To assess vision-specific quality of life (QOL), based on abbreviated surveys derived from the National Eye Institute Visual Function Questionnaire (NEI-VFQ), in a cohort of United States women who participated in the Study of Osteoporotic Fractures.
Prospective, observational cohort study.
Age-related macular degeneration (AMD) status, based on a 3-level classification (no AMD, early AMD, late AMD), and vision-specific QOL, based on abbreviated NEI-VFQ surveys, were calculated for 1674 women enrolled in the Study of Osteoporotic Fractures at 4 centers within the United States who had gradable fundus photographs at both the 10-year and 15-year follow-up visits. The associations among 5-year changes in NEI-VFQ composite scores, change in AMD status, and distance visual acuity were examined.
Compared with study participants without AMD at both visits, study participants with late AMD at both visits and those who progressed from early AMD to late AMD demonstrated the greatest declines in adjusted NEI-VFQ composite scores, up to a mean decrease of 16.2 from a scale of 100. Visual acuity declines also were most prominent for patients with late AMD at both visits and for those who progressed from early AMD to late AMD. Change in visual acuity was found to correlate significantly with change in vision-specific QOL.
The abbreviated NEI-VFQ surveys provide reliable assessments of vision-specific QOL in AMD patients. The decline in vision-specific QOL associated with the progression of AMD is clinically meaningful.
Age-related macular degeneration (AMD) is a devastating cause of visual impairment among individuals 65 years of age and older and currently is the leading cause of blindness and severe vision loss in the developed world. In the United States, it is estimated that 9 million Americans have AMD, which include patients with both early and late forms of the disease. Although early AMD accounts for 80% to 90% of all AMD cases, late AMD (i.e., neovascular AMD and subfoveal geographic atrophy) is responsible for approximately 90% of severe vision loss associated with AMD.
Given the aging of the population and the established risk of AMD associated with increasing age, it is important to understand the impact of AMD on quality of life (QOL). Several studies have assessed the impact of AMD on QOL in patients with advanced disease, patients with early disease, as well as patients across the spectrum of disease, including one study that assessed the impact of progression from early to advanced AMD on QOL in the Age-Related Eye Disease Study. Methods used for assessing the impact of AMD on QOL in these studies include overall health-related QOL assessments such as utility analyses (time trade-off and standard gamble methods) as well as general health questionnaires including the Medical Outcomes Study 36-item Short Form survey and the abbreviated 12-item Short Form-12 survey.
Although general health-related QOL assessments provide a good benchmark for comparison of QOL impact across diseases affecting different organ systems, instruments developed specifically to measure vision-targeted health-related QOL may provide improved accuracy for assessing the impact of vision-threatening disease, particularly with advancing disease progression. Among the validated vision-specific function instruments of this nature used to assess the impact of AMD on QOL in previous studies, the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ) has been used most commonly. The 25-item NEI-VFQ was developed as a short form of the originally validated 51-item NEI-VFQ, recognizing that survey length may substantially impact both data quality and costs. Further abbreviated questionnaires subsequently were devised by the original developers of the 51-item NEI-VFQ using similar qualitative and quantitative analyses used in the development of the 25-item NEI-VFQ. These include a 9-item instrument (NEI-VFQ-9) as well as an 8-item instrument (NEI-VFQ-8), which omits a question regarding difficulty with daytime driving. The NEI-VFQ-9 had been used in the National Health and Nutrition Examination Survey since 1999 and the data currently are being analyzed (Mangione C, personal communication, 2009). Recently, both the NEI-VFQ-9 and NEI-VFQ-8 have been validated in patients with vision-threatening diseases, including AMD.
The primary objective of this study was to assess the impact of AMD on vision-specific QOL based on data obtained from the 10-year and 15-year follow-up clinic visits of the previously described incidence of AMD (IAMD) sub-study of the longitudinal Study of Osteoporotic Fractures (SOF). Given that the SOF is a large, population-based study with multiple objectives, the recently validated NEI-VFQ-9 was chosen as a convenient instrument for assessment of vision-specific QOL. Furthermore, because a relatively large percentage of SOF patients (33%) were not driving at the 10-year follow-up clinic visit of the SOF (the baseline visit for this study), composite scores of the NEI-VFQ-8 were also used to assess vision-specific QOL. Since the IAMD sub-study also provides longitudinal data over 5-years in AMD patients, including collection of visual acuity data, this study also aims to assess correlations between visual acuity and vision-specific QOL in AMD patients with progression of disease.
