdalevich M, et al.
Seasonality trends of Pediculosis capitis and Phthirus
pubis in a young adult population: Follow-up of 20
years. J Eur Acad Dermatol Venereol 2002;
16(3):257-9.
9. Schenone H. Eyelid infestation by
Phthirus pubis in a boy. Bol Chil Parasitol
2000;55(1-2):25-6.
CHALAZION
Signs and Symptoms
Patients with chalazia typically
present with one or more focal, firm
nodules in the upper or lower eyelid,
seeking care primarily because of cos-
metic concern or obstruction of
vision. The lesions are generally pain-
less, although a history of painful lid
infection (i.e., hordeolum or “stye”)
prior to chalazion development is pos-
sible. Enlargement of the lesion over
time may be reported. Often, there is
a history of concurrent blepharitis,
usually in the form of meibomian
gland obstruction/dysfunction. In
some patients, chalazia may be recur-
rent and indicative of chronic ble-
pharitis or lid hygiene issues. Men
appear to be affected somewhat more
frequently than women.
Pathophysiology
According to the historical literature,
chalazia are the most common inflam-
matory lesions of the eyelid.1-3 They are
by definition non-infectious and sterile,
representing a lipogranulomatous
inflammation of the sebaceous meibo-
mian gland(s). The typical etiology is
obstruction of meibomian ducts, with

microscope with a jeweler’s forceps is
time consuming, but is the preferred
method of treatment.
• Live organisms will cling tightly
to the eyelashes and many lashes will
be removed during this process.
Advise the patient to expect some
discomfort associated with inadver-
tent lash removal.
10. Yoon KC, Park HY, Seo MS, et al.
Mechanical treatment of phthiriasis palpe-
brarum. Korean J Ophthalmol 2003;
17(1):71-3.
11. Ashkenazi I, Desatnik HR, Abraham FA.
Yellow mercuric oxide: a treatment of choice
for phthiriasis palpebrarum. Br J
Ophthalmol 1991;75(6):356-8.
12. Mathew M, D’Souza P, Mehta DK. A
new treatment of phthiriasis palpebrarum.
Ann Ophthalmol 1982;14(5):439-41.

• Smearing the lids and lashes with
an ophthalmic ointment may make
removal easier, because the organisms
cannot grasp the greasy lashes as
firmly. However, this may make visu-
alizing and grasping the organisms
with forceps more difficult.
• There is virtually no chance that
13. Kumar N, Dong B, Jenkins C. Pubic lice
Hard, non-tender chalazion
effectively treated with Pilogel. Eye
2003;17(4):538-9.
14. Burkhart CN, Gunning W, Burkhart CG. Scanning resultant retention of glandular secre-
electron microscopic examination of the egg of the tions. This frequently occurs in cases of
pubic louse (Anoplura: Phthirus pubis). Int J Dermatol chronic posterior blepharitis.4 Occa-
2000;39(3):201-2.
sionally, however, chalazia may form
15. Burkhart CN, Burkhart CG. Oral ivermectin thera-
py for phthiriasis palpebrum. Arch Ophthalmol from the collection of inflammatory cells
2000;118(1):134-5. following eyelid infection, such as a

10A REVIEW OF OPTOMETRY MARCH 15, 2006

 ® EYELIDS AND ADNEXA
hordeolum or preseptal cellulitis; this is ment, although repeat injections may be through the palpebral conjunctiva
referred to as a secondary chalazion. necessary for larger chalazia.9 Should diminishes this risk, the adverse reaction
Histological evaluation of the cha- intralesional steroid injections prove remains a possibility.
lazion reveals an inert collection of cor- ineffective, or should the patient be • Recurrent chalazia, especially those
ticosteroid-sensitive histiocytes, multi- unable to tolerate the procedure, surgi- that recur in the same location within
nucleate giant cells, plasma cells, cal curettage under local anesthesia is the same lid after surgical excision, or
polymorphonuclear leukocytes and indicated.10 lesions associated with madarosis, war-
eosinophils.4,5 The nodule is encapsu- rant excisional biopsy. The greatest con-
lated by connective tissue, often inter- Clinical Pearls cern in these cases is malignant seba-
digitating with the tarsal plate. • While vision problems are uncom- ceous gland carcinoma. This is an
mon with chalazia, large lesions may extremely aggressive form of eyelid can-
Management cause a mechanical ptosis and result in cer, which carries a high mortality rate
Chalazia without cellulitis represent obscuration of the vertical visual field. and great propensity toward metastasis.
sterile lid inflammation; hence, the use For this reason, it is important to treat The majority of misdiagnosed recurrent
of oral antibiotics is not prudent. chalazia in young children aggressively. chalazia represent sebaceous gland car-
Although chalazia do respond to cinomas; however other significant
anti-inflammatory therapy, the deep lesions include basal cell carcinoma
nature of this condition renders any and pyogenic granuloma.4
topical medication virtually ineffec-
tive. Approximately 25% of these
1. Aurora AL, Blodi FC. Lesions of the eyelids: A
lesions resolve spontaneously.6 For clinicopathological study. Surv Ophthalmol
those that persist, warm compresses 1970;15(2):94-104.
(to clear the meibomian ducts of 2. Tesluk GC. Eyelid lesions: Incidence and com-
parison of benign and malignant lesions. Ann
stagnant oils) accompanied by digi-
Ophthalmol 1985;17(11):704-7.
tal massage (to rupture and express
3. Scat Y, Liotet S, Carre F. Epidemiological study
the nodule) should be advocated on of benign tumors and inflammatory pseudotumors
a TID-QID basis. Unfortunately, of the eye and its adnexa. J Fr Ophthalmol
1996;19(8-9):514-9.
this therapy tends to be effective only Chalazion upon lid eversion
4. Ozdal PC, Codere F, Callejo S, et al. Accuracy of
about 40% of the time in cases
the clinical diagnosis of chalazion. Eye
known to be of recent onset.7 Obscuration of the visual field in young 2004;18(2):135-8.
Chalazia that do not respond to tra- patients has been shown to produce a 5. Lederman C, Miller M. Hordeola and chalazia.
ditional therapy often will resolve with deprivational amblyopia. Also, the Pediatr Rev 1999;20(8):283-4.
intralesional corticosteroid injection. chronic external pressure produced by 6. Cottrell DG, Bosanquet RC, Fawcett IM. Chalazions:
The frequency of spontaneous resolution. Br Med J
Studies involving this form of therapy larger lesions can induce alterations in
(Clin Res Ed) 1983;287(6405):1595.
show a success rate of approximately 80 corneal curvature. Several cases of cha-
7. Garrett GW, Gillespie ME, Mannix BC.
to 90%.8-10 Using a standard 1 cc tuber- lazion-induced-astigmatism have been Adrenocorticosteroid injection vs. conservative therapy
culin syringe and 30-gauge needle, 0.1 documented.11,12 in the treatment of chalazia. Ann Ophthalmol
1988;20(5):196-8.
to 0.3 ml of triamcinolone acetonide 10 • While gentle massage is beneficial,
8. Mohan K, Dhir SP, Munjal VP, Jain IS. The use of
mg/ml (Kenalog®-10) or 40 mg/ml patients with chalazia should be cau-
intralesional steroids in the treatment of chalazion.
(Kenalog®-40) is injected directly into tioned against extremely vigorous mas- Ann Ophthalmol 1986;18(4):158-60.
the lesion. The approach should prefer- sage of the involved area; this may cause 9. Ho SY, Lai JS. Subcutaneous steroid injection as
ably be from the palpebral side, since further extravasation of the granuloma- treatment for chalazion: Prospective case series. Hong
Kong Med J 2002;8(1):18-20.
eyelid skin depigmentation may occur tous inflammation into the surround-
10. Ben Simon GJ, Huang L, Nakra T, et al.
when the injection occurs on the dermal ing tissue and may exacerbate or com-
Intralesional triamcinolone acetonide injection for pri-
side. This adverse effect is most com- plicate the condition. mary and recurrent chalazia: Is it really effective?
mon in dark-skinned individuals.8 The • Many practitioners consider intrale- Ophthalmol 2005;2(5):913-7.
use of a chalazion clamp and topical sional steroid injection to be contraindi- 11. Nisted M, Hofstetter HW. Effect of chalazion on
astigmatism. Am J Optom Physiol Opt
anesthesia may be helpful, but they are cated in dark-skinned individuals
1974;51(8):579-82.
not absolutely necessary. The patient because of the risk of local skin depig-
12. Cosar CB, Rapuano CJ, Cohen EJ, Laibson PR.
usually demonstrates marked improve- mentation that can persist for months or Chalazion as a cause of decreased vision after LASIK.
ment within one week of initial treat- become permanent. Although injecting Cornea 2001;20(8):890-2.

MARCH 15, 2006 REVIEW OF OPTOMETRY 11A

 CONJUNCTIVA & SCLERA

CONJUNCTIVAL ABRASION the affected area. used prophylactically to prevent infec-

AND LACERATION tion. Patching is generally unnecessary.
Pathophysiology Similar treatment is employed for
Signs and Symptoms The conjunctiva is an exposed conjunctival lacerations. Generally, if
Men are five times more likely than mucous membrane covering the globe the globe is not perforated, small con-
women to receive conjunctival or and the inner surface of the eyelid. The junctival lacerations are easily managed
scleral trauma.1,2 These types of palpebral portion of the conjunctiva in-office. Apply topical anesthesia and
injuries are most common in younger tightly adheres to the eyelid. The bul- use a forceps or a moistened cotton-
age groups: 54% of patients receiving bar portion loosely adheres so that the tipped applicator to manipulate any
them are younger than 40 years and globe has mobility.5 The conjunctiva is ragged areas of conjunctiva back into
only 10% are older than 60 years.1 composed of nonkeratinized stratified position. Bleeding can be arrested with
Patients will present with a history of squamous epithelium overlying stro- direct pressure. Following this, a fluo-
facial or direct ocular trauma, which mal tissue. The conjunctiva is reflected roquinolone solution (or ointment if
may range from relatively mild to upon itself so that it has the ability to the eye is to be pressure patched)
severe.3,4 Complaints range from mild stretch with ocular excursion. Because should be applied. Most small lacera-
pain to a scratchy, foreign-body sen- the conjunctiva is far less innervated tions (< 1 cm) will heal without the eye
sation in the affected eye. There may than the cornea, conjunctival abra- being patched. Larger lacerations (> 2
be some tearing and photophobia; sions and lacerations are less sympto- cm) may require either pressure patch-
matic than corneal abrasions ing or suturing.6
of the same severity. Given its A dilated examination should be
position, the bulbar conjuncti- carried out to rule out internal injury
va has the greatest chance of (commotio retinae, retinal trauma, vit-
sustaining injury. reous detachment or vitreous hemor-
In a conjunctival abrasion, rhage) or the presence of some other
the surface epithelial cells are unrelated, undiscovered pathology. In
physically “rubbed off.” In a the rare instance when inflammation
conjunctival laceration, the tis- lingers, a topical steroid can be used.
sue will wrinkle and stretch to
its physical capacity, beyond Clinical Pearls
Fluorescein staining of conjunctival abrasion with small which a full-thickness section • Conjunctival lacerations are minor
conjunctival laceration. of tissue will be torn out to problems that typically resolve with
reveal bare sclera beneath. In minimal intervention, yet patients
vision is rarely impaired unless the these cases, the trauma itself acts as an often present feeling great anxiety. The
sclera is lacerated and the globe is antigen and sets off an inflammatory eye is very red, and hemorrhaging may
open.4 The adjacent conjunctival ves- cascade, resulting in vasodilation and be cause for great concern on the
sels will be dilated, and there is often edema of the involved and surround- patient’s part, even though there is little
a subconjunctival hemorrhage. In ing tissues. Despite the nature of the pain or few other symptoms. While it
conjunctival lacerations, there may be injury, there is rarely a significant is important to rule out a penetrating
active bleeding, and the affected white cell proliferation to the point of injury, you can safely reassure most
region of the conjunctiva appears causing an anterior chamber reaction. patients that they have a simple “cut”
torn. The edges of the compromised on their eye, and that it will heal in a
tissue may be retracted, revealing the Management few days.
underlying sclera. Fluorescein will As with any case of ocular trauma, it • Be careful to differentiate this
pool in the area of the laceration is important to rule out globe perfora- pattern of staining from simple accu-
under the cobalt filter. Eventually, tion with a Seidel test, looking careful- mulation of fluorescein within the
stain will seep underneath the con- ly for external leakage of aqueous. Also, redundant physiologic folds of the
junctiva and produce a generalized meticulously inspect the surrounding conjunctiva.
“glow” to that part of the eye. In con- area for subconjunctival foreign bodies. • While internal inflammation is
junctival abrasions, the denuded con- For a conjunctival abrasion, a broad- typically minimal in these cases, any
junctival epithelium will retain the spectrum antibiotic, such as a fourth- trauma with sufficient force to produce
vital dye, producing staining within generation fluoroquinolone, should be an abraded or lacerated conjunctiva

12A REVIEW OF OPTOMETRY MARCH 15, 2006


deserves at least some consideration for
cycloplegia.
1. Hamill MB. Corneal and scleral trauma.
Ophthalmol Clin North Am 2002;15(2):185-94.
2. Liggett PE, Pince KJ, Barlow W, et al. Ocular trau-
ma in an urban population review of 1132 cases.
Ophthalmol 1990;97:581-4.
3. Marin MI, Tejero TR, Dominguez FM, et al. Ocular
injuries in midfacial fractures. Orbit 1998;17(1):41-6.
4. Muller L, Kohnen T. Scleral and corneal laceration
with iris prolapse caused by an eagle claw. Graefes
Arch Clin Exp Ophthalmol 2005;243(4):377-9.
5. Locke LC. Conjunctival abrasions and lacerations.
J Am Optom Assoc 1987;58(6):488-93.
6. Margo CE. Tourette syndrome and iatrogenic eye
injury. Am J Ophthalmol 2002;134(5):784-5.
TOXIC CONJUNCTIVITIS
Signs and Symptoms
Toxic conjunctivitis, sometimes
referred to as toxic follicular conjunc-
tivitis, is a syndrome resulting from
chronic ocular exposure to one or
more foreign substances. The typical
scenario involves a patient who has
recently started topical therapy for
some type of conjunctivitis, yet
despite using the medication properly,
the symptoms persist or worsen.
Occasionally, this reaction may be
seen in those starting or undergoing
glaucoma therapy.1,2 Cosmetics, mois-
turizers and other personal hygiene
products can likewise induce a toxic
conjunctivitis when used in or near
the eye. The process may occur uni-
laterally or bilaterally, depending
upon exposure.
Clinical features of toxic conjunc-
tivitis commonly include ocular itch-
ing, burning, tearing and marked
injection and chemosis of the bulbar
conjunctiva. The most recognizable
feature is a pronounced follicular reac-
tion involving the inferior (and some-
times superior) tarsus. Despite the
presence of follicles—which typically
imply a viral conjunctivitis—there is a
notable absence of preauricular lym-
phadenopathy. A mild keratopathy is
often secondarily present. In cases that
® CONJUNCTIVA & SCLERA
are chronic, pannus formation may • Type I reactions are immediate
result.3 hypersensitivity reactions, also called
anaphylactic reactions. These reactions
Pathophysiology produce sudden degranulation of mast
The toxic/allergic response is classi- cells, mediated by the antibody IgE.
cally considered an inappropriate and • Type II reactions involve the
excessive response of the body’s body’s ability to distinguish itself from
immune system to sub-
stances perceived as for-
eign—antigens, immuno-
gens or allergens. This
response can be innate or
acquired.4 A variation of
this overreaction is mani-
fested when the body
responds hyperactively to
exogenous materials such
as medicines, contact lens-
es, contact lens solutions,
dust, dander or viral shed- Chronic follicular conjunctivitis secondary to Propine use.
ding. Overactivity of this
type is commonly referred to as a toxic non-self. Abnormalities in this ele-
or allergic reaction. With respect to the ment of the system give rise to autoim-
eye and its adnexa, the result is toxic mune diseases.
conjunctivitis. When the body • Type III reactions involve combina-
responds in this manner to a topical tions of antigen and antibody known as
medication, it is often referred to as immune complexes. Offending triggers
“medicamentosa.” may be intrinsic (e.g., a protein mole-
The key component to the ocular cule) or extrinsic (e.g., a penicillin mol-
allergic response is the mast cell. When ecule) and may produce a significant
a mast cell interacts with a specific aller- tissue response in an attempt to rid the
gen, the outer cell membrane is altered area of the invader.
and it releases chemical mediators into • Type IV reactions, which are
the surrounding tissues. This process is sometimes referred to as cell-mediated
referred to as mast cell degranulation. hypersensitivity reactions, involve T-
The primary chemical mediator is his- lymphocytes and lymphokines. The
tamine, which is responsible for reaction is classically delayed until suf-
increased vascular permeability, vasodi- ficient antigens are present to stimu-
lation, bronchial constriction and late the chemical cascade. In the ocular
increased secretion of mucus. Other tissues, these chemical exchanges incite
preformed mediators such as tryptase, conjunctival and adnexal vasodilation,
chymase, bradykinin and heparin con- chemosis, edema and lacrimation. The
tribute to the allergic response. individual experiences pain, itching,
Sustained allergic responses in some swelling and irritation. The discharge
bodily tissues can induce eosinophil- produced is typically serous, and the
mediated inflammation which, conjunctival findings may include fol-
through the release of prostaglandins licles (hyperplasia of lymphoid tissue
and leukotrienes, may result in severe within the eyelid stroma) and/or papil-
tissue damage. lae (hyperplastic palpebral conjuncti-
There are four recognized types of val epithelium infiltrated by lympho-
hypersensitivity reactions:5 cytes and plasma cells).
MARCH 15, 2006 REVIEW OF OPTOMETRY 13A
 1988;2(Pt 4):440-2.
Management a toxic reaction to the preservatives in
3. Dart J. Corneal toxicity: The epithelium and stroma
Management of toxic conjunctivitis medications. A substantial keratitis is in iatrogenic and factitious disease. Eye
is primarily aimed at reducing sympto- the hallmark of the medicamentosa 2003;17(8):886-92.
matology. Of course, the first step is to response. 4. Black PN. Does atopy protect against enteric infec-
remove the offending agent, if possi- • While many patients choose to tions? Allergy 2005;60(1):30-4.

ble. Palliative treatment with 5. Friedmann PS, Lee MS, Friedmann AC, Barnetson
RS. Mechanisms in cutaneous drug hypersensitivity
cold compresses and artificial reactions. Clin Exp Allergy 2003;33(7):861-72.
tears helps further ameliorate 6. Soparkar CN, Wilhelmus KR, Koch DD, et al. Acute
the response by diluting the and chronic conjunctivitis due to over-the-counter
foreign substance or physically ophthalmic decongestants. Arch Ophthalmol
1997;115(1):34-8.
washing it away. These may be
7. Lanier BQ, Gross RD, Marks BB, et al. Olopatadine
used on a PRN basis. ophthalmic solution adjunctive to loratadine com-
However, to truly address the pared with loratadine alone in patients with active
mast cell/histamine response, seasonal allergic conjunctivitis symptoms. Ann Allergy
Asthma Immunol 2001;86(6):641-8.
topical allergy preparations are
8. Abelson MB, Welch DL. An evaluation of onset and
most effective. A host of duration of action of Patanol (olopatadine hydrochlo-
options exist, although most Corneal epitheliopathy secondary to acute toxic event. ride ophthalmic solution 0.1%) compared to Claritin
practitioners rely on combina- (loratadine 10 mg) tablets in acute allergic conjunc-
tivitis in the conjunctival allergen challenge model.
tion mast-cell stabilizer/antihistamines self-treat allergic or toxic conjunctivi- Acta Ophthalmol Scand 2000;230(Suppl):60-3.
as the mainstay of therapy. These tis with topical decongestants (e.g., 9. Simons FE. Advances in H1-antihistamines. N
include drugs such as Patanol® Vasocon® or Visine®), these agents are Engl J Med 2004; 351(21):2203-17.
(olopatadine HCl 0.1%, Alcon), not recommended. While deconges-
Zaditor® (ketotifen fumarate 0.025%, tants may produce short-term vaso-
Novartis), Elestat® (epinastine HCl constriction, reducing hyperemia, the OCULAR CICATRICIAL
0.05%, Inspire) and Optivar® (azelas- effects are short-lived. In addition, PEMPHIGOID
tine HCl 0.05%, MedPointe), all of these products have been shown to
which are indicated for BID dosing. actually induce toxic conjunctivitis in Signs and Symptoms
Non-steroidal anti-inflammatory a significant percentage of patients, Ocular cicatricial pemphigoid
drugs (NSAIDs) may be added to pro- and they may cause even more severe (OCP), or mucous membrane pem-
vide mild analgesia for patients with allergic responses, such as contact der- phigoid, is the most common, progres-
corneal compromise; however, they do matitis.6 Advise patients to avoid these sive, chronic immunobullous disorder
little to address the histamine-mediat- over-the-counter remedies, and of the conjunctiva.1-6 It is classified as
ed response. Topical corticosteroids instead recommend a prescription- an autoimmune disease in which the
(e.g., Pred-Forte® or Lotemax®), which strength topical allergy medication. ocular component of the immuno-
address the effects of inflammation, • Using oral antihistamines for pure- pathology is directed at the conjuncti-
may be desirable in severe or highly ly ocular allergic responses, such as toxic val basement membrane, producing
symptomatic reactions, but they are conjunctivitis, is probably inappropri- conjunctival scar formation.1–3 The dis-
generally not necessary. ate. Studies have shown that topical ease is usually bilateral and is more
agents provide more rapid relief than commonly seen in women than in
Clinical Pearls oral antihistamines alone.7,8 In addi- men. Most cases occur in people
• A diagnosis of toxic conjunctivitis tion, many oral antihistamines (particu- between the ages of 30 and 90 years,
is based primarily upon the history larly the older generation drugs such as with the most frequent age of presenta-
and clinical course. Typically, vision is Benedryl®) can induce central nervous tion in the seventh decade.6 OCP has
unaffected, despite the unruly appear- system depression (dizziness, drowsi- an estimated incidence of 1 in 20,000
ance. Even if left untreated, toxic con- ness, etc.) as well as antimuscarinic to 1 in 46,000.6 Tear deficiency is a
junctivitis often begins to resolve with- effects (dry mouth and dry eyes).9 major cause of symptoms, with vision
in seven days, providing that the loss occurring collaterally as a result of
offending agent is identified and 1. Blondeau P, Rousseau JA. Allergic reactions to bri-
monidine in patients treated for glaucoma. Can J
corneal surface failure.1 Other ocular
removed or discontinued. Ophthalmol 2002;37(1):21-6. signs include chronic cicatricial con-
• Medicamentosa is a sub-category 2. Coleiro JA, Sigurdsson H, Lockyer JA. Follicular junctivitis, progressive conjunctival
of toxic conjunctivitis used to connote conjunctivitis on Dipivefrin therapy for glaucoma. Eye fibrosis, the potential for symble-

14A REVIEW OF OPTOMETRY MARCH 15, 2006


pharon formation and corneal epithe-
liopathy.1–6 Patients initially complain
of redness, tearing, burning, decreased
vision and foreign body sensation.
Chronic conjunctivitis is the most
common referral diagnosis for general
practitioners.6 Chronic conjunctivitis is
typically punctuated by intermittent
acute episodes of conjunctival inflam-
mation. When the ocular surface
pathology becomes severe, it may even-
tually result in progressive irreversible
cicatrization of the conjunctiva and
could lead to blindness.1–6
Extraocular involvement may
accompany the ocular symptoms with
associated lesions seen on the skin,
oral mucosa, esophagus, trachea, lar-
ynx, anus, vagina and urethra.6
Pathophysiology
OCP is an autoimmune chronic
cicatrizing conjunctivitis associated
with the deposition of immunoglobu-
lins and complement on the conjunc-
tiva.6 The most commonly identified
immunoreactants are IgG and IgA.6
The main identifying factor is a pri-
marily linear deposition of immuno-
globulins in OCP vs. a more granular
deposition in the other conditions.6
Abnormal regulation of the immune
system seems to be the key feature of
OCP.6 Increased levels of tumor
necrosis factor and decreased levels of
interleukin-6 in serum have been
identified in patients with active dis-
ease.6 The serum levels of interleukin-
1 alpha and beta have also been
detected as elevated, with levels of
interleukin-1 receptor antagonist
decreased. Dysregulation of TGF-‚ in
the inflamed conjunctiva in active
OCP is another characteristic feature.6
Further support for the autoimmune
etiology comes from the observed
association of mucous membrane
pemphigoid with other autoimmune
diseases such as rheumatoid arthritis,
ankylosing spondylitis and systemic
lupus erythematosis.6
Management
Rapid diagnosis and initiation of
appropriate therapy is critical for lim-
iting progression both of the ocular
and systemic components of the syn-
drome.2 Conjunctival biopsies using
the immunofluorescent or immuno-
peroxidase technique provide the
only definitive evidence of OCP.6
Management of the tear deficiency
Symblepharon in ocular cicatricial pemphigoid.
component of OCP must be
addressed to arrest the signs and
symptoms associated with ocular
drying. As the dry eye is managed,
therapy must be integrated with
treatments aimed at other compo-
nents of both the ocular surface dis-
ease and ocular and adnexal inflam-
mation. Artificial tear preparations
may be used to build the tear layer,
and lubricating ointments may be
helpful in eyes that lack the capacity
to achieve surface wetting. Oral
antibiotics such as tetracycline may
aid in the readjustment of lid flora
and eyelid gland chemistry, allowing
the tear lipids to overcome their
interruption and naturally prevent
evaporative disease. Lid hygiene for
the accompanying blepharitis, along
with cold compresses, are supportive.
Systemic corticosteroids are still
the agents of first choice for OCP. In
general, they are regarded as rescue
medications for curtailing acute exac-
erbations.5 However, because of their
well known long-term adverse
® CONJUNCTIVA & SCLERA
effects, corticosteroids must be com-
bined with immunosuppressive
and/or anti-inflammatory agents.5
Systemic immunomodulatory thera-
py remains the treatment of choice
for controlling overall disease activi-
ty.2-4 Systemic cyclophosphamide
with short-term adjunctive high-dose
prednisolone is a preferred treatment
for severe and/or rapidly progressing
OCP.2 Oral low-dose weekly
methotrexate is a useful first-line
treatment for mild-to-moderate
OCP.2 Salazosulfapyridine has been
documented to be of value in con-
trolling the laryngopharyngeal
lesions and persistent cutaneous blis-
tering.3 The principle drawbacks to
immunosuppressive therapy are its
adverse effects.1-5 Recently,
researchers have initiated work with
an agent known as mycophenolate
mofetil (MMF). Compared to other
immunosuppressive agents, MMF’s
risk-benefit ratio for treatment of
OCP, uveitis, atopic keratoconjunc-
tivitis, the prevention of graft rejec-
tion after penetrating keratoplasty
and scleritis was significant.4
Dapsone is another alternative for
high-risk patients. Patients who do
not show any short-term improve-
ment on this regimen can be switched
to cyclophosphamide.5 Intravenous
immunoglobulins offer another effec-
tive treatment option in high-risk
patients.5 Other systemic options
include tetracycline and nicoti-
namide, as well as azathioprine in
combination with low doses of corti-
costeroids.5 Contact lenses—either
large limbal diameter rigid gas perme-
able or gas permeable scleral lenses—
may be useful for treating dry eye and
improving vision in some patients.2
Surgical management includes
plastic surgery for malposition of the
eyelid and lashes and cataract extrac-
tion for cases in which systemic corti-
costeroid use induces premature
cataractogensis.2 Mucous membrane
MARCH 15, 2006 REVIEW OF OPTOMETRY 15A
 grafting has been used with some suc-
cess to treat severe marginal entropi-
on, keratinization, cases with fornix
destruction and trichiasis.6 Amniotic
membrane transplantation has been
used as an initial step in attempting to
reconstruct the ocular surface in
patients with advanced OCP.6
Clinical Pearls
• While OCP is classically seen in
the elderly, the disease is also known
to occur in children on occasion.1
• The management of OCP
requires a multidisciplinary approach
to optimize patient care. The oph-
thalmic specialist tends to concentrate
on ocular sequelae, but OCP requires
an integrated approach with systemic
practitioners such as dermatologists,
otolaryngologists and dentists, since
unmanaged systemic complications
can be life-threatening.2,5
• Diseases that can mimic OCP
include ocular rosacea, atopic kerato-
conjunctivitis and scleroderma.6
• The use of some topical (pilo-
carpine, epinephrine) and systemic
drugs (practolol) have been associated
with development of symblepharon
and conjunctival shrinkage.6 In such
cases, the term “pseudo-pemphigoid”
is more appropriate.6
• Patients being considered for
Dapsone therapy should have labora-
tory evaluation of their glucose-6-
phosphate dehydrogenase (G6PD)
and methemoglobin status. The drug
is contraindicated in patients with
G6PD deficiency and sulfa allergies.6
1. Dart J. Cicatricial pemphigoid and dry eye. Semin
Ophthalmol 2005;20(2):95-100.
2. Chang JH, McCluskey PJ. Ocular cicatricial pem-
phigoid: Manifestations and management. Curr
Allergy Asthma Rep 2005;5(4):333-8.
3. Dainichi T, Takeshita H, Moroi Y, et al. Cicatricial
pemphigoid with autoantibodies against the laminin 5
gamma 2 subunit. Eur J Dermatol 2005;15(3):189-
93.
4. Zierhut M, Stubiger N, Siepmann K, et al. MMF
and eye disease. Lupus 2005;14(Suppl 1):s50-s54.
5. Sacher C, Hunzelmann N. Cicatricial pemphigoid
16A REVIEW OF OPTOMETRY MARCH 15, 2006
(mucous membrane pemphigoid): Current and emerg-
ing therapeutic approaches. Am J Clin Dermatol
2005;6(2):93-103.
6. Ahmed M, Zein G, Khawaja F, et al. Ocular cicatri-
cial pemphigoid: Pathogenesis, diagnosis and treat-
ment. Prog Retin Eye Res 2004;23(6):579-92.
PINGUECULITIS
Signs and Symptoms
Pingueculae are characterized by yel-
lowish, slightly raised interpalpebral
deposits in the nasal and temporal lim-
bal conjunctiva.1-7 In most cases,
pingueculae are an ancillary finding,
causing little if any ocular symptoms.
Pterygia are wedge-shaped fibrovascu-
lar growths that extend onto the cornea
and are frequently, but not always, the
product of chronic pathophysiological
sequelae introduced by pingueculae.5
Both lesions can potentially become
vascularized and inflamed, associated
with corneal punctate epitheliopathy
and corneal dellen (corneal thinning
secondary to dryness).1-5 When a
pinguecula becomes acutely inflamed,
vascularized and irritated, the condi-
tion is referred to as pingueculitis.3-7
Pathophysiology
Pinguecula formation is typically
seen in older patients and is consid-
ered by most researchers to be a con-
junctival degenerative processes initi-
ated by exposure to noxious
environmental stimuli and ultraviolet
radiation.2-5 The initial lesion is
thought to result from the chronic
action of solar radiation, which
induces an alteration of the collagen
and elastic tissues of the conjunctival
stroma, leading to elastotic degenera-
tion and deposition of abnormal elas-
tic fibers in the conjunctival substan-
tia propria.1,2,5 Once a pinguecular
elevation is formed, depending on its
size, the tear film may become thin
and discontinuous in that zone, pro-
ducing a bed of dryness.1 When the
lesion is sufficiently affected by
inflammation, vascular dilation allows
histamine, serotonin, bradykinin and
prostaglandins to be released, produc-
ing the acute irritative symptoms that
characterize pingueculitis. In severe
cases, the conjunctival surface
becomes sufficiently dry to cause
microulceration of the surface epithe-
lium.1,2,7 When this occurs, the eye
attempts to cover the erosion, and this
is the impetus for pterygium forma-
tion.1 New research has suggested that
inflammatory cell infiltration may
contribute to conjunctival inclusion
cyst formation seen within pterygia,
pingueculae, vernal conjunctivitides
and pyogenic granulomata.7
Management
Management of pinguecula is pred-
icated mostly on symptomatology.
Patients who have occupations or
hobbies that increase the risk of
pinguecula formation should be
counseled on the preventative benefits
of sunwear, UV-blocking coatings or
goggles that limit dust exposure.3 In
cases of mild pingueculitis in which
symptoms are subtle, ocular lubricat-
ing drops such as Systane™ (Alcon
Inflamed pinguecula in pingueculitis.
Laboratories), Refresh™ (Allergan), or
Soothe™ (Alimera Sciences) are indi-
cated. When symptoms and inflam-
mation become more significant, top-
ical steroids such as 1% prednisolone
acetate suspension (Pred Mild™ and
Pred Forte™, Allergan), 0.5%
loteprednol etabonate (Lotemax™,

