Aqueous Humor Flow in Human Eyes Treated With Dorzolamide and Different Doses of Acetazolamide

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Abstract
AN EXCESS of bicarbonate in the aqueous humor1 and the presence of carbonic anhydrase (CA) activity in the ciliary body of the rabbit2 were reported in the 1950s, suggesting that inhibition of the enzyme might lead to a decrease in aqueous formation. Shortly afterwards, the inhibitor acetazolamide was introduced for the treatment of glaucoma.3 Systemic administration of CA inhibitors reduces intraocular pressure by suppressing aqueous humor formation.3-5 However, the use of these compounds in the routine medical management of glaucoma has been limited owing to adverse effects.6 Topical use of CA inhibitors was thought of as a solution to avoid systemic complications. Continuous delivery of acetazolamide soaked in a soft contact lens reduced intraocular pressure,7 but administration of acetazolamide as eye drops or as a subconjunctival injection had little effect.8 The explanation for this could be that the concentration of the CA inhibitor in the ciliary body was too low to suppress flow in the latter experiment, while it was high enough in the former study. Maren 9 has shown that approximately 99% of the enzymatic activity needs to be inhibited to result in reduced aqueous humor production. Intensive research to develop a topically effective analog to acetazolamide has identified several promising new agents. Maren and colleagues10 worked with several water-soluble compounds that also could penetrate the limiting layers of the eye, and trifluoromethazolamide11 was found to be an interesting substance. Because of its instability, it was never tested in humans. Ponticello and coworkers12 discovered a novel class of water-soluble CA inhibitors, the thienothiopyran-2-sulfonamides. Dorzolamide hydrochloride was one of the most promising agents in this group. It was extensively tested clinically13-20 and was found to lower intraocular pressure satisfactorily.