We sought to examine the responsiveness—the ability to detect changes over time—of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25, see sidebar) and examine its association with visual acuity using data from the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) trial.1 The NEI VFQ-25 measures the dimensions of self-reported vision-targeted health status that are most important for individuals who have chronic eye diseases.

Macular degeneration affects the most critical types of visual functioning, which has an impact on our patients' lifestyle and life quality. Because the NEI VFQ measures patients' subjective evaluation of their visual functioning and how impairment in vision affects their lives, this study was designed to evaluate if this subjective measure of visual function—the NEI VFQ—is reliable, valid, and responsive to a standard measure of vision utilized in clinical trials (BCVA using standardized Early Treatment of Diabetic Retinopathy Study [ETDRS] vision protocols).

Patients in the MARINA trial had minimally classic or occult, but no classic, subfoveal neovascular age-related macular degeneration (AMD). These patients were presumed to have recent disease progression and were randomized in a 1:1:1 fashion to either monthly 0.3 mg or 0.5 mg ranibizumab (Lucentis; Genentech, South San Francisco) or sham injection. Patients had only one eye treated; patient-reported visual function was collected using the NEI VFQ-25. We measured BCVA using the number of letters on the ETDRS. We defined three BCVA categories of change from baseline to the 12-month point: ≥15 letters lost, <15 letters lost or gained, and ≥15 letters gained.

STUDY PARTICIPANTS
We also analyzed model-derived least squares mean changes in NEI VFQ-25 scores by BCVA category. This study included 710 patients, with 152 in the ≥15-letter BCVA group, 444 patients in the <15-letter group, and 114 patients in the ≥15-letter group. We then used regression and analysis of covariance (ANCOVA) models, adjusted for age and gender, to examine change from baseline to 12 months in NEI VFQ-25 scores by BCVA.

For the composite score, patients who lost ≥15 letters from baseline had a mean change of -6.3 points (95% confidence interval [CI], -8.6 to -3.9) and patients who gained ≥15 letters had an estimated mean change of 8.2 points (CI, 6.1-10.2). Results were similar for the subscales that were prespecified as secondary endpoints: near activities, distance activities, and vision-specific dependency. We found a 14- to 20-point difference in mean NEI VFQ-25 composite and the previously mentioned subscale scores between patients who gained ≥15 letters from baseline versus patients who lost ≥15 letters from baseline.

COMPLEMENT TO CLINICAL INFORMATION
We concluded that the NEI VFQ-25 was responsive to changes in patients' visual acuity and was able to differentiate between patients who were responders to the clinically important endpoint of 15-letter gain versus those who were not. The NEI VFQ-25 can provide information on vision-related function from the patient's perspective, which may complement clinical information on patients' response to treatment in AMD studies.

The NEI VFQ-25 showed a large separation between the groups with improved BCVA (gained ≥15 letters), stable BCVA (gained or lost <15 letters), and worse BCVA (lost ≥15 letters). These data indicate that this subjective assessment of visual function by patients is responsive to the standardized endpoints of visual measurement in clinical trials. The NEI VFQ-25 may also provide a more broad assessment of the effect of visual function on lifestyle and vision-dependent activities than BCVA alone. In the composite NEI VFQ-25 score on average, the 15-letter or better improvement in BCVA corresponded to an increase in the NEI VFQ-25 score of 8.2 in the MARINA trial.

Gregg T. Kokame, MD, MMM, is Medical Director of the Retina Center at Pali Momi, a hospital-based research and treatment center, and Clinical Professor in the Division of Ophthalmology of the Department of Surgery of the University of Hawaii School of Medicine in Honolulu. He is also a vitreoretinal consultant to the Tripler Army Medical Center and to the Queen Emma Clinic. Dr. Kokame states that he is a paid consultant for Genentech, Alcon and Pfizer. He may be reached at retinahi@aol.com; or phone: 808-487-8928.

  1. Kokame GT, Bressler NM, Yu EB et al. Responsiveness of NEI VFQ-25 to change in visual acuity in the MARINA trial. Presented at the Retina Society Annual Scientific Meeting. Sept. 27-30, 20007. Boston.