Bausch & Lomb) or 0.25% fluo-
rometholone (Flarex™, Alcon),
Q2H–QID are acceptable.2,3,5 A pub-
lished report has recognized that 0.1%
indomethacin solution has a beneficial
effect in cases of inflamed pinguecula
or pterygium; however, a commercial
topical preparation is not currently
available.6 In severe cases, in which the
tissue interferes with vision, contact
lens wear or corneal wetting, surgical
resection is a possible modality..2,3
Clinical Pearls
• Differential diagnoses must be con-
sidered when intrapalpebral conjuncti-
val masses and elevations are discov-
ered.2-5 Such lesions are not always
benign, and include conjunctival der-
moids, intraepithelial neoplasia (squa-
mous cell carcinoma), phlyctenulosis,
pannus, conjunctival retention cysts
and limbal follicles.3
• While pingueculitis is typically self-
limiting and rarely sight-threatening,
prompt treatment with lubrication and
anti-inflammatory therapy hastens
recovery and greatly helps diminish
symptoms.
1. Archila EA, Arenas MC. The etiopathology of pinguec-
ula and pterygium. Cornea 1995;14(5):543-4.
2. Wallace W. Diseases of the conjunctiva. In: Bartlett
JD, Jaanus SD, eds, Clinical Ocular Pharmacology.
Boston: Butterworth-Heinmann, 1984, pp. 583-648.
3. Cullom RD, Chang B. Cornea: pterygium/pinguecu-
lum. In: Cullom RD, Chang B, eds., The Wills Eye
Manual: Office and Emergency Room Diagnosis and
Treatment of Eye Disease. Philadelphia: J.B.
Lippincott, 1994, pp. 65-7.
4. Bergmanson JP, Soderberg PG. The significance of
ultraviolet radiation for eye diseases: A review on the
efficacy of UV-blocking contact lenses. Ophthalmic
Physiologic Optics 1995;15(2):83-91.
5. Cohen EJ, Rapuano CJ, Laibson PR. External dis-
eases. In: Tasman W, Jaeger EA, eds., The Wills Eye
Atlas of Clinical Ophthalmology. Philadelphia: J.B.
Lippincott, 1996, pp. 1-85.
6. Frucht-Pery J, Solomon A, Siganos CS, et al.
Treatment of inflamed pterygium and pinguecula with
topical indomethacin 0.1% solution. Cornea
1997;16(1):42-7.
7. Suzuki K, Okisaka S, Nakagami T. The contribution
of inflammatory cell infiltration to conjunctival inclu-
sion cyst formation. Jpn J Ophthalmol 2000;
44(5):575.
BUILDING A THERAPEUTIC PRACTICE, PART 1
Optometry has unquestionably become
a therapeutic profession. Attend any contin-
uing education meeting or pick up any pro-
fessional publication and you will plainly
see that most of the content and curricula
center on the therapeutic management of
ocular disease. Currently, every state in the
United States permits ODs to use at least
some therapeutic agents, whether they are
topical, oral, injectable or laser. These priv-
ileges come only after many years of hard-
fought legislative battles and continuous
demonstrations of competencies. Yet many
in our profession are still not using thera-
peutics to their fullest potential in their day-
to-day practice.
Before we discuss the “how,” it is pru-
dent to discuss the “why” of therapeutic
practice. For one thing, optometry’s tradi-
tional “bread & butter”—namely, refractive
care—is in great peril. For those who may
disagree, consider that right now, opticians
are lobbying heavily for refractive privileges
in most states. Larger ophthalmology offices
routinely fit and dispense spectacles and
contact lenses today (a practice that was vir-
tually unheard of 20 years ago). We have
also seen a massive shift in contact lens
practice and profitability over the last 15
years, with the overwhelming shift to dispos-
able lenses causing profit margins to plum-
met. Declining material profits can be com-
pensated by increased professional fees.
Finally, consider the fact that in the past
year, more than 850,000 refractive surger-
ies were performed in the United States. To
quote Dr. Art Epstein, “Our refractive capac-
ity may greatly exceed refractive opportunity
in just a few short decades.”
Therapeutic practice truly represents a
large part of the future of optometry. The
keys to building a therapeutic practice are
obtaining the knowledge and tools neces-
sary for treating the many types of ocular
diseases we encounter, mustering the
courage to seize these opportunities, and
pulling the therapeutic trigger. Because we
are a primary-care profession, patients
often do not see us as providers of medical
eye care. They may not realize that we have
the skill and training to treat glaucoma,
ocular infection, uveitis—or even allergies.
We must be proactive in identifying and
educating potential therapeutic patients;
they need to be aware that we do more than
just examine eyes for fitting with glasses
MARCH 15, 2006
® CONJUNCTIVA & SCLERA
and contact lenses. If we wish to jump-start
our therapeutic potential, taking this initia-
tive is an important step.
There are several mechanisms available
by which we can relay this message to our
patients. One is direct mailings, e-mailings,
and monthly newsletters that inform
patients about new equipment, drugs and
therapies for common disorders. Web sites
are another useful tool. In-office displays
and informational pamphlets are particular-
ly helpful when they are strategically placed
in the waiting area. However, one of the best
tools for identifying therapeutic patients in
our practices is office staff. In a busy prac-
tice, these individuals may have more con-
tact time with patients than the doctor.
When properly educated, office staff and
technicians can inquire about and discuss
symptoms with patients, and then inform
them of our capability to help. Successful
offices use this technique in promoting
spectacle lens choices, contact lenses,
refractive surgery and even vision therapy.
There’s no reason not to use the same
resource to build a therapeutic practice.
In addition to educating patients, doc-
tors must take more initiative in identifying
potential therapeutic patients in the office.
A targeted intake form, or “symptoms
checklist,” can efficiently screen for a wide
range of complaints and potential disor-
ders. Such forms are extremely valuable,
provided the practitioner takes the time to
review them thoroughly and asks the
patient to elaborate on complaints. While
simply performing the exam saves time, it
does little to build patient loyalty or grow a
quality therapeutic practice.
Another factor that deters many practi-
tioners from entering the therapeutic realm
is apprehension. Where to start? Two areas
that have great therapeutic potential (and
which are all too often overlooked) are dry
eye and ocular allergy. Conservative esti-
mates indicate that there are 10 million to
20 million chronic dry eye patients in the
United States today, and perhaps 40 mil-
lion more who experience sporadic symp-
toms. According to the National Institute of
Allergy and Infectious Diseases, more than
50 million Americans suffer from allergy1
and more than half of these individuals
have ocular manifestations. Besides preva-
lence, dry eye and ocular allergy represent
excellent opportunities for a foray into ther-
REVIEW OF OPTOMETRY 17A
 apeutics because they are both relatively easy to recognize and
diagnose, and because they do not require much advanced or
expensive technology. Moreover, these conditions are generally of
less interest to ophthalmologists, since they rarely require surgical
intervention, and the associated therapeutic agents are, for the
most part, relatively innocuous and easy to prescribe. Most impor-
tant, they offer an excellent opportunity for the clinician to allevi-
ate chronic suffering.
Another critical factor in building a therapeutic practice:
always remember to write prescriptions. This may sound basic, but
many ODs simply do not use their prescription pads as often as
they should. In fact, many rely on samples for the bulk of their
treatment. While this may save the patient a few dollars, it does
little to establish the practice as a center for excellence.
Remember the old adage, “That which costs me nothing is worth
nothing.” When used improperly, samples can change patients’
BUILDING A THERAPEUTIC PRACTICE, PART 2
Is therapeutic care profitable? Certainly it can be, provided that
there is acknowledgement of and adherence to a few basic princi-
ples. First, practitioners must not devalue their professional services
or time. Many ODs are so grounded in material sales that they fail to
capitalize on their most valuable assets—namely, their diagnostic
knowledge and clinical skills (which take years to develop and
mature). Fees for service should be set at a level commensurate with
the complexity of the case and the time required to properly manage
it. Fees should be charged for each and every visit, be it consultation
or follow-up. Too often, physicians charge for the initial visit, but (out
of guilt or fear) advise patients that “there will be no charge for the
follow-up.” This is a recipe inconsistent with professional respect,
reward or financial compensation. Another infrequently practiced
policy is billing appropriately for separate procedures. Sweeping an
eyelash from the inferior cul-de-sac with a cotton swab may seem
like no big deal because of its simplicity (as compared to a glauco-
ma work-up, for example), but in reality, it takes time and practice
to understand how to properly approach the problem, remove the
eyelash and avoid complications. An eyelash, like a piece of metal,
embedded in the conjunctiva constitutes a conjunctival foreign body.
Remember: you paid someone money and time to teach you these
techniques, and it took great effort and practice to master them. It
is not appropriate to simply “give them away.” Also, some may tell a
patient to return if they don’t feel better when, in reality, the patient
should be seen at least one more time. Often this is done because
the doctor is uncomfortable with charging for the return visit.
Another common misconception is that engaging in therapeutics
may require a complete revamping of a practice, and that to do so,
practitioners will have to find these “new” patients. Not so. In fact,
the patients we desire are literally all around us. It’s just that all too
often, we fail to recognize them. As mentioned earlier, conditions like
dry eye and allergy are so prevalent that they represent a windfall of
additional revenue if we would only take the time to identify them.
18A REVIEW OF OPTOMETRY MARCH 15, 2006
perceptions from expertise to expectation. In the worst-case sce-
nario, a patient might take the medication for a few days and dis-
card the remainder because it was “free,” then never fill the pre-
scription. These patients inevitably return to your office for another
sample when the symptoms recur.
Issuing a therapeutic prescription helps establish a strong bond
between physician and patient. It shows that the doctor will need
to reassess the situation at the conclusion of therapy, or even ear-
lier. Writing prescriptions also helps establish a reason for follow-
up visits. When the patient returns (hopefully showing signs of res-
olution), the return visit solidifies and completes that doctor-patient
relationship. Grateful patients tend to reward physicians’ efforts
with word-of-mouth referrals to family and friends—which may ulti-
mately be the most significant aspect of growing a practice.
1. National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Allergy Statistics. August 2005. http://www.niaid.nih.gov/ factsheets/allergystat.htm.
Glaucoma, diabetes and macular degeneration are other disorders
that require ongoing care and monitoring with ophthalmoscopy,
tonometry, visual fields and other advanced procedures. Current
training in optometry provides the basis for each of us to adequate-
ly manage these patients in the long term. Only a small minority of
the advanced cases requires surgical intervention, so why should all
of these potential revenue-generating patients be referred immedi-
ately for ophthalmologic care?
Once you have maximized your potential within your own prac-
tice and are ready to take on additional patients, consider that you
have unlimited referral sources in other medical specialists. While
we might not expect many ophthalmologists to refer disease cases to
us, it can happen under the right circumstances. However, it is more
likely that you can build a relationship with other medical profes-
sionals, particularly those who do not perceive a therapeutic
optometrist as a risk to their livelihood. Some wonderful examples
include dentists, rheumatologists, dermatologists, allergists,
internists and pediatricians. Physician assistants and nurse practi-
tioners should not be ignored as they see many patients with acute
ocular conditions. If you are truly practicing full-scope care, you will
have plenty of opportunities to interact with these folks. Consider the
severe dry eye patient whom you suspect may have rheumatoid
arthritis and/or Sjögren’s syndrome. This patient clearly needs
rheumatologic care, and if Sjögren’s is indeed present, a good den-
tist is paramount (Sjögren’s syndrome also causes severe dry mouth,
which can result in dental carries, oral ulcers and other pathologies).
Patients with rosacea, seborrhea and other skin conditions often
demonstrate ocular manifestations, but they may not know a good
dermatologist who can treat the underlying disorder. And so it goes .
. . as you develop greater numbers of referrals to these specialists,
you can expect greater numbers of referrals to come your way.
Expanding and embracing your therapeutic practice can be a win-
win situation for all involved.
CORNEA
FUNGAL KERATITIS
Signs and Symptoms
Fungal keratitis shows no predilec-
tion for age, gender or race.1 Often,
patients have incurred corneal trauma,
usually from organic vegetative matter.
Other significant risk factors include
ocular or systemic immunosuppres-
sion, either by disease or by medical
immunosuppressive therapy (such as
for organ transplantation) or topical
steroid therapy, contact lens wear, and
chronic antibiotic use.1-4 Fungal infec-
tions are also more common in agri-
cultural and tropical environments.3
Finally, any breakdown of the corneal
epithelial barrier increases the threat of
invasive fungal disease.
Fungal infections of the cornea
often initially produce a feathery,
branching pattern. Satellite lesions are
not uncommon. The cornea takes on a
dull, gray appearance, with possible
heaping of epithelium and a dry,
rough texture. In most cases, this char-
acteristic appearance disappears over
time, and fungal keratitis begins to
resemble advanced bacterial keratitis.
Misdiagnosis at this point is very pos-
sible, and there are no easy ways to
clinically differentiate the conditions
at this point. Typically, a severe anteri-
or uveitis and plasmoid aqueous with
hypopyon appears. There will be
painful vision loss.
Pathophysiology
There are two types of fungi: molds
and yeasts. Molds (filamentary fungi)
are further subdivided into septate (the
most common causes of fungal kerati-
tis) and non-septate organisms. They
produce feathery colonies that join
together to produce hyphae. Yeasts,
however, form pseudohyphae. The
non-septate filamentary fungi are
responsible for orbital disease but
rarely infect the cornea. Of all possible
fungal infections of the cornea, the
vast majority are caused by Fusarium,
Aspergillus (both septate filamentary
fungi) and Candida (a yeast).1,2,4-6
Fungal keratitis ensues when these
organisms opportunistically, through
trauma and immunosuppression, gain
access to corneal tissue beneath the
epithelial barrier and begin coloniza-
tion within the corneal stroma.
Management
Diagnosis of fungal keratitis typi-
cally occurs late, as many cases are
mistaken for bacterial keratitis or
other surface disorders. Clinicians
often consider fungal keratitis only
after a presumed bacterial keratitis
Fungal keratitis.
worsens during seemingly appropriate
antibiotic therapy. The standard
corneal scraping performed in bacter-
ial keratitis is acceptable; however, in
addition to regular bacterial cultures
with blood and chocolate agar incu-
bated at 37°C for bacteria, blood and
Sabouraud agar plates at room tem-
perature also should be inoculated.
Anti-fungal sensitivity testing is unre-
liable and correlates poorly with clini-
cal efficacy. Corneal biopsy may be
needed. Recently, confocal micros-
copy has proven to be an accurate,
non-invasive method for identifying
fungal keratitis.7
Treating fungal keratitis is difficult.
Most antifungal medications are mere-
ly fungistatic and require an intact
immune system (which may not be
present) and a prolonged therapeutic
course. Without innate immunity
helping to suppress the organism, the
fungistatic medications are likely to be
®
CORNEA
less effective. Drug classes used to treat
fungal keratitis include the polyene
antibiotics (nystatin, amphotericin B,
natamycin); pyrimidine analogs
(flucytosine); imidazoles (clortrima-
zole, miconozole, econazole, keto-
conazole); triazoles (fluconazole, itra-
conazole); and silver sulfadiazine.
Natamycin can only be given topical-
ly; the other drugs have various routes
of administration.4 Steroids are con-
traindicated because they will exacer-
bate the disease.
For filamentary fungal infections,
topical Natacyn (natamycin 5%, Alcon)
is the first choice.8 Alternatives include
amphotericin B 0.15% and flucytosine
1% 150 mg/kg PO—the same therapy
used to treat yeast infections. An alter-
native treatment in yeast infections is
fluconazole 0.5% 200 mg PO and top-
ical miconozole 1%. All therapies are
indicated hourly around the clock.
Itraconazole, either topically or systemi-
cally, is effective in treating fungal kerati-
tis, particularly if the infections are due
to Aspergillus or Curvularia spp.8,9
Recent studies have shown that topical
Econazole 2% appears to be as effective
as natamycin 5% for managing fungal
keratitis.10 However, the combined use
of these products does not seem to have
any advantage over that of natamycin
5% alone.11
Medical therapy of fungal keratitis
often is met with poor outcomes, with
surgery necessary to effect a clinical
cure.12,13 One study examined the effi-
cacy of using phototherapeutic kera-
tectomy (PTK) in patients with
superficial fungal keratitis that had
infiltrated less than half of the corneal
thickness and responded poorly to
topical antifungal therapy. It was
shown that PTK shortened treatment
time, hastened reepithelialization and
restored reasonably good vision.14
PTK can be a valuable therapeutic
adjunct for superficial fungal keratitis,
especially in instances in which there
is poor response to treatment by topi-
cal antifungal agents alone.
MARCH 15, 2006 REVIEW OF OPTOMETRY 19A

Clinical Pearls
• While injury by organic vegeta-
tive matter is a risk factor for fungal
keratitis, it does not necessarily mean
that a patient will develop the disease.
Many patients with such injuries
never develop fungal keratitis; it is
quite uncommon. For this reason,
antifungal medications are not given
prophylactically.
• As a rule, fungal keratitis is not a
rapidly progressive condition; instead,
it is rather slow and insidious.
• A thorough history should give
insight as to which patients need the
closest observation for the develop-
ment of fungal keratitis.
1. Hofling-Lima AL, Forseto A, Duprat JP, et al.
Laboratory study of the mycotic infectious eye dis-
eases and factors associated with keratitis. Arq Bras
Oftalmol 2005;68(1):21-7.
2. Basak SK, Basak S, Mohanta A, et al.
Epidemiological and microbiological diagnosis of
suppurative keratitis in Gangetic West Bengal, east-
ern India. Indian J Ophthalmol 2005;53(1):17-22.
3. Bharathi MJ, Ramakrishnan R, Vasu S, et al.
Epidemiological characteristics and laboratory diag-
nosis of fungal keratitis. A three-year study. Indian J
Ophthalmol 2003;51(4):315-21.
4. Thomas PA. Fungal infections of the cornea. Eye
2003;17(8):852-62.
5. Chowdhary A, Singh K. Spectrum of fungal ker-
atitis in North India. Cornea 2005;24(1):8-15.
6. Doczi I, Gyetvai T, Kredics L, et al. Involvement
of Fusarium spp. in fungal keratitis. Clin Microbiol
Infect 2004;10(9):773-6.
7. Avunduk AM, Beuerman RW, Varnell ED, et al.
Confocal microscopy of Aspergillus fumigatus kerati-
tis. Br J Ophthalmol 2003;87(4):409-10.
8. Kalavathy CM, Parmar P, Kaliamurthy J, et al.
Comparison of topical itraconazole 1% with topical
natamycin 5% for the treatment of filamentous fun-
gal keratitis. Cornea 2005;24(4):449-52.
9. Agarwal PK, Roy P, Das A, et al. Efficacy of topi-
cal and systemic itraconazole as a broad-spectrum
antifungal agent in mycotic corneal ulcer: A prelimi-
nary study. Indian J Ophthalmol 2001;49(3):173-6.
10. Prajna NV, John RK, Nirmalan PK, et al. A ran-
domised clinical trial comparing 2% econazole and
5% natamycin for the treatment of fungal keratitis.
Br J Ophthalmol 2003;87(10):1235-7.
11. Prajna NV, Nirmalan PK, Mahalakshmi R, et al.
Concurrent use of 5% natamycin and 2% econazole
for the management of fungal keratitis. Cornea
2004;23(8):793-6.
12. Fong CF, Tseng CH, Hu FR, et al. Clinical char-
acteristics of microbial keratitis in a university hos-
pital in Taiwan. Am J Ophthalmol 2004;
20A REVIEW OF OPTOMETRY MARCH 15, 2006
137(2):329-36.
13. Doczi I, Gyetvai T, Kredics L, et al. Involvement
of Fusarium spp. in fungal keratitis. Clin Microbiol
Infect 2004;10(9):773-6.
14. Lin CP, Chang CW, Su CY. Phototherapeutic ker-
atectomy in treating keratomycosis. Cornea 2000;
24(3):262-8.
GRANULAR DYSTROPHY
Signs and Symptoms
Granular dystrophy (sometimes
referred to as Groenouw Type I dys-
trophy) is a bilateral condition that
affects the central regions of the
cornea while sparing the periphery.1
Patients may be diagnosed on rou-
tine examination in their teens or
twenties, although the condition
Granular corneal dystrophy in direct
illumination.
does not typically become sympto-
matic until the third or fourth decade
of life.2 Clinically, granular dystro-
phy appears as discrete, white-to-gray
corneal deposits of non-uniform size,
most closely resembling snowflakes
or breadcrumbs. Vision is usually not
affected in the early stages; however,
as the deposits become larger and
denser, visual acuity may drop off
precipitously. It is not unusual to see
older patients with this condition
manifesting vision of 20/200 or
worse. Patients may also report vary-
ing degrees of ocular irritation from a
mild foreign body sensation to pro-
nounced pain. The most significant
complication, aside from reduced
vision, is the propensity toward
recurrent epithelial erosions.
Pathophysiology
Corneal dystrophies are non-infec-
tious, non-inflammatory, hereditary
disorders that involve abnormal depo-
sition or retention of material within
the cornea, usually due to faulty cellu-
lar metabolism. The underlying etiol-
ogy is often related to a specific genet-
ic mutation.3 Corneal dystrophies are
categorized by the layer of the cornea
in which they are found, including the
superficial anterior layers (epithelium
and epithelial basement membrane),
Bowman’s layer, the corneal stroma or
the endothelium. Granular dystrophy
occurs at the level of the stroma and is,
in fact, the most common stromal
corneal dystrophy seen in clinical
practice.4,5
Granular dystrophy displays an
autosomal dominant inheritance pat-
tern with complete penetrance.1 The
specific genetic locus appears to be
chromosome 5q31.6 Studies suggest
that degenerative changes to the
epithelial cells and/or keratocytes con-
tribute to the disorder,7 and histologi-
cal examination shows that the
deposits are composed of hyaline
material.1,5 The epithelial basement
membrane and Bowman’s layer are
also altered, and this can lead to recur-
rent corneal erosions.
Management
There is no recognized therapeutic
management for granular dystrophy
of the cornea. Patients typically
endure the situation and rely on arti-
ficial tears for palliative relief of ocu-
lar irritation. In later stages involving
significant visual compromise, pene-
trating or lamellar keratoplasty may
be employed. Phototherapeutic kera-
tectomy (PTK) presents a less inva-
sive alternative to penetrating kerato-
plasty and has been successfully
utilized to restore vision in moderate-
ly advanced cases.8 However, even
after surgical intervention, the condi-
tion may recur in as many as 40% of
patients.9 Published reports suggest

that using soft contact lenses post-
operatively may diminish the likeli-
hood of recurrence.10,11
Conventional treatment of corneal
erosions associated with granular dys-
trophy involves lubrication, bandage
contact lenses, prophylactic antibiosis
and topical anti-inflammatory agents
as needed for pain. Anterior stromal
puncture is not advisable for recurrent
erosions secondary to corneal dystro-
phy, and should be employed only in
those cases in which erosion is associ-
ated with prior ocular trauma. PTK,
on the other hand, has been success-
fully used in recalcitrant recurrent
corneal erosions independent of the
etiology.12
Clinical Pearls
• Granular dystrophy is the most
common stromal corneal dystrophy
encountered in clinical practice.
Other common dystrophies include
epithelial basement membrane dys-
Granular corneal dystrophy in retroillumination.
trophy (EBMD), lattice dystrophy
and Fuch’s endothelial dystrophy.
These conditions are distinguished
based upon: 1) the involved layer of
the cornea and 2) the clinical and his-
tological appearance of the lesions.
• A unique variant of granular dys-
trophy was identified in 1988 in a
series of patients who traced their
ancestry to the Avellino province of
Italy.13 “Avellino corneal dystrophy,”
as it has come to be called, displays
characteristics of both granular and
lattice dystrophy.
• Since granular dystrophy is auto-
somal dominant, it is important to
examine family members (especially
siblings or children) of patients for
similar ocular findings.
1. Leopardi S, Cucinotta A, Chetri A, et al.
Histochemistry and electron-microscopy observation
in two cases of granular dystrophy of the cornea.
Ophthalmologica 1991;203(4):164-7.
2. Sajjadi SH, Javadi MA. Superficial juvenile granu-
lar dystrophy. Ophthalmol 1992;99(1):95-102.
3. Vincent AL, Patel DV, McGhee CN. Inherited
corneal disease: The evolving molecular, genetic and
imaging revolution. Clin Experiment Ophthalmol
2005;33(3):303-16.
4. Brownstein S, Fine BS, Sherman ME, Zimmerman
LE. Granular dystrophy of the cornea. Light and elec-
tron microscopic confirmation of recurrence in a graft.
Amer J Ophthalmol 1974;77(5):701-10.
5. Colin HB, Hendicott PL. Granular dystrophy of the
cornea. Clin Exp Optom 1999;82(5):203-6.
6. Eiberg H, Moller HU, Berendt I, Mohr J.
Assignment of granular corneal dystrophy Groenouw
type I (CDGG1) to chromosome 5q. Eur J Hum Genet
1994;2(2):132-8.
7. Johnson BL, Brown SI, Zaidman GW. A light and
electron microscopic study of recurrent granular dys-
trophy of the cornea. Amer J Ophthalmol 1981;
92(1):49-58.
8. Nassaralla BA, Garbus J, McDonnell PJ.
Phototherapeutic keratectomy for granular and lattice
corneal dystrophies at 1.5 to 4 years. J Refract Surg
1996;12(7):795-800.
9. Marcon AS, Cohen EJ, Rapuano CJ, Laibson PR.
Recurrence of corneal stromal dystrophies after pene-
trating keratoplasty. Cornea 1995;14(2):217-22.
10. Severin M, Konen W, Kirchhof B. Granular corneal
dystrophy: treatment with soft contact lenses. Graefes
Arch Clin Exp Ophthalmol 1998;236(4):291-4.
11. Roters S, Severin M, Konen W, Krieglstein GK.
Treatment of granular dystrophy with soft contact
lenses. Ophthalmologica 2004;218(1):70-2.
12. Jain S, Austin DJ. Phototherapeutic keratectomy
for treatment of recurrent corneal erosion. J Cataract
Refract Surg 1999;25(12):1610-4.
13. Folberg R, Alfonso E, Croxatto J, et al. Clinically
atypical granular corneal dystrophy with pathologic
features of lattice-like amyloid deposits: a study of
three families. Ophthalmol 1988;95(1):46-51.
CONTACT LENS ACUTE
RED EYE (CLARE)
Signs and Symptoms
Contact lens acute red eye
(CLARE), as the name implies, is an
acute inflammatory condition associ-
®
CORNEA
ated with contact lens wear. The clas-
sic presentation involves a patient in
extended-wear hydrogel contact lens-
es who, upon awakening, experiences
ocular pain (e.g., foreign body sensa-
tion), tearing, variably decreased
vision and photophobia. Clinically,
CLARE manifests as an acute kerati-
tis marked by mid-peripheral corneal
infiltrates in the most severe cases.1
These infiltrates may emanate from
and accumulate near encroaching
limbal vessels. Associated clinical
signs include moderate-to-severe con-
junctival and limbal hyperemia,
corneal edema and mild-to-moderate
blepharospasm. Pronounced lid
edema, corneal epitheliopathy and
anterior chamber reaction are notably
absent.
Often, patients with CLARE will
have a history of poor contact lens
hygiene, excessive wearing time or
frank contact lens abuse. In some
cases, the contact lens shows inade-
quate movement, and the patient
may be physically unable to remove
the lens from the eye during the ini-
tial episode. Immobility of the lens is,
however, not uniformly encountered.
CLARE may occur both with well-
fitted and poorly-fitted lenses and
may be seen with low or high dK/L
materials, including silicone hydro-
gels and gas permeable lenses.2,3
Pathophysiology
CLARE represents a sterile inflam-
matory keratitis that is associated
with bacterial colonization of the
contact lens.4-8 While all contact lens-
es harbor bacteria, obviously not all
patients experience CLARE. This
suggests that a combination of factors
is involved, including lens-induced
hypoxia, mechanical microtrauma
from the lens itself and even the type
and virulence of the specific bacteria.
Gram-negative organisms, particular-
ly Pseudomonas but also Haemophilus
and Serratia species, have been most
frequently implicated.7-9 In CLARE,
MARCH 15, 2006 REVIEW OF OPTOMETRY 21A
 these bacteria do not invade the ever, in such cases a mild agent such
cornea, but rather release endotoxins as homatropine 5% b.i.d. may be
that recruit inflammatory cells via the employed. Reevaluation should be
limbal vasculature into the corneal performed every 24 to 48 hours (or
stroma.7 This immune response trig- perhaps longer, depending upon the
gers the keratitis seen clinically.
It should be noted that CLARE
is distinctly different from micro-
bial keratitis (a.k.a. corneal ulcer):
In CLARE there are no live, repli-
cating pathogens within the
cornea. Hence, there is generally
no frank epithelial defect overlying
the infiltrated areas.
Management
Since CLARE is non-infectious
and the contact lens represents the Profound corneal vascularization secondary to
antigen in this immune reaction, continuous contact lens wear for several months.
temporary cessation of lens wear is
usually sufficient to alleviate the con- severity) while patients remain on
dition. However, depending on the therapy; after resolution, refitting of
degree of inflammation and patient contact lenses should be considered.
discomfort, additional therapeutic
intervention may be desirable. Clinical Pearls
Copious lubrication with artificial • The term “contact lens overwear
tears helps to provide palliative relief syndrome” is sometimes used inter-
of symptoms, while lid hygiene ther- changeably with CLARE to describe
apy is beneficial to reduce resident an acutely inflamed eye associated
bacterial populations. Prophylactic with lens wear. Realize that “over-
antibiosis may also be helpful in wear” implies a purely hypoxic stress
diminishing bacterial reservoirs. situation, which typically presents
Broad spectrum antibiotics with with punctate epitheliopathy and, in
Gram-negative coverage are prefer- some cases, a corneal/conjunctival
able, such as aminoglycosides (gen- indentation corresponding to the edge
tamicin, tobramycin) or fluoro- of the entrapped lens. CLARE, by
quinolones (ciprofloxacin, ofloxacin, definition, involves an immune
gatifloxacin or moxifloxacin). Topical response to bacterial pathogens. One
corticosteroids may be extremely ben- must take care to differentiate these
eficial in rapidly ameliorating symp- disorders, as the treatments may differ.
toms and clearing the cornea of infil- • CLARE must also be carefully
trates. Since the condition is differentiated from microbial kerati-
superficial, virtually any corticos- tis. True bacterial ulcers will always
teroid may be used, including pred- show an overlying epithelial defect in
nisolone, dexamethasone, fluo- association with focal corneal infiltra-
rometholone or loteprednol. Perhaps tion. If a definitive diagnosis cannot
the most effective and easiest thera- be made, treat the condition as
peutic regimen is to use an antibiotic- microbial keratitis and prescribe a flu-
corticosteroid combination, such as oroquinolone antibiotic for at least
TobraDex® or Zylet®, on a q.i.d. basis. 24 hours before considering a topical
Cycloplegia is rarely necessary as deep corticosteroid. In either case, never
inflammation is highly atypical; how- employ a pressure patch—this will
22A REVIEW OF OPTOMETRY MARCH 15, 2006
only exacerbate the edema and may
amplify the bacterial infection.
• While CLARE can occur with
virtually any type of contact lens or
wearing regimen, it has been shown
that extended-wear contact lenses
significantly increase the risk of
CLARE. Further, patients who
have endured one episode are more
susceptible to repeat occur-
rences.10,11 These individuals
should ideally be reassigned to a
lower-risk regimen, such as daily
wear, gas permeable or, ideally,
daily disposable lenses. Care should
be taken to ensure a good physio-
logic fit with adequate movement
and the greatest possible level of
oxygen permeability.
1. Stapleton F, Ramachandran L, Sweeney DF, et al.
Altered conjunctival response after contact lens-relat-
ed corneal inflammation. Cornea 2003;22(5):443-7.
2. Dumbleton K. Adverse events with silicone hydro-
gel continuous wear. Cont Lens Anterior Eye
2002;25(3):137-46.
3. Schnider C, Zabkiewicz K, Holden B. Unusual com-
plications associated with rigid gas permeable extend-
ed wear. Int Cont Lens Clin, 1988;15:124-129.
4. Willcox MDP, Thakur A, Holden BA. Some potential
pathogenic traits of Gram-negative bacteria isolated
during ocular inflammation and infections. Clin Exp
Optom 1998;81(2):56-62.
5. Willcox MDP, Hume EB. Differences in the patho-
genesis of bacteria isolated from contact-lens-induced
infiltrative conditions. Aust N Z J Ophthalmol 1999;
27(3/4):231-3.
6. Sankaridurg PR, Vuppala N, Sreedharan A, et al.
Gram-negative bacteria and contact lens induced acute
red eye. Indian J Ophthalmol 1996;44(1):29-32.
7. Holden BA, La Hood D, Grant T, et al. Gram-nega-
tive bacteria can induce contact lens related acute red
eye (CLARE) responses. CLAO J 1996;22(1):47-52.
8. Willcox MDP, Thakur A, Holden BA. Some potential
pathogenic traits of Gram-negative bacteria isolated
during ocular inflammation and infections. Clin Exper
Optom 1998;81(2):56-62.
9. Sankaridurg PR, Willcox MDP, Sharma S, et al.
Haemophilus influenzae adherent to contact lenses
associated with production of acute ocular inflamma-
tion. J Clin Microbiol 1996;34(10):2426-31.
10. Sweeney DF, Grant T, Chong MS, et al.
Recurrence of acute inflammatory conditions with
hydrogel extended wear. Invest Ophthalmol Vis Sci
1993;34:Abstract 1008.
11. Sweeney DF, Stern J, Naduvilath T, Holden BA.
Inflammatory adverse event rates over 3 years with sil-
icone hydrogel lenses. Invest Ophthalmol Vis Sci
2002;43:E-Abstract 976.
 ®
CORNEA
MICROCORNEA tion in which the entire eye, rather ist. Patients with microcornea require
than just the cornea, is smaller than ongoing care, as the likelihood to
Signs and Symptoms normal. This may result from arrest at develop angle closure glaucoma
Microcornea may present in various stages of fetal developmental increases with age.10
patients of either gender and at any and is far more significant than
age; however, since it represents a microcornea in terms of visual health. Clinical Pearls
congenital condition, it is typically Most cases of microphthalmos have • Remember that microcornea may
detected during childhood. The con- pronounced hypermetropia and be associated with a host of hereditary
dition may be unilateral or bilateral. greater risk of glaucoma. Some cases conditions. Upon diagnosing a child
In clinical terms, microcornea is demonstrate extreme deformation of with microcornea (or microphthal-
defined as a horizontal corneal diam- the eye. mos), it is important to refer the
eter of less than 11 mm in an other- patient for comprehensive medical
wise normal-sized eye.1,2 In some Management testing. Pedigree analysis and genetic
cases, the cornea may be as small as 4 Appropriate management for counseling may be indicated.
mm.3 Isolated cases of microcornea microcornea begins with a compre- • Microcornea may have a signifi-
often present with normal visual acu- hensive evaluation and education. cant impact on cosmesis. In order to
ity, though many more cases may Realize that in unilateral cases, refrac- restore a more “normal” looking
demonstrate oculosystemic complica- tive error may be substantially differ- appearance, consider having your
tions: for example, Ehlers-Danlos ent between the eyes, and hence patient fitted with opaque cosmetic
syndrome, Waardenburg’s craniofa- amblyopiagenic. Refractive correc- contact lenses. These are particularly
cial syndrome, Norrie syndrome, tion should be issued as early as pos- helpful for individuals with unilateral
Turner’s syndrome and congenital sible to decrease the likelihood of microcornea. Remember, however,
rubella.4-7 Such cases may present amblyopia. Also, polycarbonate lens- that the corneas of these patients may
with congenital cataract, glaucoma, es should be prescribed if there is any be significantly flatter or steeper than
colobomas or retinal anomalies that significant difference in functional average, so a custom lens design is
significantly compromise vision. visual acuity between the eyes. often required.
Patients with microcornea are also • Most patients with unilateral
at greater risk for developing sec- microphthalmos are poor candi-
ondary glaucomas, and this risk dates for cosmetic contact lenses;
may increase as the patient ages.8,9 however, they may achieve similar
cosmetic improvement with a scle-
Pathophysiology ral shell (ocular prosthesis). This is
Microcornea is believed to result fit over the existing eye and can be
from an arrest in corneal develop- worn like a scleral contact lens,
ment after the fifth month of fetal provided the eye has limited or no
growth.10 The condition can be a functional acuity.
feature of any number of ocular or
oculosystemic syndromes, or it Microcornea. 1. Jamieson RV, Munier F, Balmer A, et al. Pulverulent
may occur as an isolated defect. cataract with variably associated microcornea and iris
Microcornea with cataract has been Evaluation of the anterior chamber coloboma in a MAF mutation family. Br J Ophthalmol
2003;87(4):411-2.
identified as a unique syndrome, is critical in patients with microcornea
2. Rufer F, Schroder A, Erb C. White-to-white corneal
associated with a genetic defect for to accurately diagnose the condition diameter: normal values in healthy humans obtained
transcription factor MAF, a proto- and rule out anterior chamber cleav- with the Orbscan II topography system. Cornea
oncogene sometimes associated with age syndromes. Most critically, 2005;24(3):259-61.

multiple myeloma.1,11 More com- tonometry must be performed on all
monly, microcornea occurs in associ- such patients to rule out glaucoma,
ation with conditions such as Peter’s and IOP-lowering agents should be
anomaly or sclerocornea.12 initiated in those who have ocular
Microcornea must be differentiat- hypertension. Of course, congenital
ed from microphthalmos, also glaucomas often require more invasive
referred to as nanophthalmos. therapy, and these patients are likely
Microphthalmos describes a condi- best managed by a glaucoma special-
3. Dinno ND, Lawwill T, Leggett AE, et al. Bilateral
microcornea, coloboma, short stature and other skele-
tal anomalies—a new hereditary syndrome. Birth
Defects Orig Artic Ser 1976;12(6):109-14.
4. Durham DG. Cutis hyperelastica (Ehlers-Danlos
syndrome) with blue sclera, microcornea, and glauco-
ma. Arch Ophthalmol 1953;49(2):220-1.
5. Goldberg MF. Waardenburg’s syndrome with fundus
and other anomalies. Arch Ophthalmol 1966;
76(6):797-810.

MARCH 15, 2006 REVIEW OF OPTOMETRY 23A

 6. Lessell S, Forbes AP. Eye signs in Turner’s syn-
drome. Arch Ophthalmol 1966;76(2):211-3.
7. Boniuk V. Systemic and ocular manifestations of
the rubella syndrome. Int Ophthalmol Clin 1972;
12(2):67-76.
8. Wallace DK, Plager DA. Corneal diameter in child-
hood aphakic glaucoma. J Pediatr Ophthalmol Strabis
1996;33(5):230-4.
9. Sugar HS. Oculodentodigital dysplasia syndrome
with angle-closure glaucoma. Am J Ophthalmol
1978;86(1):36-8.
10. Townsend WM. Congenital anomalies of the
cornea. In: Kaufman HE, Barron BA, McDonald MB,
eds. The Cornea. Boston: Butterworth-Heinemann,
1998, pp. 365-89.
11. Chesi M, Bergsagel PL, Shonukan OO, et al.
Frequent dysregulation of the c-maf proto-oncogene
at 16q23 by translocation to an Ig locus in multiple
myeloma. Blood 1998;91(12):4457-63.
12. Salmon JF, Wallis CE, Murray AD. Variable
expressivity of autosomal dominant microcornea
with cataract. Arch Ophthalmol 1988;106:505-10.
CORNEAL LACERATION
Signs and Symptoms
Any person experiencing direct
ocular or corneal trauma can poten-
tially develop a corneal laceration.
Typically, the injury comes from a
metallic object such as a hand tool.
However, a myriad of possible trau-
mas could potentially result in a
corneal laceration, with some insults
seeming rather mild.1-9 The initial
presenting symptom is intense pain,
which will often diminish when
corneal desensitization sets in second-
ary to nerve damage. Patients are
photophobic and will tear profusely.
There will be an attendant uveitis.
The anterior chamber is shallow or
even flat in a full-thickness laceration.
Ocular hypotony is common unless
the wound self seals. Bubbles within
the anterior chamber are a key find-
ing that indicates a breach in the
cornea’s integrity. There is usually sig-
nificantly reduced visual acuity.4,7,8
Other associated findings may
include lens dislocation, iridodialysis,
iris prolapse, vitreous hemorrhage
and hyphema.1,4-7 Occasionally,
corneal laceration will allow for
intraocular introduction of an exter-
24A REVIEW OF OPTOMETRY MARCH 15, 2006
nal pathogen with infectious keratitis
or endophthalmitis ensuing.10-13
Pathophysiology
Corneal laceration results from
direct trauma to the cornea, typically
from a hard object impacting with
sufficient force. There may be either
a full- or partial-thickness laceration.
A full-thickness laceration is termed
Full-thickness corneal laceration secondary to
injury with a screwdriver. Note the bubbles in the
anterior chamber.
a penetrating injury. In full-thickness
non-sealing lacerations, there will be
a flat chamber. Seidel’s sign will be
present: As fluorescein is added,
aqueous will diffuse from the wound
amid the fluorescein. There may also
be bubbles in the anterior chamber.
Damage to the iris may result in an
irregularly shaped, unreactive pupil,
or even extrusion of uveal tissue.
Management
The diagnosis of corneal lacera-
tion must be made as quickly as pos-
sible with as little intervention as
possible. Additionally, a partial-
thickness laceration must be differ-
entiated from a full-thickness lacera-
tion via Seidel’s test. Intraocular
pressure measurement should be
avoided when a full-thickness lacera-
tion is suspected, as pressure applied
to the globe may cause uveal tissue
to extrude through the wound. Any
other examination technique that
involves pressure to the globe, such
as gonioscopy or ocular ultrasonog-
raphy, should also be avoided. Visual
acuity should be taken, or at least
attempted. Judicious use of a topical
anesthetic will alleviate patient dis-
comfort and allow the clinician to
make an appropriate diagnosis.
Open a fresh bottle of the anesthetic
to avoid intraocular contamination.
An eye with a full-thickness lacer-
ation should not be manipulated
unnecessarily. Pressure patching of
the eye is contraindicated. Several
brands of soft contact lenses have
been used successfully as bandages
for patients with corneal perfora-
tions.14,15 However, attempting to
insert a lens in a blepharospastic
patient may cause further damage,
so this option should be exercised
judiciously, if at all. An eye shield
should be used to protect the eye.
Immediately arrange for the corneal
laceration to be surgically repaired
by a specialist. Instruct the patient
not to eat or drink before the surgi-
cal consultation.
Patients with poor initial acuity,
significant hyphema, uveal prolapse,
lens damage, vitreous hemorrhage
and longer laceration length tend to
have the poorest prognosis, and these
cases often result in enucleation.
Those without such associated fac-
tors may fare rather well following
surgery.8
Patients with corneal lacerations
have several surgical options. There
exists a number of suturing tech-
niques capable of reapposing the
corneal edges with a watertight
bond.1-4,16 Viable alternatives to con-
ventional sutures include various tis-
sue adhesives and glues, as well as
amniotic membrane transplantation,
which can also form a watertight
bond while the cornea heals.17-23
Corneal suturing will frequently
produce high amounts of astigma-
tism; however, the cornea appears to
have a topographic memory, with
reduction of the astigmatism follow-
ing suture removal.24

Clinical Pearls
• With a corneal laceration, the
patient frequently is tearing too heav-
ily for the Seidel test to be performed
accurately. In such cases, a shallow or
flat anterior chamber or the presence
of bubbles within the anterior cham-
ber indicate a breach in the corneal
integrity.
• Advise the patient that the initial
entering acuity may represent the best
vision that the patient can expect to
achieve after surgical repair. Of
course, vision may improve after sur-
gical repair; however, it is best not to
elevate a patient’s expectations.
• If a medical eye shield is not
available, simply taping a paper or
Styrofoam cup over the patient’s
orbital area will provide a measure of
protection until the patient reaches a
surgeon’s office.
• Despite the seeming severity of
the injury and the potential for ocular
morbidity, it is crucial to perform a
calm, thorough and systematic evalu-
ation so that the proper management
plan can be implemented.
1. Muller L, Kohnen T. Scleral and corneal laceration
with iris prolapse caused by an eagle claw. Graefes
Arch Clin Exp Ophthalmol 2005;243(4):377-9.
2. Hamill MB. Corneal and scleral trauma. Ophthalmol
Clin North Am 2002;15(2):185-94.
3. Cosar CB, Rapuano CJ, Cohen EJ. Corneal lacera-
tion and intraocular foreign body in a post-LASIK eye.
Cornea 2002;21(2):234-6.
4. Jeng BH, Steinemann TL, Henry P, et al. Severe
penetrating ocular injury from ninja stars in two chil-
dren. Ophthalmic Surg Lasers 2001;32(4):336-7.
5. Young AL, Cheng LL, Rao SK, et al. Corneal lacera-
tion with total but isolated aniridia caused by a pecking
injury. J Cataract Refract Surg 2000;26(9):1419-21.
6. Tsuda Y, Wakiyama H, Ameniya T. Ocular injury
caused by an air bag for a driver wearing eyeglasses.
Jpn J Ophthalmol 1999;43(3):239-40.
7. Taneja S. Arora R, Yadava U. Fingernail trauma
causing corneal laceration and intraocular cilia. Arch
Ophthalmol 1998;116(4):530-1.
8. Barr CC. Prognostic factors in corneoscleral lacera-
tions. Arch Ophthalmol 1983;101(6):919-24.
9. Alfaro DV 3rd, Jablon EP, Rodriguez FM, et al.
Fishing-related ocular trauma. Am J Ophthalmol
2005;139(3):488-92.
10. Sharma S, Saffra NA, Chapnick EK. Post traumat-
ic polymicrobial endophthalmitis, including Neisseria
subflava. Am J Ophthalmol 2003;136(3):554-5.
11. Iver MN, Kranias G, Daun ME. Post-traumatic
endophthalmitis involving Clostridium tetani and
Bacillus spp. Am J Ophthalmol 2001;132(1):116-7.
12. Ryan EH Jr, Cameron JD, Carpel E. Intraocular
molluscum contagiosum after a corneoscleral lacera-
tion. Am J Ophthalmol 1997;124(4):560-1.
13. Ho AC, Rapuano CJ. Pasteurella multocida kerati-
tis and corneal laceration from a cat scratch.
®
CORNEA
Ophthalmic Surg 1993;24(5):346-8
14. Kanpolat A, Ucakhan OO. Therapeutic use of
Focus Night & Day contact lenses. Cornea 2003;
22(8):726-34.
15. Lim L, Tan DT, Chan WK. Therapeutic use of
Bausch & Lomb PureVision contact lenses. CLAO J
2001;27(4):179-85.
16. Akkin C, Kayikcioglu O, Erakgun T. A novel suture
technique in stellate corneal lacerations. Ophthalmic
Surg Lasers 2001;32(5):436-7.
17. Velazquez AJ, Carnahan MA, Kristinsson J, et al.
New dendritic adhesives for sutureless ophthalmic sur-
gical procedures: In vitro studies of corneal laceration
repair. Arch Ophthalmol 2004;122(6):867-70.
18. Skorpik C, Gnad HD, Paroussis P. Cyanoacrylate
tissue gluing in corneal perforations. Wien Klin
Wochenschr 1986;98(9):276-9.
19. Chan SM, Boisjoly H. Advances in the use of adhe-
sives in ophthalmology. Curr Opin Ophthalmol 2004;
15(4):305-10.
20. Alio JL, Mulet ME, Cotlear D, et al. Evaluation of
a new bioadhesive copolymer (ADAL) to seal corneal
incisions. Cornea 2004;23(2):180-9.
21. Sharma A, Kaur R, Kumar S, et al. Fibrin glue ver-
sus N-butyl-2-cyanoacrylate in corneal perforations.
Ophthalmol 2003;110(2):291-8.
22. Duchesne B, Tahi H, Galand A. Use of human fib-
rin glue and amniotic membrane transplant in corneal
perforation. Cornea 2001;20(2):230-2.
23. Datta H, Sarkar K, Chatterjee PR. Amniotic mem-
brane transplantation in ocular surface disorders. J
Indian Med Assoc 2004;102(12):726-9.
24. Navon SE. Topography after repair of full-thickness
corneal laceration. J Cataract Refract Surg 1997;
23(4):495-501.

