Topical Carbonic Anhydrase Inhibitors in Macular Edema: A Systematic Review

In order to systematically evaluate the efficacy and safety of topical carbonic anhydrase inhibitors (CAIs) in the treatment of macular edema across different retinal disorders, a systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to June 13, 2026, without language or publication date restrictions. Clinical studies evaluating topical dorzolamide or brinzolamide for macular edema of any etiology were included. Data regarding study characteristics, treatment protocols, visual and anatomical outcomes, and follow-up were extracted independently by two reviewers. Twenty-eight studies met the inclusion criteria, comprising randomized controlled trials, quasi-experimental studies, cohort studies, case series, and one analytical cross-sectional study. Overall, the included studies were of moderate-to-high methodological quality. Retinitis pigmentosa-associated cystoid macular edema was the most frequently investigated condition (13 studies), followed by X-linked retinoschisis (10 studies), diabetic macular edema (four studies), and one macular edema following vitrectomy and epiretinal membrane removal. Topical dorzolamide was the most commonly evaluated agent, whereas topical brinzolamide was investigated less frequently. Across retinal disorders, topical CAIs consistently reduced central macular thickness and improved retinal morphology as assessed by optical coherence tomography. Functional outcomes were more variable, with improvements in best-corrected visual acuity observed primarily in selected patients with retinitis pigmentosa and diabetic macular edema, whereas visual gains were generally modest in X-linked retinoschisis. Long-term studies reported recurrence of macular edema despite continued treatment, particularly in retinitis pigmentosa. Topical CAIs were well tolerated, with no serious ocular or systemic adverse events reported. Topical CAIs provide consistent anatomical improvement in macular edema, particularly in inherited retinal disorders, while functional benefits are less predictable. This discrepancy between anatomical and functional outcomes may be attributed to prolonged photoreceptor loss, retinal pigment epithelium dysfunction, and irreversible disruption of the ellipsoid zone. Their favorable safety profile and non-invasive administration support their use as a therapeutic option, especially for retinitis pigmentosa-associated cystoid macular edema and selected cases of X-linked retinoschisis and diabetic macular edema. However, the current evidence is limited by predominantly observational studies and clinical heterogeneity. Well-designed multicenter randomized controlled trials are needed to establish their optimal role in the management of macular edema.