Glaucoma is a multifactorial disease characterized by an elevation of intraocular pressure (IOP) beyond that which is compatible with the health of the eye. In addition to direct damage from elevated IOP, neurotoxic and ischemic insults occurring with glaucoma eventually result in permanent vision loss through progressive death of retinal ganglion cells and their axons in the optic nerve. Ocular pain and blindness results if/when the patient becomes refractory to medical and/or surgical management for glaucoma.

Anatomy/Physiology

Aqueous humor is produced by the ciliary body processes through active secretion and passive diffusion (also dialysis and ultrafiltration). Aqueous humor then flows anteriorly through the pupil and exits the iridocorneal angle (filtration angle) of the eye. Aqueous humor production (inflow) and outflow must remain in constant equilibrium, or marked fluctuations in IOP will occur. Glaucoma occurs when outflow of aqueous humor has been obstructed, and the IOP rises secondarily. Hypersecretory glaucoma (i.e., increased aqueous production) is not described in domestic animals. The peripheral cornea, anterior sclera, base of the iris, and anterior ciliary body all border the filtration angle. In domestic animals, aqueous humor flows through the pectinate ligaments to enter the filtration angle (also called ciliary cleft). Aqueous exits the angle by conventional or unconventional outflow. With conventional outflow, aqueous enters the uveal trabecular meshwork and escapes the eye through the scleral venous plexus (analogous to Schlemm's canal in primates). With unconventional outflow, aqueous diffuses through the iris and ciliary body musculature to enter the suprachoroidal space and posterior choroidal circulation.

Classification of Glaucoma

Glaucoma is generally classified as a primary or secondary disease. Regardless of the classification, reduction in aqueous humor drainage from the eye is the cause for IOP elevation. Primary, hereditary, or breed-related glaucoma is most commonly seen in purebred dogs, rarely observed in cats. Primary glaucoma results from an anatomic malformation of the aqueous humor drainage angle (narrow angle glaucoma or goniodysgenesis) or an accumulation of abnormal glycosaminoglycans in the trabecular meshwork causing increased aqueous outflow resistance (open angle glaucoma). In primary glaucoma the clinical signs are generally characteristic for the stage (or chronicity) of the disease. It is on the basis of these characteristic stages that treatment is usually prescribed.

Early, Non-Congestive Glaucoma

In the early stages of glaucoma the intraocular pressure is between the normal range of 10–25 mm Hg and less than 45–50 mm Hg. The only clinical signs that may be present during this stage are episcleral hyperemia with concurrent conjunctival hyperemia and sometimes, signs of ocular pain (lacrimation, blepharospasm). It is at this stage of disease that glaucoma is frequently misdiagnosed, but it is the stage of disease that treatment is most effective. Diagnosis requires that tonometry be done.

Acute Congestive Glaucoma

When the intraocular pressure reaches 45–50 mm Hg the blood supply to the anterior segment becomes compromised. As a consequence the pupil characteristically dilates to mid-range or slightly greater and unresponsive, further compromising aqueous humor outflow which leads to further increases in intraocular pressure. This is referred to as acute congestive glaucoma. The characteristic clinical signs are pupillary dilation, corneal edema (due to increased hydrostatic pressure against the corneal endothelium), scleral vascular congestion, behavioral changes, optic nerve edema with peripapillary retinal edema and hemorrhage, and vision loss. During this stage of the disease, permanent retinal damage and vision loss will occur within 24–36 hours.

End Stage (Absolute) Glaucoma

Characteristic signs of end stage glaucoma are buphthalmia, scleral congestion, breaks in Descemet's membrane (corneal stria), lens subluxations, cataract, optic nerve cupping and atrophy, tapetal hyperreflectivity, and blindness. With rare exceptions, an enlarged eye is a blind eye.

Secondary glaucoma occurs following various insults to the eye, and specifically, the filtration angle. Some causes of secondary glaucoma include anterior lens luxation, uveitis, aphakia, hyphema, pupillary block, intraocular neoplasia, and trauma. Aqueous outflow obstruction in secondary glaucoma may be related to pre-iridal fibrovascular membrane formation, peripheral anterior synechia, cellular deposition in the iridocorneal angle, and pupillary block mechanisms. Secondary glaucoma is often unilateral, although bilateral glaucoma may result if the underlying disease afflicts both eyes.

Intraocular Pressure

Tonometry is the measurement of intraocular pressure (IOP). Normal intraocular pressure ranges:

Dog 12–25 mm Hg

Cat 12–27 mm Hg

IOP is affected by technique, age, diurnal variation, blood pressure, and drugs. However, remember that these are just numbers - look at your patient! Dr. G's Rule of Thumb: if there is greater than 5 mm Hg pressure difference between eyes (even if pressures in normal IOP range OU), don't assume that the patient is "normal."