FOURTH-GENERATION FLUOROQUINOLONES AND BACTERIAL KERATITIS

Bacterial keratitis is a potentially sight-threatening con-
dition that demands urgent and aggressive management.
Prior to 1993, the treatment regimen for bacterial corneal
ulcers consisted of fortified antibiotics—typically
tobramycin and/or cefazolin—every 30 to 60 minutes for
the first 24 hours, and then tapered slowly to q.i.d. over the
course of two weeks. With the introduction of Ciloxan®
(ciprofloxacin 0.3% solution, Alcon) and later Ocuflox®
(ofloxacin 0.3% solution, Allergan) in the mid-90s however,
this paradigm shifted. Physicians began to recognize that
commercially available fluoroquinolones were equally effi-
cacious in managing bacterial keratitis. Furthermore, stud-
ies confirmed this.1,2 The widespread availability of fluoro-
quinolones altered the management of this disorder in other
ways, too. It shifted treatment of bacterial keratitis away
from corneal specialists and into the hands of general eye-
care providers, including optometrists. Moreover, it
increased the tendency for practitioners to employ empiric
therapy in this disorder, and it diminished the frequency of
routine culturing of corneal ulcers.3,4
Between 1995 and 2000, the early-generation fluoro-
quinolones Ciloxan® and Ocuflox® rapidly became the stan-
dard of care for bacterial keratitis. But the introduction of
newer antibiotics has again caused controversy within the
ophthalmic community. In 2003, Vigamox® (moxifloxacin
0.5%, Alcon) and Zymar® (gatifloxacin 0.3%, Allergan) both
received FDA approval. Though they are indicated only for
bacterial conjunctivitis, practitioners soon realized that these
powerful “fourth-generation” fluoroquinolones offered dis-
tinct advantages over the gold-standard Ciloxan® and
Ocuflox®. Specifically, Vigamox® and Zymar® boast expanded
coverage (particularly against Gram-positive organisms) and

MARCH 15, 2006 REVIEW OF OPTOMETRY 25A

 a purportedly lower likelihood of precipitating bacterial
resistance. Many began to speculate that the fourth-genera-
tion fluoroquinolones might be useful—even preferable—in
managing bacterial keratitis.
It is interesting to note that the
“standard of care” and FDA indica-
tions do not always coincide. While
neither of the fourth-generation fluo-
roquinolones is specifically approved
for the treatment of bacterial corneal
ulcers, practitioners are becoming
more comfortable with this applica-
tion. In fact, Vigamox® and Zymar®
are being prescribed for bacterial
keratitis with increasing frequency.
There have been numerous studies Culture-proven Pseudomonas keratitis successfully
demonstrating the efficacy of fourth- managed with Vigamox.
generation fluoroquinolones in exper-
imental keratitis,5-7 as well as several reports of successful response and resolution, starting with the titration to q.2.h.
use in clinical settings.8,9
So should fourth-generation fluoroquinolones be used
routinely for bacterial corneal ulcers? Certainly, many of us
feel that they are superior to other commercially available
options. Those who defend the continued use of older fluo-
roquinolones have a few central points to their argument.
First and foremost, some practitioners are concerned that,
by using newer drugs in an off-label capacity, they are some-
how violating the law—and hence are at risk for being sued
if a patient’s condition deteriorates. This argument, in our
opinion, is ill-conceived. While FDA guidelines suggest how
a drug may be prescribed in the treatment of a particular
disorder, they do not specifically preclude practitioners from Study Research Group. Arch Ophthalmol 1995;113(10):1257-65.
using the drug in other conditions, provided the application
is sound. For example, surgeons routinely use these same
antibiotics for pre- and post-surgical prophylaxis of the ocu- 4. McDonnell PJ. Empirical or culture-guided therapy for microbial keratitis? A plea
lar surface, yet this is not specifically an FDA-approved use
either. The more important questions one must ask are:
Does the decision make sense, and would a similarly
licensed practitioner in the same situation be likely to follow
the same course of action? This, by definition, is how the
standard of care is developed. If the answer to these ques-
tions is yes, then the standard of care has been met.
Another major concern of many practitioners is that there
® atitis. Antimicrob Agents Chemother 2004;48(6):1948-52.
is no sanctioned regimen relative to the use of Vigamox
and/or Zymar® in the management of bacterial keratitis. In
essence, doctors have said, “We would be happy to use
these drugs for corneal ulcers, but we don’t know how to
prescribe them.” This is certainly a legitimate concern, but
it is one that is easily dispelled. Some experts have sug-
26A REVIEW OF OPTOMETRY MARCH 15, 2006
gested that the new agents should be used in the same dose
and duration as those that are approved for bacterial kerati-
tis, i.e. Ciloxan® and Ocuflox®. That dosage is 1 to 2 drops
every 30 minutes while awake for
the first two days, with 1 to 2
drops instilled during the night.
Thereafter, the dosage is hourly
while awake for up to seven days
and q.i.d. for another three to five
days. It is not a requirement to
treat every ulcer with this regi-
men; instead, one may induct a
loading dose of 1 to 2 drops in
the office, followed by 1 drop
hourly while awake and once or
twice overnight. From day two
through seven the dosage may be
tapered according to the lesion’s
and ultimately diminishing to q.i.d. Topical antibiotics
should never have a dosage of less than q.i.d. In most cases,
treatment can be discontinued after 7 to 10 days.
The arguments against using fourth-generation fluoro-
quinolones are growing less defensible, and the support for
their use in cases of bacterial keratitis is growing. It is time
to embrace the future.
1. Hyndiuk RA, Eiferman RA, Caldwell DR, et al. Comparison of ciprofloxacin oph-
thalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal
ulcers. Ophthalmol 1996;103(11):1854-62.
2. O’Brien TP, Maguire MG, Fink NE, et al. Efficacy of ofloxacin vs. cefazolin and
tobramycin in the therapy for bacterial keratitis: Report from the Bacterial Keratitis
3. McLeod SD, Kolahdouz-Isfahani A, Rostamian K, et al. The role of smears, cul-
tures, and antibiotic sensitivity testing in the management of suspected infectious
keratitis. Ophthalmol 1996;103(1):23-8.
for data. Arch Ophthalmol 1996;114(1):84-7.
5. Aliprandis E, Ciralsky J, Lai H, et al. Comparative efficacy of topical moxifloxacin
versus ciprofloxacin and vancomycin in the treatment of P. aeruginosa and
ciprofloxacin-resistant MRSA keratitis in rabbits. Cornea 2005;24(2):201-5.
6. Thibodeaux BA, Dajcs JJ, Caballero AR, et al. Quantitative comparison of fluo-
roquinolone therapies of experimental gram-negative bacterial keratitis. Curr Eye
Res 2004;28(5):337-42.
7. Dajcs JJ, Thibodeaux BA, Marquart ME, et al. Effectiveness of ciprofloxacin, lev-
ofloxacin, or moxifloxacin for treatment of experimental Staphylococcus aureus ker-
8. Successful treatment of a Pseudomonas aeruginosa corneal ulcer in a human
patient with moxifloxacin 0.5%. Presented at the 22nd Congress of the European
Society of Cataract and Refractive Surgeons, Paris, France, September 2004.
9. Calderón D, Kabat AG, Schinas Z, Corella CW. Successful management of a cen-
tral bacterial corneal ulcer with topical moxifloxacin and the importance of con-
current corticosteroid use. Poster presented at the 108th Congress of the American
Optometric Association, Dallas, TX, June 2005.
UVEA AND GLAUCOMA
CHOROIDAL FOLDS
Signs and Symptoms
Choroidal folds can occur in any
patient regardless of age, race or gender.
Patients may be asymptomatic, though
many will report visual acuity reduc-
tion. Hyperopia is frequently present
and a number of patients will manifest
an increase in hyperopia coincident
with the development of choroidal
folds.1-4 The condition may be unilat-
eral or bilateral. When it is unilateral,
proptosis is often present.2 Numerous
conditions are associated with the
development of choroidal folds,
including acquired hyperopia,1-4 orbital
and sellar tumors,5-9 orbital cysts,10
papilledema,11 increased intracranial
pressure (with and without papillede-
ma) in intracranial mass lesions and
pseudotumor cerebri,12 hypotony
(often occurring post-surgically),13-16
choroidal neovascularization,17 macu-
lar degeneration,17 scleritis and other
inflammatory conditions,18 disc drusen
and disc congestion,19 sinusitis,20 dia-
betic retinopathy,21 Grave’s disease22
and cavernous sinus fistula,23 to name a
few. However, the majority of
choroidal folds occur idiopathically.
Ophthalmoscopically, choroidal folds
appear as dark and light striations across
the posterior pole of the fundus. They
can be oriented horizontally or vertical-
ly and are usually arranged in parallel.
Their appearance may be enhanced
with a red-free filter, and can be well
delineated using either fluorescein or
indocyanine green angiography.24
Pathophysiology
Choroidal folds are not a diagnosis;
they are merely a finding that may occur
either idiopathically or as a sign of asso-
ciated ocular disease. Thus, choroidal
folds must be investigated in every
patient in order to determine the precip-
itating cause. Choroidal folds are likely
to develop in association with any intra-
or extraocular process that induces suffi-
cient compressive stress within the
choroid, Bruch’s membrane and retina
to force these tissues to buckle.25
Virtually any ocular surgery (or trau-
ma) that pierces the globe can cause
choroidal folds. Hypotony secondary to
an open globe, combined with loss of
ocular contents (aqueous, vitreous, lens)
is thought to be a cause of choroidal
folds.17 Hypotony (as well as extraocu-
lar compression) can cause deformation
Horizontally radiating choroidal folds from a
retrobulbar mass.
of the sclera, especially when combined
with choroidal thickening. Folds in
Bruch’s membrane can occur due a
redundancy of tissue. Scleral shrinkage
from prolonged inflammation can also
result in choroidal folds.17 Overall, con-
gestion of the choroid seems to be a
strong precipitating factor for choroidal
fold development.17
Most cases of high hyperopia do not
show choroidal folds. Choroidal folds
typically occur in cases where hyperopia
is acquired (the globe is foreshortened,
such as from a retro-orbital mass). There
exists a well-known benign condition
involving acquired hyperopia and
choroidal folds, in which there is a flat-
tening of the posterior pole (demon-
strated with orbital ultrasound), variable
enlargement of the optic nerve, a dis-
cernible space between the optic nerve
and nerve sheath (as seen on MRI), dis-
tension of the perioptic subarachnoid
space and scleral shortening with
choroidal congestive thickening.1, 3, 4, 17
Management
While the majority of choroidal folds
occur idiopathically, this is a diagnosis of
exclusion. Unilateral choroidal folds are
often associated with a higher frequency
of orbital disease (such as retrobulbar
mass lesions) than bilateral presenta-
®
UVEA AND GLAUCOMA
tions.26 Complete ocular evaluation to
ascertain a cause is mandatory.
Tonometry will identify ocular
hypotony. Exophthalmometry will iden-
tify proptosis. Optical coherence
tomography (OCT) will identify and
differentiate choroidal folds from an
epiretinal membrane. Echography or
neuroimaging will identify retrobulbar
mass lesions.27 MRI of the brain, orbits
and chiasm and sinuses will examine for
mass lesions, sinusitis as well as enlarge-
ment of the optic nerve. Discernible
space between the optic nerve and nerve
sheath is associated with the benign syn-
drome of acquired hyperopia.
Clinical Pearls
• Most cases of choroidal folds are
idiopathic.
• Idiopathic choroidal folds are a
diagnosis of exclusion. A thorough
evaluation is required before making
this diagnosis.
• Unilateral choroidal folds are more
likely to be associated with ocular
pathology than bilateral cases.
• High hyperopia is much less likely
to be a cause of choroidal folds than
moderate acquired hyperopia.
1. Dailey RA, Mills RP, Stimac GK, et al. The natural
history and CT appearance of acquired hyperopia with
choroidal folds. Ophthalmol 1986;93(10):1336-42.
2. Friberg TR, Grove AS Jr. Choroidal folds and refrac-
tive errors associated with orbital tumors. An analysis.
Arch Ophthalmol 1983;101(4):598-603.
3. Kalina RE, Mills RP. Acquired hyperopia with
choroidal folds. Ophthalmol 1980;87(1):44-50.
4. Murdoch D. Merriman M. Acquired hyperopia with
choroidal folds. Clin Experiment Ophthalmol
2002;30(4):292-4.
5. Lutz SC, Anderson SF, Wu CY, et al. Non-Hodgkin’s
orbital lymphoma. Optom Vis Sci 2001;78(9):639-45.
6. D’hermies F, Cherif N, Berges O, et al. Unusual pre-
septal location of an orbital cavernous hemangioma in
African patient. J Fr Ophthalmol 2000;23(6):631-4.
7. Soylev MF, Saatci O, Saatci I, et al. Choroidal folds
associated with a sellar mass. Int Ophthalmol 1996-
97;20(5):259-61.
8. Shields JA, Shields CL, Rashid RC.
Clinicopathologic correlation of choroidal folds:
Secondary to massive cranioorbital hemangiopericy-
toma. Ophthal Plast Reconstr Surg 1992;8(1):62-8.
9. Steuhl KP, Richard G, Weidle EG. Clinical observa-
tions concerning choroidal folds. Ophthalmologica
1985;190(4):219-24.
10. Amrith S, Baratham G, Khoo CY, et al.
Spontaneous hematic cysts of the orbit presenting
with acute proptosis. A report of three cases. Ophthal
Plast Reconstr Surg 1990;6(4):273-7.
11. Cassidy LM, Sanders MD. Choroidal folds and papil-
loedema. Br J Ophthalmol 1999;83(10):1139-43.
12. Griebel SR, Kosmorsky GS. Choroidal folds
MARCH 15, 2006 REVIEW OF OPTOMETRY 27A
 associated with increased intracranial pressure. Am J
Ophthalmol 2000;129(4):513-6.
13. Kokame GT, deLeon MD, Tanji T. Serous retinal
detachment and cystoid macular edema in hypotony
maculopathy. Am J Ophthalmol 2001;131(3):384-6.
14. Akova YA, Dursun D. Aydin P, et al. Management
of hypotony maculopathy and a large filtering bleb
after trabeculectomy with mitomycin C: Success with
argon laser therapy. Ophthalmic Surg Lasers
2000;31(6):491-4.
15. Fannin LA, Schiffman JC, Budenz DL. Risk fac-
tors for hypotony maculopathy. Ophthalmol 2003;
110(6):1185-91.
16. Ichibe M, Yoshizawa T, Funaki S, et al. Severe
hypotony after macular translocation surgery with
360-degree retinotomy. Am J Ophthalmol 2002;
134(1):139-41.
17. Jaworshi A. Wolffsohn JS, Napper GA. Aetiology
and management of choroidal folds. Clin Exp Optom
1999;82(5):169-76.
18. Biswas J, Mittal S, Ganesh SK, et al. Posterior
scleritis: Clinical profile and imaging characteristics.
Ind J Ophthalmol 1998;46(4):195-202.
19. Sarraf D. Schwartz SD. Bilateral choroidal folds
and optic neuropathy: a variant of the crowded disk
syndrome? Ophthalmol 2003;110(5):1047-52.
20. Mansour AM, Salti H, Uwaydat S, et al. Ethmoid
sinus osteoma presenting as epiphora and orbital cel-
lulitis: Case report and literature review. Surv
Ophthalmol 1999;43(5):413-26.
21. Fagundez VMA, Jimenez PR, Bermudez UL.
Choroidal folds in diabetic retinopathy. Arch Soc Esp
Oftalmol 2000;75(12):797-802.
22. Kowal L, Georgievski Z. Choroidal folds in Graves’
ophthalmopathy. Aust NZ J Ophthalmol 1994;22(3):216.
23. Gonshor LG, Kline LB. Choroidal folds and dural
cavernous sinus fistula. Arch Ophthalmol
1991;109(8):1065-6.
24. Haruyama M, Yuzawa M, Kawamura A, et al.
Indocyanine green angiographic findings of chorioreti-
nal folds. Jpn J Ophthalmol 2001;45(3):293-300.
25. Friberg TR. The etiology of choroidal folds. A bio-
mechanical explanation. Graefes Arch Clin Exp
Ophthalmol 1989;227(5):459-64.
26. Leahey AB, Bruckner AJ, Wyszynski RE, et al.
Choroidal folds: a comparison of unilateral and bilat-
eral cases. Arch Ophthalmol 1993;111: 357-9.
27. Atta HR, Byrne SF. The findings of standardized
echography for choroidal folds. Arch Ophthalmol
1988;106(9):1234-41.
CHOROIDAL NEVUS &
CHOROIDAL MELANOMA
Signs and Symptoms
Choroidal nevi and choroidal
melanomas both represent space-occu-
pying masses of the uveal tract.
Choroidal nevi appear as round or
oval, flat or slightly elevated (1 mm or
less) lesions within the posterior fun-
dus; the margins are typically
detectable but indistinct.1 Nevi may
present in a variety of hues, but most
commonly they appear slate-blue or
greenish-gray.1 There may be overlying
areas of drusen noted as well.1,2 The
vast majority of choroidal nevi remain
28A REVIEW OF OPTOMETRY MARCH 15, 2006
less than two disc diameters (DD) or 3
mm.1 Larger nevi, particularly those
greater than 4 DD/6 mm, carry
increased suspicion of malignancy.3,4
Generally, patients with choroidal nevi
are asymptomatic, with the lesion
detected upon ophthalmoscopy.
Choroidal melanomas, in contrast
to nevi, appear as mottled, often dome-
shaped lesions of the ocular fundus.
Coloration varies widely, ranging from
complete amelanosis (white) to jet
black. Most commonly, lesions are a
non-uniform greenish-gray.4,5 There
may be significant elevation in some
cases. As they grow, melanomas may
break through Bruch’s membrane, tak-
ing on a mushroom-shaped appear-
ance. Serous retinal detachments are
commonly associated with this presen-
tation.4-6 Overlying orange pigmenta-
tion, known as lipofuscin, may also be
seen; this is considered by many to be a
pathognomonic sign of malignancy.7
Many patients with choroidal
melanomas are entirely asymptomatic;
in most cases, lesions are detected via
dilated, indirect ophthalmoscopy on
routine optometric visits. However,
larger lesions or those in close proximi-
ty to the macula may induce visual
symptoms that prompt the patient to
Amelanotic malignant melanoma.
seek attention. These symptoms may
include photopsia, visual field deficit,
metamorphopsia, or decreased acuity
secondary to subretinal fluid accumula-
tion and/or hyperopic refractive shift.4
The vast majority of patients with
choroidal melanoma are older than 50
years, though rarely the tumor may
occur in childhood.8,9 Race also plays a
significant role in the distribution of
choroidal melanoma. Caucasians are
perhaps three times more likely than
Asians to manifest choroidal mela-
noma10 and at least eight times more
likely than those of African descent.11,12
Not surprisingly, patients with light-
colored irides (blue or grey) also seem to
be at greater risk for developing uveal
melanomas.13 The presence of numer-
ous cutaneous nevi—particularly dys-
plastic nevi—is another risk factor.13,14
Pathophysiology
Choroidal nevi and melanomas are
both derived from uveal melanocytes.
In the mid-1960s, Naumann and asso-
ciates identified the four atypical cell
types inherent in choroidal nevi.15 In
order of prevalence, these include:
plump, polyhedral cells; slender spindle
cells; intermediate cells and balloon
cells.15 In contrast, melanomas are com-
prised of malignant melanocytes. The
Callendar classification system for
choroidal melanomas suggests that
there are also four types of cells in these
lesions: spindle A, spindle B, fascicular,
and epithelioid.16,17 In general, the pres-
ence of epithelioid cells within a mela-
noma heralds a poorer prognosis.18
There is some controversy regarding
the precise pathogenesis of melanomas.
It is believed that nevi may convert to
malignancy in a small percentage of
individuals; historically, the annual rate
of malignant transformation is about
one in 5,000 cases.19 A more recent
study suggests that the rate is lower,
perhaps one in 8,845 cases.20 Risk fac-
tors for malignant transformation of
nevi include diameter (>5 mm) thick-
ness (>1 mm), the presence of lipofus-
cin and serous retinal detachment.1
Ultraviolet (UV) radiation has also
been associated with the development
of ocular and non-ocular melanoma.4
However, the specific role of UV in the
development of choroidal melanoma is
uncertain. While some studies indicate
a causal relationship, others are less
conclusive.21-25 Current opinion sug-
gests that UV radiation may not be a
significant factor in the pathogenesis of
choroidal melanoma.

Management
While some choroidal nevi possess
the capacity for malignant growth, the
majority are completely benign and
require only periodic monitoring. Of
course, differentiating between a large,
atypical nevus and a small, choroidal
melanoma requires experience and
expertise. Ancillary procedures that may
facilitate an accurate diagnosis include
stereo photography, standardized ultra-
sonography, fluorescein angiography
and optical coherence tomography
(OCT).26 More invasive procedures,
including transvitreal fine needle aspira-
tion biopsy, are also sometimes used to
differentiate suspicious lesions.27
Patients who are diagnosed with
choroidal melanoma should be referred
for prompt medical evaluation by an
internist and/or an oncologist. Spe-
cifically, this is done to ascertain
whether there are any additional pri-
mary or metastatic malignancies pres-
ent. The systemic work-up should
include a thorough medical and family
history, physical examination and
directed laboratory evaluation.
Therapy for choroidal melanoma has
changed radically in the last 30 years.
Until the late 1970s, enucleation was
considered the only definitive treatment
and the best option for survival among
those with melanoma. In 1978, howev-
er, a pivotal paper by Zimmerman and
associates challenged conventional
thinking, suggesting that enucleation
might actually contribute to systemic
metastasis.28 This article and a subse-
quent publication29 provided the impe-
tus to develop alternative therapies for
choroidal melanoma, most notably
radiotherapy and tumor resection.
Today, therapy for choroidal
melanoma is dictated primarily by the
size of the lesion. The Collaborative
Ocular Melanoma Study (COMS)
defined tumors as small (5 to 16 mm in
basal diameter and 1.0 to 2.5 mm in
height), medium (<16 mm diameter
and 2.5 to 10.0 mm in height) or large
(>16 mm diameter and/or >10 mm in
height).30 Small tumors may be treated
by simple observation, but therapy is ini-
tiated if any sign of growth or visual
compromise is encountered. Focal laser
photocoagulation and, more recently,
transpupillary thermotherapy, have been
employed successfully for selected small
melanomas.31,32 For some small cho-
roidal melanomas and the majority of
medium-sized choroidal melanomas,
radiation remains the treatment of first
choice.31 Brachytherapy—in which a
plaque with embedded radioactive mate-
rial is temporarily sutured to the episcle-
ra overlying the tumor—is the most
common method today. Charged parti-
cle irradiation (also called external beam
irradiation) may also be employed for
certain tumors. Overall, the success rates
and complications (including radiation
retinopathy and cataract formation) for
plaque therapy and external beam thera-
py are similar. However, since external
beam irradiation does not require sur-
gery, it may be preferred in some cases.
Another treatment option for medium-
sized tumors is local resection using a
partial lamellar sclerouvectomy tech-
nique.33 This procedure, when success-
ful, offers significant advantages over
radiation therapy. However, the tech-
nique is quite challenging, even for the
most experienced surgeons, and carries
significant risks for vitreous hemorrhage,
retinal detachment and cataractogenesis.
Local resection of choroidal melanoma is
preferred for smaller, more anteriorly
located tumors.
Despite controversy over the proce-
dure, enucleation is still used for the
treatment of some large uveal
melanomas. Generally, enucleation is
reserved for advanced melanomas that:
a) occupy most of the intraocular space,
b) have induced a secondary glaucoma
or c) have invaded the optic nerve.
When enucleation is performed on an
eye with melanoma, care is taken not to
clamp the optic nerve or aggressively
handle the eye so as to reduce potential
tumor seeding and metastasis.31 For
advanced tumors that demonstrate
massive extrascleral extension into the
orbit and in which the eye is blind and
painful, eyelid-sparing orbital exentera-
tion is typically justified.34
®
UVEA AND GLAUCOMA
Clinical Pearls
• The etymology of the term
choroidal melanoma is somewhat
interesting. Historically, scientists
defined a non-malignant accumulation
of melanocytes— which we refer to
today as a choroidal nevus—as a
benign choroidal melanoma. As
recently as 1994, Alexander’s Primary
Care of the Posterior Segment (2nd
edition, McGraw-Hill) continued to
use this nomenclature. To avoid misin-
terpretation and unnecessary emotion-
al stress for patients, it is perhaps best to
use the terms “nevus” and “melanoma”
to refer to benign and malignant
choroidal lesions, respectively.
• While the majority of choroidal
melanomas occur in older, white
patients, bear in mind that younger
patients and those of African or Asian
descent are not immune.
• Choroidal melanoma presents a
potentially life-threatening situation
because of its propensity to metastasize.
The tumors have been known to
spread to numerous organs and sys-
tems including the liver, lungs, skin
and gastrointestinal tract. In addition
to ocular therapy, patients with newly
detected melanomas should be referred
for laboratory testing including hema-
tology, chest CT and liver function
studies, among others. The liver is a
particular area of interest, since it rep-
resents the primary site of metastasis
for uveal melanoma.4
• The COMS study, initiated in
1986, yielded some interesting results.
In one COMS trial, comparable sur-
vival rates were observed for individu-
als with medium-sized melanomas
undergoing radiotherapy vs. enucle-
ation.35 In another trial, pre-enucle-
ation radiotherapy for large tumors
did not appear to significantly alter the
rate of survival as compared to those
who underwent enucleation alone.36
These results have forced experts to
again ponder the issues raised by
Zimmerman in 1978; namely,
whether enucleation, as a treatment
option for choroidal melanoma, is a
better or worse option in the long run.
MARCH 15, 2006 REVIEW OF OPTOMETRY 29A
 1. Sumich P, Mitchell P, Wang JJ. Choroidal nevi in a
white population: The Blue Mountains Eye Study.
Arch Ophthalmol 1998;116(5):645-50.
2. Shields CL, Mashayekhi A, Materin MA, et al.
Optical coherence tomography of choroidal nevus in
120 patients. Retina 2005;25(3):243-52.
3. Butler P, Char DH, Zarbin M, et al. Natural history
of indeterminate pigmented choroidal tumors.
Ophthalmol 1994;101(4):710-6.
4. Char DH. Ocular melanoma. Surg Clin North Am
2003;83(2):253-74.
5. Ou JI, Wheeler SM, O’Brien JM. Posterior pole
tumor update. Ophthalmol Clin North Am 2002;
15(4):489-501.
6. Kalkman E, Baxter G. Melanoma. Clin Radiol
2004;59(4):313-26.
7. Shields JA, Shields CL, Donoso LA. Management of
posterior uveal melanoma. Surv Ophthalmol
1991;36(3):161-95.
8. Grin JM, Grant-Kels JM, Grin CM, et al. Ocular
melanomas and melanocytic lesions of the eye. J Am
Acad Dermatol 1998;38(5, Pt 1):716-30.
9. Stanford DG, Hart R, Thompson JF. Ocular
melanoma in childhood. Aust NZ J Surg
1993;63(9):729-31.
10. Biswas J, Krishnakumar S, Shanmugam MP.
Uveal melanoma in Asian Indians: A clinicopatholog-
ical study. Arch Ophthalmol 2002;120(4):522-3.
11. Egan KM, Seddon JM, Glynn RJ, et al.
Epidemiologic aspects of uveal melanoma. Surv
Ophthalmol 1988;32(4):239-51.
12. Neugut AI, Kizelnik-Freilich S, Ackerman C.
Black-white differences in risk for cutaneous, ocular
and visceral melanomas. Am J Public Health
1994;84(11):1828-9.
13. Vajdic CM, Kricker A, Giblin M, et al. Eye color
and cutaneous nevi predict risk of ocular melanoma in
Australia. Int J Cancer 2001;92(6):906-12.
14. Hammer H, Olah J, Toth-Molnar E. Dysplastic
nevi are a risk factor for uveal melanoma. Eur J
Ophthalmol 1996;6(4):472-4.
15. Naumann G, Yanoff M, Zimmerman LE.
Histogenesis of malignant melanomas of the uvea: I.
Histopathologic characteristics of nevi of the choroid
and ciliary body. Arch Ophthalmol 1966;76(6):784-96.
16. Callender GR. Malignant melanotic tumors of the
eye: A study of histologic types in 111 cases. Trans
Am Acad Ophthalmol Otolaryngol 1931;36:131-42.
17. McLean IW, Foster WD, Zimmerman LE, Gamel
JW. Modifications of Callender’s classification of uveal
melanoma at the Armed Forces Institute of Pathology.
Am J Ophthalmol 1983;96(4):502-9.
18. Augsburger JJ, Gonder JR, Amsel J, et al. Growth
rates and doubling times of posterior uveal
melanomas. Ophthalmol 1984;91(12):1709-15.
19. Ganley JP, Comstock GW. Benign nevi and malig-
nant melanomas of the choroid. Am J Ophthalmol
1973;76(1):19-25.
20. Singh AD, Kalyani P, Topham A. Estimating the
risk of malignant transformation of a choroidal nevus.
Ophthalmol 2005;112(10):1784-9.
21. Tucker MA, Shields JA, Hartge P, et al. Sunlight
exposure as risk factor for intraocular malignant
melanoma. N Engl J Med 1985;313(13):789-92.
22. Lutz JM, Cree IA, Foss AJE. Risk factors for
intraocular melanoma and occupational exposure. Br
J Ophthalmol 1999;83(10):1190-3.
23. Holly EA, Aston DA, Char DH, et al. Uveal
melanoma in relation to ultraviolet light exposure and
host factors. Cancer Res 1990;50(18):5773-7.
24. Seddon JM, Gragoudas ES, Glynn RJ, et al. Host
factors, UV radiation, and risk of uveal melanoma: A
30A REVIEW OF OPTOMETRY MARCH 15, 2006
case-control study. Arch Ophthalmol 1990;
108(9):1274-80.
of floaters. Visual acuity tends to be
25. Schwartz LH, Ferrand R, Boelle PY, et al. Lack of worse in children with pars planitis
correlation between the location of choroidal than in adults, both at time of diagno-
melanoma and ultraviolet-radiation dose distribution.
Radiat Res 1997;147(4):451-6. sis and at follow-up.9 In children, vitre-
26. Muscat S, Parks S, Kemp E, Keating D. Secondary ous hemorrhage also appears to be a
retinal changes associated with choroidal naevi and more common complication than in
melanomas documented by optical coherence tomog-
raphy. Br J Ophthalmol 2004;88(1):120-4. adults.10,11 Visual acuity ranges from
27. Augsburger JJ, Correa ZM, Schneider S, et al. 20/20 to no perception of light, with a
Diagnostic transvitreal fine-needle aspiration biopsy mean range of 20/40 to 20/50.12,13 Pars
of small melanocytic choroidal tumors in nevus versus
melanoma category. Trans Am Ophthalmol Soc planitis is typically bilateral, with both
2002;100:225-32. eyes affected in 85% of the cases in one
28. Zimmerman LE, McLean IW, Foster WD. Does
enucleation of the eye containing a malignant
report.12 This disease has a good prog-
melanoma prevent or accelerate the dissemination of nosis, with a final mean visual acuity of
tumour cells. Br J Ophthalmol 1978;62(6):420-5.
20/30 to 20/40 in 90% of cases.7,12,14
29. Zimmerman LE, McLean IW. An evaluation of
enucleation in the management of uveal melanomas. Vitritis is present in virtually all
Am J Ophthalmol 1979;87(6):741-60. patients with pars planitis.12 Vitritis may
30. Singh AD, Kivela T. The collaborative ocular cause subsequent vitreous degeneration,
melanoma study. Ophthalmol Clin North Am 2005;
18(1):129-42. with a resultant posterior vitreous
31. Shields CL, Shields JA. Recent developments in detachment (PVD). There will fre-
the management of choroidal melanoma. Curr Opin
Ophthalmol 2004;15(3):244-51.
quently be an accumulation of inflam-
32. Shields CL, Shields JA, Perez N, et al. Primary
matory exudates. This accumulation
transpupillary thermotherapy for small choroidal may be small (snowballs) or extensive
melanoma in 256 consecutive cases: outcomes and
limitations. Ophthalmol 2002;109(2):225-34.
33. Shields JA, Shields CL, Shah P, et al. Partial
lamellar sclerouvectomy for ciliary body and choroidal
tumors. Ophthalmol 1991;98(6):971-83.
34. Shields JA, Shields CL, Demirci H, et al.
Experience with eyelid-sparing orbital exenteration.
The 2000 Tullos O. Coston Lecture. Ophthal Plast
Reconstr Surg 2001;17(5):355-61.
35. Diener-West M, Earle JD, Fine SL, et al. The
COMS randomized trial of iodine 125 brachytherapy
for choroidal melanoma. III. Initial mortality findings.
COMS report no. 18. Arch Ophthalmol
2001;119(7):969-82.
36. Collaborative Ocular Melanoma Study Group. The Hazy fundus secondary to vitritis in pars plani-
Collaborative Ocular Melanoma Study (COMS) ran- tis. Cystoid macular edema is present.
domized trial of pre-enucleation radiation of large
choroidal melanoma. II. Initial mortality findings.
COMS report no. 10. Am J Ophthalmol
1998;125(6):779-96.
(snowbanks) and may occur anywhere
in the fundus. However, these inflam-
matory aggregates are typically regulat-
PARS PLANITIS ed by gravity to the inferior fundus.
There is also likely to be cataracts (espe-
Signs and Symptoms cially posterior subcapsular cataracts),
Pars planitis typically affects younger secondary glaucoma, retinal neovascu-
patients between 5 and 40 years.1 It has larization with vitreous hemorrhage
long been believed that patients with and tractional retinal detachment,
pars planitis have no significant associat- exudative retinal detachment, retinal
ed medical history and are otherwise vascular sheathing, papillitis and cys-
healthy. However, that concept appears toid macular edema (CME).7,10-12,14-19
to be incorrect, as pars planitis seems to While vitreous snowballs and snow-
have an association with Crohn’s disease, banks are frequently encountered, they
and especially multiple sclerosis (MS).2-8 are by no means present in every eye
Patients are frequently asympto- with pars planitis, and need not be
matic, but may present with modestly present to make this diagnosis.12,18,20
diminished vision that is slowly pro- CME and cataract are the most fre-
gressive. Typically, they will complain quently encountered visual complica-

