Abstract
Purpose.:
To evaluate the psychometric characteristics of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with age-related macular degeneration (AMD) who participated in two clinical trials.
Methods.:
A secondary analysis of data from two randomized clinical trials was performed. NEI VFQ-25 data were collected from 1134 of 1146 patients with subfoveal choroidal neovascularization due to AMD with minimally classic or occult with no classic types and predominantly classic type. The NEI VFQ-25 was administered at baseline and months 1, 2, 3, 6, 9, and 12, and the SF-36 Health survey was administered at baseline and months 6 and 12. Visual acuity assessments were completed monthly throughout the studies. Internal consistency reliability and construct validity were examined.
Results.:
The average age was 77 years (SD = 7.5; range, 52–96) with 59% women. At baseline, internal consistency reliability was 0.96 for the NEI VFQ-25 total score and ranged from 0.62 (ocular pain) to 0.91 (near activities) for the subscales. NEI VFQ-25 total and subscale scores correlated significantly with SF-36 scores (P < 0.05), and total, near activities, distance activities, and dependency scores correlated significantly with best corrected visual acuity (BCVA) in the better (P < 0.0001) and worse seeing eye (P < 0.0001). Mean NEI VFQ-25 total and subscale scores, except for ocular pain and general health, varied by BCVA group (P < 0.001), with higher impairment scores seen in the lower visual acuity groups.
Conclusions.:
The NEI VFQ-25 demonstrated good reliability and construct validity as a measure of vision-related functioning outcomes in patients with AMD.
Age-related macular degeneration (AMD) is a condition affecting central vision, resulting in low vision and blindness. The neovascular form of the disease, characterized by abnormal growth of new blood cells under or within the macula, usually causes severe vision loss. In the United States, prevalence of AMD is estimated at 1.47% among those 40 years of age and older, affecting approximately 1.75 million individuals.
1 Globally, AMD is the third leading cause of blindness and the primary cause of blindness in developed countries.
2,3 As a result of the aging of populations, it has been estimated that, by 2020, approximately 7.5 million people worldwide will have AMD.
AMD markedly affects visual functioning and can lead to a decline in the health-related quality of life and impaired daily functioning. Assessments of visual acuity provide an objective assessment of a patient's clinical status and response to treatment, but do not comprehensively capture the effect on a patient's well-being and functioning in everyday life.
4–10 Comprehensive assessment of the impact of visual impairment is essential, as patients with similar visual acuity or comparable areas of affected macula often report different levels of difficulty in performing visual tasks and other related functions.
11
Visual impairment and progression to blindness significantly impact health-related quality of life and are accompanied by an increase in functional disability and dependency, accidents, and depression. Decline in visual acuity is often accompanied by a decline in physical function and mental health.
9,12,13 Clinician assessments tend to underestimate the impact of vision loss and impairment.
8 Measurement of health-related quality of life and patient-reported visual function outcomes has increased understanding of the impact of visual impairment on everyday activities in patients with eye diseases.
4,14–18
The most frequently used measure of patient-reported, vision-related functioning in AMD studies is the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25).
4,10,13,16,18–21 Based on qualitative research with patients, the NEI VFQ-25 was developed to measure the range of vision-related functioning experienced by persons with a variety of chronic eye diseases.
13,22 Although there is evidence supporting the psychometric characteristics of NEI VFQ-25,
21,23 few studies have been conducted to examine the relationship between clinical measures and the NEI VFQ-25 in patients with AMD. Understanding these relationships is essential as the correlations between visual acuity, the NEI VFQ-25, and other vision-specific measures
4,8–10,23,24 suggest that clinical and vision-related functional assessments are not interchangeable.
The NEI VFQ-25 was recently used in two phase III clinical trials of ranibizumab.
25,26 The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA) study was a 2-year, prospective, randomized, double-blind, sham-controlled study of the safety and efficacy of repeated intravitreal injections of ranibizumab among patients with choroidal neovascularization associated with AMD.
26 The Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) trial was an international, multicenter, randomized, double-blind, active-treatment–controlled study comparing ranibizumab and verteporfin.
25 A prevention rate was approximately 95% in loss of visual acuity and an improvement in 36% to 40% of patients was observed in the MARINA and ANCHOR clinical trials in those receiving monthly intravitreal injections of ranibizumab.
In the present study, a secondary analysis of the MARINA and ANCHOR clinical trial data were performed to evaluate the psychometric characteristics of the NEI VFQ-25 in patients with subfoveal choroidal neovascularization due to AMD. We report on the reliability and construct validity of the NEI VFQ-25 total and subscale scores. Given that few studies have been performed to evaluate of the psychometric qualities of the NEI VFQ-25 in patients with AMD, we present this report as a contribution to the greater understanding of the measurement properties of this vision-related function instrument. These study findings complement those of Suner et al.
27 who recently used the ANCHOR and MARINA data to report on the responsiveness of the NEI VFQ-25 to changes in visual acuity.
NEI VFQ-25.
SF-36 Health Survey.
