Update on glaucoma in dogs (Proceedings)

The glaucomas are a group of conditions in dogs characterized by increased intraocular pressure and progressive optic nerve and retinal degeneration. This can be one of the most devastating and frustrating ophthalmic conditions, both for the general practitioner and the ophthalmologist. This article will discuss the current clinical understanding of glaucoma and the treatment options.

Glaucoma can be either a primary or a secondary condition, and the distinction is critical for proper management. Secondary glaucoma is an increase in intraocular pressure that is a direct consequence of a pre-existing condition, such as chronic uveitis, lens luxation, trauma, hyphema, or delevopmental anomalies. This form of glaucoma can occur in any breed and age. Treatment is primarily by correcting the underlying abnormality. Primary glaucoma occurs as a genetic condition due to the structural anatomy of the iridocorneal angle and the ciliary cleft. This is a bilateral disease, although it typically affects each eye at different times, and it will be the primary focus of this article.

A basic understanding of the physiology of aqueous humor production and outflow is required to understand glaucoma and the relevant treatments. Aqueous is produced in the ciliary body, specifically the non-pigmented epithelium. The reversible carbonic anhydrase catalyzed reaction H2O + CO2 ←→ HCO3 - + H+ is essential for the production of aqueous humor. Bicarbonate and sodium are actively transported into the posterior chamber and water follows by osmosis. The majority of the aqueous flows through the pupil and exits the eye through the iridocorneal angle, where it must pass through the pectinate ligaments and trabecular meshwork before entering the angular aqueous plexus. This plexus joins with the intrascleral venous plexus which then leads to the vortex venous plexus for passage out of the eye. An alternative pathway for aqueous drainage is referred to as the unconventional or uveoscleral pathway. Aqueous passes directly through the iris stroma into the suprachoroidal space and out through the choroidal veins. The significance of this pathway varies with the species (dog – 15%, cat – 3%). Glaucoma in dogs is almost exclusively due to decreased aqueous outflow. A "sink" analogy where the drain is clogged works well to describe what is happening with glaucoma.

Signalment is very important in identifying primary glaucoma. While it has been observed in many breeds, certain breeds, such as Cocker Spaniels, Shar Peis, Chow Chows, Siberian Huskies, Basset Hounds, and Beagles are afflicted with much greater frequency. Females are more affected than males, on balance, and most are middle aged (5-7 years old). Clinical sign recognition is also important. True glaucoma is nearly always associated with some combination of clinical signs, including scleral injection, diffuse corneal edema, elevated third eyelid, mydriasis, blepharospasm, buphthalmos, corneal striae, or vision loss. If an elevated tonometry value is obtained without any of the above clinical signs, the restraint and tonometry techniques should be evaluated and the reading repeated as falsely elevated pressures are common with improper techniques.

Buphthalmos is an exclusive sign of chronic glaucoma in adult dogs, but this is often confused with exophthalmos. The latter is anterior globe displacement due to a space occupying orbital mass. In this situation, the globe is typically normal in most ways apart from being anteriorly displaced. There is typically minimal scleral injection, a normal cornea, normal PLR, and normal visual reflexes. The third eyelid is elevated and there is a reduced ability to retropulse the globe. Ophthalmoscopy may reveal a scleral indentation which confirms an orbital lesion. If there is still doubt, the horizontal diameter of the cornea can be measured with calipers and compared to the fellow eye.

Other diagnostic tests utilized in the ophthalmic examination include a menace response, dazzle reflex (bright light used to elicit a blink), pupilary light reflex, assessment of resting pupil size, and tonometry. It is important to remember that these tests are not perfect for evaluating the presence of vision as some normally visual dogs may not have a positive menace or dazzle, especially if they are stressed. Gonioscopy (evaluation of the iridocorneal angle) can be performed on the contralateral eye to assess the anatomic predisposition to developing glaucoma.

Tonometry is the main diagnostic tool for diagnosing glaucoma, but it is important to remember the limitations and potential sources of error of this test, regardless of which instrument is used. Several things should be noted prior to taking a reading that could influence the interpretation. First, the dog's emotional state is important. A dog that is overly stressed and worked up can have a falsely elevated pressure. Second, the restraint technique is very important. Ideally, there should be minimal restraint and the dog should be calm. Excessive pressure around the neck or eyelids can elevate the tonometry reading. Third, the health of the cornea can affect the reading. Tonometers are indirect measures of intraocular pressure and are calibrated based on normal corneal structure and firmness. Excessive cornea fibrosis, as with advanced keratoconjunctivitis sicca, or severe corneal edema may affect the measurement. The Tonopen is the most commonly used instrument in general practice today and is very accurate when used correctly. It is an applanation tonometer that estimates the intraocular pressure based on the amount of pressure required to flatten a given area of the cornea. After application of topical anesthesia, the tip of the instrument is brought toward the center of the cornea (or the most "normal" area if significant corneal pathology is present). The tip must be perpendicular to the corneal surface and should make VERY LIGHT contact. If you see the cornea indent when it is touched, you are pressing too hard. The instrument will take several readings and then display an average measurement along with a percentage error. The error should be less than 5% to feel confident in the measuremet. There is a 2 mmHg margin of error for this instrument. A newer tonometer that is becoming increasingly popular is the TonoVet. This is a rebound tonometer that estimates intraocular pressure by measuring the amount of reverberation in a small probe after it bounces off the corneal surface. This machine is very easy to use and does not require topical anesthesia. Most studies to date have shown comparable accuracy with the tonopen.

