OPHTHALMOLOGY 0749-0739/92 $0.00 + .

20

OCULAR NEOPLASIA
Steven John Dugan, DVM, MS

General surveys of equine tumors have shown that the skin, eyes,
and genitalia are most frequently affected by neoplastic conditions. 1, 49
Sarcoid, squamous cell carcinoma (SCC), papilloma, melanoma, nerve
sheath tumors, and lipoma, in descending order of prevalence, are the
most common neoplasms of equidae. 29 , 48, 60 Sarcoids are most common
on the forehead, eyelids, and face;29, 60 sec most commonly involves
the ocular region. 29 , 48, 60 Retrospective studies of tumors affecting the
equine eye, adnexa, and orbit have revealed that sec is most common,
representing 48% to 75% of the tumors. Sarcoid ranks second among
tumors of the equine ocular region (8%-38%). Papilloma, melanoma,
and nerve sheath tumors, combined, represent 7% to 9% of equine
ocular neoplasms; although less frequent, these tumors are the only
other commonly reported neoplasms of the equine ocular regionS, 36
(Dugan SJ, Severin GA, Roberts SM, et aI, unpublished data, 1988).
Thus, literature regarding equine ocular oncology is limited in scope.
As a result, this article briefly reviews general diagnostic modalities
and treatment alternatives available for ocular/periocular neoplasia.
Clinical aspects (prevalence, risk factors, differential diagnosis, treat-
ment, prognosis, and prevention) of specific tumor types affecting the
eyelids, nictitating membrane, cornea, bulbar conjunctiva and/or sclera,
intraocular structures, and orbit also are reviewed.

EXAMINATION AND DIAGNOSTIC TECHNIQUES

History and Examination

The age, breed, gender, haircoat and skin color, geographic loca-
tion, husbandry practices, duration of the ocular problem, season in

From the Animal Eye Specialists, Phoenix, Arizona

VETERINARY CLINICS OF NORTH AMERICA: EQUINE PRACTICE

VOLUME 8 • NUMBER 3 • DECEMBER 1992 609

610 DUGAN

which the problem began, and previous medical or surgical treatment

may assist the practitioner in making a sound judgment regarding the
differential diagnosis of an ocular, adnexal, or orbital mass. Because
the common ocular tumors of horses (SCC, sarcoid, melanoma, and
papilloma) frequently affect other anatomic regions, a thorough physical
examination should always be performed. The salivary glands and
regional lymph nodes should be palpated critically because these
structures are common sites for metastasis. When concentrating on the
ocular system, avoid the obvious and examine the unaffected eye first
to establish a baseline for normalcy. Then, a thorough ophthalmic
examination should be performed on the abnormal eye. Horses with
ocular or adnexal pain generally exhibit some degree of blepharospasm,
epiphora, and photophobia. An accurate diagnosis partly depends on
the quality of the examination; a thorough examination often requires
sedation. Fractious and painful horses are most easily examined after
some form of chemical restraint has been administered. Xylazine alone
or in combination with butorphanol tartrate produces excellent anal-
gesia and prolonged sedation. 34 Detomidine hydrochloride, a potent
0.- 2 agonist, also provides effective chemical restraint.
Blepharospasm accompanying ocular pain often hampers or pre-
vents a thorough ophthalmic examination. Eyelid akinesia is achieved
with an aUriculopalpebral nerve block (motor innervation of the orbic-
ularis oculi muscle) by injection of an anesthetic agent such as 2%
lidocaine into the depression just caudal to the temporal portion of the
zygomatic arch. This facilitates manual retraction of the eyelids. This
regional nerve block does not affect eyelid sensation. 55 The conjunctiva
and cornea are effectively anesthetized following instillation of 0.5%
proparacaine hydrochloride. Using minimal restraint, most horses per-
mit manual palpation of the eyelids, conjunctival fornices, and nictitat-
ing membrane; scrapings for exfoliative cytology; and conjunctival
biopsies. Complete anesthesia of the eyelid region requires regional
blocks of the frontal, lacrimal, zygomatic, and infratrochlear nerves.
These sensory nerves can be blocked by injecting 2% lidocaine in the
respective anatomic location of each nerve,40 or an upper and/or lower
eyelid line block can be performed as described by Lavach. 34 Additional
examination techniques and considerations are discussed in the article
by Cooley.

