Glaucoma: The 5 o'clock emergency (Proceedings)

Glaucoma is a syndrome in which progressive elevation in intraocular pressure (IOP) of the eye results in damage to the optic disk and retina, causing blindness. This starts occurring at IOPs above 25mmHg in dogs and above 30mmHg in cats.

The elevated IOP is due to a disharmony between production and outflow of the aqueous humor. More specifically, a reduction in the outflow rate of the aqueous humor is responsible for the elevated IOP, not the overproduction of the aqueous humor.

Aqueous humor dynamics and physiology

In order to better understand these processes, it is first important to understand the normal fluid dynamics of the eye. The aqueous humor is formed at a constant rate of approximately 2% of the anterior chamber volume per minute. In the dog, that is about 2.5µl/min and in the cat 15µl/min.

Aqueous humor is produced in the non-pigmented epithelium of the ciliary processes located posterior to the iris and is formed via three basic mechanisms, namely: passive diffusion, ultra filtration and active transport/secretion. Active transport/secretion is the greatest contributor to aqueous humor formation, with the carbonic anhydrase enzyme catalyzing the reaction: CO2 + H2O HCO3- + H+. Thus, every time a bicarbonate ion enters the aqueous, it is associated with movement of water into the posterior chamber.

There are two mechanisms for aqueous outflow: the conventional/corneoslceral outflow and the unconventional/uveoscleral outflow.

In conventional outflow, aqueous humor passes from the posterior chamber through the pupil then into the anterior chamber. The aqueous humor exits the eye near the periphery of the iris at the iridocorneal angle, where it passes through the Spaces of Fontana between the pectinate ligaments to enter the trabecular network of the ciliary cleft. The aqueous humor is then filtered between the corneoslceral trabecular meshwork to enter a series of radially oriented, blood free collecting vessels called the aqueous capillaries or, collectively, the angular aqueous plexus.

With the uveoscleral outflow, the aqueous humor passes through the iris and interstitial spaces of the ciliary muscle to reach the supraciliary space. This outflow is independent of the IOP.

Glaucoma classification

Glaucoma is classified as primary, secondary, or congenital glaucoma. Primary glaucoma should be considered a bilateral disease; hence, the unaffected eye should be considered predisposed due to the conformation of its iridocorneal angle. Thus, it is important to treat the unaffected eye prophylactically to decrease the incidence of glaucoma.

Many canine breeds are predisposed to primary glaucoma. However, the most commonly seen breeds with primary glaucoma include the American Cocker Spaniel, Basset Hound, Bouvier des Flanders, Chow Chow, Shar Pei and Siberian Husky. Primary glaucoma has also been reported, albeit rarely, in Burmese and Siamese cats.

The most common form of primary glaucoma that is seen in dogs is primary angle closure glaucoma (PACG), in which the iridocorneal angle is narrowed or closed due to pectinate ligament dysplasia. Primary open angle glaucoma (POAG) is also seen dogs, with the Beagle being the breed most well known for this type of glaucoma. In POAG, the iridocorneal angle appears gonioscopically normal and the impediment to aqueous outflow is deep to the pectinate ligaments.

Secondary glaucoma occurs due to obstruction of the aqueous humor flow at the ciliary process diaphragm, pupil or iridocorneal angle, as a consequence of an unrelated intraocular pathologic process. The increased IOP may be secondary to a variety of intraocular pathologic processes, including chronic uveitis, hyphema, lens luxation, intraocular neoplasia, pigment dispersion syndromes and aqueous misdirection syndrome. These conditions may block the normal flow of aqueous through the pupillary aperature or close the iridocorneal angle secondary to peripheral anterior synechia, fibrovascular membrane formation, or accumulation of cellular debris within the angle.

Congenital glaucoma is rare and usually occurs within a few months of being born. These cases typically present with prominent buphthalmos. Congenital glaucoma is generally secondary to a congenital malformation of the anterior segment.

Diagnosis of glaucoma

Clinical signs of glaucoma may vary depending on the classification.

Gonioscopy is a useful tool for diagnosing primary glaucoma and the predisposition for glaucoma of the fellow eye. By using gonioscopy, you can classify the iridocorneal angle as either open or closed based on the pectinate ligaments. Any dog that presents with glaucoma in one eye should have gonioscopy performed on the contralateral eye.

