Statement / BY-Line

Aqueous Humor Dynamics and Intraocular Pressure

Aqueous humor is produced in the ciliary body by active secretion and ultrafiltration of plasma. The enzyme carbonic anhydrase participates in the energy-dependent secretory phase of aqueous production. Most of the aqueous humor flows from the posterior chamber, through the pupil, to the anterior chamber, and exits at the iridocorneal angle into the intrascleral venous plexus. A small percentage of the outflow in dogs and cats (uveoscleral or nonconventional) also exits through the iris, ciliary body, choroid, and sclera. The balance between formation and drainage of aqueous humor maintains intraocular pressure (IOP) within a normal range of 15 to 25 mm Hg.

By definition, glaucoma is increased IOP with associated visual deficits. In most cases in dogs and cats, glaucoma is caused by obstruction of the aqueous humor outflow pathways. It remains a challenge to the veterinarian to detect the early subtle disturbances of glaucoma and to effectively treat this condition. Delayed or inadequate therapy can lead to irreversible blindness and a painful, cosmetically unacceptable eye.

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Pathologic Effects of Glaucoma

All ocular tissues are eventually affected by the elevated IOP. The presence, individually or as a group, of a "red eye," corneal edema, mydriasis, blepharospasm, blindness, and buphthalmos can be explained by the increased IOP. If the IOP cannot be reduced, an overall increase in the size of the globe may result (buphthalmos). This change may occur more rapidly in young dogs and cats. Ruptures of the cornea's inner limiting (Descemet's) membrane may accompany the elevated corneal tension and buphthalmos to produce multiple, linear corneal striae. Persistent corneal endothelial damage can result in corneal edema. Buphthalmos causes increased tension on the lens zonules. Zonular disinsertion results in lens subluxation or luxation.

Pupillary light reflexes may be normal, slow, or absent in early glaucoma, depending on the functional status of the iris sphincter muscle, retina, and optic nerve. Acute elevation of IOP (greater than 45 mm Hg) causes paralysis of the iris sphincter and dilator muscles. Prolonged or recurrent elevations of IOP lead to degeneration of the retina and optic nerve, with excavation or cupping of the optic nerve head.

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Types of Glaucoma

Glaucoma is divided into primary (including congenital) and secondary categories. The iridocorneal angle may be open, narrow, or closed in either type. Abnormal development of the iridocorneal angle (goniodysgenesis) has been noted in some breeds. Evaluation of the iridocorneal angle is performed with gonioscopy in the dog but may be performed with focal illumination in the cat.

Primary glaucoma in dogs is a breed-related, hereditary condition. Predisposition to primary open-angle glaucoma in the Persian and Siamese cat breeds has also been noted, but in the author's experience, domestic short-hairs are more often affected. In both dogs and cats, affected animals may present with only one eye involved, but the risk is very high for development of glaucoma in the other eye.

Secondary glaucoma is more commonly encountered than primary glaucoma in dogs and cats. The elevated IOP results from other disease processes within the eye. The glaucoma may be open or closed angle, and in some instances is associated with pupillary block. The condition tends to be unilateral without an inherited basis.

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Clinical Signs of Acute and Chronic Glaucoma

Figure 11 Lens lux with ciliary process

Figure 12 Optic nerve atrophy with cupping

The presentation of a patient with a painful, red eye requires that glaucoma be ruled out among the possible diagnoses of conjunctivitis, uveitis, or keratitis. Pain manifested as depression, anorexia, rubbing at the eye, and squinting is common. Congestion of episcleral vessels, diffuse corneal edema, a fixed and dilated pupil, and blindness will occur as the IOP increases. The onset of clinical signs in cats is often insidious, as cats are less likely to demonstrate the acute intense corneal edema and episcleral congestion exhibited in dogs. Signs of chronic glaucoma are dramatic. They include combinations of the early signs with buphthalmos, lagophthalmos, exposure keratitis, luxated lens, corneal striae, optic nerve atrophy with cupping, and retinal atrophy (Figure 11 and 12).

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Tonometry

IOP must be accurately measured to diagnose glaucoma. The normal canine and feline IOP is 15 to 25 mm Hg. An IOP greater than 30 mm Hg is considered pathologic and diagnostic for this condition. It is possible to crudely evaluate IOP digitally if the IOP is very high or low, but this is not satisfactory to evaluate clinical response to therapy. The Schiotz's indentation tonometer allows the practitioner to diagnose and evaluate treatment in small animals with glaucoma. The human Schiotz table is accurate for the dog. The Tonopen applanation tonometer has made it much easier to diagnose and treat the animal glaucomas.

