Lost to Follow-Up in Neovascular Age-Related Macular Degeneration: A Systematic Review of Global Trends, Risk Factors, and Clinical Consequences.

INTRODUCTION

Loss to follow-up (LTFU) among patients receiving anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) remains a critical challenge for maintaining visual outcomes. This systematic review and meta-analysis evaluated the prevalence, risk factors, and impact on visual prognosis of LTFU across real-world studies.

METHODS

A comprehensive literature search of PubMed, Embase, Cochrane, Scopus, and Google Scholar identified studies published between 2015 and 2025. Eligible studies included observational cohorts and registry-based analyses that reported the LTFU rates, risk factors, and visual outcomes following treatment discontinuation. Random-effects meta-analysis (DerSimonian-Laird) estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs); heterogeneity was assessed via I2 and Cochran's Q. Continuous predictors were analysed using regression-based ORs or standardized mean differences (SMDs), where appropriate.

RESULTS

We included 52 studies. Short-term LTFU was defined as 6-12 months without treatment; long-term LTFU as ≥12 months. LTFU rates ranged from <5% to >75% over up to 10 years. Older age was moderately associated with LTFU (SMD = 0.47, 95% CI: 0.37-0.57; ≈6-7 years older). Greater travel distance increased LTFU risk (OR = 1.35 per 10-km increase, 95% CI: 1.14-1.60). Male sex (OR = 1.20, 95% CI: 1.05-1.37) and caregiver/transport dependence (OR = 2.00, 95% CI: 1.45-2.75) were also associated with a higher likelihood of LTFU. Treat-and-extend (T&E) regimens showed lower LTFU than pro re nata. Patients who were LTFU had worse visual outcomes even after resuming care.

CONCLUSION

LTFU in nAMD treatment is common and driven by demographic (age, sex, and race), socioeconomic (income and insurance), and access (distance and caregiver need) factors. Continuous treatment, early response, and structured regimens (e.g., T&E) mitigate dropout risk. Interventions to improve access and personalize support are essential to reduce LTFU and preserve visual outcomes.