Diagnostic Ophthalmology

History and clinical signs

A 10-year-old spayed female domestic shorthaired cat was examined at the ophthalmology serviceat the Western College of Veterinary Medicine. This cat was presented for evaluation of pigmented lesions in the left iris. The menace responses, and palpebral, occulocephalic, direct and consensual pupillary light reflexes were present bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 16 and 21 mm/min in the right and left eyes, respectively. The intraocular pressures were estimated with a rebound tonometer (Tonvet; Tiolat, Helsinki, Finland) and were 13 and 25 mmHg in the right and left eyes, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) was negative bilaterally. On direct examination there was brown discoloration of the left iris extending approximately 300° and mainly involving the peripheral iris. Biomicroscopic examination (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) revealed the darkly pigmented areas to be flat and the pigmentation to extend into the iridocorneal angle involving the pectinate ligaments. Examination of the right eye was within normal limits. Following topical application of 0.5% tropicamide (Mydriacyl; Alcon Canada, Mississauga, Ontario) indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examination was completed and did not identify abnormalities in either eye. A photograph of the left eye at presentation is provided for your assessment (Figure 1).

Figure 1.

Photograph of the left eye of a 10-year-old domestic shorthaired cat.

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Discussion

The clinical diagnosis was diffuse iris melanoma in the left eye. The differential diagnosis for pigmented iris lesions is benign melanosis or iris freckles/nevi. Diffuse iris melanoma is a progressive pigmentation of the iris and is usually unilateral. Pigmentation often develops in multifocal areas on the surface of the iris with these areas gradually increasing in size and coalescing over time to become a diffuse lesion (1). The pigmented areas may be slightly raised and velvety in appearance. As diffuse iris melanoma progresses, the tumor invades deeper into the iris stroma and may lead to changes in pupil shape and mobility (1). Benign melanosis may be congenital or acquired, and unilateral or bilateral. These pigment spots are small clusters of normal melanocytes on the surface of the iris and tend to have sharp borders and remain superficial. Freckles are smaller spots, while nevi are somewhat larger in area. These lesions can be congenital or acquired and tend to increase in number with age (2).

Melanocytic tumors are the most common type of primary intraocular neoplasia in dogs and cats. Cats typically develop flat, diffuse tumors of the iris as described, while dogs typically develop raised, nodular lesions. In both species, infiltration of the iridocorneal angle in advanced disease leads to secondary glaucoma. While canine uveal menanocytic neoplasia is typically benign in regard to systemic spread, feline diffuse iris melanoma has the potential for metastasis and rates of 19% to 63% have been reported (3–6). The lymph nodes, lungs, liver, and spleen are the most common sites; however, radial bone metastasis has been reported in 1 cat (1,7).

Definitive diagnosis of diffuse iris melanoma requires light microscopic examination of the affected uveal tissue. Uveal biopsy is rarely completed due to the invasiveness of the procedure. Thus, the clinical diagnosis of diffuse iris melanoma is based on the appearance and photographic documentation of progressive, expanding, and coalescing areas of hyperpigmentation, with possible changes in pupil shape and mobility. When cats present with small pigmented lesions, it is recommended that serial photographs be taken over several months to years in order to document changes and progression of the lesions. Once a clinical diagnosis of diffuse iris melanoma is made, however, the question remains what is the most appropriate therapy.

Definitive treatment is currently limited to enucleation of the globe as adjunctive therapy protocols have not been developed. Use of diode laser by a veterinary ophthalmologist to photoablate small, focal, iris lesions may be an option in very early stages; however, the efficacy in preventing progression of the tumor is not known and as the tumor is multifocal in nature, new lesions can be expected to form (1). The clinical dilemma is, therefore, determining the appropriate time to perform enucleation. Ideally, the clinician should be convinced of the clinical diagnosis in order to avoid enucleation of an eye with benign melanosis. Referral examination by a veterinary ophthalmologist is recommended to help confirm the clinical diagnosis. Diffuse iris melanoma is slowly progressive and although it is not known exactly when metastasis occurs in the course of disease, it is presumed to be in the latter stages. Thus clinicians should avoid premature or unnecessary removal of a healthy and visual eye. Nevertheless, the goal is to remove the eye prior to development of metastasis. Staging with thoracic radiographs and abdominal ultrasound is not useful as these modalities are not sensitive enough to reveal the miliary nature of tumor metastasis in distant organs.

Several studies have attempted to correlate histopathologic features of enucleated globes at various stages of disease with metastasis (4–6,8). Unfortunately, metastasis of diffuse iris melanoma is rarely confirmed and may not be noted until postmortem examination if this is completed. There is a strong correlation between the extent of local tumor infiltration and survival time (4). When enucleation is performed while the tumor is still confined to the iris stroma affected cats survive as long as control cats (4). When enucleation is performed after invasion of the ciliary body stroma, there is a progressively poorer prognosis. Cats with glaucoma attributable to tumor infiltration have significantly reduced survival time compared to control cats (4). Histopathologic features associated with increased presumed metastasis include the presence of tumor in the scleral venus plexus, extrascleral extension, necrosis within the neoplasm, a mitotic index of > 7 mitoses in 10 high-power (×400) fields, choroidal invasion, and increased E-cadherin and melan-A immunoreactivity of the tumor cells (5,6,8).

Most of the current literature suggests that metastasis is more likely to occur with more extensive tumors. Once tumor cells are within the filtration angle and scleral venus plexus there is greater potential for spread to distant organs. Therefore, enucleation is justified based on an increased amount and size of pigmented areas, with spread of pigmentation into the iridocorneal angle. It is essential that an enucleated globe with suspected iridal melanoma be submitted for light microscopic evaluation to evaluate the extent of the neoplasia, which will in turn help determine the prognosis for the patient.

In this cat, pigmentation was confirmed on biomicroscopic examination to involve the pectinate ligaments and therefore enucleation was recommended and completed. Light microscopic examination of the globe confirmed the clinical diagnosis of diffuse iris melanoma. The cat continues to do well; however, it is recommended that she be monitored closely for development of systemic disease that may be associated with metastasis.