OPTHALMOLOGY

3A RETINA & INTRAOCULAR TUMORS

OP-09 Dr. JENALYN T . MATILA, MD, DPBO, MHA | September 2019

TOPIC OUTLINE RETINA ANATOMY AND PHYSIOLOGY

I. RETINA ANATOMY AND PHYSIOLOGY Retina
a. Retina - Most complex of the ocular tissues with a highly organized
b. Rods and Cones structure.
c. Fovea - Divided into10 distinct histological layers:
d. Night (Scotopic) vision 1. Pigmented epithelial cells
e. Daylight (Photopic) vision 2. Photoreceptor Layer
f. Twilight (Mesopic) vision 3. Outer limiting membrane
II. AGE-RELATED MACULAR DEGENERATION 4. Outer nuclear layer
a. Early AMD 5. Outer Plexiform layer
b. Late AMD 6. Inner nuclear layer
c. Neovascular (Wet AMD) 7. Inner Plexiform layer
d. Myopic Macular degeneration 8. Ganglion cell layer
III. RETINAL VASCULAR DISEASE 9. Optic Nerve Fibers
a. Diabetic Retinopathy
b. Retinal Vein Occlusion Rods and Cones
c. Retinal Artery Occlusion - Responsible for initial transformation of light stimuli into the
IV. RETINAL ARTERIAL MACROANEURYSM nerve impulses.
V. RETINOPATHY OF PREMATURITY - Increased density of cones in the center of macula (fovea),
VI. RETINAL DETACHMENT & RELATED RETINAL decreasing in the density.
DEGENERATIONS - Higher density of rods in the periphery
a. Rhegmatogenous Retinal Detachment - Located in the vascular outermost layer of the retina.
b. Traction Retinal Detachment
c. Serous Hemorrhagic Retinal Detachment Fovea
d. Lattice Degeneration - Responsible for good spatial resolution (visual acuity) and
e. Peripheral Chorioretinal Atrophy color vision, both requiring high ambient light (photopic
VII. RETINOSCHISIS vision and best at foveola.)
a. Typical degenerative retinoschisis
b. Reticular degenerative retinoschisis  The remaining retina is utilized primarily for
VIII. MACULAR HOLE motion, contrast, and night (scotopic vision).
IX. EPIMACULAR MEMBRANES
X. TRAUMATIC & RELATED MACULOPATHIES Night (Scotopic) Vision
a. Commotio retinae - Mediated entirely by rod photoreceptors.
b. Traumatic choroidal rupture - With this dark-adapted form of vision, varying shades of grey
c. Purtscher retinopathy are seen, but colors cannot be distinguished.
d. Terson syndrome
e. Solar Retinopathy Daylight (Photopic) Vision
XI. CENTRAL SEROUS CHORIORETINOPATHY - Mediated primarily by cone receptors
XII. MACULAR EDEMA
XIII. ANGIOD STREAKS Twilight (Mesopic) vision
XIV. INFLAMMATORY DISEASES AFFECTING RETINA, - Combination of cones and rods.
RETINAL PIGMENT EPITHELIUM & CHOROID
a. Presumed Ocular Histoplasmosis Syndrome  Photoreceptors are maintained by the retinal
b. Acute Multifocal Posterior Placoid Pigment pigment epithelium, w/c plays an important
Epitheliopathy role in the visual process.
c. Serpiginous (Geographic Helicoid Peripapillary)
Choroidopathy  Responsible for phagocytosis of the outer
d. Birdshot Retinochoroidopathy Vitiliginous segments of the photoreceptors, transport of
Chorioretinitis vitamins, and reduction of lights cutter, as well
e. Acute Macular Neuroretinopathy as providing a selective barrier between
f. Multiple Evanescent White Dot Syndrome choroid and retina.
g. Macular Dystrophies
XV. HEREDITARY RETINAL DEGENERATIONS EXAMINATION:
a. Retini Pigmentosa - Can be examined by:
b. Fundus Albipunctatus  Direct or indirect ophthalmoscope or
c. Leber Congenital Amaurosis  Slitlamp (biomicroscope)
d. Gyrate Atrophy  Handheld or contact biomicroscopy lens
XVI. COLOR VISION DEFECTS - Allows identification of the type, level and extent of retinal
a. Dichromacy disease.
b. Monochromacy
XVII. RETINAL TUMORS
a. Benign Retinal Tumors
b. Retinal Tumors of Intermediate Character
c. Malignant Retinal Tumors

