Diagnostic Ophthalmology

History and clinical signs

An 8-year-old, spayed female Basset hound was examined at the ophthalmology service at the Western College of Veterinary Medicine for evaluation of a red left eye which had been abnormal for at least 2 months prior to presentation. The menace response was absent on the left side. Palpebral and occulocephalic reflexes were present bilaterally. The left pupil was dilated and did not have a direct or right-to-left consensual pupillary light reflex. A direct pupillary light reflex was present on the right side, but the left-to-right consensual pupillary light reflex was absent. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 15 mm/min and 16 mm/min in the right and left eye respectively. The intraocular pressures (IOP) were estimated with a rebound tonometer (Tonvet; Tiolat, Helsinki, Finland) and were 23 mmHg and 50 mmHg in the right and left eye, respectively. Results from fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) were negative bilaterally. On direct examination, the left globe was buphthalmic with episcleral vascular congestion. Biomicroscopic (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) and indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examinations following dilation with 0.5% tropicamide (Mydriacyl; Alcon, Canada, Mississauga, Ontario) were completed. Mild corneal edema was present in the left eye. The lens was displaced ventromedially in the posterior chamber causing a dorsolateral aphakic crescent. Fundic examination was normal in the right eye but in the left revealed diffuse tapetal hyperreflectivity, vascular attenuation, and an atrophic optic nerve. Gonioscopy was completed on the right eye which confirmed goniodysgenesis. A photograph of the left eye is provided for your assessment (Figure 1).

Figure 1.

Photograph of the left eye of a 8-year-old Basset hound.

What are your clinical diagnosis, differential diagnoses, therapeutic plan, and prognosis?

Discussion

Our clinical diagnosis was chronic primary glaucoma of the left eye causing buphthalmos, secondary posterior lens luxation, and retinal and optic nerve degeneration. The differential diagnoses for glaucoma are primary, secondary, and congenital. Primary glaucoma is an inherited condition in which IOP elevation develops without concurrent ocular disease (1). It is reported in several breeds, but may be most common in the American cocker spaniel and Basset hound (2). Primary glaucoma is associated with goniodysgenesis which is caused by failed rarefaction of primitive uveal neural crest tissue spanning the filtration angle. This is seen on gonioscopy as a sheet of tissue with no visible pectinate ligaments spanning the iridocorneal angle (1,3). Goniodysgenesis is not the etiology of primary glaucoma, only an anatomical marker, and the role of goniodysgenesis in the pathogenesis of primary glaucoma is unknown (3). Secondary glaucoma is an acquired condition in which elevation in IOP occurs due to antecedent or concurrent ocular disease causing obstruction of aqueous humor circulation through the pupil, ciliary cleft, or trabecular meshwork (3). Secondary glaucoma has been recognized to occur in association with lens luxation and subluxation, intumescent cataract, intraocular neoplasia, uveitis, and retinal detachment (2,3). Congenital glaucoma is a rare condition in which elevation in IOP develops prior to or soon after birth. It is associated with multiple anterior segment anomalies (1).

The clinical manifestations of glaucoma depend on the stage of disease as well as the etiology. Acute primary glaucoma will most often present in middle-aged purebred dogs with a red eye due to episcleral vascular congestion, generalized corneal edema due to decompensation of the endothelial pump mechanism, and a dilated, poorly responsive pupil due to pressure-induced impairment of iris constrictor muscle function (1,4). In the early phase, blindness may be temporary and vision may return with return to normal IOP. With chronicity, globe enlargement occurs (buphthalmos). Subsequent to this, breaks in the corneal endothelium cause corneal striae, and stretching and breakage of lens zonules can result in lens subluxation or luxation (1,4). Retinal and optic nerve degeneration eventually occur due to pressure-induced damage to theses tissues leading to irreversible blindness (1). The clinical manifestations of secondary glaucomas are similar; however, subtle clinical signs of the underlying cause are evident. Congenital glaucomas occur in neonates and the primary clinical sign is rapid globe enlargement which occurs due to the elastic nature of the immature sclera. Multiple anterior segment anomalies are usually present and include uveal hypoplasia, and microphakia (1,3).

The diagnosis of glaucoma is made based on tonometry and documentation of an intraocular pressure > 30 mmHg (5). Differentiation between congenital, primary, and secondary glaucomas requires consideration of signalment, as well as complete ocular examination to evaluate for antecedent ocular disease. Gonioscopy is needed to visualize the iridocorneal angle and investigate for goniodysgenesis. Goniodysgenesis is most commonly confirmed with gonioscopy of the contralateral eye as the affected eye usually has too much corneal edema to allow adequate visualization of the iridocorneal angle. Gonioscopy is particularly important when lens subluxation or luxation is present as these can be a cause of secondary glaucoma, as well as a consequence of chronic primary glaucoma.