Details of the design and methods of the IAMD sub-study and the SOF appear elsewhere. Only the major features of the IAMD and SOF studies relevant to the participant status at the time of the 10-year follow-up clinic visit are presented here. Subjects selected for the SOF were white women aged ≥65 years at original study enrollment (1986–1988) and black women aged ≥65 years at the 10-year follow-up visit (1997–1998). The participants were recruited from four centers in the United States located in Oregon, Minnesota, Pennsylvania, and Maryland. All individuals in the study gave informed consent to participate after obtaining Institutional Review Board approvals from all participating institutions. Subjects were included in the present study if they attended the 10-year and 15-year follow-up clinic visits of the SOF in 1997–1998 and 2002–2004, respectively, and had gradable fundus photographs in both eyes at both visits.
Of the 9704 white women enrolled at baseline in the SOF, 4820 attended the 10-year clinic visit. All 662 black women enrolled in 1997–1998 attended the 10-year clinic visit. Of these 5482 women attending the 10-year clinic visit, 2252 were eligible for the study of incidence AMD. Among them, 578 (26%) were excluded due to the lack of fundus photographs or ungradable fundus photographs in both eyes at 10-year and/or 15-year clinic visits. Thus, 1674 were included in the present study. Grading for AMD was determined based on 45 degree stereoscopic fundus photos using a modification of the Wisconsin Age-Related Maculopathy Grading System (WARMGS) used in the National Health and Nutrition Examination Survey III. AMD characteristics and severity were graded on a 6-level scale used in the Beaver Dam Eye Study and modified for use with 45 degree stereoscopic photos ( Table 1 ). Based on AMD severity scale level in both eyes, participants were classified into 3 categories of AMD status: no AMD, early AMD, and late AMD, as outlined at the bottom of Table 1 . In cases of a discrepancy in the AMD status categorization of a participant, or in cases where fundus photos were deemed not gradable by at least one grader, photographs were evaluated by a retina specialist whose grading was taken as final.
|Unilateral Eye Grading Level||Description|
|Level 10||No drusen, or hard drusen, or small drusen <95 μm in diameter only, regardless of area of involvement, and no pigmentary abnormality present|
|Level 20||Hard drusen or small drusen <95 μm in diameter, regardless of area of involvement, with increased retinal pigment present but no RPE depigmentation; or soft drusen (≥95 μm) with drusen area less than that of a circle with diameter of 960 μm and no pigment abnormalities present|
|Level 30||Soft drusen (≥95 μm) with drusen area less than that of a circle with diameter of 960 μm and RPE depigmentation present; or soft drusen with drusen area of a circle with a diameter of 960 μm or more with or without increased retinal pigment but no RPE depigmentation|
|Level 40||Soft drusen (≥95 μm) with drusen area of a circle with a diameter of 960 μm or more and RPE depigmentation present with or without increased retinal pigment|
|Level 50||Geographic atrophy under the fovea|
|Level 60||Exudative macular degeneration with or without geographic atrophy present|
|Participant AMD category|
|No AMD||Level 10 or 20 in both eyes|
|Early AMD||Level 30 or 40 in at least 1 eye, but neither levels 50 or 60 in either eye|
|Late AMD||Level 50 or 60 in at least 1 eye|
Distance visual acuity (VA) was assessed in all participants and both 10-year and 15-year follow-up clinic visits. Bailey-Lovie charts were used to measure VA in each eye separately with habitual correction. Vision-specific QOL was also assessed at both visits, based on administration of the NEI-VFQ-9 questionnaire to all participants. The NEI-VFQ-9 includes seven questions regarding visual functions: general vision, near vision (3 sub-questions—seeing well up close, going down stairs at night, and finding objects on a crowded shelf), distance vision, driving, peripheral vision, role limitation, and well-being/mental health. The NEI-VFQ-9 takes only three to four minutes to complete. As 33% of SOF participants did not drive at the 10-year follow-up visit, composite scores for both the NEI-VFQ-9 and the NEI-VFQ-8 (omits the driving question), were both calculated. For both questionnaires, composite scores range from 0 to 100, with 100 representing the highest possible vision-specific QOL rating. NEI-VFQ-9 composite scores were available at both the 10-year and 15-year follow-up visits for 1,021 participants and 1,584 participants at both visits for the NEI-VFQ-8 composite scores.
