Outcome measures for future trials for autosomal dominant vitelliform macular dystrophy caused by BEST1 mutations.

Researchers at the Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, have reported that outcome measures for future clinical trials should include evaluations of “rod sensitivity within central lesions and quantitative measures of outer retinal structure in normal-appearing regions surrounding the lesions” (IOVS December 2022, Vol. 63, Issue 13). The study was aimed to evaluate rod and cone function, and outer retinal structures within macular lesions, for patients with autosomal dominant Best vitelliform macular dystrophy (BVMD), caused by BEST1 mutations. Although BVMD is currently not curable or treatable for the disorder, future clinical trials may be important to use a micro-perimetric methods, “which can be interpreted confidently in terms of the function of the underlying photoreceptor system”, according to the clinical researchers at the University of Pennsylvania.

BVMD is caused by mutations within the BEST1 gene (VMD2, vitelliform macular dystrophy 2), located on chromosome 11q12.3 with an autosomal dominant inheritance pattern and with variable penetrance.  Patients have an estimated prevalence of between 1 to 9 per 100,000 in Europe and males are more affected than females (3:1). The disorder is a macular dystrophy characterized by loss of central visual acuity, metamorphopsia and a decrease in the Arden ratio (the final electro-oculogram [EOG] calculation) secondary to an egg yolk-like lesion located in the foveal or parafoveal region, generally characterized by atrophy of the retinal pigment epithelium (RPE). Although the diagnosis is often made during childhood years, it is more frequently made much later and into the sixth decade of life.

In the current study that recruited seventeen patients from seven families, results showed that central lesions had large serous retinal detachments, severely reduced rod sensitivity, but relatively retained sensitivity for cone and visual acuity. In addition, the surrounding extra-lesional areas showed a mild but detectable widening of the subretinal space in some patients and some retinal areas, consistent with subretinal widening causing slower dark-adaptation kinetics. In terms of outcome measures, the researchers commented that, “cross sectional imaging with OCT is a key outcome for BVMD clinical trials. The extent of the vitelliform lesions can be quantified. Additionally, current results strongly suggest that hyper-thickening of the ONL and widening of the distance between the IS/OS and the RPE may be the only subclinical abnormalities in para-lesional retinal areas that can be evaluated quantitatively for efficacy and safety experimental interventions in clinical trials.”