Definition and Classification
Glaucoma is one of the leading causes of blindness in small animals affecting 1–2% of our canine patients. It is also a cause of ocular pain and is the most common reason for enucleation in dogs. Canine glaucoma is defined as “an elevation in intraocular pressure (IOP) beyond that which is compatible with healthy ocular tissues” and encompasses a diverse group of diseases associated with an increase in intraocular pressure resulting in retinal ganglion cell death. Canine glaucomas are classified on the basis of the possible cause (congenital, primary or secondary), the gonioscopic appearance of the drainage angle (open, narrow or closed as well as the degree of pectinate ligament dysplasia) and stage of the disease (acute, subacute, or chronic).
Congenital glaucoma develops early in life (<1 year of age) and is associated with severe abnormalities of the iridocorneal angle (ICA).
Primary glaucoma is inherited and several breeds appear to be predisposed to developing the disease including the Cocker Spaniel, Basset Hound, Chow Chow, Shar-Pei, Boston Terrier, Husky, Poodle, Akita, Malamute, Chihuahua, Beagle, and several others. Primary glaucoma is not associated with any antecedent eye condition, but have been associated with dysgenesis of mesenchymal structures (pectinate ligament dysplasia) in the ICA and/or narrowing or closure of the ICA and/or the ciliary cleft (CC) in some breeds. Despite the suspicion of an inherited defect clinical signs of primary glaucoma usually do not become evident until relatively late in life. Primary glaucoma is a bilateral disease although onset of disease varies between eyes (it takes on average 8 months from the first eye is diagnosed till the other eye is showing clinical signs).
Secondary glaucoma results from obstruction of the normal flow of fluid out of the eye caused by other intraocular diseases. The signs include those usually associated with glaucoma (see below), along with associated signs of the underlying problem (i.e., aqueous flare, swollen iris, hypopyon, lens dislocation, iridal mass, etc.). Anything capable of obstructing the flow of aqueous through the pupil or its exit through the trabecular mesh work can cause secondary glaucoma. Secondary glaucoma is the most frequently encountered type of glaucoma in veterinary medicine and occur two to three times as frequently as primary glaucoma. Multiple eye conditions are known to cause secondary glaucoma including anterior uveitis, primary lens luxation, trauma to the globe, intraocular surgery, intraocular neoplasia, intraocular cysts, hyphema, cataracts and ocular melanosis. Depending on the cause of secondary glaucoma this condition may be treatable if the underlying condition can be treated and the intraocular pressure reduced in a timely manner.
Diagnosis
Acute clinical symptoms include episcleral injection, corneal edema, mydriasis, varying degrees of pain, and in the early stages there is often no obvious vision loss. Intraocular pressures can vary throughout the day. In early stages of glaucoma dogs might have intermittent pressures spikes and therefore initial IOPs measured in the clinic may be normal or high normal. Chronic glaucoma symptoms include all the acute symptoms described above as well as varying degrees of buphthalmos, lens subluxation, or luxation, a dark and cupped optic nerve head, and loss of vision.
Tonometry combined with clinical signs is essential in diagnosing glaucoma. An IOP above 25 mm Hg as measured by tonometry and clinical signs as described above is consistent with a diagnosis of glaucoma. Proper technique is required to obtain accurate tonometry reading as falsely elevated pressured can occur if there is pressure on the neck or the globe itself or if the head is positioned below the heart. The most commonly used tonometers utilized in veterinary medicine are the rebound tonometers and the applanation tonometers, both of which can obtain accurate and reliable IOP measurements in dogs and are relatively easy to use. While topical anesthesia is required for applanation tonometry it is not necessary for rebound tonometry.
Therapy
Therapeutic targets for canine glaucomas include reduction of fluid production and improvement of fluid outflow.
Emergency Management
If a dog develops acute glaucoma, the goal is to reduce the IOP as soon as possible to prevent permanent optic nerve damage and loss of vision. The most commonly used strategies to decrease IOP in acute glaucomas include hyperosmotic agents, prostaglandin analogues.
