Date of Award

January 2021

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Lucian V. Del Priore


Vision-related quality of life (VRQoL) is a patient-centered metric that is often utilized to examine the impact of advanced age-related macular degeneration (AMD) on patients’ lives. Prior studies of VRQoL have examined advanced AMD as a single group or focused on neovascular AMD (nAMD), even though advanced AMD can refer to either central geographic atrophy (GA) or nAMD. Also, little is known about the relationship between VRQoL and functional and structural GA biomarkers such as lesion area, and prior work has not accounted for GA lesion location, which may be as important as lesion size. Thus, we compared the natural progression of VRQoL in central GA versus nAMD. Additionally, in a secondary analysis, we examined the influence of the topographic distribution of atrophy on VRQoL in patients with GA secondary to nonexudative AMD.The primary analysis included Age-Related Eye Disease Study (AREDS) participants with central GA (n=206) or nAMD (n=198) who completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ) between 1997 and 2005. The rate of change of VRQoL was calculated as the slopes of linear models fit to longitudinal individual-level NEI-VFQ scores. Multivariable regressions identified factors associated with experiencing a decline in VRQoL during the study period and cross-sectional VRQoL score. In the secondary analysis, we manually segmented GA lesions on color fundus photographs of 161 AREDS participants with GA secondary to nonexudative AMD. We calculated the total area of atrophy in the better eye, total atrophic area in the worse eye, and area of atrophy in each of the nine subfields of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid in each eye. We assessed associations between VRQoL and area of atrophy in each topographic region of the better and worse eye utilizing linear mixed-effects models. There was a minor decline in VRQoL prior to the development of nAMD, but a significantly steeper decline after progression to nAMD (0.49 ± 2.91 vs. 3.30 ± 5.58 NEI-VFQ units/year; p<0.001). The rates of VRQoL decline were similar before and after the development of central GA (1.99 ± 4.97 vs. 1.68 ± 4.65 NEI-VFQ units/year; p = 0.66). Prior to the development of advanced AMD, the rate of VRQoL decline was greater for participants destined to develop central GA versus nAMD (p = 0.007), while post-progression to advanced disease, the rate was greater in nAMD compared with central GA (p = 0.012). Female gender (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.38-5.06; p = 0.003) and higher baseline VRQoL score (OR 1.03, 95% CI 1.01-1.06; p = 0.006) were independently associated with experiencing a longitudinal decline in VRQoL. In the secondary analysis, there was no significant association between VRQoL and total area of atrophy in the better eye (β, -0.22; 95% CI, -0.84 to 0.40; p = 0.49) or worse eye (β, -0.27; 95% CI, -0.73 to 0.19; p = 0.25). When examining the topographic distribution of GA in the better eye, lower VRQoL was significantly associated with greater area of atrophy in the central 1-mm-diameter zone (β, -3.65; 95% CI, -6.85 to -0.45; p = 0.026), but not with area of atrophy in any of the other eight ETDRS subfields. In the worse eye, VRQoL was not significantly associated with area of atrophy in any of the topographic regions. The natural progression of VRQoL differed in central GA versus nAMD, both before and after the development of advanced disease, suggesting that future studies should consider separating these phenotypes. Female participants and those with a higher baseline VRQoL were more likely to experience a longitudinal decline in VRQoL following progression to advanced AMD. Additionally, in patients with GA secondary to nonexudative AMD, the area of atrophy in the central 1-mm-diameter zone of the better eye was the only measure of atrophy that was associated with VRQoL and could be the anatomic outcome that best reflects the patient experience.


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