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Macular laser photocoagulation (MLP) is inferior to intravitreal vascular endothelial growth factor (VEGF) inhibitors in the treatment of center-involved diabetic macular edema (DME). Ultra-widefield fluorescein angiography-guided laser photocoagulation to presumed ischemic areas of the peripheral retina or MLP do not reduce the treatment burden nor improve the visual outcomes of eyes treated with anti-VEGF drugs. Destruction of retinal tissue is not necessary to induce a therapeutic response in DME. Modern lasers are capable of producing invisible laser “burns” that do not destroy the targeted tissue using micropulse subthreshold (ST) mode where the laser's duty cycle is modified or alternatively selective retinal therapy (SRT) where ultrashort pulses of continuous wave laser selectively target the RPE. The best results with micropulse ST laser are obtained in eyes with a central macular thickness ≤400 μm. Eyes need to be treated in a continuous manner with no spaces between burns in the edematous area. Micropulse ST-MLP downregulates inflammatory biomarkers produced by activated microglial cells and Müller cells. Micropulse ST-MLP may reduce the anti-VEGF injection burden in DME. In SRT, the diseased RPE is targeted and heated with the laser with the hope that the adjacent RPE migrates and proliferates into these areas to heal the diseased RPE. There is much less experience with SRT, but the results are promising and deserve further study.

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