by Noelle La Croix, DVM, Dip. ACVO
Glaucoma is a disease of the optic nerve in which retinal ganglion cells atrophy, often resulting in blindness (Figure 1). Elevated intraocular pressure (IOP) is a major risk factor for the development of glaucoma. The key to glaucoma management is to determine its underlying cause. Different etiologies require different treatments. A veterinary ophthalmologist will explore both surgical and pharmaceutical options to reduce IOP. This article will summarize the most common antiglaucoma medications used by a veterinary ophthalmologist to preserve vision in dogs.
There are a number of variables that contribute to IOP simplified in a single equation as: IOP = aqueous humor production – (conventional + unconventional outflow). Antiglaucoma medications lower IOP by decreasing aqueous humor production, increasing conventional outflow, and/or increasing unconventional outflow. The greatest reductions in IOP will be achieved when all variables (rather than a single variable) in the equation are changed. Combinations of medications are therefore used to achieve the greatest reductions. For example the drug Trusopt, which decreases aqueous humor production, is best used in combination with Xalatan, which increases both unconventional and conventional outflow. The combination of Trusopt and Timolol is less effective at reducing IOP as both drugs only reduce aqueous humor production.
Decreasing aqueous humor production
Antiglaucoma medications which decrease aqueous humor production include beta-blockers (Timolol, Betaxolol) and carbonic anhydrase inhibitors (Azopt, Trusopt, methazolamide, Daranide, Diamox).
The precise mechanisms by which the beta-blockers Timolol 0.5% and Betaxolol decrease aqueous humor production are unknown. Prophylactic administration of Betaxolol has been shown to prevent glaucoma in canine goniodysgenesis. Beta-blockers are contra-indicated in animals with severe heart failure or bronchial asthma as these drugs may exert cardiopulmonary side effects.
Carbonic anhydrase inhibitors decrease bicarbonate ion production by ciliary epithelia, thereby decreasing sodium and water transport into the posterior chamber. These drugs are available in topical (Azopt, Trusopt) and oral forms (methazolamide, Daranide, Diamox). In glaucomatous dogs, methazolamide has been shown to decrease IOP at a lower dosage than Daranide or Diamox. The oral carbonic anhydrase inhibitors can cause systemic side effects including diuresis, gastrointestinal disturbances, hypokalemia, and increased respiratory rates secondary to metabolic acidosis. Administration of both oral and topical forms do not substantially lower IOP over either drug used alone.
Decreasing aqueous humor production and increasing conventional outflow
Osmotic agents (oral glycerol/glycerin, intravenous mannitol) increase blood plasma osmolarity drawing fluid from intraocular spaces. The ultra-filtration process contributing to aqueous humor production decreases. The vitreous shrinks displacing the iris/lens plane posteriorly. This shrinkage widens the iridocorneal angle and thereby increases conventional outflow. Following administration of an osmotic agent, the patient is deprived of water for 4 hours to maximally reduce IOP. Osmotic agents are limited to short-term emergency treatment of glaucoma as chronic use can cause renal damage. The drugs should not be used in patients with pre-existing heart or renal failure. Glycerol/glycerin cannot be prescribed to diabetic patients that will metabolize it to glucose.
Increasing conventional outflow
Parasympathomimetics (pilocarpine, demecarium bromide) are thought to increase conventional outflow by affecting the ciliary body. Pilocarpine mimics acetylcholine and directly causes contraction of the ciliary muscles. It is most commonly prescribed as a 1% solution. Demecarium bromide inhibits acetylcholinesterase increasing the lifespan of acetylcholine at the neuromuscular junctions of the ciliary body. It is compounded in 0.125% for small dogs (< 10 lb) to prevent systemic toxicity, and used at 0.25% for larger dogs. Demecarium bromide has been shown to delay the onset of glaucoma in dogs with goniodysgenesis.
Systemic signs of parasympathomimetic toxicity include: lacrimation, sweating, respiratory distress, gastrointestinal spasm, nausea, vomiting, diarrhea, atrioventricular block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, and tremor.
Increasing conventional and unconventional outflow
The prostaglandin analogs (Xalatan, Travatan, Lumigan) increase both conventional and unconventional outflow thereby decreasing IOP. In an acute closed-angle glaucoma spike these drugs are used to induce miosis. Miosis will break any pupillary blockage releasing fluid trapped behind the iris. Miosis will also open a collapsed ciliary cleft increasing conventional outflow. Prostaglandin analogs also remodel the extracellular matrix of the ciliary muscle increasing unconventional (uveoscleral) outflow. The precise mechanism of this remodeling is not completely understood.
This review of anti-glaucoma medications is by no means extensive. However, it may help clarify your veterinary ophthalmologist’s patient-specific and balanced approach to IOP reduction. A veterinary ophthalmologist should always be consulted when treating a glaucomatous eye with the potential of vision.
Noelle La Croix, DVM, Dip. ACVO
Veterinary Medical Center of Long Island
75 Sunrise Highway
West Islip, New York 11795
(631) 587-0800; fax (631) 587-2006
Figure 1: A glaucomatous left eye of a 6-year-old mixed breed dog.