Ranked Importance of Visual Function Outcome Measures in Choroideremia Clinical Trials.

Purpose: Clinical trials of novel therapies for choroideremia require robust and clinically meaningful visual function outcome measures. Best-corrected visual acuity (BCVA) is mostly insensitive to changes in disease state, until late stages, and hence also to potential therapeutic gains after gene therapies. While the insensitivity of BCVA as an effective outcome measure is common wisdom, its low importance has not been rigorously demonstrated in the literature. This work uses statistical techniques to rank the relative importance of potential functional outcome measures in choroideremia.

Methods: Retrospective dominance analysis was performed on data from a longitudinal interventional clinical trial performed at the Oxford Eye Hospital. Functional data from the untreated eye were analyzed and correlated with an anatomic measure of disease progression in the form of blue fundus autofluorescence area of the surviving outer retinal island. Each functional measure was then ranked in terms of variable importance.

Results: Microperimetry was the functional measure ranking first in terms of variable importance, followed by time since baseline visit, Pelli-Robson contrast sensitivity, high spatial frequency contrast sensitivity function, and low luminance visual acuity. Early Treatment Diabetic Screening chart BCVA under standard lighting conditions was ranked lowest among the panel of test modalities.

Conclusions: Clinical trials in choroideremia for early and mid-stage disease would be justified in moving away from using standard BCVA as a clinical trial outcome measure as we have shown its sensitivity to be relatively low compared to microperimetry. We have also demonstrated how functional measures rank in terms of importance.