Potential confounders measured included age at the 10-year follow-up visit, clinical site of enrollment, ethnicity, years of education, self-reported health status, and number of comorbidities. Self-administered questionnaires were used to determine potential participant-related confounders. For health status, subjects were asked to rate their overall health, compared with others their own age, as excellent, good, fair, poor, or very poor. For the purposes of this study, health status was dichotomized as excellent or good versus fair, poor, or very poor. For comorbidities, participants were asked about having been told by a doctor whether that they had been diagnosed with any of 17 comorbidities including heart attack or myocardial infarction, stroke, diabetes, high blood pressure or hypertension, Parkinson disease, and dementia or Alzheimer disease.
All statistical analyses were performed using SAS statistical software version 9.1 (SAS Institute, Cary, North Carolina, USA). A P value of <.05 was considered to be statistically significant. Summary statistics of the participant characteristics, AMD status, and composite scores of NEI-VFQ-9 and NEI-VFQ-8 were calculated for all women who participated in the study. Changes in composite scores of NEI-VFQ-9 and NEI-VFQ-8 were evaluated among all participants and by AMD status using an analysis of variance. The impact of the change in AMD status on changes in composite scores from the NEI-VFQ-9 and NEI-VFQ-8 were analyzed further using multiple linear regression models after controlling for potential confounders listed above as well as NEI-VFQ-9 and NEI-VFQ-8 composite scores at the 10-year visit. The associations between AMD status and VA also were examined.
To control for the potential selection bias primarily resulting from loss to follow-up, all analyses were also performed using attrition weights. The attrition weights were calculated based on the assumption that subjects with a certain profile of characteristics are more likely to be included in the analysis than others. Details of the attrition weights calculation were described elsewhere.
The results from analyses with and without attrition weights were similar. Except for the descriptive tables, in which both results are presented, only attrition weight-adjusted results are presented. Characteristics of the study participants at the 10-year visit are presented in Table 2 . There were 1674 female participants in the study with a mean age of 78 years. Eighty-eight percent of participants were white, and the large majority of participants were at least high school graduates (83%) in excellent or good general health (86%) with a median of 1 reported comorbidity. The large majority of women (89%) had 10-year VA of 20/40 or better (≤0.30 logarithm of the minimal angle of resolution [logMAR] units); however, 25% of the study participants were not driving at the 10-year visit. At the 15-year follow-up visit for the SOF, 34% were not driving, and overall, 61% of participants were driving at both the 10-year and 15-year SOF follow-up visits.
