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We thank Mathis et al for their comments on our publication1Zarubina A.V. Neely D.C. Clark M.E. et al.Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging.Ophthalmology. 2016; 123: 1090-1100Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar in which we demonstrated that 49% of persons ≥60 years of age with early age-related macular degeneration (AMD) had subretinal drusenoid deposits (SDD, also called reticular pseudodrusen) assessed with multimodal imaging including spectral-domain optical coherence tomography. We especially thank Mathis et al for bringing to our attention that their group had previously reported 71% prevalence of SDD in patients with early AMD in their retina clinic-based study,2De Bats F. Mathis T. Mauget-Faÿsse M. et al.Prevalence of reticular pseudodrusen in age-related macular degeneration using multimodal imaging.Retina. 2015; 36: 46-52Crossref Scopus (40) Google Scholar and not 31%, as we incorrectly cited. In eyes at different AMD stages and in eyes in good macular health,1Zarubina A.V. Neely D.C. Clark M.E. et al.Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging.Ophthalmology. 2016; 123: 1090-1100Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 3Schmitz-Valckenberg S. Alten F. Steinberg J.S. et al.Reticular drusen associated with geographic atrophy in age-related macular degeneration.Invest Ophthalmol Vis Sci. 2011; 52: 5009-5015Crossref PubMed Scopus (148) Google Scholar SDD follow the topography of rod photoreceptors4Curcio C.A. Sloan K.R. Kalina R.E. et al.Human photoreceptor topography.J Comp Neurol. 1990; 292: 497-523Crossref PubMed Scopus (1906) Google Scholar and are frequently found along the superior vascular arcades and in the peripapillary area nasal to the optic nerve head. Owing to this topography, most SDD lies outside the Early Treatment Diabetic Retinopathy Study grid, and thus out of the range of commonly used diagnostic technologies and progression metrics. In our study we determined prevalence within an expanded ascertainment area, namely, spectral-domain optical coherence tomography volumes of both macula and optic nerve head.1Zarubina A.V. Neely D.C. Clark M.E. et al.Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging.Ophthalmology. 2016; 123: 1090-1100Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Likewise, Mathis et al determined prevalence within a larger macular volume (30°×25°) than typically used in clinic-based studies.2De Bats F. Mathis T. Mauget-Faÿsse M. et al.Prevalence of reticular pseudodrusen in age-related macular degeneration using multimodal imaging.Retina. 2015; 36: 46-52Crossref Scopus (40) Google Scholar We agree wholeheartedly that the 49% to 71% prevalence of SDD in early AMD reported in these 2 publications underscores the urgency of understanding the role of these recently recognized lesions in the progression to advanced AMD. We further echo the importance of extramacular, periarcade spectral-domain optical coherence tomography scans in addressing these questions. Currently, physicians are unlikely to examine optical coherence tomography images outside the macula in the absence of pathology via en face imaging, which we showed is rare with sparse SDD lesions not forming a pattern. We appreciate the interest of Mathis et al in our hypothesis that the biogenesis of both SDD and drusen involves an outer retinal lipid-recycling program, with participation of the retinal pigment epithelium squarely in the middle. Fortunately, new data on the regulation of cholesterol homeostasis in outer retina are now emerging from laboratory studies.5Zheng W. Mast N. Saadane A. Pikuleva I.A. Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments.J Lipid Res. 2015; 56: 81-97Crossref PubMed Scopus (48) Google Scholar Thus, our understanding of the biology of both SDD and drusen will be eventually clarified. Re: Zarubina et al.: Prevalence of subretinal drusenoid deposits in older persons with and without age-related macular degeneration, by multimodal imaging (Ophthalmology 2016;123:1090-1100)OphthalmologyVol. 124Issue 2PreviewWe read with great interest the article by Zarubina et al.1 This article highlights the high prevalence of subretinal drusenoid deposits (SDD), previously called “reticular pseudodrusen” (RPD), in older adults (≥60 years) enrolled in the Alabama Study of Early Age-Related Macular Degeneration.2 Indeed, the authors found that SDD were present in 23% of participants with healthy maculae and in 52% of persons with early to intermediate age-related macular degeneration (AMD) using multimodal imaging methods. Full-Text PDF