Visual Analog Scale.
Visual Acuity Outcomes.
Contrast Sensitivity.
A total of 1134 of 1146 patients completed the VFQ-25 at baseline, with the majority female (59.3%) and Caucasian (97%). Mean age was 77 years (SD 7.5), with participants ranging between 52 and 96 years of age.
Table 1 presents the clinical characteristics of the study population. A mean of 0.6 years (SD 1.23) had elapsed since diagnosis of AMD. Median visual acuity in the study eye was 20/100 and ranged from 20/63 to 20/160. Forty-five percent of participants had not received any therapy for AMD in the study eye.
Table 1. Clinical Characteristics: Pooled ANCHOR and MARINA Studies
Table 1. Clinical Characteristics: Pooled ANCHOR and MARINA Studies
Characteristic | All Patients* (n = 1134) |
Years since diagnosis, mean (SD) | 0.6 (1.2) |
Range | (0.1–18.9) |
Missing, n (%) | 61 (5.4%) |
Median visual acuity - Worse seeing eye† | 20/125 |
Quartiles | 20/80–20/250 |
Median visual acuity - Better seeing eye† | 20/40 |
Quartiles | 20/25–20/80 |
Prior therapies received for AMD in study eye, n (%) | |
None | 538 (45.0%) |
Laser photocoagulation | 110 (9.2%) |
Medication | 10 (0.8%) |
Other | 14 (1.2%) |
Supplements | 524 (43.8%) |
Mean subscale scores of the NEI VFQ-25 ranged from 51.2 (SD 36.4) for driving to 88.7 (SD 15.6) for ocular pain (
Table 2). The mean NEI VFQ-25 total score was 69.5 (SD 19.9). The near vision subscale had a mean score of 57.6 (SD 26.3), whereas the mean score on the distance vision subscale was 66.2 (SD 25.3). Few missing items were observed (<1.2%), except for the driving subscale (13%).
Table 2. Descriptive Statistics of the NEI VFQ-25 Total and Subscale Scores
Table 2. Descriptive Statistics of the NEI VFQ-25 Total and Subscale Scores
Subscale/Total Score | n | Mean | SD | Median | Range |
Near vision | 1134 | 57.6 | 26.34 | 58.3 | 0–100 |
Distance vision | 1134 | 66.2 | 25.28 | 70.8 | 0–100 |
General health | 1134 | 63.5 | 22.18 | 75.0 | 0–100 |
General vision | 1134 | 55.4 | 19.86 | 60.0 | 20–100 |
Driving | 987 | 51.2 | 36.38 | 58.3 | 0–100 |
Peripheral vision | 1131 | 80.5 | 24.34 | 100.0 | 0–100 |
Color vision | 1120 | 87.7 | 21.94 | 100.0 | 0–100 |
Ocular pain | 1134 | 88.7 | 15.61 | 100.0 | 13–100 |
Vision specific | | | | | |
Role difficulties | 1134 | 64.3 | 30.44 | 75.0 | 0–100 |
Dependency | 1134 | 73.0 | 29.84 | 83.3 | 0–100 |
Social functioning | 1133 | 80.2 | 25.21 | 87.5 | 0–100 |
Mental health | 1134 | 58.6 | 27.16 | 62.5 | 0–100 |
Total score | 1134 | 69.5 | 19.91 | 73.5 | 12–100 |
Subscale-to-subscale correlations ranged from 0.10 (driving and general health) to 0.84 (near vision and distance vision). Subscale to NEI VFQ-25 total correlations ranged from 0.18 (general health) to 0.91 (distance vision). The near and distance vision subscales correlated moderately 0.69 to 0.79 with the other NEI VFQ-25 subscale scores.
Table 3 presents the correlations between the NEI VFQ-25 scores and BCVA for the better- and worse-seeing eyes. The NEI VFQ-25 total score correlated strongly with the BCVA of the better-seeing eye (
r = 0.68,
P < 0.0001). Overall, stronger correlations were observed between the NEI VFQ-25 subscales and the visual acuity of the better-seeing than the worse-seeing eye. With the exception of general health and ocular pain, all correlations between the NEI VFQ-25 subscale scores and BCVA in the better- and worse-seeing eyes were significant.
Table 3. Correlations between NEI VFQ-25 Scores and Visual Acuity in the Better- and Worse-Seeing Eyes*
Table 3. Correlations between NEI VFQ-25 Scores and Visual Acuity in the Better- and Worse-Seeing Eyes*
VFQ-25 Subscale/Total Score | VA (Better-Seeing Eye) | VA (Worse-Seeing Eye) |
Near vision | 0.71† | 0.46† |
Distance vision | 0.64† | 0.44† |
General health | 0.05 | 0.01 |
General vision | 0.60† | 0.40† |
Driving | 0.64† | 0.43† |
Peripheral vision | 0.30† | 0.24† |
Color vision | 0.33† | 0.26† |
Ocular pain | 0.04† | 0.03 |
Vision specific | | |
Role difficulties | 0.51† | 0.34† |
Dependency | 0.61† | 0.39† |
Social functioning | 0.56† | 0.41† |
Mental health | 0.56† | 0.35† |
Total score | 0.68† | 0.46† |
Correlations between the NEI VFQ-25 total score and the SF-36 variables were mostly low and significant, with the exception of the correlation between bodily pain and driving (r = 0.06, NS; data not shown). The near and distance vision subscales demonstrated generally low but significant correlation with the SF-36 subscale and summary scores, range: r = 0.10 (P < 0.01) to 0.31 (P < 0.0001). Correlations between the NEI VFQ-25 total score and the physical and mental component summary scores were 0.24 (P < 0.0001) and 0.32 (P < 0.0001), respectively.