Diagnostic Work-up

Accurate diagnosis is based on a thorough history, clinical findings,

and cytologic and histologic analysis. A complete hemogram and serum
chemistry profile may be indicated when an ocular manifestation of
metastatic disease is suspected or before general anesthesia of unhealthy
or aged horses.
 OCULAR NEOPLASIA 611

Imaging Techniques
B-scan, two-dimensional ultrasonography is a useful, noninvasive
diagnostic technique that can be used to delineate the extent of intra-
ocular as well as retrobulbar masses. If extensive corneal or lenticular
disease precludes examination of the intraocular structures, the globe
can be examined effectively by ultrasonography. Ultrasonography is
the best method (with the exception of computed tomography and
magnetic resonance imaging) for defining the characteristics (e.g., solid
mass versus cellulitis) of retrobulbar disease. 13
Thoracic radiography should be performed if metastatic disease is
suspected. Conventional skull radiography for diagnostic evaluation of
the equine orbit requires general anesthesia and multiple radiographic
projections or views. Insertion of Flieringa's rings within the conjunc-
tival sacs assists interpretation. The complicated facial anatomy may
conceal identifiable radiologic signs of orbital disease despite adequate
radiographic technique. A special procedure that uses a radiopaque
dye to outline the nasolacrimal system, dacryocystorhinography, can
be used to identify the anatomic location of an obstruction.

Cytology and Biopsy Techniques

Techniques for obtaining tissue samples from the ocular, adnexal,
and orbital regions include exfoliative cytology, fine-needle aspiration
and cytology, incisional or wedge biopsy, and excisional biopsy. A
properly procured, fixed, and interpreted tissue biopsy is the corner-
stone for diagnosis, prognosis, and treatment of most neoplasms.
Knowledge of tumor type allows formulation of a logical plan of attack
on the mass. 70 Excisional biopsy may allow incorporation of treatment
and diagnosis in one step. Lesions involving the eyelids, conjunctiva,
nictitating membrane, cornea, or sclera are well-suited for evaluation
via exfoliative cytology and incisional and excisional biopsy procedures.
Partial to complete superficial keratectomies frequently serve as exci-
sional biopsies. Aspiration and incisional biopsy procedures using
sleeved biopsy needles allow sampling of space-occupying orbital dis-
ease conditions. Intraocular paracentesis (aqueous or vitreous) and
iridial excisional biopsy procedures have been described, but should be
reserved for selected cases because these techniques are difficult to
perform and may cause serious complications. 20

TREATMENT
Methods of tumor treatment are determined by the nature of the
primary disease, its biologic behavior, the size and anatomic location
of the lesion, and the presence or absence of distant metastases. In
addition, the skills of the clinician, equipment available, and financial
restrictions imposed by clients may favorably or unfavorably influence
612 DUGAN

the choice of treatment methods. 39 Routine tetanus prophylaxis should

be administered before any invasive procedure.

Complete Excision

The success of surgery as the sole modality of treatment depends

on tumor type, location, and size. Surgical procedures may include
wedge resection of the eyelid, partial or complete removal of the
nictitating membrane, superficial keratectomy, sector iridectomy, enu-
cleation, and exenteration. Careful histologic evaluation of excised
tissue margins is imperative and worth the additional expense. Without
such rigorous evaluation, an accurate prognosis and the need for
adjunctive treatment are difficult to determine.

Cytoreductive Surgery and Adjunctive Therapy

Some neoplastic lesions preclude complete surgical removal. Ade-

quate samples for diagnosis can be obtained by biopsy, but clinicians
must realize that only cytoreduction has been performed and additional
treatment is needed for tumor destruction.

Cryotherapy
Maximum cellular destruction results from a rapid freeze and slow
thaw cycle. Tumors are destroyed as intercellular ice crystals form,
causing dehydration of cells and their constituent organelles. Overall,
the best cryogen is liquid nitrogen. Liquid nitrogen may be applied as
a spray or with a probe tip. Ideally, two or three freeze-thaw cycles
are performed and a thermocouple is used to monitor tissue tempera-
0 0
ture. The tumor's temperature should be decreased to -20 to -30
C. Deep tumor margins should be monitored with thermocouples
because the depth of a freeze is difficult to judge based on the surface
ice ball size. Temporary vascular occlusion by means of clamps (e.g.,
Chalazion clamp) or direct pressure on tumor tissue facilitates freezing.
A freeze margin of normal tissue 5 to 10 mm around the malignancy is
desirable. Following cryosurgery, the acute tissue reaction is profound
and includes swelling, transudation, exudation, and necrosis. Transient
skin depigmentation (vitiligo) and permanent whitening of the hair
(poliosis) occurs. When eyelids are frozen, some contracture occurs;
excessive or repeated treatment therefore may cause blepharophimo-
sis. 35 The advantages of cryotherapy are: It is a simple, rapid, and
inexpensive procedure; it is excellent for suspicious, premalignant
lesions; and it may be repeated.

