The impact of dry eye disease on corneal nerve parameters::  A systematic review and meta‐analysis

Jeremy Chung Bo Chiang; Vincent Tran; James S. Wolffsohn

doi:10.1111/opo.13186

The impact of dry eye disease on corneal nerve parameters: A systematic review and meta‐analysis

Jeremy Chung Bo Chiang^*, Vincent Tran, James S. Wolffsohn

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

Abstract

Purpose: Dry eye disease (DED) is a growing global health problem with a significant impact on the quality of life of patients. While neurosensory abnormalities have been recognised as a contributor to DED pathophysiology, the potential role of in vivo corneal confocal microscopy in detecting nerve loss or damage remains unclear. This systematic review with meta‐analysis (PROSPERO registered CRD42022381861) investigated whether DED has an impact on sub‐basal corneal nerve parameters. Methods: PubMed, Embase and Web of Science Core Collection databases were searched from inception to 9 December 2022. Studies using laser scanning confocal microscopy to compare corneal nerve parameters of DED with healthy eyes were included. Study selection process and data extraction were performed by two independent members of the review team. Results: Twenty‐two studies with 916 participants with DED and 491 healthy controls were included, with 21 of these studies included in subsequent meta‐analyses. There was a decrease in total corneal nerve length (−3.85 mm/mm2; 95% CI −5.16, −2.55), corneal main nerve trunk density (−4.81 number/mm2; 95% CI −7.94, −1.68) and corneal nerve branch density (−15.52 number/mm2; 95% CI −27.20, −3.84) in DED eyes compared with healthy eyes, with subgroup analysis demonstrating that these differences were more evident in studies using NeuronJ software, a semi‐automated procedure. While this review found evidence of loss of corneal nerve parameters in eyes with DED compared with healthy controls, particularly with the use of a semi‐automated image analysis method, it is evident that there is substantial heterogeneity between studies in terms of corneal nerve imaging methodology. Conclusions: Standardisation is required in terms of terminology and analysis, with more research needed to potentially improve the clinical applicability and practicality of corneal nerve imaging. Further investigation is also required to confirm the diagnostic accuracy of this imaging modality and its potential for monitoring DED treatment efficacy.

Original language	English
Pages (from-to)	1079-1091
Number of pages	13
Journal	Ophthalmic and Physiological Optics
Volume	43
Issue number	5
Early online date	25 Jun 2023
DOIs	https://doi.org/10.1111/opo.13186
Publication status	Published - Sept 2023

Bibliographical note

Copyright © 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funding Information:
The authors would like to thank Dr Daniel Phan (Monash University, Melbourne, Australia) for providing access support for the Covidence systematic review software.

Publisher Copyright:
© 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

Keywords

dry eye disease
in vivo corneal confocal microscopy
corneal nerves
keratoconjunctivitis sicca

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Copyright © 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Cite this

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title = "The impact of dry eye disease on corneal nerve parameters:: A systematic review and meta‐analysis",

abstract = "Purpose: Dry eye disease (DED) is a growing global health problem with a significant impact on the quality of life of patients. While neurosensory abnormalities have been recognised as a contributor to DED pathophysiology, the potential role of in vivo corneal confocal microscopy in detecting nerve loss or damage remains unclear. This systematic review with meta‐analysis (PROSPERO registered CRD42022381861) investigated whether DED has an impact on sub‐basal corneal nerve parameters. Methods: PubMed, Embase and Web of Science Core Collection databases were searched from inception to 9 December 2022. Studies using laser scanning confocal microscopy to compare corneal nerve parameters of DED with healthy eyes were included. Study selection process and data extraction were performed by two independent members of the review team. Results: Twenty‐two studies with 916 participants with DED and 491 healthy controls were included, with 21 of these studies included in subsequent meta‐analyses. There was a decrease in total corneal nerve length (−3.85 mm/mm2; 95% CI −5.16, −2.55), corneal main nerve trunk density (−4.81 number/mm2; 95% CI −7.94, −1.68) and corneal nerve branch density (−15.52 number/mm2; 95% CI −27.20, −3.84) in DED eyes compared with healthy eyes, with subgroup analysis demonstrating that these differences were more evident in studies using NeuronJ software, a semi‐automated procedure. While this review found evidence of loss of corneal nerve parameters in eyes with DED compared with healthy controls, particularly with the use of a semi‐automated image analysis method, it is evident that there is substantial heterogeneity between studies in terms of corneal nerve imaging methodology. Conclusions: Standardisation is required in terms of terminology and analysis, with more research needed to potentially improve the clinical applicability and practicality of corneal nerve imaging. Further investigation is also required to confirm the diagnostic accuracy of this imaging modality and its potential for monitoring DED treatment efficacy.",

keywords = "dry eye disease, in vivo corneal confocal microscopy, corneal nerves, keratoconjunctivitis sicca",

author = "Chiang, {Jeremy Chung Bo} and Vincent Tran and Wolffsohn, {James S.}",

note = "Copyright {\textcopyright} 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding Information: The authors would like to thank Dr Daniel Phan (Monash University, Melbourne, Australia) for providing access support for the Covidence systematic review software. Publisher Copyright: {\textcopyright} 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.",

year = "2023",

month = sep,

doi = "10.1111/opo.13186",

language = "English",

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pages = "1079--1091",

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T1 - The impact of dry eye disease on corneal nerve parameters:

