Optical coherence tomography grading reproducibility during the Comparison of Age-related Macular Degeneration Treatments Trials

Ophthalmology. 2012 Dec;119(12):2549-57. doi: 10.1016/j.ophtha.2012.06.040. Epub 2012 Aug 28.


Objective: To report reading center reproducibility during grading of Stratus optical coherence tomography (OCT) (Carl Zeiss Meditec, Dublin, CA) images obtained during the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

Design: Prospective, clinical trial.

Participants: Independent reading teams reevaluated 270 OCT scans randomly sampled from the first 2 years of CATT enrollment. To assess temporal drift, a cohort of 23 scans submitted during the initial portion of the CATT study was longitudinally followed with serial reproducibility analysis.

Intervention: The CATT readers performed standardized grading of OCT images. A reader team, composed of 2 independent readers and a senior reader, evaluated each scan. Grading included the CATT OCT end points of total thickness at the foveal center point and intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (RPE) fluid. Independent reading teams masked to the results of initial grading reevaluated scans to determine the reproducibility of qualitative grading and measurements.

Main outcome measures: Categorical grading agreement was reported using percent agreement and kappa statistic, and measurement agreement was reported using intraclass correlations and paired differences.

Results: Reading center teams reproducibly graded IRF (percent agreement = 73%, kappa = 0.48; 95% confidence interval [CI], 0.38-0.58), SRF (percent agreement = 90%; kappa = 0.80; 95% CI, 0.73-0.87), and sub-RPE fluid (percent agreement 88%; kappa = 0.75; 95% CI, 0.67-0.83). For independent reading center team measurements of total thickness at the foveal center point, the intraclass correlation was 0.99 (95% CI, 0.99-0.99), and the mean paired difference between reading center teams was 4 μm (95% limits of agreement, -55 to 47 μm). There was no qualitative or quantitative grading drift.

Conclusions: The standardized protocols used to evaluate OCT scans from the CATT study were reproducible. The methods used are suitable to monitor OCT imaging data from a large, neovascular age-related macular degeneration, interventional, multicenter study.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Double-Blind Method
  • Epiretinal Membrane / diagnosis
  • Humans
  • Macular Degeneration / classification
  • Macular Degeneration / diagnosis*
  • Macular Degeneration / drug therapy
  • Observer Variation
  • Prospective Studies
  • Quality Control
  • Ranibizumab
  • Reproducibility of Results
  • Retina / pathology
  • Subretinal Fluid
  • Tomography, Optical Coherence / standards*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Ranibizumab