Long-term Natural History of Atrophy in Eyes with Choroideremia-A Systematic Review and Meta-analysis of Individual-Level Data

Ophthalmol Retina. 2020 Aug;4(8):840-852. doi: 10.1016/j.oret.2020.03.003. Epub 2020 Mar 14.


Purpose: To conduct a systematic review and meta-analysis of the natural history of atrophy secondary to choroideremia (CHM).

Clinical relevance: A sensitive and reliable anatomic measure to monitor disease progression is needed in treatment trials for CHM. However, the long-term natural history of the residual retinal pigment epithelium (RPE) is unclear, with reported RPE area decline rates varying widely among patients.

Methods: We searched in 7 literature databases up through July 17, 2019, to identify studies that assessed the residual RPE area in untreated eyes with CHM using fundus autofluorescence (FAF). We sought individual-eye data and investigated the RPE decline pattern using 3 models: the area linear model (ALM), radius linear model (RLM), and area exponential model (AEM), in which the area, radius, and log-transformed area of RPE change linearly with time, respectively. To account for different eyes' entry times into the studies, we added a horizontal translation factor to each dataset. The RPE decline rate was estimated using a 2-stage random-effects meta-analysis. We assessed the risk of bias using the Quality In Prognosis Studies tool.

Results: Of 807 articles screened, we included 9 articles containing cross-sectional data (257 eyes) from 6 studies and longitudinal data (229 visits from 68 eyes) from 5 studies. The residual RPE area followed a trend of exponential decay as a function of patient age. After the introduction of horizontal translation factors to longitudinal datasets of individual eyes, the datasets fit along a straight line in the AEM over nearly 60 years (r2 = 0.997). The decline rate of log-transformed RPE area was 0.050 (95% confidence interval, 0.046-0.055) log(mm2)/year and was independent of the baseline RPE area (r = -0.18; P = 0.15) and age (r = 0.06; P = 0.63). In contrast, the decline rates of the area and effective radius of residual RPE strongly correlated with the baseline RPE area (r = 0.90 and 0.61, respectively; P < 0.001).

Conclusions: The loss of residual RPE area in untreated eyes with CHM follows the AEM over approximately 60 years. Log-transformed residual RPE area measured by FAF can serve as an anatomic endpoint to monitor CHM.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Atrophy / diagnosis
  • Choroideremia / diagnosis*
  • Disease Progression
  • Fluorescein Angiography
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Retinal Pigment Epithelium / pathology*
  • Time Factors
  • Tomography, Optical Coherence
  • Visual Acuity*