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To evaluate changes in cystic-appearing macular lesions and visual acuity in patients with X-linked retinoschisis while being treated with a carbonic anhydrase inhibitor.A retrospective analysis of 68 eyes from 36 patients between the ages of 5 years and 61 years with X-linked retinoschisis were monitored while on a carbonic anhydrase inhibitor. Macular cystic-appearing lesions were monitored with optical coherence tomography. Snellen visual acuity measurements were converted to logarithm of the minimum angle of resolution equivalent Early Treatment Diabetic Retinopathy Study letters for analysis. Analyses for changes in both visual acuity and macular cysts included comparisons between treatment and pretreatment segments.Forty-five eyes (66%) had a reduction of their cysts while on a carbonic anhydrase inhibitor. Twenty eyes (29%) showed no cystic change, whereas 3 eyes (4%) demonstrated worsening of their cysts with treatment when compared with pretreatment. There was a statistically significant improvement in logarithm of the minimum angle of resolution visual acuity while on treatment relative to pretreatment (P < 0.0001). The estimated average Early Treatment Diabetic Retinopathy Study equivalent improvement was 0.09 (slightly less than one line on the Early Treatment Diabetic Retinopathy Study chart) with a 95% confidence interval of 0.08 to 0.11.Considering the entire 36 patients in this cohort, while statistically significant, the average improvement in visual acuity was modest. Nonetheless, in individual patients, the improvement was more substantial. Improvement in the extent of cystic macular lesions was observed in a high percentage of cases.