We read with interest the article “Macular Atrophy Progression and 7-Year Vision Outcomes in Subjects From the ANCHOR, MARINA, and HORIZON Studies: the SEVEN-UP Study” by Bhisitkul and associates. The authors follow one of the oldest cohorts of patients of age-related macular degeneration (ARMD) treated with intravitreal ranibizumab (IVR) and discuss the prognostic factors for visual acuity and the possible effects of these agents toward causing macular atrophy.

The results of the study indicate that macular atrophy, the most significant correlate of final visual acuity, was present in 98% of patients at 7 years of follow-up, while central macular thickness (CMT) did not correlate with visual acuity. Using Fourier-domain optical coherence tomography for deriving such measurements in patients of wet ARMD, especially those with type 2 choroidal neovascular membranes, is often erroneous whether done manually or using macular thickness maps. This is due to similar reflectivity of retinal pigment epithelium (RPE) and dense scars/membranes. Since subretinal fibrosis was present in 61% of the eyes, CMT measurements would have been error prone.

Contribution of anti–vascular endothelial growth factor (VEGF) drugs toward macular atrophy is a highly debated issue, very meticulously discussed by the authors. As the patients of the study group in question had received monthly IVR in the first 2 years followed by as-needed dosage, it becomes important to assess the rate of growth of macular atrophy during the 7 years of follow-up. If the progression was greater during the first 2 years, anti-VEGF agents can be the cause, whereas a later progression may be indicative of the disease process itself. A higher rate of progression during the HORIZON phase followed by decline of progression may even indicate upregulation of VEGF receptors owing to constant use of IVR previously during the ANCHOR/MARINA phase. Hence this is a very important question and needs further investigation of the records.

Thirdly, the current protocols on use of antioxidants focus largely on prevention of wet ARMD in eyes with the dry form of the disease. The progression and high prevalence of macular atrophy and it being the most significant correlate of best-corrected visual acuity in this study indicates possible role of these drugs in wet ARMD by slowing the RPE damage.

We keenly await the comments of the authors.