Safety margins of anti-VEGF therapy using treat and extend treatment protocol-lessons from the COVID-19 pandemic

Purpose : To analyze the consequences of delaying intravitreal (IVI) anti-vascular endothelial growth factor (VEGF) therapy in patients under treat-and-extend (TAE) protocol. Methods : A retrospective review of medical records of a consecutive group of patients receiving IVI using TAE protocol before and during the COVID-19 pandemic. Data collected included diagnosis, demographics, treatment schedule, compound used and anatomical outcome according to spectral-domain optical coherence tomography (SD-OCT). Results : A total of 923 eyes (691 patients) were included;58.8% (543 eyes) were treated for neovascular age-related macular degeneration (nvAMD), 25% (231 eyes) had diabetic macular edema (DME), and 16.2% (149 eyes) with retinal vein occlusion (RVO). The average patient age (±SD) was 74.5 ± 11.7 years. The Female/male ratio was 1.08:1. Delayed therapy during the pandemic (?7 days) occurred in 56.3% of the eyes. This included 56.2%, 61.5%, 49.0% of nvAMD, DME and RVO patients respectively. The overall average delay (±SD) was 15.3±23.4 days. RVO patients were on average less late (9.3±16.1 days) compared to nvAMD (15.8±23.8) and DME (18.2±25.6) eyes (P=0.002). Multivariate analysis showed that in nvAMD duration of the disease and type of anti-VEGF were predictors of the number of days late (P=0.011 and 0.019). In eyes ? 7days late, 45.7%, 58.5%, and 58.9% of nvAMD, DME, and RVO eyes respectively showed an increase in central subfield thickness (CST). Worsening was related to absolute numbers of days late, and not to the percentage of delay of the recommended interval. A positive correlation was found between delay to treatment and an increase in CST. Conclusions : Delaying IVI in eyes under TAE regimen was common during the COVID-19 pandemic. These delays were associated with macular thickening having potential visual consequences.