|Sample size||1674 (100%)|
|Mean ± SD (range)||78.2 ± 3.6 (65 to 92)|
|65 to 74||149 (9%)|
|75 to 79||990 (59%)|
|80 to 84||453 (27%)|
|African American||200 (12%)|
|Education (yrs), n = 1673|
|≥12 (High school graduate or above)||1381 (83%)|
|Self-rated health status|
|Fair/poor/very poor||241 (14%)|
|Number of comorbidities a (0 to 17)|
|Median (range)||1 (0 to 9)|
|Habitual distance visual acuity in the better eye (logMAR); n = 1671|
|Mean ± SD (range)||0.15 ± 0.15 (−0.10 to 1.32)|
|≤0 (20/20 or better)||176 (11%)|
|0.01 to 0.30 (20/25 to 20/40)||1302 (78%)|
|0.31 to 0.99 (20/50 to better than 20/200)||189 (11%)|
|≥1.0 (20/200 or worse)||4 (<1%)|
|Driving status; n = 1670|
|Driving without any difficulty||1219 (73%)|
|Driving with difficulty||35 (2%)|
|Not driving||416 (25%)|
a Includes: (1) heart attack, coronary, or myocardial infarction; (2) angina; (3) congestive heart failure or enlarged heart; (4) other heart disease; (5) stroke; (6) diabetes (definitive, not borderline); (7) Parkinson disease; (8) dementia or Alzheimer disease; (9) other neurologic disease; (10) depression; (11) chronic obstructive lung disease, chronic bronchitis, asthma, emphysema, or chronic obstructive pulmonary disease; (12) arthritis of hips; (13) arthritis of knees; (14) osteoarthritis or degenerative arthritis; (15) rheumatoid arthritis; (16) hyperthyroidism (high thyroid); and (17) high blood pressure.
Table 3 summarizes the AMD status of participants at the 10-year and 15-year SOF follow-up visits. Seventy-two percent of participants had no AMD at year 10, whereas 60% of participants had no AMD at the 15-year visit, indicating overall progression in the study population toward development of some form of AMD. In addition, the number of late AMD participants almost doubled from the 10-year to the 15-year visits (96 to 190), indicating progression toward more severe AMD with time. Forty-seven percent (90 of 190) of women with late AMD had neovascular AMD in at least 1 eye. These trends also are reflected by the 5-year change in AMD status, whereby 17% of participants progressed from no AMD to early AMD, 5% progressed from early AMD to late AMD, and 1% progressed from no AMD to late AMD. In addition, 6% of women also regressed from early AMD to no AMD.
|Status of AMD||No. (%)||Weighted % a|
|AMD status at 10-year SOF visit|
|No AMD||1212 (72%)||72%|
|Early AMD||366 (22%)||22%|
|Late AMD||96 (6%)||6%|
|AMD status at 15-year SOF visit|
|No AMD||1003 (60%)||60%|
|Early AMD||481 (29%)||29%|
|Late AMD||190 (11%)||12%|
|5-year change in AMD status|
|No AMD at both visits||908 (54%)||54%|
|No AMD to early AMD||286 (17%)||17%|
|No AMD to late AMD||18 (1%)||1%|
|Early AMD to no AMD||95 (6%)||6%|
|Early AMD at both visits||195 (12%)||12%|
|Early AMD to late AMD||76 (5%)||5%|
|Late AMD at both visits||96 (6%)||6%|
As described above, composite scores for the NEI-VFQ-9 (for those participants who were driving at both follow-up visits) and the NEI-VFQ-8 (for the large majority of participants) were calculated. Of a total possible score of 100, the mean composite score for the NEI-VFQ-9 was 92.1 ± 9.6 at the 10-year visit and 91.0 ± 11.7 at the 15-year visit. Similarly, the mean composite score for the NEI-VFQ-8 was 90.7 ± 10.9 at the 10-year visit and 89.5 ± 12.7 at the 15-year visit. Changes in NEI-VFQ composite scores from the 10-year visit to the 15-year visit by AMD status at each visit are presented in Table 4 . Participants at the 10-year visit with no AMD and those at the 15-year visit with no AMD both had mean composite scores that did not change substantially over the 5-year period, with mean NEI-VFQ composite scores changing by no more than 0.33. However, participants at the 10-year visit with late AMD and those at the 15-year visit with late AMD had mean NEI-VFQ composite scores that worsened over the 5-year period, with mean changes of up to −9.77, indicating a decline in vision-specific QOL over time in participants with late AMD at both visits. These changes were statistically significant ( P < .001) for both NEI-VFQ scores and for both participant groups at the 10-year and at the 15-year visits when comparing among the 3 AMD status groups. Table 4 also outlines the change in NEI-VFQ composite scores by participant groups based on their 5-year change in AMD status. For the larger participant group with NEI-VFQ-8 scores, the greatest mean change in unadjusted composite scores was seen in the group that progressed from early AMD to late AMD (−12.9), and notable changes also were seen in the group that had late AMD at both visits (−8.09) and the group that progressed from no AMD to late AMD (−4.66). For participants with responses to the NEI-VFQ-9, the greatest mean change in unadjusted composite scores was seen in the group that had late AMD at both visits (−9.69), with notable changes in the group that progressed from early AMD to late AMD (−6.29) and in the group that progressed from no AMD to late AMD (−4.93). These changes were statistically significant ( P < .001) for both NEI-VFQ scores when comparing among the various changes in AMD status groups.
