This study found evidence of a threshold effect in which the presence of bilateral soft drusen and depigmentation of retinal pigment epithelium was associated with substantially low health-related quality of life (HRQoL) in adult Latinos from the United States.
To assess the association of general and vision-specific HRQoL with age-related macular degeneration (AMD), overall and by bilaterality and severity, in adult Latinos.
Design, Setting, and Participants
This cross-sectional, population-based study included 4876 participants from the general urban community in 6 US Census tracts in La Puente, California. The data for these analyses were collected as part of a population-based study of ocular diseases in adult Latinos in the Los Angeles Latino Eye Study from February 1, 2000, through May 31, 2003. The analysis was performed from November 2010 to February 2011. Additional analyses were performed in June 2014.
Main Outcomes and Measures
Mean-adjusted HRQoL scores and effect sizes.
Of the 4876 participants included in the analysis, 4402 (90.3%) had no AMD, and 474 (9.7%) had any AMD, with 453 having early (9.3%) and 21 (0.4%) having late stages of the disease. The mean (SD) age of the cohort was 54.8 (10.7) years. Of the 4876 participants, 2001 (41.0%) were male and 2875 (59.0%) were female. In this cohort of Latinos, participants with AMD had lower vision-specific HRQoL scores. General HRQoL was assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey and self-reported vision-related HRQoL by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Composite NEI-VFQ-25 scores were 59.5 (95% CI, 50.8-68.1) for those with late-stage AMD and 79.4 (95% CI, 72.5-86.1) for those with early-stage AMD, compared with participants without AMD 80.7 (95% CI, 73.9-82.4); P < .001. Several lesions of early AMD were associated with lower NEI-VFQ-25 composite scores and 8 to 10 individual scales. Large effect sizes and lower mean scores were observed for those with late AMD lesions, overall and specifically for geographic atrophy and neovascular AMD, compared with those without AMD. With the use of concatenated bilateral severity levels for AMD, decreases in the NEI-VFQ-25 composite and individual scale scores were observed at the transition from a unilateral to bilateral severity level of 40, which corresponds to having bilateral soft drusen (>125 μm in diameter with drusen area ≥196 350 μm2) and depigmentation of retinal pigment epithelium (slope of −19.17 for the NEI-VFQ-25 composite score). Measures of general health, as assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey, were not affected in this cohort.
Conclusions and Relevance
In this study of adult Latinos, early AMD lesions are associated with lower self-reported, vision-specific HRQoL but not general HRQoL. Severity and bilaterality of AMD are associated with measurably lower HRQoL scores, with the largest difference in scores occurring for individuals with both eyes affected. A concatenated approach to incorporate bilateral severity might be more useful and provide better insight into the association of AMD and HRQoL.
Age-related macular degeneration (AMD) is a chronic, progressive disorder that mainly affects people older than 50 years and is the leading cause of irreversible blindness in adults older than 60 years in the Western world.1-5 With limited and expensive treatment options available and an aging world population, this ocular disorder is expected to continue to increase as a major public health problem, with substantial clinical, emotional, and financial effects on patients and marked adverse consequences for the economy.6-11
Central vision affects a person’s interaction with the environment and plays a crucial role in daily activities. Therefore, central vision impairment that results from AMD can lead to compromised health-related quality of life (HRQoL).6,7,9,10 People with AMD may find performing daily tasks much more challenging than people without the disease, even when the disease is in its earlier stages.5,6,9,10
The effect of AMD on HRQoL has been investigated in a number of studies5-7,9,10; most of these studies5-7,9,10 have been conducted on clinic-based samples, predominantly in non-Hispanic whites. These associations among Latinos remain largely unexplored, even though Latinos constitute the largest and fastest-growing minority segment of the US population.12,13 Studies14-16 on Latinos have found this population to have a different pattern of AMD prevalence, incidence, progression, and risk factors. Moreover, the lower level of health care access and use in this group is likely to affect follow-up care of these patients and may render them more susceptible to diminished HRQoL.17,18 The effect of bilaterality and severity of AMD on patients’ visual function and HRQoL has not been well documented.5,9,10 Data from the Los Angeles Latino Eye Study (LALES), a population-based, ocular epidemiologic study in adult Latinos, offered us a unique opportunity to address these issues.13
Box Section Ref ID
Question What is the association between general and vision-specific health-related quality of life (HRQoL) and age-related macular degeneration (AMD) in a population-based data set from the Los Angeles Latino Eye Study?