Topical prostaglandin analogues decrease IOP by increasing outflow. These are very potent IOP reducing medications and are often very effective in rapidly reducing IOP. Prostaglandin analogues might exacerbate uveitis and causes miosis and are contraindicated in patients with anterior lens luxation, feline aqueous humor misdirection syndrome and other causes of pupillary block glaucoma as miosis will exacerbate IOP elevation in such cases. Therefore, they should not be used if any of these conditions cannot be ruled out. Latanoprost 0.005% (Xalatan) is currently more commonly employed in veterinary medicine (compared to bimatoprost or travoprost) and is usually administered every 12 hours.
Systemic Hyperosmotic Agents
These medications can be used to treat acute glaucoma by dehydrating the vitreous to decrease IOP. The effect of these agents is transient only. Hyperosmotic agents are contraindicated in patients with cardiovascular disease or renal insufficiency. Mannitol is safe to use in diabetics whereas glycerol should not be used in diabetics. Nausea is commo n in patients treated with glycerin. They are primarily used to quickly reduce IOP in acute glaucoma and can help allow time for topically applied antiglaucoma medications to take effect. The agents that are most commonly used are mannitol (1–2 g/kg) and oral glycerol (1–2 g/kg). Ocular hypotensive effects occur within 30 minutes and may last for 6–10 hours.
Aqueocentesis can be performed on an anesthetized patient by a veterinary ophthalmologist if prostaglandin analogues and hyperosmotic agents are contraindicated or not effective, but the effect of this is often very short and there is a risk of hemorrhage or damage to intraocular structures with this technique.
Chronic Management
Chronic management can include both medical and surgical therapies and the target IOP should ideally be <15 mm Hg as studies suggest that even high normal IOPs can be damaging in eyes who have had previous pressure spikes. The most commonly used strategies to decrease IOP in chronic glaucomas include carbonic anhydrase inhibitors, beta-blockers, and prostaglandin analogues.
Prostaglandin analogues are the most potent hypotensive agents in this group and are usually given every 12 hours (see above).
Topical carbonic anhydrase inhibitors (CAIs) decrease production of aqueous humor. These include dorzolamide (Trusopt) and brinzolamide (Azopt) and are administered every 8 hours. Dorzolamide can be combined with timolol to form Cosopt which is administered every 12 hours to obtain similar hypotensive effects as TIO dosing of dorzolamide alone. Although these drops are typically safe to use local irritation can occur in some patients.
Systemic CAIs includes acetazolamide and methazolamide and reduced production of aqueous humor. These medications cause systemic acidosis, which can lead to excessive panting and vomiting, and diarrhea. They can also cause mild hypokalemia. They are usually given 2–3 times daily. Methazolamide (3–4 mg/kg PO BID) is often preferred over acetazolamide since the latter can have more severe adverse effects.
Beta-blockers lower IOP by reducing aqueous humor production, although the exact mechanism has yet to be elucidated. They include timolol and betaxolol. They should be used 2–3 times daily. Adverse effects include bradycardia and they should be avoided in asthmatic patients. Timolol 0.5% is the most commonly employed in veterinary medicine. It is nonspecific, meaning it blocks both B1 and B2 receptors. Timolol has been shown to lower IOP in dogs, cats, and horses. However, potency is minimal when used alone in comparison with CAIs and prostaglandin analogues in veterinary species.
Surgical management is often combined with medical management when medical management is starting to fail. If the animal is still visual surgical management strategies can include gonioimplants, iridencleisis, and cyclodialysis. In endstage glaucoma where the eye is blind and painful, enucleation or evisceration and placement of an intrascleral prosthesis can be performed. lntravitreal injection of gentamicin or cidofovir is usually reserved for cases in which surgery cannot be performed.
Prophylactic Medication
In a multicenter clinical topical 0.5% betaxolol twice daily or topical 0.25% demecarium bromide once daily and a topical corticosteroid once daily, significantly delayed or prevented the onset of glaucoma in the second eye in dogs diagnosed with primary glaucoma in one eye. Untreated control dogs developed glaucoma in the second eye earlier (median: 8 months) than eyes treated with prophylactic medication (median: approximately 31 months).