Equine Ocular & Periocular Neoplasia: SCC & Beyond
ACVIM 2008
Caryn E. Plummer, DVM, DACVO
Gainesville, FL, USA

Any description of disease afflicting the periocular region must address the differences in etiology, clinical signs and prognosis of each individual tissue. The reactions of and treatments available can be vastly different between the various structures of the eye and the orbit. Therefore, this report will be organized by structure. Aside from two notable exceptions, ocular and periocular neoplasms, namely squamous cell carcinomas (SCC) and sarcoids, are fortunately uncommon in the horse. A thorough work-up, often with advanced imaging and always with histopathologic confirmation, is necessary to establish a diagnosis and an accurate prognosis. In most, if not all cases, the first attempt at treatment has the highest chance to affect a cure, so prompt, aggressive therapy should be elected from the start.

Orbit

Fortunately, orbital neoplasia in the horse is uncommon. However, when it occurs it carries a guarded to poor prognosis for the animal. Tumors of the orbit may arise from tissues within the orbit or secondarily from extension from adjacent tissues or structures, particularly the frontal or maxillary sinuses. Clinical signs of retrobulbar tumors may include unilateral progressive exophthalmos, distension of the supraorbital fossa, epiphora, resistance to globe retropulsion, vision loss, and efferent pupillary dysfunction. Severe exophthalmos may result in chemosis and exposure keratitis. Sinus and nasal tumors with orbital extension may also cause ipsilateral nasal discharge, hemorrhage, air flow restriction, respiratory stridor and a fetid odor. In most cases, particularly secondary tumors, the disease process is quite advanced before signs of disease are obvious in the orbit due to the large potential space for tissue expansion within the orbit. SCC may enter the orbit either from progression of an ocular or adnexal SCC or from expansion of a primary sinus SCC through the medial orbital wall. These tumors are locally very aggressive, although they rarely metastasize. Tumors that arise from the third eyelid are particularly prone to orbital extension as they grow deep to the base of the nictitans behind the globe. A variety of tumors have been identified in the equine orbit, including neuroendocrine tumors, and their treatment and prognosis depend upon their tissue of origin, extent and biological behavior. Imaging of the orbit and sinuses via computed tomography or magnetic resonance is often necessary to accurately assess the extent of disease and make an aggressive surgical plan, if possible. Discrete tumors may be excised during an exploratory orbitotomy, but this globe sparing procedure is the exception rather than the rule. More often, extensive or infiltrative disease requires orbital exenteration. Nasal or sinus tumors pose an ever greater challenge to treatment.

Eyelid

Squamous cell carcinoma is the most common sort of eyelid neoplasia. In fact, it is the most common sort of neoplasia affecting the eye and adnexa. Sarcoid, the overall most common neoplasm of the horse, comes in a close second in the periocular region. There is a tremendous geographic difference in the prevalence of these two tumors, with SCC affecting more animals in the southern United States and other areas that receive a comparatively high level of UV radiation. Signalment also dictates which subset of animals is more likely to be afflicted with one tumor or another. Draft breeds and lightly pigmented breeds such as Paints and Appaloosas have a higher prevalence of SCC than others and aged animals are the more likely to develop this tumor. Sarcoids, on the other hand, are seen most often on Thoroughbreds and have no predilection for specific coat colors. Animals affected by periocular sarcoids tend to be younger, many less than 7 years of age.

Treatment of eyelid SCC depends upon the size and location of the lesion and the success or failure of prior treatments. Small lesions are best treated and cured with excision that achieves clean surgical margins. This can be difficult, however, in the horse because there is not much facial skin available for reconstructive blepharoplasties. Large eyelid defects that impair the protective functions of the eyelids will lead to corneal ulceration and potential loss of the globe. Surgery alone is insufficient in many cases. The advent of a vast array of adjunctive therapies, including radiation therapy, cryotherapy, intralesional chemotherapy with cisplatin or carboplatin, immunotherapy, hyperthermia and laser ablation, underscores the fact that there is not a singular gold-standard therapy that will work for all or most cases. Of these modalities, radiation therapy is by far the most effective since SCC is radiosensitive, however, its availability is remarkably limited and it is particularly expensive. External beam radiation requires multiple sessions under general anesthesia and few facilities have linear accelerators that can accommodate large patients. Interstitial radiation, which involves surgical implantation of radioisotope impregnated beads, is very effective but quite hazardous to personnel and therefore tightly regulated. Its availability is also limited. Despite the modality chosen, an aggressive approach should be undertaken, since the neoplastic cells which remain after incomplete therapy are often resistant and particularly aggressive themselves.