Common signs of acute glaucoma include severely elevated IOP, blepharospasm, elevated third eyelid, severe episcleral congestion, a fixed and dilated pupil, and prominent corneal edema. These dogs are typically blind on presentation, the globe is a normal size, and fundic examination reveals a swollen and hyperemic optic nerve head.

Chronic glaucoma, on the other hand, has a different set of presenting signs. These dogs typically also exhibit signs of pain (blepharospasm and elevated third eyelid); however, in these cases, the globe is usually buphthalmic and sometimes, depending on the globe enlargement, lagophthalmos with accompanying signs of corneal dessication is seen. Also in these cases, there is often a posterior subluxation of the lens. Fundic examination of these cases usually reveals retinal changes, including tapetal hyper-reflectivity and retinal vascular attenuation, and the optic nerve heads are cupped with a darkened border.

Signs of secondary glaucoma vary depending on the primary ocular disease. Secondary glaucoma due to chronic uveitis frequently has an accompanying posterior synechiation, and the pupils will be either miotic or irregular, causing a pupillary block. With pupillary block glaucoma, the anterior chamber is typically shallow, and the peripheral iris is seen billowing forward, thus obliterating the peripheral anterior chamber. Other instances of secondary glaucoma also exhibit a chronic fibrin deposition within the anterior chamber, thus occluding the iridocorneal angle. Once again, these often present with signs of chronic uveitis. Another major cause of secondary glaucoma is anterior lens luxations. Terrier breeds are the most common breed seen for this condition.

Medical treatment of glaucoma

The initial medical treatment of glaucoma is aimed at dropping IOP as soon as possible if vision is to be restored or retained.

In acute glaucoma cases, dropping the IOP as soon as possible is essential for regaining or preserving vision. Therefore, systemic hyperosmotics like Mannitol (1-2 grams/kg) given intravenously over 20-30 minutes or oral glycerin (2mL/kg) should be considered as the initial treatment protocol.

Hyperosmotic agents temporarily increase the plasma osmolality relative to the vitreous, thereby resulting in dehydration of the vitreous body and lowering IOP. These agents may not work as effectively without an intact blood ocular barrier (e.g., as a consequence of uveitis).

Topical prostaglandin analogues such as Latanoprost can also be used for treating cases of acute primary glaucoma to quickly reduce IOP. Latanoprost can be used on its own or, better yet, in conjunction with emergency hyperosmotic therapy. Latanoprost exerts its effect by increasing the uveoscleral outflow pathway of aqueous humor. Before applying Latanoprost, it is important to ensure that the glaucoma is not secondary to an anterior lens luxation. This is extremely important as the resulting miosis will incarcerate a lens displaced in the anterior chamber, thus exacerbating the glaucoma. Caution should be used when Latanoprost is applied to glaucomas that are secondary to uveitis or pigmentary glaucoma, such as that seen in Cairn terriers.

For long-term medical management of glaucoma, carbonic anhydrase inhibitors (CAIs) have good pressure lowering abilities. They inhibit the production of aqueous humor, thus lowering IOP; however, this class of drugs must inhibit 98-99% of the carbonic anhydrase enzyme to be effective. Hence, topical CAIs (e.g., Trusopt, Azopt) work most effectively at three times daily dosing, and oral CAIs (e.g., Methazolamide) work most effectively at twice daily dosing. This class of glaucoma drugs is effective in treating both primary and secondary glaucoma patients.

Beta blockers, such as Timolol, also work by decreasing the production of aqueous by blocking beta receptors in the ciliary processes, thus inhibiting active transport and ultrafiltration mechanisms of aqueous production. This class of glaucoma drugs also has a mild miotic effect on the pupil and is good for treating primary and most secondary glaucoma patients. Beta blockers are best used in combination with other pressure-lowering medications.

Alpha adrenergic agonists, such as epinephrine, can also lower IOP and should be considered for glaucoma secondary to lens luxation until surgical removal of the lens can be performed.

One last concern is the aforementioned neuropathy associated with glaucoma, for which new neuroprotective medical agents need to be considered for the long-term protection of the optic nerve and retina. An example of a neuroprotective medical drug is Memantine, which is an NMDA inhibitor that decreases the effects of glutamate excito toxicity, thus protecting retinal glangian cells from the negative effects of free-radical expression.