tions in patients with pars plani-
tis.12,17,18
A detailed family history (or exami-
nation) may disclose other family
members with pars planitis. The genet-
ic predisposition of pars planitis is
unknown; however, the frequent
occurrence of this condition among
family members suggests that a com-
mon hereditary and/or environmental
factor contributes to the disease.21-25
Pathophysiology
Pars planitis is an idiopathic posteri-
or/intermediate uveitis.1 There are
exacerbations and remissions, and typ-
ically this disorder runs a very long
course. Inflammatory mediators will
increase vasopermeability of retinal
capillaries, resulting in posterior seg-
ment inflammatory cells and CME.
The chronic inflammation in pars
planitis appears to consist of helper T-
cells in the pars plana and the retinal
vasculature.24 Snowbanks consist of
posteriorly detached and collapsed vit-
reous with cellular proliferation from
the retina with non-pigmented ciliary
epithelium. Electron microscopy has
demonstrated the presence of fibrous
astrocytes and collagen. Vitreous snow-
balls consist of granulomatous inflam-
mation.19,26
Serologic evaluation of patients sug-
gests an immunogenic predisposition
to pars planitis. Several studies
attempting to identify frequencies of
human leukocyte antigen (HLA) class
II alleles with pars planitis have shown
a strong association with the HLA-
DR2 suballeles, -DR15, HLA-DR51
and HLA-DR17.8,14,24,27 A common
immunogenetic link between MS and
pars planitis may be associated with the
HLA-DR15 allele. This association
may represent genetic linkage to the
HLA-DR locus or a role for the HLA-
DR15 gene product in the pathogene-
sis of both diseases.14 The strong associ-
ation of pars planitis with HLA-DR2
and the temporal development of MS
in some patients with pars planitis fur-
ther supports an association between
pars planitis and MS.8
Management
Pars planitis generally has a favorable
outcome.6,7,12,13,14,17 Treatment should
be conservative, and it often involves
only periodic monitoring, especially if
vision is only minimally disturbed by
vitritis and CME.
If treatment is undertaken because of
vision loss from CME or vitreous cloud-
ing, then steroids form the cornerstone
Inferiorly located inflammatory exudate
("snowball") in pars planitis.
of management.7,12,17,18,28,29 Periocular,
intravitreal and systemic corticosteroids
and other immunosuppressive drugs
have been employed. However, once a
commitment to use systemic steroids is
made, they are typically used for
months. With this treatment comes the
possible attendant complications of
steroid-induced cataracts and glauco-
ma.30 Topical steroids are employed if
there is a concomitant anterior uveitis or
CME. However, in these cases, the ante-
rior chamber reaction is not a true ante-
rior uveitis, but a spillover from the pos-
terior uveitis. Topical non-steroidal
anti-inflammatory drugs (NSAIDs) for
CME remain a consideration.
In severe or unresponsive cases,
transscleral cryoretinopexy or thermal
laser photocoagulation can be directed
against the snowbanks to destroy the
inflamed areas along with the infil-
trates.15,30-33 These treatments can
reduce intraocular inflammation,
increase visual acuity and decrease
dependence upon systemic steroids.
Vitrectomy can also be used to clear the
vitreous of cells and hemorrhage.34
Due to the strong association of pars
planitis and MS, MRI testing for MS is
indicated as part of management. This is
®
UVEA AND GLAUCOMA
especially true for women between ages
20 and 40 years.6,7
Clinical Pearls
• PVD is rare in younger patients;
however, it is quite common in pars
planitis. Consider pars planitis when
encountering PVD in younger patients.
• Always consider pars planitis in
cases of asymptomatic vitreous cells in
healthy, younger patients.
• When suspecting pars planitis, care-
fully examine the inferior retina and vit-
reous for snowballs and snowbanking.
• Children with pars planitis are more
likely than adults to experience vitreous
hemorrhage. Pars planitis should be
considered in the differential diagnosis
of pediatric vitreous hemorrhage.
• Other conditions such as systemic
lupus erythematosus, sarcoidosis, and
syphilis can have findings similar to
pars planitis and remain among the dif-
ferential diagnoses.
1. Maris K, Van Calster J, Wouters C, et al. Clinical
symptoms and complications of pars planitis in child-
hood. Bull Soc Belge Ophtalmol 2005;295:29-33.
2. Gorrono-Echebarria MB, Albarran F, et al.
Inflammatory bowel disease (Crohn’s disease) in a
Spanish patient with pars plana exudates: Report of a
new case and review of the literature. Ocul Immunol
Inflamm 2002;10(1):65-8.
3. Rosenbaum JT, Kurz D. An old crone finds a new
home: Crohn’s disease and pars planitis. Ocul
Immunol Inflamm 2002;10(3):157-60.
4. Vidovic T, Cerovski B, Jukic T. The appearance of
pars planitis in multiple sclerosis. Coll Antropol
2005;29(1):203-6.
5. Soheilian M, Heidari K, Yazdani S, et al. Patterns
of uveitis in a tertiary eye care center in Iran. Ocul
Immunol Inflamm 2004;12(4):297-310.
6. Zein G, Berta A, Foster CS. Multiple sclerosis-asso-
ciated uveitis. Ocul Immunol Inflamm 2004;
12(2):137-42.
7. Prieto JF, Dios E, Gutierrez JM, et al. Pars planitis:
Epidemiology, treatment, and association with multiple
sclerosis. Ocul Immunol Inflamm 2001;9(2):93-102.
8. Malinowski SM, Pulido JS, Goeken NE, et al. The
association of HLA-B8, B51, DR2, and multiple scle-
rosis in pars planitis. Ophthalmol
1993;100(8):1199-1205.
9. Guest S, Funkhouser E, Lightman S. Pars planitis:
A comparison of childhood onset and adult onset dis-
ease. Clin Experiment Ophthalmol 2001;29(2):81-4.
10. Phillips WB 2nd, Bergren RL, McNamara JA. Pars
planitis presenting with vitreous hemorrhage.
Ophthalmic Surg 1993;24(9):630-1.
11. Lauer AK, Smith JR, Robertson JE, et al. Vitreous
hemorrhage is a common complication of pediatric
pars planitis. Ophthalmol 2002;109(1):95-8.
12. Arellanes-Garcia L, Navarro-Lopez L, Recillas-
Gispert C. Pars planitis in the Mexican Mestizo popu-
lation: Ocular findings, treatment, and visual out-
come. Ocul Immunol Inflamm 2003;11(1):53-60.
13. Malinowski SM, Pulido JS, Folk JC. Long-term
MARCH 15, 2006 REVIEW OF OPTOMETRY 31A
 visual outcome and complications associated with
pars planitis. Ophthalmol 1993;100(6):818-24.
14. Raja SC, Jabs DA, Dunn JP, et al. Pars planitis:
Clinical features and class II HLA associations.
Ophthalmol 1999;106(3):594-9.
15. Pollack AL, McDonald HR, Johnson RN, et al.
Peripheral retinoschisis and exudative retinal detach-
ment in pars planitis. Retina 2002;22(6):719-24.
16. Merayo-Lloves J, Power WJ, Rodriguez A, et al.
Secondary glaucoma in patients with uveitis.
Ophthalmologica 1999;213(5):300-4.
17. Ortega-Larrocea G, Arellanes-Garcia L. Pars plani-
tis: Epidemiology and clinical outcome in a large com-
munity hospital in Mexico City. Int Ophthalmol
1995;19(2):117-20.
18. Henderly DE, Genstler AJ, Rao NA, et al. Pars
planitis. Trans Ophthalmol Soc UK 1986;105(Pt
2):227-32.
19. Green WR, Kincaid MC, et al. Pars planitis. Trans
Ophthalmol Soc UK 1981;101(Pt 3):361-7.
20. Henderly DE, Haymond RS, Rao NA, et al. The
significance of the pars plana exudate in pars planitis.
Am J Ophthalmol 1987;103(5):669-71.
21. Tejada P, Sanz A, Criado D. Pars planitis in a fam-
ily. Int Ophthalmol 1994;18(2):111-3.
22. Biswas J, Raghavendran SR, Vijaya R.
Intermediate uveitis of pars planitis type in identical
twins. Report of a case. Int Ophthalmol 1998;
22(5):275-7.
23. Duinkerke-Eerola KU, Pinckers A, Cruysberg JR.
Pars planitis in father and son. Ophthalmic Pediatr
Genet 1990;11(4):305-8.
24. Wetzig RP, Chan CC, Nussenblatt RB, et al.
Clinical and immunopathological studies of pars plani-
tis in a family. Br J Ophthalmol 1988;72(1):5-10.
25. Culbertson WW, Giles CL, West C, et al. Familial
pars planitis. Retina 1983;3(3):179-81.
26. Abu El-Asrar AM, Geboes K. .An immunohisto-
chemical study of the “snowbank” in a case of pars
planitis. Ocul Immunol Inflamm 2002;10(2):117-23.
27. Oruc S, Duffy BF, Mohanakumar T, et al. The
association of HLA class II with pars planitis. Am J
Ophthalmol 2001;131(5):657-9.
28. Benitez Del Castillo Sanchez JM, Garcia Sanchez
J. Intravitreal injection of triamcinolone acetonide in
non infectious uveitis. Arch Soc Esp Oftalmol
2001;76(11):661-4.
29. Duguid IG, Ford RL, Horgan SE, et al. Combined
orbital floor betamethasone and depot methylpred-
nisolone in uveitis. Ocul Immunol Inflamm
2005;13(1):19-24.
30. Ermakova NA. Preference for transscleral cryoco-
agulation of peripheral exudate in intermediate uveitis
before traditional methods of treatment. Vestn
Oftalmol 2002;118(6):29-31.
31. Pulido JS, Mieler WF, Walton D. Results of periph-
eral laser photocoagulation in pars planitis. Trans Am
Ophthalmol Soc 1998;96:127-37.
32. Verma L, Kumar A, Garg S, et al. Cryopexy in pars
planitis. Can J Ophthalmol 1991;26(6):313-5.
33. Okinami S, Sunakawa M, Arai I, et al. Treatment
of pars planitis with cryotherapy. Ophthalmologica
1991;202(4):180-6.
34. Potter MJ, Myckatyn SO, Maberley AL, et al.
Vitrectomy for pars planitis complicated by vitreous
hemorrhage: Visual outcome and long-term follow-up.
Am J Ophthalmol 2001;131(4):514-5.
ACUTE ANGLE CLOSURE
GLAUCOMA
Signs and Symptoms
While any person can experience
32A REVIEW OF OPTOMETRY MARCH 15, 2006
acute angle closure glaucoma (AACG),
this condition is most common in
patients of Asian descent.1-6 Patients are
also likely to be older, hyperopic and
female.2-8 The etiology of angle closure
in young individuals differs from the
older population and is typically associ-
ated with structural and developmental
anomalies.9
Patients with AACG typically mani-
fest the signs and symptoms of ocular
and facial pain, unilateral blurring of
vision, photopsia in the form of colored
haloes around lights and occasionally
nausea and vomiting. Acuity may be
reduced significantly in the involved eye,
often to 20/80 or worse.6,10,11 AACG is
frequently unilateral but may be bilater-
al and, as a rule, should always be con-
sidered to have bilateral potential.2,3
The hallmark signs of AACG
include significantly elevated intraocu-
lar pressure (IOP), a closed angle upon
gonioscopic evaluation, deep conjunc-
tival and episcleral injection in a cir-
cumlimbal fashion and a fixed, mid-
dilated pupil. Biomicroscopically, there
will commonly be an edematous or
“steamy” cornea and shallow anterior
chamber. There actually may be a flat
anterior chamber or a significant iris
bombé, depending upon the mecha-
nism of angle closure.
Applanation tonometry reveals IOP
in the range of 30 mm Hg to 60 mm
Hg, occasionally higher in some cases.12-
14
Gonioscopy, which may prove diffi-
cult because of microcystic corneal
edema, reveals no visible angle struc-
tures. There may be evidence of previ-
ous angle closure episodes in the form of
peripheral anterior synechiae (PAS) in
the involved or fellow eye.15,16
Medication history is important in
patients with AACG, as the attack may
be medically induced. Of particular
importance is the use of the sulfa-based
anti-epileptic medication Topiramate
(Topamax, Ortho-McNeil Pharma-
ceutical). Topiramate has recently been
associated with the development of uni-
lateral and bilateral AACG and acquired
myopia in patients previously not at risk
for angle closure.6,17-21
Pathophysiology
Anatomically, patients with pri-
mary angle closure glaucoma, either
acute or non-acute, have smaller eyes.
Studies indicate that these patients
have axial lengths 5% shorter, lenses
that are 7% thicker, anterior chambers
that are 24% shallower and anterior
chambers with 37% less volume than
other age-matched individuals.22
There is a high resistance to forward
movement of aqueous through the
iris-lens channel due to tight apposi-
tion between the posterior iris and
anterior lens capsule. This resistance is
known as relative pupil block. Pupil
block is a normal physiological phe-
nomenon occurring in virtually every
person. In rare cases, however, this
resistance becomes pathological and
Fixed pupil and ocular congestion in a patient
with acute pupil block angle closure glaucoma.
results in AACG. These individuals
have an increased pressure differential
between the anterior and posterior
chambers, with resultant iris bombé
and angle closure. When this occurs,
there is a marked bowing forward
(convexity) of the iris.
Angle closure occurs when the
peripheral iris physically opposes the
trabecular meshwork or corneal
endothelium and impedes aqueous
outflow. Several mechanisms are possi-
ble. This may be simply due to genetic
predisposition and anterior segment
anatomy (primary pupil block) or from
posterior synechiae, lenticular enlarge-
ment or displacement of the lens or IOL
(secondary pupil block).1 23
Another mechanism that may induce
angle closure involves an abnormal con-
figuration of the iris, the so-called

“plateau iris syndrome.” Patients with
this presentation may have a deep ante-
rior chamber centrally; however, the
iris demonstrates an unusual laxity,
coming into close approximation with
the angle peripherally. These patients
may be prone to “angle crowding” and
subsequent closure during physiologic
or pharmacologic dilation.23
Expansion of the choroid appears to
be a significant contributory factor for
AACG in some cases.21,24-27 Ultra-
sound biomicroscopy has clearly
demonstrated choroidal expansion and
shallow choroidal effusions in patients
undergoing angle closure attacks. This
is associated with anterior rotation of
the ciliary body and forward move-
ment of the iris and lens, with subse-
quent shallowing of the anterior cham-
ber and closure of the angle.6,21,24-27
Because of expansion of the choroid
and ciliary body edema (with possible
choroidal effusion), there is a relaxation
of the lens zonules, with increased lax-
ity and thickening of the lens. Along
with angle closure glaucoma is refrac-
tive error shift, with several diopters of
acquired myopia. The clinical picture
of choroidal expansion-induced
AACG differs from that seen in pupil
block in that there is a flat anterior
chamber without iris bombé.
A number of conditions may lead to
choroidal expansion and angle closure
in previously normal eyes not at risk
for angle closure. They include scleritis,
Vogt-Koyanagi-Harada syndrome,
pan-retinal photocoagulation, HIV
infection and cavernous sinus fistula.25
Choroidal expansion–induced angle
closure glaucoma has also been report-
ed frequently as a result of administer-
ing sulfa-based medications such as
sulfonamide, acetazolamide (Diamox),
topiramate and hydrochlorothiazide.
Topiramate, which is also used to man-
age chronic headache as well as induce
weight loss, has been strongly implicat-
ed in choroidal expansion–induced
bilateral angle closure glaucoma along
with induced myopia.21,26 The theo-
rized mechanism may be an inflamma-
tory allergic reaction.6
Management
The paramount concern in manag-
ing a pupil block angle closure attack is
to alter the physiologic mechanisms that
cause the cornea to appose the trabecu-
lar meshwork.1 In primary pupil block,
the tight apposition of the posterior iris
to the anterior lens surface in the mid-
dilated state must be broken. This is
done by lowering the IOP so that the
iris can function normally and move
from this mid-dilated, pupil-blocking
state. This iris movement is actually
what breaks the apposition. This must
be done quickly—structural damage to
the nerve fiber layer and trabecular
meshwork and functional damage to
the visual field can occur within 48
hours.11,12,28
Choice of primary medication
depends upon the pressure at presenta-
tion. As most miotics are ineffective at
pressures higher than 40 mm Hg due to
iris ischemia, aqueous suppressants such
as topical beta-blockers, alpha-2 adren-
ergic agonists and carbonic anhydrase
inhibitors should be used initially.30
Prostaglandin analogs also appear to be
an efficacious topical therapy for
patients with AACG.31-35
Once the IOP is below 40 mm Hg,
topical pilocarpine 2% can be used to
abate the attack, move the iris from the
mid-dilated state, and reopen the angle.
Higher concentrations of pilocarpine
should be avoided as they can lead to
uveal congestion and worsen the condi-
tion. Topical steroids such as pred-
nisolone acetate 1% can be used for the
resultant inflammation. If the patient
does not achieve significant reduction in
IOP after 60 minutes, an oral carbonic
anhydrase inhibitor (acetazolamide 2 x
250 mg tablets) can be employed. A
hyperosmotic agent, such as 3 to 5
ounces of oral glycerin or isosorbide
over ice, may also assist in lowering the
IOP and breaking the attack. It is safe to
discontinue acute medical intervention
when the IOP falls below 30 mm Hg
and the angle structures are again visible
with gonioscopy. The patient should be
maintained on the following medica-
tions until surgical therapy can be
®
UVEA AND GLAUCOMA
employed: pilocarpine 2% and pred-
nisolone acetate 1% q.i.d., a topical beta
blocker and an alpha-2 adrenergic ago-
nist b.i.d.
The quintessential treatment for
pupil block AACG is laser peripheral
iridotomy (LPI).6,8,11,16,35-39 This should
be performed as soon as safely possible.
LPI will allow the aqueous fluid pressure
to equilibrate between the posterior and
anterior chamber. This allows the iris to
relax backward with dissipation of iris
bombé, allowing deepening of the ante-
rior chamber and the ability to visualize
angle structures again. LPI should also
be performed on any fellow eye that is
potentially occludable.40 Adjunctively,
laser peripheral iridoplasty can be per-
formed to physically pull the iris taught
and away from the trabecular mesh-
work. In fact, laser peripheral iridoplas-
ty has been shown to be a safe primary
treatment for AACG.8,36,37 Incisional
ocular surgery—trabeculectomy, cata-
ract extraction, cyclodestructive proce-
dures, glaucoma implant and gonios-
ynechialysis—remain options for cases
unresponsive to medical and laser thera-
pies.36,41-43 Trabeculectomy and goni-
osynechialysis are often combined with
cataract extraction.
In cases of AACG that are precipitat-
ed by a systemic medication, therapy is
different. Often, discontinuation of the
medication will resolve the glaucoma.
This often occurs in patients that were
previously normal and not at risk for
angle closure prior to medication use.
However, when the choroid contributes
to angle closure glaucoma (which is
often the mechanism of medicine-
induced AACG), the use of a potent
cycloplegic agent such as atropine, as
well as topical steroids, will allow for cil-
iary relaxation and posterior rotation
with resolution of the angle clo-
sure.6,17,21,24,25,27 Aqueous suppressants
can be used concurrently, but miotics
should be avoided in these cases.
Following successful LPI, IOP may
still be elevated secondary to damage to
the trabecular meshwork caused by the
prolonged or repeated iris-meshwork
apposition.29 For this reason, long-term
MARCH 15, 2006 REVIEW OF OPTOMETRY 33A

medical therapy may be necessary.
Aqueous suppressants are a good choice,
and it appears that prostaglandin
analogs also work especially well.30-32
Clinical Pearls
• The most important considerations
in handling an acute angle closure attack
are accurate diagnosis and prompt inter-
vention. First, AACG must de differen-
tiated from other acute open angle con-
ditions such as uveitic glaucoma,
glaucomatocyclitic crisis and phacolytic
glaucoma. Next, the mechanism of
angle closure, such as primary pupillary
block, plateau iris, secondary pupillary
block or choroidal expansion, must be
delineated. If the etiology is uncertain or
if an inflammatory glaucoma may be
present, a miotic should not be used, as
this will only exacerbate the condition.
• In a case of suspected AACG, the
cornea may be too edematous to allow
for gonioscopic evaluation of the anteri-
or chamber angle. In such a case,
gonioscopy can be performed on an
uninvolved fellow eye. In the vast major-
ity of cases, by nature of symmetry, the
fellow eye will have an occludable
angle.44 If the fellow eye demonstrates a
non-occludable angle, it is not likely that
the patient has an acute angle closure. If
both corneas are edematous, topical
glycerin can provide appropriate
deturgescence.
• The presence of a patent peripheral
iridotomy does not necessarily ensure
that a patient is safe to dilate.
Gonioscopy must still be performed
prior to pharmacologic dilation.45
• The ultimate goal in managing
AACG attack is not merely to lower the
IOP but to assist in ending the apposi-
tion of the iris to the trabecular mesh-
work. Reduction of IOP is the means
by which clinicians can alter this
anatomic relationship, as it allows the
iris to regain mobility.
• Often following successful LPI for
AACG, the angle will be open but the
IOP will be elevated and the patient is
said to have “mixed mechanism glauco-
ma.” The use of this term indicates a
clinician’s unfamiliarity with the status
34A REVIEW OF OPTOMETRY MARCH 15, 2006
of the angle damage that compromises
the outflow facility following apposi-
tional closure. Thus, there is one mech-
anism for the residual IOP elevation—
and the term “mixed mechanism
glaucoma” should be avoided.
1. Wang N, Wu H, Fan Z. Primary angle closure glau-
coma in Chinese and Western populations. Chin Med
J (Engl) 2002;115(11):1706-15.
2. Foster PJ. The epidemiology of primary angle clo-
sure and associated glaucomatous optic neuropathy.
Semin Ophthalmol 2002;17(2):50-8.
3. Xu L, Zhang L, Xia CR, et al. The prevalence and
its effective factors of primary angle-closure glaucoma
in defined populations of rural and urban in Beijing.
Zhonghua Yan Ke Za Zhi 2005;41(1):8-14.
4. Wojciechowski R, Congdon N, Anninger W, et al.
Age, gender, biometry, refractive error, and the anteri-
or chamber angle among Alaskan Eskimos.
Ophthalmol 2003;110(2):365-75.
5. Congdon NG, Youlin Q, Quigley H, et al. Biometry
and primary angle-closure glaucoma among Chinese,
white, and black populations. Ophthalmol 1997;
104(9):1489-95.
6. Congdon NG, Friedman DS. Angle-closure glauco-
ma: impact, etiology, diagnosis, and treatment. Curr
Opin Ophthalmol 2003;14(2):70-3.
7. Fuchs J, Holm K, Vilhelmsen K, et al. Hereditary
high hypermetropia in the Faroe Islands. Ophthalmic
Genet 2005;26(1):9-15.
8. Huang S, Yu M, Qiu C, et al. The management of
secondary glaucoma in nanophthalmic patients. Yan
Ke Xue Bao 2002;18(3):156-9.
9. Ritch R, Chang BM, Liebmann JM. Angle closure in
younger patients. Ophthalmol 2003;110(10):1880-9.
10. Sowka JW. Pupil block glaucoma from traumatic
vitreous prolapse in a patient with posterior chamber
lens implantation. Optom 2002;73(11):685-93.
11. Wong JS, Chew PT, Alsagoff Z, et al. Clinical
course and outcome of primary acute angle-closure
glaucoma in Singapore. Singapore Med J
1997;38(1):16-18.
12. Lai JS, Tham CC, Chan JC, et al. Scanning laser
polarimetry in patients with acute attack of primary
angle closure. Jpn J Ophthalmol 2003;47(6):543-7.
13. Lam DS, Chua JK, Tham CC, et al. Efficacy and
safety of immediate anterior chamber paracentesis in
the treatment of acute primary angle-closure glauco-
ma: A pilot study. Ophthalmol 2002;109(1):64-70.
14. Aung T, Ang LP, Chan SP, et al. Acute primary
angle-closure: Long-term intraocular pressure out-
come in Asian eyes. Am J Ophthalmol 2001;
131(1):7-12.
15. Choi JS, Kim YY. Relationship between the extent
of peripheral anterior synechiae and the severity of
visual field defects in primary angle-closure glauco-
ma. Korean J Ophthalmol 2004;18(2):100-5.
16. Lim LS, Aung T, Husain R, et al. Acute primary
angle closure: configuration of the drainage angle in
the first year after laser peripheral iridotomy.
Ophthalmol 2004;111(8):1470-4.
17. Bhattacharyya KB, Basu S. Acute myopia induced
by topiramate: Report of a case and review of the lit-
erature. Neurol India 2005;53(1):108-9.
18. Fraunfelder FW, Fraunfelder FT, Keates EU.
Topiramate-associated acute, bilateral, secondary
angle-closure glaucoma. Ophthalmol 2004;111
(1):109-11.
19. Craig JE, Ong TJ, Louis DL, et al. Mechanism of
topiramate-induced acute-onset myopia and angle
closure glaucoma. Am J Ophthalmol 2004;
137(1):193-5.
20. Banta JT, Hoffman K, Budenz DL, et al.
Presumed topiramate-induced bilateral acute angle-
closure glaucoma. Am J Ophthalmol 2001;
132(1):112-4.
21. Chen TC, Chao CW, Sorkin JA. Topiramate
induced myopic shift and angle closure glaucoma. Br
J Ophthalmol 2003;87:648-9.
22. Friedman DS, Gazzard G, Foster P, et al.
Ultrasonographic biomicroscopy, Scheimpflug photog-
raphy, and novel provocative tests in contralateral eyes
of Chinese patients initially seen with acute angle clo-
sure. Arch Ophthalmol 2003;121(5):633-42.
23. Sellem E. Angle closure mechanisms of glauco-
ma. J Fr Ophtalmol 2004;27(6, Pt 2):693-6.
24. Waheeb S, Feldman F, Velos P, et al. Ultrasound
biomicroscopic analysis of drug-induced bilateral angle
closure glaucoma associated with supraciliary choroidal
effusion. Can J Ophthalmol 2003; 38:299-302.
25. Quigley HA, Friedman DS, Congdon NG. Possible
mechanisms of primary angle closure and malignant
glaucoma. J Glaucoma 2003;12:167-80.
26. Ikeda N, Ikeda T, Nagata, et al. Ciliochoroidal
effusion syndrome induced by sulfa derivatives. Arch
Ophthalmol 2002;120:1775.
27. Sakai H, Morine-Shinjyo S, Shinzato M, et al.
Uveal effusion in primary angle-closure glaucoma.
Ophthalmol 2005;112(3):413-9.
28. Aung T, Husain R, Gazzard G, et al. Changes in
retinal nerve fiber layer thickness after acute primary
angle closure. Ophthalmol 2004;111(8):1475-9.
29. Sihota R, Lakshmaiah NC, Walia KB, et al. The
trabecular meshwork in acute and chronic angle clo-
sure glaucoma. Indian J Ophthalmol 2001;
49(4):255-9.
30. Hoh ST, Aung T, Chew PT. Medical management
of angle closure glaucoma. Semin Ophthalmol 2002;
17(2):79-83.
31. Kook MS, Cho HS, Yang SJ, et al. Efficacy of
latanoprost in patients with chronic angle-closure glau-
coma and no visible ciliary-body face: A preliminary
study. J Ocul Pharmacol Ther 2005;21(1):75-84.
32. Aung T, Chan YH, Chew PT, et al. (EXACT Study
Group) Degree of angle closure and the intraocular
pressure-lowering effect of latanoprost in subjects
with chronic angle-closure glaucoma. Ophthalmol
2005;112(2):267-71.
33. Chew PT, Hung PT, Aung T. Efficacy of
latanoprost in reducing intraocular pressure in
patients with primary angle-closure glaucoma. Surv
Ophthalmol 2002;47(S1):25-8.
34. Hung PT, Hsieh JW, Chen YF, et al. Efficacy of
latanoprost as an adjunct to medical therapy for resid-
ual angle-closure glaucoma after iridectomy. J Ocul
Pharmacol Ther 2000;16(1):43-7.
35. Saw SM, Gazzard G, Friedman DS. Interventions
for angle-closure glaucoma: An evidence-based
update. Ophthalmol 2003;110(10):1869-78.
36. Renard JP, Giraud JM, Oubaaz A. Treatment of
acute angle-closure glaucoma. J Fr Ophtalmol
2004;27(6, Pt 2):701-5.
37. Lai JS, Tham CC, Chua JK, et al. Laser peripher-
al iridoplasty as initial treatment of acute attack of
primary angle-closure: a long-term follow-up study. J
Glaucoma 2002;11(6):484-7.
38. Alsagoff Z, Aung T, Ang LP, et al. Long-term clini-
cal course of primary angle-closure glaucoma in an
Asian population. Ophthalmol 2000;107(12):2300-4.
39. Choong YF, Irfan S, Menage MJ. Acute angle clo-
sure glaucoma: an evaluation of a protocol for acute
treatment. Eye 1999(Pt 5):613-6.
40. Stefanescu-Dima A. Preventive iridotomy—a

prospective study. Oftalmologia 2004;48(3):61-71.
41. Harasymowycz PJ, Papamatheakis DG, Ahmed I,
et al. Phacoemulsification and goniosynechialysis in
the management of unresponsive primary angle clo-
sure. J Glaucoma 2005;14(3):186-9.
42. Lai JS, Tham CC, Lam DS. Incisional surgery for
angle closure glaucoma. Semin Ophthalmol
2002;17(2):92-9.
43. Wang JK, Lai PC. Unusual presentation of angle-
closure glaucoma treated by phacoemulsification. J
Cataract Refract Surg 2004;30(6):1371-3.
44. Sawada A, Sakuma T, Yamamoto T, et al.
Appositional angle closure in eyes with narrow angles:
Comparison between the fellow eyes of acute angle-
®
UVEA AND GLAUCOMA
closure glaucoma and normotensive cases. J
Glaucoma 1997;6(5):288-92.
45. Tanasescu I, Grehn F. Acute angle-closure glau-
coma despite previous Nd:YAG laser iridotomy: A
report on 13 cases. Ophthalmologe 2003;
100(10):832-5.

Contemporary Glaucoma Therapy: Lowering Intraocular Pressure

Or Controlling Intraocular Pressure?
The goals of glaucoma management are preserva-
tion of the health of the optic nerve and nerve fiber
layer and the integrity of the visual field. To achieve
these aims, the intraocular pressure (IOP), which is the
only modifiable risk factor in this disease, is lowered.
In cases where glaucomatous optic neuropathy exists,
regardless of the level of IOP at the time of diagnosis,
medical or surgical lowering of the IOP has been con-
clusively demonstrated as helpful. However, is it ade-
quate merely to lower the IOP, or is it better to main-
tain control of IOP levels throughout the day?
Lowering IOP and truly controlling IOP—that is,
maintaining it at an acceptable level at all times—can
be two different things. There are two important factors
involved in controlling the IOP in a patient with glau-
coma. First is the patient’s consistent ability to adhere
to a prescribed therapeutic regimen. Second is the
ability of the prescribed medical regimen to dampen
the circadian rhythm of IOP.
Many patients have difficulty adhering to prescribed
drug regimens.1,2 It is also difficult for clinicians to
determine the true rate of patient adherence to pre-
scribed drug regimens.3 Often, patients overstate or
overestimate their degree of adherence to a prescribed
regimen. Some have physical limitations that interfere
with their ability to use topical therapy. One study rec-
ognized that about one-half of the patients had diffi-
culty aiming the drop into the eye, and many had other
problems including squeezing the bottle, blinking and
seeing the tip of the bottle. These same patients also
had difficulty with the other movements required to
administer drops.2
While physical limitations certainly can be a barrier
to patient adherence to medical therapy, there are
clearly other factors involved. A recent study showed
that forgetfulness was the number-one reported reason
for non-adherence to glaucoma medical therapy.4 Com-
munication between physicians and patients is a key
factor in adherence for glaucoma patients. Specifically,
patients would like their physicians to teach them how
to instill their eye drops, tell them about new and/or
alternate medications and procedures as they become
available and offer new ways to make their regimen
easier or more convenient. Patients do not claim to be
non-adherent specifically because of adverse effects.
Often, patients do not tell their physician if they expe-
rience an adverse effect unless it is intolerable to
them.4 Another study has provided initial evidence that
patient satisfaction with a treatment regimen may be
related to the patient’s level of adherence, and hence
the perceived effectiveness of the treatment.5 Adverse
effects, ease and convenience of use, acceptance of ill-
ness and knowledge of glaucoma all play a role.5
In patients with glaucoma, large fluctuations in diur-
nal IOP have been shown to be a significant risk factor for
disease progression, independent of parameters obtained
in the office. Reducing fluctuations in IOP may be more
important in managing glaucoma patients than we have
realized.6 While lowering the IOP from baseline is obvi-
ously important, recent evidence suggests that it is just as
important to minimize the diurnal fluctuations char-
acteristic of the disease.
When choosing a topical medication as a therapy for
glaucoma, patient adherence to treatment regimen and
minimization of diurnal IOP fluctuation are among the
main concerns. For these reasons, prostaglandin analogs
appear to be excellent medical options. Once-daily dosing
provides advantages when considering patient adherence
to prescribed drug regimens. When considering the fact
that patients may forget to take a prescribed dose,
prostaglandin analogs provide the benefit of ongoing pres-
sure reduction. In one study, travoprost was shown to pro-
duce IOP reductions that were sustained for up to 84
hours after dosing.7 Further, it was seen that
prostaglandin analogs significantly lowered IOP from
baseline in patients with open-angle glaucoma and pro-
vided excellent diurnal IOP control throughout a 24-hour
period.7,8 When considering ease of therapy (once-daily
administration) as well as the treatment’s ability to flatten
the diurnal pressure curve—known to be an inherent
property of the disorder—it is easy to understand why
prostaglandin analogs are, and should be, a first choice of
many clinicians who manage patients with glaucoma.
1. Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glau-
coma. Ophthalmic Surg 1995;26(3):233-6.
2. Winfield AJ, Jessiman D, Williams A, et al. A study of the causes of non-com-
pliance by patients prescribed eyedrops. Br J Ophthalmol 1990;74(8):477-80.
3. Kass MA, Gordon M, Meltzer DW. Can ophthalmologists correctly identify
patients defaulting from pilocarpine therapy? Am J Ophthalmol 1986;
101(5):524-30.
4. Taylor SA, Galbraith SM, Mills RP. Causes of non-compliance with drug reg-
imens in glaucoma patients: A qualitative study. J Ocul Pharmacol Ther
2002;18(5):401-9.
5. Day DG, Sharpe ED, Atkinson MJ, et al. The clinical validity of the treatment
satisfaction survey for intraocular pressure in ocular hypertensive and glaucoma
patients. Eye 2005 Jun 3;[Epub ahead of print].
6. Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocu-
lar pressure are an independent risk factor in patients with glaucoma. J
Glaucoma 2000;9(2):134-42.
7. Dubiner HB, Sircy MD, Landry T, et al. Comparison of the diurnal ocular
hypotensive efficacy of travoprost and latanoprost over a 44-hour period in
patients with elevated intraocular pressure. Clin Ther 2004;26(1):84-91.
8. Walters TR, DuBiner HB, Carpenter SP, et al. 24-Hour IOP control with once-
daily bimatoprost, timolol gel-forming solution, or latanoprost: a 1-month, ran-
domized, comparative clinical trial. Surv Ophthalmol 2004;49:S26-35.