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AGE-RELATED MACULAR DEGENERATION (AMD) PROPHYLACTIC THERAPY
- Affects people over 55 and is leading cause of irreversible  Treatment with oral vitamins (C, E,
blindness in the developed world. Betacarotene) and antioxidants was found to
- Complex multifactorial reduce the 5 year risk of progression to late AMD.
 Increasing age  Smoking is a proven risk factor for development
 White race of all forms of macular degeneration.
 Smoking
- Genetic Factors TREATMENT
 The two most important loci are at:  Ranibizumab - treatment of choice for all forms of
 1q25-31 (complement factor H-CFH) neovascular AMD.
 10q26 (age-related maculopathy susceptibility 2-  Retinal laser photocoagulation can achieve
ARMS2/HTRA1) direct destruction of a choroidal neovascular
 These genes can be divided into: membrane.
 Influence on structural (HTRA1)
 Inflammatory (CFH, C3, C2, factor B) MYOPIC MACULAR DEGENERATION
 Lipid pathways (APOE) - Pathologic Myopia is one of the leading causes of blindness
- Individuals with genetic predisposition are even more likely in US and more common in Far East Japan.
to develop the disease if they smoke or have low intake of - Characterized by:
antioxidants.  Progressive elongation of the eye with subsequent
thinning and atrophy of the choroid and retinal pigment
HTRA1 epithelium in the macula.
 Heat shock protein that is involved in the  Flourescein angiography shows delayed in the filling
degradation of extracellular proteins such of choroidal and retinal blood vessel and helpful in
as that found in the Bruch’s membrane. identifying and locating the site of choroidal
neovascularization.
CHF
 Involved in the alternative complement RETINAL VASCULAR DISEASE
pathway, thereby identifying an DIABETIC RETINOPATHY
inflammatory component in the - Leading cause of blindness in Western world
pathogenesis of AMD. - Progressive microangiopathy characterized by:
 Small vessel damage
C3, C2, Factor B  Occlusion
 C3 mutations confer a 3x increased risk, C2 - Earliest pathologic changes:
and factor B protective effect.  Thickening of capillary endothelial basement
membrane
EARLY AMD  Reduction of Pericytes
- Characterized by:
 Drusen - yellow deposits, w/c are situated within Bruch NONPROLIFERATIVE RETINOPATHY
membrane. Discrete or confluent.
 Pigmentary change - maybe due to focal clumps of
MILD  1 microaneurysm
pigmented cells in the Subretinal space and outer  Extensive microaneurysm
retina. intraretinal hemorrhages
MODERATE
 Retinal or Pigment Epithelial atrophy (flame shaped)
 Venous beading
LATE AMD  Cotton wool spots
- Geographic atrophy (Dry AMD)  Cotton wool spots
- Responsible for up to 20% of legal blindness attributable to SEVERE  Venous beading
AMD.  Intraretinal microvascular
- Manifests as: abnormalities
 Well demarcated areas larger than 2 disk dm
 Atrophy of retinal pigment epithelium and  Microaneurysm - tiny dot like
photoreceptor cells (Visual loss occurs once the fovea outpouchings in the capillary.
is affected)  Risk factors:
- Best monitored with autofluorescence imaging.  Chronic Hyperglycemia
 HPN
NEOVASCULAR (WET AMD)  Hypercholesterolemia
- Characterized by the development of:  Smoking
 Choroidal neovascularization or  Screening:
 Serous retinal pigment epithelial detachment  Seven Field Photography –
- Choroidal neovascularization is classified into: GOLD STANDARD
 Classic - is characterized by early
hyperfluorescence w/c is usually circumscribed and
may have lacy pattern.
 Occult - is characterized by ill-defined and late
hyperfluorence

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MACULOPATHY
- Focal or diffuse retinal
thickening or edema.
- Breakdown of inner
blood retinal barrier at
the level of retinal
capillary endothelium
which allows fluid and
plasma leakage.
PROLIFERATIVE RETINOPATHY
- Most severe complication of DM.
- Formation of new vessels leak serum proteins.
RETINA & INTRAOCULAR TUMORS
- d/t branch RVO - grid pattern macular argon laser
photocoagulation
IRIS AND RETINAL NEOVASCULARIZATION
- Neovascular glaucoma
- PRP - standard treatment
RETINAL ARTERY OCCLUSION
CENTRAL RAO
- Painless catastrophic visual
loss occurring over period of
seconds.
- Amaurosis fugax -
antecedent transient visual
loss
- Visual acuity - counting
fingers and light perception
- Ciliorenal arteries - continue
to perfuse macula preserves
central vision

Foveal cherry-red spot - d/t preservation of the

relatively normal appearance of the choroidal
pigment and retinal pigment epithelium.

- TREATMENT: BRANCH RETINAL ARTERY OCCLUSION

 Mainstay of prevention - Sudden painless visual loss
 Good control of: - Impairment of visual fields
 Hypergylcemia - Foveal involvement - visual acuity impairment
 Hypercholesterolemia - TREATMENT:
 HPN  Anterior chamber paracentesis
 Focal laser  Intravenous acetazolamide
 Focal macular edema
RETINAL ARTERIAL MACROANEURYSM
 Grid laser
- Retinal macroaneurysms
 Diffuse macular edema
are fusiform or round
 Pan-retinal photocoagulation (PRP) dilations of retinal arterioles
 Vitrectomy occurring within the first
three orders of arteriolar
RETINAL VEIN OCCLUSION bifurcation.
- Sudden painless loss of vision - Result in edema, exudation
- Few small scattered retinal hemorrhage or hemorrhage typically with
- Cotton wool spots an “hourglass”
- Deep and superficial retinal hemorrhages configuration.
- Hemorrhage is usually
 Central retinal vein occlusion
followed by fibrosis of the
 All four quadrants of the fundus
macroaneurysm.
 Branch retinal vein occlusion - TREATMENT:
 One quadrant, at the site of an arteriovenous  Confluent laser photocoagulation
crossing  Direct hit
 Hemispheric branch - upper or lower half
 Macular branch - macula only RETINOPATHY OF PREMATURITY
- Retinopathy of prematurity (ROP) is a vasoproliferative
retinopathy that affects premature and low birth weight
infants
- Stages of ROP:

