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To determine the value of a topical carbonic anhydrase inhibitor for the treatment of foveal lesions in patients with X-linked retinoschisis (XLRS).Eight patients with XLRS and foveal cystic-appearing spaces by fundus examination and by optical coherence tomography (OCT) were treated with a topical form of carbonic anhydrase inhibitor. Changes in “foveal thickness” and “foveal zone thickness” were measured by OCT, and changes of best-corrected visual acuity were measured by Early Treatment Diabetic Retinopathy Study (ETDRS) charts.Seven of eight patients treated with 2% dorzolamide had a noticeable reduction in foveal thickness as well as cystic-appearing spaces by OCT. This reduction was found in both eyes in four of these patients and in one eye in one patient after 1 month of treatment. After an additional 1 month to 2 months of the same treatment regimen, two additional patients also had a noticeable reduction in foveal thickness as well as cystic-appearing spaces. Of these seven patients who had an improvement shown by OCT with treatment, five also had improvement of their visual acuity by ≥7 letters in at least one eye on ETDRS charts.The present study shows the efficacy of topical dorzolamide for treating foveal cystic-appearing lesions in patients with XLRS.