Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies

<b>Background/Objectives:</b> Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology para...

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Main Authors: Prajna Vidyasagar, Scott F. Farrell, Luisa Holguin Colorado, Samantha Dando, Katie Edwards
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/7/1675
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author Prajna Vidyasagar
Scott F. Farrell
Luisa Holguin Colorado
Samantha Dando
Katie Edwards
author_facet Prajna Vidyasagar
Scott F. Farrell
Luisa Holguin Colorado
Samantha Dando
Katie Edwards
author_sort Prajna Vidyasagar
collection DOAJ
description <b>Background/Objectives:</b> Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology parameters; corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), and corneal nerve branch density (CNBD), measured through in vivo confocal microscopy (IVCM), as potential tools for differentiating painful and painless forms of diabetic neuropathy. <b>Methods:</b> A systematic review was performed comparing corneal nerve morphology across four groups: painful diabetic neuropathy (pDPN), non-painful diabetic neuropathy (npDPN), diabetes without neuropathy (DPN-), and healthy controls. Literature search extended over MEDLINE, EMBASE, Web of Science, and Cochrane Library, focusing on studies published since 2000. Study quality was assessed using the Newcastle–Ottawa Scale, while evidence certainly followed GRADE guidelines. Random-effects meta-analyses calculated mean differences (MDs) with 95% confidence intervals (CIs) for CNFL, CNFD, and CNBD. <b>Results:</b> Seven observational studies comprising 803 participants (213 pDPN, 275 npDPN, 99 DPN-, and 216 controls) revealed no significant differences between pDPN and npDPN groups in CNFL (MD = 0.79, 95% CI −0.64 to 2.22), CNFD (MD = 1.67, 95% CI −0.14 to 3.47), or CNBD (MD = 1.84, 95% CI −4.31 to 7.98). However, all metrics were markedly reduced in pDPN compared to DPN- and healthy controls. <b>Conclusions:</b> While effective in identifying diabetic neuropathy, common corneal nerve morphology parameters cannot reliably distinguish pDPN from npDPN. This highlights the need for research into mechanisms like central sensitization, inflammation, and micro-neuromas, which could refine diagnostic and therapeutic approaches for pDPN.
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spelling doaj-art-e15e771a07dd436a810911cee1db45c52025-08-20T03:35:58ZengMDPI AGBiomedicines2227-90592025-07-01137167510.3390/biomedicines13071675Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy StudiesPrajna Vidyasagar0Scott F. Farrell1Luisa Holguin Colorado2Samantha Dando3Katie Edwards4Centre of Vision and Eye Research, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD 4059, AustraliaRECOVER Injury Research Centre & NHMRC Centre for Research Excellence, The University of Queensland, Herston, QLD 4029, AustraliaCentre of Vision and Eye Research, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD 4059, AustraliaCentre of Immunology and Infection Control, School of Biomedical Sciences, Queensland of University of Technology, Brisbane, QLD 4059, AustraliaCentre of Vision and Eye Research, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD 4059, Australia<b>Background/Objectives:</b> Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology parameters; corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), and corneal nerve branch density (CNBD), measured through in vivo confocal microscopy (IVCM), as potential tools for differentiating painful and painless forms of diabetic neuropathy. <b>Methods:</b> A systematic review was performed comparing corneal nerve morphology across four groups: painful diabetic neuropathy (pDPN), non-painful diabetic neuropathy (npDPN), diabetes without neuropathy (DPN-), and healthy controls. Literature search extended over MEDLINE, EMBASE, Web of Science, and Cochrane Library, focusing on studies published since 2000. Study quality was assessed using the Newcastle–Ottawa Scale, while evidence certainly followed GRADE guidelines. Random-effects meta-analyses calculated mean differences (MDs) with 95% confidence intervals (CIs) for CNFL, CNFD, and CNBD. <b>Results:</b> Seven observational studies comprising 803 participants (213 pDPN, 275 npDPN, 99 DPN-, and 216 controls) revealed no significant differences between pDPN and npDPN groups in CNFL (MD = 0.79, 95% CI −0.64 to 2.22), CNFD (MD = 1.67, 95% CI −0.14 to 3.47), or CNBD (MD = 1.84, 95% CI −4.31 to 7.98). However, all metrics were markedly reduced in pDPN compared to DPN- and healthy controls. <b>Conclusions:</b> While effective in identifying diabetic neuropathy, common corneal nerve morphology parameters cannot reliably distinguish pDPN from npDPN. This highlights the need for research into mechanisms like central sensitization, inflammation, and micro-neuromas, which could refine diagnostic and therapeutic approaches for pDPN.https://www.mdpi.com/2227-9059/13/7/1675diabetic peripheral neuropathypainful diabetic neuropathyin vivo corneal confocal microscopycorneal nerve fibre lengthcorneal nerve fibre densitycorneal nerve branch density
spellingShingle Prajna Vidyasagar
Scott F. Farrell
Luisa Holguin Colorado
Samantha Dando
Katie Edwards
Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
Biomedicines
diabetic peripheral neuropathy
painful diabetic neuropathy
in vivo corneal confocal microscopy
corneal nerve fibre length
corneal nerve fibre density
corneal nerve branch density
title Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
title_full Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
title_fullStr Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
title_full_unstemmed Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
title_short Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
title_sort corneal nerve morphology in painful diabetic neuropathy a meta analysis of in vivo confocal microscopy studies
topic diabetic peripheral neuropathy
painful diabetic neuropathy
in vivo corneal confocal microscopy
corneal nerve fibre length
corneal nerve fibre density
corneal nerve branch density
url https://www.mdpi.com/2227-9059/13/7/1675
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