Findings The findings of this study of adult Latinos reveal lower mean vision-specific HRQoL in people with AMD, even in the earlier stages of the disease. Concatenated bilateral severity provided evidence of measurably lower HRQoL scores with severity and bilateral AMD.
Meaning A concatenated approach to incorporate bilateral severity might provide insight into the association of AMD and HRQoL.
The data for these analyses were collected as part of LALES from February 1, 2000, through May 31, 2003. The analysis was performed from November 2010 to February 2011. Additional analyses were performed in June 2014. Details of the study design, sampling plan, and baseline data have been previously reported.13 In brief, a census of all residents living within 6 US Census tracts in La Puente, California, was conducted to identify eligible individuals.13
All eligible participants (aged ≥40 years at the time of the census and self-identified as Latino) were informed of the study and invited to participate. After written informed consent was obtained, an interview was conducted to obtain detailed data on demographics, ocular and medical condition, and health care access and use, followed by a detailed eye examination. Institutional review board approval was obtained from the Los Angeles County/University of Southern California Medical Center Institutional Review Board.13 Participants were assigned unique identifiers, and the data were deidentified.
A modification of the Wisconsin Age-Related Maculopathy Grading System (WARMGS)19 was used by masked graders at the Wisconsin Ocular Epidemiology Reading Center to grade individual AMD lesions. Detailed descriptions of all grading procedures and definitions were previously reported.15,19 Each eye was graded independently of the contralateral eye, with adjudication by a senior grader (R.K.) to address discrepancy.
The WARMGS19-21 defined early AMD as the absence of signs of advanced AMD and the presence of (1) soft indistinct or reticular drusen or (2) hard distinct or soft distinct drusen with pigmentary abnormalities (depigmentation of retinal pigment epithelium [RPE] or increased retinal pigment [IRP]).
Advanced or late AMD was defined as the presence of (1) geographic atrophy (GA) or (2) neovascular (exudative) AMD. Neovascular AMD was defined as the presence of any of the following lesions: (1) pigment epithelial detachment or age-related retinal detachment, (2) subretinal hemorrhage, (3) subretinal scar (subretinal fibrous scar), or (4) laser treatment for neovascular AMD.
To assess the qualitative association between AMD severity and HRQoL, we used the modified WARMGS 6-step severity scale (levels 10-60) for a subgroup of the total sample (eTable 1 in the Supplement). According to this scheme, a severity level of 10 corresponds to no AMD, levels 20 to 40 correspond to different levels of early AMD, and levels 40 and 50 represent late AMD.
We derived a per-person composite scale to incorporate severity and bilaterality for each person by concatenating per-person bilateral severity using a scheme similar to that previously used by Klein et al22 for diabetic retinopathy. In brief, the severity of AMD for a participant was derived by combining the severity levels for each eye but giving greater weight to the eye with the higher level of severity (eTable 2 in the Supplement). This approach resulted in an 11-step scale (eTable 2 in the Supplement). If the severity of AMD could not be graded in 1 eye, that eye was considered to have a score equivalent to the score of the other eye.
We evaluated HRQoL using general and vision-specific instruments. General HRQoL was assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12), version 1.23 The standard US norm-based SF-12 physical component summary (PCS) and mental component summary (MCS) scores were calculated.23 Self-reported, vision-related HRQoL was assessed by the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25),24 which consists of 12 vision-targeted scales based on 25 questions that has been validated in different populations, including Hispanics25,26 and patients with AMD.27,28 Eleven of the 12 scale scores (excluding the general health rating question) were averaged to yield a composite score,24,26 with higher scores representing better visual functioning and well-being.
