Dark-adaptation functions in molecularly confirmed achromatopsia and the implications for assessment in retinal therapy trials

Invest Ophthalmol Vis Sci. 2014 Aug 28;55(10):6340-9. doi: 10.1167/iovs.14-14910.

Abstract

Purpose: To describe the dark-adaptation (DA) functions in subjects with molecularly proven achromatopsia (ACHM) using refined testing conditions with a view to guiding assessment in forthcoming gene therapy trials.

Methods: The DA functions of nine subjects with ACHM were measured and compared with those of normal observers. The size and retinal location of the stimuli used to measure DA sensitivities were varied in four distinct testing condition sets, and the effect of altering these parameters assessed.

Results: In three of the four testing condition sets, achromats had significantly higher mean final thresholds than normal observers, whereas in the fourth condition set they did not. A larger, more central stimulus revealed the greatest difference between the final DA thresholds of achromat and normal subjects, and also demonstrated the slowest rate of recovery among the achromat group.

Conclusions: In this, the largest study of DA functions in molecularly proven ACHM to date, we have identified optimal testing conditions that accentuate the relative difference between achromats and normal observers. These findings can help optimize DA testing in future trials, as well as help resolve the dichotomy in the literature regarding the normality or otherwise of DA functions in ACHM. Furthermore, the shorter testing time and less intense adaptation light used in these experiments may prove advantageous for more readily and reliably probing scotopic function in retinal disease, and be particularly valuable in the frequent post therapeutic assessments required in the context of the marked photophobia in ACHM.

Keywords: achromatopsia; dark adaptation; gene therapy; rod monochromatism; rod vision.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism*
  • Color Vision Defects / diagnosis*
  • Color Vision Defects / metabolism
  • Color Vision Defects / therapy
  • Dark Adaptation*
  • Electroretinography
  • Female
  • Genetic Markers*
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques / methods*
  • Prognosis
  • Retina / physiopathology*
  • Young Adult

Substances

  • Biomarkers
  • Genetic Markers