Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology.

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases

Analysis of peripapillary choroidal thickness in unilateral amblyopia

Purpose: To evaluate the peripapillary choroidal thickness (CT) in children with unilateral amblyopia using spectral-domain optical coherence tomography (SD-OCT). Methods: One hundred and six eyes of 53 children with unilateral amblyopia and 20 eyes of 20 children with normal vision were involved in this study. Of the 53 children with unilateral amblyopia, 29 (54.7%) had hyperopic anisometropic amblyopia and 24 (45.3%) had strabismic amblyopia. Peripapillary CT was measured from 6 mm length radial B-scans at the optic nerve head using the enhanced depth imaging program of an SD-OCT (Heidelberg Engineering, Germany). Age, sex, refractive error, and best-corrected visual acuity were also recorded. Results: The average peripapillary CT was greater in amblyopic eyes than in the fellow eyes of the children with amblyopia (P = 0.002), and control eyes (P < 0.001). There was no significant difference between the fellow eyes of children with amblyopia and the control eyes (P = 0.158). The average peripapillary CT was negatively correlated with axial length (AL) in amblyopic eyes (r = -0.381; P = 0.005) and fellow eyes (r = -0.392; P = 0.004) but not in control eyes (r = -0.232; P = 0.325). After adjustment for the possible effects of AL, the average peripapillary CT in amblyopic eyes was still greater than in fellow eyes (P = 0.014) and control eyes (P = 0.022). Conclusion: The peripapillary choroid of eyes with amblyopia was thicker than that of the fellow eyes and control eyes. No significant difference was observed between fellow eyes and control eyes

In vivo corneal confocal microscopic analysis in patients with keratoconus

AIM: To quantify corneal ultrastructure using laser scanning in vivo confocal microscopy (IVCM) in patients with keratoconus and control subjects. METHODS: Unscarred corneas of 78 keratoconic subjects without a history of contact lens use and 36 age-matched control subjects were evaluated with slit-lamp examination (SLE), corneal topography and laser scanning IVCM. One eye was randomly chosen for analysis. Anterior and posterior stromal keratocyte, endothelial cell and basal epithelial cell densities and sub-basal nerve structure were evaluated. RESULTS: IVCM qualitatively demonstrated enlarged basal epithelial cells, structural changes in sub-basal and stromal nerve fibers, abnormal stromal keratocytes and keratocyte nuclei, and pleomorphism and enlargement of endothelial cells. Compared with control subjects, significant reductions in basal epithelial cell density (5817±306 cells/mm(2) vs 4802±508 cells/mm(2), P<0.001), anterior stromal keratocyte density (800±111 cells/mm(2) vs 555±115 cells/mm(2), P<0.001), posterior stromal keratocyte density (333±34 cells/mm(2) vs 270±47 cells/mm(2), P<0.001), endothelial cell density (2875±223 cells/mm(2) vs 2686±265 cells/mm(2), P<0.001), sub-basal nerve fiber density (31.2±8.4 nerves/mm(2) vs 18.1±9.2 nerves/mm(2), P<0.001), sub-basal nerve fiber length (21.4±3.4 mm/mm(2) vs 16.1±5.1 mm/mm(2), P<0.001), and sub-basal nerve branch density (median 50.0 (first quartile 31.2 - third quartile 68.7) nerve branches/mm(2) vs median 25.0 (first quartile 6.2 - third quartile 45.3) nerve branches/mm(2), P<0.001) were observed in patients with keratoconus. CONCLUSION: Significant microstructural abnormalities were identified in all corneal layers in the eyes of subjects with keratoconus using IVCM. This non-invasive in vivo technique provides an important means to define and follow progress of microstructural changes in patients with keratoconus

Effects of panretinal laser photocoagulation on the corneal nerve plexus and retinal nerve fiber layer in retinal vein occlusion

Purpose To determine the effects of panretinal photocoagulation (PRP) on corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with unilateral central retinal vein occlusion (CRVO) who had previously undergone PRP treatment. Methods Sixty-four eyes of 32 patients (19 male, 13 female) with unilateral ischemic type CRVO who had undergone PRP treatment at least 6 months previously were included in this cross-sectional study. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the PRP-treated eyes were compared with those of the fellow unaffected eyes. Results The mean age of patients was 63.5 ± 10.7 years (range 45-85 years). The mean nerve fiber density (NFD), nerve branch density, and nerve fiber length (NFL) were significantly lower in PRP-treated eyes compared with fellow eyes (p&lt;0.001 for all). Average peripapillary RNFL thickness was significantly lower in PRP-treated eyes than in fellow eyes (p = 0.007). The NFD and NFL showed a modest but significant positive correlation with average peripapillary RNFL thickness (r = 0.310, p = 0.013 and r = 0.272, p = 0.030, respectively). Conclusions Significant reductions in corneal SBNP parameters and average peripapillary RNFL thickness were observed in the eyes of patients receiving PRP for the treatment of ischemic CRVO. </jats:sec

Assessment of corneal sensation, innervation and retinal nerve fiber layer in patients treated with multiple intravitreal ranibizumab injections

PURPOSE: To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD). METHODS: Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects. RESULTS: The mean number of ranibizumab injections per eye was 8.9±5.0 (range 3–20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P = 0.237), and the eyes of healthy control subjects (P = 0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters. CONCLUSIONS: Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD

In Vivo Confocal Microscopic Evaluation of Corneal Nerve Fibers and Dendritic Cells in Patients With Behçet’s Disease

Central and peripheral nervous system involvement may occur during the course of Behçet’s disease (BD). In vivo corneal confocal microscopy (CCM) can detect corneal small fiber damage and immune cell density. The aim of this study was to assess central corneal sensitivity, corneal subepithelial nerve plexus morphology and dendritic cell (DC) density in patients with BD. Forty-nine consecutive patients with BD and 30 healthy control subjects were included in this cross-sectional study conducted at a tertiary referral university hospital. Central corneal sensitivity was measured using the contact corneal esthesiometer (Cochet-Bonnet; Luneau, France). The laser scanning CCM (Heidelberg, Germany) was used to quantify corneal nerve fiber density (NFD), nerve branch density (NBD), nerve fiber length (NFL), and DC density. There was a significant reduction in NFD (P = 0.001) and NFL (P = 0.031) and an increase in DC density (P = 0.038) in patients with BD compared to healthy controls, whereas corneal sensitivity (P = 0.066) and NBD (P = 0.067) did not differ significantly. There was no difference in corneal sensitivity, corneal nerve parameters, or DC density between BD patients with [n = 18 (36.7%)] and without a previous history of uveitis (P &gt; 0.05 for all). Disease duration [median (IQR), 6.5 (4.0–14.5) years] correlated with corneal sensitivity (ρ = −0.463; P = 0.001) and NFD (ρ = −0.304; P = 0.034) and corneal sensitivity correlated with NFD (ρ = 0.411; P = 0.003) and NFL (ρ = 0.295; P = 0.039) in patients with BD. CCM demonstrates corneal sub-basal nerve fiber loss and increased DC density, providing a non-invasive ophthalmic means to identify peripheral neuropathy and inflammation in patients with BD