Hereditary Glaucoma
World Small Animal Veterinary Association World Congress Proceedings, 2006
Ron Ofri, DVM, PhD, DECVO
Koret School of Veterinary Medicine, Hebrew University of Jerusalem
Rehovot, Israel

The definition of glaucoma is rapidly changing as our understanding of the pathogenesis of damage to the retina & optic nerve improves. However, the disease can still be generally described as an elevation in intraocular pressure (IOP) which is incompatible with normal ocular function. IOP is the result of a balance between production and drainage of aqueous humor. In clinical practice, glaucoma is caused by drainage disturbances, and cases of increased production are not recognized.

Production and Drainage of Aqueous Humor

Aqueous humor is produced in the ciliary processes from where it flows into the posterior chamber, and through the pupil into the anterior chamber. After circulating in the anterior chamber and supplying the metabolic requirements of the lens and cornea, the aqueous exits the eye through the iridocorneal angle (between the cornea and iris), which is spanned by pectinate ligaments. The drainage continues through the uveal and corneoscleral meshworks, eventually exiting the eye into systemic venous circulation

Aqueous may also exit the eye through an unconventional path, in which it diffuses through the iris and ciliary body (or through the vitreous) into the suprachoroidal space, and from there it drains into the venous circulation. The importance of this route changes between species, accounting for 15% of the total drainage in dogs and 33% in horses, but only 3% in humans.

Classifying Glaucoma

Glaucoma may be classified in one of 2 ways. Based on the cause, it may be classified as primary, where there is no other ocular disease/abnormality that affects the drainage (rather, outflow problems are due to genetic abnormalities in the drainage pathway) or secondary, where another ocular disease/abnormality (e.g., lens luxation, uveitis) decreases outflow. Alternatively, glaucoma may be classified according to the state of the drainage angle. The angle may be open (in which case the obstruction is further downstream), narrow or closed.

The 2 classifying methods complement each other, and in dogs it is possible to encounter all 4 possible combinations, e.g., primary open angle glaucoma, secondary closed angle glaucoma, etc. This talk is devoted to the inherited (i.e., primary) glaucomas.

Inherited Glaucoma

Since this disease has a strong genetic component, diagnosis of primary glaucoma in one eye mandates prophylactic treatment in the other eye.

Primary Open Angle Glaucoma

Primary, open angle glaucoma (POAG) is an inherited disease, which has been investigated extensively in the Beagle dog (in which it was shown to be an autosomal recessive disorder), but has also been documented in the Keeshond, Norwegian elkhound, poodle and other breeds.

As the name implies, the angle and pectinate ligaments are normal. It is assumed the outflow obstruction is in the uveal and corneoscleral meshworks, and is the result of biochemical changes in the basement membrane of these regions. The disease is chronic in nature, with IOP increasing slowly over many months or years. Though the dog may present with buphthalmous, or even with secondary lens luxation, vision is frequently retained in advanced stages of the disease.

Primary Narrow- and Closed-angle Glaucoma/Goniodysgenesis

Primary narrow angle glaucoma is an inherited disease in the American & English Cocker Spaniels, Flat coat, Labrador & Golden Retrievers, Basset hounds, Samoyeds, Chow-chows, Great Dane, Siberian Husky, and other breeds. A developmental abnormality results in the formation of dysplastic pectinate ligaments, which can be see as sheets of tissue spanning the drainage angle. In the first years of life, aqueous exits the eye through flow holes in the sheets, but eventually these fail, resulting in IOP elevation. Most patients present with an acute attack of glaucoma, including congestion, edema, fixed, dilated pupils and loss of sight. Though only one eye may initially be affected, both eyes should be carefully evaluated and treated. IOP can be successfully lowered, but progressive angle narrowing and closure may develop, and the long-term prognosis for vision is guarded.

Diagnosing Glaucoma

1. Measuring IOP--Tonometry

In most animal species, normal IOP range is 15-25 mm Hg. Elevation in IOP is defined as glaucoma (while low IOP is usually a sign of uveitis, due to increased unconventional outflow). IOP should be similar in the 2 eyes. Differences > 10 mm Hg between eyes may also indicate glaucoma. IOP can not be measured digitally with one's fingers. It should be recorded with using a Schiotz (indentation) or Tono-Pen (applanation) tonometer.

2. Examining the Iridocorneal Angle--Gonioscopy

It is important to examine the angle to determine the risk of glaucoma (in case of a breed with goniodysgenesis or primary glaucoma, or if the other eye developed the disease). The state of the angle may also dictate treatment--there is no point in giving drugs that open the angle in cases of open angle glaucoma, or in cases of goniodysgenesis. Drugs that reduce aqueous production, or increase unconventional outflow may be more suitable in such cases.

Gonioscopy is performed using a special lens (goniolens) which is placed on the cornea. The lens refracts the outgoing light, and allows us to visualize the entire angle, and to classify its state.

