Idiopathic glaucoma in an 11-year-old crossbred mare

Abstract

An 11-year-old crossbred mare was presented with left eye buphthalmia, a mydriatic minimally responsive pupil, locally extensive ventral corneal edema, and corneal striae. Intraocular pressures exceeding 80 mmHg lead to a presumptive diagnosis of glaucoma. Following several days of treatment there was no improvement and enucleation was performed.

A previously healthy 11-year-old gray Arabian-Quarter Horse crossbred mare was presented to the veterinarians of Springer Animal Hospital with complaint of a “swollen left eye” of 1 day duration. On neuro-ophthalmic examination of the left eye there was a diminished direct dazzle and pupillary light reflex. The indirect pupillary light reflex was normal. Palpebral reflexes of the left eye were normal, the eye was fluorescein stain negative with a positive Jones test, and the mare appeared to be visual with a positive menace response. Ocular lesions noted in the left eye were buphthalmia, brown pigmentation of the sclera, mild episcleral injection, a 5-mm diameter semi-circular area of edema located ventrally within the cornea, linear corneal band opacities extending from limbus to limbus, and the pupil appeared dilated with a diminished response to light (Figure 1). No other ocular abnormalities were noted in the left eye but it was difficult to perform a thorough fundic examination due to the presence of obscuring edema; what we were able to evaluate appeared normal. No anomalies were noted in the right eye.

Figure 1.

Generalized corneal edema, scleral pigmentation, and linear band opacities noted in the glaucomatous eye.

Initially, the patient was treated with a 1-cm strip of sodium chloride, 5% (Muro 128; Bausch & Lomb, Vaughan, Ontario) applied topically q6h, and 500 mg of flunixin meglumine (Banamine; Merck AH, Toronto, Ontario) given IV initially, then PO, q12h. Two days after initial presentation, intraocular pressures were measured with a tonometer (Tono-Pen; Reichert Technologies, New York, New York, USA) while the horse was lightly sedated with 0.7 mg of xylazine (Xylamax; Bimeda, Cambridge, Ontario) given IV, and 2 drops of topical proparacaine hydrochloride, 0.5% (Alcaine; Alcon Canada, Missisauga, Ontario) were applied, with intraocular pressures averaging 88 mmHg (left eye) and 22 mmHg (right eye). On neuro-ophthalmic examination, the edematous area in the cornea was now almost completely encircling the pupil, measuring approximately 7 mm in diameter, the linear corneal band opacities were more prominent, and the pupil had become fixed and minimally responsive to light stimulus. The horse had minimal tearing and did not appear to be in pain. Working with a presumptive diagnosis of glaucoma, 1 to 2 drops of 20 mg/mL dorzolamide hydrochloride and 5 mg/mL timolol maleate (Cosopt; Merck AH) applied topically to the left eye q8h was added to the treatment protocol to control intraocular pressure (IOP).

Three days later, on re-check examination, the corneal edema had dissipated by approximately 1/3, leaving a 5-mm circular area in the ventrum of the cornea. Intraocular pressures were averaging 86 mmHg (left eye) and 22 mmHg (right eye). All further treatment options were discussed with the owner including long-term medical management, referral, surgical treatment, and enucleation as a salvage procedure. One week later, the owner elected to enucleate. On pre-operative examination of the eye, it was noted that there were several centrally located pinpoint areas of fluorescein stain uptake, implying micro-ulceration of the cornea. The eye was enucleated using a standing subconjunctival surgical approach. The eye was fixed in formalin solution and sent to the Animal Health Laboratory, University of Guelph for histopathological evaluation.

The histopathology report included a diagnosis of glaucomatous retinal atrophy along with axonal depletion from the optic nerve, with no histologic evidence of an underlying cause. Superficial peripheral corneal stromal vascularization was also noted with no other evidence of intraocular inflammation or granulation tissue.

Discussion

Glaucoma is a disease affecting aqueous humor outflow pathways in the eye that result in phasic elevations of intraocular pressure to levels incompatible with eye health (1,2). This condition is not commonly diagnosed in horses and its mechanisms are poorly understood. Glaucoma occurs in stages; initially there is an event that leads to the hindrance of aqueous outflow systems, followed by the system becoming fully obstructed through morphological changes and intraocular pressures begin to increase (1). High intraocular pressures are what lead to the clinical signs associated with glaucoma, including scleral blood vessel congestion, corneal edema, and fixed pupils. The intraocular pressure eventually exceeds a level at which the optic nerve and retinal ganglion cells can function, leading to optic nerve axon degeneration, progressive loss of vision, and eventually, blindness (1).

In a normal eye, aqueous outflow exits the globe through the iridocorneal angle (ICA) and the uveoscleral pathway (3). Obstruction of the pathways can result from the development of pre-iridal fibrovascular membranes, blockage of the ICA with inflammatory debris, pupillary block resulting from posterior synechia and development of iris bombé, trabecular compression, and angle closure (1). It has also been proposed that uveal atrophy after an inflammatory event may predispose the ICA to collapse, along with blockage of the ICA by a tumor or other pathologic processes (1).

While all glaucomas occur secondary to a causative mechanism, equine glaucoma is frequently categorized into 3 types: congenital, primary, and secondary. Congenital glaucoma is associated with developmental abnormalities of the anterior segment (4). Primary glaucoma is seen with acquired, but often inherited ICA degeneration (2). Secondary glaucoma is the type most commonly diagnosed in horses with primary uveitis, with some hypothesized links to equine recurrent uveitis (ERU), along with neoplasia, lens luxation, and trauma (4).

