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Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials
Journal article   Open access   Peer reviewed

Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials

Juan E Grunwald, Ebenezer Daniel, Jiayan Huang, Gui-Shuang Ying, Maureen G Maguire, Cynthia A Toth, Glenn J Jaffe, Stuart L Fine, Barbara Blodi, Michael L Klein, …
Ophthalmology (Rochester, Minn.), Vol.121(1), pp.150-161
01/2014
DOI: 10.1016/j.ophtha.2013.08.015
PMCID: PMC3892560
PMID: 24084496
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3892560View
Open Access

Abstract

To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Cohort within a randomized clinical trial. We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). Development of GA. By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3. Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.
 Follow-Up Studies Geographic Atrophy - diagnosis Humans Middle Aged Geographic Atrophy - drug therapy Male Vascular Endothelial Growth Factor A - antagonists & inhibitors Genotyping Techniques Bevacizumab Incidence Ranibizumab Aged, 80 and over Angiogenesis Inhibitors - therapeutic use Female Visual Acuity - physiology Fluorescein Angiography Geographic Atrophy - epidemiology Wet Macular Degeneration - epidemiology Antibodies, Monoclonal, Humanized - therapeutic use Risk Factors Proportional Hazards Models Wet Macular Degeneration - diagnosis Wet Macular Degeneration - drug therapy Aged Cohort Studies

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