Systematic review of prognostic factors associated with progression to late age-related macular degeneration: Pinnacle study report 2

There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently, clinicians cannot provide individualised prognoses of disease progression. Moreover, enriching clinical trials with rapid progressors may facilitate delivery of shorter intervention trials aimed at delaying or preventing progression to late AMD. Thus, we performed a systematic review to outline and assess the accuracy of reporting prognostic factors for the progression of intermediate to late AMD. A meta-analysis was originally planned. Synonyms of AMD and disease progression were used to search Medline and EMBASE for articles investigating AMD progression published between 1991 and 2021. Initial search results included 3229 articles. Predetermined eligibility criteria were employed to systematically screen papers by two reviewers working independently and in duplicate. Quality appraisal and data extraction were performed by a team of reviewers. Only 6 studies met the eligibility criteria. Based on these articles, exploratory prognostic factors for progression of intermediate to late AMD included phenotypic features (e.g. location and size of drusen), age, smoking status, ocular and systemic co-morbidities, race, and genotype. Overall, study heterogeneity precluded reporting by forest plots and meta-analysis. The most commonly reported prognostic factors were baseline drusen volume/size, which was associated with progression to neovascular AMD, and outer retinal thinning linked to progression to geographic atrophy. In conclusion, poor methodological quality of included studies warrants cautious interpretation of our findings. Rigorous studies are warranted to provide robust evidence in the future.