History

A 13-year-old 28.6-kg (62.9-lb) spayed female English Setter was presented to the University of Minnesota Veterinary Medical Center's ophthalmology service for referral evaluation of a buphthalmic right eye (buphthalmia of unknown duration).

Clinical and Gross Findings

Neuro-ophthalmic examination of the right eye revealed loss of vision with no menace response, dazzle reflex, or direct or indirect pupillary light reflexes. Gross examination of the right eye revealed diffuse moderate to severe scleral injection, buphthalmia, and 2 focal areas of scleral pigmentation. The pigmented regions were smooth and localized to the dorsal and ventrolateral scleral regions (Figure 1).

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Photographs of the right eye of a 13-year-old English Setter that was evaluated owing to buphthalmia of an unknown duration. A—The right eye has focal, dorsally located plaques of scleral pigmentation (arrow), mydriasis, and diffuse iris pigmentation (asterisk). B—Notice the focal ventrolateral plaques of scleral (arrow) and limbal pigmentation in the right eye. An area of corneal endothelial pigmentation is also present (asterisk).

Citation: Journal of the American Veterinary Medical Association 258, 3; 10.2460/javma.258.3.265

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Slit-lamp biomicroscopy of the right eye revealed that the pupil was dyscoric, nonresponsive, and mydriatic and that the iris was diffusely hyperpigmented. The lens was mildly posteriorly subluxated. Flare (approx 1+ [determined on the basis of a 1+ to 4+ grading system]) was present, indicative of anterior uveitis. Nuclear sclerosis and an incipient anterior cortical cataract were evident in the lens, and asteroid hyalosis was present in the vitreous humor. Fundic examination of the right eye revealed optic nerve cupping and tapetal hyperreflectivity consistent with chronic glaucoma. For the left eye, vision was preserved and neuro-ophthalmic examination findings appeared normal. The left eye had no signs of intraocular inflammation, and the only evident abnormalities were age-related changes, including nuclear sclerosis, an incipient anterior cortical cataract, and asteroid hyalosis. Results of fundic examination of the left eye were within reference limits. Applanation tonometry^a of the right eye revealed that the eye was glaucomatous with an intraocular pressure of 26 mm Hg (reference range,¹ 10 to 25 mm Hg). The intraocular pressure in the left eye was 13 mm Hg; the magnitude of the difference in intraocular pressure between the 2 eyes further confirmed the presence of glaucoma in the right eye.¹ Schirmer tear test values for the right and left eyes were 17 and 13 mm/min, respectively (reference range, > 15 mm/min). For both eyes, results of fluorescein staining were negative, indicating no corneal ulcerations.

Clinical Interventions

Glaucoma of the right eye was presumed to be secondary to an intraocular mass or a nonneoplastic disorder. Recommendations for additional diagnostic evaluation of the right eye included ocular ultrasonography or enucleation with histologic evaluation. Enucleation of the right eye was elected, and aqueous humor paracentesis was performed immediately following enucleation and prior to placement of the globe in neutral-buffered 10% formalin. The paracentesis sample was submitted for cytologic evaluation by the clinical pathology service. The fixed right eye was submitted for histologic examination by a board-certified veterinary pathologist with expertise in ocular diseases.

For the dog's left eye, a diagnosis of mild keratoconjunctivitis sicca (dry eye) was made on the basis of reduced tear production. Keratoconjunctivitis sicca in the left eye was treated with topical application of an immunosuppressive drug^b 2 times daily and eye lubrication^c 4 times daily.

Cytologic Findings

Microscopic examination of the aqueous humor paracentesis sample from the right eye was performed. Smears of concentrated aqueous fluid were of low cellularity but contained focal, dense aggregates of heavily pigmented, uniform, oval to polyhedral cells that were characterized by a single round nucleus; very rare spindle-shaped cells were also present. The oval to polyhedral cells had abundant heavily pigmented cytoplasm that obscured most of the nuclei (Figure 2). The visible nuclei were round to oval with finely dispersed chromatin and a central single small nucleolus. Mitotic figures were not observed in the visible nuclei in any of the smears. These cells were interpreted as most likely mature melanocytes; however, the potential for the concurrent presence of melanophages could not be excluded.

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Photomicrographs of smear preparations of aqueous humor obtained by paracentesis from the right eye immediately after enucleation. A—Cells have heavily pigmented cytoplasm that obscures most of the nuclei (arrows); cells were interpreted as likely of melanocytic origin. Wright-Giemsa stain; bar = 20 μm. B—Visible nuclei are round to oval (arrow). Mitotic figures are not present in the visible nuclei. Wright-Giemsa stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 258, 3; 10.2460/javma.258.3.265

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Histopathologic Findings

Histologic examination of a parasagittal section of the enucleated right eye revealed a diffusely, heavily pigmented uvea that was regionally distorted by melanocytic proliferation. The iridocorneal angle was collapsed or effaced with heavily pigmented cells (Figure 3). The uvea was focally expanded by pigmented cells in the anterior ciliary body and choroid.

