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

Abstract

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/mm 2 ), corneal nerve fibre density (CNFD; no./mm 2 ), corneal nerve branch density (CNBD; no./mm 2 ). 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/mm 2 vs. 17.19 ± 7.19 mm/ mm 2 , p = 0.895), CNFD (254.05 ± 115.36 no./ mm 2 vs. 265.91 ± 161.63 no./mm 2 , p = 0.732) and CNBD (102.68 ± 62.28 no./mm 2 vs. 115.38 ± 96.91 no./mm 2 , 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

Comparison of Novel Wide-Field In Vivo Corneal Confocal Microscopy With Skin Biopsy for Assessing Peripheral Neuropathy in Type 2 Diabetes

“…Our automated imaging and quantification methods and strict inclusion of participants of the same age and only with type 2 diabetes may account for these differences; however, more studies without requiring selection of single IVCM images are warranted to verify our findings. Two earlier studies with substantially smaller imaged areas than in the current study also reported poor correlation of IVCM with IENFD or neuropathy disability ( 34 , 35 ). Use of corneal nerves as a surrogate marker for detecting neuropathy in diabetes should therefore be considered with caution, and studies should be assessed based on the area of the subbasal nerve plexus imaged and the potential for bias in selection of nerve images for analysis.…”

“…All subsequent quantitative analyses are ultimately limited by the subjective choice of images. These methodological deficiencies can have a large impact on the results obtained ( 31 , 35 ), and this may be limiting corneal nerve assessment in achieving the level of maturity and widespread acceptance as clinical measures of DPN.…”

“…IVCM has been suggested to be advantageous relative to invasive methods, such as skin biopsy and other clinical methods of assessing DPN ( 27 , 28 , 30 , 33 ). However, methodological limitations of quantifying corneal nerves have led to conflicting results regarding the utility of IVCM versus skin biopsy and clinical measures of DPN ( 34 , 35 ). For this reason, we aimed to evaluate the diagnostic utility and efficacy of IENFD relative to corneal nerve density using the largest area of the subbasal plexus examined to date in a diabetes cohort, using the mCNFL parameter to avoid human image selection bias.…”

In-vivo corneal confocal microscopy: Imaging analysis, biological insights and future directions

“…Sampling strategy of adequate images has been shown to produce sufficient accuracy, however for longitudinal or clinical monitoring purposes, real-time widefield imaging capabilities may provide more insight into regional changes in the cornea over time or following exposure to various stimuli 77,78 . In fact, a minimum repeatable area of 1.5 mm 2 is shown to have reliable morphological characterisation of the sub-basal nerve plexus 79,80 .…”