Sociodemographic and clinical factors across subgroups defined by status of AMD (AMD vs no AMD) were compared using t tests for continuous variables and χ2 tests for discrete variables. Covariate-adjusted mean HRQoL scores were compared among the no, early, and late AMD groups using analysis of covariance. Covariates included were age, sex, vision insurance, comorbidities, income, and other ocular disease. We added other ocular disease as an indicator variable in the final model. Because of the high correlation between age and employment status, only age was retained. These analyses were repeated for other AMD-related lesions.
Effect sizes (ESs) for the NEI-VFQ-25 and SF-12 scores were calculated. The ES is an index used to measure the magnitude of effect of 1 variable on an outcome variable.29 On the basis of Cohen’s29 suggestion, an absolute ES of 0.20 to 0.49 is considered small, 0.50 to 0.79 is moderate, and 0.80 or greater is large. To further assess the nature of the association and to examine the possible nonlinear association between these risk factors and the severity of AMD, we used local regression methods, adjusting for other covariates from the final logistic regression model, to generate LOWESS (locally weighted scatterplot smoothing) plots.30 For these analyses, predicted HRQoL values were derived for the composite NEI-VFQ-25 score and different subscale scores. We fitted models of AMD severity for both eyes (concatenated) and separately for the worse eye and the better eye.
To examine the rate of descent of the HRQoL score and to determine the inflection point or threshold at which there is a considerable decrease in HRQoL scores, we computed the slope m between all consecutive points of the LOWESS curve. We compared the change in slope values for each pair of adjacent points by measuring the decrease in consecutive slopes.
Description of Study Cohort
Of the 6357 participants who completed an ophthalmic examination, 6052 had fundus photographs, 5888 had gradable photographs for AMD, and 5464 had completed the SF-12 and NEI-VFQ-25 questionnaires. The 4876 participants with no missing values in primary HRQoL subscales were included in the analyses (eFigure in the Supplement). Of these, 2001 (41.0%) were male and 2875 (59.0%) were female, and the mean (SD) age of the cohort was 54.8 (10.7) years. Of the 4876 participants included in the analysis, 4402 (90.3%) had no AMD, and 474 had any AMD (9.7%), with 453 having early (9.3%) and 21 (0.4%) having late stages of the disease.
The comparisons of different demographic and clinical characteristics between participants with or without AMD suggest that participants with AMD were older, less likely to be female, less likely to be educated or employed, more likely to have vision insurance, and more likely to report a history of ocular disease than those without AMD (eTable 3 in the Supplement).
Table 1 summarizes the results of mean differences in HRQoL scores and ESs by AMD status. We found differences across subgroups of no, early, and late AMD in all subscales of the NEI-VFQ-25 except general health and ocular pain. Despite the mean overall differences, the ESs for each of these HRQoL scores were modest (all ESs <0.2) for early AMD. However, there were small to very large ESs with late AMD in all subscales. There were no substantial mean differences in the SF-12 HRQoL scores among the AMD groups.
HRQoL and Early AMD Lesions
We examined the mean differences in HRQoL score, stratifying them by the presence of early AMD lesions and comparing them with those without any evidence of AMD. No substantial differences were found in HRQoL scores between participants with soft distinct drusen and those without any evidence of that lesion (Table 2). However, compared with those without the lesion, participants with soft indistinct drusen had lower scores on the composite NEI-VFQ-25 scale and 9 subscales.
Table 3 summarizes the results of HRQoL analyses on those with IRP and RPE depigmentation. These pigmentary changes were associated with lower scores in composite and several other subscales. No significant associations were observed for the SF-12 MCS or PCS scores for any of the early AMD lesions.
HRQoL and Advanced AMD Lesions
Age-adjusted mean scores suggest that participants with advanced AMD lesions (GA and neovascular AMD) had statistically significant lower mean scores and substantially larger ESs than those without any AMD. Results were more pronounced when participants with neovascular AMD were compared with those without any lesion, with very large ESs for some subscales. However, sample sizes (12 for GA and 17 for neovascular AMD) precluded robust analyses in people with these advanced AMD lesions.
Bilaterality and Severity of AMD and HRQoL
On the basis of LOWESS plots, we observed decreasing scores in HRQoL with increasing severity of AMD for different HRQoL domains on the NEI-VFQ-25. This finding was true when severity was defined for the worse eye, the better eye, or both eyes.