Hyperthermia
Malignant cells are more sensitive to noncoagulating temperatures
than normal tissue. A tumor's response to heat is governed by its mass
 OCULAR NEOPLASIA 613

and type as well as the temperature and duration of heating. Hand-

held radiofrequency devices can be used to deliver local hyperthermia
to tumor tissue. It has been shown that localized hyperthermia (50 C 0

for 30 seconds) is sufficient to destroy ocular SCC cells in cattle and

horses. 24 This treatment modality is also applicable to equine sarcoids.
The major disadvantage of localized hyperthermia is its limited ability
to treat deeper tissues. 35 Small lesions are easily treated following
regional anesthesia and sedation. If necessary, treatment can be re-
peated.

Strontium 90 ~ Irradiation
Strontium 90 (90Sr) ~ irradiation is primarily used as adjunctive
treatment for corneal and limbal SCC. The irradiation dose fall-off is
rapid, so tissue penetration is not greater than 1 to 2 mm. The usual
dosage is 45 to 100 Gray (4500 to 10,000 rads).35 A sealed probe
containing 90Sr is used by holding the device in direct contact with the
target tissue until the calculated radiation dose is delivered. Retreatment
is possible, but the total accumulated dose should not exceed 200 to
250 Gray. Doses approaching 200 Gray or more cause permanent
radiation damage to normal tissue.

Chemotherapy
An intralesional matrix chemotherapeutic modality for treatment
of SCC in horses has been described. 38 The drug delivery system for
sustained release of 5-fluorouracil and cisplatin is still in the develop-
mental stages. The goal is to obtain high intratumoral drug concentra-
tions for extended periods by the passive association of chemothera-
peutic agents with a high molecular weight matrix. 38 This delivery
system and the antineoplastic drugs incorporated in it are not approved
for use in horses. Proper client informed consent should be obtained
and treated horses prevented from entering the food chain. Parenteral
administration of antineoplastic drugs may be feasible in certain situa-
tions, but the precautions just stated are also applicable.

Immunotherapy

Equine periocular sarcoid can be successfully treated by active,

nonspecific immunotherapy with bacillus of Calmette-Guerin (BCG).35, 47
Commercial mycoplasmal cell wall preparations are available for veter-
inary use (Nomagen, Fort Dodge Laboratories, Fort Dodge, IA; Regres-
sin-V, Vetrepharm Research, Athens, GA). The exact mechanism of
action of BCG in initiating sarcoid regression is not known. Intralesional
inoculation of purified BCG cell walls in oil suspension is believed to
stimulate cellular and humoral immune responses to BCG antigenic
determinants and unrelated tissue antigens. A sarcoid should be satu-
614 DUGAN

rated with approximately 1 mL vaccine/cm2 of tumor surface. Injections

may be combined with debulking procedures if a large mass of necrotic
tumor tissue is present. Treatment must be repeated if the tumor
persists following resolution of the postinoculation inflammatory reac-
tion. Generally, one to six treatments are needed to effect complete
regression, so the greatest disadvantage of BCG immunotherapy is the
potentially long course of therapy. Nonetheless, BCG immunotherapy
has been reported to yield complete regression in 26 of 26 horses with
periocular sarcoids with no recurrences developing during 24 months
of follow-up. In addition, BCG immunotherapy offers the advantage
that the eyelid remains free from significant scarring or altered func-
tion. 37
Complete excision is the treatment of choice for intraocular mela-
noma in horses, but risks inherent in the surgical procedure, tumor
size, and expense often eliminate the possibility of surgical manage-
ment. These cases are usually monitored; treated symptomatically; and,
when painful, secondary complications develop, the affected globe is
removed. Complete and partial regressions of equine cutaneous mela-
nomas have been reported following cimetidine treatment. 23 Although
the specific mechanisms of action for cimetidine are unknown, it may
be a beneficial immunomodulator. 23 The efficacy of cimetidine for the
treatment of equine intraocular melanoma has not been evaluated.

Interstitial Radiotherapy

Radiotherapy is indicated for tumors that cannot be excised com-

pletely, for those that have invaded adjacent tissues, or in situations in
which surgery would leave a serious cosmetic or functional defect. 39
Several forms of interstitial radiotherapy have reportedly been used
with good results to treat eyelid SCC and equine sarcoid, and include
60cobalt, 137cesium, 222 ra don, 125iodine, 1989old, and 192iridium.19, 69, 71 This
treatment modality is rarely used, however, because it is expensive,
potentially dangerous, and requires the expertise of an oncologist or
radiation biologist.

