**Background:** Age-related macular degeneration (AMD) is a chronic, progressive disease of the central retina and a leading cause of blindness in industrialized nations. First described in 1874, AMD remained largely untreatable until the advent of anti-VEGF therapy in the early 2000s. The disease is classified into dry (atrophic) and wet (neovascular) forms, with approximately 80% of patients having dry AMD and 20% having wet AMD. The hallmark lesions are drusen, which are extracellular deposits between the retinal pigment epithelium (RPE) and Bruch membrane. The review aims to provide a mechanistic understanding of AMD, covering anatomy, epidemiology, genetics, pathogenesis, prevention, and treatment strategies.
**Methods:** This is a narrative review that synthesizes findings from a wide range of published literature, including clinical trials, epidemiological studies, genetic association studies, and basic science research. Key studies referenced include the Age-Related Eye Disease Study (AREDS), AREDS2, the MARINA and ANCHOR trials for ranibizumab, the CATT and IVAN trials comparing bevacizumab and ranibizumab, the VIEW trials for aflibercept, and the EVEREST and PLANET studies for polypoidal choroidal vasculopathy. The review also incorporates data from the GWAS Catalog and the European Eye Epidemiology (E3) consortium.
**Key Results:** The global prevalence of AMD was estimated at 196 million in 2020 and is projected to reach 284 million by 2040, with Asia accounting for 113 million cases. Prevalence is highest in Europe (12.33%), followed by Africa (7.50%) and Asia (7.38%). Major genetic risk loci include CFH (rs1061170, 402H allele) and HTRA1 (rs10490924), which can increase AMD risk up to 15-fold. At least 103 loci have been associated with AMD, involving complement factors, lipid metabolism, and angiogenesis. Smoking interacts with CFH and HTRA1 genotypes to amplify risk. The AREDS formulation (vitamins C and E, beta-carotene, zinc) reduced the risk of advanced AMD by 25% in high-risk individuals. AREDS2 found that replacing beta-carotene with lutein/zeaxanthin was slightly more effective and safer for smokers. Anti-VEGF therapies (ranibizumab, bevacizumab, aflibercept) have dramatically reduced blindness rates; in Denmark and Scotland, blindness from AMD decreased by approximately 50% since their introduction. However, long-term outcomes remain suboptimal: in the CATT study, after 5 years, 20% of eyes had visual acuity of 6/60 or worse, and mean visual acuity was 3 letters worse than baseline. Treat-and-extend regimens have become standard, with about 8-9 injections per year needed to maintain vision. For geographic atrophy, complement inhibitors (lampalizumab, eculizumab) have not shown benefit in phase III trials. Polypoidal choroidal vasculopathy (PCV) responds well to anti-VEGF monotherapy, with aflibercept showing 81.7% polyp inactivity in the PLANET study.
**Clinical Implications:** AMD is a multifactorial disease with systemic components, including associations with cardiovascular disease, diabetes, rheumatoid arthritis, and systemic lupus erythematosus. The review underscores the importance of early detection and treatment, as baseline visual acuity is the strongest predictor of final vision. Lifestyle modifications—including a Mediterranean diet rich in antioxidants, regular exercise, smoking cessation, and weight control—are critical for prevention. Personalized risk prediction models incorporating genetic, phenotypic, and molecular factors are needed to optimize management. Despite advances, no definitive cure exists, and ongoing research into complement inhibition, combination therapies, and novel drug delivery systems is essential to further reduce the burden of AMD-related visual impairment.