When we looked at the severity of AMD in the worse eye and the composite NEI-VFQ-25 score, the decrease in median predicted HRQoL score begins relatively early in the moderate stages of early AMD, with the decrease in scores beginning at a severity level of 40 with a slope of −0.6 (Figure 1). When we repeated the analyses for the better eye, the decrease in the HRQoL score from level 30 to 40 was more pronounced, with a slope of –2.79 (Figure 1).
To explore the role of bilaterality, we plotted the bilateral concatenated severity of AMD against the HRQoL scores. Figure 2 shows the LOWESS plot for 11 steps of bilateral severity of AMD and its association with the NEI-VFQ-25 composite score and the SF-12 PCS score. The slopes in Figure 2 were suggestive of no substantial association between HRQoL in the initial stages of early AMD (slope m10/10-40/<40 = −0.53) up to a unilateral severity of level 40, after which there is evidence of a pronounced negative association of HRQoL and AMD severity between steps 6 and 7 (slope m40/<40-40/40 = −19.17), corresponding to a bilateral severity of level 40. The change in slope is also evident along the severity scale, with another sharp decrease between steps 60/<60 (unilateral neovascular AMD) and 60/60 (bilateral neovascular AMD). In comparison, there was very little change in the SF-12 PCS score until advanced bilateral AMD (Figure 2).
Similar trends of decrease in median predicted score were observed when these plots were repeated in most of the other NEI-VFQ-25 subscales. The Wilcoxon rank sum test used to examine the magnitude of the threshold effect or turning point revealed that, even in patients with bilateral intermediate stages of AMD, which is still considered early in the disease, HRQoL is substantially diminished.
Data from LALES provided a unique opportunity to study the effect of AMD on HRQoL in the largest and fastest-growing minority population of the United States that is known to have different patterns of AMD prevalence and risk factors13,15,16,31 as well as health care access and use. To our knowledge, this analysis provides the largest population-based data to address the association of AMD and HRQoL.
Using the NEI-VFQ-25, we found that participants with AMD had lower vision-specific HRQoL scores compared with participants without AMD. Participants with early AMD lesions, including soft indistinct drusen and pigmentary abnormalities, had lower mean scores for several vision-specific HRQoL subscales, such as driving, near vision, distant vision, role, and social function. These results were more pronounced in participants with advanced AMD. Measures of general health, as indicated by the SF-12, were not affected in our cohort.
We observed a strong inverse association between severity of AMD and vision-specific HRQoL. Severity and bilaterality of disease were associated with lower HRQoL scores, such that participants with more severe AMD had lower HRQoL scores than participants with early AMD, and participants with bilateral disease had lower scores than those with unilateral disease. When examining the pattern of HRQoL scores with increasing severity of AMD, the scores were lower in participants with moderate or higher levels of AMD and with involvement of both eyes. Specifically, the presence of bilateral drusen of 125 μm or greater with an area of involvement of 196 350 μm2 or greater, accompanied by bilateral RPE depigmentation in both eyes, was associated with the lowest mean HRQoL scores in this population.
Our results are consistent with previously published results on AMD and HRQoL. A number of studies2,6,7,9-11,32,33 have found similar evidence of the effect of late AMD on HRQoL. Few studies have been performed on the effect of early AMD on HRQoL despite the fact that early AMD is much more common than advanced AMD.7,9,10 However, our results for early AMD lesions are consistent with those reported by Scilley et al,34 who found that persons with early AMD are more likely to experience difficulty driving and to have trouble with daily tasks that involve near and far vision than people without AMD.
