Long-Term Assessment of Macular Atrophy in Patients with Age-Related Macular Degeneration Receiving AntieVascular Endothelial Growth Factor Ang Li, MD, Nathaniel B. Rieveschl, BS, Felipe F. Conti, MD, Fabiana Q. Silva, MD, Jonathan E. Sears, MD, Sunil Srivastava, MD, Justis P. Ehlers, MD, Andrew P. Schachat, MD, Amy S. Babiuch, MD, Peter K. Kaiser, MD, Daniel F. Martin, MD, Rishi P. Singh, MD Purpose: Although intravitreal anti-vascular endothelial growth factor (VEGF) injection has become the mainstay treatment for neovascular age-related macular degeneration (nAMD), emerging studies suggest that anti-VEGF may be correlated with the development of macular atrophy (MA) in chronic therapy. The purpose of the current study is to determine the prevalence and progression of MA in nAMD treated with chronic anti-VEGF in a routine clinical practice. Design: Retrospective cohort. Participants: Patients with nAMD who were previously treatment-naïve and treated with anti-VEGF at the Cole Eye Institute for at least 4 years. Methods: This is chart review on anti-VEGF treated patients with nAMD with baseline and yearly follow-up spectral domain-OCT for at least 4 years. Retinal pigment epithelium subillumination analysis was used to automate identification of atrophy. Segmentation errors were manually corrected by 4 expert raters using a standardized grading protocol to quantify MA size. Patient baseline characteristics and treatment course were analyzed to identify predictive factors for the development of MA. Main Outcome Measures: MA growth rate and prevalence in cohorts with and without baseline atrophy. Results: A total of 79 eyes from 66 patients (79.87.4 years, 63% were female) with nAMD and 4 years of follow-up with anti-VEGF injections were identified. The mean baseline visual acuity was 0.480.25 logarithm of the minimum angle of resolution (20/60 Snellen equivalent), and the mean final visual acuity was 0.480.49 logarithm of the minimum angle of resolution (20/44 Snellen equivalent, P ¼ 0.23). The average number of in- jections was 19.89.8. MA was observed in 12.7% of eyes at baseline with an average annual growth rate of 0.70.5 mm 2 . In eyes without baseline MA, atrophy developed in 53.6% eyes by year 4 with a growth rate of 0.20.4 mm 2 per year. Multiple linear regression analysis revealed that the progression of MA was positively correlated with age (R ¼ 0.02, P ¼ 0.009). Conclusions: More than half of patients with nAMD treated with anti-VEGF injections for 4 years developed new MA. Atrophy progression was most strongly correlated with age, which suggests that baseline disease characteristics may be more predictive of MA progression than cumulative anti-VEGF treatment. Ophthalmology Retina 2017;-:1e8 ª 2017 by the American Academy of Ophthalmology Age-related macular degeneration (AMD) is a major cause of blindness in the elderly in the United States. 1,2 In exudative AMD, patients develop choroidal neo- vascularization (CNV), which accelerates vision loss. Intravitreal antievascular endothelial growth factor (VEGF) injection has been shown to prevent early loss of vision due to CNV and is the current gold standard treatment for neovascular AMD (nAMD). 3e8 Geographic atrophy is the process of retinal pigment epithelium (RPE) loss that causes irreversible vision loss in end-stage nonexudative AMD. Emerging studies have raised the question of whether long-term anti-VEGF therapy may be correlated with a similar but separate process of outer retinal atrophy in nAMD. 3,4,9e14 A cohort within the Comparison of AMD Treatments Trial (CATT) trial showed that treatment with monthly injections was associated with an increased risk of atrophy development in comparison with pro re nata (PRN) treatment. 9,15 Lois et al 16 and Abdelfattah et al 17 similarly showed an association between total number of anti-VEGF injections and the development of atrophy with follow-up times of 1.3 years and 2 years respectively. 16 The IVAN, 18 SEVEN-UP, 19 and PACORES 20 studies and Gillies et al 21 demonstrated that the prevalence of atrophy increased with long-term anti- VEGF therapy. Abdelfattah et al 17 coined the phrase “macular atrophy” as a general descriptor for this 1 Ó 2017 by the American Academy of Ophthalmology Published by Elsevier Inc. https://doi.org/10.1016/j.oret.2017.10.010 ISSN 2468-6530/17