Glaucoma

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Glaucoma02.jpg
Glacuoma in the right eye of a dog
Glaucoma secondary to lens luxation

Glaucoma is been defined as an elevated intraocular pressure (IOP) beyond that which permits normal visual function[1].

Glaucoma is a common end point of several ophthalmic diseases. Canine glaucoma can be classified as congenital, primary, or secondary. Congenital glaucoma is rare in dogs. It is caused by abnormalities in the aqueous humor outflow pathways. Puppies generally present young (3 to 6 months of age) with an acute onset of buphthalmia and corneal edema. The disease may be unilateral or bilateral and may be associated with other ocular anomalies[2].

Primary glaucoma is considered a heritable condition in some breeds. The disease is progressive and may result from changes in the iridocorneal angle or from abnormal metabolism of the trabecular cells within the outflow pathway. Primary glaucoma is further classified as open-, narrow-, or closed-angle, based on the appearance of the drainage angle[3]. It is always a bilateral condition.

Secondary glaucoma results when another condition disrupts aqueous humor outflow. Several disease conditions can lead to secondary glaucoma, including cataract, lens luxation, hyphema, intraocular neoplasia, retinal detachment, and uveitis. In some of these conditions, the release of vasoactive factors may lead to the formation of a preiridal fibrovascular membrane and subsequent secondary glaucoma. Although secondary glaucoma is not considered heritable, some of the inciting causes do have a genetic basis (e.g., cataract, lens luxation). Dogs of breeds that are predisposed to these conditions that have developed a high IOP in one eye should have the contralateral eye routinely monitored for the development of disease[4]. Additionally, if cataract surgery is performed, postoperative glaucoma is a potential complication that can be vision threatening[5]. If secondary glaucoma can be diagnosed early and managed appropriately, vision may be preserved.

Aqueous humor is produced by the ciliary body and flows through the pupil into the anterior chamber of the eye. In dogs, most aqueous humor exits the eye through the iridocorneal angle; approximately 10% to 15% exits the eye through uveoscleral outflow. Normal intraocular pressure (IOP; range: 10 to 25 mm Hg) is maintained by an equilibrium between aqueous humor production and drainage. Canine glaucoma is usually due to a disturbance in the conventional outflow pathway that results in an increased IOP.

Clinical Signs

Glaucoma can be a painful condition. Signs of ocular pain include blepharospasm, epiphora, and an elevated third eyelid. Episcleral congestion or corneal edema may also be present, and owners may describe the eye as reddish or blue[6]. Dogs may also present without vision, lacking menace responses, pupillary light reflexes (PLRs), and dazzle reflexes[7].

Unfortunately, most subtle or transient increases in IOP lack overt clinical signs in the acute phases, and most dogs present with chronic glaucoma. IOP, corneal edema, and visual status may be similar in acute and chronic glaucoma. Globe size and fundic examination help determine the duration of the disease. Signs of acute glaucoma may include a normal-sized globe with corneal edema, mydriasis, and a relatively normal retina. Dogs with chronic glaucoma generally present with buphthalmia, blindness, corneal edema, and fixed, dilated pupils in one or both eyes. Fundic examination may reveal retinal degeneration and optic disc cupping[8].

Ophthalmic Examination

The first objective of the ophthalmic examination is to determine the visual status and potential of each eye. Menace responses and direct and consensual PLRs should be assessed. If these responses are absent, dazzle reflexes should be assessed by shining a bright light into each eye in turn and monitoring for a blink response. A recent study demonstrated that dogs with acute glaucoma and absent menace responses, PLRs, and dazzle reflexes may regain some visual function in days to weeks if aggressive medical or surgical management is pursued early in the course of the IOP elevation.

Determination of IOP in both eyes involves proper restraint (avoiding neck pressure) and correct use of equipment to obtain accurate measurements. A recent study13 demonstrated that body position can affect IOP readings in dogs without glaucoma; therefore, it is important to keep the dog's body position consistent during IOP measurement. There are three methods of measuring IOP: indentation, applanation, and rebound tonometry. Indentation tonometers, such as the Schiotz, indent the corneal surface and provide a measurement that can be converted for use in dogs by using the accompanying human conversion table.14 Applanation tonometers, such as the Tono-Pen VET (Reichert), measure IOP by flattening the corneal surface and are commonly used in general practice. Rebound tonometers (e.g., TonoVet, Icare) measure IOP by projecting a small probe at the corneal surface and analyzing the characteristics of its rebound. Rebound tonometers have been shown to be as accurate and easy to use as applanation tonometers[9]. Because IOP measurements obtained using different instruments vary, it is recommended that the same instrument be consistently used when monitoring a patient.

