Ординатура / Офтальмология / Английские материалы / Small Animal Ophthalmology Secrets_Riis_2002

88 Medical Treatment of Glaucoma

Internet Antiglaucoma Medication Price Comparison*

*Price as of 2000. "Generic drug.

9.What are the indications and contraindications for using a miotic agent as part of the treatment for glaucoma?

Topical miotic agents produce pupillary constriction, contraction of the ciliary musculature, and increased outflow of aqueous through a configurational change in the trabecular meshwork. Pilocarpine is a direct-acting cholinergic miotic available in several concentrations; 2% appears most effective in the dog. Theoretically, pilocarpine is most effective in treating primary openangle glaucoma (POAG), the least common form found in dogs. Most forms of canine glaucoma are due to narrowing or closure of the iridocorneal angle, not the trabecular meshwork, making the effectiveness of pilocarpine questionable for closed-angle glaucoma (CAG), the more common form found in dogs. Advantages of pilocarpine include its effectiveness for some forms of glaucoma and its relatively inexpensive cost. Disadvantages include its topically irritating qualities and the frequency of administration (3-4 times daily). A 4% pilocarpine gel (Pilopine HS, Alcon) is available and has the advantage of once-daily administration. Because it can potentiate breakdown of the blood aqueous barrier, pilocarpine should not be used when uveitis is present or when treating secondary glaucoma. Indirect-acting miotics include echothiophate iodide (Phospho line Iodide, Wyeth-Ayerst) and demecarium bromide (Humorsol, Merck) and act by inhibiting cholinesterase, thus increasing endogenous acetylcholine. These agents are less irritating and longer-acting than pilocarpine but are more expensive. As with pilocarpine, they can activate latent uveitis and intensify concurrent uveitis. Thus, they are most useful in primary glaucoma. They are especially useful in primary glaucoma with early lens luxation or subluxation because they produce miosis and discourage a luxated lens from gaining access to the anterior chamber, resulting in acute pupillary block glaucoma, which necessitates surgical intervention.

10.Which of the (3-adrenergic blocking agents are commonly used in veterinary ophthalmology and when are they useful?

Although topical (3-blockers are the most frequently prescribed agents for treating glaucoma in man, their efficacy in dogs and cats is controversial. (3-blockers reduce lOP by decreasing aqueous production. The most commonly used drug is 0.5% timolol maleate (Timoptic, Merck). Tim- 0101 is useful in both primary and secondary glaucoma and unlike topical miotic agents, does not potentiate uveitis. Because (3-blockers decrease aqueous production by a mechanism other than CAls, their ocular hypotensive effect when used together with CAls is additive. Timolol is most commonly used as an adjunctive therapy and combined with oral CAls. Although it is not adequate as the sole agent when treating a glaucomatous eye, it may be useful in prophylactic therapy for the fellow eye in cases of primary glaucoma. Timolol is also available in an ophthalmic gel forming solution (Timoptic-Xli, Merck) that allows for once daily dosing. Be careful to dis-

pense or prescribe timolol in the 0.5% concentration as the 0.25% concentration that is also available is ineffective in dogs and cats. A common side effect of timolol (a nonselective J3-blocker) in humans is bronchoconstriction and bronchospasm (predominantly in patients with preexisting bronchospastic disease). Although this side effect is uncommon in animals, betaxolol (Betoptic, Alcon), a selective J3-blockerhas fewer side effects and can be used as an alternative. Betaxolol does not appear to be as potent as timolol in reducing lOP.

[3-Adrenergic Blocking Agents

11. How do sympathomimetic agents reduce lOP?

Adrenergic compounds decrease lOP by stimulating a-receptors and increasing aqueous outflow, and by stimulating J3-receptors and decreasing production. As with J3-blockers, they are minimally effective when used as sole agents but can be useful adjuncts when combined with other classes of drugs. Topical epinephrine and epinephrine-pilocarpine combinations are available. Dipivefrin hydrochloride (Propine, Allergan) is an epinephrine prodrug that is converted to epinephrine in the anterior chamber. Dipivefrin hydrochloride is the drug of choice in this group because it is less irritating, has better intraocular penetration into ocular tissues, and has more potency and less toxicity. However, it is more expensive than either epinephrine or epinephrine-pi- locarpine combinations.