MARCH 15, 2006 REVIEW OF OPTOMETRY 35A

 FREQUENCY DOUBLING TECHNOLOGY (FDT MATRIX™ PERIMETRY)
Glaucoma is a leading cause of blindness worldwide.1–10 Retinal
ganglion cell death is its pathological hallmark.1-8 There is accu-
mulating evidence that glaucomatous optic neuropathy extends
from the retinal ganglion cells deep into the vision centers of the
brain.6-8 Retinal nerve fibers may be classified into three main
subtypes of cells, each responding to and transmitting unique
information from their receptors to the lateral geniculate body and
ultimately to the visual cortex.1,7-10 These are: the magno-cellular
(parasol cells), the parvo-cellular (midget cells) and the konio-cel-
lular (short wavelength–sensitive cones [s-cones]) pathways.7-9
Analyzed dendritic field sizes and coverage for the three types of
cells suggest that their relative densities vary with eccentricity.9 Of
the total ganglion cells in the human fovea, midget cells consti-
tute about 90%, parasol cells about 5% and s-cones about 1%.9
In the retinal periphery, midget cells make up about 40 to 45%,
parasol cells about 20% and small bistratified cells about 10% of
the total.9
The M-cell pathway is responsible for low-contrast, high tem-
poral frequency (or motion) stimulus detection.1,7,8 The P-cell
pathway is responsible for high-contrast, low temporal frequency
(static, detail) stimulus detection.1,7,8 The konio-cellular receptors
and their pathway are documented to be responsible for blue and
yellow stimulus recognition.7,10 In his now classic work, Quigley
established that optic nerve fibers having a larger diameter than
the mean were compromised more rapidly than smaller fibers in
the pathologic process of glaucoma.10 Quigley also demonstrated
that no fiber was completely spared at any stage of the process.10
Most importantly, he and his team confirmed suspicions that the
death of a substantial proportion of optic nerve fibers may pre-
cede detectable visual field loss.10 Histological studies of glauco-
matous atrophy have uncovered that larger neurons with the
largest cell bodies and largest diameter neurons (parasol cells of
the magno-cellular pathway and s-cones of the konio-cellular
pathway) are among the first to succumb to the effects of glau-
comatous optic neuropathy.1,2,8-10 This unique pathological calling
card founded the basis for frequency doubling perimetry.1-10
The test itself is accomplished by presenting a low spatial fre-
quency sinusoidal grating in the form of alternating light and dark
bands. When this pattern undergoes a rapid counterphase flicker
sequence (in which the black bands reverse to become white and
the white bands reverse to become black, rapidly and in succes-
sion), the pattern is interpreted by the visual system of the subject
to possess twice as many light and dark bands than are actually
there—hence the “frequency doubling effect.”1-3 The effect itself
seems to be mediated by a combination of retinal ganglion and
cortical mechanisms.1,2,11 Since it has been hypothesized that vul-
nerable retinal cell neurons thought to participate, at least in some
part, to this illusion are casualties of early neurologic diseases
such as glaucoma, selec-
tive testing by this modal-
ity may serve to reveal
early fluctuations, signify-
ing beginning, impending
or worsening pathology.1-
14
As most of the
histopathological and
psychophysical studies in
glaucoma implicate dam-
age to the magno-cellular
pathway and parvo-cellu-
lar pathways, and
because it has been Matrix field of patient with anterior
demonstrated that 20 to ischemic optic neuropathy.
36A REVIEW OF OPTOMETRY MARCH 15, 2006
40% of ganglion cells can be lost before standard, white–on-white
automated field defects are detected, new strategies have been
developed, cast at the focus of early detection.1-14 Frequency dou-
bling technology has been harnessed by Humphrey/Welch-
Allyn/Zeiss in the form of their Matrix™ frequency doubling perime-
ter (FDP).
The Matrix™ FDP is small, light, and portable. It has been
designed to allow 6 diopters of blur and is not affected by exter-
nal room illumination or variations in pupil size so long as pupil
diameter is greater than 2 mm. The instrument presents a series
of touch-sensitive menu screens that allow the practitioner to
select a test and input patient data. The test itself consists of the
presenting of a 5-degree-square banded pattern that undergoes
counterphase flicker in 17 different locations within the instru-
ment’s central 20-by-20-degree field.
The FDT perimeter uses central static fixation with the classic
Heijl-Krakau (blind spot) fixation check. Defects are noted on the
printout using gray scale probability symbols. The darker the color
of gray/black, the more probable (based on age-related norms) that
the defect is legitimate. Reliability indices (fixation errors, false
positive errors and false negative errors) are included in the data
to aid the clinician in interpreting the validity of the evaluation.
Like other automated units, the overall field’s mean deviation and
pattern standard deviation are included in the statistical analysis.
While some published reports suggest that Matrix™ threshold
testing and the standard 24-2 automated white-on-white perime-
try compare favorably,3 other reports acknowledge that the two
techniques do not necessarily share perfect correlation, and in
fact may be identifying different subgroups of patients.4
While it is at least controversial to conclude that concept of
motion perception visual field testing is specifically affected in
glaucomatous disease, at the bare minimum, localized motion
perception tests using FDT should be considered as one of the
diagnostic tools within the armamentarium.
1. Yudcovitch L. Understanding frequency doubling perimetry: A practical
approach. http://www.opt.pacificu.edu/ce/catalog/web019/FDT_Text.html.
2. McKendrick AM. Recent developments in perimetry: test stimuli and procedures.
Clin Exp Optom 2005;88(2):73-80.
3. Spry PG, Hussin HM, Sparrow JM. Clinical evaluation of frequency doubling
technology perimetry using the Humphrey Matrix 24-2 threshold strategy. Br J
Ophthalmol 2005;89(8):1031-5.
4. Haymes SA, Hutchison DM, McCormick TA, et al. Glaucomatous visual field pro-
gression with frequency-doubling technology and standard automated perimetry in
a longitudinal prospective study. Invest Ophthalmol Vis Sci 2005;46(2):547-54.
5. Spry PG, Johnson CA, Mansberger SL, et al. Psychophysical investigation of gan-
glion cell loss in early glaucoma. J Glaucoma 2005;14(1):11-19.
6. Yucel YH, Zhang Q, Weinreb RN, et al. Effects of retinal ganglion cell loss on
magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual
cortex in glaucoma. Prog Retin Eye Res 2003;22(4):465-81.
7. Gupta N, Yucel YH. Brain changes in glaucoma. Eur J Ophthalmol 2003;
13(S3):S32-5.
8. Shabana N, Cornilleau Peres V, Carkeet A, et al. Motion perception in glaucoma
patients: a review. Surv Ophthalmol 2003;48(1):92-106.
9. Dacey DM. Physiology, morphology and spatial densities of identified ganglion cell
types in primate retina. Ciba Found Symp 1994;184:12-28; discussion 28-34, 63-70.
10. Quigley HA, Dunkelberger GR, Green WR. Chronic human glaucoma causing
selectively greater loss of large optic nerve fibers. Ophthalmol 1988;95(3):357-63.
11. White AJ, Sun H, Swanson WH, et al. An examination of physiological mecha-
nisms underlying the frequency-doubling illusion. Invest Ophthalmol Vis Sci
2002;43(11):3590-9.
12. Johnson CA. Recent developments in automated perimetry in glaucoma diag-
nosis and management. Curr Opin Ophthalmol 2002;13(2):77-84.
13. Anderson AJ, Johnson CA. Frequency-doubling technology perimetry.
Ophthalmol Clin North Am 2003;16(2):213-25.
14. Robin TA, Muller A, Rait J, et al. Performance of community-based glaucoma
screening using frequency doubling technology and Heidelberg retinal tomography.
Ophthalmic Epidemiol 2005;12(3):167-78.
VITREOUS AND RETINA
IDIOPATHIC POLYPOIDAL
CHOROIDAL VASCULOPA-
THY (POSTERIOR UVEAL
BLEEDING SYNDROME)
Signs and Symptoms
Idiopathic polypoidal choroidal
vasculopathy (IPCV), also known as
posterior uveal bleeding syndrome, is
a unilateral disease entity that pro-
duces numerous periodic bouts of
retinal pigment epithelium (RPE)
detachment secondary to serosan-
guinous leakage of the peripapillary
region.1-7 Though frequently mistaken
for age-related macular degeneration
(AMD), its differentiation is based on
age of onset (younger individuals) and
angiographic findings.1-4 Once
believed to be a disease of middle-
aged, African-American women, it is
now recognized as more common in
populations with increased pigmenta-
tion, without obvious gender predilec-
tion.1-4 Funduscopically, IPCV
appears as orange nodules represent-
ing polyps within the choroidal vascu-
lature.1-4 Angiographically, intraven-
ous fluorescein angiography (IVFA)
poorly delineates the choroidal circu-
lation. However, indocyanine green
angiography (ICGA) permeates the
RPE, overlying fluids and the chorio-
capillaris, allowing detailed imaging.1-4
Active IPCV will appear as a “hot
spot” at the location of the leaking
polyps.1-4 Since IPCV sometimes pro-
gresses to frank choroidal neovascular-
ization, ICGA is a powerful and use-
ful tool.1-4
Pathophysiology
IPCV has been considered by many
as a distinct choroidal abnormality
characterized by an intrachoroidal vas-
cular network of vessels ending in
polyp-like structures, which may be
identified and confirmed using indo-
cyanine green angiography.7-10 It affects
mostly those of African and Asian her-
itage.7 The exact nature of the vascular
structure of the lesion remains unclear.7
Recently, researchers have suggested
that the IPCV lesions should be con-
sidered a variety of choroidal neovascu-
larization (CNV) rather than a distinct
clinical entity.7 Some scientists have
described the IPCV lesion as one sin-
gle, large neovascular complex present-
ing with well-defined arterial neovascu-
lar vessels arising from one major
“ingrowth site”; these drain from ves-
sels that present with aneurysm-like
dilations and are the classic correspon-
ding polyp-like structures.7 Others
maintain that the IPCV is unique,
caused by inner choroidal vessel abnor-
malities and not CNV.9,10
Management
IPCV, whether a distinct clinical
entity or a variant of the choroidal
neovascular processes known to exist
in age-related maculopathy, seems to
be vulnerable to currently available
treatment modalities.3-7 Photo-
Idiopathic polypoidal choroidal vasculopathy.
Note the polyps within the choroidal
vasculature inferior to the macula.
(Photo courtesy of Dr. Diana Shechtman)
dynamic therapy applied to polyp
regions has been shown to be some-
what effective in treating this disease,
but to date no studies have been per-
formed to quantify the success of this
treatment.1-3,5,7 Laser photocoagula-
tion targeted exclusively to the feeder
vessels supplying the IPCV lesions
seems to be a safe and effective
method of improving vision in eyes
that have developed an associated
serous retinal detachment in or adja-
cent to the macula.6 ICGA-guided
laser photocoagulation can be consid-
® VITREOUS AND RETINA
ered one of the modalities for deliver-
ing treatment in IPCV.6 Like AMD
itself, IPCV may be treated even when
lesions are subfoveal.7
Clinical Pearls
• Macular exudative manifestations
secondary to choroidal neovascular
lesions remain the leading cause of
visual impairment and legal blindness
in those older than 65 years.3-10
• Since choroidal neovascular mem-
branes have the capability of growing at
a rate of 10 to 15 microns per day,
prompt referral to a retinal specialist
upon suspicion of any CNV with the
ability to breech the foveal integrity is
paramount.
• All modern imaging techniques,
such as fluorescein angiography, indo-
cyanine green angiography and optical
coherence tomography, have a poten-
tial role in the accurate diagnosis of
IPCV.
• Patients with exudative, hemor-
rhagic retinopathy without signs of
active inflammation or precursors to
age-related pathology should be con-
sidered suspicious for IPCV.
1. Stanga PE, Lim JL, Hamilton P. Indocyanine green
angiography in chorioretinal diseases: Indications and
interpretation. Ophthalmol 2003;110(1):15-21.
2. Kumar A, Nainiwal S, Prakash G. Indocyanine
green angiography in age-related macular degenera-
tion. Bombay Hosp J 2002;44(3):333-9.
3. Alexander LJ. Exudative and nonexudative macular
disorders. In: Alexander LJ, ed. Primary Care of the
Posterior Segment, 3rd ed. New York: McGraw-Hill,
2002, pp. 75-208.
4. Fernandes LH, Freund KB, Yannuzzi LA, et al. The
nature of focal areas of hyperfluorescence or hot spots
imaged with indocyanine green angiography. Retina
2002;22(5):557-68.
5. Berger JW, Maguire MC, Fine SL. The macular pho-
tocoagulation study. In: Kertes PJ, Conway MD, eds.
Clinical Trials in Ophthalmology: A Summary And
Practice Guide, 1st ed. Philadelphia: Lippincott,
Williams and Wilkins, 1998, pp. 71-96.
6. Nishijima K, Takahashi M, Akita J, et al. Laser pho-
tocoagulation of indocyanine green angiographically
identified feeder vessels to idiopathic polypoidal
choroidal vasculopathy. Am J Ophthalmol
2004;137(4):770-3.
7. Quaranta M, Mauget-Faysse M, Coscas G.
Exudative idiopathic polypoidal choroidal vasculopa-
thy and photodynamic therapy with verteporfin. Am J
Ophthalmol 2002;134(2):277-80.
MARCH 15, 2006 REVIEW OF OPTOMETRY 37A
 8. Costa RA, Navajas EV, Farah ME, et al. Polypoidal
choroidal vasculopathy: Angiographic characterization
of the network vascular elements and a new treatment
paradigm. Prog Retin Eye Res 2005;24(5):560-86.
9. Yuzawa M, Mori R, Kawamura A. The origins of
polypoidal choroidal vasculopathy. Br J Ophthalmol
2005;89(5):602-7.
10. McCleary CD, Guier CP, Dunbar MT. Polypoidal
choroidal vasculopathy. Optom 2004;75(12):756-70.
COMMOTIO RETINAE
Signs and Symptoms
Commotio retinae presents as an
area of milky white neurosensory reti-
nal edema following blunt ocular trau-
ma. Visual acuity varies depending
upon the extent and location of the
lesion. The rate of emergency depart-
ment-treated eye injury in the United
States is roughly 3.15 per 1,000 indi-
viduals.1 Injury rates are highest among
males in their 20s and 30s, of
American Indian and African descent.1
The majority of ocular injuries meas-
ured by statistical analysis occur in or
around the home; contusions and
abrasions are the most common.1-4
Pathophysiology
The classic work of Sipperly,
Quigley and Gass,6 using an owl mon-
key model, determined that immedi-
ately after injury, the predominant
retinal abnormality was disruption of
the photoreceptor outer segments.6
From one to six days after a traumatic
event, photoreceptor cells undergo
degeneration. The retinal pigment
epithelium (RPE) attempts to phago-
cytize any degenerating injured pho-
toreceptor outer segments. These seg-
ments occasionally migrate into the
retina. The owl monkey model
showed no evidence of extracellular
retinal edema. Instead, the opacity of
commotio retinae seems to be repre-
sented by the disrupted photoreceptor
cells themselves.6 The capacity for
visual disability depends upon the vol-
ume and location of permanently lost
photoreceptors. Interestingly, the
RPE’s response to traumatic photore-
ceptor damage seems to be similar to
38A REVIEW OF OPTOMETRY MARCH 15, 2006
that observed in experimental retinal
detachment and light-induced retinal
damage.5,6 Recent in-vivo investiga-
tions using optical coherence tomogra-
phy (OCT) confirm what was postu-
Traumatic commotio retinae from volleyball
injury. (Courtesy Chris Suhr)
lated by previous histological studies:
Commotio retinae is caused by, and
consists of, a disruption and fragmen-
tation of the photoreceptor segments
and RPE.5
Management
There is no treatment for commotio
retinae.4-6 Management consists of
repairing the traumatic collateral dam-
age and emotionally supporting the
patient, especially if vision is poor.
Visual acuity monitoring, Amsler grid
testing, and interferometry can provide
data indicating the progress of recov-
ery; however, no known topical, oral or
surgical solution has been offered as a
treatment for the commotio proper. If
patients initially have decreased acuity,
they should be counseled that, in the
majority of cases, improvement takes
place spontaneously.4-6 However, they
should also be informed that in some
instances acuity remains disabled.
Concurrent treatment of any resultant
uveitis should include a topical cyclo-
plegic and, when appropriate, a topical
corticosteroid. Cystoid macular edema
(CME) is a classical complication of
ocular inflammation.9 CME can result
from a rupture of the inner or outer
blood-ocular barrier, and it responds
poorly to topical and surgical modali-
ties. Topical nonsteroidal and steroidal
preparations along with oral carbonic
anhydrase inhibitors and injected
steroidal depots have been used, but
with varied results.9
Clinical Pearls
• Any blow to the eye capable of dis-
rupting RPE cells and photoreceptor
outer segments is also capable of pro-
ducing collateral damage, such as sub-
conjunctival hemorrhage, angle reces-
sion, iridodialysis, hyphema, lens
dislocation or subluxation, posterior
vitreous detachment, retinal tears,
optic nerve avulsion, choroidal rupture
(with its potential for choroidal neovas-
cularization) and multiple choroidal
and retinal tears known as sclopteria.7,8
• If a 360-degree subconjunctival
hemorrhage is observed, imaging and a
surgical consult should be obtained to
rule out ruptured globe.
• If angle recession is present, signi-
fying the presence of angle and most
likely trabecular meshwork damage,
careful monitoring for late glaucoma is
required over the patient’s lifetime.
1. McGwin G Jr, Owsley C. Ocular morbidity associat-
ed with airbag deployment: A report of seven cases
and a review of the literature. Arch Ophthalmol
2005;23(5):662-6.
2. Parver LM, Dannenberg AL, Blacklow B, et al.
Characteristics and causes of penetrating eye injuries
reported to the National Eye Trauma System Registry,
1985-91. Public Health Rep 1993;108(5):625-32.
3. Conn JM, Annest JL, Gilchrist J, et al. Injuries from
paintball game related activities in the United States,
1997-2001. Inj Prev 2004;10(3):139-43.
4. Kiel J, Chen S. Contusion injuries and their ocular
effects. Clin Exp Optom 2001;84(1):19-25.
5. Meyer CH, Rodrigues EB, Mennel S. Acute com-
motio retinae determined by cross-sectional optical
coherence tomography. Eur J Ophthalmol 2003;13(9-
10):816-8.
6. Sipperley JO, Quigley HA, Gass DM. Traumatic
retinopathy in primates. The explanation of commotio
retinae. Arch Ophthalmol 1978;96(12):2267-73.
7. Brouzas D, Charakidas A, Papagiannakopoulos D,
et al. Elastic cord–induced ocular injuries. Injur
2003;34(5):323-6.
8. Ball DC, Bouchard CS. Ocular morbidity associat-
ed with airbag deployment: A report of seven cases
and a review of the literature. Cornea
2001;20(2):159-63.
9. Guex-Crosier Y. The pathogenesis and clinical pres-
entation of macular edema in inflammatory diseases.
Doc Ophthalmol 1999;97(3-4):297-309.

POSTERIOR VITREOUS
DETACHMENT
Signs and Symptoms
Patients developing posterior vitre-
ous detachment (PVD) are commonly
older adults with myopia; women
appear to be more prone.1 Although
PVD is clinically found most com-
monly in older patients, it has been
Weiss ring in PVD
demonstrated to begin as an incom-
plete or partial PVD as early as the
fourth decade of life.2 However, while
the incidence of PVD is known to
increase with age, PVD in elderly
patients is not as common as initially
thought: Only 46% of patients
between ages 80 to 89 years demon-
strate complete detachment.3
PVD is typically seen bilaterally, but
it does not frequently occur simultane-
ously.1 Patients with unilateral PVD
tend to be younger.1 Those who devel-
op PVD before age 30 often show the
presence of associated diseases such as
retinitis pigmentosa, non-diabetic reti-
nal vascular disorders or posterior
uveitis with vitritis; PVD at this age
may also follow ocular trauma.4 Once
PVD has developed, the risk for fellow
eye development within three years is
90%.5
The patient will present with a sud-
den onset of floaters.6 There is usually
one floating spot that is especially large
and troublesome to the patient and
often is the impetus to seek immediate
care.7 Patients may also complain of
multiple floaters or a moving cloud or
curtain in their vision.8 Ophthalmos-
copically, there may be an annular cir-
cle—termed Weiss’s ring—present.
This represents the former attachment
of the vitreous to the optic disc and
may appear as a complete or partial
ring, a ball-like opacity or a hole with-
out a ring.7 However, a visible ring is
not present in every case and is not
necessary to make this diagnosis.
There may also be associated pho-
topsia if the patient is experiencing vit-
reoretinal traction.8,9 If the patient
presents with multiple floaters, there
may be an associated vitreous hemor-
rhage. In cases where there is also a vit-
reous hemorrhage, there may be a
reduction in visual acuity.10 While acu-
ity is typically not affected by PVD
alone, visual reduction can result from
vitreous hemorrhage, cystoid macular
edema, epiretinal membrane or macu-
lar hole formation.10-14 In addition to
pre-retinal and vitreous hemorrhage,
there may also be pigmented cells
within the anterior vitreous (Shafer's
sign).15 There also always exists the
possibility of a tractional retinal tear
and/or rhegmatogenous retinal
detachment.8-10, 16-22
Pathophysiology
The vitreous is 98% water, with the
remaining constituents being collagen
and hyaluronic acid.23 The collagen, in
the form of fibrils, forms a scaffolding
that is inflated by hyaluronic acid mol-
ecules.24 If hyaluronic acid is removed,
the vitreous gel contracts.
The vitreous cortex is the outermost
aspect of the vitreous body, containing
the greatest density of collagen and
hyaluronic acid. There appears to be an
intervening extracellular matrix that
bonds the vitreous to the internal limit-
ing membrane (ILM) of the retina (and
not an insertion of the collagen fibrils
into the ILM, as previously thought).23
The vitreous cortex strongly adheres to
the optic disc and vitreous base and
along blood vessels. There is a weaker
adhesion at the macula.
Throughout life, there is a decrease
® EVYIET LRIEDOSU SA NADN DA DR NE TE IXNAA
in the vitreous gel volume and a subse-
quent increase in the liquid vitreous
volume.24 This results in the formation
of pockets of liquid vitreous termed
lacunae. A PVD occurs when loss of
adherence takes place between the vit-
reous cortex and ILM, with an increase
in vitreous liquefaction. This allows liq-
uid vitreous to enter the retro-cortical
space. Volume displacement from the
central vitreous to the pre-retinal space
results in the collapse of the vitreous
body.23
In an uncomplicated PVD, there is
a simultaneous weakening of the vitre-
oretinal adhesions and the develop-
ment of vitreous liquefaction. In this
case, the collapsing vitreous separates
from the retina without incident. In a
complicated PVD, vitreous liquefac-
tion exceeds the breakdown of vitreo-
retinal adhesion, the vitreous body col-
lapses and traction is exerted at the
vitreoretinal interface. The result may
include retinal tears and detachment,
Weiss ring in PVD
hemorrhage and vitreomacular traction
syndromes.8,10-12,14,17,21,23 Conditions
associated with vitreous liquefaction in
excess of vitreoretinal adhesion weak-
ening include Marfan’s, Ehlers-Danlos,
and Wagner-Stickler-Jansen’s syn-
dromes, as well as high myopia.23,25
Management
Any patient reporting a sudden
onset of new or increased floaters,
either with or without photopsia,
needs prompt inspection of the vitre-
ous and retina through a dilated pupil.
A thorough examination includes the
MARCH 15, 2006 REVIEW OF OPTOMETRY 39A
 use of binocular indirect ophthal-
moscopy (preferably with scleral
indentation), non-contact fundus lens
biomicroscopy and three-mirror con-
tact lens evaluation. While the presence
of a PVD is visually troubling, it
imparts no risk to a patient’s ocular
health. However, tractional tears result-
ing from a PVD can result in a rheg-
matogenous retinal detachment and
must be detected and prophylactically
treated promptly.10,17,19,21
Careful delineation of patient com-
plaints and thorough inspection of the
vitreous and retina will aid in proper
management. It is not possible to pre-
dict, based upon symptoms alone,
which patients will have a retinal tear
concurrent with PVD.15 Approxi-
mately 7% to 14% of patients experi-
encing acute PVD will have a con-
comitant retinal break.15,20-22 The
presence of pigment cells or hemor-
rhage within the vitreous strongly pre-
dicts the presence of a concurrent reti-
nal break.8,10,15,18,22 The prevalence of
retinal tears in the setting of acute pos-
terior detachment associated with vit-
reous hemorrhage alone, pigment
alone or vitreous hemorrhage and pig-
ment was noted in one study to be
54%.22 Patients with PVD who have
vitreous pigment granules or hemor-
rhage are 52 times more likely to have
a retinal tear, compared with those who
have normal findings on qualitative vit-
reous examination.22
A patient with acute uncomplicated
PVD still must be followed for the
development of new retinal breaks.
Dayan, et al., noted that 3% of patients
with acute PVD developed retinal
breaks later that were detected only at
follow-up, and recommended routine
re-evaluation at 6 weeks of all patients
with acute PVD (though the patients
developing subsequent retinal tears in
this study had also reported concurrent
vision decrease).20 However, van
Overdam, et al., recommend that only
patients with multiple floaters, a cur-
tain or cloud, hemorrhages (retinal or
40A REVIEW OF OPTOMETRY MARCH 15, 2006
vitreous) or Shafer’s sign at the initial
examination should be scheduled for
re-examination;8,18 all other patients
need return only if the number of
floaters increases or vision worsens.
Clinical Pearls
• Patients with acute PVD with a
small amount of pre-retinal or vitre-
ous hemorrhage and without an
observable retinal break need a
detailed peripheral exam using scleral
indentation as well as 3-mirror and/or
non-contact fundus lens biomi-
croscopy. If no retinal break is detect-
ed, the patient needs repeat evaluation
every two weeks for six weeks to look
for an occult break not found upon
the initial exam.18 If no retinal break is
detected after six weeks, by exclusion
the blood can likely be attributed to
torn retinal or disc capillaries, with the
patient considered to be out of imme-
diate danger.
• Patients with acute PVD must be
advised to report immediately if they
note an increase in the number of
floaters or decreased vision.
• Routine follow-up of patients
with uncomplicated PVD may be
unwarranted if they have no increased
symptoms.
1. Hayreh SS, Jonas JB. Posterior vitreous detach-
ment: Clinical correlations. Ophthalmologica
2004;218(5):333-43.
2. Uchino E, Uemura A, Ohba N. Initial stages of pos-
terior vitreous detachment in healthy eyes of older per-
sons evaluated by optical coherence tomography. Arch
Ophthalmol 2001;119(10):1475-9.
3. Weber-Krause B, Eckardt C. Incidence of posterior
vitreous detachment in the elderly. Ophthalmologe
1997;94(9):619-23.
4. Hikichi T, Trempe CL. Ocular conditions associated
with posterior vitreous detachment in young patients.
Ophthalmic Surg Lasers 1996;27(9):782-6.
5. Hikichi T, Yoshida A. Time course of development
of posterior vitreous detachment in the fellow eye
after development in the first eye. Ophthalmol
2004;111(9):1705-7.
6. Kakehashi A, Inoda S, Shimizu Y, et al. Predictive
value of floaters in the diagnosis of posterior vitreous
detachment. Am J Ophthalmol 1998;125(1):113-5.
7. Akiba J, Ishiko S, Yoshida A. Variations of Weiss's
ring. Retina 2001;21(3):243-6.
8. Van Overdam KA, Bettink-Remeijer MN, Klaver CC,
et al. Symptoms and findings predictive for the devel-
opment of new retinal breaks. Arch Ophthalmol
2005;123(4):479-84.
9. Margo CE, Harmon LF. Posterior vitreous detach-
ment. How to approach sudden-onset floaters and
flashing lights. Postgrad Med 2005;117(3):37-42.
10. Sarrafizadeh R, Hassan TS, Ruby AJ, et al.
Incidence of retinal detachment and visual outcome
in eyes presenting with posterior vitreous separation
and dense fundus-obscuring vitreous hemorrhage.
Ophthalmol 2001;108(12):2273-8.
11. Matsumura N, Ikuno Y, Tano Y. Posterior vitreous
detachment and macular hole formation in myopic
foveoschisis. Am J Ophthalmol 2004;138(6):1071-3.
12. Johnson MW, Van Newkirk MR, Meyer KA.
Perifoveal vitreous detachment is the primary patho-
genic event in idiopathic macular hole formation. Arch
Ophthalmol 2001;119(2):215-22.
13. Van Newkirk MR, Johnson MW, Hughes JR, et al.
B-scan ultrasonographic findings in the stages of idio-
pathic macular hole. Trans Am Ophthalmol Soc
2000;98:163-9;disc 169-71.
14. Johnson MW. Tractional cystoid macular edema: A
subtle variant of the vitreomacular traction syndrome.
Am J Ophthalmol 2005;140(2):184-92.
15. Tanner V, Harle D, Tan J, et al. Acute posterior vit-
reous detachment: The predictive value of vitreous pig-
ment and symptomatology. Br J Ophthalmol
2000;84(11):1264-8.
16. Gonzales CR, Gupta A, Schwartz SD, et al. The fel-
low eye of patients with phakic rhegmatogenous retinal
detachment from atrophic holes of lattice degeneration
without posterior vitreous detachment. Br J
Ophthalmol 2004;88(11):1400-2.
17. Sharma MC, Regillo CD, Shuler MF, et al.
Determination of the incidence and clinical character-
istics of subsequent retinal tears following treatment of
the acute posterior vitreous detachment-related initial
retinal tears. Am J Ophthalmol 2004;138(2):280-4.
18. Van Overdam KA, Bettink-Remeijer MW, Mulder
PG, et al. Symptoms predictive for the later develop-
ment of retinal breaks. Arch Ophthalmol
2001;119(10):1483-6.
19. Byer NE. Can rhegmatogenous retinal detachment
be prevented? Reflections on the history of "prophylac-
tic" treatment of retinal detachment. Ophthalmologe
2000;97(10):696-702.
20. Dayan MR, Jayamanne DG, Andrews RM, et al.
Flashes and floaters as predictors of vitreoretinal
pathology: Is follow-up necessary for posterior vitreous
detachment? Eye 1996;10(Pt 4):456-8.
21. Byer NE. Natural history of posterior vitreous
detachment with early management as the premier
line of defense against retinal detachment.
Ophthalmol 1994;101(9):1503-13.
22. Sharma S, Walker R, Brown GC, et al. The impor-
tance of qualitative vitreous examination in patients
with acute posterior vitreous detachment. Arch
Ophthalmol 1999;117(3):343-6.
23. Sebag J. Anomalous posterior vitreous detachment:
A unifying concept in vitreo-retinal disease. Graefes
Arch Clin Exp Ophthalmol 2004;242(8):690-8.
24. Sebag J. Aging of the vitreous. Eye 1987;1:254-62.
25. Maumenee IH. Vitreoretinal degenerations as a
sign of generalized connective tissue diseases. Am J
Ophthalmol 1979;88:432-49.

OPTOMAP TECHNOLOGY
Douglas Anderson, following a tragic
loss of vision in his five-year-old son from
an undiagnosed retinal detachment,
founded Optos® of North America,
Britain and Denmark in 1992. Although
his son had regular eye exams, the tests
seemed especially uncomfortable for
children. This made proper and com-
plete evaluation of the retina extremely
difficult without the added complication
of sedation. Anderson, who at the time
was an industrial engineer and obviously Peripheral retinal tear and detachment.
distressed by his personal situation, put
his company, Crombie Anderson Design Consultants, to work to
find a way to examine the entire retina in a more efficient, objec-
tive way. Anderson and his team labored for three years before
developing the OptoMap® Retinal Exam (Panoramic200™), the
world’s first ophthalmic device capable of producing a single,
high-resolution, ultra-widefield digital image of the retina.
The OptoMap® is able to capture ultra widefield images due
to its patented Virtual Point™ technology. The ultra-widefield
image is produced by allowing capture of the scan beam into the
eye via a large, concave ellipsoidal mirror. The ellipsoidal mirror
has two conjugate focal points. When lasers are scanned through
one focal point, the effect is translated to the other focal point.
This allows the imaging of the optical pathways to be substan-
tially separated from the object scanned. When a patient is
“scanned,” the red and green lasers are combined. The first focal
point the lasers pass through is located high on the ellipsoidal
mirror. The second, a “virtual point,” is located at a plane behind
the patient’s iris. This is where the scan is directed. As long as
the patient is positioned so that the virtual point remains within
the proper range (i.e., placed behind the patient’s iris), large cap-
ture angles are possible. The energy reflected from the retina is
collected by the ellipsoidal mirror and returned through the same
system. There, color-specific detectors analyze the data and feed
INDOCYANINE GREEN ANGIOGRAPHY (ICG) PRIMER
Indocyanine green angiography (ICGA) is an adjunct pro-
cedure to intravenous sodium fluorescein angiography
(IVFA).1-5 It is used to diagnose choroidal pathologies when
standard angiographic techniques cannot be employed or
would provide poor yield.1-23 Innovations such as digital pho-
tography and the scanning laser ophthalmoscope (SLO)
have made ICGA accessible to the clinician.1,5-7
® EVYIET LRIEDOSU SA NADN DA DR NE TE IXNAA
it to a frame grabber card that produces
high-resolution (2000 x 2000 pixel)
color images for display on a dedicated
computer system. Once in the computer,
the image may be electronically magni-
fied, manipulated, printed and stored as
desired.
OptoMap® technology provides
numerous benefits. First, it allows for a
widefield view of the fundus. Second, it
is capable of capturing up to 80% of the
retina with a single, on-axis image; this
can be accomplished without pharmaco-
logic dilation (provided the pupil is 2mm or greater). The process
is patient-friendly—image capture takes less than a second—and
does not require instrument contact. The resulting 200-degree
image can be digitally manipulated and inspected, making it an
additional tool for retinal and systemic disease detection. The
photograph can also be used to help educate patients regarding
their condition. The image can be stored in different electronic
formats, imported to other computer programs or prepared for e-
mail transfer. Finally, the technology is helpful for those who can-
not tolerate dilating drops and those who might be inclined to
otherwise refuse a standard dilated examination of the retina.
The OptoMap® technology and its yield can be augmented by
asking patients to position their eyes into differing fields of gaze
(this is known as the steering technique). A new advancement is
the system’s capability for obtaining angiographic studies. Even
with this addition, however, the instrument has not reached
acceptance in the ophthalmic community as a replacement for
the traditional dilated binocular indirect ophthalmologic exami-
nation or standard angiographic techniques.
1. http://www.optos.com.
2. Nataloni, R. Ultra wide field imaging with angiography enhances disease detec-
tion. Retinal Phys 2005;2(4):52-6.
Indocyanine green dye has different properties than sodi-
um fluorescein that make it better suited to image the
choroidal vasculature. Its excitation and emission peaks,
800 to 810 nm and 835 nm, respectively, are in the near-
infrared spectrum, allowing for better penetration of viewing
through pigments such as xanthophyll, hemoglobin and
melanin.1-7,9,10,13,14 ICG dye demonstrates 98% plasma pro-
MARCH 15, 2006 REVIEW OF OPTOMETRY 41A
 tein binding (mostly albumin), which permits it to remain
mainly intravascular, even as the dye circulates through the
fenestrated capillaries of the choriocapillaris.1-7,9,16 The SLO
has increased image resolution and increased image con-
trast, providing a system that helps visualize pathology.1,4-7
ICGA should not be performed on patients who are preg-
nant or individuals with established uremia or hepatic dys-
function.1,4,6,9 In that ICG dye contains 5% iodine by weight,
patients with potential hypersensitivities should be pre-
screened for iodine and seafood allergies to avoid cross-sen-
sitivity.1,4,6,9,10 Transient nausea, vomiting, itching, urticaria,
syncope and anaphylaxis have all occurred from ICGA.1,4,9
The interpretation of ICGAs is similar to that of IVFA, and
the test and the injection sequence are also similar, with a
minor difference in the digital image recording. The first or
early phase of the test has three stages: The initial stage
begins approximately 2 seconds after injection and is
marked by a rapid filling of the choroidal arteries and chori-
ocapillaris, with early filling of the choroidal veins.1,6,10 The
retinal blood vessels are still dark on the angiogram, along
with the choroidal “watershed zone” around the optic nerve
head.1,6,10 In the second stage, from 3 to 5 seconds after
injection, the larger choroidal veins begin to fill and fluo-
resce along with the retinal arteries as the ICG perfuses.1,6,10
The final stage of the early phase occurs from 6 seconds to
3 minutes after injection; the watershed zone is now filled,
but the choroidal arteries and larger choroidal veins begin to
fade.1,6,10
The middle phase (3 to 15 minutes after injection) is
marked by continuing fading of the choroidal and retinal
vessels.1,6,10 The late phase (15 to 60 minutes after injec-
tion) demonstrates staining of the extrachoroidal tissue, giv-
ing the choroidal vasculature the illusion of hypofluores-
cence compared to the background tissue.1,6,10
Abnormal areas on an ICGA show as either hypo- or
hyperfluorescent. Hypofluorescence can be attributed to
blockage of the dye by overlying retinal abnormalities such
as blood, serous fluid, pigment or exudation.1,4,10,13,15
Anything capable of blocking perfusion may also cause
hypofluorescence by interrupting blood flow through a given
area of the choroid.1,4,6,15,17 Further, any loss of choroidal tis-
sue (e.g., acute posterior multifocal placoid pigment epithe-
liopathy) will show up as hypofluorescent.1,3,10,17,18
Hyperfluorescence can be caused by a lack of overlying
tissue (retinal pigment epithelium dropout, lacquer cracks),
leakage from normal vessels, staining of surrounding tissues
or leakage from abnormal blood vessels (e.g., neovascular-
ization or idiopathic polypoidal vasculopathy).1-4,10,19
Hot spots and plaques are areas of intense hyperfluores-
cence that occur during the middle and late phases of the
ICGA. These diagnostic lesions can be attributed to poly-
poidal choroidal neovascularization, retinal angiomatous
proliferation and occult choroidal neovascularization.1,4,6,10,19
ICGA has been highly recommended for identification of
occult age-related macular degeneration (AMD), idiopathic
polypoidal choroidal vasculopathy, neovascularization asso-
ciated with retinal pigment epithelial detachments and
recurrent choroidal neovascularization (CNV).1,4 ICGA is also
recommended for new cases of suspected CNV, delineation
42A REVIEW OF OPTOMETRY MARCH 15, 2006
of feeder vessels in AMD, chronic central serous chori-
oretinopathy, multiple effenescent white dot syndrome, reti-
nal vasculitis, acute multifocal posterior placoid epithe-
liopathy, Vogt-Koyanagi-Harada syndrome, angioid streaks
and birdshot chorioretinopathy.1,3
1. Dzurinko VL, Gurwood AS, Price JR. Intravenous and indocyanine green angiog-
raphy. Optom 2004;75(12):743-55.
2. Slakter JS, Yannuzzi LA, Guyer DR, et al. Indocyanine-green angiography. Curr
Opin Ophthalmol 1995;6(3):25-32.
3. Schneider U, Sherif-Adel S, Gelisken F, et al. Indocyanine green angiography
and transmission defects. Acta Ophthalmol Scand 1997;75(6):653-6.
4. Stanga, PE, Lim JL, Hamilton P. Indocyanine green angiography in chorioretinal
diseases: Indications and interpretation. Ophthalmol 2003;110(1):15-21.
5. Bischoff, PM, Niederberger HJ, Torok B, et al. Simultaneous indocyanine green
and fluorescein angiography. Retina 1995;15(2):91-9.
6. Kumar A, Nainiwal S, Prakash G. Indocyanine green angiography in age-related
macular degeneration. Bombay Hosp J 2002;44(3):333-9.
7. Nagpal M, Banait S. Scanning laser ophthalmoscopy in macular degeneration.
Bombay Hosp J 2002;44(3):340-50.
8. Bennett TJ. Fundamentals of fluorescein angiography. Curr Concepts
Ophthalmol 2001;9(3):43-9.
9. Chopdar A. Manual of Fundus Fluorescein Angiography. Toronto, CA:
Butterworths 1989, pp. 1-134.
10. Kanski, JJ. Acquired macular disorders. In: Kanski, JJ. Clinical
Ophthalmology: A Systemic Approach, 4th ed. New York: Butterworth-Heinemann,
1999, pp. 396-436.
11. Garcia CR, Rivero ME, Bartsch DU, et al. Oral fluorescein angiography with the
confocal scanning laser ophthalmoscope. Ophthalmol 1999;106(6):1114-8.
12. Alexander LJ. Exudative and nonexudative macular disorders. In: Alexander LJ.
Primary Care of the Posterior Segment, 3rd ed. New York: McGraw-Hill, 2002, pp.
75-208.
13. Gupta D. Fluorescein angiography refresher course. Rev Optom
2001;138(11):60-6.
14. Atmaca LS, Batioglu F, Atmaca P. Evaluation of choroidal neovascularization
in age-related macular degeneration with fluorescein and indocyanine green
videoangiography. Ophthalmologica 1996;210(3):148-51.
15. Kramer M, Mimouni K, Priel E, et al. Comparison of fluorescein angiography
and indocyanine green angiography for imaging of choroidal neovascularization in
hemorrhagic age-related macular degeneration. Am J Ophthalmol
2000;129(4):495-500.
16. Yang CS, Lin CL, Lee FL, et al. Digital indocyanine green angiography in chori-
oretinal diseases. Chin Med J 1995;56(6):411-7.
17. Reichel E, Duker JS, Puliafito CA. Indocyanine green angiography and
choroidal neovascularization obscured by hemorrhage. Ophthalmol 1995;
102(12):1871-6.
18. Howe L, Stanford M, Graham E, et al. Indocyanine green angiography in
inflammatory eye disease. Eye 1998;12(5):761-7.
19. Howe LJ, Woon H, Graham EM, et al. Choroidal hypoperfusion in acute poste-
rior multifocal placoid pigment epitheliopathy: An indocyanine green angiography
study. Ophthalmol 1995;102(5):790-8.
20. Fernandes LH, Freund KB, Yannuzzi LA, et al. The nature of focal areas of
hyperfluorescence or hot spots imaged with indocyanine green angiography. Retina
2002;22 (5):557-68.
21. Berger JW, Maguire MC, Fine SL. The macular photocoagulation study. In:
Kertes PJ, Conway MD. Clinical Trials in Ophthalmology: A Summary and Practice
Guide, 1st ed. Philadelphia: Lippincott, Williams and Wilkins 1998, pp. 71-96.
22. Guyer DR, Yannuzzi LA, Slakter JS, et al.. Digital indocyanine-green videoan-
giography of occult choroidal neovascularization. Ophthalmol
1994;101(10):1727-35.
23. Guyer DR, Yannuzzi LA, Slakter JS, et al. Classification of choroidal neovas-
cularization by digital indocyanine green videoangiography. Ophthalmol
1996;103(12):2054-60.
NEURO-OPHTHALMIC DISEASE
ABERRANT REGENERATION
OF CRANIAL NERVE III
Signs and Symptoms
In that there are two types of aber-
rant regeneration of cranial nerve
(CN) III, that is, primary and second-
ary, the onset of presentation will vary.
Patients with secondary aberrant
regeneration of CN III present follow-
ing an identified CN III palsy.1-7
However, patients with primary aber-
rant regeneration of CN III will not
have an antecedent CN III palsy in
their history.8-14
Patients with either form of aber-
rant regeneration will have character-
istic eyelid positioning and action as
well as ocular motility deficits.
Secondary aberrant regeneration often
demonstrates residual adduction, ele-
vation and depression deficits, as well
as some degree of ptosis. The ptosis
and ophthalmoplegia are less pro-
nounced than what is observed during
the clinical phase of the CN III palsy.
The full-blown features of the syn-
drome include horizontal gaze–eyelid
synkinesis (the patient’s upper eyelid
will lower on abduction and elevate
on adduction), pseudo-Graefe sign
(the eyelid will elevate when the
patient looks down), limitation of ele-
vation and depression of the eye with
retraction of the globe on attempted
vertical movements, adduction of the
involved eye on attempted elevation
or depression, pseudo-Argyll
Robertson pupil (the pupil constrict-
ing with attempted adduction) and
absent vertical optokinetic response.
Pseudo-Graefe sign is the most com-
mon finding.1,2,4-6,15
Pathophysiology
CN III is the only cranial nerve
with a subnuclear complex that arises
in the dorsal mesencephalon at the
level of the superior colliculus.
Fascicles pass through the red nucleus
and corticospinal tract of the mid-
brain. They exit the mesencephalon
and emerge into the subarachnoid
space between the cerebral peduncles.
CN III enters the lateral wall of the
cavernous sinus, bifurcating into
superior and inferior divisions before
exiting. Finally, it enters the superior
orbital fissure, where it divides to
innervate the muscles. Nerve fibers of
CN III innervate the medial rectus,
inferior rectus, inferior oblique,
superior rectus, levator palpebrae
superioris of the eyelid and the iris
sphincter.
Aberrant regeneration occurs
when damage to the CN III results
in a resprouting and miscommunica-
tion of portions of the nerve to the
muscles. Fibers meant for certain
muscles innervate the wrong mus-
cles..9,12 For example, the inferior rec-
tus and medial rectus both commu-
nicate with the levator palpebrae
superioris. As a result, when the medi-
al rectus receives stimulation to con-
tract and adduct the eye, it also stim-
ulates the levator palpebrae superioris.
In this case, upon adduction, there
will also be lid elevation and widening
Primary aberrant regeneration of CN III.
of the palpebral fissure. With attempt-
ed abduction, the medial rectus and
the levator will be inhibited. Here, the
lid assumes a ptotic state when the eye
abducts. The inferior rectus also shares
fibers with the levator palpebrae supe-
rioris. Thus, when the patient looks
down, the eyelid will retract, increas-
ing the interpalpebral fissure. The
medial rectus shares communication
with the pupil. When the patient
adducts, the pupil constricts.
Secondary aberrant regeneration
commonly occurs after CN III palsy,
resulting from direct damage to CN
® NEURO-OPHTHALMIC DISEASE
III. Aneurysm, trauma and compres-
sion by tumor are typical causes.1-3,5-7
Inflammatory causes of CN III palsy
may result in aberrant regeneration.
Aberrant regeneration does not typi-
cally occur after CN III palsy from
ischemic infarct.4
Pseudo-Graefe sign in primary aberrant regenera-
tion of CN III secondary to intracavernous dis-
ease. (Photo courtesy of Dr. Steven Spear).
Primary aberrant regeneration
occurs independently of antecedent
CN III palsy. Likely, subclinical com-
pression of CN III damages the nerve
fibers, producing ongoing simultane-
ous regeneration and aberrant re-
sprouting of fibers to incorrect mus-
cles. The patient may not complain of
diplopia or ptosis and may not even
be aware of the changes as they are
occurring. A slow-growing mass, such
as an aneurysm or meningioma, with-
in the cavernous sinus, typically caus-
es this variant.11-14 Such lesions have a
low potential for causing morbidity or
mortality. However, not all cases of
primary aberrant regeneration of CN
III occur from benign causes.
Intracranial aneurysms of the posteri-
or communicating artery have result-
ed in primary aberrant regeneration of
CN III.8
Management
Secondary aberrant regeneration
requires no management beyond
recognition, unless it follows a pre-
sumed ischemic vascular CN III palsy.
In such a case, one should look for
another potential etiology.
Cases of primary aberrant regenera-
tion of CN III mandate investigation
for a meningioma or internal carotid
artery aneurysm within the ipsilateral
MARCH 15, 2006 REVIEW OF OPTOMETRY 43A
 cavernous sinus, as well as other, more
sinister compressive lesions. Neuro-
radiological imaging of the chiasm,
cavernous sinuses and parasellar
areas—preferably MRI with con-
trast—is appropriate. Neurosurgical
consultation will be necessary if imag-
ing reveals a mass lesion within the
cavernous sinus.
Clinical Pearls
• Primary aberrant regeneration of
CN III typically represents a menin-
gioma or internal carotid artery
aneurysm within the cavernous sinus.
• The most clinically identifiable
sign in CN III aberrant regeneration
is lid elevation and retraction in down
gaze (pseudo-Graefe sign).
• Secondary aberrant regeneration
commonly occurs after non-ischemic
vascular CN III palsy.
• Occasionally, lesions that have the
potential to cause morbidity or even
mortality can cause primary aberrant
regeneration of CN III. All primary
aberrant CN III regenerations deserve
neuroradiological scans of the brain,
orbits and chiasm.
1. Preechawat P, Sukawatcharin P, Poonyahalang A,
et al. Aneurysmal third nerve palsy. J Med Assoc Thai
2004;87(11):1332-5.
2. Chua HC, Tan CB, Tjia H. Aberrant regeneration of
the third nerve. Singapore Med J 2000;41(9):458-9.
3. Schumacher-Feero LA, Yoo KW, Solari FM, et al.
Third cranial nerve palsy in children. Am J
Ophthalmol 1999;128(2):216-21.
4. Trobe JD. Isolated third nerve palsies. Semin
Neurol 1986;6(2):135-41.
5. Hamer J. Prognosis of oculomotor palsy in patients
with aneurysms of the posterior communicating artery.
Acta Neurochir (Wien) 1982;66(3-4):173-85.
6. Laguna JF, Smith MS. Aberrant regeneration in
idiopathic oculomotor nerve palsy: Case report. J
Neurosurg 1980;52(6):854-6.
7. Keane JR. Bilateral aberrant regeneration of the
third cranial nerve following trauma. Case report. J
Neurosurg 1975;43(1):95-7.
8. Carrasco JR, Savino PJ, Bilyk JR. Primary aberrant
oculomotor nerve regeneration from a posterior com-
municating artery aneurysm. Arch Ophthalmol
2002;120(5):663-5.
9. Landau K. Discovering a dys-covering lid. Surv
Ophthalmol 1997;42(1):87-91.
10. Cohen DA, Bosley TM, Savino PJ, et al. Primary
aberrant regeneration of the oculomotor nerve.
Occurrence in a patient with abetalipoproteinemia.
44A REVIEW OF OPTOMETRY MARCH 15, 2006
Arch Neurol 1985;42(8):821-3. erochromia and absence of a horizon-
11. Mori M, Yokoyama N, Kinoshita N, et al. A case tal eyelid fold or crease in the ptotic
of primary aberrant oculomotor regeneration due to
intracavernous aneurysm. Rinsho Shinkeigaku eye.1-5,9 Iris pigmentation (which is
1984;24(8):765-8. under sympathetic control during
12. Sibony PA, Lessell S, Gittinger JW Jr. Acquired development) is completed by this
oculomotor synkinesis. Surv Ophthalmol 1984; age, making heterochromia an
28(5):382-90.
uncommon finding in Horner’s syn-
13. Cox TA, Wurster JB, Godfrey WA. Primary aberrant
oculomotor regeneration due to intracranial aneurysm. dromes acquired later in life.1-3 Old
Arch Neurol 1979;36(9):570-1. photographs can aide the clinician in
14. Schatz NJ, Savino PJ, Corbett JJ. Primary aber- distinguishing congenital Horner’s by
rant aculomotor regeneration. A sign of intracavernous documenting heterochromia present
meningioma. Arch Neurol 1977;34(1):29-32.
at birth.1-5
15. Lotufo DG, Smith JL, Hopen G, et al. The pupil in
congenital third nerve misdirection syndrome. J Clin
Neuroophthalmol 1983;3(3):193-6. Pathophysiology
Sympathetic innervation to the eye
consists of a three-neuron arc.1-9 The
HORNER’S SYNDROME first neuron originates in the dorsolater-
al hypothalamus. It descends through
Signs and Symptoms the reticular formation of the brain
Horner’s syndrome is characterized stem and travels to the ciliospinal center
by an interruption of the oculosympa- of Budge, between the levels of the
thetic nerve supply somewhere eighth cervical and fourth thoracic ver-
between its origin (in the hypothala- tebrae (C8-T4) of the spinal cord.
mus) and the eye.1-9 The classic clini- There, it synapses with second-order
cal findings associated with Horner’s neurons whose preganglionic cell bod-
syndrome are ptosis, pupillary miosis, ies give rise to axons, which exit the
facial anhidrosis, apparent enophthal- white rami communicantes of the
mos, increased amplitude of accom- spinal cord via the anterior horn. These
modation, heterochromia of the irides axons pass over the apex of the lung and
(if congenital or occurring before the enter the sympathetic chain in the neck,
age of two years), paradoxical con- synapsing in the superior cervical gan-
tralateral eyelid retraction, transient glion.1-9 Here, cell bodies of third-order
neurons give rise to postganglion-
ic axons that course to the eye
with the internal carotid artery via
the cavernous sinus.1-9 Fibers from
these axons form the long and
short posterior ciliary nerves of the
eye. These sympathetic nerve
fibers course anteriorly through
the uveal tract and join the fibers
of long posterior ciliary nerves,
which course with branches of the
fifth cranial nerve, to innervate the
dilator of the iris. Postganglionic
Iris heterochromia in Horner's syndrome. Note: patient
is of African descent with a blue iris; the other iris sympathetic fibers also innervate
was brown. the muscle of Mueller, responsible
for initiating eyelid retraction dur-
decrease in intraocular pressure and ing eyelid opening. Postganglionic sym-
changes in tear viscosity.1-9 Horner’s pathetic fibers responsible for facial
syndrome has no predilection for age, sweating follow the external carotid
race, gender or geographic location. artery to the sweat glands of the face.1-9
Horner’s syndromes of congenital ori- Interruption at any location along
gin present around age two, with het- this pathway (pre-ganglionic or post-

