Diagnostic Ophthalmology

HISTORY AND CLINICAL SIGNS

A 21-month-old Brittany spaniel dog was examined by the ophthalmology service at the Western College of Veterinary Medicine. This dog was presented for evaluation of a pigmented spot on the iris of the right eye. The menace responses, and palpebral, oculocephalic, direct and consensual pupillary light reflexes were normal bilaterally (OU). Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 29 and 31 mm/min in the right (OD) and left eye (OS), respectively. The intraocular pressures were estimated with a rebound tonometer (Tonovet; Tiolat, Helsinki, Finland) and were 14 and 15 mmHg in OD and OS, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) of the cornea was negative OU. Retropulsion of both globes was unremarkable. On direct examination an oval, darkly pigmented lesion was present on the iris between the 2 o’clock and 5 o’clock pupillary zone and collarette. Examination with the handheld biomicroscope (Kowa SL-17 Portable Slit Lamp; Kowa Co, Tokyo, Japan) revealed the lesion to be mildly raised within the stroma of the iris. Following application of 0.5% tropicamide (Mydriacyl; Alcon Canada, Mississauga, Ontario), examination of both eyes using a transilluminator (Welch Allyn Finoff Transilluminator; Welch Allyn, Mississauga, Canada) and handheld biomicroscope revealed no further abnormalities. Indirect ophthalmoscopic (Heine Omega 500; Heine Instruments Canada, Kitchener, Ontario) examination was completed and did not reveal abnormalities in either eye. A photograph of the right eye at presentation is provided for your assessment (Figure 1).

FIGURE 1.

Anterior segment photograph of the right eye of a 21-month-old Brittany spaniel.

WHAT ARE YOUR CLINICAL DIAGNOSES, DIFFERENTIAL ETIOLOGIC DIAGNOSES, THERAPEUTIC PLAN, AND PROGNOSIS?

Discussion

The ophthalmic diagnosis was presumed melanocytic neoplasia of the iris OD. Differential diagnoses for a pigmented lesion of the iris include benign or malignant melanocytic neoplasia, non-neoplastic areas of hyperpigmentation such as a freckle or nevus, as well as inherited uveal melanocytosis (1–3).

Non-neoplastic hyperpigmented lesions are common in the canine iris. These present as well-circumscribed, focal, or sometimes multifocal areas of iris hyperpigmentation that may be flat or slightly raised from the iris surface. Iris freckles or benign melanosis represent clusters of benign hyperplasia or increased pigmentation of normal melanocytes in the superficial iris stroma. They do not tend to distort normal iris architecture, do not affect iris mobility, and are not usually raised from the iris surface (2,4). Similarly, an iris nevus is a benign proliferation of cells of neuroectodermal origin, which may cause focal thickening in the iris stroma (2). Nevi are less common than freckles and tend to occur more commonly in young dogs (2,3).

Uveal melanocytosis (also called uveal melanosis) is a slowly progressive, bilateral condition described in the Cairn terrier breed and occasionally in Labrador retrievers, boxers, Shih Tzus, and German shepherds (5,6). The condition is characterized by accumulation of non-neoplastic melanocytes and variable numbers of melanophages throughout the uvea (6). The iris appears diffusely hyperpigmented in the early stage of the condition; however, as melanosis progresses, the iris base becomes thickened, melanocytes infiltrate the anterior sclera, resulting in scleral pigmentation, and eventually glaucoma develops due to infiltration of the ciliary cleft and trabecular meshwork (7). Melanosis is an inherited condition in the Cairn terrier and an autosomal-dominant mode of inheritance is thought to be likely (5).

Melanocytic tumors are the most common intraocular neoplasia in dogs and the anterior uvea (iris and ciliary body) is the most common site for these to develop (1,2). The terminology of melanocytoma is generally applied to benign melanocytic neoplasms, whereas melanoma is used to indicate malignant melanocytic neoplasms (8). Melanocytic uveal neoplasia in dogs most commonly exhibits benign biological behavior, with low rates of metastasis; around 5% based on the literature (4,8–11). The best criterion for histologic identification of ocular melanoma with high metastatic potential in dogs is mitotic index; benign tumors have a mitotic index of ≤ 2 per 10 high power fields (HPF) (approximately 430×), whereas tumors with known malignant behavior have a mitotic index of 4, and often greater than 10 (8).