Correlations between the NEI VFQ-25 and contrast sensitivity were low to moderate and significant (r = 0.06–0.56, P < 0.05–0.0001), with the exception of the correlation with general vision (r = 0.059, NS) and the worse-seeing eye and ocular pain in both the better- and worse-seeing eyes (r = 0.5 and 0.01, respectively, NS; data not shown). The visual analogue scale correlated only with the general health (r = 0.40, P < 0.0001), near vision (r = 0.18, P < 0.05) and ocular pain (r = 0.21, P < 0.01) subscales of the NEI VFQ-25 (data not shown).
ANCOVA models, controlling for age and sex, were used to examine the association between visual acuity in the better-seeing eye and the NEI VFQ-25 subscale and total scores (
Table 4). Mean NEI VFQ-25 total scores were significantly higher in those groups with better visual acuity (all
P < 0.05), indicating better vision-related function. Statistically significant differences in mean NEI VFQ-25 subscale scores by BCVA category of the better eye were observed (all
P < 0.01), with the exception of general health. As visual acuity decreased, NEI VFQ-25 subscale scores decreased, indicative of worsening vision-related functioning and health-related quality of life.
Table 4. NEI VFQ-25 Scores by Visual Acuity in the Better-Seeing Eye
Table 4. NEI VFQ-25 Scores by Visual Acuity in the Better-Seeing Eye
VFQ-25 Subscale/Total Score LS Mean (SE) | BCVA (Snellen Equivalent) | Overall F Value | Pair-wise Comparison* |
Group 1 20/20–20/80 (n = 822) | Group 2 20/100–20/160 (n = 153) | Group 3 ≥20/200 (n = 66) |
Near vision | 62.46 (0.80) | 32.69 (1.83) | 25.41 (2.79) | 88.68† | A† B† |
Distance vision | 71.07 (0.79) | 44.71 (1.81) | 34.59 (2.76) | 78.14† | A† B† C‡ |
General health | 63.67 (0.79) | 63.85 (1.80) | 58.69 (2.75) | 1.79 | |
General vision | 58.66 (0.63) | 39.69 (1.45) | 33.43 (2.21) | 60.68† | A† B† |
Driving | 58.31 (1.17) | 16.79 (2.68) | 8.33 (4.34) | 86.71† | A† B† |
Peripheral vision | 82.89 (0.86) | 70.42 (1.96) | 66.57 (3.01) | 15.173 † | A† B† |
Color vision | 90.17 (0.78) | 77.05 (1.77) | 71.21 (2.71) | 20.97† | A† B† |
Ocular pain | 89.06 (0.56) | 88.27 (1.28) | 87.54 (1.95) | 3.95‡ | |
Vision specific | | | | | |
Role difficulties | 68.18 (1.01) | 42.20 (2.30) | 36.09 (3.51) | 43.27† | A† B† |
Dependency | 78.96 (0.94) | 46.54 (2.15) | 36.25 (3.27) | 80.05† | A† B† C§ |
Social functioning | 84.79 (0.82) | 61.33 (1.89) | 49.81 (2.87) | 60.37† | A† B† C‡ |
Mental health | 62.68 (0.89) | 38.86 (2.03) | 31.52 (3.09) | 48.33† | A† B† |
Total score | 73.49 (0.61) | 51.14 (1.40) | 44.29 (2.13) | 89.19† | A† B† C§ |
A similar pattern of differences in mean NEI VFQ-25 scores were observed by BCVA for the worse-seeing eye (data not shown). Mean NEI VFQ-25 total and subscale scores, except for general health, significantly varied by BCVA group (all P < 0.01).
The ANCOVA models, controlling for age and sex, used to examine the association between contrast sensitivity and the NEI VFQ-25 subscale and total scores showed a similar pattern of differences in mean NEI VFQ-25 scores as those found with BCVA (data not shown). Mean NEI VFQ-25 total scores were significantly higher in patients with better contrast sensitivity (all P < 0.05), indicating better vision-related function. Statistically significant differences in mean NEI VFQ-25 subscale scores between the best and worst contrast sensitivity categories were observed (all P < 0.05), with the exception of general vision. As contrast sensitivity decreased, NEI VFQ-25 subscale scores decreased, indicative of worsening vision-related functioning and health-related quality of life.