The following is a summary of the “Therapy with voretigene neparvovec. How to measure success?,” published in the January 2023 issue of Progress in retinal and eye research by Stingl, et al.

Voretigene neparvovec, the first approved retinal gene supplementation therapy, replaces a defective gene copy with a fully functional one, allowing protein transcription in retinal cells and restoring vision. As a result of gene therapy for the underlying genetic defect, a complex network of functional regeneration ensues, the extent of which depends greatly on the patient. Traditional diagnostic and functional tests used by ophthalmologists to establish a diagnosis may no longer be applicable in identifying subtle but significant shifts in visual function. 

A fresh perspective on retinal diagnostics is required to make sense of the processes that establish the treatment’s viability and effectiveness. Until recently, there was a lack of objective readouts of local retinal function for rods and cones separately, and this is just one of the many facets of vision that require specialized evaluations and imaging methods. Rare diseases, like inherited retinal dystrophies, require a reliable test-retest variability because statistics are often not applicable due to a small sample size. 

There must be and can be methods for a trustworthy individual evaluation of the success of the therapy. In this manuscript, we present an expansion on retinal diagnostics that integrates psychophysics (such as full-field stimulus threshold or dark-adapted perimetry) with objective measures for local retinal function (such as photopic and scotopic chromatic pupil campimetry) and retinal imaging for a useful workflow to apply in assessing the individual success of patients undergoing gene therapy for photoreceptor diseases.

Source: sciencedirect.com/science/article/pii/S1350946222000751