STAGES CLINICAL FINDINGS

1 Demarcation line
2 Intraretinal ridge
Ridge w/ extraretinal fibrovascular
3
MACULAR EDEMA proliferation
- Occurs in almost all eyes with central RVO. 4 Subtotal retinal detachment
- Impairment of visual acuity in branch retina vein occlusion. 5 Total retinal detachment
- d/t central RVO - doesn’t respond to laser treatment

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- Treatment SEROUS HEMORRHAGIC RETINAL DETACHMENT
 Screening from 2-4 - Serous and hemorrhagic retinal detachment occurs in the
weeks after birth until absence of either retinal break or vitreoretinal traction.
the retina is fully - They form as a result of accumulation of fluid beneath the
vascularized sensory retina and are caused primarily by diseases of the
 Peripheral retinal laser retinal pigment epithelium and choroid.
 Vitreoretinal surgery
LATTICE DEGENERATION
- A significant number of infants - Most common vitreoretinal degeneration
with ROP undergo - Produces localized round, oval, or linear areas of retinal
spontaneous regression. thinning, with pigmentation, branching white lines, and
- Peripheral retinal changes of regressed ROP include: whitish yellow flecks, and firm vitreoretinal adhesions at its
 Avascular retina margins.
 Peripheral folds - Rarely warrant prophylactic treatment with cryosurgery or
 Retinal breaks laser photocoagulation.
- Others:
 Myopia (which may be asymmetric) PERIPHERAL CHORIORETINAL ATROPHY
- Due to choroidal vascular insufficiency and is associated
 Strabismus
with peripheral vascular disease.
 Cataract
- The lesions appear as isolated or grouped, small, discrete,
 Angle-closure Glaucoma
yellow white areas with prominent underlying choroidal
vessels and pigmented borders.
RETINAL DETACHMENT AND RELATED RETINAL
DEGENERATIONS RETINOSCHISIS
- Retinal detachment is the separation of the sensory retina, - Degenerative retinoschisis is a common acquired peripheral
ie, the photoreceptors and inner retinal layers, from the retinal disorder that is believed to develop from coalescence
underlying retinal pigment epithelium of preexisting peripheral cystoid degeneration.
- The cystic elevation is most commonly found in the
inferotemporal quadrant, followed by the superotemporal
quadrant.
- It develops into one of two forms, typical or reticular, although
clinically the two are difficult to differentiate
1. Typical Degenerative Retinoschisis
 Round or ovoid area of retinal splitting in the outer
plexiform layer
 Posterior extension and hole formation is
uncommon
 Low risk of progression to retinal detachment
RHEGMATOGENOUS RETINAL DETACHMENT 2. Reticular Degenerative Retinoschisis
- Most common type  Nerve fiber layer
- Full thickness break (a “rhegma”) in the sensory retina.
 Bullous elevation of an extremely thin inner layer
- Usually preceded or accompanied by a posterior vitreous  23% - retinal holes
detachment and is associated with myopia, aphakia, lattice  Posterior extension to rhegmatogenous retinal
degeneration, and ocular trauma. detachment may occur and requires tx
- The location of retinal breaks varies according to type.
- TREATMENT: Differentiation from Retinal Detachment:
 Pneumatic Retinopexy  Retinoschisis causes an absolute
 Scleral Buckling scotoma in the visual field.
 Pars Plana Vitrectomy  The cystic elevation of retinoschisis is
usually smooth with no associated
TRACTION RETINAL DETACHMENT vitreous pigment cells.
- Traction retinal detachment is most commonly due to  If argon laser photocoagulation to the
proliferative diabetic retinopathy outer retinal layer, aimed through an
- Associated with proliferative vitreoretinopathy, ROP, or inner layer break, creates an equal gray
ocular trauma response as in an adjacent area of
- In comparison to rhegmatogenous retinal detachment, normal retina, this is thought to be
traction retinal detachment has a more concave surface diagnostic of retinoschisis.
and is likely to be more localized usually not extending to
the ora serrata MACULAR HOLE
- Tractional forces actively pull the sensory retina away from - Full thickness absence of the sensory
the underlying pigment epithelium toward the vitreous base retina in the macula
- Focal traction from cellular membranes can produce a retinal - Visual acuity is impaired, and
tear and lead to combined traction rhegmatogenous retinal metamorphopsia and a central
detachment scotoma are present on Amsler grid
- TREATMENT: testing.
 Pars Plana Vitrectomy - The Watzke Allen slit beam test
 Retinotomy and/or Injection of Perfluorocarbons or correlates well with the presence of a
heavy liquids full thickness macular hole.
 Gas tamponade, silicone oil, or scleral buckling

