July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Retinal degeneration in choroideremia follows an exponential decay function
Author Affiliations & Notes
  • James William Aylward
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  • Kanmin Xue
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Maria In?s Patrício
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Jasleen K Jolly
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Jonathan Charles Wood
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  • Jonathan Brett
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  • Kirti Jasani
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  • Robert E MacLaren
    Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships   James Aylward, None; Kanmin Xue, University of Oxford (E); Maria Patrício, University of Oxford (P), University of Oxford (E); Jasleen Jolly, University of Oxford (E); Jonathan Wood, None; Jonathan Brett, University of Oxford (E); Kirti Jasani, University of Oxford (E); Robert MacLaren, Choroideremia Research Foundation (F), Euretina (S), Nightstar Therapeutics Inc (I), Nightstar Therapeutics Inc (C), Nightstar Therapeutics Inc (E), Nightstar Therapeutics Inc (P), Nightstar Therapeutics Inc (F), Spark Therapeutics Inc (C), University of Oxford (E), University of Oxford (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6060. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      James William Aylward, Kanmin Xue, Maria In?s Patrício, Jasleen K Jolly, Jonathan Charles Wood, Jonathan Brett, Kirti Jasani, Robert E MacLaren; Retinal degeneration in choroideremia follows an exponential decay function. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6060.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Choroideremia (CHM) is a monogenic retinal dystrophy caused by mutations in the CHM gene encoding REP1, and is phenotypically unique in displaying an island of surviving retina, which undergoes progressive shrinkage with age and can be quantified using fundus autofluorescence imaging (AF). Cross-sectional analysis has suggested that AF area in CHM undergoes exponential decline, however, longitudinal data are lacking, and it is not known whether individuals progress at different rates depending on genetic, epigenetic and environmental factors. We conducted a retrospective, observational study characterising the rate and pattern of retinal degeneration by measuring the loss of AF over time, and correlated disease progression with levels of CHM gene expression.

Methods : The residual areas of retinal AF were serially measured in 31 early stage CHM patients (mean age 28 years) over two years using Heidelberg Eye Explorer. Mathematical modelling of area shrinkage and analysis of inter-eye symmetry were undertaken. In 10 patients, the levels of CHM mRNA and REP1 protein expression were measured in primary fibroblasts. Pearson r correlation coefficient, ANOVA and two-tailed t-tests were used to assess the significance of correlation between two variables as the data were normally distributed.

Results : The rate of AF loss was strongly correlated to baseline AF area (multiple regression coefficient = 0.81, P < 0.01) but independent of age (correlation coefficient = -0.005, P = 0.06), supporting an exponential decay model with a mean half-life of 5.5 years (95%CI 5.0 – 6.1). The age of onset of degeneration involving the 55° posterior pole was mathematically predicted and shown to span from 0 - 20 years. Inter-eye symmetry was observed in the shape of surviving AF islands, suggesting underlying anatomical factors that influence the pattern of degeneration. All patients were found to be null for REP1, despite individual variations in the rate of disease progression.

Conclusions : The data suggest that the rate of degeneration in CHM, in terms of half-life, is similar across all patients. As with all half-life functions, the absolute loss of cells becomes progressively less as the residual area decreases. The apparent variation in disease severity between patients is most likely determined not by the rate of decay, but by the age at which the degeneration starts.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×