Carbon Dioxide Laser Ablation

Use of a carbon dioxide laser for the treatment of limbal SCC in

horses has recently been described. 16 Carbon dioxide laser systems have
many advantages over routine scalpel excision of neoplastic tissue,
including (1) precise cutting, (2) hemostasis and therefore a clearer
surgical field, (3) sealing of nerve endings and lymphatics, (4) steriliza-
tion of tissue, (5) shorter surgery time, and (6) decreased postoperative
inflammation and patient discomfort. The disadvantages of carbon
dioxide laser versus scalpel incisions are (1) cost of equipment, (2)
potential risk to personnel, and (3) longer wound healing times. 16
 OCULAR NEOPLASIA 615

TUMORS OF THE EYELID

Review of histopathologic reports from the Colorado State Univer-

sity Veterinary Teaching Hospital (January 1981 through July 1988)
revealed 46 eyelid tumors in horses (Dugan SJ, Severin GA, Roberts
SM, et al; unpublished data, 1988). Squamous cell carcinoma was most
common (27 of 46), followed by sarcoid (10 of 46), melanoma (3 of 46),
neurofibroma (2 of 46), and one fibroma, hamartoma (developmental
malformation of vascular tissue), mast cell tumor, and myxosarcoma.
The article by Moore contains additional information on eyelid neo-
plasms.

Squamous Cell Carcinoma

Squamous cell carcinoma (Fig. 1) is the most common tumor of the

eye and its adnexa in horses. 36, 59, 60 The etiopathogenesis of see
involving the equine ocular and periocular region is not known but
solar radiation and nonpigmented ocular adnexa likely influence its
development. The prevalence of ocular and periocular see increases
with age. Several horse breeds (Belgians, Clydesdales, Shires, Appa-
loosas, American Paints, and Pintos) are more likely to develop see.
Stallions are five times and mares two times less likely to have ocular
and periocular sce than geldings. l l
The largest retrospective study to date regarding equine ocular and
periocular SCC reported clinical findings from 147 cases. 12 Most (84%)
of the horses had unilateral involvement. The nictitating membrane,
nasal canthus, or both (28%); limbus (28%); and eyelids (23%) were
most commonly affected. In addition to the ocular and periocular
locations, see was found at other body sites in 14 (9.5%) horses on
initial examination. Thus, a complete physical examination should
always be performed in horses with ocular lesions resembling see. 12
The gross appearance of see depends on its anatomic location
and stage of development. A low-grade inflammatory reaction accom-

Figure 1. Sparse pigmentation is

commonly associated with squa-
mous cell carcinoma. The local-
ized tumor of the right eyelid (na-
sal aspect) should respond well to
treatment. There was also in-
volvement at the inferior nasal and
temporal corneal limbus. (Cour-
tesy of S. M. Roberts.)
616 DUGAN

panies early tumor growth when lesions are circumscribed, hyperplastic

plaques or papilloma-like structures. If left untreated, they become
irregular, invasive, and necrotic in appearance. Histologic confirmation
of presumptive eyelid see should always be obtained because the
clinical appearance may resemble sarcoid, cutaneous habronemiasis,
foreign body granuloma, papilloma, or other uncommon neoplastic
processes.
Equine ocular sec is usually locally aggressive but may metastasize
to regional lymph nodes, salivary glands, and rarely, the thorax.
Survival analysis of 125 horses with ocular and periocular sce revealed
a good overall prognosis. 12 Tumor location influenced survival, with
SCC involving the eyelid or orbit associated with the poorest prognosis.
Tumor size (maximum dimension) was inversely related with survival.
In addition, one or more recurrences of sec markedly reduced the
likelihood of survival. 12 The risk of sec development may be reduced
by decreasing exposure to UV radiation. Similarly, tatooing nonpig-
mented eyelids and margins of the nictitating membranes may protect
susceptible tissue. 35
Once eyelid SCC has been definitively diagnosed, treatment op-
tions include simple excision, surgical reduction and adjunctive therapy
(cryotherapy and localized hyperthermia), and interstitial radiotherapy.
Complete surgical removal usually is not possible if the tumor is at all
advanced because extensive blepharoplastic procedures are made dif-
ficult by the dearth of movable facial skin in horses. 51

