Abstract
PURPOSE OF REVIEW: This paper provides a detailed overview of systemic carbonic anhydrase inhibitors (CAIs) and their application in managing ophthalmic conditions, including glaucoma, cystoid macular edema, and idiopathic intracranial hypertension. Despite their recognized clinical benefits, the potential for severe systemic adverse effects often discourages clinicians from prescribing these agents. By examining the pharmacology, pharmacokinetics, safety profile, and clinical indications of systemic CAIs, this review highlights strategies to mitigate treatment challenges, particularly in patients with comorbidities and complex medical backgrounds. RECENT FINDINGS: New insights into the diverse roles and distribution of carbonic anhydrase (CA) isozymes have expanded our understanding of both the mechanisms and clinical implications of systemic CAIs. In the eye, CA-II and CA-IV are key contributors to aqueous humor production and ocular blood flow modulation, with dose-dependent improvements in choroidal perfusion observed upon enzyme inhibition. Beyond mechanism of action, tissue-bound drug concentration is a key factor in achieving maximal intraocular pressure (IOP) reduction. Moreover, some CAIs exhibit activity independent of CA blockade, such as inhibiting aquaporin-4. Clinical data further indicate that despite theoretical risks of systemic toxicity-particularly in individuals with comorbidities-severe adverse events are relatively rare. SUMMARY: In specific ocular diseases, the use of systemic CAIs is vital for maintaining vision. Although systemic CAIs carry risk of systemic adverse events, with higher risk, the incidence of severe adverse events is low and in some studies were comparable to that of topical therapy. It's important to be aware of potential side effects and ensure the correct usage of oral CAIs, especially in individuals with other systemic diseases. A tailored evaluation of risks and benefits carried out for each individual, particularly in case of prolonged usage, should decrease the risk of adverse events.