Glaucoma--Is Effective Treatment a Reality
World Small Animal Veterinary Association World Congress Proceedings, 2003
P.G.C. Bedford, BVetMed, PhD, FRCVS, DVOphthal, DECVO, ILTM
Professor, Department of Veterinary Clinical Sciences, The Royal Veterinary College
North Mymms, Hatfield Herts, UK

INTRODUCTION

The many inherent difficulties always encountered in all the domesticated species in the attempted management of glaucoma to retain useful vision range from difficulty in diagnosis to the prevention of retinal ganglion cell death. Clinical experience alone dictates the expected poor prognosis for sight, but recent awareness of the mechanisms almost certainly involved the ganglionopathy clearly indicates that adequate neuroprotection might never be achieved. Not only are possible therapies still conjecture, but the early occurrence of what is probably a self-propagating process of neurodegeneration renders effective therapy particularly difficult in the species we treat. Currently our existing therapies must fall short of the mark and the practical difficulties associated with the assessment of outflow facility, the accurate monitoring of therapy and the complexity of surgical techniques all combine to confound the prognosis. The overriding factor in all glaucoma is the degeneration of the retinal ganglion cell, thus neuroprotection through effective ocular hypotension is the essential requirement of any therapy we utilise. However we are often too late in instituting that therapy and although we may contain associated pain and discomfort, the process of neuroretinal degeneration currently can neither be reversed nor stopped.

What do we understand by the term "glaucoma"? It has been simply defined as the process of ocular tissue destruction caused by a sustained elevation of the IOP above its normal physiological limits. It is the specific effect of that elevated pressure upon the composite parts of the optic nerve which renders glaucoma an emergency. Fortunately open-angle glaucoma has limited incidence in the domesticated species for seldom are we in a position to diagnose its early presence and thus inhibit ganglion cell degeneration early in the process. Only in those glaucomas in which there is demonstrable primary or induced defect in aqueous outflow through the iridocorneal angle can we say that the elevated pressure rise is directly responsible for the ensuing ganglion cell death. Even so, such knowledge does not ensure effective therapeutic control. It is likely that all the glaucomas we commonly experience as veterinarians are due to maintenance of a physiologically incompatible rise in IOP and it is the characteristics of that elevated IOP which have been prompted the consultation, whether they be pain, episcleral congestion, corneal oedema, globe enlargement or defective vision. Based on the clinical picture we simply record the elevated IOP, diagnose glaucoma and set about treatment along the traditional hypotensive lines, with the knowledge that effective, long-term reduction in the IOP will approach the best we can achieve. There is a sufficiency of experimental evidence to demonstrate that the process of ganglion cell degeneration, whether it be necrosis or apoptosis, starts within the first few hours of the rise in IOP becoming established and that once triggered this process cannot be stopped. Thus currently the prognosis for sight must always be poor, with the moderating influence of any hypotensive therapy being variably expressed from one patient to another.

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 drug: the aqueous formation suppressors; miotics; uveoscleral outflow enhancers; 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.

A. 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.

1.  Carbonic anhydrase inhibitors--Acetazolamide (Diamox; Lederle). An oral dose rate of 50 to 75mg 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. 2% dorzolamide HCl (Trusopt; Merck) a topical carbonic anhydrase inhibitor and brinzolamide (Azopt-Alcon) would appear to be as effective and is less irritant.

2.  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 per cent 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.

3.  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.

B. 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., demecarium 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. Demecarium 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.

C. Uveoscleral Outflow Enhancers

Latanoprost increases the rate of outflow by the uveoscleral route. It is effective against the peptides which 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.

D. 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.

Speaker Information
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P.G.C. Bedford, BVetMed, PhD, FRCVS, DVOphthal, DECVO, ILTM
Professor, Department of Veterinary Clinical Sciences
The Royal Veterinary College
North Mymms, Hatfield Herts, UK


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