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FOUR STAGES: CENTRAL SEROUS CHORIORETINOPATHY
Occult hole, there is a yellow spot at the foveola - Characterized by serous
with loss of the foveal reflex. This stage is detachment of the sensory
Stage 1
reversible if a posterior vitreous detachment retina due to multi-focal areas
occurs. of hyperpermeability of the
Stage 2 Enlargement with a deep perifoveal yellow ring. choroidal vessels and
The well circumscribed full thickness macular alteration in the pumping
Stage 3
hole is surrounded by a cuff of subretinal fluid. function of the retinal pigment
The full thickness hole is associated with a epithelium.
Stage 4
posterior vitreous detachment. - Presentation: sudden onset
of blurred vision,
micropsia,
metamorphopsia, central
scotoma
- Visual acuity is often only moderately decreased and may be
improved to near normal with a small hyperopic correction
- Round or oval area of retinal elevation
OCT (Optical Coherence Tomography) - Yellowish gray spots
- Is the best method of diagnosis and assessment before and - Decrease in color sensitivity, micropsia or relative scotoma
after surgery. - “smokestack” configuration of fluorescein dye leaking from
the choriocapillaris followed by accumulation below the
Treatment to reattach the retina of the cuff surrounding the retinal pigment epithelium or sensory retina
macular hole involves: - Complications, including subretinal neovascularization and
 Vitrectomy chronic CME have been described in patients with frequent
 Separation of the posterior hyaloid and prolonged serous detachments.
 Removal (peeling) of the retinal internal limiting
membrane MACULAR EDEMA
- Causes:
EPIMACULAR MEMBRANES (EEM)  Intraocular inflammatory disease
- Contraction of EEM causes varying degrees of visual  Retinal vascular disease
distortion, intraretinal edema and degeneration of the  Epimacular membrane
underlying retina.  Intraocular surgery (cataract is the MCC of CME)
- Biomicroscopy usually shows wrinkling (striae) of the retina  Inherited or acquired retinal degeneration
and distortion of retinal vessels.  Drug therapy
- Rarely there may be retinal hemorrhages cottonwool spots,  Idiopathic
serous retinal detachment, and macular changes that - Can be:
simulate a macular hole (pseudo macular hole) 1. Diffuse
- Posterior vitreous detachment is nearly always present  When nonlocalized intraretinal fluid results in
- Disorders associated with EMM include: thickening of macula.
 Retinal tears with or without rhegmatogenous 2. Focal
retinal detachment  Fluid accumulation in honeycomb-like spaces of
 Vitreous inflammatory diseases the outer plexiform and inner plexiform layers
 Trauma (cystoid macular edema).
 Variety of retinal vascular diseases
- Visual acuity usually remains stable, suggesting that
contraction of EMM is a short lived and self-limited process
- Surgical peeling of severe EMM can be performed to treat
visual distortion, but recurrence occurs

TRAUMATIC AND RELATED MACULOPATHIES

1. Commotio retinae - results from blunt trauma to anterior Optical Coherence Tomography of CME. Flower petal
segment of the eye. pattern of fluorescein dye in patient with CME after cataract
2. Traumatic choroidal rupture - may result in permanent surgery
visual loss.
3. Purtscher retinopathy - bilateral multiple patches of - TREATMENT:
superficial retinal whitening and hemorrhages.  Topical steroid, NSAID
- Occurs after severe compression injury to head or trunk.  Orbital floor or intravitreal triamcinolone for
4. Terson syndrome - Retinal, pretinal or vitreous resistant cases
hemorrhage.  YAG laser vitreolysis or vitrectomy if with vitreous
- 20% of patients with IC hemorrhage and elevated ICP traction
(assoc. with SA hemorrhage d/t rupture of IC aneurysm).
5. Solar Retinopathy - bilateral sharply demarcated and after ANGIOD STREAKS
irregularly shaped partial thickness hole or depression in the - Appear as irregular, jagged tapering lines that radiate from
center of fovea (After sun gazing) the peripapillary retina into the macula and peripheral
fundus
- The streaks represent linear, crack-like dehiscence in
Bruch's membrane

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- Active stage manifests itself as sharply demarcated gray
yellow lesions with irregular borders that appear to involve
the pigment epithelium and choriocapillaris.
Multiple angioid streaks - Local or systemic corticosteroid treatment may be of
extending from optic benefit when active inflammation is present.
nerve
BIRDSHOT RETINOCHOROIDOPATHY VITILIGINOUS
CHORIORETINITIS
- Diffuse cream colored patches at the level of the pigment
epithelium and choroid, retinal vasculitis associated with
cystoid macular edema, and vitritis.
- Associated systemic diseases: - Strong association with a subtype of HLA-A 29, genetic
 Pseudoxanthoma elasticum due to mutations in the predisposition, retinal autoimmunity.
recessive ABCC 6 gene - Electroretinography is useful for diagnosis and monitoring
 Paget disease of bone disease progression and response to treatment.
 Ehlers Danlos syndrome - Treatment with corticosteroids alone does not seem to be
 Hemoglobinopathy effective. Other immunosuppressants may be beneficial.
 Hemolytic disorder
- Patients with angioid streaks should be warned of the ACUTE MACULAR NEURORETINOPATHY
potential risk of choroidal rupture from even relatively mild - Acute onset of paracentral scotomas and mild visual acuity
eye trauma. loss accompanied by wedge-shaped parafoveal retinal
- TREATMENT: Retinal laser photocoagulation lesions in the deep sensory retina of one or both eyes.
- The macular lesions are subtle, reddish-brown, and best
INFLAMMATORY DISEASES AFFECTING THE RETINA, seen with a red-free light.
RETINAL PIGMENT EPITHELIUM, AND CHOROID - The patients are usually young adults with a history of acute
PRESUMED OCULAR HISTOPLASMOSIS SYNDROME viral illness.
- Characterized by serous and
hemorrhagic detachments MULTIPLE EVANESCENT WHITE DOT SYNDROME
of the macula due to subretinal (MEWDS)
neovascularization. - Acute and self-limited unilateral disease that affects mainly
- Associated with multiple young women.
peripheral atrophic - Characterized clinically by multiple white dots at the level of
chorioretinal scars (histo the pigment epithelium, vitreous cells, and transient
spots) and peripapillary. electroretinographic abnormalities.
- Chorioretinal scarring in the - Cause is unknown
absence of vitreal - The retinal lesions gradually regress in a matter of weeks,
inflammation. leaving only minor retinal pigment epithelial defects.
- Important to perform Amsler - Occasionally it progresses to become acute zonal occult
Grid Test outer retinopathy (AZOOR) with enlarged blind spots and
- TREATMENT: Intravitreal bevacizumab progressive visual field loss.

