Spatial analysis improves the detection of early corneal nerve fiber loss in patients with recently diagnosed type 2 diabetes

Abstract

Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the distribution of corneal nerve branching points (CNBPs) may contribute to improving the detection of early CNF loss. We hypothesized that early CNF decline follows a clustered rather than random distribution pattern of CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed in a cross-sectional study including 86 patients recently diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern analysis (SPPA) including 10 indices and functional statistics. Compared to controls, patients with diabetes showed lower CNBP density and higher nearest neighbor distances, and all SPPA parameters indicated increased clustering of CNBPs (all P<0.05). SPPA parameters were abnormally increased >97.5th percentile of controls in up to 23.5% of patients. When combining an individual SPPA parameter with CNFL, ≥1 of 2 indices were >99th or <1st percentile of controls in 28.6% of patients compared to 2.1% of controls, while for the conventional CNFL/CNFD/CNBD combination the corresponding rates were 16.3% vs 2.1%. SPPA parameters correlated with CNFL and several NCS and QST indices in the controls (all P<0.001), whereas in patients with diabetes these correlations were markedly weaker or lost. In conclusion, SPPA reveals increased clustering of early CNF loss and substantially improves its detection when combined with a conventional CCM measure in patients with recently diagnosed type 2 diabetes.

The Utility of Corneal Nerve Fractal Dimension Analysis in Peripheral Neuropathies of Different Etiology

“…In ophthalmology research, fractal dimension analysis has been used to study alterations in the retinal vascular network in diabetic retinopathy 47 and maculopathy 48 and to detect glaucoma in digital images. 49,50 A recent study has used spatial analysis to show increased clustering of corneal nerve loss in patients with early diabetic neuropathy 51 and we have shown altered CNFrD in patients with DPN. 26 In this context, our findings suggest that in addition to demonstrating corneal nerve loss, there may be specific imaging traits of remaining nerve fibers associated with the underlying etiology.…”

Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis

“…Using standard anatomic reference locations along with high-quality IVCM image data, automated approaches for identifying and quantifying secondary nerve branches could be employed, for example, using sophisticated algorithms as recently proposed. 37 Although the whorl position itself may not be consistent across eyes, the suggested approach for systematic analysis of the SBP referenced to the whorl location represents a step toward standardization. The whorl is an anatomic feature marking the corneal apical region.…”

Diagnosing Diabetic Neuropathy: Something Old, Something New

“…DPN may also induce clustering of corneal nerve fibers compared to the equally distributed nerve fibers in the healthy cornea. Spatial pattern analysis of CCM mosaics, an advanced computing method which allows the estimation of corneal nerve branching points, has been found to improve the detection of corneal nerve loss when used in combination with conventional measures of nerve morphometry [ 91 ].…”