Corneal Confocal Microscopy

Abstract

OBJECTIVEThe accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies.RESEARCH DESIGN AND METHODSA total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM).RESULTSCorneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74).CONCLUSIONSCCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity.

Corneal Confocal Microscopy Predicts 4-Year Incident Peripheral Neuropathy in Type 1 Diabetes

“…This approach has been validated as a viable alternative for assessing DPN (3)(4)(5). Increased severity of DPN is associated with reduced corneal nerve fiber length (CNFL) (4,5) and corneal sensitivity (6,7), assessed using CCM and noncontact corneal esthesiometry (NCCE), respectively.…”

“…Unmyelinated nerve fibers can now be examined at approximately original magnification 3500 using a laser scanning corneal confocal microscope (CCM) to image the subbasal nerve plexus of the human cornea in vivo (2). This approach has been validated as a viable alternative for assessing DPN (3)(4)(5). Increased severity of DPN is associated with reduced corneal nerve fiber length (CNFL) (4,5) and corneal sensitivity (6,7), assessed using CCM and noncontact corneal esthesiometry (NCCE), respectively.…”

Distal Sensorimotor Neuropathy: Improvements in Diagnosis

“…In diabetes, it has been shown that reductions in corneal innervation occur early in the disease, are symmetrical between left and right eye, worsen with increasing severity of DSPN, and that such changes are parallel to similar changes in IEFND in the feet [47][48][49]. Tavakoli et al from the Manchester group have demonstrated that all parameters measured in CCM correlate strongly with NDS and indeed with DPSN severity (corneal nerve fiber density r = -0.475, p < 0.0001; nerve branch density r = -0.511, p < 0.0001; nerve fiber length r = -0.581, p < 0.0001) [48]. Receiver operating characteristic curve analysis for the diagnosis of neuropathy (using NDS >3 to indicate clinical neuropathy) defined a sensitivity of 82% and specificity of 52%.…”

“…This has been shown to be a rapid, non-invasive ophthalmic technique that can accurately quantify corneal innervation in the human subbasal plexus [46]. In diabetes, it has been shown that reductions in corneal innervation occur early in the disease, are symmetrical between left and right eye, worsen with increasing severity of DSPN, and that such changes are parallel to similar changes in IEFND in the feet [47][48][49]. Tavakoli et al from the Manchester group have demonstrated that all parameters measured in CCM correlate strongly with NDS and indeed with DPSN severity (corneal nerve fiber density r = -0.475, p < 0.0001; nerve branch density r = -0.511, p < 0.0001; nerve fiber length r = -0.581, p < 0.0001) [48].…”

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining

“…Alterations of SBP morphological parameters derived from IVCM images serve as potential biomarkers for early diagnosis of various neurodegenerative diseases. [1][2][3][4] However, the ability of IVCM to adequately resolve intimate details of SBP anatomy remains incompletely understood since the field of view of a conventional IVCM image is relatively small (400 × 400 μm 2 ) and might be insufficient for reliable assessment of SBP morphology. 5 Advancements in imaging extended areas of the corneal SBP by creating large-scale montages [6][7][8] have substantially alleviated this principal limitation of IVCM.…”