Automated Evaluation of Ellipsoid Zone At-Risk Burden for Detection of Hydroxychloroquine Retinopathy

Overview

Journal J Pers Med

Date 2024 May 25

PMID 38793030

Authors

Katherine E Talcott

Gagan Kalra

Hasan Cetin

Yavuz Cakir

Jon Whitney

Jordan Budrevich

Jamie L Reese

Sunil K Srivastava

Justis P Ehlers

Affiliations

Soon will be listed here.

Abstract

Background: Screening for hydroxychloroquine (HCQ) retinopathy is crucial to detecting early disease. A novel machine-learning-based optical coherence tomography (OCT) biomarker, Ellipsoid Zone (EZ) At-Risk, can quantitatively measure EZ alterations and at-risk areas for progressive EZ loss in a fully automated fashion. The purpose of this analysis was to compare the EZ At-Risk burden in eyes with HCQ toxicity to eyes without toxicity.

Methods: IRB-approved image analysis study of 83 subjects on HCQ and 44 age-matched normal subjects. SD-OCT images were reviewed for evidence of HCQ retinopathy. A ML-based, fully automatic measurement of the percentage of the macular area with EZ At-Risk was performed.

Results: The mean age for HCQ subjects was 67.1 ± 13.2 years and 64.2 ± 14.3 years for normal subjects. The mean EZ At-Risk macular burden in the "toxic" group (n = 38) was significantly higher (10.7%) compared to the "non-toxic" group (n = 45; 2.2%; = 0.023) and the "normal" group (1.4%; = 0.012). Additionally, the amount of EZ At-Risk burden was significantly correlated with the HCQ dose based on the actual ( = 0.016) and ideal body weight ( = 0.033).

Conclusions: The novel biomarker EZ-At Risk was significantly higher in subjects with evidence of HCQ retinopathy as well as significantly associated with HCQ dose. This novel biomarker should be further evaluated as a potential screening tool for subjects on HCQ.

References

De Sisternes L, Hu J, Rubin D, Marmor M . Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea. Invest Ophthalmol Vis Sci. 2015; 56(5):3415-26. PMC: 4455312. DOI: 10.1167/iovs.14-16345. View

Chen E, Brown D, Benz M, Fish R, Wong T, Kim R . Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign). Clin Ophthalmol. 2010; 4:1151-8. PMC: 2964950. DOI: 10.2147/OPTH.S14257. View

De Sisternes L, Pham B, Durbin M, Marmor M . TOPOGRAPHIC OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION SHOWS LIMITED ELLIPSOID ZONE RECOVERY IN MILD HYDROXYCHLOROQUINE RETINOPATHY. Retin Cases Brief Rep. 2020; 16(3):263-269. DOI: 10.1097/ICB.0000000000000993. View

Pasadhika S, Fishman G, Choi D, Shahidi M . Selective thinning of the perifoveal inner retina as an early sign of hydroxychloroquine retinal toxicity. Eye (Lond). 2010; 24(5):756-62. PMC: 3711255. DOI: 10.1038/eye.2010.21. View

Ahn S, Joung J, Lim H, Lee B . Optical Coherence Tomography Protocols for Screening of Hydroxychloroquine Retinopathy in Asian Patients. Am J Ophthalmol. 2017; 184:11-18. DOI: 10.1016/j.ajo.2017.09.025. View

Marmor M, Kellner U, Lai T, Melles R, Mieler W . Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016; 123(6):1386-94. DOI: 10.1016/j.ophtha.2016.01.058. View

Ehlers J, Uchida A, Hu M, Figueiredo N, Kaiser P, Heier J . Higher-Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index. Ophthalmol Retina. 2019; 3(12):1056-1066. PMC: 6899163. DOI: 10.1016/j.oret.2019.06.010. View

Itoh Y, Ehlers J . ELLIPSOID ZONE MAPPING AND OUTER RETINAL CHARACTERIZATION AFTER INTRAVITREAL OCRIPLASMIN. Retina. 2016; 36(12):2290-2296. PMC: 5115947. DOI: 10.1097/IAE.0000000000001110. View

Kalra G, Talcott K, Kaiser S, Ugwuegbu O, Hu M, Srivastava S . Machine Learning-Based Automated Detection of Hydroxychloroquine Toxicity and Prediction of Future Toxicity Using Higher-Order OCT Biomarkers. Ophthalmol Retina. 2022; 6(12):1241-1252. PMC: 9722508. DOI: 10.1016/j.oret.2022.05.031. View

10.