Sympathomimetics

12.What are prostaglandin analogues?

Prostaglandin analogues (prostanoids) are a new class of topical glaucoma medications de-

veloped for once-daily usage in humans. The prototype in this class is latanaprost 0.005% (Xalatan, Pharmacia and Upjohn). Several similar drugs currently are becoming available. Prostaglandin analogues reduce lOP by increasing aqueous outflow by the unconventional or uveoscleral route. The mechanism of action is different from that of other antiglaucoma medications. In dogs and cats, the uveoscleral outflow has been considered a less important avenue for normal aqueous loss than the conventional outflow pathway through the iridocorneal angle. However, latanaprost has been very useful in treating some cases of acute primary glaucoma in dogs (used alone or in combination with conventional hyperosmotic and oral CAl therapy). Although this particular prostaglandin analogue has not been extensively evaluated for efficacy in animals, topical appli-

cation of prostaglandin FZa (PGF Za ) and similar drugs was shown to cause significant lOP reduction in rabbits, cats, dogs, and monkeys. The recommended dosage in humans is once daily at bedtime, and the most common side effect is an iris color change with long-term use. The iris color change has not yet been noted in animals. Latanaprost, in addition to its antiglaucoma effects, is also a very potent miotic and often produces profound pupillary constriction in cats and dogs. It is usually administered once or twice daily in animals. It is expensive but can be very useful in selected cases.

uz-Selective Agonists and Prostaglandin Analogues

13.What is acute glaucoma?

Acute glaucoma results from a rapid increase in lOP over a course of several hours. Clinical

signs include acute blindness, ocular pain, conjunctival and episcleral vascular congestion, and diffuse corneal edema. The pupil is usually dilated and unresponsive or sluggishly responsive to bright light stimulation. The combination of these clinical signs is very suggestive of acute glaucoma but they are not pathognomonic. Because any or all of these signs can be seen in other ocular disorders, tonometry is essential for accurate diagnosis. When in doubt about the visual potential of the eye, institute emergency therapy to reduce lOP. If the eye is irreversibly blind, this will become apparent soon (see Figure I).

Figure 1. Acute glaucoma in an American cocker spaniel. The intraocular pressure was 60 mmHg. Also note the cataract, which is insignificant to the glaucoma.

14.How should emergency treatment of acute glaucoma be approached?

A complete ophthalmic examination including tonometry is the first step. The clinician

should look closely for any sign of underlying intraocular disease such as uveitis, hemorrhage, or intraocular tumor. If primary glaucoma is diagnosed (no underlying abnormalities) or if a cause of secondary glaucoma is addressed, the focus of therapy should be on reducing lOP as rapidly as possible. Permanent ganglion cell and optic nerve damage can occur within hours following marked elevations in lOP. Therefore, rapid intervention is critical. Emergency medical treatment should consist of the administration of a hyperosmotic agent such as intravenous mannitol or oral glycerol. Mannitol is preferred because it is more potent and has fewer side effects. Hyperosmotic agents are the most potent medications available for the acute reduction of lOP. In addition, an

oral carbonic anhydrase inhibitor such as methazolamide or dichlorphenamide should be administered. These oral CAls begin to reduce lOP 2-3 hours after administration. lOP should be measured every hour until it normalizes. Mannitol can be repeated in 4-6 hours if necessary. Methazolamide or dichlorphenamide are continued at a dose of 2--4 mglkg every 8-12 hours. Referral to a veterinary ophthalmologist should be considered.

15.Which topical drugs are useful for acute glaucoma?

