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Title: Multivariate normative comparison, a novel method for improved use of retinal nerve fiber layer thickness to detect early glaucoma
Authors: Chua, Jacqueline
Schwarzhans, Florian
Wong, Damon
Li, Chi
Husain, Rahat
Crowston, Jonathan G.
Perera, Shamira A.
Sng, Chelvin C. A.
Nongpiur, Monisha E.
Majithia, Shivani
Tham, Yih Chung
Thakur, Sahil
Soh, Zhi Da
Cheng, Ching-Yu
Aung, Tin
Fischer, Georg
Vass, Clemens
Schmetterer, Leopold
Keywords: Engineering::Bioengineering
Issue Date: 2022
Source: Chua, J., Schwarzhans, F., Wong, D., Li, C., Husain, R., Crowston, J. G., Perera, S. A., Sng, C. C. A., Nongpiur, M. E., Majithia, S., Tham, Y. C., Thakur, S., Soh, Z. D., Cheng, C., Aung, T., Fischer, G., Vass, C. & Schmetterer, L. (2022). Multivariate normative comparison, a novel method for improved use of retinal nerve fiber layer thickness to detect early glaucoma. Ophthalmology Glaucoma, 5(3), 359-368.
Project: CG/C010A/2017
Journal: Ophthalmology Glaucoma
Abstract: Purpose: Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). This study assessed whether compensating the RNFL thickness for multiple demographic and anatomic factors improves the detection of glaucoma. Design: Cross-sectional study. Participants: Three hundred eighty-seven patients with glaucoma and 2699 healthy participants. Methods: Two thousand six hundred ninety-nine healthy participants were enrolled to construct and test a multivariate compensation model, which then was applied in 387 healthy participants and 387 patients with glaucoma (early glaucoma, n = 219; moderate glaucoma, n = 97; and advanced glaucoma, n = 71). Participants underwent Cirrus spectral-domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. The RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. Main Outcome and Measures: Measured and compensated RNFL thickness measurements. Results: After applying the Asian-specific compensation model, the standard deviation of RNFL thickness reduced, where the effect was greatest for Chinese participants (16.9%), followed by Malay participants (13.9%), and Indian participants (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC, 0.90 vs. 0.85; P < 0.001), moderate glaucoma (AUC, 0.94 vs. 0.91; P < 0.001), and advanced glaucoma (AUC, 0.98 vs. 0.96; P < 0.001). Conclusions: The multivariate normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting that accounting for demographic and anatomic variance in RNFL thickness may have usefulness in improving glaucoma detection.
ISSN: 2589-4234
DOI: 10.1016/j.ogla.2021.10.013
Schools: School of Chemical and Biomedical Engineering 
Organisations: Singapore National Eye Centre
Duke- NUS Medical School
Research Centres: SERI-NTU Advanced Ocular Engineering (STANCE)
Rights: © 2021 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license ( Published by Elsevier Inc.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCBE Journal Articles

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