Sarcoid

Sarcoid is the most common equine tumor, but if only ocular and
periocular tumors are considered, see is the most common. In contrast
to equine ocular and periocular SCC, sarcoid usually affects younger
horses (7 years of age or less) and does not have a predilection for any
breed, gender, or hair coat color. 18, 27 The cause of equine sarcoid
remains uncertain, but two viruses, bovine papilloma virus66 and a
C-type retrovirus,7 have been implicated.
Sarcoids are biologically benign, fibroblastic tumors of the skin
affecting horses, donkeys, and mules. Single or multiple lesions may
develop and grow in a locally aggressive fashion. 39 Sarcoids in the
periocular region are reportedly less aggressive than those appearing
in other locations. 47 Nonetheless, sarcoid affecting an eyelid may stub-
bornly resist treatment and cause marked clinical disease.
Sarcoids have considerable variation in their clinical appearance.
Three morphologic types have been described: (1) Verrucous or wart-
like sarcoid is characterized by a dry, cauliflower-like, hairless lesion,
usually less than 6 em in diameter. (2) Fibroblastic sarcoid often
resembles granulation tissue and may be greater than 20 em in diameter.
And (3) mixed sarcoid is a combination of the first two types. 50
Differential diagnoses should include SCC, fibroma, fibrosarcoma, pap-
 OCULAR NEOPLASIA 617

illoma, nerve sheath tumors, granulation tissue, cutaneous habrone-

miasis, and phycomycosis. 59, 64 A definitive diagnosis of equine sarcoid
can be made only by histologic examination.
Sarcoids are notoriously difficult to treat. Recurrence and appear-
ance of tumors at new sites in the same animal complicate successful
treatment. 39 It is often impossible to completely remove all sarcoid
tissue by conventional surgical excision and wound closure, especially
when the tumor is periocular. Thus, resection alone will likely result in
high rates of recurrence. 39 For small eyelid lesions, localized hyperther-
mia may provide effective control. 27, 39 Radiotherapy is efficacious but
not necessarily practical. 39, 71 Currently, the most successful treatment
modalities for sarcoid are immunotherapy with a killed, purified com-
mercial BCG product (Fig. 2) and cryotherapy. 18, 32, 35, 47,51

Papilloma

Papillomas or warts are common cutaneous tumors of young horses

(12 to 24 months of age) caused by either an equine papilloma virus or
noninfectious irritants. 8, 65 Only the infectious variety is referred to as
papillomatosis. Papillomas frequently affect the muzzle, eyelids, and
ears. Grossly, lesions are elevated, horny masses with fronds, and they
characteristically exist in clusters measuring 2 to 10 em in diameter. 39
Once a premise is infected by a papilloma virus, the disease may recur
yearly, involving subsequent offspring. 65 Administration of a commer-
cially prepared vaccine to foals 2 to 3 months of age reportedly prevents
wart development. 39
Equine papillomas are benign tumors, usually spontaneously re-
gressing in 1 to 6 months, eliminating the necessity for intervention. 39, 51
Nonetheless, "autovaccination"-removal of a few papillomas as a
means of inducing rapid remission of other warts-has been advo-
cated. 39 A recent study 6l reported partial removal of papillomas as
ineffective in expediting lesion regression, however. Cryotherapy and

Figure 2. A, This large sarcoid had been injected twice with BCG. Minimal change in the
tumor volume was noted. B, After the third injection, a 75% reduction in volume occurred.
Following the fourth BCG injection, tumor resolution was complete. (Courtesy of S. M.
Roberts.)
618 DUGAN

intradermally administered autogenous vaccines have also been used

to treat papillomas.

Nerve Sheath Tumors (Neurofibroma and

Schwannoma)

Nerve sheath tumors are of neurectodermal origin arising from

nerve sheath or Schwann cells and perineural fibroblasts. 39 The cause
of nerve sheath tumors is unknown. Neurofibroma of the upper and
lower eyelid appears to be a specific entity in the horse. Seventeen
neurofibromas all occurred subcutaneously in the upper or lower eyelids
as single or multiple, small 2- to 3-mm shot-like lesions that increased
in size up to 10 mm. 48 Because of local extension, recurrence is common
following attempted surgical excision. 39 Cryotherapy, BCG immuno-
therapy, and interstitial radiotherapy are alternative, possibly more
effective, treatment modalities for large nerve sheath tumors. 35

Melanoma

Melanoma is an infrequent tumor when all horses are considered.

Horses with gray or white hair coats show a marked increase in the
prevalence of melanoma. Increased likelihood of melanoma develop-
ment in gray horses may be related to pigment changes associated with
aging: A disturbance in melanin metabolism may be associated with
graying and act to stimulate melanoblastic proliferation, resulting in
focal areas of overproduction in the dermis. Arabian, Lippizaner,
Percheron, and related breeds have an increased risk for cutaneous
melanoma. In general, equine melanomas of the skin are slow growing,
pigmented, localized neoplasms that do not metastasize. 39 Surgical
cytoreduction plus adjunctive cryotherapy is an effective method of
treating extraocular melanomas. 35

