Melanocytic glaucoma in a cairn terrier

Abstract

Melanocytic glaucoma, previously known as pigmentary glaucoma, is characterized by diffuse intraocular infiltration of heavily pigmented melanocytes. This unusual ocular disorder has been documented only in the cairn terrier and is considered familial. Treatment strategies are based on evidence that the condition is slowly progressive but not neoplastic.

A 14-year-old neutered male cairn terrier was referred to the Ophthalmology Service, Veterinary Medical Teaching Hospital, Cornell University, for a suspected melanoma in the right eye. The owners had first noticed swelling and abnormal coloration of the eye 6 mo earlier. Progressive deterioration of night vision and bilateral lens cloudiness had been developing for about 1 y. The eyes had not been treated at the time of referral, and the dog had no history of medical problems other than seasonal flea allergy dermatitis. A pedigree was not available.

The dog was bright, responsive, and able to navigate around a well-lit examination room. The respiratory rate was elevated, and there were harsh lung sounds bilaterally. The heart rate was 120 beats/min, the pulse was regular and strong, and the rectal temperature was normal (39.1°C). Severe periodontal disease and halitosis were evident. A firm, raised, pigmented cutaneous mass 0.5 cm in diameter was discovered on the dog's head about 1 cm to the right of the midline, 7 cm caudal to the right eye, and 4 cm medial to the right ear.

Ocular examination revealed that the right eye was blind, lacking both a pupillary light reflex and a menace response. The eye was buphthalmic, with a 2-cm, poorly delineated, raised, pigmented mass protruding from the dorsolateral aspect of the sclera and episclera (Figure 1). The scleral vessels appeared engorged. A 1-cm, flattened, irregular area of pigmentation was present on the dorsal area of the sclera and episclera of the left eye. Pigment invasion of the lateral limbal border of the cornea was noted bilaterally. The right lens was subluxated anteriorly, creating an irregular shallow depth of the anterior chamber. Nuclear sclerosis was present bilaterally, with early cataract changes on the right. Applanation tonometry indicated that the right eye was glaucomatous, with an intraocular pressure (IOP) of 40 mmHg. The IOP was normal in the left eye (19 mm Hg). Clear visualization of the vitreous and fundus was difficult owing to the decreased transparency of both lenses.

Figure 1. Photograph of the right eye showing a pigmented mass on the dorsolateral aspect of the sclera and episclera. The mass protrudes from the surface of the eye about 0.5 cm and is about 2 cm in diameter, with irregular borders. Pigment invasion and neovascularization may be seen along the lateral limbal border of the cornea. Chronic glaucoma and anterior subluxation of the lens have caused buphthalmia. Cloudiness of the anterior chamber is secondary to inflammation associated with the subluxated lens.

A tentative diagnosis of melanocytic glaucoma was made on the basis of the clinical signs and the breed of dog. Differential diagnoses for the pigmented ocular mass included other intraocular neoplasms, such as melanocytoma and melanoma (1).

As the right eye was buphthalmic, blind, and painful, treatment by enucleation or intraocular prosthesis was suggested. The dog was admitted for enucleation of the right eye (day 1). A blood sample was taken for a preanesthetic complete blood cell (CBC) count and serum biochemical profile. Thrombocytosis was the only significant abnormality in the CBC count. Mildly elevated levels of blood urea nitrogen and serum alkaline phosphatase were also reported but were not considered significant with regard to anesthetic risk for the scheduled surgery. The fundus of both eyes was visualized before surgery by ultrasonography. Findings included asteroid hyalosis in the left eye, lens subluxation in the right eye, and absence of retinal detachment bilaterally.

Therapy with amoxicillin trihydrate (Amoxi-tabs; Pfizer, New York, New York, USA), 20 mg/kg body weight (BW) PO, q12h, for 14 d, was started on day 1. Timolol maleate drops (Ophthalmic Solution Liq-0.5%; Akorn, Buffalo Grove, Illinois, USA) were instilled in the left eye (1 drop q12h). Photographs were taken of the left eye to monitor progression of scleral pigment deposition. On day 2, enucleation of the right eye was performed, and the pigmented mass on the head was excised. Recovery from anesthesia was uneventful. Oxymorphone (Numorphan; DuPont-Merck, Philadelphia, Pennsylvania, USA), 0.05 mg/kg BW subcutaneously, was administered postoperatively.

The enucleated right eye was preserved in 10% buffered formalin solution and submitted for histopathologic examination. Five-micron sections were prepared and stained with hematoxylin and eosin. Pathological changes attributable to chronically elevated IOP were observed in the retina, optic disc, and optic nerve. Retinal degeneration was present in multiple levels, with some areas completely devoid of ganglion cells. High IOP had caused compression of the optic disc head into the cribriform area, resulting in Schnaubble's cavernous atrophy of the optic disc, which was visible as a large cup (1).

Histopathologic examination of the cornea revealed neovascularization and infiltration of melanocytes or melanin-laden macrophages along the limbal border. Although the anterior chamber was clear of exudate, the trabecular meshwork and vascular drainage at the iridocorneal angles were completely occluded with invading melanocytic cells, resulting in angle recession. Melanocytic infiltration had obliterated a significant portion of the dilator and constrictor iridal musculature. There were significant accumulations of melanocytes and macrophages containing melanin within the sclera and its draining vessels. The mass on the dorsal part of the sclera was composed of a bilobed area of proliferating melanocytes with invasive characteristics. Heavy melanocyte infiltration was also present in the uvea, optic nerve, surrounding meninges, and adjacent arterial walls. These findings were consistent with a diagnosis of melanocytic glaucoma. In contrast to the expected benign pigmentary process, proliferation of melanocytes in the scleral mass demonstrated invasion and growth patterns characteristic of malignancy, with metastasis a potential concern.