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Photomicrographs of a parasagittal section of the enucleated right eye. A—Notice the diffuse anterior uveal pigmentation and expansion and unapparent iridocorneal angle structures. H&E stain; bar = 5 mm. B—The iridocorneal angle has pigmented cell infiltration and a nodular mass at the inferior aspect. H&E stain; bar = 0.5 mm. C—Optic nerve head cupping (arrow) and retinal atrophy are present. H&E stain; bar = 1 mm.

Citation: Journal of the American Veterinary Medical Association 258, 3; 10.2460/javma.258.3.265

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Melanocytic cells were large and round to polygonal; intracellular pigment obscured the nucleus of many cells. Visible nuclei had an indistinct, central single small nucleolus and evenly dispersed chromatin. The pigmented cells also extended into the perivascular adventitia of scleral blood vessels, optic nerve meninges, and the peripheral optic nerve parenchyma. Examination of several sections revealed a small region of melanocytic cells with increased atypia, including spindle-shaped and stellate cells located at the inferior aspect of the iridocorneal angle, suggesting the potential for a developing melanocytoma rather than the sole process of ocular melanosis. Lesions consistent with glaucoma included iridocorneal angle collapse, optic nerve head cupping and parenchymal atrophy, and inner retinal atrophy that was more severe in the nontapetal regions. Secondary histologic lesions included chronic keratitis, segmental retinal detachment with mild intraocular hemorrhage, and suspected lens luxation.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: ocular melanosis with secondary chronic glaucoma in an English Setter.

Comments

The case described in the present report involved an English Setter with ocular melanosis and uveal melanocytoma along with secondary glaucoma. To the authors’ knowledge, ocular melanosis in this breed has not been reported. Ocular melanosis is described as a genetic disease in Cairn Terriers.² Case reports of other dog breeds with this disease have involved Boxers³ as well as Labrador Retrievers⁴ and Golden Retrievers.^4,5 In Cairn Terriers, the condition is often bilateral.² Ocular melanosis is characterized by infiltration and deposition of pigment-laden melanocytes and melanophages within the sclera, episclera, anterior uvea, and posterior segment.^2,6 A form of secondary glaucoma, previously referred to as pigmentary glaucoma, is associated with extensive pigment deposition and blockage of the iridocorneal angle; clinical signs include a gradual increase in intraocular pressure, buphthalmia, signs of pain, and eventual irreversible blindness. On the basis of histopathologic examination findings for the enucleated eye from the dog of the present report, the pathophysiologic changes in the right eye appeared similar to those associated with the disease previously reported for other dog breeds.^2,3,4,5,6 Hence, it is our opinion that English Setter should be added to the list of dog breeds that may develop ocular melanosis.

Histologic examination of an enucleated affected eye is the standard procedure for the diagnosis of ocular melanosis. Anterior chamber paracentesis and cytologic examination of the collected sample have been shown to be useful in the diagnosis and management of uveitis in dogs, depending on the cause.⁷ In contrast to most ocular neoplasms that form discrete nodules, melanocyte infiltration associated with ocular melanosis in dogs is diffuse, which may increase the likelihood of obtaining a sample of reasonable cellularity by means of aqueous humor paracentesis. In the case described in the present report, a cytospin technique⁸ was used to maximize the cell yield from the aqueous fluid sample. Cytologic analysis of aqueous humor could be useful in certain dogs, specifically those with optical media opacities. Regardless of its diagnostic value, aqueous humor paracentesis can be associated with potentially serious complications and should be performed by experienced personnel.

Findings of the histologic evaluation of the enucleated eye from the dog of the present report were consistent with diffuse ocular melanosis, as well as a small focal melanocytoma that was characterized by a more nodular profile admixed with spindle-shaped and stellate cells and mildly increased nuclear atypia. Benign melanocytic tumors are referred to as melanocytomas and can be composed of large, round, heavily pigmented cells in clusters or streams of spindle-shaped to stellate cells in variable proportions. Nuclei in both cell types are small, centrally located, and oval to round and have small or indistinct multiple nucleoli. Mitotic figures are rare or absent in melanocytomas.⁹ Although intraocular melanocytomas have no metastatic potential, they are often locally destructive to the globe and can cause blinding glaucoma if the area of melanocytoma is obstructing a large portion of the iridocorneal angle. A diagnosis of malignant intraocular melanoma is indicated by the presence of moderate cellular atypia (anisokaryosis, increased number and size of the nucleoli, and open chromatin patterns) and a mitotic rate > 4 mitoses/10 hpf (400×), none of which were evident in the English Setter of the present report. The dog most likely developed ocular melanosis–induced glaucoma because the melanocytoma appeared too small to cause iridocorneal angle obstruction and glaucoma.

The present report has described a case of ocular melanosis and uveal melanocytoma with secondary chronic glaucoma in an English Setter. English Setter should be included in the list of dog breeds affected by ocular melanosis. This report has also highlighted the fact that cytologic examination of an aqueous humor paracentesis sample may augment initial clinical diagnostic evaluation.