Corneal nerve alterations in different stages of Fuchs’ endothelial corneal dystrophy: an in vivo confocal microscopy study

Purpose

To analyze potential alterations in corneal nerve morphology and function in different stages of Fuchs’ endothelial corneal dystrophy (FECD).

Methods

Thirty eyes with FECD underwent in vivo confocal microscopy using the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and the Rostock Cornea Module (RCM) to quantify the morphology of the central subbasal corneal nerve plexus (total nerve length, total nerve number, number of main nerve trunks, number of nerve branches) as well as esthesiometry (using the Cochet-Bonnet esthesiometer) of the central cornea to determine central corneal sensation as a measure of nerve function. Findings were correlated with an age-matched control group of 30 healthy individuals. Comparisons to biomicroscopical stage of FECD, visual acuity and central corneal thickness were performed using Spearman correlation.

Results

Depending on slit-lamp examination, all 30 eyes were classified into FECD stage 1–4 (stage 1: six eyes; stage 2: 15 eyes; stage 3: six eyes; stage 4: three eyes). Total nerve length (ρ?=??0.8, p?<?0.001), total nerve number (ρ?=??0.7, p?<?0.001), number of main nerve trunks (ρ?=??0.6, p?<?0.001), and number of nerve branches (ρ?=??0.7, p?<?0.001) decreased significantly with increasing FECD stages. Comparing to the visual acuity, significant positive correlations were found for total nerve length (ρ?=?0.5, p?=?0.012), total nerve number (ρ?=?0.5, p?=?0.005), number of main nerve trunks (ρ?=?0.4, p?=?0.017), and number of nerve branches (ρ?=?0.5, p?=?0.009). With central corneal thickness, there were significant inverse correlations for total nerve length (ρ?=??0.6, p?=?0.001), total nerve number (ρ?=??0.5, p?=?0.012), number of main nerve trunks (ρ?=??0.4, p?=?0.015), and number of nerve branches (ρ?=??0.4, p?=?0.017). Central corneal sensation was full in all FECD stage 1, stage 2 and stage 3 eyes, but mildly reduced in FECD stage 4 eyes.

Conclusions

Increasing severity of Fuchs’ endothelial corneal dystrophy (FECD) is concurrent with marked attenuation of the density, as well as mild diminishment of the function, of the subbasal corneal nerve plexus in late stage of the disease.     

In vivo confocal microscopic study of corneal innervation in Sjögren's Syndrome with or without small fiber neuropathy

PurposeTo study changes in the subbasal nerve plexus by In vivo confocal microscopy (IVCM) in Sjögren's Syndrome (SS) with or without associated Small Fiber Neuropathy (SFN), in order to prevent diagnostic delay.MethodsSeventy-one patients with SS, including 19 with associated SFN, 20 healthy volunteers and 20 patients with Meibomian gland dysfunction (MGD) were included in this retrospective case-control study. IVCM was used to investigate subbasal nerve plexus density and morphology.ResultsCorneal sensitivity as evaluated with the Cochet-Bonnet aesthesiometer was significantly reduced in the SS group versus the control group (P = 0.026) and the MGD group (P = 0.037). The number of inflammatory cells was significantly increased in the SS group to 86.2 ± 82.1 cells/mm² compared to the control group (P < 0.001). The density of the subbasal nerve plexus was significantly reduced to 16.7 ± 6.5 mm/mm² in the SS group compared to the control group (P < 0.005) and the MGD group (P = 0.042). The tortuosity of the nerves in the SS group was significantly increased compared to the control group (P < 0.001) and the MGD group (P = 0.025). The average number of subbasal nerve plexus neuromas was significantly increased in the SS group compared to the control group (P = 0.001), with a significant increase in the average number of neuromas in SS patients with associated SFN compared to SS patients without SFN (P = 0.008).ConclusionIVCM can be useful to detect corneal nerve changes in SS patients and may allow earlier diagnosis of the disease and to consider new therapeutic approaches.     

