Abstract
Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, and so continued research into new treatment options remains a priority. No systematic review has yet analysed the effectiveness and safety of higher-dose aflibercept across the available literature. We aimed to systematically evaluate the efficacy and safety of higher-dose intravitreal aflibercept (>2 mg) on Central Retinal Thickness (CRT) and Best Corrected Visual Acuity (BCVA) in patients with neovascular AMD (nAMD). In order to achieve this, a systematic literature search was conducted in January 2025 using PubMed and Ovid MEDLINE databases. Results were screened, and inclusion criteria were applied. Studies were included if they reported outcome data for intravitreal aflibercept doses above 2 mg for the treatment of nAMD. Of 382 identified articles, eight studies met inclusion criteria, encompassing data from 903 eyes. Analysis of all studies combined revealed a statistically significant improvement at 10 months, with a 33% reduction in CRT and a 29% improvement in BCVA. Subgroup analysis suggested greater effectiveness of 8 mg compared to 3 mg doses, particularly for CRT reduction (36% at 10 months vs. 28% at 12 months). However, small sample sizes and high heterogeneity across studies, including variations in dose, injection intervals, and patient characteristics (e.g., treatment-naïve vs. treatment-resistant), limit the reliability and conclusions of these outcome findings. There was a complication rate of 1.7% for serious adverse effects. In conclusion, higher doses of aflibercept (>2 mg) are safe and effective for treating nAMD, but further research is needed to analyse the comparison of different high doses and the effect of injection frequency on outcomes.