Vidyasagar Prajna, Farrell Scott F, Colorado Luisa Holguin, Dando Samantha, Edwards Katie
Centre of Vision and Eye Research, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD 4059, Australia.
RECOVER Injury Research Centre & NHMRC Centre for Research Excellence, The University of Queensland, Herston, QLD 4029, Australia.
Biomedicines. 2025 Jul 8;13(7):1675. doi: 10.3390/biomedicines13071675.
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. 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. 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. 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.
疼痛性糖尿病周围神经病变(pDPN)显著影响生活质量,但由于依赖主观疼痛报告且客观生物标志物有限,其诊断仍然具有挑战性。这项荟萃分析评估了通过体内共聚焦显微镜(IVCM)测量的角膜神经形态参数,即角膜神经纤维长度(CNFL)、角膜神经纤维密度(CNFD)和角膜神经分支密度(CNBD),作为区分疼痛性和无痛性糖尿病神经病变形式的潜在工具。进行了一项系统评价,比较了四组的角膜神经形态:疼痛性糖尿病神经病变(pDPN)、非疼痛性糖尿病神经病变(npDPN)、无神经病变的糖尿病(DPN-)和健康对照。文献检索范围涵盖MEDLINE、EMBASE、科学网和考克兰图书馆,重点关注2000年以来发表的研究。使用纽卡斯尔-渥太华量表评估研究质量,证据确定性遵循GRADE指南。随机效应荟萃分析计算了CNFL、CNFD和CNBD的平均差异(MDs)及95%置信区间(CIs)。七项观察性研究共纳入803名参与者(213名pDPN、275名npDPN、99名DPN-和216名对照),结果显示pDPN组和npDPN组在CNFL(MD = 0.79,95%CI -0.64至2.22)、CNFD(MD = 1.67,95%CI -0.14至3.47)或CNBD(MD = 1.84,95%CI -4.31至7.98)方面无显著差异。然而,与DPN-组和健康对照相比,pDPN组的所有指标均显著降低。虽然常见的角膜神经形态参数在识别糖尿病神经病变方面有效,但不能可靠地区分pDPN和npDPN。这突出了对中枢敏化、炎症和微神经瘤等机制进行研究的必要性,这些研究可能会完善pDPN的诊断和治疗方法。