Other Eyelid Tumors

Adenocarcinoma,57 adenoma,5 basal cell tumor,5 fibroma,6o heman-

giosarcoma,35, 43 lymphosarcoma,45, 52 mast cell tumor, 5 and sebaceous
adenoma29 are rarely reported to involve the equine eyelid. Reliable
information therefore is scarce and information is needed regarding
natural behavior, preferred treatment modalities, and prognosis for
these rare neoplasms.
Two of three adenocarcinomas of the equine eyelid have been
reported to metastasize following incomplete excision, thus warranting
a guarded prognosis. 57 Equine basal cell tumors are usually benign,
solitary, and grow slowly. Surgical excision is the treatment of choice
and cryotherapy is an alternative approach; prognosis is favorable and
 OCULAR NEOPLASIA 619

recurrences are not expected. 65 Lymphosarcoma is uncommon, no

treatment is currently practical or effective, and the disease is usually
fatal. 45, 51, 52 Equine mast cell tumors have been successfully removed by
excision, as well as cryotherapy, and they metastasize infrequently.35, 65

Cutaneous Habronemiasis

Habronemiasis, an important differential consideration for any

tumor-like growth of the eyelid, usually occurs in the spring and
summer, during periods of increased fly activity. Lesions appear rapidly
in the region of the medial canthus or on the nictitating membrane.
Eyelid lesions may be greater than 2 cm in diameter and hemorrhagic,
and display yellowish canals of necrotic debris. Histologic examination
may reveal foci of necrosis containing sections of Habronema larvae
surrounded by an intense eosinophilic inflammatory reaction. 48, 51

TUMORS OF THE NICTITATING MEMBRANE

Squamous cell carcinoma is overwhelmingly the most common

tumor of the equine nictitating membrane (Fig. 3); of 35 histologically
confirmed neoplasms of the nictitating membrane, 31 (89%) were SCC.
The remaining neoplasms were basal cell tumor, hemangiosarcoma,
papilloma, and neurofibroma (Dugan SJ, Severin GA, Roberts SM, et
al; unpublished data, 1988). Lipoma,60 lymphangiosarcoma,25 primary
lymphosarcoma22 and sebaceous adenocarcinoma 31 of the nictitating
membrane have also been reported. The entire nictitans was excised,
leading to curative treatment of primary lymphosarcoma. 22 Two horses
with lymphangiosarcoma and a horse with sebaceous adenocarcinoma
underwent euthanasia at the owners' requests and metastasis was
documented in all three. 25, 31
The nictitating membrane and nasal canthus were the most com-
mon locations for equine ocular and periocular see in 147 cases.

Figure 3. Third eyelid squamous

cell carcinoma lesions may not be
noticed until the majority of the
margin is involved. Fortunately,
complete excision is usually pos-
sible. Horses do well following
amputation of the nictitating mem-
brane. (Courtesy of S. M. Rob-
erts.)
620 DUGAN

Recurrence was least likely and, consequently, survival time greatest

following treatment of see in these locations. 12 Treatment modalities
available for see of this region include partial or complete resection of
the nictitating membrane and cytoreductive surgery followed by ad-
junctive cryotherapy or 90Sr ~ irradiation. Wide surgical margins may
be obtained by complete resection of the nictitans in appropriate cases.

TUMORS OF THE CORNEA, BULBAR CONJUNCTIVA,

OR SCLERA

Squamous cell carcinoma is also the most common tumor of the

equine cornea (Fig. 4), bulbar conjunctiva, or sclera. Of 34 histologically
confirmed tumors of the cornea, bulbar conjunctiva, or sclera, 32 were
sec. An angiosarcoma and a hemangiosarcoma were also diagnosed
(Dugan SJ, Severin GA, Roberts SM, et al; unpublished data, 1988).
Superficial keratectomy and conjunctivectomy combined with adjunc-
tive 90Sr ~ irradiation or localized hyperthermia have been shown to be
effective for the treatment of limbal sce in the horse. 12, 69 Adjunctive
therapy with 90Sr ~ irradiation is less invasive than hyperthermia, but
in contrast to ~ irradiation, localized hyperthermia is readily available
and inexpensive. Despite the potential for persistent corneal scarring
and conjunctival depigmentation at limbal treatment sites, localized
hyperthermia can be considered a rational therapeutic modality with
minimal lasting untoward effects on normal equine ocular tissues. 46 As
described earlier, carbon dioxide laser ablation has also been used
successfully to remove limbal sec in the horse. 16 Onchocerca-induced
keratoconjunctivitis is a common, non-neoplastic equine parasitic con-
dition that should be considered as a differential diagnosis.
Equine corneal or conjunctival neoplasms that have been rarely
reported include hemangioma,6, 9, 67 hemangiosarcoma,6, 25 lymphosar-
coma,52 mastocytoma,2S,41 melanocytoma,26 and papilloma. 5 Heman-
gioma has been successfully removed by surgery alone and in conjunc-
tion with 90Sr ~ irradiation or cryotherapy from the lateral limbus of

