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Editors Selection IGR 11-1

Medical treatment: CAI and corneal effects

Comment by James Brandt on:

19896 Effect of dorzolamide hydrochloride on central corneal thickness in humans with cornea guttata, Wirtitsch MG; Findl O; Heinzl H et al., Archives of Ophthalmology, 2007; 125: 1345-1350

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Throughout nature, essential physiologic functions are usually carried out by redundant and overlapping mechanisms. Why this is so makes sense from an evolutionary standpoint ‐ a mutation or disease that knocks out a crucial process leads to death or disability, and having redundant processes confers an obvious survival advantage favored by natural selection. Keeping the cornea clear is certainly one such function, and so the corneal endothelium employs several parallel mechanisms for maintaining corneal clarity. Carbonic Anhydrase (CA) isoenzymes II and IV play an important role in the pump function of the endothelium, keeping the cornea in a relatively steady state of dehydration. Dorzolamide is a potent inhibitor of CA II. In normal eyes, both original regulatory safety data and in subsequent studies, dorzolamide exhibited little in the way of corneal toxicity. There are, however, numerous anecdotal and published reports of irreversible corneal decompensation during dorzolamide therapy in some patients. Might patients with already-compromised corneas, in whom the endothelium is overly dependent on CA-mediated pump function, be more susceptible to corneal thickening? Wirtitsch et al. (1442) performed a prospective, randomized, placebo-controlled two-drug crossover study in a cohort of patients with reduced endothelial cell counts and compared them to a matched normal group. After four weeks, central corneal thickness increased in patients with compromised endothelium, but not in patients with normal cell counts. Their data suggests that patients with pre-existing endothelial disease are more susceptible to the adverse corneal effects of topical carbonic anhydrase inhibitors (CAIs).

What does this mean for the practicing clinician? We certainly should not abandon topical CAIs, as they play an important role in our glaucoma toolkit. However, the glaucoma clinician should pay more attention to the corneal endothelium, and in patients with compromised endothelia (e.g., Fuchs' dystrophy, bullous keratopathy, penetrating keratoplasty) consider other drugs before topical CAIs.

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