Quantification of Fluid Resolution and Visual Acuity Gain in Patients With Diabetic Macular Edema Using Deep Learning: A Post Hoc Analysis of a Randomized Clinical Trial

Abstract

Importance: Large amounts of optical coherence tomographic (OCT) data of diabetic macular edema (DME) are acquired, but many morphologic features have yet to be identified and quantified.

Objective: To examine the volumetric change of intraretinal fluid (IRF) and subretinal fluid (SRF) in DME during anti-vascular endothelial growth factor treatment using deep learning algorithms.

Design, setting, and participants: This post hoc analysis of a randomized clinical trial, the Diabetic Retinopathy Clinical Research Network (protocol T), assessed 6945 spectral-domain OCT volume scans of 570 eyes from 570 study participants with DME. The original trial was performed from August 21, 2012, to October 18, 2018. This analysis was performed from December 7, 2017, to January 15, 2020.

Interventions: Participants were treated according to a predefined, standardized protocol with aflibercept, ranibizumab, or bevacizumab with or without deferred laser.

Main outcomes and measures: The association of treatment with IRF and SRF volumes and best-corrected visual acuity (BCVA) during 12 months using deep learning algorithms.

Results: Among the 570 study participants (302 [53%] male; 369 [65%] white; mean [SD] age, 43.4 [12.6] years), the mean fluid volumes in the central 3 mm were 448.6 nL (95% CI, 412.3-485.0 nL) of IRF and 36.9 nL (95% CI, 27.0-46.7 nL) of SRF at baseline and 161.2 nL (95% CI, 135.1-187.4 nL) of IRF and 4.4 nL (95% CI, 1.7-7.1 nL) of SRF at 12 months. The presence of SRF at baseline was associated with a worse baseline BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) score of 63.2 (95% CI, 60.2-66.1) (approximate Snellen equivalent of 20/63 [95% CI, 20/50-20/63]) in eyes with SRF vs 66.9 (95% CI, 65.7-68.1) (approximate Snellen equivalent, 20/50 [95% CI, 20/40-20/50]) without SRF (P < .001) and a greater gain in ETDRS score (0.5; 95% CI, 0.3-0.8) every 4 weeks during follow-up in eyes with SRF at baseline vs 0.4 (95% CI, 0.3-0.5) in eyes without SRF at baseline (P = .02) when adjusted for baseline BCVA. Aflibercept was associated with greater reduction of IRF volume compared with bevacizumab after the first injection (difference, 79.8 nL; 95% CI, 5.3-162.5 nL; P < .001) and every 4 weeks thereafter (difference, 10.4 nL; 95% CI, 0.7-20.0 nL; P = .004). Ranibizumab was associated with a greater reduction of IRF after the first injection compared with bevacizumab (difference, 75.2 nL; 95% CI, 1.4-154.7 nL; P < .001).

Conclusions and relevance: Automated segmentation of fluid in DME revealed that the presence of SRF was associated with lower baseline BCVA but with good response to anti-vascular endothelial growth factor therapy. These automated spectral-domain OCT analyses may be used clinically to assess anatomical change during therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT01627249.

Conflict of interest statement

Conflict of interest Disclosures: Dr Roberts reported receiving grants from Christian Doppler Research Association during the conduct of the study. Dr Vogl reported receiving grants from Christian Doppler Forschungsgesellschaft during the conduct of the study. Dr Gerendas reported receiving grants from Wiener Wissenschafts- Forschungs- und Technologiefonds during the conduct of the study, receiving personal fees and reading center service fees from Novartis, personal fees from Roche/Genentech, receiving personal fees from Kinarus, receiving grants from IDx outside the submitted work, and having a patent to analyze optical coherence tomographic images pending. Dr Glassman reported receiving grants from National Eye Institute, Regeneron, and Genentech during the conduct of the study. Dr Schmidt-Erfurth reported receiving grants from Christian Doppler Research Association and Austrian Federal Ministry for Digital and Economic Affairs during the conduct of the study and receivng personal fees from Boehringer Ingelheim, Heidelberg Engineering, Roche, Genentech, Novartis, and Kodiak outside the submitted work. No other disclosures were reported.

Figures

Figure.. Trajectory of Best-Corrected Visual Acuity (BCVA) in Eyes With and Without Subretinal Fluid (SRF) at Baseline

A, BCVA scores for all eyes. B, Eyes divided into better visual acuity (VA) (a baseline Early Treatment Diabetic Retinopathy Study [ETDRS] score of ≥69 [approximate Snellen equivalent of 20/32-20/40]) and worse VA (baseline ETDRS score of