Benign uveal melanocytoma is the most common form of melanocytic uveal neoplasia in dogs. Uveal melanocytomas are more frequently diagnosed in older dogs (9,10). There may be some breed predilection as German shepherds, and retrievers are more often reported in the literature (10–12). These tumors tend to grow as non-painful nodular and expansive masses within the uvea. As the mass enlarges, the iris and pupil become distorted, and eventually, the tumor extends into the iridocorneal angle and causes intraocular inflammation both leading to painful and blinding secondary glaucoma. The nodular presentation and tendency toward benign behavior contrast with uveal melanocytic neoplasia in cats, which tends to develop as diffuse iris infiltration and has much higher malignant potential, thus the term feline diffuse iris melanoma (13).

Differentiating melanocytic neoplasia from nonneoplastic pigmented foci in the iris is usually based on history, signalment, and serial clinical examination findings. A raised pigmented lesion that is progressively increasing in size and thickness is more likely to be melanocytic neoplasia than a freckle or nevus (2). It is common practice among ophthalmologists to monitor with periodic examinations and clinical photography for several months to monitor for growth or progression of a pigmented lesion to support a presumptive diagnosis. However, definitive diagnosis requires histopathologic examination of the affected iris tissues. Iris tissues may be sampled by biopsy performed by an ophthalmologist or examined following surgical removal of the entire globe to confirm the diagnosis of uveal melanocytoma. Surgical removal of a sighted and non-painful globe is not recommended, however, due to the benign biological behavior of most of these tumors.

Treatment of canine uveal melanocytoma depends on many factors, including the size of the lesion at the time of diagnosis, clinician skill, and client preference. Because most are benign, a conservative approach may be taken to monitor with a plan to enucleate the globe when the tumor becomes extensive enough that it has developed secondary glaucoma.

Interventional therapies aimed at preventing tumor growth, and therefore loss of the globe, include diode laser photocoagulation and surgical excision by an ophthalmologist. These are more likely to be successful if the tumor is small and well-circumscribed at the time of diagnosis. Diode laser photocoagulation is a non-invasive treatment in which application of diode laser energy produces a thermal effect with preferential absorption in melanin-containing tissues resulting in coagulation necrosis (14). Treatment is completed under general anesthesia through a trans-corneal beam. Laser energy is applied to the tumor “to effect” with the goal of causing destruction of neoplastic cells and prevent further growth within the eye. Aside from the potential for inadequate treatment leading to continued tumor development, complications associated with diode laser photocoagulation are minor and include a distorted pupil (dyscoria) due to destruction of iris tissues, and corneal edema due to collateral hyperthermia (14). Diode laser photocoagulation can be repeated if the initial treatment is inadequate or unsuccessful.

Sector iridectomy (or iridocyclectomy) is a surgical procedure employed to remove localized masses of the iris (and ciliary body) that encompass less than a 3-hour clock quadrant or 90 degrees of the iris surface (12). Surgery is completed through a peripheral corneal incision, adjacent to the lesion. The affected iris is excised and submitted for histopathology to confirm the diagnosis and evaluate surgical margins. Following surgery, the pupil has a distorted appearance due to the removal of iris tissue. Complications of this procedure include intra- and post-operative iris hemorrhage, uveitis, focal posterior synechia, and focal nonprogressive cataract (12). Recurrence is uncommon even when inconclusive margins are obtained (12).

In this case, the well-circumscribed nature of the lesion and its small size made it a good candidate for sector iridectomy. This was completed and the resected iris tissue was submitted for histopathology which confirmed a completely excised, well-differentiated melanocytic neoplasm arising from the iris surface. The mitotic count was less than 1 per 10 HPF verifying a benign melanocytoma. This dog recovered well after surgery and follow-up revealed minor post-operative uveal hemorrhage that resolved within a few days after the procedure. Dyscoria was present, as expected; however, this did not noticeably affect vision or comfort level. We continue to monitor the eye and there has been no re-growth of the tumor > 1 y after surgery.

Anterior uveal melanocytic neoplasia is the most common intraocular neoplasia in dogs. The prognosis for survival is excellent as these tumors are most often benign in their biological behavior. The long-term prognosis for the globe and vision is unfortunately poor, as eventually, infiltration of the iridocorneal angle and uveitis will lead to secondary glaucoma unless these are effectively treated early in their development. Smaller, well-circumscribed lesions may be treated with diode laser photocoagulation or sector iridectomy with a goal of preventing further growth and preserving the eye. For large lesions that are not amenable to these interventions, the conservative route of clinical monitoring until the eye develops glaucoma, with a plan for enucleation, is advised. The enucleated globe should always be submitted for histopathology to confirm the diagnosis and evaluate for potential for malignancy, though this is rare.