OBJECTIVE This study aimed to determine the efficacy of photocoagulation to the retinal pigment epithelial (RPE) cells and fluid-gas exchange (FGX) in the treatment of persistent macular holes. METHODS A clinical trial. METHODS Thirteen eyes of 12 patients who had undergone photocoagulation to the RPE and FGX for persistent macular holes after initial vitrectomy and gas tamponade were examined. All eyes had persistent full-thickness macular holes (diameter range, 290-820 microns; 610 +/- 190, mean +/- standard deviation) and no vitreous cortex around the holes on biomicroscopic examination. METHODS Argon laser photocoagulation was applied to the RPE in the hole bed, and FGX with 20% sulfur hexafluoride was then performed, followed by 2 weeks with the patient in a prone position. The follow-up period of the patients ranged from 3 to 18 months (10.2 +/- 4.2; mean +/- standard deviation). METHODS Anatomic success and final visual outcome were measured. RESULTS Macular holes were closed successfully after treatment in 12 (92%) of 13 eyes, and visual acuity improved 2 or more lines in 6 eyes (46%). Two eyes (15%) attained visual acuities of 20/40 or better, and seven eyes (54%) attained 20/67 or better visual acuity. There were no intraoperative complications. Cataract formation or progression was recognized during follow-up in five (83%) of six phakic eyes. CONCLUSIONS Although this study includes only a small number of patients, it suggests that photocoagulation and FGX can be effective in the treatment of persistent macular holes.