ACUTE MULTIFOCAL POSTERIOR PLACOID PIGMENT MACULAR DYSTROPHIES

EPITHELIOPATHY
- Develop rapidly progressive
bilateral vision loss in
association with multifocal flat
gray white subretinal lesions
involving the pigment
epithelium.
- Precede viral illness.
- Characteristic feature of the
disease is the rapid resolution
of the fundus lesions and a
delayed return of visual
acuity to near normal levels.
- TREATMENT:
 Immunosuppressants X-LINKED JUVENILE RETINOSCHISIS
 Anti VEGF therapy - X-linked recessively inherited disease thought to be due to
Muller cell dysfunction, affects young males and is
SERPIGINOUS (GEOGRAPHIC HELICOID characterized by a macular lesion called "foveal schisis”.
PERIPAPILLARY) CHOROIDOPATHY - The disorder is slowly progressive
- Chronic progressive and recurrent inflammatory - Fifty percent of patients have peripheral retinoschisis with
disease of the retinal pigment epithelium, choriocapillaris peripheral visual field abnormalities
and choroid. - There is a negative electroretinogram (ERG) (normal a
- It characteristically involves the juxtapapillary retina and wave amplitude with reduced b wave amplitude), which is
extends radially to involve the macula and peripheral typical of disorders affecting the inner retina leaving the
retina. photoreceptor cells intact. Female carriers have normal
- Affected areas are contiguous. ERGs.

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- On slitlamp examination, foveal schisis appears as small LEBER CONGENITAL AMAUROSIS
superficial retinal cysts arranged in a stellate pattern - Autosomal recessive disorder of rods and cones
accompanied by radial striae centered in the foveal area. - Triad of presentation
- The genetic abnormality in X-linked juvenile retinoschisis is  Severe visual impairment or blindness (1st year of
a mutation in the RS 1 gene, which codes for a retina specific life)
extracellular protein (retinoschisin) secreted by  Nystagmus
photoreceptors but involved in cell-cell interactions and  Generalized retinal dystrophy
cellular adhesion in the inner retina - A markedly reduced or absent ERG indicates generalized
- Carriers can be identified by DNA analysis photoreceptor dysfunction

CONE-ROD DYSTROPHIES GYRATE ATROPHY

- Autosomal recessive - Autosomal recessive disorder
- Mutation of the ABCA 4 gene - Reduced activity of ornithine aminotransferase
- Predominant involvement of the cone photoreceptor - Characteristic: sharply demarcated circular areas of
- PHOTOPHOBIA - most common early symptom chorioretinal atrophy develop in the mid periphery of the
- FUNDUS AUTOFLUORESENCE - preferred method for fundus
diagnosis and monitoring - Initially present with myopia and nyctalopia within the first
- ELECTRORETINOGRAPHY - marked loss of cone function decade of life
and moderate loss of rod function
COLOR VISION DEFECTS
STARGARDT DISEASE - Cone Receptors responsible for color vision, visual
- Associated with Fundus Flavimaculatus pigments (opsins) in their outer segments absorbing light
- Most common macular dystrophy wavelengths of 400-700 nm.
- Characteristic: multiple yellow-white fleck lesions of
variable size and shape, confined to the retinal pigment DICHROMACY
epithelium RED GREEN COLOR DEFICIENCY
- Typically presents before age 15 with reduced central vision  It results from mutation in the gene encoding of
- MACULAR abnormality: develops a bronze appearance either Red (Protanopia) or Green (Deutanopia)
with mid peripheral retinal flecks cone opsin
 Visual acuity is normal
JUVENILE-ONSET VITELLIFORM DYSTROPHY TRITANOPIA
- BEST Disease  Loss of blue-yellow discrimination due to defect
- Childhood onset in the blue cone opsin
- FUNDOSCOPIC appearance: “egg yolk” lesion located in
the central macula MONOCHROMACY
- This cyst like lesion is generally quite round and well CONE MONOCHROMACY
demarcated and contain homogenous opaque yellow  Mutation in genes encoding for both red and green
material cone opsin
- Abnormal Electro oculogram-hallmark of the disease ROD MONOCHROMACY
- Visual acuity remains good  Mutation in genes encoding proteins of the
- enetic Abnormality Mutation in BEST 1 (VMD 2) gene photoreceptor cation channel or cone transducin.
- Encodes a transmembrane calcium sentitive chloride
channel (bestrophin) expressed in the retinal pigment
epithelium

