Topical carbonic anhydrase inhibitors: potential adjuvants to glaucoma therapy in the future

Systemically administered carbonic anhydrase inhibitors lower intraocular pressure (IOP) by decreasing aqueous production. Their clinical usefulness is limited, however, because they often cause ill-tolerated side effects, and on occasion may be associated with serious adverse reactions. In the past, attempts at topical formulations of carbonic anhydrase inhibitors did not achieve desired results. Recent modifications to improve pharmacokinetics have lead to the development of topical carbonic anhydrase inhibitors that decrease IOP with minimal side effects. Thus, this class of drugs may soon become an additional therapy for treating open-angle glaucoma. This paper discusses the development of topical carbonic anhydrase inhibitors, including both unsuccessful and promising endeavors. It also summarizes the current understanding of the chemistry, mechanisms of action, pharmacokinetics, and side effects of these future glaucoma therapy adjuvants.