Overall, the differences in HRQoL scores between persons with unilateral and bilateral moderate levels of AMD (with large drusen and RPE depigmentation) were the largest and most substantial across the spectrum of AMD severity in our study.7,9,10 A number of studies5,9,32 have found lower HRQoL scores in patients with bilateral AMD, especially in the late stages, compared with patients with unilateral disease. Moderate macular degeneration of one eye is compensated for by the better eye, allowing individuals with unilateral AMD to sustain a relatively good HRQoL.5,9,32 The detrimental effect of bilateral eye disease had also been observed in other ocular conditions in the LALES population.35-37
The lower scores in the HRQoL scales, such as driving difficulty, near vision, and distant vision, can be explained by the decrease in visual acuity and impaired contrast sensitivity of those with advanced AMD. Although visual acuity is not affected in early AMD, empirical evidence suggests that contrast sensitivity is associated with early AMD,38-40 resulting in reduced visual function. Specifically, scotopic dysfunction is a marker of early AMD in some studies.34,40
These results suggest that participants with bilateral large drusen and depigmentation had the most substantial decrease in HRQoL despite the fact that visual acuity might not be affected at this stage. Given that most treatment focuses on advanced AMD, the development of strategies to prevent bilateral progression would offer the most potential benefit for patient HRQoL and satisfaction, which also highlights the importance of assessing patient-reported outcomes, such as HRQoL. Objective measurements, such as visual acuity, may not adequately characterize the total effect of an ocular condition on a patient. Therefore, HRQoL instruments are increasingly being used to assess patient’s overall perception of relative well-being, even as a tool to evaluate treatment efficacies.41
In this analysis, we found no negative association of AMD with general measures of HRQoL as assessed by the SF-12 PCS and MCS scores. These findings are consistent with other studies8,9 that found these instruments not to be sensitive to ocular disease, including AMD. Studies35-37 with the LALES data on other ocular conditions also reported similar low responsiveness. Patients with AMD or other ocular disease may otherwise be considerably healthy. Therefore, general measures of health status might not be sensitive to capture difficulty in visual functioning that results from ocular conditions.8,9
The current analysis has several strengths. It was performed on a large population-based sample with adequate statistical power to study different phenotypes, especially the early AMD lesions. Use of a standardized protocol for objective measurement and grading of AMD cases minimized the chance of measurement error.13,19 Although HRQoL is a self-reported patient outcome, we used measures of HRQoL that have been validated in different populations (including Hispanics) and for different ocular conditions, including AMD.9,27,42 This instrument has also been used previously for the LALES population.35-37,42-44
The common concern of the potential effect of the participant’s knowledge of having AMD on the responses to the HRQoL questionnaire was not likely to be an issue in this study because the HRQoL interview was completed before AMD was graded and ascertained. Although our overall sample of AMD was large compared with previous studies,2,6,9,32,33 we did not have a large number of participants with late AMD. The use of cross-sectional data limited our ability to make conclusions on the effect of longitudinal changes in AMD on HRQoL. Because our study focused primarily on the adult Latino population in Los Angeles County, our findings may not be generalizable to the entire adult US population or US Latinos.
In this cohort of Latinos, patients with AMD reported worse HRQoL. We observed a strong inverse association between severity and bilaterality of AMD and HRQoL in which participants with bilateral large drusen and depigmentation had a substantially lower HRQoL than people with a unilateral condition of the same severity. Further research is warranted to focus on intervention programs that target patients at risk for the most severe decline in visual functioning and HRQoL.
Submitted for Publication: November 25, 2015; final revision received February 22, 2016; accepted February 23, 2016.
Corresponding Author: Rohit Varma, MD, MPH, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo St, Ste 4900, Los Angeles, CA 90033.
Published Online: April 28, 2016. doi:10.1001/jamaophthalmol.2016.0794.
Author Contributions: Drs Varma and Azen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Choudhury, Varma.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Choudhury, McKean-Cowdin.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Choudhury, Gauderman, Azen.
Obtained funding: Varma.
Administrative, technical, or material support: Varma, Klein.
Study supervision: Varma, Gauderman, McKean-Cowdin.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: This work was supported by grants EY-11753 and EY-03040 from the National Eye Institute and the National Center on Minority Health and Health Disparities, National Institutes of Health and an unrestricted grant from Research to Prevent Blindness (Dr Varma).
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.
