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To determine the long-term safety of high-density subvisible diode micropulse photocoagulation (810 nm), compare the clinical findings with computational modeling of tissue hyperthermia and to report results for a subset of eyes treated for diabetic macular edema (ME) documented pre- and postoperatively by spectral-domain optical coherence tomography.All eyes treated for ME from diabetic retinopathy (diabetic ME) and branch retinal vein occlusion between April 2000 and January 2010 were reviewed for subvisible diode micropulse laser-induced retinal damage. Therapeutic outcomes were reviewed for a subgroup treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography. Laser-induced retinal thermal effects were modeled computationally using Arrhenius formalism.A total of 252 eyes (212 diabetic ME, 40 branch retinal vein occlusion) of 181 patients qualified. None of the 168 eyes treated at irradiance <350 W/cm2 and 7 of 84 eyes at ≥590 W/cm2 had retinal damage (P = 0.0001) (follow-up 3–120 months, median, 47). Sixty-two eyes of 48 patients treated for diabetic ME with pre- and postoperative spectral-domain optical coherence tomography with median 12 months follow-up had no retinal injury by infrared, red-free, or fundus autofluorescence photos; fluorescein angiography or indocyanine green angiography; or spectral-domain optical coherence tomography. Central foveal thickness (P = 0.04) and maximum macular thickness decreased (P < 0.0001). Modeling of retinal hyperthermia demonstrates that the sublethal clinical regimen corresponds to Arrhenius integral >0.05, while damage is likely to occur if it exceeds 1.Subvisible diode micropulse can effectively treat retinovascular ME without laser-induced retinal damage, consistent with Arrhenius modeling of pulsed hyperthermia.