Fellow Eye Status Is a Biomarker for the Progression Rate of Geographic Atrophy: A Systematic Review and Meta-analysis

Abstract

Systematic review and meta-analysis of how fellow eye status predicts the progression rate of geographic atrophy (GA). The status of age-related macular degeneration (AMD) in the fellow eye has been used as an indicator of the GA progression rates in primary eyes, but the reported growth rates vary widely in prior clinical studies. We searched MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov, and PubMed up to September 12, 2018, for studies that classified treatment-naive GA patients based on different AMD manifestations in the fellow eyes and that monitored GA progression in the primary eyes. Three fellow eye statuses were analyzed: (1) no GA or choroidal neovascularization (CNV) in the fellow eye, (2) GA in the fellow eye, and (3) CNV in the fellow eye. To account for the patients' different entry times, we introduced a horizontal translation factor to shift each dataset within each group. We determined the translation factor by adjusting it 1 month at a time until the r2 in weighted least squares regression (r2WLS) was maximized for the cumulative linear trend line of all datasets. Heterogeneity and study quality were assessed using the I2 statistic and Newcastle-Ottawa scale, respectively. Publication bias was evaluated by funnel plots, the Egger test, and the Begg test. We included 9 studies with 2134 eyes from 1835 patients. After the introduction of translation factors, the datasets in each fellow eye group fit along a straight line with a high r2WLS. The GA radius growth rate in fellow eyes with GA (0.179±0.003 mm/year) and fellow eyes with CNV (0.159±0.015 mm/year) was significantly higher than that in fellow eyes without GA or CNV (0.110±0.009 mm/year; P < 0.001 and P= 0.02, respectively). We found no significant difference in the GA radius growth rates between fellow eyes with GA and fellow eyes with CNV (P= 0.42). We confirmed that the presence of advanced AMD in the fellow eye, defined as GA or CNV, can serve as a biomarker of the GA enlargement rate in the primary eye. This may assist the design of clinical trials and may shed light on the natural history of GA expansion.