Sarcoids are fibroblastic tumors of the skin that appear as single or multiple lesions and grow in a locally aggressive fashion. The causes of these tumors are multifactorial and not completely understood, however, individual genetic predisposition in combination with non-host viral infections are undoubtedly involved. Sarcoids have a variety of gross clinical appearances. They can be nodular, ulcerative, granulomatous, flat, verrucose or mixed. Biopsy is necessary to make a proper diagnosis, but because of their unpredictable behavior and the possibility of rapid progression of disease following any manipulation, plans should be in place so that treatment quickly follows any biopsy treatment. In order to make an accurate diagnosis, a biopsy sample should include both epidermal and dermal samples of any suspected sarcoid. These tumors are notoriously difficult to treat and many different treatment options have been attempted. Cryosurgery, intralesional chemotherapy, immunotherapy, radiation, laser ablation and surgical excision have been proposed. The highest success rates have been achieved with radiation therapy, the limitations of which have already been discussed, and immunotherapy with Bacille Calmette-Guerin (BCG), which consists of a series of intralesional injections. Sharp surgical excision alone and laser ablation alone are more likely to exacerbate the tumor than affect a cure and are ill-advised unless an adjunctive method of treatment is employed.

Melanomas, papillomas, lymphomas are among the extensive list of other potential neoplasms of the equine eyelid. Melanomas are much more prevalent in grey horses than in horses of any other coat color. There are 2 forms that occur. Older, grey animals tend to have multiple lesions throughout their bodies that grow and metastasize, albeit slowly. Surgical cytoreduction coupled with cryotherapy can be an effective treatment method for eyelid melanomas, but will not prevent the formation of new tumors. Another type of eyelid melanoma occurs in younger animals and is much more aggressive with a rapid clinical course. These tumors are usually singular, or if multiple, confined to a small anatomical area of skin. These tumors grow rapidly and can significantly compromise eyelid structure and function, and therefore corneal health. Cryotherapy is the preferred method of treatment for these in order to minimize cicatricial complications of sharp surgery.

Nictitans, Conjunctiva, Nasolacrimal Apparatus

The third eyelid (TE) is essentially a semilunar fold of conjunctiva with a core of cartilage and a gland at it base. The tumors that affect the TE, most often arise from the conjunctiva, therefore, the tumor types affecting the TE are the same as those that commonly arise from the conjunctiva. Tumors within the nasolacrimal duct either invade from surrounding structures or arise from the epithelium lining the duct.

Squamous cell carcinoma is the overwhelmingly most common tumor affecting the nictitans of the horse. Additionally, the nictitans is the most common location for the development of ocular and adnexal SCC. Early diagnosis is crucial to successful management of this process. Complete excision of the entire nictitating membrane even if not necessary due to limited extent of involvement is often prudent. Incomplete resection of third eyelid SCC can result in extension of the tumor into the orbit and a poor prognosis for the animal. It is imperative that the proximal margin of the excised nictitans be marked and examined histologically. Other tumor types have been reported on the third eyelid with prognosis highly dependent upon tumor type. Cases of tumors of vascular origin and adenocarcinomas of the third eyelid have reported metastatic spread.

