Purpose: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered.Methods: This retrospective observational study analyzed data from patients with sudden severe visual decline ($15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Bestcorrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected.Results: 1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1-38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of .20% or a decrease of .5%. Conclusion:In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a $15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.RETINA 43:1081-1087, 2023N eovascular (wet) age-related macular degeneration (nAMD) is a chronic, progressive, degenerative disease and a leading cause of visual impairment among patients over 60 years. 1 To date, therapy with intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care; anti-VEGF therapy has spared many patients from legal blindness. 2 Several randomized clinical trials demonstrated the efficacy of intravitreal treatment in restoring or stabilizing visual acuity (VA), but a small subgroup of patients experienced visual impairment despite appropriate therapy. The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the Treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly From the Eye Clinic, Azienda Ospedaliero-
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