Diagnosis of glaucoma in equine patients is challenging, as horses tend to exhibit the initial clinical signs of glaucoma more subtly than other species. Diagnosis can be confirmed if elevated intraocular pressure (anything exceeding normal pressures which range from 17 to 28 mmHg) can be documented in the presence of clinical signs of glaucoma, as described for the present case (2). This may prove difficult if the horse is concurrently afflicted with equine recurrent uveitis, as intraocular pressure may not be consistently elevated and a diseased globe can experience large diurnal fluctuations (1). For accurate diagnosis, an auriculopalpebral nerve block can be performed to reduce the chances of a false positive secondary to manipulation of the eye and eyelids. Variation among different devices and normal diurnal pressure fluctuations should be taken into account when taking IOPs for diagnostic purposes. Comparing IOPs with the normal or unaffected eye can also help confirm the diagnosis as there should not be large IOP differences between the right and left eyes, as occurred in this case.

During the acute or active phase of glaucoma, a mydriatic pupil may be seen along with mild to moderate corneal edema, mild to severe blepharospasm, aqueous flare, corneal striae, uveitis, and lens luxation (1). When glaucoma becomes chronic, corneal edema may be severe or permanent, corneal striae are often seen along with extensive posterior synechia, optic nerve atrophy with the lamina cribrosa exposed, hydrophthalmos, inconsistent aqueous flare, lens luxation (typically posterior), and blindness. Horses may display a range of none to all of these clinical signs, and tend to remain somewhat visual even in the late stages of disease, making detection and diagnosis of glaucoma even more challenging. In the current case, we suspected the horse to be in the acute/active stage of glaucoma, which was further supported by the histological analysis of the eye.

A histopathological retrospective study done by Curto et al (3), found that the most common histological lesions found in glaucomatous eyes included corneal stromal vascularization, multiple breaks in Descemet’s membrane, loss of nerve fibers and ganglion cells from the inner retina, optic disc cupping, gliosis, and axonal loss from the optic nerve. This study also determined that there appeared to be no sex predilection for development of glaucoma, that horses over the age of 15 are at the highest risk for development of secondary glaucoma, and Appaloosas (a breed susceptible to ERU) are highly susceptible to developing glaucoma (3).

Treatment for glaucoma involves both medical and surgical management. Several factors including the vision status of the eye, the presence of concurrent disease, the horse’s activity, economic factors, and ease with which the owner can apply treatments will determine which treatment protocols are recommended and optimally used (2). Treatment should focus on reducing intraocular pressure to levels compatible with optic nerve and retinal health (levels ≤ 20 mmHg are suggested as acceptable in a glaucomatous eye), decreasing aqueous humor production, and increasing outflow via conventional and unconventional pathways (1). To reduce aqueous humor production, topical β-adrenergic blockers such as timolol maleate and topical carbonic anhydrase inhibitors such as dorzolamide hydrochloride have proven effective in lowering IOPs (5). Some sources recommend topical atropine treatment to prevent glaucoma in cases of uveitis; however, this is only recommended for use when tonometry is consistently available and uveitis is the underlying cause of the glaucoma (1). Anti-inflammatory therapy with topical corticosteroids such as prednisolone acetate and systemic administration of non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylbutazone or flunixin meglumine can control uveitis and provide pain control (1). With long-term NSAID use, it is recommended that the horse be carefully observed for signs of common complications such as kidney disease or right dorsal colitis.

When medical management is no longer controlling glaucoma, one of several surgical interventions should be considered. Laser transscleral cyclophotocoagulation or ablation is the current surgical treatment of choice; it uses laser energy to preferentially destroy ciliary body epithelium and the stroma of the pars plicata, thereby reducing the amount of aqueous humor produced (2). Transscleral cyclocryosurgery is another option involving cryodestruction of the ciliary body using nitrous oxide (1). This method is associated with more severe ocular side effects, and has been limited to use in blind eyes (1). Chemical ablation of the ciliary body with gentamicin may also be used in blind eyes to reduce pain and hydrophthalmos (1). A recent report by Lassaline (6) introduced a new surgical technique that involved placing a Baerveldt glaucoma shunt in an equine eye that had become refractory to treatment, resulting in the reduction of intraocular pressures and retention of vision (7). Finally, salvage procedures including enucleation or evisceration should be considered if the eye cannot be managed with either technique or if the eye is severely painful or buphthalmic. Silicone implants can be placed for a more esthetically pleasing look, but as in all surgeries complications need to be discussed. In the present case, a combination of economic factors, feasibility of long-term treatment, and failure to respond to treatment lead to the decision to enucleate the affected eye.

With respect to aqueous outflow, the uveoscleral pathway in the horse may be just as important as the ICA pathway is in other species such as the dog (3). There are several features of the anatomy of the iridocorneal angle in the horse that account for these differences (1,3). This is thought to account for the perceived resistance of equine eyes to glaucoma and lower prevalence seen in the population (7). However, it is also possible that lack of diagnostic equipment could also contribute to infrequent diagnosis in the early stages (7). In this case, it was difficult to assess which causative mechanism lead to the secondary development of glaucoma. We hypothesized that it may have been a rare form of primary glaucoma that presents in aged horses, due to the sudden onset of clinical signs with no previous history of ocular pathology and lack of histological evidence of causation. Throughout the investigation and management of this case it became apparent that there is a general lack of literature exploring the pathophysiology of equine glaucoma. Increased understanding of how horses maintain vision in the face of chronically elevated intraocular pressures and the connection between glaucoma and ERU will be paramount in controlling the disease in the future. This is an area that needs to be explored further for us to understand and treat this debilitating disease.