Canine glaucoma does not usually present symmetrically, and because primary glaucoma is always a bilateral disease, it is critical to thoroughly evaluate and routinely monitor the contralateral eye. Depending on the breed of dog, primary glaucoma usually manifests in middle or old age2; therefore, routine monitoring of at-risk puppies is not useful. When a dog presents with unilateral glaucoma, gonioscopy (iridocorneal angle examination) can be performed by a veterinary ophthalmologist to determine if the drainage angle is abnormal. This information helps differentiate primary and secondary glaucoma. Prophylactic medical therapy in the contralateral eye of an affected dog can significantly prolong visual status. In a multicenter clinical trial[10], 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. Untreated control dogs developed glaucoma in the second eye earlier (median: 8 months) than eyes treated with prophylactic medication (median: approximately 31 months). Sharing this timeline with owners of dogs with primary closed-angle glaucoma helps keep the progressive nature of the disease in perspective and provides motivation to maintain compliance with the recommended prophylactic medications.

Treatment

Success always demands the use of effective therapy and although several aetiologies are involved in the glaucoma complex, the absolute determinant in therapy selection is the amount of primary and/or induced change within the iridocorneal angle. Medical suppression of an elevated IOP can be attempted using four types of drugs: the aqueous formation suppressors; miotics; uveoscleral outflow enchancers; and the hyperosmotic agents. All four are used in the treatment of canine glaucoma, the first three commonly as emergency treatment and in long term control while the hyperosmotic agents are invaluable as emergency and preoperative treatment. A fifth category of drugs, the neuroprotection agents, is beginning to emerge as an important possible addition to medical therapy.

Aqueous Formation Suppressors

Carbonic anhydrase inhibitors are used traditionally in the dog and with difficulty in the cat. The alternative use of beta-adrenergic blocking agents is still being evaluated for both species.

  • Carbonic anhydrase inhibitors

Acetazolamide (Diamox; Lederle). An oral dose rate of 50 to 75 mg per kg should be used and dosage should be two to three times daily. No ocular side effects are seen, but acute overdosage or long term therapy may produce metabolic acidosis, usually indicated initially by malaise, vomition and diarrhoea.

Dichlorphenamide (Daranide; Merck, Sharpe and Dohme) has provided a useful alternative to acetazolamide in that it is accompanied by less metabolic acidosis. A dose rate of 10 to 12 mg per kg is preferred two or three times daily for the dog. Potassium depletion is prevented by supplementing potassium rich food or by specific medication. Two percent dorzolamide HCl (Trusopt; Merck) a topical carbonic anhydrase inhibitor and brinzolamide (Azopt-Alcon) would appear to be as effective and is less irritating.

Beta-adrenergic blocking agents. Timolol maleate (Timoptol; Merck Sharpe and Dohme). Usage in the small animal patient is not indicated because the low concentration of the commercial preparation renders it ineffective in the dog and cat. Concentrations of four percent plus are required to reduce normal canine IOP by any appreciable degree. Other such agents used in man are betaxolol HCl, carteolol HCl, levobunolol HCl and metipranolol. A combination of timolol and dorzolamide is marketed as Cosopt (Merck, Sharp and Dohme), but experience in the dog and cat is limited.

Alpha2—adrenoreceptor agonists. Two such drugs are currently available. Apraclonidine (Iopidine) reduces aqueous secretion poorly in dogs but brimonidine tartrate (Alphagan; Allergan) seems to be more effective.(30) It produces less allergic response, probably increases uveoscleral outflow and is also neuroprotective. This drug could prove to be of considerable value to the veterinarian but long term efficacy studies are required to assess its potential use in the dog and cat.

Miotics

Miotic drugs are either parasympathomimetics, producing direct stimulation (cholinergic) of the iridal musculature (e.g., carbachol and pilocarpine), or anticholinesterase inhibitors producing miosis indirectly by the potentiation of acetylcholine activity (e.g. demacarium bromide). Pilocarpine is perhaps the miotic most often used in the treatment of canine glaucoma. It should be remembered that although the potential to increase the outflow facility exists, the patient must have retained some trabecular meshwork function. Adversely, pilocarpine can sting and it can reactivate and contribute to iritis. Demacarium bromide has been of particular value in maintaining long-term miosis in the management of posterior primary lens luxation, but its commercial production has now ceased. Latanoprost (Xalatan—Pharmacia and Upjohn) may prove to be of similar value, although this prostaglandin F2 analogue is used primarily to improve uveoscleral outflow. It also produces long acting miosis and in the absence of a long acting miotic preparation, its use in the dog with posterior primary lens luxation could prove invaluable.

Uveoscleral Outflow Enhancers

Latanoprost increases the rate of outflow by the uveoscleral route. It is effective against the peptides that are present in the extracellular matrix, rendering the muscle more porous. Brimonidine tartrate also increases uveoscleral outflow but the mechanism for this activity has not yet been defined.

Hyperosmotic Agents

A reduction in IOP can be produced effectively and rapidly by increasing the osmolality of the plasma within the ciliary circulation to produce an osmotic pressure gradient across the blood/aqueous barrier within the ciliary epithelium. Hyperosmotic agents are valuable as emergency therapy. Their use preoperatively is an essential adjunct to glaucoma surgery, for the surgical paracentesis effect is less significant when the IOP is low, and the resultant reduction in the total blood volume of the congested globe greatly facilitates the execution of surgery. Mannitol, glycerol and urea are used routinely, all three being effective at 1.0 to 1.5 g per kg body weight.