Cornea and Sclera

The cornea and sclera make up the external, fibrous tunic of the eye. Again, SCC is the most commonly recognized tumor of these tissues. SCC arising from the limbus, at the junction of the cornea and sclera will extend and invade tissues in both directions. Fortunately, there are only rare cases of intraocular extension of these surface tumors. If left to proliferate unchecked, these masses can threaten the animal's sight and invade adnexal and orbital structures. Enucleation is a viable treatment option, however, most cases, if addressed early, may be treated via local resection with a keratectomy or sclerokeratectomy and adjunctive therapies such as cryotherapy, beta-irradiation, CO2 laser ablation or topical chemotherapeutic agents, thereby allowing retention of the visual globe. Excision followed by strontium 90 irradiation is very successful method of treatment with a lower rate of recurrence than excision alone or excision combined with another modality. The wound bed following excision is essentially a corneal ulcer that must be treated and protected during healing. Small sites may be treated with topical medications alone; conjunctival grafts or amnion transplants may be used to cover the wound bed and offer greater protection. Various other tumors, such as hemangiomas, lymphomas, melanocytomas and mastocytomas, have been sporadically reported on the cornea and sclera. Their clinical appearance is typically quite different from that of SCC, but histopathologic examination is necessary for confirmation. Their biologic behaviors vary as well, with tumors of vascular origin deserving special concern for their tendency for aggressive metastatic spread and lymphoma occurring most commonly as an ocular manifestation of a systemic or multicentric disease. Congenital corneal tumors, known as dermoids, are uncommon, non-progressive and benign. Complete excision is curative, but only necessary if the lesion is irritating for the animal, as the haired forms tend to be.

Uvea

The uveal tract is the tissue of origin of most primary intraocular neoplasms. It is the most densely vascular layer of the globe, and as such, is also the most likely ocular site for metastatic spread of a secondary tumor, such as lymphoma. The most common neoplasm arising within the uveal tract of the eye of the horses, as in other species, is melanoma or melanocytoma. These tumors may present as darkly pigmented dense mass or as a lightly or non-pigmented mass of either the iris or ciliary body. Often there is accompanying uveitis, cataract development or compromise of the iridocorneal drainage angle which results in diminished aqueous humor outflow and secondary glaucoma. Uveal melanomas are most commonly observed in grey animals, however, may occur in animals of any coat color. They have varied biologic behavior and are often quite destructive to the interior of the globe. Unfortunately, diagnostic sampling is difficult and often quite traumatic to the globe, therefore, decisions must often be made based upon appearance and extent of the mass. In these cases, treatment and sampling procedures for diagnosis often are one and the same. Enucleation is curative if metastasis has not already occurred, but if retention of the globe is desired and the tumor is well-circumscribed, local resection via sector iridectomy or iridocyclectomy may be attempted.

Differentiating between intraocular melanoma and anterior uveal cysts or hyperplasia may be difficult, but is crucial to the determination of an accurate prognosis. Uveal cysts may be variably pigmented and difficult to transilluminate, however, they tend to have a smooth surface and are obviously fluid-filled upon ultrasonographic examination. The proliferations of the corpora nigra at the margins of the pupil may appear in some cases to grow and mimic intraocular neoplasia. These lesions may be either cystic or hyperplastic and are usually benign. Ophthalmic lasers are often successful in disrupting them and causing deflation or tissue regression.

Retina and Optic Nerve

Tumors of the neurosensory retina are rarely reported and most have been tumors of primitive neuroectoderm origin. Local injury to the eye occurs, but systemic spread has not been reported in the horse. These cases eventually progress and ultimately result in enucleation of the globe. Tumors of the optic nerve, however, are fairly common and in most cases consist of benign, non-progressive, white, sometimes cauliflower-shaped masses that protrude from the optic disc into the vitreal chamber. These are frequently diagnosed as benign proliferative optic neuropathy. It is impossible to differentiate between astrocytomas and schwannomas, which most cases of benign proliferative optic neuropathy are believed to be, without histopathologic examination. Diagnostic biopsies are problematic and risky for the health and sight of the globe and, since there is usually no clinical significance to the presence of these lesions, usually unnecessary. These lesions are almost always incidental findings on an ophthalmic examination, however, their presence warrants monitoring as the rare case will enlarge and may impair vision.

References

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Speaker Information
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Caryn Plummer, DVM, DACVO
University of Florida
Gainesville, FL


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