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BACKGROUND AND OBJECTIVE: To determine the effectiveness of subthreshold (invisible) diode laser (810 nm) modified grid photocoagulation for the treatment of diffuse diabetic macular edema (DDME). METHODS: Fifty eyes of 29 patients were treated with subthreshold (invisible) diode laser modified grid photocoagulation for DDME in a prospective pilot clinical trial. Follow-up was conducted for a minimum of 6 months (average: 14.11 +/- 6.15 months). Re-treatment was performed for residual edema involving the foveal avascular zone. Ten patients were tested with Goldman visual field pre- and post-treatment. Visual improvement, visual loss, visual field, reduction/elimination of macular edema, and the number of treatments per eye were studied. RESULTS: Reduction/elimination of DDME was observed in 39% of the eyes after 1 to 3 treatments (2.22 +/- 0.84 treatments) in 6 to 12 months; and in 74% of eyes after 1 to 5 treatments (2.90 +/- 1.02 treatments) 15-24 months follow-up. The presence of cystoid macular edema, initial poor visual acuity, or a history of systemic hypertension did not affect the outcome. Patients without a history of systemic vascular diseases had a better chance of visual stabilization or improvement. Eighty-eight percent of the patients had at least stable vision at the last follow-up. Two out of 10 visual field tests showed a decrease in paracentral scotomas; no post-treatment subjective complaints of increased paracentral scotomas were encountered. CONCLUSION: Subthreshold (invisible) diode laser modified grid photocoagulation is effective in reducing/eliminating DDME, although resolution of edema may be slightly prolonged. However, this method may be advantageous in that it appears to reduce the objective and subjective effect on the paracentral visual field. Subthreshold (invisible) diode laser modified grid photocoagulation substantially reduces the post-treatment atrophic scarring.