Short-Wavelength Sensitive Cone (S-cone) Testing as an Outcome Measure for NR2E3 Clinical Treatment Trials

Int J Mol Sci. 2019 May 21;20(10):2497. doi: 10.3390/ijms20102497.

Abstract

Recessively-inherited NR2E3 gene mutations cause an unusual retinopathy with abnormally-increased short-wavelength sensitive cone (S-cone) function, in addition to reduced rod and long/middle-wavelength sensitive cone (L/M-cone) function. Progress toward clinical trials to treat patients with this otherwise incurable retinal degeneration prompted the need to determine efficacy outcome measures. Comparisons were made between three computerized perimeters available in the clinic. These perimeters could deliver short-wavelength stimuli on longer-wavelength adapting backgrounds to measure whether S-cone vision can be quantified. Results from a cohort of normal subjects were compared across the three perimeters to determine S-cone isolation and test-retest variability. S-cone perimetry data from NR2E3-ESCS (enhanced S-cone syndrome) patients were examined and determined to have five stages of disease severity. Using these stages, strategies were proposed for monitoring efficacy of either a focal or retina-wide intervention. This work sets the stage for clinical trials.

Keywords: cone; outcomes for therapeutic clinical trial; photoreceptor; retinal degeneration; visual thresholds.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Clinical Trials as Topic
  • Eye Diseases, Hereditary / diagnosis*
  • Eye Diseases, Hereditary / metabolism
  • Eye Diseases, Hereditary / physiopathology
  • Humans
  • Middle Aged
  • Mutation*
  • Orphan Nuclear Receptors / genetics*
  • Outcome Assessment, Health Care
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Degeneration / diagnosis*
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / physiopathology
  • Vision Disorders / diagnosis*
  • Vision Disorders / metabolism
  • Vision Disorders / physiopathology
  • Visual Field Tests / methods*
  • Young Adult

Substances

  • NR2E3 protein, human
  • Orphan Nuclear Receptors

Supplementary concepts

  • Enhanced S-Cone Syndrome