Neuroprotection and Neuroregeneration

Undoubtedly elevation of the IOP is the most significant trigger factor for glaucomatous optic neuropathy and lowering of the IOP to a normal or subnormal level is the essential factor in treatment. However, observation that the NOS and glutamate levels are elevated in glaucoma and that they are involved in retinal ganglion cell necrosis or apoptosis has raised the possibility of neuroprotective therapies and even neuroregeneration. Thus NOS inhibitors, exciting amino acid antagonists, glutamate receptor antagonists, apoptosis inhibitors and calcium channel blockers are all involved potentially in the development of future glaucoma therapies. The calcium channel blockers may reduce the effect of impaired microcirculation to the optic nerve head whilst potentially increasing outflow facility at the level of the trabecular cells.

Surgical treatment

The difficulty of achieving adequate reduction of the IOP in canine glaucoma by the medical means currently available has prompted the use of several surgical techniques in this species. A reduction in aqueous production can be achieved by cyclodestruction utilising cryosurgery, heat or laser. The amount of ciliary body damage must be sufficient to ensure that balance is regained between the resultant impaired aqueous production and whatever aqueous drainage is possible. The reopening of a closed ciliary cleft by cyclodialysis involves the breaking down of collapsed cleft tissue and synechiae to separate the ciliary body from the underlying sclera, allowing the anterior chamber to become confluent with the suprachoroidal space. The certain failure to control glaucoma is due to the subsequent closure of the cleft by the rapid formation of postoperative adhesions.

In the dog, surgical bypass of the collapsed ciliary cleft is most easily achieved either by iridencleisis or by a corneoscleral (limbal) trephination technique combined with peripheral iridectomy. These techniques allow aqueous to pass directly from the anterior chamber to the subconjunctival tissues where it is absorbed by the vascular and lymphatic elements present. Both may prove successful initially but in the short-term, fibrin may occlude the sclerostomy wound and long-term control may be denied by fibrosis of both the sclerostomy and the subconjunctival tissues[11].

Shunt (or gonioimplant) surgery offers a realistic approach to the control of IOP for it counteracts the effects of subconjunctival fibrosis to some extent. Several types of shunt exist: those with or without valves. Satisfactory results may be obtained using a one-piece silastic drainage implant consisting of an anterior chamber tube and an attached large surface area strap. The shunt allows aqueous to be diverted from the anterior chamber to the large subconjunctival scar sac that develops around the strap. Further modification of this technique resulting in smaller gonioimplants and even simpler surgery will be possible using fibroblast inhibitor drugs. In the future simple sclerostomy may be all that is necessary to offer the patient effective long term IOP control.

References

  1. Gelatt KN, Brooks DE, Kallberg ME. (2007) The canine glaucomas. In: Gelatt KN, ed. Veterinary Ophthalmology. 4th ed. Ames, Iowa: Blackwell Publishing; pp:753-811
  2. Abrams KL. (2001) Medical and surgical management of the glaucoma patient. Clin Tech Small Anim Pract 16(1):71-76
  3. Reilly CM, Morris R, Dubielzig RR. (2005) Canine goniodysgenesis-related glaucoma: a morphologic review of 100 cases looking at inflammation and pigment dispersion. Vet Ophthalmol 8(4):253-258
  4. Gelatt KN, MacKay EO. (2004) Secondary glaucomas in the dog in North America. Vet Ophthalmol 7(4):245-259
  5. Lannek EB, Miller PE. (2001) Development of glaucoma after phacoemulsification for removal of cataracts in dogs: 22 cases (1987-1997). JAVMA 218(1):70-76
  6. Gelatt KN. (2005) The canine glaucomas. In: Essentials of Veterinary Ophthalmology. Ames, Iowa: Blackwell Publishing; 2005:165-196
  7. Grozdanic SD, Matic M, Betts DM, et al (2007) Recovery of canine retina and optic nerve function after acute elevation of intraocular pressure: implications for canine glaucoma treatment. Vet Ophthalmol 10(suppl 1):101-107
  8. Martin CL. (2001) Evaluation of patients with decreased vision or blindness. Clin Tech Small Anim Pract 16(1):62-70
  9. Gorig C, Coenen RT, Stades FC, et al (2006) Comparison of the use of new handheld tonometers and established applanation tonometers in dogs. Am J Vet Res 67(1):134-144
  10. Miller PE, Schmidt GM, Vainisi SJ, et al (2000) The efficacy of topical prophylactic antiglaucoma therapy in primary closed angle glaucoma in dogs: a multicenter clinical trial. JAAHA 36(5):431-438
  11. Offri, R., Samuelson, D.A., Strubbe, D.T., et al (1994) Altered retinal recovery and optic nerve fibre loss in primary open-angle glaucoma in the Beagle. Exp Eye Res 58:245