On day 3 the incision for the right eye was healing without complication, and the IOP had stabilized in the left eye at 16 mmHg. The dog was discharged with instructions to the owners to continue amoxicillin trihydrate for 12 d. Timolol maleate, a β-adrenergic blocker, was prescribed for the left eye, 1 drop, q12h indefinitely, to slow development of glaucoma by decreasing aqueous production and potentially increasing aqueous outflow (2). Pigmentary changes and the IOP in the left eye were to be assessed every 2 to 3 mo.

Canine glaucoma is classified as primary or secondary. Primary glaucoma affects certain breeds and occurs independently of other ocular diseases. Secondary glaucoma arises from an antecedent ocular disease that causes elevated IOP, such as lens luxation, vitreous prolapse, anterior uveitis, acute trauma, hyphema, or intraocular neoplasia (3). An unusual form of secondary glaucoma known as melanocytic glaucoma has been recognized in the cairn terrier. This form of glaucoma develops slowly as a result of abnormal pigmentary cell proliferation, which eventually infiltrates the iridocorneal angle and obstructs aqueous drainage (4).

Middle-aged to older cairn terriers are affected, the initial presentation commonly occurring between 9 and 13 y of age (5,6). One or both eyes may be involved, and clinical signs vary according to the stage of disease at first examination. In the early stages the eye is not glaucomatous, and only darkening of the iris and circumferential swelling of the iris base are evident. As the disease progresses, pigment can be seen in the aqueous humor and as a band on the endothelial surface of the ventral part of the cornea. Small patches of intrascleral pigment appear, gradually enlarge, and become raised (7). Because of its insidious onset, the disease is usually not noticed until invasion of pigment-laden cells has completely occluded the iridocorneal angle, causing intractable glaucoma (4). This advanced stage of disease was present in this case: the dog's right eye was blind, buphthalmic, and painful, with lens subluxation and a markedly elevated IOP (40 mmHg). Globe enlargement secondary to chronic glaucoma often results in lens subluxation due to tearing of the lens zonules as the sclera stretches. In this case, retinal degeneration, optic atrophy, and cupping of the optic disc were additional secondary changes attributed to a chronically elevated IOP (1,5).

Melanocytic glaucoma arises from the abnormal proliferation of pigmented cells, believed to be melanocytes or melanomacrophages, located primarily in the anterior uvea (7). These cells are relatively large, heavily pigmented, and oval to round, and they often have small, peripheral nuclei. Significant numbers of proliferating melanocytes at the base of the iris cause pathological thickening (8) and gradually infiltrate the surrounding tissues, producing extensive cellular accumulations, which completely obliterate the iridocorneal angle and ciliary cleft (7). Raised episcleral pigment patches develop either from local proliferation of pigmented cells or secondary to aqueous drainage of pigmented particles through the scleral venous plexus (4). In addition, histopathologic examination reveals that melanocytes invade the peripheral cornea, choroid, retina, and anterior meninges. In contrast to ocular neoplasia, melanocyte infiltration in melanocytic glaucoma follows a diffuse rather than nodular pattern (5). Although the exact cause of the abnormal melanocyte proliferation is unknown, the disease process appears to be similar to a benign type of iris melanoma (6).

Although it was originally hypothesized that melanocytic glaucoma in cairn terriers might be a useful model for pigment dispersal syndrome (PDS) in humans, the canine disorder does not demonstrate the classic signs of PDS (8). Krukenberg's spindle, a central pigmentation of the corneal endothelium commonly seen in PDS, is not a feature of melanocytic glaucoma (5). Radial thinning of the iris in PDS, caused by melanin release from the posterior surface of the iris, does not occur in cairn terriers (4). Lastly, free melanin granules are frequently observed in PDS, but in the canine disease the pigment particles are always found within large, epithelioid cells (5).

Treatment of melanocytic glaucoma is often not rewarding, as the condition is progressive, inevitably causing pigmented cell accumulation and secondary glaucoma. Surgical and medical therapies to prevent glaucoma by opening the drainage angle are not corrective: proliferating melanocytes ultimately occlude any bypass of the anterior chamber that is created or established (6). Surgical treatment for chronic glaucoma is usually indicated, as most dogs are not presented until the eye is irreversibly blind, painful, and buphthalmic (3). However, in contrast to malignant intraocular neoplasms, which necessitate enucleation or exenteration, melanocytic glaucoma is considered benign, and an intraocular prosthesis or cyclocryosurgery is a treatment option. Treated dogs enjoy a good quality of life, without postsurgical metastasis (5). In this case, enucleation was an appropriate treatment for the right eye, as melanocyte abnormalities consistent with malignancy were found histologically. Regular examinations were recommended to allow early detection of metastasis.

Melanocytic glaucoma has been identified as a familial condition in cairn terriers, according to studies in the United Kingdom and North America. An insufficient number of affected dogs have been available to determine the exact mode of inheritance (4,5). Research is being conducted using blood samples and pedigrees from affected cairn terriers with the goal of discovering the exact gene locus responsible for this unusual condition (9).