HEREDITARY RETINAL DEGENERATIONS

RETINIS PIGMENTOSA
- Heterogenous hereditary retinal degenerations
characterized by progressive dysfunction of the
photoreceptors
- Hallmark Symptoms:
 Night blindness (Nyctalopia)
 Gradual peripheral visual field loss
 Coalescing ring scotomas
- Fundoscopic Finding:
 Attenuated retinal arterioles, waxy pale optic disk
 Mottling of the retinal pigment epithelium
 “Bone Spicule formation” - peripheral retinal pigment
clumping
RETINAL TUMORS
FUNDUS ALBIPUNCTATUS
 Benign Neoplasms - Acquired tumors of cells that are
- Retinitis Punctata Albescens
atypical but not sufficient to be classified as malignant.
- Autosomal recessive nonprogressive dystrophy
 Hamartomas - Congenital tumors composed of normal or
- Characteristic: myriad of discrete small white dots at the
near normal cells and tissues for the anatomic site but in
level of the pigment epithelium sprinkled about the posterior
excessive amounts.
pole and mid periphery of the retina
 Choristomas - Congenital tumors consisting of normal
cells and tissue elements but not occurring normally at the
anatomic site.

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BENIGN RETINAL TUMORS
RETINAL ASTROCYTOMA
- “Retinal Astrocytic Hamartoma”
- Rarely present at birth or identified in the neonatal period. Classic retinal capillary
- Acquired benign neoplasm that arises from the astrocytes hemangioma inferiorly. The
within the retinal nerve fiber layer tumor is fed and drained by
- May be part of an inheritable syndrome dilated tortuous retinal blood
 Tuberous Sclerosis vessels. Note intraretinal and
 Non-inherited Isolated Entity subretinal exudates along the
 Tuberous Sclerosis blood vessels
 Multifocal and bilateral lesions frequently seen
 Non-syndromic Retinal Astrocytomas
 Almost exclusively unilateral and unifocal - As the tumor enlarges, the exudative retinal detachment
- Manifested during first or second decade of life usually increases in extent
 When small  Becomes associated with substantial vitreoretinal
 Appear as ill-defined translucent lesions of the fibrosis resulting in additional tractional retinal
inner retina (opalescent patches) detachment.
 Slightly larger lesions - Tumors of this type occur anywhere in the fundus from the
 Appear as discrete, opaque white nodules of the optic disc to the peripheral retina
inner retina  But most frequently in the equatorial or post-equatorial
 Occasional larger, more mature lesions region.
 Exhibit an irregular nodular character that has - Not present at birth
been likened to a “white mulberry”  Frequently starting to develop - teenage years

- Treatment
 Small von Hippel tumors
Solitary retinal  Laser photocoagulation, or
astrocytoma  Cryotherapy
superior to right  Larger lesions
fovea in an 11 year  Vitreoretinal surgery - to address the associated
old boy with exudative tractional retinal detachment
tuberous sclerosis Depending on the size and location of the retinal
tumors and extent of exudative-tractional retinal
detachment when the lesions are first detected,
vision in treated eyes can range from excellent to
no perception of light
- When identified early
in life typically enlarge slightly during follow-up
- But most lesions in individuals over the age of 25 years COMBINED HAMARTOMA OF THE RETINA
remain stable - Benign congenital malformation
- Rarely, a retinal astrocytoma of either the syndromic or - Composed of overgrown and disorganized normal retinal
isolated variety undergoes substantial progressive components with a characteristic clinical appearance
enlargement associated with malignant transformation - Three typical features:
- Generally no treatment is indicated  Deep gray color - due to involvement of retinal
 Unless substantial enlargement is documented pigment epithelium
 Superficial white “gliosis
RETINAL CAPILLARY HEMANGIOMA  Prominent angulated retinal blood vessels within
- von Hippel tumor the lesion
- Acquired benign neoplasm of the retina.
- Composed of neural retinal cells transformed into poorly Combined hamartoma of the
differentiated small cells with prominent nuclei and little retina involving the right
cytoplasm by a mutation of both alleles of the VHL gene, macula. Tumor exhibits deep
which is located on the short arm of chromosome 3 (p 25.5 gray color due to retinal
region). pigment epithelial
- May be part of a syndrome (von Hippel Lindau disease) involvement, superficial white
 Multifocal and bilateral lesions, or color due to retinal gliosis, and
 An isolated entity, likely to be a solitary, unilateral angulated retinal blood
lesion vessels with the lesion.
- In response to angiogenic factor(s) produced by its cells, the
tumor attracts a dense collection of blood vessels that gives - Usually adjacent to or surrounding the optic nerve (juxta- or
it the appearance of an intraretinal red sphere circumpapillary)
 Supplied by a dilated, tortuous retinal arteriole - Virtually always unifocal and unilateral
 Drained by a dilated, tortuous retinal venule - If the macula is involved, usually vision is impaired
- The tumor blood vessels tend to be leaky, resulting in - No treatment is indicated
accumulation of intraretinal edema and exudates and  But there is a frequent association with Type 2
subretinal fluid and exudates. neurofibromatosis
 Affected children may need to be screened for
vestibular schwannoma