3. Based on Clinical Signs.

Glaucoma is a disease that may affect all ocular layers and structures.

1.  Pain: Glaucoma is a painful disease. The pain can be expressed as blepharospasm, or as general depression--many owners report a dramatic improvement in the animal's behavior following enucleation of a glaucomatous eye.

2.  Buphthalmous: Glaucoma may cause an increase in the size of the globe, due to stretching of the collagen fibers of the cornea and sclera. Buphthalmous is more frequent in chronic cases, and in young patients (where the sclera is more elastic and stretches more easily).

3.  Congestion of blood vessels: The eye will appear red due to congestion of vessels (see "red eye" notes).

4.  Corneal pathology: Elevated IOP damages the corneal endothelium, which is responsible for maintaining corneal dehydration, resulting in edema. The stretching of the corneal fibers in buphthalmous may cause rupture of the endothelial basement membrane. These ruptures, seen as straight white lines in the cornea, are called striate keratopathy and are pathognomonic for glaucoma.

5.  PLR: In the early stages of the disease the pupil may be slightly dilated, and PLR will be sluggish. In advanced or acute stages of the disease, the pupils are dilated and non-responsive.

6.  Lens: The lens may luxate (or sub-luxate) due to stretching and tearing of the zonules.

7.  Retina, optic nerve & vision: Glaucoma will cause atrophy of the ganglion cell layer and other inner retinal layers. This atrophy is a result of local ischemia, due to pressure on the retinal blood vessels (the outer retina is supplied by the choroid, and is less affected by ischemia). Additional damage to the ganglion cells occurs as a result of kinking of their axons as they exit the eye at the lamina cribrosa region. In this part of the eye, the effect of elevated IOP may be seen ophthalmoscopically as cupping of the optic disc. As a result of the damage to the inner (and, eventually, outer) retina, the patient will suffer progressive loss of vision, which may lead to complete blindness.

8.  End stage glaucoma: Due to chronic elevation of IOP, the ciliary body may atrophy, causing decreased aqueous production, lowering of pressure, and atrophy of the eye (phthisis bulbi).

Principles of Glaucoma Treatment

The aims of glaucoma treatment are to prevent further loss of vision and decrease the pain caused by IOP elevation. Currently, it is impossible to restore vision which has been lost due to glaucoma. Cases of primary glaucoma require lifelong treatment. The owner must understand that the aim of the therapy is to stabilize the IOP, and that the disease can never be fully cured.

Medical Therapy of Glaucoma

1.  Osmotic diuretics: These drugs are not used for long-term treatment of glaucoma. Instead, they serve for emergency lowering of pressure in cases of acute attacks. The most commonly-used drug in this category is mannitol (IV, 1-2 g/kg). The fluid is administered slowly, over 30 min., and water is withheld for 3-4 hours.

2.  Prostaglandin analogues: These drugs act by increasing the unconventional outflow. They are most effective in dog, because their effect is independent of the state of the angle (which is frequently blocked). The drugs are ineffective in cats (which lack the receptor), and are contra-indicated in uveitis. Latanoprost, travoprost and other drugs in this category are given 1-2 times daily.

3.  Carbonic anhydrase inhibitors: Carbonic anhydrase is a key enzyme in the production of aqueous humor, and therefore its inhibition will result in lower production and decreased IOP. Just like prostaglandin analogues, this effect is independent of the state of the angle. The topical form of the drug (dorzolamide, brinzolamide) has none of the systemic side-effects observed with systemic drugs. It is given twice daily. Systemic drugs, such as acetazolamide (10 mg/kg) and methazolamide (2.5-5 mg/kg) are given BID-TID. They may cause metabolic acidosis. Monitoring of side-effects and potassium levels is mandatory. Also, they are not well-tolerated in cats.

4.  Topical miotics:. These drugs increase drainage by opening the irido-corneal angle (through contraction of the iris and ciliary muscle). The most commonly-used drug in this category is pilocarpine (1-4%, BID-TID).

5.  ß blockers: These are sympatholytic drugs that reduce aqueous production by reducing flow of blood to the ciliary body. They are commonly used in humans, but their effectiveness in animals is controversial. Systemic side-effects are common in small dogs, cats, and animals with pulmonary/cardiovascular diseases. Drugs in this category include timolol, levobunolol and betaxolol (use SID-BID).

Surgical Treatment of Glaucoma

Referral ophthalmology clinics may perform surgery to increase aqueous outflow (usually by implanting drainage tubes in the eye), or to decrease aqueous production (through partial destruction of the ciliary body, using laser or cryo). However, frequently the (surgical or medical) treatment fails, and the practitioner is faced with a blind and painful eye. Patient welfare requires the removal of this eye, through enucleation or evisceration (implanting a prosthesis in an empty scleral "shell", to provide a more cosmetic appearance).

Speaker Information
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Ron Ofri, DVM, PhD, DECVO
Koret School of Veterinary Medicine
Hebrew University of Jerusalem
Rehovot, Israel

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