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Treatment

The objectives of therapy are to maintain vision and eliminate pain by (1) increasing aqueous outflow, (2) decreasing aqueous production, and (3) preventing or delaying glaucoma in the other eye. Primary glaucoma may be more difficult to control than secondary glaucoma because it is eventually bilateral, and blindness is a possible sequela despite therapy. I nevertheless recommend prophylactic therapy for the unaffected eye in animals afflicted with unilateral primary glaucoma. In secondary glaucoma, the inciting cause is identified and either removed or suppressed. Topical corticosteroids may be indicated to diminish inflammation when nonseptic anterior uveitis is also present.

Medical therapy is the treatment of choice in animals with a history of acute primary or secondary glaucoma. Treatment should be instituted to reduce the IOP as soon as possible to alleviate pain and preserve vision. Animals presented with a history and clinical signs of chronic glaucoma should be considered for medical and surgical therapy. The iridocorneal angle gradually closes in most types of glaucoma and the initially effective treatment becomes inadequate. Surgery is the only option available when vision continues to diminish in spite of maximum medical therapy.

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Medical Therapy

Multiple drug therapy to decrease IOP by reducing production of aqueous humor and diminishing the resistance to aqueous humor outflow is the most effective approach.

Treatment of the ocularly normotensive eye in a purebreed dog with apparently unilateral glaucoma can delay the onset of overt ocular hypertension in the second eye a median of 30 months. Betaxolol and demecarium were each effective at delaying onset of glaucoma in dogs when administered topically.

Carbonic-anhydrase inhibitors reduce ciliary-body production of aqueous humor independent of diuresis. These drugs can cause metabolic acidosis, and the dosage should be carefully adjusted to minimize side effects, which include panting, nausea, and vomiting. Non-carbonic anhydrase-inhibiting diuretics do not significantly reduce IOP!

Topical parasympathomimetic drugs act primarily to cause ciliary muscle contraction, increasing the outflow of aqueous humor. This action is independent of their effect on the iris sphincter muscle. Parasympathomimetics are contraindicated in glaucoma associated with anterior uveitis. They should be used with caution in glaucoma associated with anterior lens luxations. Sympathomimetic drugs reduce IOP by increasing production of aqueous humor and increasing outflow. These drugs are most effective in reducing IOP when combined with parasympathomimetics. ß-adrenergic antagonists decrease production of aqueous humor, but the specific mechanism of action is not known. The ocular hypotensive effects are additive to those of carbonic-anhydrase inhibitors and parasympathomimetics.

Oral and intravenous hyperosmotic agents lower IOP rapidly by osmotically reducing the volume of the vitreous. They are used in the emergency treatment of acute glaucoma but are ineffective or impractical for long-term or maintenance therapy.

Intravitreal glutamate levels are elevated in canine glaucoma. Glutamate is extremely toxic to the retinal ganglion cells. It overstimulates them. Glutamate excitotoxicity is mediated by intraneuronal calcium influx. Intraneuronal homeostatic imbalance induces apoptosis and cell death. The use of glutamate receptor antagonists and calcium channel blocking drugs to protect the retina and optic nerve is being studied.

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Surgical Therapy

Surgical procedures are divided into those that increase aqueous humor outflow and those that decrease aqueous humor production. Surgery should be considered when the IOP cannot be controlled medically, especially when vision is still present. Anteriorly luxated lenses should be removed in functioning eyes to relieve pupillary block and prevent corneal damage due to the lens touching the corneal endothelium.

Cyclocryotherapy has been found to be effective in decreasing production of aqueous humor by the transcleral freezing of the ciliary body with nitrous oxide. This may require repeated applications for optimal IOP control.

The YAG laser is preferred over nitrous oxide by the author to cause ciliary body necrosis (cyclophotocoagulation). The eye is less irritated postoperatively and the IOP stays low for longer periods of time. Only 6% of dogs with cyclophotocoagulation will still be visual at one year after installation.

Gonioimplant. Several types are available to passively shunt aqueous humor to the subconjunctival space. They tend to fail by fibrosing shut in dogs. Only 18% of dogs with gonioimplants will still be visual at one year after installation.

Enucleation or evisceration with prosthetic silicone implants is indicated when vision is lost in uncontrolled glaucoma. The source of pain is removed, and no further medication is necessary. The cosmetic appearance of the prosthetic implant is sometimes preferred to that of enucleation. Prosthetic implants should not be used when glaucoma is or may be associated with intraocular infection or neoplasia.

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Vitreous Aspiration and Pharmacological Ciliary Body Destruction

Vitreous aspiration and pharmacological destruction of the ciliary body by intravitreal injection of gentamicin combined with dexamethasone has been used for the management of chronic glaucoma. This procedure may be indicated in permanently blind glaucomatous eyes without intraocular neoplasia or infection.