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 OP-09 RETINA & INTRAOCULAR TUMORS
CONGENITAL HYPERTROPHY OF THE RETINAL PIGMENT ATYPICAL MULTIFOCAL BILATERAL NON
EPITHELIUM (CHRPE) CLUSTERED VARIETY OF CHRPE
- Benign focal congenital malformation of the retinal pigment  Occur in individuals with Gardner’s syndrome
epithelium characterized pathologically by: and related familial colonic polyposis-
 Increased size (hypertrophy) carcinoma disorders
 Increased number (hyperplasia) of retinal pigment  Outline tends to be angulated, sometimes having
epithelial cells in a localized region of the fundus areas of depigmentation along its margin
- Abnormal RPE cells tend to be densely packed with large  Lesions are scattered across the fundus, not
melanin granules clustered in a single area
- Always present at birth  Affected individuals need to be screened for
 But is frequently not identified until late childhood or polyps and cancer of the colon, and possibly be
adulthood advised to undergo prophylactic colectomy
- Occurs in three distinct clinical patterns
 Typical unifocal CHRPE BENIGN ADENOMA OF THE NON-PIGMENTED CILIARY
 Typical multifocal clustered variety of CHRPE EPITHELIUM
 A typical multifocal bilateral non-clustered variety of - Fuchs Adenoma
CHRPE - Acquired benign neoplasm of the non-pigmented ciliary body
epithelium
TYPICAL UNIFOCAL CHRPE  Essentially a neuroepithelial adenoma
 Appears as a nummular flat black to dark gray - Usually detected in middle aged or older individuals
lesion  Women > men
 Most frequently in the peripheral fundus - Unilateral and unifocal in almost all affected persons
 Ranges in size from a tiny dot of black pigment to - May become large enough to be visible on peripheral fundus
a geographic lesion 5 mm or more in diameter, examination or during cataract surgery
with well-defined smooth margins and no  But in many cases is noted only at autopsy
detachment of the overlying retina - Once detected, the tumor tends to enlarge very slowly in
 May undergo focal or diffuse depigmentation most cases
 Rarely has been noted to give rise to an adenoma - If such a lesion is suspected and shows progression during
or adenocarcinoma of the retinal pigment follow up
epithelium  Transscleral surgical excision can be performed
 Periodic monitoring for nodular change is - As tumors of this type clinically cannot be distinguished
advisable reliably from ciliary body melanomas
 Enucleation is still performed occasionally
Typical unifocal
peripheral CHRPE. RETINAL TUMORS OF INTERMEDIATE CHARACTER
In spite of the RETINOMA
appearance of the - Benign, spontaneously arrested form of retinoblastoma
lesion suggesting - “Retinocytoma” - benign appearing neuroepithelial cells
considerable - May not be detected until older childhood or even adulthood
thickness, B scan - Unilateral and unifocal
ultrasonography - Opalescent or off white
showed no measurable retinal tumor of limited size,
thickness. <7 mm in diameter and <2
mm in thickness
- No retinal detachment
overlying vitreous is normal
TYPICAL MULTIFOCAL CLUSTERED VARIETY OF - Tendency to transform into
CHRPE active retinoblastoma later in
 Grouped pigmentation of the retina, retinal bear life
tracks”
 Characterized by multiple small to intermediate Macular Retinoma
size, oval to cigar shaped, CHRPE lesions
clustered in one region of the fundus of one eye MEDULLOEPITHELIOMA
 Do not affect vision - Benign to malignant intraocular neoplasm
 Do not appear to have any potential to give rise to - Arises from the primitive neuroepithelium of the
RPE neoplasms - ciliary body during embryologic development
- Unilateral, unifocal tumor
- Occur in children less than 10 years old
- Cords of primitive neuroepithelial cells and multiple epithelial
Typical unilateral lined cysts, the fluid within them having
clustered CHRPE, - The same staining characteristics as vitreous
commonly referred to - Have heterotopic elements such as cartilage, glandular
as “bear tracks” tissue, and hair follicles, and are then regarded as “teratoid”
- White to pink ciliary body tumor that not infrequently invades
the peripheral iris
- Can be identified by ultrasound biomicroscopy
- Present at birth, frequently not detected until the child is
between 2 and 6 years old

