March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Detecting Glaucomatous Progression from Localized Rates of Retinal Height Changes in Parametric and Non-Parametric Frameworks
Author Affiliations & Notes
  • Madhusudhanan Balasubramanian
    Hamilton Glaucoma Center, Department of Ophthalmology,
    University of California, San Diego, La Jolla, California
  • Christopher Bowd
    Hamilton Glaucoma Center, Department of Ophthalmology,
    University of California, San Diego, La Jolla, California
  • Robert N. Weinreb
    Hamilton Glaucoma Center, Department of Ophthalmology,
    University of California, San Diego, La Jolla, California
  • David J. Kriegman
    Department of Computer Science & Engineering,
    University of California, San Diego, La Jolla, California
  • Michael Holst
    Department of Mathematics and Department of Physics,
    University of California, San Diego, La Jolla, California
  • Pamela A. Sample
    Hamilton Glaucoma Center, Department of Ophthalmology,
    University of California, San Diego, La Jolla, California
  • Linda M. Zangwill
    Hamilton Glaucoma Center, Department of Ophthalmology,
    University of California, San Diego, La Jolla, California
  • Footnotes
    Commercial Relationships  Madhusudhanan Balasubramanian, None; Christopher Bowd, None; Robert N. Weinreb, Alcon (C), Allergan (C), Bausch & Lomb (C), Carl Zeiss Meditec (C), Carl Zeiss Meditec, Inc. (F), Heidelberg Engineering, GmbH (F), Merck (C), Nidek (F), Novartis (F), Optovue (C), Optovue, Inc. (F), Pfizer (C), Topcon Medical Systems, Inc. (F); David J. Kriegman, None; Michael Holst, None; Pamela A. Sample, None; Linda M. Zangwill, Carl Zeiss Meditec, Inc. (F), Heidelberg Engineering, GmbH (F), Nidek (F), Optovue Inc. (F), Topcon Medical Systems Inc. (F)
  • Footnotes
    Support  NEI EY020518, EY011008, EY008208, EY021818 and participant retention incentive grants in the form of glaucoma medication at no cost from Alcon Laboratories Inc, Allergan, Pfizer Inc, and Santen Inc
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 238. doi:
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      Madhusudhanan Balasubramanian, Christopher Bowd, Robert N. Weinreb, David J. Kriegman, Michael Holst, Pamela A. Sample, Linda M. Zangwill; Detecting Glaucomatous Progression from Localized Rates of Retinal Height Changes in Parametric and Non-Parametric Frameworks. Invest. Ophthalmol. Vis. Sci. 2012;53(14):238.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To evaluate 3 new strategies that extend the statistic image mapping (SIM)1 and detect glaucomatous progression from pixelwise rates of retinal height changes (PixR) with type I error controlled in parametric (PixR-P) and non-parametric frameworks (PixR-NP).

Methods: : In all techniques, the rate of retinal height change at each pixel was estimated using linear regression. Regression errors were assumed to be independent and identically distributed for non-parametric analysis (exchangeability criterion) and normally distributed with a constant variance over time for parametric analysis. 1) In PixR-NP cluster test (CT), familywise error rate (FWER) was controlled at both pixel-level (5%) and cluster-level (1%) using permutation tests. 2) In PixR-NP single-threshold test (STT), and 3) in PixR-P STT, k-FWER2 was controlled at pixel-level (5%), respectively, using permutation tests and p-values (from t-tests) of the rate of change at each pixel. Permutation tests in PixR were conducted by permuting regression errors under the null hypothesis3,4. For PixR-P and PixR-NP STTs, k was set to 5% of optic disk size to control k-FWER and an observed positive rate (OPR) was calculated as the ratio of number of pixels with significant rate of retinal height decrease (red-pixel) in disk to disk size. The criterion of progression was: for PixR-NP CT and SIM, p(cluster size) < 1% for at least one red-pixel cluster in disk; and for PixR-NP STT and PixR-P STT, OPR > 5%. Diagnostic accuracy was estimated using 267 eyes of 187 participants with at least 4 HRT-II exams from the UCSD Diagnostic Innovations in Glaucoma Study. 36 eyes progressed by stereophotos or visual field guided progression analysis; 210 patient eyes were non-progressing and 21 eyes were longitudinal normals.

Conclusions: : At 90% specificity, PixR strategies had better sensitivity than SIM. In contrast to SIM that controls false clusters only, PixR controlled both false locations and clusters of progression. Also, PixR strategies illustrated the use of k-FWER to control false positives in parametric and non-parametric analysis of rates of progression. The parametric PixR-P is computationally less intensive and thus, shows promise for wider adoptability in clinics.

Clinical Trial: : http://www.clinicaltrials.gov NCT00221897

Keywords: imaging/image analysis: clinical • optic disc • computational modeling 
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