A 5- to 10-point Visual Function Questionnaire improvement signifies meaningful change in vision, researchers find

April 15, 2008

An analysis of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) results from a large clinical trial of ranibizumab (Lucentis, Genentech) in patients with age-related macular degeneration has shown that an improvement of 5 to 10 points on the VFQ-25 score correlated with meaningful clinical improvement in vision.

Key Points

Indian Wells, CA-Investigators using data from the Minimally Classic/Occult Trial of the Anti-VEGF Antibody fragment Ranibizumab in the treatment of Neovascular AMD (MARINA) trial have determined what constitutes clinically meaningful change in the National Eye Institute (NEI) Visual Function Questionnaire (VFQ-25).

The clinically meaningful difference in the NEI-VFQ-25 was about 5 points in most of the different subscales, and these data confirm that changes of even fewer than 10 points in the NEI-VFQ can bring about clinically meaningful improvement in patients' ability to perform activities related to near vision, distance vision, and vision-specific dependency, said Gregg T. Kokame, MD, MMM, who spoke on behalf of the MARINA Study Group here at the annual meeting of the American Society of Retina Specialists. He is medical director of the Retina Center at Pali Momi and clinical professor, ophthalmology division, Department of Surgery, University of Hawaii School of Medicine, Honolulu.

VFQ-25 scores

A clinically meaningful change in the VFQ-25 is considered to be greater than or equal to a 15-letter change in best-corrected visual acuity. Several studies, however, have suggested that a lesser change in the VFQ-25 score also could be clinically meaningful, so investigators performed an analysis to see whether a clinically meaningful change in the VFQ-25 was related to the best-corrected visual acuity letter score in the MARINA study, Dr. Kokame said.

In MARINA, subjects with minimally classic or occult lesions with no classic subfoveal neovascular AMD and presumed disease progression were randomly assigned 1:1:1 to monthly sham injection or injection with 0.3 or 0.5 mg ranibizumab (Lucentis, Genentech).

Investigators previously reported significant differences in mean change from baseline VFQ-25 scores over time for patients treated with ranibizumab versus patients treated with sham in the MARINA trial. The test had been administered at baseline, 1, 2, 3, 6, 9, and 12 months in the first year of the study, and at 18 and 24 months in the second year. In the new analysis, the researchers wanted to determine whether the effect on the VFQ-25 was driven more by the better-seeing eye.

A regression analysis adjusted for age and gender was used to examine change from baseline to 12 months in VFQ-25 scores by visual acuity. All treatment groups were pooled for the analysis for a total of 716 patients; 308 were treated in their better-seeing eye, and 408 were treated in their worse-seeing eye. Because a significant effect of treatment had been found at 12 months, investigators were able to evaluate groups of data for patients with loss of vision as well as improvement in vision, Dr. Kokame said.

The results of the regression analysis showed a significant positive correlation between a 15-letter change in visual acuity and the VFQ-25 composite score (4.4-point change) as well as the near activities (6.0-point change), distance activities (5.4-point change), and vision-specific dependency (5.0-point change) subscale scores.

The estimates of change, however, rose significantly in the patients treated in their better-seeing eye, suggesting that much of the effect may be driven by the better-seeing eye, Dr. Kokame said. The estimates increased to a 7.4-point change for the composite score, 10.0 points for near activities, 9.4 points for distance activities, and 10.0 points for vision-specific dependency.

The correlation between the VFQ-25 score and the letter visual acuity score, however, still was significant for patients treated in their worse-seeing eye, Dr. Kokame said.

"We feel that it's important to identify the clinically meaningful difference for the NEI-VFQ so that we can understand and use this in making decisions for our patients in future trials," he added. "The NEI-VFQ may provide a broader measure of visual function and how therapies actually affect our patients' ability to function visually in their day-to-day activities."