Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study

Abstract

Background: For those in the field of managing diabetic complications, the accurate diagnosis and monitoring of diabetic peripheral neuropathy (DPN) continues to be a challenge. Assessment of sub-basal corneal nerve morphology has recently shown promise as a novel ophthalmic marker for the detection of DPN. Methods: Two hundred and thirty-one individuals with diabetes with predominantly mild or no neuropathy and 61 controls underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10 g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length, branch density and tortuosity were measured using corneal confocal microscopy. Differences in corneal nerve morphology between individuals with and without DPN and controls were investigated using analysis of variance and correlations were determined between corneal morphology and established tests of, and risk factors for, DPN. Results: Corneal nerve fibre length was significantly reduced in diabetic individuals with mild DPN compared with both controls (p < 0.001) and diabetic individuals without DPN (p = 0.012). Corneal nerve branch density was significantly reduced in individuals with mild DPN compared with controls (p = 0.032). Corneal nerve fibre tortuosity did not show significant differences. Corneal nerve fibre length and corneal nerve branch density showed modest correlations to most measures of neuropathy, with the strongest correlations to nerve conduction study parameters (r = 0.15 to 0.25). Corneal nerve fibre tortuosity showed only a weak correlation to the vibration detection threshold. Corneal nerve fibre length was inversely correlated to glycated haemoglobin (r = -0.24) and duration of diabetes (r = -0.20). Conclusion: Assessment of corneal nerve morphology is a non-invasive, rapid test capable of showing differences between individuals with and without DPN. Corneal nerve fibre length shows the strongest associations with other diagnostic tests of neuropathy and with established risk factors for neuropathy.

Early Detection of Nerve Fiber Loss by Corneal Confocal Microscopy and Skin Biopsy in Recently Diagnosed Type 2 Diabetes

“…In the current study, several CCM measures correlated with IENFD and with median and ulnar motor and sensory NCV, as well as sural SNAP, in the entire study population, but the relationship was modest to moderate. This is in line with the aforementioned studies (12,32,34) supporting the notion that the pathophysiology underlying the manifestation of neuropathy in the cornea may be different from DSPN affecting the lower limbs. Indeed, vascular factors including reduced endoneurial blood flow and microvascular alterations appear to contribute to the pathogenesis of DSPN (35,36), whereas the normal cornea, albeit being the most densely innervated tissue in the human body (several 100-fold higher than skin) (37), is devoid of blood vessels.…”

Rapid Automated Diagnosis of Diabetic Peripheral Neuropathy With In Vivo Corneal Confocal Microscopy

“…Our results are cross-sectional and ongoing longitudinal studies 38 will determine the ability of IVCCM to predict the development and progression or regression of DSPN. Recent data generated from wide-field assessment of the subbasal plexus have suggested that both central and inferior whorl nerve density may be reduced early and therefore future studies should explore this further.…”

Utility of Assessing Nerve Morphology in Central Cornea Versus Whorl Area for Diagnosing Diabetic Peripheral Neuropathy

“…Quantification of the SNP using CCM as a noninvasive and reiterative modality has been shown to be a promising marker for the detection and stratification of diabetic peripheral neuropathy (DPN) in several studies over the past decade. [5][6][7][8][9][10][11] Because of the convenience and ease of imaging from the central cornea, this region has been the main focus in almost all of these studies. However, recent investigations in diabetic patients 4 and animals 12 have provided evidence of more pronounced and earlier corneal neural loss at the inferior whorl.…”