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Detecting Changes in Retinal Function: Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement (ANSWERS)

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  • Haogang Zhu
  • Richard A Russell
  • Luke J Saunders
  • Stefano Ceccon
  • David F Garway-Heath
  • David P Crabb

Abstract

Visual fields measured with standard automated perimetry are a benchmark test for determining retinal function in ocular pathologies such as glaucoma. Their monitoring over time is crucial in detecting change in disease course and, therefore, in prompting clinical intervention and defining endpoints in clinical trials of new therapies. However, conventional change detection methods do not take into account non-stationary measurement variability or spatial correlation present in these measures. An inferential statistical model, denoted ‘Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement’ (ANSWERS), was proposed. In contrast to commonly used ordinary linear regression models, which assume normally distributed errors, ANSWERS incorporates non-stationary variability modelled as a mixture of Weibull distributions. Spatial correlation of measurements was also included into the model using a Bayesian framework. It was evaluated using a large dataset of visual field measurements acquired from electronic health records, and was compared with other widely used methods for detecting deterioration in retinal function. ANSWERS was able to detect deterioration significantly earlier than conventional methods, at matched false positive rates. Statistical sensitivity in detecting deterioration was also significantly better, especially in short time series. Furthermore, the spatial correlation utilised in ANSWERS was shown to improve the ability to detect deterioration, compared to equivalent models without spatial correlation, especially in short follow-up series. ANSWERS is a new efficient method for detecting changes in retinal function. It allows for better detection of change, more efficient endpoints and can potentially shorten the time in clinical trials for new therapies.

Suggested Citation

  • Haogang Zhu & Richard A Russell & Luke J Saunders & Stefano Ceccon & David F Garway-Heath & David P Crabb, 2014. "Detecting Changes in Retinal Function: Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement (ANSWERS)," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-11, January.
  • Handle: RePEc:plo:pone00:0085654
    DOI: 10.1371/journal.pone.0085654
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    Cited by:

    1. Sampson Listowell Abu & Iván Marín-Franch & Lyne Racette, 2020. "A framework for assessing glaucoma progression using structural and functional indices jointly," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-15, July.

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