Given the recalcitrant nature of glaucoma in veterinary patients, combination anti-glaucoma medical therapy is more effective than any single method alone. Furthermore, for the long-term control of IOP, medical treatment alone has been shown to be largely ineffective. Medical treatment should be used as an adjunctive therapy with surgical treatment.

Surgical treatment of glaucoma

The surgical treatment options for glaucoma are varied, and which particular option is best, depends upon whether the eye is visual or potentially visual or the eye is irreparably blind and/or painful.

For a blind eye, the goal of surgical treatment is to ensure long-term comfort and, if possible, salvage procedures are performed to save the eye. Surgical treatments available for blind and/or painful eyes include cyclophotocoagulation (laser), cyclocyrothermy (freezing), ciliary body ablation (chemical ablation of the ciliary body), enucleation, and intrascleral prosthesis. These procedures help to ensure comfort in patients with blind, painful, chronic glaucoma and allow resources to be focused on the visual eye and any systemic health issues.

A ciliary body ablation is an inexpensive option for treating the blind glaucomatous eye. In a ciliary body ablation, Gentomycin is injected into the posterior segment after an equal to or slightly greater volume of vitreous has been removed. The Gentomycin is toxic to the ciliary processes and thus effectively minimizes fluid production. The most common side effect of ciliary body ablation is pthisis bulbi.

Enucleation is the most definitive option in which the painful glaucomatous eye is removed. Cyclodestructive modalities can also be employed on painful eyes using a nitrous oxide probe to freeze the ciliary body via a transscleral approach. After the intraocular contents have been removed, an intrascleral prosthesis can be placed within the empty tunic. This procedure is indicated for clients who are looking for an aesthetically pleasing alternative to removing the eye. The most common long-term complications can include corneal degeneration.

Most surgical treatment options available for glaucomatous patients with a chance for vision target the ciliary processes to slow fluid production, including transscleral cyclophotocoagulation and endocyclophotocoagulation. However, the goal of placing an anterior chamber shunt is to create an alternative path for aqueous humor to exit the eye. The major complication concerning these anterior chamber shunts is fibrous occlusion of either the tube or the conjunctival bleb.

Transscleral cyclophotocoagulation with a diode or ND:Yag laser is used to ablate the ciliary processes and thus reduce fluid production. This procedure is non-invasive as it delivers the laser energy transsclerally. Unfortunately, the major drawback to this procedure is that it does not allow visualization of the ciliary processes and relies solely on their estimated anatomic locations. The effective energy that is delivered is also somewhat estimated by the number of "pops" one hears. It has a reported success rate of approximately 50%. In the past, this treatment modality was preferred for want of something better. Newer technologies, however, have the potential to improve glaucoma surgery by being more precise in their delivery of laser energy to ablate the ciliary processes.

For example, the recent development of a diode endolaser enables the surgeon to place the laser into the eye, therefore enabling visualization of the ciliary processes which then can be ablated using the precise direction of energy and the precise amount energy. This also decreases the amount of damage to neighboring structures within the eye.

The new endocyclophotocoagulation surgical modality is performed using this new diode endolaser. Endocyclophotocoagulation administers accurate energy to ablate the ciliary processes from between 270 to 360 degrees. Additionally with this procedure, the lens is surgically removed via phacoemulsification to reduce crowding of the iridocorneal angle as the lens enlarges with age. This procedure is relatively new and only a small amount of data regarding its success rates is available. That said, the reported success rates thus far are very encouraging and higher than any of the other surgical modalities. In my experience, I have had only two out of approximately 40 eyes in which I have been unable to control the IOP using this surgical modality alone.

As with medical therapy, using a combination of these surgical procedures can be more effective in controlling IOP than using one surgical procedure alone. For example, phaco-assisted lens removal performed in conjunction with endocyclophotocoagulation and implanting an anterior chamber shunt can be more effective at controlling IOP than any one of these surgical treatment options used alone.

Even after surgical treatment, medical treatment is still necessary as adjunctive therapy for the long-term control of IOP.

Conclusion

In conclusion, early aggressive medical therapy and consultation with a veterinary ophthalmologist regarding the short- and long-term management of glaucoma is indicated. Although treatment for glaucoma in the past has yielded limited success, technology is rapidly changing and is enabling us as ophthalmologists to have a better chance at saving vision, if this blinding and painful condition is addressed early and these patients are identified in a timely manner.