Mosaic vs. Single Image Analysis with Confocal Microscopy of the Corneal Nerve Plexus for Diagnosis of Early Diabetic Peripheral Neuropathy.

INTRODUCTION: The assessment of the corneal nerve fibre plexus with corneal confocal microscopy (CCM) is an upcoming but still experimental method in the diagnosis of early stage diabetic peripheral neuropathy (DPN). Using an innovative imaging technique-Heidelberg Retina Tomograph equipped with the Rostock Cornea Module (HRT-RCM) and EyeGuidance module (EG)-we were able to look at greater areas of subbasal nerve plexus (SNP) in order to increase the diagnostic accuracy. The aim of our study was to evaluate the usefulness of EG instead of single image analysis in diagnosis of early stage DPN. METHODS: This prospective study was performed on 60 patients with type 2 diabetes mellitus, classified equally into two subgroups based on neuropathy deficient score (NDS): patients without DPN (group 1) or with mild DPN (group 2). The following parameters were analysed in the two subgroups: corneal nerve fibre length (CNFL; mm/mm2), corneal nerve fibre density (CNFD; no./mm2), corneal nerve branch density (CNBD; no./mm2). Furthermore, we compared the data calculated with the novel mosaic, EG-based method with those received from single image analysis using different quantification tools. RESULTS: Using EG we did not find a significant difference between group 1 and group 2: CNFL (16.81 ± 5.87 mm/mm2 vs. 17.19 ± 7.19 mm/mm2, p = 0.895), CNFD (254.05 ± 115.36 no./mm2 vs. 265.91 ± 161.63 no./mm2, p = 0.732) and CNBD (102.68 ± 62.28 no./mm2 vs. 115.38 ± 96.91 no./mm2, p = 0.541). No significant difference between the EG method of analysing the SNP and the single image analysis of 10 images per patient was detected. CONCLUSION: On the basis of our results it was not possible to differentiate between early stages of large nerve fibre DPN in patients with type 2 diabetes mellitus via SNP analysis. To improve sensitivity and specificity of this method newer technologies are under current evaluation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05326958.

Atypical Cellular Elements of Unknown Origin in the Subbasal Nerve Plexus of a Diabetic Cornea Diagnosed by Large-Area Confocal Laser Scanning Microscopy.

In vivo large-area confocal laser scanning microscopy (CLSM) of the human eye using EyeGuidance technology allows a large-scale morphometric assessment of the corneal subbasal nerve plexus (SNP). Here, the SNP of a patient suffering from diabetes and associated late complications was analyzed. The SNP contained multiple clusters of large hyperintense, stellate-shaped, cellular-like structures. Comparable structures were not observed in control corneas from healthy volunteers. Two hypotheses regarding the origin of these atypical structures are proposed. First, these structures might be keratocyte-derived myofibroblasts that entered the epithelium from the underlying stroma through breaks in Bowman's layer. Second, these structures could be proliferating Schwann cells that entered the epithelium in association with subbasal nerves. The nature and pathophysiological significance of these atypical cellular structures, and whether they are a direct consequence of the patient's diabetic neuropathy/or a non-specific secondary effect of associated inflammatory processes, are unknown.

Thickness of Intraretinal Layers in Patients with Type 2 Diabetes Mellitus Depending on a Concomitant Diabetic Neuropathy: Results of a Cross-Sectional Study Using Deviation Maps for OCT Data Analysis.

Optical coherence tomography (OCT) supports the detection of thickness changes in intraretinal layers at an early stage of diabetes mellitus. However, the analysis of OCT data in cross-sectional studies is complex and time-consuming. We introduce an enhanced deviation map-based analysis (MA) and demonstrate its effectiveness in detecting early changes in intraretinal layer thickness in adults with type 2 diabetes mellitus (T2DM) compared to common early treatment diabetic retinopathy study (ETDRS) grid-based analysis (GA). To this end, we obtained OCT scans of unilateral eyes from 33 T2DM patients without diabetic retinopathy and 40 healthy controls. The patients were categorized according to concomitant diabetic peripheral neuropathy (DN). The results of MA and GA demonstrated statistically significant differences in retinal thickness between patients and controls. Thinning was most pronounced in total retinal thickness and the thickness of the inner retinal layers in areas of the inner macular ring, selectively extending into areas of the outer macular ring and foveal center. Patients with clinically proven DN showed the strongest thinning of the inner retinal layers. MA showed additional areas of thinning whereas GA tended to underestimate thickness changes, especially in areas with localized thinning. We conclude that MA enables a precise analysis of retinal thickness data and contributes to the understanding of localized changes in intraretinal layers in adults with T2DM.