Figure 4. Corneal squamous cell

carcinoma lesions start at the
limbus and expand to involve
the adjacent cornea. Treatment
should be instituted while lesions
are small. This case required a
superficial keratectomy followed
by adjunctive 90Sr J3 irradiation.
(Courtesy of S. M. Roberts.)
 OCULAR NEOPLASIA 621

two horses and the cornea of another with no evidence of recurrence. 6 ,

9, 67 A hemangiosarcoma of the bulbar conjunctiva was completely
removed by surgical excision, whereas a hemangiosarcoma originating
on the cornea of another horse was resistant to surgery and radiother-
apy and eventually metastasized. 6 , 25 Two cases with mastocytomas of
the corneal-scleral junction have been described; one horse developed
a recurrence following surgical excision whereas the other responded
to surgery and adjunctive 90Sr f3 irradiation. 28, 41 A benign epibulbar
melanocytoma has been described and was successfully removed by
surgery alone. 26 Cryotherapy reportedly is another effective treatment
modality for extraocular melanomas. 35 Dermoids, which are rare in
horses and tend to have short, stiff hairs that are very irritating, should
also be considered when a pigmented lesion is identified on the globe
of a horse. 51

INTRAOCULAR TUMORS

Melanoma

Intraocular tumors are rare in horses. Melanoma, the most fre-

quently reported primary intraocular tumor, is usually locally expansive
and destructive, suggesting malignancy, but an absence of metastasis
and histologic appearance imply a benign biologic behavior. 35, 42 As
discussed earlier, gray horses have a higher incidence of cutaneous
melanoma, but only recently has an association been made between
gray hair-coat color and intraocular melanoma. The occurrence of
intraocular melanoma in gray horses appears, however, to be less age-
related than that of cutaneous melanoma. 3 ,42
Equine anterior uveal melanoma may present as a slowly or rapidly
expanding, darkly pigmented, dense mass with secondary pupil dis-
tortion or, possibly, obliteration of the anterior chamber. Marked uveal
involvement may also cause uveitis and cataract. If the mass extends
to the iris base, gonioscopy should be performed to assess potential
involvement of the iridocorneal drainage angle. In addition, mydriasis
should be induced pharmacologically and the posterior chamber, ciliary
body, lens, and fundus thoroughly examined.
Management of an intraocular mass depends on the clinical find-
ings and intended use of the horse. Small, uncomplicated tumors can
be monitored for progression. A well-circumscribed but enlarging iridial
melanoma that does not involve the iridocorneal angle may be removed
by sector iridectomy. When involvement of the ciliary body is docu-
mented, an iridocyclectomy might be attempted, but the likelihood of
serious postoperative complications and incomplete excision would be
great. Enucleation ensures complete excision. Exenteration should be
reserved for cases with extraocular extension. 33 As described earlier,
immunotherapy, using cimetidine, may be an alternative to surgical
therapy.
622 DUGAN

Differentiating between intraocular melanoma and anterior uveal

cysts may be difficult. Anterior uveal cysts involving the nonpigmented
epithelium of the ciliary body or posterior pigment epithelium of the
iris usually appear as bilateral, spherical to ellipsoid, dark brown-black,
smooth bodies in older ponies with blue irides. 14, 56 Anterior uveal cysts
vary considerably in their density of pigmentation. Heavily pigmented
cysts that prevented transillumination of a focused beam of light have
been described. 56 Occasionally, uveal cysts appear thin-walled and
translucent. Hypertrophic (solid) and cystic changes of granula iridica
(corpora nigra) have also been described and may be suspected in the
differential diagnosis of a pigmented mass in the anterior chamber.
Uveal cysts may become detached and float freely in the anterior
chamber or may rupture spontaneously.3 An ophthalmic nd:YAG laser
has been successful in disrupting the wall of large cysts within the
corpora nigra. 10

Medulloepithelioma

Medulloepitheliomas, exceedingly rare, congenital, neuroepithelial

intraocular tumors, usually arise from the ciliary body but have been
reported to originate from the retina and optic nerve. 15 Several case
reports have been published and describe these neoplasms as nonpig-
mented, vascular, and slow-growing. The affected globe should be
enucleated. If orbital extension has occurred, exenteration is indicated.
Because long-term follow-up of horses with medulloepitheliomas has
not been documented, the biologic behavior of these tumors is un-
known. 63