ganglionic) will induce an ipsilateral
Horner’s syndrome.
The diagnosis and localization of a
Horner’s syndrome can be accom-
plished with pharmacological test-
ing.5-9 Topically applied 10% cocaine
works as an indirect acting sympath-
omimetic agent, producing pupillary
dilation in the normally innervated
pupil by inhibiting the reuptake of
norepinephrine at the nerve ending.4-9
A Horner’s pupil will dilate poorly
compared to a normal eye because of
the absence of norepinephrine at the
nerve ending.4-9 The eye should be
evaluated 30 minutes after instillation
of the drops to ensure accuracy. The
cocaine test is used to confirm or deny
the presence of a Horner’s syndrome.
A positive cocaine test does not local-
ize the lesion.1-9 To identify the lesion
as either pre-ganglionic (neurons 1 or
2 before the synapse in the superior
cervical ganglion) or post-ganglionic
(after exiting the superior cervical gan-
glion), Paredrine 1% (hydroxy-
amphetamine) or Pholedrine 5%
(n-methyl derivative of hydroxy-
amphetamine) can be instilled 48
hours later. Pholedrine and Paredrine
act similarly, by producing the forced
release of endogenous norepinephrine
from the presynaptic vesicles. If the
third neuron is damaged, the pupil
will not dilate, indicating a post-gan-
glionic lesion.1-9 There is currently no
method of topical testing to differen-
tiate a first order pre-ganglionic lesion
from a second order pre-ganglionic
lesion.7
The common etiologies of acquired
Horner’s syndrome include but are
not limited to: trauma, aortic dissec-
tion, carotid dissection, tuberculosis
and Pancoast tumor.1-9 Aortic dissec-
tion is a tear in the intimal region of
the ascending aorta near the aortic
valve.1-9 It often occurs along the right
lateral wall of the ascending aorta,
where the hydraulic stress is the great-
est.1-9 Compression of adjacent tissues
(e.g., superior cervical ganglia, superi-
or vena cava, bronchus, esophagus) by
the expanding dissection can result in
Horner’s syndrome, superior vena
cava syndrome, vocal cord paralysis,
hoarseness, dysapnea and dysphagia.
Patients with longstanding systemic
hypertension, Marfan’s syndrome or
Ehlers-Danlos syndrome are at
increased risk.1-9
Tuberculosis (TB) is a chronic
infectious disease caused by the organ-
ism Mycobacterium tuberculosis.1-9 It
is an airborne disease that is transmit-
ted from person to person by the
inhalation of infected air droplets. It
can infect any organ in the body;
however, the lungs are the most preva-
lent site of involvement.8,9 Tubercles
(from which the name of the disease is
derived) are granulomatous inflam-
mations that invade the lung and
induce tissue necrosis, referred to as
caseations.9 If the tubercle occupies a
position at the lung apex, it may com-
press pre-ganglionic sympathetic
axons, producing a Horner’s syn-
drome. Diagnosis can be made with a
purified protein derivative (PPD)
accompanied by an anergy panel.9
Chest X-ray and erythrocyte sedimen-
tation are also helpful in confirming
diagnosis.9
Pancoast tumor, or superior pul-
monary sulcus carcinoma, was first
described in 1924 by H. K. Pan-
coast.10 Clinical characteristics of
Pancoast tumor include shoulder
pain, loss of limb function, atrophy of
the muscles of the hand, Horner’s syn-
drome and dullness of feeling in the
region of the upper chest.10 A true
Pancoast tumor usually extends
through the visceral pleura into the
parietal pleura and chest wall. The
tumor is considered epithelial in its
histopathology, but its exact origin
remains uncertain. Despite a small size
and general lack of metastasis,
Pancoast tumor has a rapid and almost
universal mortality rate. Approximately
80% to 90% of all lung cancers are
linked or associated with smoking.10
Other risk factors include exposure to
asbestos, radon gas, uranium, arsenic
fumes, isopropyl oil, nickel, metallic
iron, iron oxide or beryllium.
® NEURO-OPHTHALMIC DISEASE
Management
In general, the treatment for
Horner’s syndrome depends upon the
cause. In many cases, there is no treat-
ment to improve or reverse the condi-
tion. Treatment in acquired cases is
directed toward irradiating the disease.
Recognizing the signs and symptoms
is paramount to making an early diag-
nosis, as is making expedient referrals
to appropriate medical specialists. The
unique presentation of unilateral
headache, partial Horner’s syndrome
and V1 sensory disturbance in the
presence of negative neuroimaging
studies may identify the rare entity
known as Raeder’s syndrome.11 This
vasculopathic, post-ganglionic malady
produces a painful Horner’s syndrome
and may remedied, in most cases, with
pharmacologic agents.12 One report in
the literature has linked this unusual
syndrome to the cluster migraine
headache, either proposing a relation-
ship or placing it onto a continum.11
Clinical Pearls
• Topical cocaine is used to confirm
the clinical diagnosis of Horner’s syn-
drome. Cocaine blocks the re-uptake
of norepinephrine at the sympathetic
nerve terminals in the iris dilator mus-
cle, transiently increasing its concen-
tration in the synaptic junction. The
norepinephrine activates alpha-1
receptors in the iris dilator to cause
pupillary dilation. A positive test
demonstrates poor or no dilation,
compared to the unaffected side.
• Hydroxyamphetamine causes the
third neuron to release norepinephrine
from its synaptic vesicles. In the event
that a pupil dilates following adminis-
tration of hydroxyamphetamine, one
may conclude that the third neuron is
intact, indicating a preganglionic
source for the interruption.
• The time frame for completing
testing is important. Since cocaine
also has the ability to inhibit the
uptake of hydroxyamphetamine into
the presynaptic vesicle, it can reduce
the second test’s accuracy.5-9 These
tests should absolutely be performed
MARCH 15, 2006 REVIEW OF OPTOMETRY 45A
 on different days.
• A recently investigated practical
and reliable alternative to cocaine is
apraclonidine12 (Iopidine, Alcon
Laboratories), an ocular hypotensive
agent that has a weak, direct action on
alpha-1 receptors and therefore mini-
mal to no clinical effect on the pupils
of normal eyes.12 Since patients with
Horner’s syndrome acquire a denerva-
tion supersensitivity to norepineph-
rine, an increase of the alpha-1 recep-
tors in the iris stroma of the affected
eye occur, making the muscle respon-
sive to this preparation.
1. Wilkins RH, Brody IA, Durham NC. Horner’s syn-
drome. Arch Neurol 1968;19:540-2.
2. Horner F. Uber eine form von ptosis. Klin Monatsbl
Augenh 1869;7:193.
3. Tantum LA. Pupil anomalies. In: Onofrey BE, ed.
Clinical Optometric Pharmacology and Therapeutics.
Philadelphia: J. B. Lippincott, 1991, pp. 1-13.
4. Burde RM, Savino RJ, Trobe JD. Anisocoria and
abnormal pupillary light reaction. In: Burde RM,
Savino PJ, Trobe JD, eds. Clinical Decisions in Neuro-
Ophthalmology, 2nd ed. St. Louis; Mosby, 1992, pp.
321-46.
5. Myles WM, Maxner CE. Localizing value of concur-
rent sixth nerve paresis and postganglionic Horner’s
syndrome. Can J Ophthalmol 1994;29(1):39-42.
6. Maloney WF, Younge BR, Moyer NJ. Evaluation of
the causes and accuracy of pharmacologic localiza-
tion in Horner’s syndrome. Am J Ophthalmol
1980;90(3):394-402.
7. Bates AT, Chamberlain S, Champion M, et al.
Pholedrine: A substitute for hydroxyamphetamine as a
diagnostic eyedrop test in Horner’s syndrome. J
Neurol Neurosurg Psych 1995;58(2):215-7.
8. Thompson HS, Pilley SFJ. Unequal pupils—a flow
chart for sorting out the anisocorias. Surv Ophthalmol
1976;21(1):45-8.
9. Cullom RD, Chang B. Neuro-ophthalmology:
Horner’s Syndrome. In: Cullom RD, Chang B, eds. The
Wills Eye Manual, 2nd ed. Philadelphia: J. B.
Lippincott, 1993, pp. 241-6.
10. Sartori F, Rea F, Calabro F, et al. Carcinoma of the
superior pulmonary sulcus. J Thorac Cardiovasc Surg
1992;104:679-83.
11. Ikeuchi T, Tokutake T, Sakamaki Y, et al.
Progression of cluster headache to Raeder’s syndrome
with marked response to corticosteroid therapy: A
case report. Rinsho Shinkeigaku 2005;45(4):321-3.
12. Freedman KA, Brown SM. Topical apraclonidine
in the diagnosis of suspected Horner syndrome.
Neuroophthalmol 2005;25(2):83-5.
TONIC PUPILS
Signs and Symptoms
Tonic pupils (sometimes referred to
46A REVIEW OF OPTOMETRY MARCH 15, 2006
as internal ophthalmoplegia) are the tive and pupillary responses increase.
result of damage to the parasympa- Tonic pupils can occur at any age and
thetic innervation to the eye, resulting in both genders; however, 70% of
in decreased function of the iris them occur in females between 20
sphincter as well as the ciliary body.1-10 and 50 years.1-7
The tonic pupil responds both to light
Pathophysiology
Afferent input to the
parasympathetic pathway
results in pupillary constric-
tion (the direct light reac-
tion). The pathway origi-
nates in the photoreceptors
and retinal ganglion cells
and travels via the optic
nerve, chiasm and optic
tract. Some fibers leave the
tract prior to the lateral
Note the iris sector paralysis from 6 o'clock to 11 o'clock. geniculate body via the
superior colliculus and the
and near stimuli with extremely slow brachium conjunctivum. These fibers
constriction and re-dilation. Patients synapse in the pretectum and are dis-
typically present with a chief com- tributed bilaterally to the Edinger-
plaint of unilaterally reduced near Westphal Nucleus (EWN) of the ocu-
vision and anisocoria (asymmetry of lomotor nerve in the midbrain.1-7
pupil size). When first noted by the Parasympathetic tone of the irides
patient in ambient light, the tonic originates in this complex group of
pupil is often the larger of the two. paired midline nuclei. The efferent
However, if viewed in dim illumina- fibers travel with the third cranial
tion, it becomes the smaller pupil.1,2 nerve, entering the orbit and synaps-
Interestingly, the anisocoria may ing in the ciliary ganglion.1-7 Post
diminish as the tonic pupil becomes synaptic fibers leave the ganglion trav-
more miotic over time.1-3,5-7,9 The eling as the short ciliary nerves, pierc-
tonic pupil is typically unilateral ing the sclera to arrive at their end
(90%), but may become bilateral at a organ destinations, the iris and ciliary
rate of 4% per year.1-3,7 body.1,2 Ninety-three to 97% of these
Along with the pupil anomaly, parasympathetic fibers go on to sup-
parasympathetic damage may result in ply the ciliary body, resulting in the
dysfunction of the ciliary body, caus- stimulation of accommodation. The
ing accommodative spasm, accom- remaining 3% to 7% innervate the
modative insufficiency and induced pupillary sphincter, allowing constric-
astigmatism and generating com- tion of the pupil in response to
plaints of blur at distance and near.1,2 light.1,2,5-7 The hypothesized reason for
Accommodation, like pupillary con- this uneven distribution is the
striction and re-dilation, is tonic as the unequal masses of the ciliary muscle
patient changes fixation from distance and the sphincter.1,2,5,6
to near and back again. As a result, Interruption of the above pathway
patients with tonic pupil often com- anywhere along its route can result in
plain that vision transiently blurs incomplete parasympathetic innerva-
(until the ciliary muscle catches up or tion, causing pupillary dilation,
relaxes) during attempts at focusing. decreased speed and amplitude of
Accommodative amplitude is also constriction and decreased speed and
reduced in these individuals.1,2 Over amplitude of accommodation. Since
time, the tonicity of the accommoda- the input to the EWN is crossed and

innervation of the pupillary sphincters
is bilateral, the pupils are expected to
be equal in size.5 Acquired anisocoria
indicates a lesion in one of the efferent
pathways or the iris muscle.
Also playing a role in pupillary con-
striction are three synkinetic reactions:
1) The near reflex (miosis, accommo-
dation and convergence); 2) Bell’s
phenomenon (levator inhibition,
superior rectus activation and miosis);
and 3) The Westphal-Piltz reaction
(orbicularis contraction and mio-
sis).2,3,5,7
Specific clinical signs may be seen
following injury to the ciliary gan-
glion or the short ciliary nerves. These
include light-near dissociation
(LND), tonicity of the pupillary light
reaction and accommodation, seg-
mental palsy of the iris sphincter and
denervation hypersensitivity to dilute
cholinergic agents.1-10 In the 8 to 12
weeks following injury to the ciliary
ganglion, surviving nerve cells sprout
collaterals to re-innervate the ciliary
body and the pupil.1,2,4,6 Because of
the 30:1 ratio of fibers originally
favoring the ciliary muscle, this re-
innervation results in a pupil that con-
stricts more to near stimulation than
to light.1-7 This is LND.
In addition, the re-established con-
nections are less efficient, and this fur-
ther contributes to the latency and
slow pupillary constriction.1,2 The
tonic pupil also dilates poorly due to
inappropriate tone secondary to aber-
rant reinnervation.5,6 The tonic char-
acteristic of both constriction/redila-
tion is also due in part to the
decreased number of intact neuro-
muscular junctions following injury.
Segmental palsy results from the
fact that the sphincter is made up of
70 to 80 separate motor units, each
served by a separate parasympathetic
nerve fiber.8 Partial denervation will
then result in partial or segmental
constriction of the iris in response to
light and near stimuli. Unlike light
near dissociation, which takes weeks
to months to develop, hypersensitivity
can be observed in days to weeks.1,2,5,6
Management
The first step in proper diagnosis is
determining whether the anisocoria is
benign and physiologic or acquired
and pathologic. This is accomplished
by comparing the amount of anisoco-
ria in bright illumination with the
amount in dim illumination. Pupils
with physiological anisocoria will
show a relative size difference that
does not vary between illumination
levels. Pupils suffering from sympa-
thetic pathway lesions (i.e., Horner’s
syndrome) will possess greater aniso-
coria in dim illumination because of
failure of the iris dilator.1-5,9,10 Pupils
suffering from parasympathetic path-
way interruptions will demonstrate
anisocoria that is larger in bright
light.1-5,9,10
The second step is to observe and
grade the pupil’s ability to react to
light (both direct and consensual
response). Third, the amount of con-
striction accompanying accommoda-
tive effort should be assessed and
compared to the light response,
checking for LND. It is also helpful to
know how long the anisocoria has
been present, as a more acute onset is
more likely to herald a true neurolog-
ical emergency. If the patient cannot
offer a time frame, a high plus power
condensing lens can be used to exam-
ine old photographs.
The tonic pupil can be diagnosed
upon examination with the biomicro-
scope.8 With the slit beam opened
wide and directed from a 60 degree
angle, the details of the iris can be eas-
ily observed. When tonic pupils are
present, the clinician will observe large
sectors of the iris that do not constrict
to light as the illumination is turned
on and off; rather are dragged by
neighboring functional segments.8
This phenomenon, referred to as
“stromal streaming,” is the result of
sectoral palsy of the sphincter mus-
cle.1,2,4,6-9 Thompson observed 122
patients with Adie’s tonic pupil.8
Every pupil exhibited this sectoral
paralysis. He also observed the ten-
dency for sphincter function to
® NEURO-OPHTHALMIC DISEASE
decrease over time. The near reaction
in tonic pupils is often segmental as
well. Interestingly, segments that are
reactive during accommodation may
not be the same ones that react to
light.8 The pupillary constriction that
accompanies accommodation is slow,
and after the near effort is relaxed,
redilation may take minutes to hours.2
Pharmacological testing helps in
diagnosing tonic pupil. In 80% to
90% of patients with tonic pupil,
dilute pilocarpine (0.125%) or metha-
choline (2.5%) will induce pupillary
constriction; normal pupils do not
respond to these low concentra-
tions.1,2,5-7 To accurately test for hyper-
sensitivity, the corneal epithelium
must be intact. Any pathology, proce-
dure (for example, tonometry) or
medication that compromises corneal
integrity may produce a false-positive
result. Alternatively, profuse tearing or
blinking may dilute the already weak
pilocarpine, resulting in false-negative
findings.1-3 Observations of pupil
diameter should be made while fixa-
tion is directed at distance to elimi-
nate any contribution of the near syn-
kinetic response.1,2 One drop of
0.125% pilocarpine is then instilled
into the inferior fornix of both eyes,
and the pupil diameters are re-evaluat-
ed 45 minutes later.1-3 If denervation
hypersensitivity is present, one of two
things will be observed: 1) The
involved pupil will constrict more
than 0.5mm relative to the fellow eye,
or 2) the suspicious pupil, larger in
size before instillation of the drop, will
become the smaller pupil following
instillation.1,2 It is important to note
that hypersensitivity is not limited to
post-ganglionic lesions of the ciliary
ganglion. It may also occur in pre-
and post-ganglionic lesions of the
third nerve.1,2,4 Jacobsen found
cholinergic supersensitivity in his
study of oculomotor palsy, noting the
phenomenon in 4 of 5 traumatic
palsies, 2 of 2 congenital palsies, 5 of
11 compressive palsies and 0 of 13
ischemic palsies.5,6 If the pupil fails to
constrict from 0.125% pilocarpine,
MARCH 15, 2006 REVIEW OF OPTOMETRY 47A

the next step is to instill a 1% pilo-
carpine solution. If the pupil also fails
to constrict from 1% pilocarpine, the
dilation is likely due to pharmacolog-
ical mydriasis (e.g., atropine, sco-
polomine, cyclopentolate or homat-
ropine), traumatic iridoplegia,
sphincter ischemia secondary to angle
closure or iatrogenic damage from
intraocular surgery.1,2,4-6,10
No definitive treatment for the
tonic pupil exists. Patients primarily
seek relief from glare associated with
mydriasis and cosmetic improvement
related to anisocoria. In these cases, an
opaque cosmetic contact lens may
provide a solution. Visual complaints
associated with ciliary body dysfunc-
tion occasionally respond to low con-
centrations of cholinergic drugs.
Clinical Pearls
• Any pathology causing damage to
the ciliary ganglion or short ciliary
nerves will result in a tonic pupil. This
includes but is not limited to: neu-
rotrophic viral infection (e.g., varicel-
la), orbital tumor, diffuse peripheral
neuropathy and neurosyphillis.1-7
Transient unilateral dilation with
decreased light reaction and reduced
accommodation have also been docu-
mented in association with migraine
headaches.2,7,8,10,13
• Giant cell arteritis may result in
ciliary ganglion ischemia, resulting in
a tonic pupil.1,2
• Blunt trauma to the globe may
cause segmental iridoplegia.8
• Interruption of the parasympa-
thetic innervation may also occur dur-
ing anterior segment surgery or exten-
sive cryotherapy of the retina and
choroid, diffuse laser photocoagula-
tion of the retina and choroid or fol-
lowing retrobulbar alcohol injections.7
• Segmental palsy and LND have
also been observed in Parinaud’s syn-
drome, a condition usually associated
with midbrain lesions, especially
tumors of the pineal gland.8,11
• Bilateral tonic pupils have been
found in association with other dys-
functions of the autonomic nervous
48A REVIEW OF OPTOMETRY MARCH 15, 2006
system including Ross’ syndrome
(hyporeflexia, tonic pupil and pro-
gressive segmental anhidrosis), ortho-
static hypotension and Riley Day
Syndrome (familial dysautono-
mia).1,2,11,12
• Most cases of isolated internal
ophthalmoplegia are idiopathic and
can appropriately be referred to as
Adie’s tonic pupil.7
• In the absence of other signs and
symptoms, a tonic pupil is a benign
finding and heralds no systemic or
neurological disease emergency.1,2
However, until other etiologies have
been ruled out, it is inappropriate to
refer to the tonic pupil as Adie’s tonic
pupil.
• Tonic pupils, especially if they are
bilateral, should elicit testing for
syphilitic infection (e.g., FTA-Abs and
VDRL).2,7,10 A pupil with a weak light
reaction but no segmental palsy usual-
ly indicates drug-induced mydriasis.
1. Slamovits TL, Glaser JS. The pupils and accommo-
dation. In: Tasman W, Jaeger EA, eds. Duane’s Clinical
Ophthalmology (CD-ROM). Philadelphia: J. B.
Lippincott, 1998, pp. 1-24.
2. Slamovits TL, Glaser JS. The pupils and accommo-
dation. In: Glaser JS, ed. Neuro-Ophthalmology.
Philadelphia: J. B. Lippincott, 1990, pp. 459-83.
3. Tantum LA. Pupil anomalies. In: Onofrey BE, ed.
Clinical Optometric Pharmacology and Therapeutics.
Philadelphia: J. B. Lippincott, 1994, pp. 1-13.
4. Kardon RH. The pupils. In: Yanoff M, Duker JS, eds.
Ophthalmology. Philadelphia: Mosby International,
1999, pp. 20.1-20.10.
5. Newman NM. The pupil. In: Newman NM, ed.
Neuro-Ophthalmology: A Practical Text. Norwalk, CT:
Appleton and Lange, 1992, pp. 239-252.
6. Kardon RH, Thompson HS. The pupil. In: Rosen ES,
Thompson HS, Cumming WJK, eds. Neuro-
Ophthalmology. Philadelphia: Mosby International,
1998, pp. 13.1-13.19.
7. Burde RM, Savino PJ, Trobe JD. Anisocoria and abnor-
mal pupillary light reactions. In: Burde RM, Savino PJ,
Trobe JD, eds. Clinical Decisions in Neuro-Ophthalmology.
Philadelphia: Mosby, 1992, pp. 321-46.9.
8. Thompson HS. Segmental palsy of the iris sphincter
in Adie’s syndrome. Arch Ophthalmol 1978;
96(9):1615-20.
9. Thompson HS, Pilley SFJ. Unequal pupils: A flow
chart for sorting out the anisocorias. Surv Ophthalmol
1976;21(1):45-8.
10. Lee AG, Taber KH, Hayman LA, et al. A guide to the
isolated dilated pupil. Arch Fam Med 1997;6(4):385-8.
11. Friel JP, ed. Dorland’s Illustrated Medical
Dictionary. Philadelphia: W. B. Saunders, 1994, pp.
1637-8.
12. Wolfe GI, Galetta SL, Teener JW, et al. Site of auto-
nomic dysfunction in a patient with Ross’ syndrome
and postganglionic Horner’s syndrome. Neurol
1995;45(11):2094-6.
13. Purvin VA. Adie’s tonic pupil secondary to migraine.
J Neuroophthalmol 1995;15(1):43-4.
THE ARGYLL ROBERTSON
PUPIL
Signs and Symptoms
In 1869, Douglas Argyll Robertson
was the first to describe several
patients whose pupils reacted poorly
to light with a normal near response.1
It wasn’t until 30 years later that
physicians realized that the etiology of
this pupillary anomaly was a manifes-
tation of tertiary syphilis.1-5
Afferent visual fibers (beginning
with the retinal ganglion cells) course
backward as the optic nerve. They
pass through the optic chiasm and
travel in the optic tract toward the lat-
eral geniculate body (LGB). Just
before reaching the LGB, approxi-
mately 1% of optic tract fibers branch
off and terminate in the pretectal
nuclei at the level of the midbrain.
These nuclei are interconnected
through a series of fibers that form the
posterior commissure. This intercon-
nection is responsible for the consen-
sual light response (light in one eye
stimulates pupillary constriction in
the fellow eye). From the pretectal
nuclei, fibers leave and synapse in the
Edinger-Westphal nuclei (EWN).
The ipsilateral and contralateral
innervation to the EWN also con-
tributes to the consensual response.
Parasympathetic pre-ganglionic fibers
(efferent pupillary fibers) exit the
EWN and travel with the oculomotor
nerve. These pupillary fibers branch
just before reaching the superior
orbital fissure and follow the inferior
division of the third nerve. Within the
orbit, pupillary axons follow with
oculomotor fibers destined for the
inferior oblique muscle and course to
their synapse in the ciliary ganglion.
Short ciliary nerves leave the ciliary
ganglion as parasympathetic postgan-
glionic fibers to innervate both the

