Establishing the ground truth for keratoconus progression: combining repeated measures and adapting precision limits to disease severity in tomography.

Purpose: Keratoconus progression is defined with reference to precision limits in corneal tomography. We set out to analyse measurement precision using a contemporary tomography device (MS-39, CSO Italia, Florence, Italy) in a large sample of keratoconus patients.

Setting: Moorfields Eye Hospital, London, UK.

Design: Prospective and retrospective analysis of clinical data.

Methods: For a range of key corneal tomographic indices, repeatability and reproducibility were compared in a prospective series of 1,248 scans (n= 208 eyes) with 2 observers each acquiring 3 scans per eye. Measurement repeatability for single measures versus the mean of 3 consecutive measures was then compared using the same dataset. 95% repeatability coefficients (RC) were mapped at each unit interval through the measurement range in a retrospective analysis of 13,734 scans (n=4,578 eyes) to adapt progression thresholds to disease severity. Finally, keratoconus classification using alternate progression definitions was compared at 1 and 2 year time points.

Results: For all corneal tomographic indices examined, no significant differences were found between MS-39 measurement repeatability and reproducibility (p>0.05), repeatability was (average) 44% improved using the mean of 3 consecutive measures, and measurement repeatability deteriorated as keratoconus advanced. Progression was classified incorrectly in over 50% of cases at both time points where adaptive thresholds and repeated measures were not used.

Conclusions: MS-39 measurement precision is not significantly influenced by the operator. Consecutive repeated measures and adaptive thresholds for observed change in key tomographic parameters based on device specific precision limits tailored to disease severity are necessary for accurate classification of progression.