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 OP-09 RETINA & INTRAOCULAR TUMORS
- Grow slowly and progressively
- Metastasis from intraocular medullepithelioma is extremely
rare
- Treatment
 Transscleral tumor resection
 Plaque radiation therapy
 Enucleation.
Congenital medulloepithelioma
MALIGNANT RETINAL TUMORS
RETINOBLASTOMA
- Primary malignant intraocular tumor that arises from
immature neuroepithelial cells of the developing retina
(etinoblasts)
- Epidemiology: The cumulative lifetime incidence of
retinoblastoma has been estimated to be about 1 in 15, 000
to 1 in 18, 000 individuals in most western countries
- Either unilateral (usually unifocal) or bilateral (usually
multifocal)
- Develop within the first few years of life, Some are present
at birth
- Pathogenesis: mutation or deletion involving one allele of the
retinoblastoma gene (a tumor suppressor gene localized to
the q 14 locus of the long arm of chromosome 13)
transmitted to any offspring as an autosomal dominant
condition with approximately 90% penetrance
- Intralesional necrosis and foci of calcification are usually
evident
- Risk factors for occurrence positive parental history of
bilateral, multifocal, and/or familial retinoblastoma and the
presence of chromosome 13 q deletion syndrome
- Median age at initial diagnosis is about 12 months for
bilateral and about 24 months for unilateral retinoblastoma
- Tendency to invade the optic disc with extraocular extension
along the orbital optic nerve, the choroid with transcleral
extension via vascular and neural foramina into the orbit, and
the trabecular meshwork with extraocular extension into the
anterior orbit or conjunctival lymphatics.
- Untreated, children with metastatic retinoblastoma rarely
survive for more than one year.
Retinoblastoma
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Finely dispersed
and clumped
retinoblastoma
seeds in vitreous
Multinodular
macular
intraretinal
retinoblastoma
tumor
- Retinoblastoma in children with a positive family history of
the disease identified by screening examinations when the
extent of intraocular disease is limited (ie few tumors, small
tumors and no vitreous seeds)
- Retinoblastoma in children with unilateral and/or non-familial
- Retinoblastoma is usually not detected until the parents or
pediatrician note a white pupil “leukocoria”
Leukocoria in the right eye due to a retinoblastoma
- For a child with retinoblastoma confined within the eye, the
recommended initial treatment depends on
- Number, size, locations, and types (primary intraretinal
tumors, tumor seeds, implantation tumors) of intraocular
tumors, the visual status and potential of the affected eye(s),
whether the disease is unilateral or bilateral, the types and
severity of secondary abnormalities of the eye (eg, retinal
detachment, iris neovascularization), the general health of
the child, and available resources
- Children with familial and/or bilateral-multifocal
retinoblastoma develop an independent retinoblastoma-like
malignant neoplasm in the brain (most commonly in the
pineal gland, where it is regarded as a pineoblastoma or
ectopic intracranial retinoblastoma)
- MRI of orbits and brain is performed routinely prior to
treatment
- TREATMENT:
 Focal laser therapy for posterior postequatorial
tumors
 Focal cryotherapy for anterior tumors
 Plaque radiation therapy
 Intravenous chemotherapy using a carboplatin-
based drug regimen
 OP-09 RETINA & INTRAOCULAR TUMORS
 Fractionated external beam radiation therapy
(EBRT)
 Selective catheterization of the orifice of the
ophthalmic artery followed by slow pulsed infusion of a
chemotherapeutic drug, such as melphalan
 Enucleation of the affected eye with intensive
chemotherapy and orbital irradiation
Initial treatment for a potentially salvageable child
with extraorbital retinoblastoma or retinoblastoma
associated pineoblastoma at presentation:
 Intensive initial intravenous
chemotherapy, surgical debulking of the
residual intracranial and/or extracranial
tumor(s), focal adjuvant radiation therapy
to metastatic sites, and bone marrow
 Transplantation
NON-OPHTHALMIC PRIMARY CANCER METASTATIC TO
THE RETINA
- Give rise to metastases to the retina, optic disk and/or
vitreous
- Occur in middle aged or older individuals with a history or
other evidence of a non-ophthalmic primary cancer capable
of metastasizing
- Appear as patchy pale infiltrative lesions obscuring the
retinal blood vessels
- Except from primary skin melanoma dark brown to black
infiltrative lesion
- Treatment options for retinal and optic
 Disc metastases include EBRT and chemotherapy
appropriate to the cancer type
 Metastatic cancer cells in the vitreous can be removed
by posterior vitrectomy, but then the eye must
usually be treated by EBRT to prevent reaccumulation
posterior vitrectomy (or in rare cases from discrete
geographic subretinal pigment epithelial infiltrates by fine
needle aspiration biopsy or endo-incisional biopsy), or
pathologic confirmation of primary CNS lymphoma in the
context of characteristic intraocular features in one or both
eyes
- Specific treatment options for the residual primary intraocular
lymphoma include:
 Intravenous chemotherapy usually a methotrexate
based regimen
 EBRT to one or both eyes (and the brain if it is involved
clinically)
 Series of intravitreal injections of methotrexate
- Discrete lymphoid infiltrates in the eye typically regress
rapidly in response to these treatments, and long-term
remissions frequently but not always occur
- Unfortunately, median patient survival following diagnosis of
primary vitreoretinal lymphoma is generally about 3 years,
with death usually caused by relapse and progression of the
CNS lymphoma
Primary
vitreoretinal
lymphoma in
right eye

Retinal metastasis
from primary
breast cancer to
just below the right
macula

PRIMARY VITREORETINAL LYMPHOMA

- Distinct subtype of primary intraocular lymphoma
- Diffuse infiltration of the vitreous by malignant lymphoid cells
and geographic
- Accumulations of malignant lymphoid cells beneath the
retinal pigment epithelium
- Associated with independent (nonmetastatic) foci of
lymphoma within the brain and cerebrospinal fluid (primary
central nervous system lymphoma) in the absence of
systemic lymphoma
- B-cell lineage, and the CNS and intraocular tumors are
typically characterize histopathology as diffuse large cell
lymphoma
- Older middle aged to elderly individuals are usually affected
with involvement of both eyes, simultaneously or
sequentially, in 80% of cases
- Requires cytopathologic and immunocytochemical analysis
of the lymphoid cells in a vitreous sample obtained by

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