A CNN-aided method to predict glaucoma progression using DARC (Detection of Apoptosing Retinal Cells)

Expert Rev Mol Diagn. 2020 Jul;20(7):737-748. doi: 10.1080/14737159.2020.1758067. Epub 2020 May 3.

Abstract

Background: A key objective in glaucoma is to identify those at risk of rapid progression and blindness. Recently, a novel first-in-man method for visualising apoptotic retinal cells called DARC (Detection-of-Apoptosing-Retinal-Cells) was reported. The aim was to develop an automatic CNN-aided method of DARC spot detection to enable prediction of glaucoma progression.

Methods: Anonymised DARC images were acquired from healthy control (n=40) and glaucoma (n=20) Phase 2 clinical trial subjects (ISRCTN10751859) from which 5 observers manually counted spots. The CNN-aided algorithm was trained and validated using manual counts from control subjects, and then tested on glaucoma eyes.

Results: The algorithm had 97.0% accuracy, 91.1% sensitivity and 97.1% specificity to spot detection when compared to manual grading of 50% controls. It was next tested on glaucoma patient eyes defined as progressing or stable based on a significant (p<0.05) rate of progression using OCT-retinal nerve fibre layer measurements at 18 months. It demonstrated 85.7% sensitivity, 91.7% specificity with AUC of 0.89, and a significantly (p=0.0044) greater DARC count in those patients who later progressed.

Conclusion: This CNN-enabled algorithm provides an automated and objective measure of DARC, promoting its use as an AI-aided biomarker for predicting glaucoma progression and testing new drugs.

Keywords: Artificial Intelligence; Biomarker; CNN; apoptosis; glaucoma; imaging.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Algorithms*
  • Annexin A5 / administration & dosage
  • Apoptosis*
  • Automation
  • Clinical Trials, Phase II as Topic
  • Disease Progression
  • Female
  • Glaucoma / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Male
  • Middle Aged
  • Neural Networks, Computer*
  • Observer Variation
  • Retinal Ganglion Cells / pathology*
  • Tomography, Optical Coherence

Substances

  • Annexin A5