T2 - A systematic review and meta‐analysis

AU - Chiang, Jeremy Chung Bo

AU - Tran, Vincent

AU - Wolffsohn, James S.

N1 - Copyright © 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding Information: The authors would like to thank Dr Daniel Phan (Monash University, Melbourne, Australia) for providing access support for the Covidence systematic review software. Publisher Copyright: © 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

PY - 2023/9

Y1 - 2023/9

N2 - Purpose: Dry eye disease (DED) is a growing global health problem with a significant impact on the quality of life of patients. While neurosensory abnormalities have been recognised as a contributor to DED pathophysiology, the potential role of in vivo corneal confocal microscopy in detecting nerve loss or damage remains unclear. This systematic review with meta‐analysis (PROSPERO registered CRD42022381861) investigated whether DED has an impact on sub‐basal corneal nerve parameters. Methods: PubMed, Embase and Web of Science Core Collection databases were searched from inception to 9 December 2022. Studies using laser scanning confocal microscopy to compare corneal nerve parameters of DED with healthy eyes were included. Study selection process and data extraction were performed by two independent members of the review team. Results: Twenty‐two studies with 916 participants with DED and 491 healthy controls were included, with 21 of these studies included in subsequent meta‐analyses. There was a decrease in total corneal nerve length (−3.85 mm/mm2; 95% CI −5.16, −2.55), corneal main nerve trunk density (−4.81 number/mm2; 95% CI −7.94, −1.68) and corneal nerve branch density (−15.52 number/mm2; 95% CI −27.20, −3.84) in DED eyes compared with healthy eyes, with subgroup analysis demonstrating that these differences were more evident in studies using NeuronJ software, a semi‐automated procedure. While this review found evidence of loss of corneal nerve parameters in eyes with DED compared with healthy controls, particularly with the use of a semi‐automated image analysis method, it is evident that there is substantial heterogeneity between studies in terms of corneal nerve imaging methodology. Conclusions: Standardisation is required in terms of terminology and analysis, with more research needed to potentially improve the clinical applicability and practicality of corneal nerve imaging. Further investigation is also required to confirm the diagnostic accuracy of this imaging modality and its potential for monitoring DED treatment efficacy.

AB - Purpose: Dry eye disease (DED) is a growing global health problem with a significant impact on the quality of life of patients. While neurosensory abnormalities have been recognised as a contributor to DED pathophysiology, the potential role of in vivo corneal confocal microscopy in detecting nerve loss or damage remains unclear. This systematic review with meta‐analysis (PROSPERO registered CRD42022381861) investigated whether DED has an impact on sub‐basal corneal nerve parameters. Methods: PubMed, Embase and Web of Science Core Collection databases were searched from inception to 9 December 2022. Studies using laser scanning confocal microscopy to compare corneal nerve parameters of DED with healthy eyes were included. Study selection process and data extraction were performed by two independent members of the review team. Results: Twenty‐two studies with 916 participants with DED and 491 healthy controls were included, with 21 of these studies included in subsequent meta‐analyses. There was a decrease in total corneal nerve length (−3.85 mm/mm2; 95% CI −5.16, −2.55), corneal main nerve trunk density (−4.81 number/mm2; 95% CI −7.94, −1.68) and corneal nerve branch density (−15.52 number/mm2; 95% CI −27.20, −3.84) in DED eyes compared with healthy eyes, with subgroup analysis demonstrating that these differences were more evident in studies using NeuronJ software, a semi‐automated procedure. While this review found evidence of loss of corneal nerve parameters in eyes with DED compared with healthy controls, particularly with the use of a semi‐automated image analysis method, it is evident that there is substantial heterogeneity between studies in terms of corneal nerve imaging methodology. Conclusions: Standardisation is required in terms of terminology and analysis, with more research needed to potentially improve the clinical applicability and practicality of corneal nerve imaging. Further investigation is also required to confirm the diagnostic accuracy of this imaging modality and its potential for monitoring DED treatment efficacy.

KW - dry eye disease

KW - in vivo corneal confocal microscopy

KW - corneal nerves

KW - keratoconjunctivitis sicca

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