|Status of AMD||Change in NEI-VFQ Score, b Mean ± SD (Median)|
|8-Item Composite Score (n = 1584)||9-Item Composite Score (n = 1021)|
|AMD status at 10-year SOF visit (baseline)|
|No AMD||−0.11 ± 9.79 (0.0)||0.14 ± 8.60 (0.0)|
|Early AMD||−3.46 ± 13.2 (−0.63)||−2.89 ± 9.55 (−2.22)|
|Late AMD||−8.09 ± 21.5 (−6.62)||−9.69 ± 20.6 (−5.89)|
|P value c||<.001||<.001|
|AMD status at 15-year SOF visit|
|No AMD||0.32 ± 9.52 (0.0)||0.33 ± 8.17 (0.0)|
|Early AMD||−1.34 ± 10.6 (0.0)||−1.30 ± 9.29 (0.0)|
|Late AMD||−9.77 ± 19.5 (−6.63)||−7.81 ± 16.8 (−4.44)|
|P value c||<.001||<.001|
|5-year change in AMD status|
|No AMD at both visits||0.25 ± 9.48 (0.0)||0.49 ± 8.17 (0.0)|
|No AMD to early AMD||−0.99 ± 10.3 (0.0)||−0.72 ± 9.24 (0.0)|
|No AMD to late AMD||−4.66 ± 15.6 (−4.12)||−4.93 ± 17.6 (−3.67)|
|Early AMD to no AMD||1.03 ± 9.97 (0.0)||−1.30 ± 8.06 (0.0)|
|Early AMD at both visits||−1.85 ± 11.0 (0.0)||−2.28 ± 9.34 (−2.22)|
|Early AMD to late AMD||−12.9 ± 17.2 (−8.37)||−6.29 ± 11.1 (−3.67)|
|Late AMD at both visits||−8.09 ± 21.5 (−6.62)||−9.69 ± 20.6 (−5.89)|
|P value c||<.001||<.001|
Of 56 women with unilateral late AMD at the 10-year visit, 17 (30%) progressed to bilateral AMD. Only 10 of the 17 subjects drove at the 10-year visit and 7 of them still drove at the 15-year visit. The mean change in NEI-VFQ-8 from the 10-year visit to the 15-year visit for these 17 subjects was −14.8 ± 25.4 (median, −10.2; range, −81.9 to 39.6; n = 16).
Table 5 outlines the effects of change in AMD status on changes in mean NEI-VFQ composite scores over the 5-year study period based on linear regression models controlling for potential confounders, including NEI-VFQ scores at the 10-year visit. For both NEI-VFQ scores, change in AMD status had the greatest influence on NEI-VFQ scores in participants with late AMD at both visits (−16.2 for NEI-VFQ-8 and −14.2 for NEI-VFQ-9) and in participants who progressed from early AMD to late AMD (−13.3 for NEI-VFQ-8 and −7.91 for NEI-VFQ-9). In all 4 cases, these effects were highly statistically significant in the regression models ( P < .001). In addition, statistically significant influences on both NEI-VFQ scores also were found for participants with early AMD at both visits (−2.17 for NEI-VFQ-8 [ P = .009; −2.30 for NEI-VFQ-9 [ P = .014]). All aforementioned statistically significant changes are consistent with an anticipated negative impact of progression within the AMD continuum on vision-specific QOL. In addition, progression from no AMD to late AMD did not have a significant influence on changes in either NEI-VFQ composite scores. These findings are addressed further in the discussion.