Other Intraocular Tumors

Unhindered growth of primary ocular or orbital neoplasms (e.g.,

SCC) and metastasis (e.g., lymphosarcoma) may result in intraocular
disease. An uncommon, apparently benign proliferation of the optic
disc and adjacent retina has been described in the horse and named
proliferative optic neuropathy. 58 Affected horses are characteristically aged
and asymptomatic. The growth routinely involves one optic disc,
protrudes into the vitreous, and is well-circumscribed, whitish-gray to
pink, and nonprogressive. Interestingly, all descriptions mention a
mass that occupied approximately 200/0 of the disc surface area. The
proliferative growth has also been called an astrocytoma, glioma, granular
cell tumor, and xanthoma. 2I , 54 Disregarding the controversial nomencla-
ture, the clinically important message is its benign behavior. Because
this condition does not rapidly progress or cause a clinically detectable
visual deficit, periodic re-examination to monitor potential change is
the most prudent clinical approach. 68
 OCULAR NEOPLASIA 623

ORBITAL TUMORS

Orbital neoplasia is uncommon in horses. 2, 10, 17 Retrobulbar tumors

are usually slowly progressive and nonpainful unless marked exoph-
thalmos results in secondary lagophthalmos and concomitant exposure
keratitis. In addition, orbital neoplasia may cause shallowing of the
supraorbital fossa, periorbital swelling, protrusion of the nictitating
membrane and accompanying conjunctival inflammation, strabismus,
and a resistance of the globe to retropulsion. If the optic nerve is
involved, vision may be decreased or absent. Invasive neoplasms can
also cause scleral deformation, retinal separation, inflammation, and
pressure atrophy of the optic nerve.
Diagnosis of orbital disease can be very challenging because the
clinical signs may be confusing and the diagnostic work-up difficult.
Exophthalmos is caused by a space-occupying lesion, usually a retro-
bulbar tumor or abscess. 2 Exophthalmos must be differentiated from
buphthalmos, in which the globe is enlarged as a consequence of
chronic glaucoma. An orbital abscess or cellulitis may be caused by a
migrating foreign body, guttural pouch mycosis, and extension of
suppurative disease from the frontal or maxillary sinus. Although
uncommon, a granulomatous mass caused by Actinomyces, phycomy-
cetes, and other organisms may develop in the orbit. 51 Herniation, or
prolapse, of the retrobulbar fat 44 and an orbital cyst2 should also be
included as differential considerations. Because these conditions must
be differentiated from neoplasia, biopsy and tissue cultures are indi-
cated in all cases. 51

Primary Orbital Tumors

Reported equine primary orbital tumors include undifferentiated

adenocarcinoma,36 carcinoma of neuroepithelial origin,17 lipoma,36 med-
ulloepithelioma, 5 melanoma,62 meningioma, 2 multilobular osteoma
(chondroma rodens),53 neuroepithelial tumor of the optic nerve,4 and
granulocytic sarcoma. 30 If the neoplastic mass is well-circumscribed and
relatively small, an exploratory orbitotomy may result in complete
excision of the localized mass;30, 53 the presence of extensive, infiltrative
disease, however, usually mandates orbital exenteration. Several pri-
mary orbital neoplasms have been reported to enter the calvarium and
cause neurologic manifestations that have resulted in the horse's hu-
mane destruction. 4 , 17

Secondary Orbital Tumors

Local extension from adjacent tissue is the most common secondary

form of orbital neoplasia. A hemangiosarcoma of the medial canthus
has been reported to undergo secondary invasion of the orbit and
624 DUGAN

maxillary sinus. 6 The orbit may eventually become involved by ocular

or adnexal see that is untreated or recurs despite therapy. Horses with
orbital see have a poor prognosis. 12 Neoplastic extension from the
periorbital sinus cavities can also occur. If maxillary or frontal sinus
inflammatory or neoplastic disease is suspected, percussion of the skull
should be performed carefully. Neoplastic conditions of the sinus such
as carcinomas seldom are amenable to treatment and have a poor
prognosis. 51
Although rare, metastasis to the orbit from a distant primary site
may occur. Multicentric lymphosarcoma has been reported to include
the orbit. 36, 52 As mentioned earlier, there currently is no treatment
available for disseminated equine lymphosarcoma. 51

SUMMARY
Except for two neoplasms, notably see and sarcoid, ocular and
periocular tumors are uncommon in horses. The practitioner must
accurately determine the type of tumor by histopathology so appropri-
ate treatment and a legitimate prognosis can be offered. The first
attempt at treatment has the greatest chance to result in a cure; an
aggressive treatment regimen therefore should be selected from the
start.

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Steven John Dugan, DVM, MS
Animal Eye Specialists
2322 West Northern Avenue
Phoenix, AZ 85201