ciliary body and iris sphincter muscle.
The majority of the fibers (97%) ter-
minate within the ciliary body.1,6
Argyll Robertson pupils are typical-
ly small (2mm), irregularly shaped
and react poorly or not at all to light.
The response to both accommodation
and convergence remains intact.
Visual acuity is usually normal.
Dilation with mydriatic agents is typ-
ically poor. The dysfunction begins
unilaterally and becomes bilateral
with time.1-5 The pupillary findings
consistent with Argyll Robertson
develop over months to years. The
abnormality in pupillary function
begins with a sluggish response to
light and eventually progresses to a
complete loss of the light reflex. Iris
atrophy with a loss of its radial folds
and crypts has been reported.1
Pathophysiology
The pathophysiologic mechanism
that produces an Argyll Robertson
pupil is unclear. Studies have failed to
demonstrate a focal localizing lesion.
Research has implicated the rostral
midbrain in the vicinity of the
Sylvian aqueduct of the third ventri-
cle as the most likely region of dam-
age.1 A lesion in this area would
involve efferent pupillary fibers on
the dorsal aspect of the EWN (associ-
ated with the response to light), while
sparing the fibers associated with the
response to near (which lie slightly
more ventrally).1
Argyll Robertson pupil is most
commonly associated with tertiary
syphilis; however, other etiologies
include diabetes mellitus, encephali-
tis, midbrain tumors, sarcoidosis and
Lyme disease.1-3
Management
Ultimately, treatment depends on
the underlying cause. In cases of
syphilis, penicillin by injection is the
method of choice. The more
advanced the disease process, the
longer and more potent the doses of
penicillin must be to eradicate the dis-
ease. A two- to four-week course of
oral doxycycline or tetracycline may
be used as alternative therapy.7 Most
patients do well after treatment.
Patients who have suffered permanent
cardiac or nerve damage have the
poorest prognosis for a healthy and
completely normal life, since the man-
ifestations of such an advanced disease
cannot be reversed.7
Once treatment has begun, patients
can be followed using the rapid plas-
ma reagin (RPR) test. Because the
RPR measures the level of antibodies
to cardiolipin and not antibodies to
the Treponema pallidum organism,
the titer will vary based on the effec-
tiveness of the treatment.5 Once the
individual is infected with the organ-
ism, both the FTA-Abs and the
MHA-TP will always remain positive,
since these tests detect the presence of
antibodies specific to Treponema.
Clinical Pearls
• Patients who present with miotic
pupils should be further assessed for
Argyll Robertson pupil.
• The detection of this pupillary
anomaly is significant and requires
immediate neurological, physical and
laboratory evaluations. The systemic
manifestations associated with this
condition carry life-impacting conse-
quences.
• The earlier a firm diagnosis can be
made, the better the prognosis will be
for the patient. Once a diagnosis is
established, treatment should be swift
and potent in order to eradicate the
infectious organism and prevent
organ degradation.
1. Miller NR, Thompson HS. Disorders of pupillary func-
tion, accommodation, and lacrimation. In: Miller NR,
Newman NJ, eds. Clinical Neuro-Ophthalmology, 5th ed.
Philadelphia: Williams & Wilkins, 1998, pp. 961-94.
2. Cullom RD, Chang B. Neuro-ophthalmology. In:
Cullom RD, Chang B, eds. Will’s Eye Manual, 2nd ed.
Philadelphia: J. B. Lippincott, 1993, pp. 241-6.
3. Friedman NJ, Pineda R, Kaiser PK. Iris/pupils. In:
Friedman NJ, Pineda R, Kaiser PK, eds. The
Massachusetts Eye and Ear Infirmary Illustrated
Manual of Ophthalmology. Philadelphia: W.B.
Saunders, 1998, pp. 187-216.
4. Ravin JG. Argyll Robertson: Twas better to be his
pupil than to have his pupil. Ophthalmol
1998;105(5):867-70.
® NEURO-OPHTHALMIC DISEASE
5. Chronister CL, McGreal JA. Infectious diseases. In:
Muchnick BG, ed. Clinical Medicine in Optometric
Practice. Philadelphia: Mosby, 1994:104-28.
6. Gertz SD. Visual pathways and optic reflexes. In:
Gertz SD, ed. Neuroanatomy Made Easy and
Understandable. Gaithersburg, MD: Aspen
Publishers, 1996, pp. 58-61.
7. Berkow R, Beers MH, Fletcher AJ. Sexually trans-
mitted diseases. In: Berkow R, Beers MH, Fletcher
AJ, eds. The Merck Manual. Whitehouse Station, NJ:
Merck Research Laboratories, 1997, pp. 937-48.
MIGRAINE
Signs and Symptoms
Migraine is a chronic, episodic condi-
tion chiefly heralded by headache, but
additionally characterized by a specific
group of signs and symptoms. Migraine
affects women approximately two to
three times as often as men, and the
peak incidence is between ages 35 and
45.1 The condition usually ensues in the
teens or early 20s and may persist
throughout life. About 75% of migraine
sufferers—called migraineurs—have a
family history of the disorder or some
other form of vascular headache (e.g.,
cluster headaches).2
Most of the time, a migraine episode
is preceded by the prodrome, a premon-
itory sensory experience that occurs
hours or days before the headache. More
than 60% of migraineurs experience a
prodrome, which may present as a
change in mood, behavior or general
well being.1 Migraine prodrome must
be distinguished from migraine aura;
the latter is a complex of neurological
symptoms that occur antecedent to or
along with the headache. About one-
third of migraineurs experience these
phenomena.3 Auras typically develop
over 5 to 10 minutes and last less than
one hour.1 They may occur as visual,
sensory or motor phenomena, or they
may occur in a combination of these
three. The classic visual aura is described
as a “scintillating scotoma” or “fortifica-
tion scotoma” and begins as a small
blurry area of vision near fixation, slow-
ly expanding to a large hemifield defect
surrounded by a shimmering, undulat-
ing border of light. Patients who cannot
articulate the visual aura may simply
report flashing lights and/or distortion
MARCH 15, 2006 REVIEW OF OPTOMETRY 49A
 of vision. Non-visual auras include (resulting in the aura phase), followed International Headache Society (IHS)
paresthesias (progressive numbness or by rebound vasodilation, which recognizes the following categories:
tingling in the extremities or face), gen- induces the headache via stimulation • Migraine without aura: Also
eralized motor weakness, speech/lan- of perivascular sensory nerves.4 This known as “common migraine,” this
guage disturbances (aphasia), hearing relatively simplistic view of migraine condition involves the typical pulsatile
disturbances or olfactory hallucinations. has been abandoned by most contem- migraine headache associated with
Headache is the overwhelming com- porary headache experts in favor of the nausea and/or vomiting, photophobia
plaint reported by migraineurs. The more complex neurovascular theory. or phonophobia, but with no demon-
headaches are typically described as The neurovascular theory suggests strable sensory or motor aura.
throbbing or pulsatile, with pain inten- that the migraineur’s brain remains in a • Migraine with aura: Sometimes
sity ranging from moderate to referred to as “classic migraine,”
severe. Even routine physical this variety manifests some form
activity may exacerbate the pain. of aura (for example, visual,
Headaches are most often unilat- somatosensory, motor) in the
eral initially and localize to the early phase of the attack. The
frontotemporal and ocular area. headache associated with this
Over several hours, the headache form of migraine may be some-
builds and progresses posteriorly, what diminished in severity
and may persist anywhere from and/or duration than that of a
4 hours to more than 24 hours. migraine without aura. In some
More than half of migraineurs cases, the headache may not
report concurrent nausea and ensue at all—a condition that is
vomiting during the attack. subcategorized as “typical aura
Artistic representation of what a migraine sufferer might
Many will become sickened sim- experience visually. without headache.” Other sub-
ply at the sight or thought of categories include familial hemi-
food. Photophobia and/or phonopho- constant state of neuronal hyperex- plegic migraine and basilar-type
bia (sensitivity to loud sounds or noise) citability, a condition that may be due migraine.
also commonly accompany the in part to diminished intracellular • Ophthalmoplegic migraine: An
headache, prompting migraineurs to magnesium and elevated lactic acid lev- exceedingly rare condition, ophthal-
seek out a dark and quiet place. els.5 When challenged by certain con- moplegic migraine involves a headache
The headache and other symptoms ditions or stimuli, a neurochemical unilaterally localized to the eye, fol-
associated with migraine tend to dimin- imbalance ensues that may be per- lowed by a transient ocular motility
ish gradually. After the attack, most ceived by the patient as prodrome. deficit. The ophthalmoplegia usually
migraineurs experience a postdrome, Ultimately, as conditions persist within involves the third or fourth cranial
sometimes referred to as the “migraine the cortex, a depolarizing wave of neu- nerve and may last several days to more
hangover.” Fatigue and irritability are ronal depression is generated. This than a week.
common during this phase, which may wave moves forward across the brain • Retinal migraine: Sometimes
last a day or more following the attack. from the occipital cortex, activating referred to as “ocular migraine” or
Additional postdrome symptoms may sensory nerves within the face and “ophthalmic migraine,” this is an
include scalp tenderness and difficulty head. Neuropeptides are released from uncommon phenomenon encoun-
concentrating. the trigeminal nerve, triggering platelet tered in some migraineurs. It presents
aggregation and serotonin release.6 as recurrent, transient monocular
Pathophysiology Serotonin tends to cause vasoconstric- vision impairment, which may range
Although migraine is one of the tion, which may contribute to the from a scintillating scotoma to an alti-
oldest known medical conditions migraine aura. Neuropeptides (includ- tudinal defect to complete monocular
(with descriptions dating back some ing substance P and calcitonin gene- field loss. Retinal migraine may be
5,000 years), there is still no absolute related peptide) stimulate inflamma- brought on by exertion or postural
consensus on the etiology or patho- tion of the meningeal arteries, which is change.1,9 Commonly, the visual
physiology of this condition. The vas- believed to potentiate the headache episodes persist for less than 30 min-
cular theory of migraine—described and other symptoms associated with utes but may range from several sec-
in the 1940s—is perhaps the most the migraine attack.6 onds to several hours. Headache and
well known. It holds that migraine A classification scheme has been neurologic symptoms are usually
results from an abrupt vasoconstric- developed to categorize migraines absent, though localized discomfort
tion of intracranial blood vessels based upon their presentation.7,8 The may occur around the affected eye

50A REVIEW OF OPTOMETRY MARCH 15, 2006


before, during or after the visual
episode. When encountering a retinal
migraine attack in progress, fundus-
copy may reveal a narrowing of the
retinal vessels, disc pallor and a “cherry
red” macula (similar to a retinal artery
occlusion).10
• Childhood periodic syndromes
that may be precursors to or associated
with migraine: While not actually con-
stituting a form of migraine, these syn-
dromes are often seen as markers or
predictors that migraine will develop
later in life. Included in this category
are conditions such as benign paroxys-
mal vertigo, cyclical vomiting and
abdominal migraine. Even a history of
severe motion sickness in a child may
be seen as a predisposing factor toward
migraine development.
• Complications of migraine: The
IHS denotes “complications of
migraine” as a distinct subcategory of
the disease. The complications include
severe and unusual sequelae associated
with migraine, including chronic
migraine (migraine headaches occur-
ring at least 15 days of every month for
at least two months.), status migrain-
osus (a severe, incapacitating migraine
attack that persists for more than 72
consecutive hours), persistent aura
without infarction, migrainous infarc-
tion and migraine-triggered seizure.
Management
When patients communicate symp-
toms suggestive of migraine, the
attending physician is obligated to
obtain a neurologic consultation for
definitive diagnosis. While migraine is
typically diagnosed by clinical presen-
tation alone, more serious conditions
(e.g., aneurysms, impending stroke,
etc.) must be ruled out. Neuroimaging
and serology are not commonplace;
however, these tests may be appropriate
in certain individuals.
Initial management of migraine
consists of identifying “triggers” that
can initiate the migraine attack.
Common triggers include foods such
as caffeinated drinks, cheese, chocolate,
monosodium glutamate (MSG), nuts,
smoked meats and red wine; strong
smells such as perfumes or cigarette
smoke; hormonal changes; glaring or
flickering lights; physical exertion and
emotional stress. Patients are urged to
keep a daily diary so that precipitating
factors can be detected and subse-
quently avoided.
Pharmacologic therapy for migraine
falls into two broad categories: abortive
therapies, used to terminate an ensuing
migraine episode, and prophylactic
medications, taken daily to prevent
attacks. The choice of medication
depends on the severity and frequency
of the episodes. Those with relatively
minor sporadic migraine attacks may
be adequately controlled with non-spe-
cific, oral analgesic/anti-inflammatory
agents such as aspirin, ibuprofen, or
naproxen sodium.11 More severe pre-
sentations may warrant an ergotamine
derivative, such as Cafergot® (ergota-
mine tartrate with caffeine, Novartis).
However, in recent years the triptans—
potent serotonin receptor agonists—
have supplanted ergotamines as first-
line therapy for severe migraine
attacks.12 Sumatriptan (Imitrex®,
GlaxoSmithKline) was the first of these
compounds to be developed. Other
commonly used drugs in this category
include Zomig® (zolmitriptan,
AstraZeneca), Amerge® (naratriptan,
GlaxoSmithKline), Maxalt® (rizatrip-
tan, Merck), Axert® (almotriptan,
Ortho-McNeil) and Relpax® (eletrip-
tan, Pfizer).
Patients who experience more than
two acute migraine attacks monthly or
those whose attacks are severe enough
to compromise their daily activities are
candidates for prophylactic therapy.
Numerous drugs have been used in this
capacity with varying success. These
include hypertensive medications such
as the beta-blockers (propranolol,
nadolol), calcium channel blockers
(verapamil, nimodipine), and alpha-
adrenergic blockers (clonidine).
Tricyclic antidepressants (amitripty-
line) and anticonvulsive agents includ-
ing Depakote® (divalproex sodium,
Abbott) may also be valuable as pro-
® NEURO-OPHTHALMIC DISEASE
phylactic therapy for migraine. Sansert
(methysergide maleate, Novartis), a
derivative of LSD, was once approved
by the FDA for migraine prophylaxis;
however, in 2003 the drug was
removed from the U.S. market because
of safety concerns.13 Most recently,
Topamax (topiramate, Ortho-McNeil)
has been shown to be effective in pre-
venting migraine attacks.13,14
Clinical Pearls
• Many patients do not understand
that migraine is a complex syndrome of
neurologic signs and symptoms, and
thus they may attempt to “self-diag-
nose” any severe headache—chronic or
otherwise—as migraine. These indi-
viduals need to be questioned carefully
and enlightened about the various
forms of headache, including cluster,
muscle tension, sinus, and so on.
• It is important for migraineurs to
recognize their specific prodromal
symptoms, as abortive therapy may be
helpful in diverting an attack. Some of
the more commonly reported sensa-
tions include neck pain, dizziness,
fatigue, difficulty concentrating, irri-
tability, depression, photophobia
and/or phonophobia, lack of appetite,
hyperactivity and (ironically) euphoria.
• Lifestyle modification and the use
of medications can significantly
improve the quality of life for
migraineurs; however, patients must
realize that there is no cure for the dis-
order.
• Migraine headache is a diagnosis of
exclusion.
1. Arunagiria G, Santhi S. Migraine: an ophthalmolo-
gist’s perspective. Curr Opin Ophthalmol 2003;
14(6):344-52.
2. Bartleson JD. Transient and persistent neurological
manifestations of migraine. Stroke 1984;15(2):383-6.
3. Launer LJ, Terwindt GM, Ferrari MD. The prevalence
and characteristics of migraine in a population-based
cohort: the GEM study. Neurol 1999;53(3):537-42.
4. Marcussen RM, Wolff HG. A formulation of the
dynamics of the migraine attack. Psychosom Med
1949;11(5):251-6.
5. Welch KMA, D’Andrea G, Tepley N, et al. The concept
of migraine as a state of central neuronal hyperex-
citability. Neurol Clin 1990;8(4):817-28.
6. Moskowitz MA. The neurobiology of vascular head
MARCH 15, 2006 REVIEW OF OPTOMETRY 51A
 pain. Ann Neurol 1984;16(2):157-68.
7. Headache Classification Committee of the
International Headache Society. Classification and diag-
nostic criteria for headache disorders, cranial neuralgias
and facial pain. Cephalalgia 1988;8(S7):1-96.
9. Jehn A, Dettwiler B, Fleischhauer J, et al. Exercise-
induced vasospastic amaurosis fugax. Arch Ophthalmol
2002;120:220-2.
10. Doyle E, Vote BJ, Casswell AG. Retinal migraine:
caught in the act. Br J Ophthalmol 2004;88(2):301-2.
Pharmacokinetics and pharmacodynamics of the triptan
antimigraine agents: A comparative review. Clin
Pharmacokinet 2001;40(3):189-205.
13. Blumenfeld A. Clinical approaches to migraine pro-
phylaxis. Am J Manag Care 2005;11(S2):S55-61.

8. Olesen J, Lipton RB. Migraine classification and diag- 11. Goadsby PJ. Migraine: diagnosis and management. 14. Diamond M, Dahlof C, Papadopoulos G, et al. Topira-
nosis. International Headache Society criteria. Neurol Intern Med J 2003;33(9/10):436-42. mate improves health-related quality of life when used
1994;44(S4):S6-10. 12. Jhee SS, Shiovitz T, Crawford AW, Cutler NR. to prevent migraine. Headache 2005;45(8):1023-30.

DIFFERENTIAL DIAGNOSIS OF HEADACHE

I. Pain-sensitive structures in the head 2) Cluster
A. Intracranial 3) Complicated
1. Bones 4) Ocular/ophthalmoplegic/retinal
2. Sinuses 5) Raeder’s syndrome (Painful distribution of
3. Meninges (Dura mater) CN V, V1 with Horner’s)
4. Arteries of the dura mater b. Toxic exposure
5. Great venous sinuses c. Exertion/increased blood pressure
6. Intracerebral arterie d. Tension
7. Cranial nerves V, VII, IX, X e. Dental abscess
B. Extracranial f. Uveitis
1. Skin g. Optic neuritis
2. Faci h. Traumatic
3. Subcutaneous tissues 2. Chronic
4. Muscles a. Sinus infection/abnormality
5. Arteries b. Post-concussion syndrome
6. Veins c. Muscle contraction headache
II. Etiologies of headache d. Postural/environmental etiologies (stress)
A. Life-threatening e. Pseudotumor cerebri
1. Acute f. Hydrocephalus
a. Giant cell arteritis h. Cranial neuralgia (Trigeminal neuralgia–tic
b. Subarachnoid hemorrhage douloureux)
c. Meningitis III. Symptoms requiring immediate referral
d. Subdural hematoma A. Claudication
e. Tumor (traction-based) B. Recurrent fevers
f. Hypertensive crisis C. History of unwanted weight loss
g. Venous sinus thrombosis D. Transient ischemic attack/visual loss/visual
h. Aneurysm disturbance
i. Cranial fracture E. Vomiting
j. Intracranial infection/abscess F. Increased postural/exertive pain
k. Mucocele G. Change in mental status
2. Chronic H. Loss of consciousness
a. Cellulitis I. Wakes patient from sleep
b. Tumor (traction-based) J. Observation of disc edema/papilledema
c. Toxic exposure (CO, CO2, etc.) K. Systemic complications (paralysis, dysarthria,
d. Blood dyscrasias tinnitus, etc.)
e. Sinus infection L. Presence of absolute scotomata
f. Otologic infection (otitis media, otitis interna)
g. Dental inflammation/infection 1. Biondi DM. Physical treatments for headache: a structured review.
h. Arteriovenous malformation Headache 2005;45(6):738-46.
i. Ischemic cerebrovascular disease 2. Blaustein BH. Chronic recurring headache. In: Blaustein BH, ed. Problems
j. Hypertension in Optometry: Ocular Manifestations of Neurologic Disease. Philadelphia:
B. Non life–threatening Lippincott, 1992, pp. 516-532.
1. Acute 3. O’Conner PS. Headache. In: Bajandas FJ, Kline LB, eds. Neuro-
a. Migraine (Diagnosis of exclusion) ophthalmology Review Manual. Thorofare, NJ: Slack, 1988, pp. 157-61.
1) Classic or common

52A REVIEW OF OPTOMETRY MARCH 15, 2006

OCULOSYSTEMIC DISEASE
STURGE-WEBER SYNDROME
Signs and Symptoms:
Sturge-Weber syndrome (SWS)
represents a constellation of signs and
symptoms involving the skin, eyes
and central nervous system. A con-
genital condition, SWS typically
presents at birth with a characteristic
facial lesion that is referred to as a
“port-wine stain” or “nevus flam-
meus.” Clinically, this may be seen as
one or more flat, well-demarcated
red-to-purplish lesions involving the
skin of the face. Lesions may be bilat-
eral and/or extend beyond the vertical
midline.1,2 The classic ocular finding
is choroidal hemangioma, ipsilateral
to the port-wine stain and found in
approximately 40 to 70% of patients
with SWS.3,4 Dilated, tortuous con-
junctival and episcleral vessels are also
common in SWS. Glaucoma is
encountered with considerable fre-
quency in these patients, with a
reported incidence as high as 60 to
70%.4,5 Typically, the glaucoma is
unilateral and ipsilateral to the port-
wine stain, with its onset during
childhood. When present, glaucoma
may be associated with pain and
Choroidal hemangioma in Sturge Weber syndrome
buphthalmos (an enlarged globe).
Aside from dermatologic and ocu-
lar findings, most patients with SWS
manifest some type of neurological
deficit. Seizures are reported to be the
most common neurologic manifesta-
tion, frequently beginning in early
childhood.1,6 Typically, focal motor
seizures are seen in patients with
SWS, although more generalized
epilepsy may develop later in some
individuals. The majority of those
with SWS also show some level of
developmental delay and progressive
mental retardation.5,6 Other neuro-
logical manifestations may include
recurrent headaches (33 to 50%),
contralateral hemiparesis, hemiplegia
and hemianopsia.2,5-7
Pathophysiology
Sturge-Weber Syndrome, some-
times referred to in the historical lit-
erature as encephalofacial or
encephalotrigeminal angiomatosis, is
classified as one of the phakomatoses.
The phakomatoses represent a group
of congenital disorders heralded by
benign cutaneous lesions and neuro-
logical deficit. Other examples
include tuberous sclerosis, neurofi-
bromatosis, and Von Hippel-Lindau
syndrome.
SWS is typified by capillary venous
angiomas involving the face, choroid
and leptomeninges of the brain. Not
all patients will manifest involvement
of all areas, however. SWS is
considered complete when
both facial and central nerv-
ous system angiomas are pres-
ent; it is considered incom-
plete when only one of these
regions is involved. Individual
cases may be classified via the
Roach Scale:
• Type I: This is the most
common presentation of
SWS. Patients display both
facial and leptomeningeal
angiomas. Glaucoma may or
may not be present.
• Type II: Patients display only a
facial angioma without CNS involve-
ment. Glaucoma may or may not be
present.
• Type III: Patients manifest isolat-
® OCULOSYSTEMIC DISEASE
ed leptomeningial angiomas without
cutaneous involvement. Glaucoma is
usually not present.
Several theories have been pro-
Port-wine stain in Sturge Weber syndrome
posed as to the precise etiology of
SWS. Some believe that the condi-
tion results from failure of the primi-
tive cephalic venous plexus to regress
in the embryonic fetus.8 Others have
implied that damage to the superficial
cortical veins early in development
results in redirection of blood flow
into the developing leptomeninges
and deep venous system, causing
venous stasis and vessel dilatation.9
The exact pathogenic mechanism
remains disputed.
Management
Systemic management of patients
with SWS begins with a thorough
neurological evaluation. Neuro-
imaging of the head is essential for
detecting and locating lep-
tomeningeal angiomas. MRI with
gadolinium is preferred, but CT is
also often used to detect cortical cal-
cification, a sign of more advanced
disease.
While SWS cannot be cured, the
associated manifestations—glauco-
ma, choroidal hemangiomas,
headaches, seizures, and even port
wine staining—can be managed
through medical and surgical inter-
vention.
Glaucoma therapy in SWS initially
follows the same treatment algorithm
MARCH 15, 2006 REVIEW OF OPTOMETRY 53A
 as primary open-angle glaucoma.
IOP-lowering agents — including
beta-blockers, prostaglandin analogs
and carbonic anhydrase inhibitors —
are all reasonable options. Alpha-
Port-wine stain in Sturge Weber syn-
drome.
adrenergic agonists, such as brimoni-
dine, should be avoided in younger
children.10,11 In that the glaucoma
develops secondary to an elevation in
episcleral venous pressure caused by
the vascular anomalies, prostaglandin
analogs tend to be the best medical
choices due to their ability to bypass
the episcleral venous system. Over
time, the glaucoma associated with
SWS typically becomes recalcitrant,
warranting surgery. Multiple tech-
niques, including argon laser trabecu-
loplasty, selective laser trabeculoplas-
ty, trabeculectomy, goniotomy or
YAG laser goniotomy, and Seton
devices (Molteno or Baerveldt
implants) have been used with vary-
ing success. However, the long-term
results for all of these procedures are
less than encouraging.
Choroidal hemangiomas associat-
ed with SWS are treated only if symp-
tomatic. Most often, the lesions
remain stable; however, larger heman-
giomas may leak, leading to the
development of cystoid macular
edema and/or exudative neurosensory
retinal detachment. Laser photocoag-
ulation has been used to treat
choroidal hemangiomas since the late
1970s.12 More recently, photodynam-
ic therapy with verteporfin has
emerged as an outstanding treatment
option for patients with choroidal
54A REVIEW OF OPTOMETRY MARCH 15, 2006
hemangioma.13,14 Other techniques
that have been successfully employed
include transpupillary thermothera-
py, gamma knife radiosurgery and
episcleral plaque radiotherapy.
Analgesic anti-inflammatory
agents are generally used to manage
headache in SWS. Aspirin is an excel-
lent choice, as it also possesses antico-
agulant properties that may prevent
thrombosis and reduce the risk of
stroke. There is also some evidence to
suggest that daily aspirin therapy
helps to diminish the frequency of
epileptic seizures in SWS.15 The typi-
cal prophylactic dose is 2mg/kg/day;
however, aspirin should be utilized
with caution in younger children
because of a purported association
with Reye’s syndrome (a poorly
understood inflammatory disease
affecting primarily children, in which
all organs of the body, but primarily
the liver and brain, swell following
aspirin therapy).16
Seizures associated with SWS are
treated medically when possible,
using anticonvulsant medications
such as carbamazepine (Tegretol®,
Dilated episcleral vessels secondary to
increased venous pressure in Sturge Weber
syndrome.
Novartis), phenytoin (Dilantin®,
Pfizer), valproic acid (Depakote®,
Abbott) or phenobarbital. Newer
drugs, such as gabapentin (Neurontin®,
Pfizer) or topiramate (Topamax®,
Ortho-McNeil), may also be of bene-
fit. In cases of refractory seizures, sur-
gical intervention is indicated.
Facial port-wine stains may be
treated for cosmetic reasons with
pulsed dye laser therapy. The primary
limitations of this technique include
cost, pain and the potential for multi-
ple treatments, but there are few
long-term risks. In fact, studies sug-
gest that diminishing or removing
these unsightly lesions at an early age
may actually improve patients’ self-
image and social interaction later in
life.17,18
Clinical Pearls:
• Port wine staining in SWS always
involves the skin innervated by the
first branch of the trigeminal nerve
(V1),1,19 but may involve other
branches as well (V2 and/or V3).20 If
V1 is not involved, it is not Sturge-
Weber syndrome.
• The age at which seizures begin
may actually correlate with the degree
of intellectual impairment in patients
with SWS. Those without epilepsy or
with onset of seizures after 48 months
old have been shown generally to
have normal development and intelli-
gence.5
1. Baselga E. Sturge-Weber syndrome. Semin Cutan
Med Surg 2004;23(2):87-98.
2. Pascual-Castroviejo I, Diaz-Gonzalez C, Garcia-
Melian RM, et al. Sturge-Weber syndrome: Study of
40 patients. Pediatr Neurol 1993;9(4):283-8.
3. Celebi S, Alagoz G, Aykan U. Ocular findings in
Sturge-Weber syndrome. Eur J Ophthalmol 2000;
10(3):239-43.
4. Sullivan TJ, Clarke MP, Morin JD. The ocular man-
ifestations of the Sturge-Weber syndrome. J Pediatr
Ophthalmol Strabis 1992;29(6):349-56.
5. Sujansky E, Conradi S. Outcome of Sturge-Weber
syndrome in 52 adults. Am J Med Genet 1995;
57(1):35-45.
6. Sujansky E, Conradi S. Sturge-Weber syndrome:
Age of onset of seizures and glaucoma and the prog-
nosis for affected children. J Child Neurol 1995;
10(1):49-58.
7. Klapper J. Headache in Sturge-Weber syndrome.
Headache 1994;34(9):521-2.
8. Comi AM. Pathophysiology of Sturge-Weber syn-
drome. J Child Neurol 2003;18(8):509-16.
9. Griffiths PD. Sturge-Weber syndrome revisited: The
role of neuroradiology. Neuroped 1996;27(6):284-94.
10. Bowman RJ, Cope J, Nischal KK. Ocular and

systemic side effects of brimonidine 0.2% eye drops
(Alphagan) in children. Eye 2004;18(1):24-6.
11. Enyedi LB, Freedman SF. Safety and efficacy of
brimonidine in children with glaucoma. J AAPOS
2001;5(5):281-4.
12. Sanborn GE, Augsburger JJ, Shields JA.
Treatment of circumscribed choroidal hemangiomas.
Ophthalmol 1982;89(12):1374-80.
13. Michels S, Michels R, Simader C, Schmidt-
Erfurth U. Verteporfin therapy for choroidal heman-
gioma: A long-term follow-up. Retina
2005;25(6):697-703.
14. Huiskamp EA, Muskens RP, Ballast A, Hooymans
JM. Diffuse choroidal haemangioma in Sturge-Weber
syndrome treated with photodynamic therapy under
general anaesthesia. Graefes Arch Clin Exp
Ophthalmol 2005;243(7):727-30.
15. Maria BL, Neufeld JA, Rosainz LC, et al. Central
nervous system structure and function in Sturge-Weber
syndrome: Evidence of neurologic and radiologic pro-
gression. J Child Neurol 1998;13(12):606-18.
16. Hardie RM, Newton LH, Bruce JC, et al. The
changing clinical pattern of Reye’s syndrome 1982-
1990. Arch Dis Child 1996;74(5):400-5.
17. Leaute-Labreze C, Boralevi F, Pedespan JM, et al.
Pulsed dye laser for Sturge-Weber syndrome. Arch Dis
Child 2002;87(5):434-5.
18. Chapieski L, Friedman A, Lachar D. Psychological
functioning in children and adolescents with Sturge-
Weber syndrome. J Child Neurol 2000;15(10):660-5.
19. Tallman BF, Tan OT, Morelli JG, et al. Location of
port-wine stains and the likelihood of ophthalmic
and/or central nervous system complications.
Pediatrics 1991;87(3):323-7.
20. Enjolras O, Riche MC, Merland JJ. Facial port-
wine stains and Sturge-Weber syndrome. Pediatrics
1985;76(1):48-51.
LYME DISEASE
Signs and Symptoms
Lyme disease (LD), also known as
Lyme borreliosis, is a worldwide, tick-
borne, multi-system inflammatory
disorder caused by the pathogen
Borrelia burgdorferi. The patient with
LD will often have a history of a tick
bite, though in some cases no such
history can be elicited.1,2 LD is dis-
tributed throughout North America,
Europe and Asia.3 In the United
States, it is the single most prominent
vector-borne disease.4 Left untreated,
it can produce severe cardiac, joint,
ocular and neurological difficulties.
The most common early sign of
LD is erythema migrans, the classic
bull’s-eye-shaped skin rash denoting
the point of inoculation. This
pathognomonic lesion occurs in
approximately 70 to 80% of patients
with LD.5,6 Over time, the inflamma-
tion expands outward from the site of
the tick bite, forming a spreading,
concentric red ring that can measure
several centimeters.
Cardiac complications occur in
approximately 10% of untreated LD
patients.3,7 These include acute onset
atrial-ventricular conduction block
and myocarditis. Musculoskeletal
manifestations typically consist of a
transient oligoarthropathy affecting
the large joints (knees, hips and
shoulders). Intermittent arthritis is a
common chronic late-stage symptom
refractory to treatment.
Virtually every part of the eye and
ocular adnexa can be affected. Early
ocular manifestations consist primari-
ly of follicular conjunctivitis; less
commonly, periorbital edema and
subconjunctival hemorrhage may
occur. Later, inflammations ranging
from iridocylitis to panuveitis are pos-
sible. Bilateral keratitis is recognized
as a late manifestation of LD.8,9
Ten to 15% of patients experience
nervous system involvement.10
Neurologic complications include
lymphocytic meningitis, cranial neu-
ropathy, radicular neuropathy and,
rarely, encephalomyelitis. The most
common cranial nerve affected is the
facial nerve (CN VII). Resultant uni-
lateral or bilateral Bell’s palsies typi-
cally resolve without treatment over
weeks.11
A small percentage of late-stage
patients may experience nerve palsies
associated with the extraocular mus-
cles. Abducens palsy (unilateral or
bilateral CN VI) is the most com-
mon, followed by CN III and CN IV
pareses.9 Chronic fatigue, neuropsy-
chiatric involvement, chronic
encephalitis and relapsing multiple
sclerosis-like encephalomyelitis are all
® OCULOSYSTEMIC DISEASE
typical of late-stage neurological
LD.12
Pathophysiology
B. borgdorferi is categorized as a
spirochete—a highly specialized,
motile, spiral-shaped bacterium that
exists primarily as an extracellular
pathogen. It is a close genomic rela-
tive of Treponema pallidum, the spiro-
chete responsible for causing
syphilis.13 B. burgdorferi is harbored,
Lid swelling from tick bite.
nurtured and transmitted by the
Ixodides species of tick. In the United
States, rodents—such as the white-
footed mouse, wood rat and chip-
munk—serve as the principle hosts
for the nymph-stage of Ixodides; this
stage is primarily responsible for
human infection.14 White-tailed deer,
often implicated in Lyme disease,
actually serve as hosts to adult ticks,
which rarely transmit the disease to
humans.14 Incidental hosts include
birds, lizards, cats, dogs, horses, sheep
and cattle. The distinct endemic areas
in the United States include the
Northeast, the North Central and the
Northwestern Coastal regions.
B. burgdorferi does not directly
destroy tissue; rather, the infection
initiates nonspecific activation of
monocytes, macrophages, B cells and
compliment, resulting in a cascade of
pro-inflammatory materials. From
the initial site of infection, the spiro-
chete has the potential to spread to
virtually any organ system via blood
and lymphatic channels.
As a chronic, progressive, inflam-
MARCH 15, 2006 REVIEW OF OPTOMETRY 55A
 matory disorder, for purposes of
clinical evaluation, LD is typically
categorized as a three-stage process.15
Stage 1 (early infection) is character-
ized by erythema migrans and flu-
like symptoms. The typical incuba-
tion period from inoculation to
manifestation of the lesion is 3 to 32
days. The rash and constitutional
symptoms will ultimately resolve
even without treatment, but the
spirochete remains viable.
As the spirochete undergoes repli-
cation and systemic dissemination,
patients enter Stage 2 of the disease
(early dissemination), marked by
cardiac and neurological complica-
tions and numerous ocular sequelae.
If untreated during Stage 2, LD may
progress to the most severe form,
Stage 3 (chronic disease), in which
life-threatening rheumatologic and
central nervous system disorders
may develop.
It should be noted that the time of
progression between Stage 2 and
Stage 3 varies widely between
patients, ranging from months to
years.
Management
Clinical suspicion of LD should
prompt the optometric physician to
obtain confirmatory lab testing. A
Lyme-specific enzyme-linked immu-
nosorbent assay (ELISA ) is typical-
ly the study of first choice. Some cli-
nicians prefer to obtain
Lyme-specific indirect immunofluo-
rescent assay (IFA) titers. If the
results of the initial test are positive,
secondary immunoblot testing (on
the same blood sample) for IgM
and/or IgG is recommended.12 It is
also important to consider syphilis
testing, since T. pallidum and B.
burgdorferi can cause similar sys-
temic manifestations. A Venereal
Disease Research Laboratories
(VDRL) and Fluorescent Trepone-
mal Antibody Absorption Study
56A REVIEW OF OPTOMETRY MARCH 15, 2006
(FTA-ABS) are standard for ruling
out active syphilis. Be aware, howev-
er, that false-positives are high in
testing for both organisms.
Ocular involvement, such as uveitis,
neuroretinitis or cranial nerve palsies
(III, IV, VI or VII), in known cases of
LD warrants a lumbar puncture to rule
out CNS infection. Serological investi-
gation is recommended in all cases of
Hypopyon in Lyme-associated anterior uveitis.
idiopathic uveitis or cranial neu-
ropathies. Ocular inflammation asso-
ciated with LD can typically be man-
aged effectively with topical
cycloplegia and topical corticosteroid
preparations, though ultimately, sys-
temic treatment is required.
The prognosis of LD is variable,
depending upon the stage of the dis-
ease. In the early stages, oral antibi-
otics are used to eradicate the
pathogen and prevent systemic dis-
semination. Doxycycline 100 mg p.o.
b.i.d. (first choice), amoxicillin
500mg p.o. t.i.d. or cefuroxine axetil
500mg p.o. b.i.d. for 10 to 20 days
are the current recommended medi-
cines.14 Children and expectant or
lactating mothers should be treated
with amoxicillin (50mg/kg/day under
age 8) or cefuroxine axetil. In later
stages of LD with organ-system
involvement, intravenous antibiotics
such as ceftriaxone, cefotaxime or
sodium penicillin G may be required
for 30 days or longer.14
Clinical Pearls
• Other conditions that may
mimic the ocular manifestations of
LD include syphilis, multiple sclero-
sis, viral syndromes, sarcoidosis, Vogt
Koyanagi-Harada disease, lym-
phoma, Guillain-Barré syndrome and
Behçet’s disease.
• Prophylactic antibiotic therapy is
recommended for patients in endem-
ic regions who experience a tick bite.
Studies have shown that a single 200-
mg dose of oral doxycycline within
72 hours after inoculation virtually
eliminates the likelihood of develop-
ing LD.16
• Be aware that patients with Lyme
disease may demonstrate coinfection
by a variety of other tick-borne
pathogens, most commonly Babesia
microti (an erythrocyte parasite) and
Anaplasma phagocytophila (the agent
responsible for Ehrlichiosis).17,18
Coinfection with Bartonella henselae
(“cat-scratch disease”) has also been
reported.19
• Ocular inflammation may be the
first and only sign of a systemic dis-
ease process such as Lyme disease.
When encountered, appropriate lab-
oratory studies are required to deter-
mine the underlying cause. Idiopathic
uveitis is a diagnosis of exclusion.
1. Smith RP, Schoen RT, Rahn DW, et al. Clinical
characteristics and treatment outcome of early Lyme
disease in patients with microbiologically confirmed
erythema migrans. Ann Intern Med
2002;136(6):421-8.
2. Steere AC, Sikand VK. The presenting manifesta-
tions of Lyme disease and the outcomes of treatment.
N Engl J Med 2003;348(24):2472-4.
3. Singh SK, Girschick HJ. Lyme borreliosis: From
infection to autoimmunity. Clin Microbiol Infect
2004;10(7):598-614.
4. Orloski KA, Hayes EB, Campbell GL, Dennis DT.
Surveillance for Lyme disease—United States,
1992–1998. MMWR CDC Surveill Summ
2000;49(3):1-11.
5. Smith RP, Schoen RT, Rahn DW, et al. Clinical
characteristics and treatment outcome of early Lyme
disease in patients with microbiologically confirmed
erythema migrans. Ann Intern Med
2002;136(6):421-8.
6. Steere AC, Sikand VK. The presenting manifesta-
tions of Lyme disease and the outcomes of treatment.
N Engl J Med 2003;348(24):2472-4.