There is a wide variety of topical medications. Topical r'l-blockers such as timolol or Betax-

0101 are useful becauase they can be used in all forms of glaucoma and provide an additive effect to hyperosmotic agents and oral CAIs. They are not useful as sole agents for acute glaucoma because they only reduce lOP by 5-10 mmHg. Pilocarpine is useful for primary open-angle glaucoma and in some cases of primary closed-angle glaucoma, but it should not be used in cases of secondary glaucoma because it can worsen uveitis. A sympathomimetic agent such as dipivefrin can be used in conjunction with a topical r'l-blocker if necessary. The prostaglandin analogue latanoprost is also very useful in breaking high-pressure attacks of primary glaucoma in affected dogs when used alone or in conjunction with intravenous mannitol and an oral CAl.

16. If immediate referral to an ophthalmologist is impossible, what are the best medications for treating acute glaucoma?

For acute primary glaucoma, administer topical latanoprost and oral methazolarnide and recheck lOP in 30-60 minutes. IflOP is not significantly reduced (to less than 30 mmHg), begin intravenous mannitol. Add 0.5% timolol (b.i.d.), dipivefrin (b.i.d.), and/or 2% pilocarpine if necessary. If latanoprost is unavailable, begin mannitol administration immediately. For acute secondary glaucoma, avoid latanoprost and pilocarpine and use topical and/or systemic anti-inflam- matory agents as necessary for any underlying uveitis. Topical drugs causing miosis (latanoprost and pilocarpine) should not be used in cases of glaucoma due to anterior lens luxation.

17. Which medications are most useful after lOP has normalized?

There is not a single correct method for long-term medical management of the visual but glaucomatous eye. In general, the clinician should try to find the one medication or combination of medications that will control lOP and result in the fewest side effects. In some cases, topical administration of one agent is sufficient. In others, multiple medications are required. If lOP remains controlled for several weeks, the drug dosages or frequency of administration can be gradually reduced. Long-term medical management is challenging and requires frequent and careful monitoring, dosage adjustments, and drug changes. Most patients are best managed with an oral CAl and one or more topical agents of different classes. Remember that most antiglaucoma medications lose their efficacy over time and eventually surgical intervention becomes necessary. If the eye is irreversibly blind and painful, a surgical salvage procedure is indicated. Glaucomatous eyes require frequent monitoring, and tonometry should be performed at least every 3 months.

18.What is the prognosis for acute glaucoma?

Although many cases of acute glaucoma can be successfully managed for a period of time,

the long-term prognosis for preserving vision in most cases is guarded to poor. Initial response to therapy can be a useful indicator of future success. With aggressive medical or surgical intervention, many animals regain or retain vision for several months or longer. However, even with successful management of the lOP, glaucoma is almost always progressive and incurable. Fortunately, there are many surgical options available for the blind painful eye that provide comfort and alleviate the need for chronic medication.

19.When is surgery indicated for glaucoma?

There is considerable controversy within the veterinary ophthalmology community regard-

ing when surgical intervention is appropriate. Some ophthalmologists prefer to manage glaucoma in the visual eye medically until medical management begins to fail. Others advocate early sur-

gical intervention in hopes of alleviating the need for chronic medical management and prolonging vision in the affected eye. It remains to be seen which method works best. The surgical modalities employed all have potential complications, are expensive, and have risks. As with medical management, they can prolong vision in an affected eye but do not cure the disease.

20. Can primary glaucoma be prevented from developing in the fellow eye?

Primary glaucoma always has bilateral potential. In at least 50% of cases, the initially normotensive fellow eye becomes overtly glaucomatous within 6-12 months after the onset of disease in the affected eye. In dogs with primary glaucoma, it appears that prophylactic therapy using a topical l3-blocker, sympathomimetic, or miotic is effective in prolonging the period of time until the fellow eye becomes affected, but does not necessarily prevent glaucoma. In addition, prior prophylactic therapy may make glaucoma-if it occurs-easier to manage.