Kalra G, Cetin H, Whitney J, Yordi S, Cakir Y, McConville C . Automated Identification and Segmentation of Using Deep Learning on SD-OCT for Predicting Progression in Dry AMD. Diagnostics (Basel). 2023; 13(6). PMC: 10047385. DOI: 10.3390/diagnostics13061178. View

11.

Ugwuegbu O, Uchida A, Singh R, Beven L, Hu M, Kaiser S . Quantitative assessment of outer retinal layers and ellipsoid zone mapping in hydroxychloroquine retinopathy. Br J Ophthalmol. 2018; 103(1):3-7. PMC: 6397800. DOI: 10.1136/bjophthalmol-2018-312363. View

12.

Cukras C, Huynh N, Vitale S, Wong W, Ferris 3rd F, Sieving P . Subjective and objective screening tests for hydroxychloroquine toxicity. Ophthalmology. 2014; 122(2):356-66. PMC: 8356134. DOI: 10.1016/j.ophtha.2014.07.056. View

13.

Greenstein V, Amaro-Quireza L, Abraham E, Ramachandran R, Tsang S, Hood D . A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy. Doc Ophthalmol. 2014; 130(1):13-23. PMC: 4303510. DOI: 10.1007/s10633-014-9474-6. View

14.

Rodriguez-Padilla J, Hedges 3rd T, Monson B, Srinivasan V, Wojtkowski M, Reichel E . High-speed ultra-high-resolution optical coherence tomography findings in hydroxychloroquine retinopathy. Arch Ophthalmol. 2007; 125(6):775-80. PMC: 1993817. DOI: 10.1001/archopht.125.6.775. View

15.

Garrity S, Jung J, Zambrowski O, Pichi F, Su D, Arya M . Early hydroxychloroquine retinopathy: optical coherence tomography abnormalities preceding Humphrey visual field defects. Br J Ophthalmol. 2019; 103(11):1600-1604. DOI: 10.1136/bjophthalmol-2018-313350. View

16.

Lally D, Heier J, Baumal C, Witkin A, Maler S, Shah C . Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation. Int J Retina Vitreous. 2016; 2:18. PMC: 5088472. DOI: 10.1186/s40942-016-0042-y. View

17.

Kellner S, Weinitz S, Kellner U . Spectral domain optical coherence tomography detects early stages of chloroquine retinopathy similar to multifocal electroretinography, fundus autofluorescence and near-infrared autofluorescence. Br J Ophthalmol. 2009; 93(11):1444-7. DOI: 10.1136/bjo.2008.157198. View

18.

Marmor M . Comparison of screening procedures in hydroxychloroquine toxicity. Arch Ophthalmol. 2011; 130(4):461-9. DOI: 10.1001/archophthalmol.2011.371. View

19.

Membreno R, de Silva T, Agron E, Keenan T, Cukras C . Quantitative analysis of optical coherence tomography imaging in patients with different severities of hydroxychloroquine toxicity. Br J Ophthalmol. 2022; 107(6):849-855. PMC: 11323113. DOI: 10.1136/bjophthalmol-2021-319197. View

20.

De Sisternes L, Hu J, Rubin D, Marmor M . Analysis of Inner and Outer Retinal Thickness in Patients Using Hydroxychloroquine Prior to Development of Retinopathy. JAMA Ophthalmol. 2016; 134(5):511-519. DOI: 10.1001/jamaophthalmol.2016.0155. View