The Los Angeles Latino Eye Study Group:USC Eye Institute, University of Southern California: Rohit Varma, MD, MPH (principal investigator), Sylvia H. Paz, MS, Stanley P. Azen, PhD, Lupe Cisneros, COA, Elizabeth Corona, Carolina Cuestas, OD, Denise R. Globe, PhD, Sora Hahn, MD, Mei-Ying Lai, MS, George Martinez, Susan Preston-Martin, PhD, Ronald E. Smith, MD, LaVina Tetrow, Mina Torres, MS, Natalia Uribe, OD, Jennifer Wong, MPH, Joanne Wu, MPH, and Myrna Zuniga; Battelle Survey Research Center, St Louis, Missouri: Sonia Chico, BS, Lisa John, MSW, Michael Preciado, BA, and Karen Tucker, MA; Ocular Epidemiology Grading Center, University of Wisconsin, Madison: Stacy M. Meuer (senior grader), and Ronald Klein, MD, MPH (coinvestigator).
Previous Presentation: This study was presented at the Association for Research in Vision and Ophthalmology Annual Meeting; May 1, 2011; Fort Lauderdale, Florida.
et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health
. 2014;2(2):e106-e116.PubMedGoogle ScholarCrossref
JI. Age-Related Macular Degeneration. 2nd ed. New York: Informa Healthcare; 2008.
R. Quality of life and health economic assessments of age-related macular degeneration. Surv Ophthalmol
. 2007;52(suppl 1):S20-S25.PubMedGoogle ScholarCrossref
et al; STAR Collaboration. Three-particle coincidence of the long range pseudorapidity correlation in high energy nucleus-nucleus collisions. Phys Rev Lett
. 2010;105(2):022301.PubMedGoogle ScholarCrossref
et al. Optical remote sensing to quantify fugitive particulate mass emissions from stationary short-term and mobile continuous sources, part I: method and examples. Environ Sci Technol
. 2011;45(2):658-665.PubMedGoogle ScholarCrossref
C. Quality of life in age-related macular degeneration: a review of the literature. Health Qual Life Outcomes
. 2006;4:97.PubMedGoogle ScholarCrossref
M. Quality of life in patients with age-related macular degeneration: impact of the condition and benefits of treatment. Surv Ophthalmol
. 2005;50(3):263-273.PubMedGoogle ScholarCrossref
et al; ALICE Collaboration. Elliptic flow of charged particles in Pb-Pb collisions at √(SNN
) = 2.76 TeV. Phys Rev Lett
. 2010;105(25):252302.PubMedGoogle ScholarCrossref
NG. The Hispanic Population 2010 US Census Press Releases. Washington, DC: US Census Bureau; 2010.
et al; Los Angeles Latino Eye Study Group. The Los Angeles Latino Eye Study: design, methods, and baseline data. Ophthalmology
. 2004;111(6):1121-1131.PubMedGoogle ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Four-year incidence and progression of diabetic retinopathy and macular edema: the Los Angeles Latino Eye Study. Am J Ophthalmol
. 2010;149(5):752-761.e1, 3.PubMedGoogle ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Prevalence of age-related macular degeneration in Latinos: the Los Angeles Latino Eye Study. Ophthalmology
. 2004;111(7):1288-1297.PubMedGoogle ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Risk factors for four-year incidence and progression of age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol
. 2011;152(3):385-395.PubMedGoogle ScholarCrossref
et al; Submacular Surgery Trials Research Group. Responsiveness of the National Eye Institute Visual Function Questionnaire to changes in visual acuity: findings in patients with subfoveal choroidal neovascularization–SST Report No. 1. Arch Ophthalmol
. 2003;121(4):531-539.PubMedGoogle ScholarCrossref
J. Quality of life with visual acuity loss from diabetic retinopathy and age-related macular degeneration. Arch Ophthalmol
. 2002;120(4):481-484.PubMedGoogle ScholarCrossref
L. The Wisconsin age-related maculopathy grading system. Ophthalmology
. 1991;98(7):1128-1134.PubMedGoogle ScholarCrossref
T. The relationship of cardiovascular disease and its risk factors to age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology
. 1993;100(3):406-414.PubMedGoogle ScholarCrossref
SC. The relation of cardiovascular disease and its risk factors to the 5-year incidence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology
. 1997;104(11):1804-1812.PubMedGoogle ScholarCrossref
DL. The Wisconsin epidemiologic study of diabetic retinopathy, XI: the incidence of macular edema. Ophthalmology
. 1989;96(10):1501-1510.PubMedGoogle ScholarCrossref
SDA. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care
. 1996;34(3):220-233.PubMedGoogle ScholarCrossref
RD; National Eye Institute Visual Function Questionnaire Field Test Investigators. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol
. 2001;119(7):1050-1058.PubMedGoogle ScholarCrossref
et al. Psychometric properties of the 25-item NEI-VFQ in a Hispanic population: Proyecto VER. Invest Ophthalmol Vis Sci
. 2001;42(3):606-613.Google Scholar
RD; NEI-VFQ Field Test Investigators. Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ). Arch Ophthalmol
. 1998;116(11):1496-1504.PubMedGoogle ScholarCrossref
et al. Validation of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in age-related macular degeneration. Invest Ophthalmol Vis Sci
. 2011;52(6):3354-3359.PubMedGoogle ScholarCrossref
NM. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: validation studies from two phase 3 clinical trials. Invest Ophthalmol Vis Sci
. 2009;50(8):3629-3635.PubMedGoogle ScholarCrossref
J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Orlando, FL: Academic Press Inc; 1988.
