Geographic atrophy risk factors in participants of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT)

Abstract

 

Purpose

 

To describe baseline risk factors for geographic atrophy (GA) during anti-VEGF therapy of choroidal neovascularization (CNV) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).

 

Methods

 

Participants included 1020 CATT participants with no GA visible on digital color photographs (CP) or fluorescein angiograms (FA) at enrollment. Participants were randomly assigned to ranibizumab (0.5mg) or bevacizumab (1.25mg) treatment and to a 2-year monthly or PRN injection dosing regimen, or monthly injections for 1 year and PRN injections the following year. Demographic, baseline ocular characteristics, and baseline lesion features of CP/FA and OCT were evaluated as risk factors for development of GA within 2 years using univariate and multivariate time-dependent Cox proportional hazard models. Adjusted hazard ratios (aHR) and associated 95% confidence intervals (CIs) were estimated. Among 770 participants in the CATT genetic study, the associations between AMD-associated SNPs (CFH, ARMS2, HTRA1, and C3) and risk of GA were evaluated using linear trend p-value, with adjustment for age, gender and smoking status.

 

Results

 

GA developed in 187 (18.3%) of 1020 participants by 2 years. In multivariate analysis, poor baseline visual acuity, presence of retinal angiomatous proliferation (RAP), absence of blocked fluorescence on FA, presence of GA in the fellow eye, ranimizumab treatment and monthly treatment regimen (Table 1), thinner sub-retinal fluid, decreased sub-RPE height, and foveal center intra-retinal fluid (Table 2), were independently associated with increased risk of GA. ARMS2 (rs10490924) (aHR=1.7, 95% CI (1.1, 2.7)) and HTRA1 (rs11200638) (aHR=1.8 (1.2, 3.0)) risk alleles were associated with increased incidence of GA, but no association was observed for CFH (rs1061170) (p=0.57) or C3 (rs2230199) (p=0.50).

 

Conclusions

 

Approximately one-fifth of CATT participants developed GA within 2 years. Independent baseline risk factors included poor visual acuity, RAP, intra-retinal fluid, monthly dosing, and ranibizumab treatment. ARMS2 and HTRA1 risk genotypes were also associated with incident GA. Anti- VEGF therapy may have a role in the development of GA.

 

 

Table 1: Multivariate analysis of baseline risk factors for geographic atrophy (GA) incidence

 

 

Table 2: Multivariate analysis of baseline risk factors for geographic atroophy (GA) incidence

 

Keywords: 412 age-related macular degeneration • 464 clinical (human) or epidemiologic studies: risk factor assessment • 413 aging