Digital tonometry (i.e., pressing fingers on the globe) is highly a qualitative rather than a quantitative technique and is of little value in the vast majority of cases. A quantitative technique is required for accurate diagnosis and for monitoring an animal's response to therapy. Schiötz tonometry is readily available, inexpensive, but rarely used for a variety of reasons. Applanation tonometry is easier to perform and is more accurate than either digital or Schiötz tonometry.

Spurious (usually elevated) tonometry values may be obtained related to:

1.  Patient excitement/fear/stress

2.  Excessive physical restraint

3.  Blepharospasm or globe retraction

4.  Applying digital pressure to the eye when holding eyelids open

Medical Therapy of Glaucoma

Although there are several important factors involved in the pathogenesis and progression of glaucoma, a common feature of the condition in all cases in dogs is abnormally high IOP. Accordingly, most attempts at management of glaucoma are currently directed towards controlling IOP. However, with increasing recognition of vascular and neurotoxic factors and their respective roles in the vision loss associated with glaucoma, new directions in canine glaucoma management are beginning to emerge. All treatments for glaucoma (medical or surgical) work by one of two mechanisms. That is by either increasing aqueous outflow from the eye, or by decreasing aqueous inflow (i.e., production). Five classes of glaucoma drugs are commonly used: 1) cholinergics, 2) adrenergics, 3) carbonic anhydrase inhibitors, 4) osmotic agents, and 5) prostaglandins. These drugs must usually be used in various combinations to effectively lower and maintain a normal IOP.

Hypotensive Agents

1) Cholinergics

Cholinergics are parasympathomimetic drugs that work primarily by opening the filtration angle and increasing aqueous outflow. They do so by stimulating contraction of ciliary body musculature that inserts anteriorly in the filtration angle. There are both direct and indirect-acting cholinergic drugs. Direct acting drugs (e.g., pilocarpine) are structural analogues of acetylcholine and stimulate the muscle directly (thus the term cholinergic). Indirect acting drugs are acetylcholinesterase inhibitors. Examples: [sic].

Note: The cholinergic agents cause mild ocular irritation, and they may worsen a pre-existing uveitis. They should be used judiciously to treat glaucoma where uveitis is a substantial factor. Concurrent application of topical corticosteroids may be deemed necessary to reduce inflammation. Also, atropine is an anticholinergic drug often used to treat corneal ulcers and uveitis. However, atropine is antidotal to the cholinergic drugs, and therefore, topically applied atropine is contraindicated in the presence of glaucoma.

2) Adrenergic Drugs

Adrenergic drugs act on α and β-adrenergic receptors within the ciliary body and filtration angle to reduce IOP, but their exact mechanisms of action are still under investigation. Two classes are commonly used; the adrenergic agonists (i.e., epinephrine derivatives) and the adrenergic antagonists (i.e., beta blockers). Although it may seem contradictory, both types of adrenergic drugs may be used simultaneously or in combination with other drugs (e.g., cholinergics) where they are considered synergistic in reducing IOP. Examples: [sic].

3) Carbonic Anhydrase Inhibitor

Carbonic anhydrase inhibitor (CAI) drugs are diuretics that reduce IOP by reducing aqueous humor production rather than by diuresis. This is because the enzyme, carbonic anhydrase, is required for normal aqueous humor production. CAI drugs are usually used in combination with other hypotensive agents. Potential side effects include metabolic acidosis, gastrointestinal signs, panting, hypokalemia, and even behavioral changes. Furosemide is a diuretic that works through a different mechanism of action and is not effective in therapy of glaucoma.

4) Osmotic Agents

The osmotic agents (i.e., mannitol, glycerin) work by osmotic properties to remove fluid from the eye. Prostaglandins have largely replaced their use in veterinary ophthalmology.

5) Prostaglandins

Prostaglandins reduce intraocular pressure primarily by increasing outflow of aqueous humor. They can cause extreme miosis. Prostaglandins are capable of rapidly and dramatically reducing IOP in acute glaucoma, so is very effective for emergency IOP reduction and may be used for this indication in lieu of hyperosmotic medications.

6) Other

Treat/manage underlying condition if glaucoma is secondary to another ophthalmic disease process. Use of medications to provide pain relief (e.g., NSAIDs, narcotic analgesics) is appropriate with intractable high IOP.

References

References are available upon request.