A Cross-Sectional and Longitudinal Study of Retinal Sensitivity in RPE65-Associated Leber Congenital Amaurosis

Invest Ophthalmol Vis Sci. 2018 Jul 2;59(8):3330-3339. doi: 10.1167/iovs.18-23873.


Purpose: RPE65-associated Leber congenital amaurosis (RPE65-LCA) is an early-onset severe retinal dystrophy associated with progressive visual field loss. Phase I/II and III gene therapy trials have identified improved retinal sensitivity but little is known about the natural history of retinal sensitivity in RPE65-LCA.

Methods: A total of 19 subjects (aged 9 to 23 years) undertook monocular full-field static perimetry of which 13 subjects were monitored longitudinally. Retinal sensitivity was measured as mean sensitivity (MS) and volumetrically quantified (in decibel-steradian) using visual field modeling and analysis software for the total (VTOT), central 30° (V30) and central 15° (V15) visual field. Correlation was evaluated between retinal sensitivity and age, best-corrected visual acuity (BCVA), contrast sensitivity, vision-related quality of life, and genotype. Test-retest reliability was also investigated.

Results: V30 was identified to have a strong, weak, and moderate correlation with age, BCVA and contrast sensitivity respectively. Furthermore, V30 was identified as having a weak linear relationship with the mobility and independence domains of the vision-related quality of life questionnaire. Longitudinal analysis demonstrated a slow loss of retinal sensitivity in this cohort. Subjects with at least one RPE65 nonsense variant appeared to show greater progressive loss of retinal sensitivity in the second decade of life than those without.

Conclusions: Volumetric assessment of central 30° visual field sensitivity, V30, is a useful independent measure of retinal function and, in our data, represented the best metric to monitor deterioration of retinal sensitivity in RPE65-LCA. Furthermore, functional correlation with genotype may enable more informed prognostic counseling. (ClinicalTrials.gov number, NCT02714816.)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Contrast Sensitivity / physiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Leber Congenital Amaurosis / genetics*
  • Leber Congenital Amaurosis / physiopathology*
  • Longitudinal Studies
  • Male
  • Quality of Life
  • Retina / physiopathology*
  • Surveys and Questionnaires
  • Visual Acuity / physiology
  • Visual Field Tests
  • Visual Fields / physiology*
  • Young Adult
  • cis-trans-Isomerases / genetics*


  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Associated data

  • ClinicalTrials.gov/NCT02714816