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We are pleased that Dr Ophir agrees with the importance of our retrospective analysis of pooled data from the DRCR.net Protocol I study 1 Gonzalez V.H. Campbell J. Holekamp N.M. et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol I data. Am J Ophthalmol. 2016; 172: 72-79 Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar , 2 Elman M.J. Aiello L.P. Beck R.W. et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010; 117: 1064-1077 Abstract Full Text Full Text PDF PubMed Scopus (1116) Google Scholar and the need for the development of alternate approaches to diagnosis and treatment of diabetic macular edema (DME). In his letter, Dr Ophir re-emphasizes the modest gains received by many patients from intensive treatment and monitoring with ranibizumab plus prompt focal/grid laser treatment in the Protocol I study. 2 Elman M.J. Aiello L.P. Beck R.W. et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010; 117: 1064-1077 Abstract Full Text Full Text PDF PubMed Scopus (1116) Google Scholar , 3 Elman M.J. Qin H. Aiello L.P. et al. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012; 119: 2312-2318 Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar In response to our statement that an effective treatment algorithm for DME is uncertain in this group of suboptimal responders, he offers a systematic evidence-based approach to diagnosis and treatment of diffuse diabetic macular edema (DDME) that relies on the choice of full-field 3D optical coherence tomography figures and video clips to accurately assess the most common tractional mechanisms of DDME, usually overlooked with the use of other imaging studies. Once the presence of extrafoveal vitreous traction is confirmed, pars plana vitrectomy should be considered for achieving a long-term effect. If no extrafoveal traction, central epiretinal membrane, or vitreofoveal traction exists, he indicates that grid laser photocoagulation provides a highly successful treatment. Early and Long-term Responses to Anti–Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema: Analysis of Protocol I DataAmerican Journal of OphthalmologyVol. 177PreviewIn an important study, Gonzales and associates1 analyze the 3-year study data from patients in the Diabetic Retinopathy Clinical Research Network's Protocol I study2 who were treated with ranibizumab plus prompt or deferred laser and provided an observed best-corrected visual acuity (BCVA) reading at 12 weeks. The analysis reveals that after 3-monthly ranibizumab injections plus prompt focal/grid laser treatment in part of the eyes, 40% (135/340) of diabetic macular edema (DME) eyes showed at best only limited BCVA gain (<5 letters). Full-Text PDF