The purpose of this study was to evaluate the efficacy of topical dorzolamide 2% eye drops on macular function and thickness in a case of enhanced S-cone syndrome (ESCS). A 24-year-old Asian man with enhanced S-cone syndrome treated with topical dorzolamide in the left eye participated in the study. Examinations performed before and during treatment were included visual acuity (VA), contrast sensitivity measured with briefly presented grating targets (grating CS) and the Pelli-Robson chart (P-R CS), microperimetry (MP), and spectral-domain optical coherence tomography (SD-OCT). Following 4 months of treatment, the mean thickness of the central 1-mm foveal subfield of the left eye, as measured by SD-OCT, decreased from 551 to 242 μm. Mean MP sensitivity within the central 12 degrees (28 points) increased from 9.4 dB at baseline to 11.2 dB. Although Pelli-Robson contrast sensitivity improved only minimally in the left eye, grating contrast sensitivity improved by more than a factor of two. Mean log MAR VA was 0.22 OD and 1.00 OS (at baseline), which improved to 0.10 OD and 0.66 OS after 4 months of treatment. The results indicate that in our patient with enhanced S-cone syndrome, treatment with topical dorzolamide was effective in improving macular thickness, VA, microperimetry sensitivity, and grating contrast sensitivity. These measures of retinal structure and function are sensitive tools for evaluating the effects of treatment in enhanced S-cone syndrome patients with cystoid macular edema. Further investigation is warranted to assess the relationships among visual performance for daily activities, visual sensitivity, and macular thickness.