Age-Related Macular Degeneration and Inherent Challenges of Drug Delivery to Posterior Segment of Eye Due to Ocular Barriers

Aim: To comprehensively review age-related macular degeneration (AMD) pathophysiology and elucidate the pharmacokinetic challenges in delivering therapeutic agents across ocular barriers to the posterior eye segment, with emphasis on current treatment strategies and future perspectives. Materials and Methods: A systematic literature review was conducted using PubMed, Google Scholar, and Scopus databases from 2015 to 2025. Search terms included "age-related macular degeneration," "ocular drug delivery," "blood-retinal barrier," "intravitreal injection," and "posterior segment drug delivery." Studies were selected based on relevance to AMD pathophysiology and drug delivery mechanisms. Data extraction focused on epidemiological trends, barrier mechanisms, clinical outcomes of anti-VEGF therapy, and novel delivery approaches. Statistical analysis was performed using descriptive methods to synthesize findings from randomized controlled trials and observational studies. Results: Current literature demonstrates that AMD affects 8.69% of adults aged 45-85 years globally, with prevalence expected to increase to 15.3 million cases by 2034. Intravitreal anti-VEGF therapy remains the gold standard for neovascular AMD, with endophthalmitis rates of 0.16% per injection during year 1, decreasing to 0.06% by year 3. The blood-retinal barrier (BRB) and retinal pigment epithelium (RPE) present major impediments to systemic drug delivery, restricting molecules >2 nm. Novel delivery systems including sustainedrelease implants and nanoparticles demonstrate promising results in overcoming these barriers. Conclusion: Despite remarkable advances in intravitreal delivery systems, the inherent complexity of ocular anatomy and barrier physiology necessitates continued innovation in drug delivery technologies. Enhanced understanding of BRB dynamics and RPE function is crucial for developing next-generation therapeutics for AMD. The integration of nanotechnology and sustained-release formulations offers potential for improved therapeutic outcomes and reduced treatment burden.