7. Steere AC. Lyme disease. N Engl J Med
1989;321(9):586-96.
8. Zaidman GW. The ocular manifestations of Lyme
disease. Int Ophthalmol Clin 1997;37(2):13-28.
9. Lesser RL. Ocular manifestations of Lyme disease.
Am J Med 1995;98(4A):60S-62S.
10. Deltombe T, Hanson P, Boutsen Y, et al. Lyme bor-
reliosis neuropathy. A case report. Am J Phys Med
Rehabil 1996;75(4):314-6.
11. Halperin JJ, Golightly M. Lyme borreliosis in Bell’s
palsy. Long Island Neuroborreliosis Collaborative
Study Group. Neurol 1992;42(7):1268-70.
12. Nadelman RB, Wormser GP. Lyme borreliosis.
Lancet 1998;352(9127):557-65.
13. Porcella SF, Schwan TG. Borrelia burgdorferi and
Treponema pallidum: A comparison of functional
genomics, environmental adaptations, and pathogen-
ic mechanisms. J Clin Invest 2001;107(6):651-6.
14. Steere AC, Coburn J, Glickstein L. The emergence
of Lyme disease. J Clin Invest 2004;113(8):1093-
101.
15. Hengge UR, Tannapfel A, Tyring SK, et al. Lyme
borreliosis. Lancet Infect Dis 2003;3(8):489-500.
16. Nadelman RB, Nowakowski J, Fish D, et al.
Prophylaxis with single-dose doxycycline for the pre-
vention of Lyme disease after an Ixodes scapularis tick
bite. N Eng J Med 2001;345(2):79-84.
17. Steere AC, McHugh G, Suarez C, et al.
Prospective study of coinfection in patients with ery-
thema migrans. Clin Infect Dis 2003;36(8):1078-81.
18. Stricker RB, Gaito A, Harris NS, Burrascano JJ.
Coinfection in patients with Lyme disease: How big a
risk? Clin Infect Dis 2003;37(9):1277-8.
19. Eskow E, Rao RV, Mordechai E. Concurrent infec-
tion of the central nervous system by Borrelia burgdor-
feri and Bartonella henselae: Evidence for a novel
tick-borne disease complex. Arch Neurol 2001;
8(9):1357-63.
NEURALLY MEDIATED
SYNCOPE
Signs and Symptoms
The word syncope originates from
the Greek word “synkopen” meaning
“to cut short.” Medically, syncope is
defined as a transient loss of con-
sciousness from a common fainting
spell.1 Syncope represents an expan-
sive entity in clinical medicine and is
a significant cause of hospital admis-
sion.2 Causes of syncope are numer-
ous, ranging from the benign to those
with significant morbidity and mor-
tality. There are so many types of syn-
cope that it could easily be its own
medical discipline. For that reason,
the discussion here is limited solely to
the type most likely to be encoun-
tered in the ophthalmic practice,
namely neurally mediated syncope
(NMS), formerly known as vasovagal
syncope, vasodepressor syncope or
neurocardiogenic syncope.
Incidence of syncope in the gener-
al population is 3% in men and 3.5%
in women.3 NMS is the most com-
mon form of syncope in healthy
adults4 and occurs in all ages.1
Younger patients tend to exhibit a
benign vasovagal reflexive syncope,
while older adults often manifest
carotid sinus hypersensitivity as the
cause.5,6
The occurrence of NMS is often
unpredictable and unexpected.
Patients may have a history of previ-
ous syncope episodes, especially in
phobic response to a blood or injury
stimulus.7 Prolonged standing, par-
ticularly in warm, crowded spaces,
can elicit a syncope response.3,8,9
However, patients with NMS fre-
quently appear to be relaxed during
the course of ophthalmic examina-
tion and often demonstrate no out-
ward anxiety.
Eye care practitioners need to
understand NMS, as ocular manipu-
lation is a trigger factor. Globe com-
pression has been used to precipitate
NMS in clinical studies.10-12 In fact,
we have personally seen patients
undergo syncope reactions from
applanation tonometry, gonioscopy,
contact lens insertion, instillation of
topical diagnostic eye drops, scleral
indentation, foreign body removal,
biomicroscopy, eyelid eversion and
subcutaneous eyelid injection.
Patients will experience a pro-
drome immediately prior to a full
NMS episode. Prodromal symptoms
include dizziness, lightheadedness,
nausea, diaphoresis, overall body
warmth, tunnel vision or blurred
vision, abdominal discomfort, pallor
and dyspnea.1,4,13,14 Immediately fol-
® OCULOSYSTEMIC DISEASE
lowing the prodrome, there will be a
sudden loss of postural tone and con-
sciousness. During the episode, the
patient may exhibit seizure-like activ-
ity, and there is increased diaphoresis
(often to the point of the patient
sweat-drenching clothes and the
exam chair), peristalsis (often accom-
panied by vomiting) and possible uri-
nary incontinence. Within several
minutes, the patient will sponta-
neously recover without assistance.
Pathophysiology
The underlying pathophysiology
of NMS is poorly understood.3
Neurally mediated syncope is a vaso-
vagal response evoked by common
physical or psychological stress factors
in susceptible individuals, and it is
believed to be a reflex response with
afferent, central and efferent path-
ways.15
Characteristic autonomic changes
in NMS involve an increase in
parasympathetic efferent activity (via
the vagus nerve, a major parasympa-
thetic cranial nerve controlling many
systems, including vasculature, heart
and glands), which causes bradycar-
dia and a reduction in sympathetic
vasoconstrictor outflow with result-
ing vasodilation.4 This reduction in
sympathetic outflow may actually be
a reflex inhibitory response to initial
sympathetic overstimulation from
anxiety. With sympathetic inhibition,
the parasympathetic system will take
over. The central nervous system may
have a role in NMS, particularly the
left hemisphere, which has a signifi-
cant parasympathetic predomi-
nance.16
During NMS, profound bradycar-
dia and hypotension occur. Marked
peripheral vasodilation is a major
cause of the fall in arterial pressure.
The major site of the vasodilation is
in skeletal muscle, with blood pool-
ing in the legs at the expense of brain
tissue. Muscle sympathetic nerve
MARCH 15, 2006 REVIEW OF OPTOMETRY 57A
 activity is suppressed just before and
during NMS, indicating that sympa-
thetic withdrawal contributes to the
dilation. However, the skeletal muscle
vasodilation seen during syncope is
greater than that caused by sympa-
thetic withdrawal alone. Likely, neu-
rally mediated “active” vasodilation
occurs during syncope. Which of the
afferent neural pathways evoke the
profound vasodilation during NMS
remains controversial. The neural
pathways responsible for the active
component of the dilation are also
unknown.17
Management
Recognition of the prodromal
symptoms of NMS is important
because the syncope episode can be
averted by having the patient imme-
diately lie flat with legs elevated
(Trendelenburg position). Should the
patient experience a full NMS
episode, the clinician should act to
protect the patient from injury. This
means preventing the patient from
falling from the exam chair and/or
choking on vomit. Of course, any
patient experiencing prodrome
should not be allowed to stand,
because he or she may sustain signifi-
cant injury should a full NMS
episode occur. However, a patient can
be directed to quickly lie on the floor.
The episode will spontaneously sub-
side within a few minutes, though the
patient will often have residual symp-
toms of nausea, lightheadedness and
disorientation. Support and protect
the patient and allow him or her to
revive naturally. Initiation of the
emergency medical system is not nec-
essary unless the patient does not
respond in a few minutes, indicating
something other than NMS.
Clinical Pearls
• Because syncope is common in
the general population, it may be of
value to include a question regarding
58A REVIEW OF OPTOMETRY MARCH 15, 2006
previous history of fainting on patient
history intake forms. This can ease
the anxiety of an unexpected syncope
occurring during examination.
• Do not let patients stand when
you are delivering bad news.
• Do not traumatize the syncope
victim with ammonia capsules, slap-
ping or dousing with cold water.
Nothing should ever be placed in the
patient’s mouth.
• Typically, the patient will seem
relaxed prior to the initiation of a syn-
cope reaction.
• Very minor ophthalmic proce-
dures can precipitate NMS.
• When NMS occurs following
instillation of topical ophthalmic
drops during examination, many cli-
nicians mistakenly think that the
patient has had an anaphylactic reac-
tion to the medications. Recognize
the clinical picture of syncope so that
proper measures are taken while
avoiding inappropriate responses.
• Don’t confuse NMS with epilep-
sy. Many patients with NMS have
been misdiagnosed as having epilepsy,
which severely affects a patient’s
lifestyle.18
1. Sealey B, Lui K. Diagnosis and management of
vasovagal syncope and dysautonomia. AACN Clin
Issues 2004;15(3):462-77.
2. Maisel WH, Stevenson WG. Syncope—getting to
the heart of the matter. N Engl J Med 2003;
347(12):931-3.
3. Nair N, Padder FA, Kantharia BK. Pathophysiology
and management of neurocardiogenic syncope. Am J
Manag Care 2003;9(4):327-34
4. Kaufmann H, Bhattacharya K. Diagnosis and treat-
ment of neurally mediated syncope. Neurol
2002;8(3):175-85.
5. Lewis T. Vasovagal syncope and the carotid sinus
mechanism with comments on Gower’s and
Nothnagel’s syndrome. Br Med J 1932;1:873-7.
6. Kenny RA, McIntosh SJ. Carotid sinus syndrome.
In Kenny Ra, ed. Syncope in the older patient.
London: Chapman & Hall, 1996, pp. 107-22.
7. Accurso V, Winnicki M, Shamsuzzaman AS, et al.
Predisposition to vasovagal syncope in subjects with
blood/injury phobia. Circul 2001;104(8):903-7.
8. Grub BP, Karas B. Clinical disorders of the auto-
nomic nervous system associated with orthostatic
intolerance: An overview of classification, clinical
evaluation, and management. PACE 1999;
22(5):798-810.
9. Brignole M. Neurally-mediated syncope. Ital Heart
J 2005;6(3):249-55.
10. Brignole M, Menozzi C, Gianfranchi L, et al.
Carotid sinus massage, eyeball compression, and
head-up tilt test in patients with syncope of uncertain
origin and in healthy control subjects. Am Heart J
1991;122(6):1644-51.
11. Oddone D, Brignole M, Menozzi, et al.
Spontaneous occurrence of the induced cardioin-
hibitory vasovagal reflex. Pacing Clin Electrophysiol
1991;14(3):415-9.
12. Brignole M, Menozzi C. Methods other than tilt
testing for diagnosing neurocardiogenic (neurally
mediated) syncope. Pacing Clin Electrophysiol
1997;20(3 Pt 2):795-800.
13. Sutton R. Vasovagal syncope: prevalence and
presentation. An algorithm of management in the avi-
ation environment. Eur Heart J 1999;1Suppl
D:D109-13.
14. Zaqqa M, Massumi A. Neurally mediated syn-
cope. Tex Heart Inst J 2000;27(3):268-72.
15. Hamer AW, Bray JE. Clinical recognition of neu-
rally mediated syncope. Intern Med J. 2005;
35(4):216-21.
16. Mercader MA, Varghese PJ, Potolicchio SJ, et al.
New insights into the mechanism of neurally mediat-
ed syncope. Heart 2002;88(3):217-21.
17. Dietz NM, Joyner MJ, Shepherd JT. Vasovagal syn-
cope and skeletal muscle vasodilatation: the continu-
ing conundrum. Pacing Clin Electrophysiol
1997;20(3 Pt 2):775-80.
18. Passman R, Horvath G, Thomas J, et al. Clinical
spectrum and prevalence of neurologic events pro-
voked by tilt table testing. Arch Intern Med.
2003;163:1945-1948.
ROSACEA
Signs and Symptoms
Rosacea (formerly referred to as
acne rosacea) is a dermatologic condi-
tion that presents with characteristic
skin findings on the face and nose.1-21
Rosacea-specific signs may include
periodic skin flushing, visible telang-
iectasis of the affected skin, inflam-
matory papules or pustules and
rhinophyma (the “W.C. Fields” pres-
entation on the nose). Patients often
report a burning sensation that coin-
cides with instances of flushing.
Ocular signs associated with rosacea
may include a recalcitrant posterior
blepharitis with inspissation of the
meibomian and related sebaceous

glands. When present, this blepharitis
can induce secondary inflammation
of the cornea and conjunctiva (ble-
pharokeratoconjunctivitis) with pap-
illary hypertrophy of the palpebral
conjunctiva.1 Left unattended, ocular
rosacea can produce chronic dry eye
secondary to evaporative processes,
spawning a perpetual cycle of local
inflammation and degenerative
Rhinophyma secondary to rosacea.
changes in the skin (ulcerative ble-
pharitis). These may result in meibo-
mianitis, hordeola, chalazia and, in
severe cases, scarring of the tissues of
the eyelid and globe.7 While the con-
dition seems to demonstrate a slight
predilection toward women over men
and toward individuals of northern
European descent, it can affect indi-
viduals of all races, usually after age
30.1-6 In fact, it is probably an under-
diagnosed ailment in races with dark-
er skin color.
There are four recognized subtypes
of rosacea:
• Subtype 1, erythematotelang-
iectatic rosacea, is characterized by
flushing and persistent redness of the
skin, and may also include visible
blood vessels in the form of telangiec-
tasia.
• Subtype 2, erythematotelang-
iectatic rosacea, is characterized by
persistent redness with transient
papules and pustules.
• Subtype 3, phymatous rosacea, is
characterized by skin thickening,
often resulting in an enlargement of
the nose from excess tissue (rhino-
phyma).
• Subtype 4, ocular rosacea, is char-
acterized by ocular manifestations,
® OCULOSYSTEMIC DISEASE
such as dry eye, tearing and burning, which opens just posterior to the lid’s
swollen eyelids, recurrent hordeola gray line. 9
and potential vision loss from corneal There is growing laboratory and
damage.8 clinical evidence implicating the mei-
bomian glands as playing a critical
Pathophysiology role in the pathogenesis of various
Rosacea represents a generalized ocular surface diseases, particularly
disorder of the sebaceous glands but evaporative dry eye.10 The meibomi-
most specifically involves the glands an glands produce a lipid material
of the face. The condition may be ini- whose synthesis is dependent on fac-
tiated when the glands become colo- tors such as stem cells, neurological
nized by bacteria (typically Staphy- stimulants and hormones.10 The lipid
lococcus aureus, and possibly Helicobacter material produced by these special-
pylori or Propionibacterium), which ized glands is fluid, spreads easily and
release enzymes that upset the lipid functions as a surfactant while simul-
component’s proper chemistry.10,22,23 taneously serving as an aqueous barri-
Biopsy samples from rosacea er.10 Even more remarkably, it
patients have demonstrated increased remains functional after a blink.
levels of cathelicidins, a chemical tool Before its delivery to the ocular sur-
of the body used to protect against face, it can be modified by factors
infection. These cathelicidins are such as flow obstructions and hor-
vasoactive and inflammatory, and monal abnormalities; after delivery, it
have the ability to produce the classic may be modified by lipases produced
telangiectasias (visible blood vessels) by normal and abnormal ocular sur-
as well as the papules (bumps) and face bacteria.10
pustules (pimples) often associated Rosacea is known to be exacerbat-
with rosacea.23 Certain microorgan- ed by exposure to certain endogenous
isms, such as H. pylori, that have been factors. Documented triggers that
linked to rosacea are better
able to stimulate an increase
in the cathelicidins than other
skin organisms.23
Ocular rosacea occurs when
the sebaceous glands of the
eyelids become involved. The
eyelids protect the globe
directly by providing a
mechanical barrier to insult.
They also indirectly protect
Vascularized corneal phylectenule secondary to rosacea
the eye via lashes, which trap (Photo courtesy of Dr. Maryke Neiberg)
airborne debris and via glands,
which form vital elements of the pro- amplify rosacial symptoms include
tective and nurturing precorneal tear hot weather, sun or UV exposure,
film.9 The meibomian glands reside wind, exercise, spicy foods, hot bever-
within the tarsus of both eyelids (25 ages and alcohol consumption.22
to 50 in the upper, 20 to 25 in the Essentially, anything that raises the
lower eyelids).9 These multi-lobulated skin temperature or induces sweating
holocrine (secreting) glands, which can induce the flushing phenomenon
are not associated with lash follicles, associated with rosacea.
empty their lipid payload onto the The etiology of flushing is likely
eyelid margin via a central ductile, rooted in a vasodilatory process, but
MARCH 15, 2006 REVIEW OF OPTOMETRY 59A
 this is not completely understood.18
Management
The first step in managing rosacea
is to avoid the elements or substances
known to initiate the symptomatic
cascade. Beta-blockers, atenolol in
particular, have been investigated in
prophylactic trials examining for their
efficacy in treating the flushing asso-
ciated with rosacea.18 Currently,
clonidine is the only drug consistent-
ly prescribed for treating chronic
flushing.18
Prophylactic use of UV-blocking
sunscreens should also be included in
the initial preventive management of
rosacea, since affected individuals are
typically fair-skinned and at risk for
sun exposure pathology.
The traditional therapy for the
pustular component of rosacea con-
sists of oral therapy: 250mg of oral
tetracycline q.i.d. (or its equivalent)
or 250 mg of oral erythromycin q.i.d.
A topical component such as metron-
idazole, applied to the affected skin
areas t.i.d., usually accompanies the
oral medications,7,11-18 Because tetra-
cycline can damage and discolor the
teeth of children, it is contraindicated
in patients younger than 10 years of
age; it is also contraindicated for preg-
nant or lactating women. In these
cases, erythromycin may be substitut-
ed.7,13-15 Doxycycline is not an ade-
quate substitute for patients younger
than 8 years, since it has a safety pro-
file similar to tetracycline. Its princi-
ple advantage for individuals who can
tolerate it is dosing (100 mg b.i.d. vs.
250 mg q.i.d.). Medicated shampoo,
such as Nizoral™ (ketoconazole,
McNeil) may occasionally be added
to the regimen.
Topical ophthalmic steroidal
preparations such as Alrex™,
Lotemax™, Pred-Forte™, Pred-Mild™
or Flarex™ can be added when ocular
inflammation becomes an issue, but
these are best used in the short term.1
60A REVIEW OF OPTOMETRY MARCH 15, 2006
Topical steroid creams and oint-
ments, such as Diprolene™
(betamethasone diproprionate
0.25%) or Elocon™ (mometasone
furoate 0.1%), are actually con-
traindicated in rosacea management,
as they foster what is known as
“steroid dependency,” a quick posi-
tive reaction to the medication, incit-
ing patients into a chronic usage cycle
which, while effective against the
symptoms, actually fails to effect a
clinical cure. Furthermore, long-term
use of these agents actually decreases
the mitotic cycle of the cells of the
dermis and epidermis. This has the
potential to induce dangerous thin-
ning of the skin; this is particularly
troublesome for the periocular tissue,
which is already architecturally lean.
When an association with H.
pylori is suspected, an oral therapy
regimen lasting 1 to 2 weeks using
two antibacterials from a choice of
clarithromycin, metronidazole or
amoxicillin can be attemped.18
Demodex folliculorum may be a com-
ponent of the overall process also.18
Eurax™ (crotamiton 10%) cream or
permethrin 5% cream are document-
ed therapies for treatment of
Demodex; however, they are not
always successful in eradicating the
organism. Oral or topical ivermectin
can be considered in stubborn cases.18
The topical immunomodulators
tacrolimus and pimecrolimus have
recently been embraced by pediatri-
cians as long-awaited alternatives for
treating atopic dermatitis in children
two years and older. Their unique
appeal as nonsteroidal topical agents
with good safety profiles has led to
their frequent use for unapproved
indications.20 These drugs are new
immunosuppressants that act by
inhibiting T-cell activation and
cytokine release. They are approved
for treating atopic dermatitis, and
their safety and efficacy have been
corroborated in large-scale random-
ized, controlled trials. Anecdotal
reports have also shown topical
tacrolimus to be effective and well-
tolerated in patients with a variety of
other skin disorders, including other
types of eczema, papulosquamous
disorders, disorders of cornification,
rosacea, other inflammatory skin
conditions, vesiculobullous diseases,
vitiligo, connective-tissue diseases,
graft-versus-host disease and follicular
disorders.15,20,21 Its advantage is that it
may offer a safe and efficacious alter-
native to topical glucocorticoids,
which have the potential to cause skin
atrophy.21 While tacrolimus has been
used in the treatment of rosacea, it
has not been universally accepted by
dermatology. Confounding matters,
the New England Journal of Medicine
recently released a publication warn-
ing that tacrolimus (and pime-
crolimus) may have a link to
increased risk of cancer.24
Clinical Pearls
• Detergent-based lid scrubs may
be only marginally helpful in rosacea
and meibomian gland dysfunction,
since they may strip away the rest of
what little spreadable lipid is being
released.
• In moderate, severe or chronic
cases, multiple topical and oral med-
ications may be required.
• Flashlamp-pumped, long-pulse
dye laser or the potassium-titanyl-
phosphate laser may be used to treat
excessive, cosmetically significant
facial telangiectasias and phymatous
skin reactions.
1. Gurwood AS. Understanding the diagnosis and
management of external eye disease. Br J Optom
Dispens 1995;3(4):55-63.
2. Lane SS, Holland EJ. The chronic blepharitis and
cataract patient. In: Soll DB. Clinical Decisions in
Ophthalmology. New York: Brannigan-DeMarco
Publishers, 1993, pp. 17(3):1-15.
3. Cullom RD, Chang B. Conjunctiva/sclera/external
eye disease: blepharitis/meibomianitis. In: Cullom
RD, Chang B, eds. The Wills Eye Manual: Office and
Emergency Room Diagnosis and Treatment of Eye

Disease. Philadelphia: J.B. Lippincott, 1994, p. 130.
4. Jackson WB. Differentiating conjunctivitis of
diverse origins. Surv Ophthalmol 1993;38(3
suppl):91-104.
5. Mackley CL, Thiboutit DM. Diagnosing and manag-
ing the patient with rosacea. Cutis 2005;5(4
Suppl):25-9.
6. Chaglasian MA. Rosacea. In: Thomann KH, Marks
ES, Adamczyk DT. Primary Eyecare in Systemic
Disease, 2nd ed. New York: McGraw-Hill, 2001, pp.
356-60.
7. Tu EY, Rheinstrom S. Dry eye. In: Yanoff M, Duker
JS, eds. Ophthalmology, 2nd ed. St. Louis: Mosby,
2004, pp. 520-6.
8. Wilkin J, Dahl M, Detmar M, et al. Standard grad-
ing system for rosacea: Report of the National
Rosacea Society Expert Committee on the classifica-
tion and staging of rosacea. J Am Acad Dermatol
2004;50(6):907-12.
9. Dutton JJ. Clinical anatomy of the eyelids. In:
Yanoff M, Duker JS, eds. Ophthalmology.
Philadelphia: Mosby, 1999,7.11-7.14.
NEW PERSPECTIVES ON ALLLERGY
According to the National Institute of Allergy and
Infectious Diseases (NIAID), more than 50 million
Americans currently suffer from some form of allergic dis-
ease.1 Allergies are the sixth leading cause of chronic ill-
ness in the United States, costing
the health-care system nearly $18
billion annually.1 Historically, it
has been suggested that about
20% of the U.S. population has
some type of allergy,2 but a recent
Gallup Survey found that as many
as 50% of Americans suffer from
allergic disease, with 83% of these
manifesting some form of ocular Injected, chemotic conjunctiva in allergic conjunctivitis.
symptoms.
Allergy is best described as an inappropriate immune
system reaction to a substance that, under normal circum-
stances and in unaffected individuals, would not and
should not pose any significant threat. A number of factors
® OCULOSYSTEMIC DISEASE
10. McCulley JP, Shine WE. The lipid layer of tears: 17. Schimmel DJ. Infiltrative keratitis. In: Onofrey
Dependent on meibomian gland function. Exp Eye BE, ed. Clinical Optometric Pharmacology and
Res 2004;78(3):361-5. Therapeutics. Philadelphia: J. B. Lippincott, 1994,
11. Mathers W. Evaporation from the ocular surface. pp. 1-13.
Exp Eye Res 2004;78(3):389-94. 18. Rebora A. The management of rosacea. Am J Clin
12. McCulley JP, Shine WE. Eyelid disorders: the mei- Dermatol 2002;3(7):489-96.
bomian gland, blepharitis, and contact lenses. Eye 19. Del Rosso JQ, Bilkowski J. Topical metronidazole
Contact Lens 2003;29(1 Suppl):S93-5;S115- combination therapy in the clinical management of
8,S192-4. rosacea. J Drugs Dermatol 2005;4(4):473-80.
13. Romero JM, Biser SA, Perry HD, et al. 20. Sidbury R. What’s new in pediatric dermatology:
Conservative treatment of meibomian gland dysfunc- Update for the pediatrician. Curr Opin Pediatr
tion. Eye Contact Lens 2004;30(1):14-19. 2004;16(4):410-4.
14. Mori A, Shimazaki J, Shimmura S, et al. 21. Woo DK, James WD. Topical tacrolimus: A review
Disposable eyelid-warming device for the treatment of of its uses in dermatology. Dermatitis 2005;16(1):6-
meibomian gland dysfunction. Jpn J Ophthalmol 21.
2003;47(6):578-86.
22. http://www.rosacea.org/patients/materials/under-
15. Yokoi N, Komuro A. Non-invasive methods of
standing/triggers.html.
assessing the tear film. Exp Eye Res
2004;78(3):399-407. 23. http://www.rosacea.org/rr/2005/fall/article_1.html.
16. Perry HD, Donnenfeld ED. Dry eye diagnosis and 24. Dantel J, Soulillou JP. Immunosuppressive drugs
management in 2004. Curr Opin Ophthalmol and the risk of cancer after organ transplantation. N
2004;15(4):299-304. Engl J Med 2005;13(352):1371-3.
contribute to the development of allergy. Certainly, genet-
ics plays a role, since parents with allergies are quite like-
ly to bear children who have allergies. More to the point, a
number of genes have been specifically linked to allergy,
including loci on chromosomes 5,
11, 12 and 16.3 In addition, the
atopic individual (atopy is a genet-
ic predisposition toward the devel-
opment of allergy) must also
undergo exposure to the specific
allergen in question, whether it be
animal dander, pollen, peanuts, or
another substance. Years ago,
these two features—genetics and
exposure—were the only factors
believed to control allergy development. Today, however,
we realize that the general allergic response is a multifac-
eted autoimmune disorder, and that the very environment
in which we live plays a crucial role in its genesis.
MARCH 15, 2006 REVIEW OF OPTOMETRY 61A
 In 1989, David Strachan observed a significant
increase in the prevalence of general allergy among British
children and those of other industrialized countries.1 He
proposed that the trend toward a cleaner, more hygienic
society (better sanitation, diminished family size and
improved standards of personal cleanliness) might actual-
ly be responsible for alterations in our immunological
1
development. Strachan’s ideas, quite provocative at the
time of their initial publication, have come to be known
as the “hygiene
hypothesis” of aller-
gic development. A
great deal of
research has been
conducted in this
area over the last
15 years, with some
startling conclu-
sions. Today, many
consider exposure
to certain viral and
bacterial pathogens
to be critical in the
development of a
normal immune sys- Severe ocular allergies, which is evidenced in erythematous, edematous lids.
tem.
According to this theory, the more potential pathogens
an individual is exposed to early in life, the better that indi-
vidual’s immune system develops to manage true patho-
logic “threats” and the less likely the person’s immune sys-
tem will be triggered by benign substances such as pollen
and dust. In essence, a moderately “dirty” environment
and a few childhood infections may actually be beneficial
in protecting against the development of allergy. Research
points toward a number of features that may control the
pathogenesis of atopy:
Family size. Strachan observed that British schoolchild-
ren who came from larger families, particularly those with
a substantial number of older siblings, were significantly
less likely to develop atopic conditions.4 Von Mutius
(1994) likewise observed that individuals from larger fam-
ilies were less likely to test positive on allergic skin test-
ing.5 Other studies have shown that children who enter
daycare facilities early in life—and are exposed to other
young children in a closed environment—are less likely to
develop atopic diseases.6-8 The conclusion of all these
reports is that greater exposure at an early age to children
with typical childhood illnesses (especially respiratory
infections) helps to set the immune system on the correct
track.
Endotoxin. Endotoxin is a component derived from cell
walls of Gram-negative bacteria, such as Haemophilus
and Pseudomonas.9
When these bacte-
ria die, endotoxin is
released into the
surrounding envi-
ronment and col-
lects as a compo-
nent of house dust.
Studies have shown
that early exposure
to higher levels of
endotoxin may also
reduce the preva-
lence of atopic dis-
ease. Research
comparing the lev-
els of endotoxin in
homes and mattresses of children with and without aller-
gies seems to confirm this theory.10,11 Thus, a moderately
dusty environment may actually be beneficial in preventing
allergy development.
Farm living. A number of researchers12-15 have suggested
that individuals who are raised in farming communities
have a lower prevalence of allergic disease. Asthma, hay
fever, and other atopic disorders were significantly less
prevalent in those who spent the early years of their life on
a farm, and this trend persisted into adulthood.12 Even
more provocative is the fact that children raised within
these same communities, but not specifically on a farm,
did not enjoy the same protection against allergy.13,14
Researchers are unsure of which specific features associ-
ated with farm life are most significant, but possibilities
include exposure to high levels of endotoxin, contact with
animal livestock and a diet rich in dairy products.15

62A REVIEW OF OPTOMETRY MARCH 15, 2006


Pets. Contact with animals other than those commonly
encountered on a farm may also potentially inhibit allergy
development. Recent studies suggest that early exposure
to house pets, particularly dogs, may protect against the
development of allergy. An inverse association between pet
ownership in the first year of life and atopic diseases—
such as asthma, allergic rhinitis and eczema—has been
16-18
demonstrated.
Intestinal bacteria and parasites. All humans harbor bac-
teria in the gastrointestinal tract as part of the normal
bowel flora. Studies suggest that the composition of this
flora, and specifically the elimination of some potentially
pathogenic organisms, may further predispose an individ-
ual to allergy. Stark differences were noted in studies of
children from locations with high and low prevalences of
19,20
atopic disease. In addition, researchers have observed
that populations in which parasitic roundworm infection is
high show a significantly lower incidence of atopy, and
children who test positive for exposure to Schistosoma, for
21
example, are less likely to develop allergic sensitization.
The supposition is that these parasites (including Ascaris,
whipworm and hookworm) may actually attenuate the aller-
gic response by virtue of certain interleukins that infection
produces.21,22
How these factors work, and what exactly transpires to
“switch on” the phenomenon of the general allergic
response in predisposed individuals, remains unclear. It is
known that the immune system produces essentially two
types of lymphocytes: T-Helper-1 (Th1) and T-Helper-2
(Th2). Th1 cells are primarily concerned with bacterial and
viral infections, while Th2 cells are associated with para-
sitic infection and the allergic response. In the normal
individual, Th1 and Th2 lymphocytes exist in a delicate
balance. However, the immature immune system favors
Th2. It has been postulated that individuals who are not
exposed to adequate numbers of pathogens may not
mature appropriately, resulting in diminished Th1 and an
overabundance of Th2.23,24 The Th2 system, having few
actual parasites to overcome, begins responding to other-
wise benign stimuli (e.g., pollen), producing the clinical
signs and symptoms that compose the response known as
allergy.
It seems quite ironic that human efforts to eliminate
® OCULOSYSTEMIC DISEASE
environmental “germs,” which cause colds, flu and other
illnesses, may have literally allowed our immune systems
to “de-evolve.” Does this mean we should stop washing our
hands or cleaning our homes? Not quite, but experts sug-
gest that fanatical cleanliness, particularly with children in
the early years of development, is probably not advisable.
Household pets may be beneficial to children as well, not
only as social companions but also as stimulators of their
immune systems. Most important, this research may ulti-
mately lead to the development of a vaccine against aller-
gy. Until that time, however, clinicians need to recognize
the vast prevalence of allergy in our health-conscious cul-
ture and be proactive in diagnosing and managing a disor-
der that has such great potential to compromise our qual-
ity of life.
1. National Institute of Allergy and Infectious Diseases, National Institutes of
Health. Allergy Statistics. December 22, 2004. http://www.niaid.nih.gov/fact-
sheets/allergystat.htm.
2. American Academy of Allergy, Asthma and Immunology. Task Force on Allergic
Disorders. Executive Summary Report, 1998.
3. Borish L. Genetics of allergy and asthma. Ann Allergy Asthma Immunol
1999;82(5):413-24.
4. Strachan DP. Hay fever, hygiene, and household size. BMJ
1989;299(6710):1259-60.
5. von Mutius E, Martinez FD, Fritsch C, et al. Skin test reactivity and number of
siblings. BMJ 1994;308(6930):692-5.
6. Kramer U, Heinrich J, Wjst M, et al. Age of entry to day nursery and allergy in
later childhood. Lancet 1999;353(9151):450-4.
7. Ball TM, Castro-Rodriguez JA, Griffith KA, et al. Siblings, day-care attendance,
and the risk of asthma and wheezing during childhood. N Engl J Med
2000;343(8):538-43.
8. Farooqi IS, Hopkin JM. Early childhood infection and atopic disorder. Thorax
1998;53(11):927-32.
9. Bufford JD, Gern JE. The hygiene hypothesis revisited. Immunol Allergy Clin
North Am 2005;25(2):247-62.
10. von Mutius E, Braun-Fahrlander C, Schierl R, et al. Exposure to endotoxin or
other bacterial components might protect against the development of atopy. Clin
Exp Allergy 2000;30(9):1230-4.
11. Gehring U, Bischof W, Fahlbusch B, et al. House dust endotoxin and allergic
sensitization in children. Am J Respir Crit Care Med 2002;166(7):939-44.
12. Riedler J, Eder W, Oberfeld G, et al. Austrian children living on a farm have less
hay fever, asthma and allergic sensitization. Clin Exp Allergy 2000;30(2):194-200.
13. Braun-Fahrlander C, Gassner M, Grize L, et al. Prevalence of hay fever and aller-
gic sensitization in farmers’ children and their peers living in the same rural com-
munity. Clin Exp Allergy 1999;29(1):28-34.
14. Adler A, Tager I, Quintero DR. Decreased prevalence of asthma among farm-
reared children compared with those who are rural but not farm-reared. J Allergy
Clin Immunol 2005;115(1):67-73.
15. von Mutius E. Environmental factors influencing the development and progres-
sion of pediatric asthma. J Allergy Clin Immunol 2002;109(6 Suppl):S525-32.
16. Hesselmar B, Aberg N, Aberg B, et al. Does early exposure to cat or dog protect
against later allergy development? Clin Exp Allergy 1999;29(5):611-7.
MARCH 15, 2006 REVIEW OF OPTOMETRY 63A
 17. Gern JE, Reardon CL, Hoffjan S, et al. Effects of dog ownership and genotype
on immune development and atopy in infancy. J Allergy Clin Immunol
2004;113(2):307-14.
18. Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year
of life and risk of allergic sensitization at 6 to 7 years of age. JAMA
2002;288(8):963-72.
19. Bjorksten B, Sepp E, Julge K, et al. Allergy development and the intestinal
microflora during the first year of life. J Allergy Clin Immunol 2001;108(4):516-20.
20. Bjorksten B, Naaber P, Sepp E, et al. The intestinal microflora in allergic
Estonian and Swedish 2-year-old children. Clin Exp Allergy 1999;29(3):342-6.
PROFESSIONAL COMMUNICATION
There is an art and decorum to efficiently communicat-
ing with colleagues and physicians. This skill is critical, as
it allows one to remain in compliance with rules set forth
by many third-party plans (written reports mandatory), and
it also serves as a tool for facilitating care. Like it or not,
the written report is a reflection of you, your office, your
operation, the way in which you think and what you were
thinking with respect to the problem at hand. It has the
ability to create a lasting impression, good or bad, and
must be executed with care and precision. Lastly, inter-
professional communications can have the practice build-
ing benefits of developing new referral sources by letting
physicians know your clinical skills.
Professional communication can be subdivided into
four subtypes: Personal communication (in person, face-
to-face), telecommunication (speaking by telephone), cor-
respondence by formal letter (the classic report) and cor-
respondence by note (brief summary with only
problem-oriented data and management).
The parceling of information and ideas regarding
patients and their cases using face-to-face personal com-
munication is all but extinct. The combination of declining
fee reimbursements and economic inflation, in the setting
of increased requirements for written reports (not to men-
tion the desire one might have for a physical paper trail),
64A REVIEW OF OPTOMETRY MARCH 15, 2006
21. van den Biggelaar AHJ, van Ree R, Rodrigues LC, et al. Decreased atopy in chil-
dren infected with Schistosoma haematobium: A role for parasite-induced inter-
leukin-10. Lancet 2000;356(9243):1723-7.
22. Cooper PJ, Chico ME, Rodrigues LC, et al. Reduced risk of atopy among school-
age children infected with geohelminth parasites in a rural area of the tropics. J
Allergy Clin Immunol 2003; 111(5):995-1000.
23. Romagnani S. Immunologic influences on allergy and the TH1/TH2 balance. J
Allergy Clin Immunol 2004;113(3):395-400.
24. Renz H, Blumer N, Virna S, et al. The immunological basis of the hygiene
hypothesis. Chem Immunol Allergy 2006;91:30-48.
has made the practice of communicating by meeting and
conversation virtually impossible and impractical.
The exception to this occurs in large multidisciplinary
or group settings, such as hospitals or medical office cen-
ters, where colleagues and other physicians work in close
physical proximity. In this type of situation, it may not be
uncommon to pass a participating provider in the hallway,
meet him or her for coffee or have discussions over a meal.
In these instances, where data is transferred by way of the
spoken word, you should be mindful of your surroundings
and the privacy regulations (using minimal identifying
data). When a conversation about a case has occurred,
upon returning to the office, make a note in the chart,
including the date, time, parties involved in the conversa-
tion and summary of the discussion. Authenticate the note
with a signature. Separate conversations require separate
notations.
An easier and more practical way of accomplishing the
same goal, although it is a bit more time consuming, is
telecommunication—the professional phone call. When
executed properly, a telephone call can leave a wonderful
and thoughtful impression, add clarity to written notes and
act as a precursor to referrals or letters. Its takes more
time, but it provides a more flexible and efficient medium
than writing. If the parties are familiar, there is no need for

formality. If the parties are unfamiliar, it’s essential to be
concise and organized. This is best accomplished by think-
ing ahead to generate a plan for the conversation. Ask
yourself these questions: What needs to be accomplished?
What data must be reported to support the conclusion?
What action plan or outcome is desired? Take a moment to
outline the important elements of the conversation, formu-
late an order in which the points should be broached and
give some thought as to how the conversation will play out.
As with personal conversations, make a note in the
patient’s chart, including the date, time, parties involved
in the conversation and summary of content. Authenticate
the note with a signature. Separate conversations require
separate notations.
A formal report or letter is by far the most common
method of exchanging patient information. Its advantages:
It creates a detailed hard copy of the information trans-
ferred, it can be edited and inspected before it is sent and
it can be completed by an assistant via dictation. Its dis-
advantages: It can be time-consuming (copy must be
proofread and corrected before distribution) and, when
done in quantity, costly (considering the price of
envelopes, stationery and postage).
Recently, computer software programs have enabled
electronic record-keeping along with electronic correspon-
dence. Automated report production is included in many
electronic medical record software programs. Such pro-
grams incorporate a designed backup (e.g., electronic
identification, time stamping and dating) to ensure against
fraud. Since the electronic documents are not hand
signed, however, limited or licensed access to the program
is all that prevents misuse. Offices that choose this type of
tool must have protocols in place to safeguard access.
The components of a well-constructed written report
vary depending on style. Many include all pieces of data
gathered with narrative descriptions and explanations.
However, when considering those who are intended to read
® OCULOSYSTEMIC DISEASE
these reports and the time it takes to analyze them, multi-
plied by five to 10 reports per day, realize that a more
abbreviated style can be more efficient and more palatable
both for the composer and the recipient. The minimum
anatomy of a proper professional letter includes the date,
an introductory paragraph, a data paragraph that describes
the essential findings, an impression and plan paragraph,
and an ending or conclusion note.
The note is used to formulate an abbreviated and infor-
mal document conveying only the critical and essential
findings concerned with a case and a suggested plan of
action for that specific malady. It is intended to be brief,
without formal grammar and designed to fit on a 5 x 7 pre-
scription pad. Most prescription pads contain some sort of
transfer to an under-copy, so a duplicate is automatically
generated for the referring doctor. Since the note is hand-
written at the time of the encounter, no additional proof-
reading or editing is required, and the patient can hand-
carry it with instructions, so no postage is required. The
disadvantages to this method: If the person to whom you
are corresponding is unfamiliar with you, the note does not
necessarily build a good first impression. Also, if one’s
handwriting is poor or rushed, notes may be illegible.
Finally, the person who carries the note could lose it or for-
get to give it to the intended provider.
Finally, as long as patient-specific identifiers are omit-
ted or secure connections are established (so as not to
compromise confidentiality) e-mail documents are permis-
sible and have the advantage of being virtually immediate,
cost-free and traceable.1 Additionally, photographs and
other images can transferred by e-mail. Technology has
enabled the perfection of programs that allow almost flu-
ent dictation-to-typewritten reports, thereby streamlining
the entire process.
1. Healthcare Benchmarks Committee. Healthcare Benchmarks Qual Improv
2005;12(5):54-6.
MARCH 15, 2006 REVIEW OF OPTOMETRY 65A