SJ. Locally weighted regression: an approach to regression-analysis by local fitting. J Am Stat Assoc
. 1988;83(403):596-610.Google ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Four-year incidence and progression of age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol
. 2010;149(5):741-751.PubMedGoogle ScholarCrossref
JM. Influence of age-related maculopathy on visual functioning and health-related quality of life. Am J Ophthalmol
. 1999;128(1):45-53.PubMedGoogle ScholarCrossref
SI. The psychosocial impact of macular degeneration. Arch Ophthalmol
. 1998;116(4):514-520.PubMedGoogle ScholarCrossref
C. Early age-related maculopathy and self-reported visual difficulty in daily life. Ophthalmology
. 2002;109(7):1235-1242.PubMedGoogle ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Severity of diabetic retinopathy and health-related quality of life: the Los Angeles Latino Eye Study. Ophthalmology
. 2011;118(4):649-655.PubMedGoogle ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Severity of visual field loss and health-related quality of life. Am J Ophthalmol
. 2007;143(6):1013-1023.PubMedGoogle ScholarCrossref
R; Los Angeles Latino Eye Study Group. The impact of change in visual field on health-related quality of life: the Los Angeles Latino Eye Study. Ophthalmology
. 2011;118(7):1310-1317.PubMedGoogle Scholar
et al. Evaluating contrast sensitivity in age-related macular degeneration using a novel computer-based test, the Spaeth/Richman Contrast Sensitivity Test. Retina
. 2015;35(7):1465-1473.PubMedGoogle ScholarCrossref
V. A new maximum color contrast sensitivity test for detecting early changes of visual function in age-related macular degeneration. Medicina (Kaunas)
. 2014;50(5):281-286.PubMedGoogle ScholarCrossref
Jr. Comparison of visual function in older eyes in the earliest stages of age-related macular degeneration to those in normal macular health. Curr Eye Res
. 2015;41(2):1-7.PubMedGoogle Scholar
NM. Use of patient-reported outcomes in medical product development: a report from the 2009 NEI/FDA Clinical Trial Endpoints Symposium. Invest Ophthalmol Vis Sci
. 2010;51(12):6095-6103.PubMedGoogle ScholarCrossref
TE. Responsiveness of the National Eye Institute Visual Function Questionnaire to progression to advanced age-related macular degeneration, vision loss, and lens opacity: AREDS Report no. 14. Arch Ophthalmol
. 2005;123(9):1207-1214.PubMedGoogle ScholarCrossref
SP; Los Angeles Latino Eye Study Group. Longitudinal changes in visual acuity and health-related quality of life: the Los Angeles Latino Eye study. Ophthalmology
. 2010;117(10):1900-1907, 1907.e1.PubMedGoogle ScholarCrossref
R; Los Angeles Latino Eye Study Group. Impact of visual field loss on health-related quality of life in glaucoma: the Los Angeles Latino Eye Study. Ophthalmology
. 2008;115(6):941-948.e1.PubMedGoogle ScholarCrossref