Topical carbonic anhydrase inhibitors: a new perspective in glaucoma therapy

Oral carbonic anhydrase inhibitors have been used extensively in the treatment of all types of glaucoma. These agents reduce intraocular pressure by suppressing the rate of aqueous humor formation. Despite their efficacy as ocular hypotensive agents, these agents are not always used for protracted therapy because of significant systemic side effects. Consequently, topically active carbonic anhydrase inhibitors have been a goal of glaucoma researchers for many years. Recently, a new class of carbonic anhydrase inhibitors has entered clinical trials as ocular hypotensive agents. The thienothiopyran-2-sulfonamides, consisting of compounds MK-927, MK-417, and MK-507, are being actively investigated. These agents possess both lipid and aqueous solubility, thereby allowing intraocular penetration through both the cornea and the sclera. They are all potent inhibitors of the human carbonic anhydrase II isoenzyme found in the nonpigmented epithelium of the ciliary body. Preliminary results indicate the order of potency is 2% MK-507 > 1.8% MK-417 > 2% MK-927. Maximum diurnal intraocular pressure reduction generally requires administration of these agents three times daily. Up to a 26.2% reduction in intraocular pressure occurs following multiple-dose therapy with 2% MK-507 given three times a day. These new topical carbonic anhydrase inhibitors appear to be tolerated extremely well; relatively minor ocular side effects, including transient stinging, burning, and tearing, have been frequently reported. In contrast to oral carbonic anhydrase inhibitors, no significant systemic side effects have been documented during clinical testing. Topical carbonic anhydrase inhibitors will probably be marketed in the near future, thus culminating many years of research effort. These agents may provide a safe, effective means of reducing aqueous humor production and intraocular pressure without producing significant systemic side effects.