Department of Medical Biochemistry, Unit of Regenerative Medicine, Oslo University Hospital, Oslo, Norway.
Department of Translational Medicine, Hand Surgery, Lund University, Malmö, Sweden.
Diabetes. 2023 Jul 1;72(7):908-917. doi: 10.2337/db22-0863.
Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, where skin biopsy assessing intraepidermal nerve fiber density (IENFD) plays an important diagnostic role. In vivo confocal microscopy (IVCM) of the corneal subbasal nerve plexus has been proposed as a noninvasive diagnostic modality for DPN. Direct comparisons of skin biopsy and IVCM in controlled cohorts are lacking, as IVCM relies on subjective selection of images depicting only 0.2% of the nerve plexus. We compared these diagnostic modalities in a fixed-age cohort of 41 participants with type 2 diabetes and 36 healthy participants using machine algorithms to create wide-field image mosaics and quantify nerves in an area 37 times the size of prior studies to avoid human bias. In the same participants, and at the same time point, no correlation between IENFD and corneal nerve density was found. Corneal nerve density did not correlate with clinical measures of DPN, including neuropathy symptom and disability scores, nerve conduction studies, or quantitative sensory tests. Our findings indicate that corneal and intraepidermal nerves likely mirror different aspects of nerve degeneration, where only intraepidermal nerves appear to reflect the clinical status of DPN, suggesting that scrutiny is warranted concerning methodologies of studies using corneal nerves to assess DPN.
Comparison of intraepidermal nerve fiber density with automated wide-field corneal nerve fiber density in participants with type 2 diabetes revealed no correlation between these parameters. Intraepidermal and corneal nerve fibers both detected neurodegeneration in type 2 diabetes, but only intraepidermal nerve fibers were associated with clinical measures of diabetic peripheral neuropathy. A lack of association of corneal nerves with peripheral neuropathy measures suggests that corneal nerve fibers may be a poor biomarker for diabetic peripheral neuropathy.
描述糖尿病患者角膜神经纤维密度与皮肤神经纤维密度的相关性。
在这项横断面研究中，我们纳入了 41 名 2 型糖尿病患者和 36 名健康对照者，采集他们的皮肤和角膜活检标本，以评估皮肤内神经纤维密度（IENFD）和角膜神经纤维密度（CNFD）。我们使用机器算法创建了宽视野图像镶嵌图，并对之前研究面积的 37 倍的区域进行神经定量，以避免人为偏差。
在所有参与者中，IENFD 与 CNFD 之间均无相关性。CNFD 与 DPN 的临床测量值（包括神经病变症状和残疾评分、神经传导研究或定量感觉测试）均无相关性。
这些发现表明，角膜和表皮内神经可能反映了神经退化的不同方面，只有表皮内神经似乎反映了 DPN 的临床状况，这表明使用角膜神经评估 DPN 的研究方法需要仔细审查。