Treatment of glaucoma depends on the cause and clinical stage of disease. The main goal of therapy for acute glaucoma is to rapidly reduce IOP in order to return vision and maintain it for as long as possible. There are multiple different types of anti-glaucoma medications. For emergency reduction of IOP intravenous mannitol administered at a dose of 1 to 2 g/kg body weight is usually effective within 30 min and lasts for up to 5 h (6). Mannitol is an osmotic diuretic which draws water from the vitreous, thus reducing its volume and consequently the IOP. Topical prostaglandin analogues such as latanaprost and travaprost rapidly and significantly reduce the IOP in dogs by increasing aqueous humor outflow, and can be used for emergency treatment and maintenance therapy for most glaucomas administered at q12h or q24h intervals (6). These agents induce dramatic miosis in dogs and are therefore contra-indicated in secondary glaucoma due to anterior lens luxation or severe uveitis (6). Carbonic anhydrase inhibitors (CAI) are useful in short- and long-term therapy of all types of glaucoma. These agents reduce the production of aqueous humor and cause modest reduction in IOP. Oral and topical forms exist and are similarly effective. Oral CAIs can be associated with systemic side effects such as gastrointestinal upset, metabolic acidosis, and hypokalemia. Topical CAIs such as dorzolamide are administered q8h and have largely replaced oral forms as they avoid these side effects (6,7). Topical parasympathomimetics such as pilocarpine increase aqueous humor outflow. Administered at a frequency of q6h, pilocarpine causes a modest reduction in IOP but has significant ocular side effects including miosis, ciliary spasm, and iritis. Because of this ocular irritation and the development of newer topical agents that are similarly or more effective, parasympathomimetics are falling out of favor with ophthalmologists (6). Adrenergic agents such as α-agonsits (such as epinephrine, dipivalyl epinephrine, apraclonidine, brimonidine) and β-blockers (for example, timolol, betaxolol, and levobunolol) provide mild reductions in IOP but are inconsistently effective in dogs (1,6). For this reason they should not be used alone but in combination with other antiglaucoma medications. Another important goal in the treatment of primary glaucoma is protection of the contralateral eye. Prophylactic treatment of the contralateral eye has been shown to delay the onset of glaucoma significantly (7). The authors most commonly use topical CAIs or β-blockers q12h for this purpose.

The primary surgical therapies for glaucoma include anterior chamber shunts (gonioimplants) to improve outflow and cyclodestructive techniques to decrease aqueous humor production. These procedures are usually performed on eyes with early primary glaucoma that still have vision or when the IOP is increasing despite maximum levels of medical therapy. Gonioimplants provide diversion of aqueous humor through a small tube placed into the anterior chamber which communicates with a valve placed in the episclera or frontal sinus (8). Potential early post-operative complications include uveitis, hypotony, and obstruction of the tube by fibrin. Long-term failure occurs due to fibrous tissue development around the episcleral implants (9). This may be avoided with valves placed in the frontal sinus due to the lack of surrounding mesenchymal tissue (9). Destruction of the ciliary processes may be achieved by laser or cryotherapy directed through the overlying sclera (1,10). Early post-operative complications of these techniques can include uveitis, hyphema, retinal detachment, corneal ulceration, and recurrent IOP elevation (10). Cataract formation, however, is an unfortunate and common long-term complication (10).

Salvage procedures are reserved for cases with irreversible loss of vision. As glaucoma is a painful condition in the dog, the main goal of therapy is to provide relief from pain. Blind glaucomatous eyes are, therefore, best treated by enucleation or evisceration with placement of an intrascleral prosthesis. The left eye in this case was blind due to chronic glaucoma, and the owner elected treatment via evisceration with placement of an intrascleral prosthesis. Prophylactic treatment was initiated for the right eye q12h with dorzolamide hydrochloride 2% (Trusopt; Merk Frosst Canada & Co., Kirkland, Quebec). When glaucoma developed in the right eye 10 mo later, an anterior chamber to frontal sinus shunt was placed surgically.

The long-term prognosis for primary glaucoma is poor. Despite advances in medical and surgical therapy, glaucoma will progress to the point where treatment is no longer effective and the eye eventually becomes blind. Although the condition initially presents in one eye, the other eye usually becomes affected in 2 to 15 mo (11). Upon diagnosis of primary glaucoma, prophylactic treatment of the contralateral eye may delay the onset of glaucoma significantly. Eyes with clinical manifestations of chronic glaucoma are usually irreversibly blind. Buphthalmos, optic nerve atrophy, and lack of a consensual pupillary light reflex to the contralateral eye are all poor prognostic indicators for vision.