Once the diagnosis of primary glaucoma has been made, the next step is to determine if it is an acute or chronic case. The patient history, specifically when the owners noticed either a change in appearance of the eye or a change in the dog's behavior, is critical in making this assessment. Chronic glaucoma is identified by an enlarged globe, lens subluxation (aphakic crescent), and a recessed or atrophied optic disk. Furthermore, dogs with chronic glaucoma often show no outward signs of ocular discomfort and the owner will usually report that they seem fine at home. However, most of these dogs are reported to be slightly more lethargic and spend more time throughout the day sleeping. Conversely, dogs in an acute glaucoma episode are typically much more outwardly uncomfortable as evidenced by blepharospasm, vocalizing upon palpation around the eye, and third eyelid elevation. There is typically intense scleral and conjunctival hyperemia and diffuse corneal edema. The pupil is dilated and the optic nerve may be swollen and gray. Acute glaucoma represents a true emergency situation and must be treated aggressively if vision is to be saved.

There are several classes of medications used for glaucoma management. Miotics, such as pilocarpine and Demecarium Bromide, help to increase aqueous outflow by opening the iridocorneal angle and the ciliary cleft. Beta blockers, such as Timolol and Betaxolol, decrease aqueous formation at the ciliary body by an unknown mechanism. These classes of medications have the benefit of being affordable and effective in mild cases of glaucoma. Carbonic anhydrase inhibitors (CAI) are a commonly used class of drugs. They decrease aqueous humor production by inhibiting the enzyme catalyst in the production of bicarbonate. Oral varieties of this class, such as acetazolamide and methazolamide, have been in use for many years. While effective, there are multiple systemic side effects possible, especially at the higher doses, including metabolic acidosis, diuresis, and GI upset. Topical CAIs include Dorzolamide (Trusopt) and Brinzolamide (Azopt). These medications have been shown to be as effective as the oral varieties without the potential side effects. Dorzolamide has recently become available as a generic, thus making this a more affordable option. Prostaglandin analogues represent the newest and most promising class. Latanoprost (Xalatan), Travaprost (Travatan), and Bimatoprost (Lumigan) are several commonly used examples of this class. These drugs can have dramatic hypotensive effects at a once or twice daily dosing in dogs, but have been shown to have minimal effects in cats. They work through several proposed mechanisms. The primary mode of action is to increase uveoscleral outflow of aqueous by modifying the extracellular matrix in the ciliary muscle. They also have potent miotic effects in dogs which may increase conventional outflow. These are excellent drugs to use in an emergency situation with acute primary glaucoma. Due to their miotic effect, they should be used with caution in eyes with significant uveitis and avoided in eyes with an anterior lens luxation. In many dogs with primary glaucoma, combinations of medications may be required to maintain the intraocular pressure in the desired range (10-14 mmHg). I treat aggressively at first and frequently recheck the pressure to titrate the medication to the desired effect. Prophylactic treatment of the normotensive eye is important in attempting to delay the onset of glaucoma and preserve vision. Studies have shown several different medications to significantly delay the onset of glaucoma when compared to untreated animals.

Hyperosmotic agents are commonly used medications, primarily in emergency situations. They are systemic medications that work by increasing the plasma osmolality, resulting in a flow of water from the intraocular compartments to the blood by diffusion. This results in decreased vitreous volume and posterior displacement of the lens which opens the iridocorneal angle. They will not be effective in cases of secondary glaucoma due to uveitis. Mannitol is the most common example. It is given by intravenously at a dose of 1-2 g/kg over 15-20 minutes. Water should be withheld for at least 4 hours after administration. Glycerin is another example and can be given orally 1-2 g/kg. Vomiting is common, especially if it is given too fast or at higher doses.

There are several surgical options for glaucoma. Too often, surgery is discussed in glaucoma only after vision has been lost and the animal is in discomfort from the uncontrolled glaucoma. Several options exist for this situation, including enucleation, intraocular prosthetic, cyclocryothermy, or chemical ciliary body ablation. The goal of all of these procedures is to improve the patient's comfort and eliminate the need for chronic, expensive medications. In eyes that are potentially visual, several other surgical options exist. The most common and widespread procedure is a transcleral cyclophotocoagulation using a diode laser. This procedure targets the ciliary body processes to decrease aqueous production. In recent years, endoscopic cyclophotocoagulation has become available, allowing more precise targeting of the ciliary processes and a more predictable result. Goniovalve implantation has been used for many years in people, but has historically had poor long term success rates in dogs due to conjunctival fibrosis around the shunt. However, a recent study suggested that the majority of patients can maintain vision and low intraocular pressures for over a year with valve placement and this option may become more commonplace. Newer surgical techniques, whereby the aqueous is drained into the frontal sinus, or the shunt is combined with cyclophotocoagulation and lens phacoemulsification, are having promising results and allowing dogs to remain visual and the glaucoma controlled for several years in some cases.

Unfortunately, most eyes with glaucoma ultimately lose vision, despite aggressive medical and surgical treatments. However, continual advances in medical and surgical options are expanding our tools to fight this frustrating disease and allowing us to preserve vision for increasingly extended periods of time.