BlBLiOGRAPHY

Gelatt KN. Brooks DE: The canine glaucomas. In Gelatt KN (ed): Veterinary Ophthalmology, 3rd ed. Baltimore, Lippincott Williams & Wilkins, 1999, pp 701-754.

Figure I. Ahmed gonioimplant with scleral strap attached to increase the surface area of the subconjunctival bleb.

capsule and sclera and between the dorsal and lateral or dorsal and medial rectus muscle insertions. The implant is usually positioned at or just posterior to the equator, its rostral end about 10-12 mm from the limbus. The anterior border of the implant should be posterior of the dorsal rectus muscle insertion. The episcleral or main portion of the anterior chamber shunt is placed between the dorsal rectus and medial rectus muscles or the space between the dorsal rectus muscle and the lateral rectus muscle. Once the surgical site has been adequately dissected and excessive epibulbar fascia excised, the area may be treated with a sterile surgical cellulose spear soaked with mitomycin-C (0.25-0.5 mg/ml) to impede the fibrosis that develops about this base. After exposure of the tissues to the intraoperative mitomycin-C for 5 minutes, the area is flushed profusely for an additional 5 minutes with lactated Ringer's solution. Mitomycin-C should not have access to the anterior chamber or to the leading edges of the conjunctival wound. All anterior chamber shunts are checked prior to placement for function and patency. A 25-27-gauge hypodermic needle is cannulated into the end of the anterior chamber tubing, and sterile lactated Ringer's solution is injected. With the shunt system filled with fluid, it is "primed" and ready for implantation. The device is carefully positioned into the sub-Tenon' s capsule space, making certain that the implant borders are in contact with the sclera. Once the device is properly positioned, it is secured to the sclera and Tenon's capsule by 2-4 nonabsorbable 7-0 sutures, usually placed at the anterior border and near the extraocular muscle insertions (Fig. 2). The overall length of the anterior chamber silicone tubing is carefully measured. If cut too long, it may contact the posterior surface of the cornea and produce focal edema. However, if cut too short, the tubing lumen can be- come obstructed by the base of the iris or preiridal inflammatory membranes. Once in the anterior chamber, the tubing should not touch either the iris or cornea and should avoid crossing the center of the pupillary axis. The tip of the tubing is usually cut in a slightly beveled position to facilitate insertion into the anterior chamber. A limbal-based partial-thickness 5 X 8 mm scleral hinge is prepared by a scalpel to prevent tube erosion through the conjunctiva due to upper lid pressure. Entry into the canine anterior chamber is usually at about the 12 o'clock with a 20-22- gauge hypodermic needle (Fig. 3). The hypodermic needle is quickly removed and the beveled silicone tubing inserted. Manipulation of the tubing with special silicone tubing thumb forceps is recommended to prevent damage to the soft silicone tubing. Aqueous humor will generally be noted flowing through the device. Provided little aqueous humor has escaped through the anterior chamber needle track, lOP should be about 10 mmHg. The comers of the scleral hinge are apposed to the underlying host sclera with four simple interrupted 6-0 to 7-0 absorbable sutures. The conjunctival flap wound is apposed using several simple interrupted or a continuous 6-0 to 7-0 absorbable suture. To minimize development of fibrin in the aqueous humor and within the implant postoperatively, 25 fLg of tissue plasminogen activator (tPA) is usually injected into the anterior chamber at the limbus.

Figure 2. Implant being attached to the sclera intraoperatively.

Figure 3. Tube present III anterior chamber of a dog.

n.What is needed for postoperative management?

The general postoperative management includes:

•Control and resolution of the iridocyclitis with topical and systemic corticosteroids and nonsteroidal anti-inflammatory agents

•Moderate pupillary dilatation and encouraging pupil movement with careful use of mydriatics, such as 1% tropicamide