Natural history and clinical biomarkers of progression in X-linked retinitis pigmentosa: a systematic review

Mark Zada, Elisa E. Cornish, Clare L. Fraser, Robyn V. Jamieson, John R. Grigg*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)


X-linked retinitis pigmentosa (XLRP) accounts for a significant proportion of certifiable blindness in working-age adults. The objectives of this study were to: (1) synthesize the best available evidence regarding the natural history of disease progression and (2) identify the best current clinical biomarkers for monitoring disease progression, which will be important in planned gene therapy trials for this condition. Patient population: XLRP affected males. Main outcomes: A systematic review of the literature was undertaken with data sought on overall annual progression for clinical biomarkers using optical coherence tomography (OCT), fundus autofluorescence (FAF), visual acuity, electroretinography and visual fields. To assess which outcome was best for monitoring progression, data on reliability, interocular correlation and structure-function correlation were extracted. A total of 17 studies met the inclusion criteria. Studies estimated progression at between 4% to 19% per year with longitudinal data. Where an overall model was produced with cross-sectional data, the trend was usually best fit by a logarithmic function with an annual exponential decline rate between 4.7% and 8.0%. The evidence suggested the ellipsoid zone (EZ) width on OCT and outer ring area (ORA) on FAF as the most useful biomarkers having excellent interocular symmetry, reproducibility and functional correlation. Using different clinical biomarkers, XLRP progresses at a rate of 4 to 19% per year. Ellipsoid zone (EZ) width and ORA are the most robust biomarkers with the potential to be used in trials where one eye serves as a control for the other.

Original languageEnglish
Pages (from-to)499-510
Number of pages12
JournalActa Ophthalmologica
Issue number5
Early online date30 Nov 2020
Publication statusPublished - Aug 2021
Externally publishedYes


  • clinical biomarkers
  • electrophysiology
  • fundus autofluorescence
  • natural history
  • optical coherence tomography
  • perimetry
  • retinitis pigmentosa
  • visual acuity
  • X-linked


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