An in vivo confocal microscopy study: correlation between morphological changes of corneal subbasal nerve and clinical symptoms of Sjögren syndrome

AIM: To observe the morphological changes of corneal subbasal nerve (SBN) plexus in patients with Sj?gren syndrome (SS) by in vivo confocal microscopy (IVCM) study and analyze its correlation with clinical symptoms.METHODS: We collected 22 cases (44 eyes) patients with SS (observation group) and 22 cases (44 eyes) healthy people with the same age (control group) for observation of central corneal SBN fibers diameter, number of beads, and tortuosity, and recorded tear film break up time (BUT), Schirmer’s I test (SIT), tear meniscus height (TMH), dendritic cell (DC) density, the results were applied to perform statistical analysis.RESULTS: Under IVCM observation, the diameter of corneal SBN fibers in the observation group became thinner, the number of beads and the degree of nerve fiber tortuosity were increased compared with the control group, and the difference was statistically significant (P<0.05). Pearson correlation analysis: the diameter of corneal SBN fibers in the observation group was significantly correlated with BUT (r=0.472, P<0.01), SIT (r=0.562, P<0.01), TMH (r=0.246, P=0.02) and DC density (r=-0.636, P<0.01). The number of nerve fiber beads was correlated with BUT (r= -0.621, P<0.01), SIT (r=-0.688, P<0.01), TMH (r=-0.438, P<0.01) and DC density (r=0.528, P<0.01). There was a significant correlation between nerve fiber tortuosity and BUT (r=-0.634, P<0.01), SIT (r=-0.713, P<0.01), TMH (r= -0.384, P<0.01) and DC density (r=0.604, P<0.01).CONCLUSION: IVCM can effectively observe the morphology of corneal nerve plexus. In SS patients, the diameter of corneal SBN fibers becomes thinner, the number of beads increases, and the tortuosity of nerve fiber increases. Moreover, the degree of nerve fiber lesions is correlated with the severity of dry eye clinical symptoms.     

Corneal nerve regeneration after herpes simplex keratitis: A longitudinal in vivo confocal microscopy study

Purpose

To evaluate the long-term alterations of corneal nerves in patients with herpes simplex virus (HSV) keratitis using in vivo confocal microscopy (IVCM).

In vivo confocal microscopy detects bilateral changes of corneal immune cells and nerves in unilateral herpes zoster ophthalmicus

Purpose

To analyze bilateral corneal immune cell and nerve alterations in patients with unilateral herpes zoster ophthalmicus (HZO) by laser in vivo confocal microscopy (IVCM) and their correlation with corneal sensation and clinical findings.

The structural and functional corneal reinnervation mechanism at different regions after LASIK—an in vivo confocal microscopy study

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the recovery of structural and functional corneal sensory nerves within the LASIK flap in order to provide insight to...     

Visualization of microneuromas by using in vivo confocal microscopy: An objective biomarker for the diagnosis of neuropathic corneal pain?

PurposeThe diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate it from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM).MethodsThis was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age- and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of microneuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density.ResultsThere was a decrease in total nerve density in both NCP (14.14 ± 1.03 mm/mm²) and DED patients (12.86 ± 1.04 mm/mm²), as compared to normal controls (23.90 ± 0.92 mm/mm²; p < 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, microneuromas were observed in all patients with NCP, while they were not present in any of the patients with conventional DED (sensitivity and specificity of 100%). DC density was significantly increased in both NCP (71.89 ± 16.91 cells/mm²) and DED patients (111.5 ± 23.86 cells/mm²), as compared to normal controls (24.81 ± 4.48 cells/mm² (p < 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31).ConclusionIVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Microneuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.     

Mapping owl’s eye cells of patients with cytomegalovirus corneal endotheliitis using in vivo laser confocal microscopy

Purpose

To produce a two-dimensional reconstruction map of owl’s eye cells using in vivo laser confocal microscopy in patients with cytomegalovirus (CMV) corneal endotheliitis, and to demonstrate any association between owl’s eye cells and coin-shaped lesions observed with slit-lamp biomicroscopy.

Method

Two patients (75- and 77-year-old men) with polymerase chain reaction-proven CMV corneal endotheliitis were evaluated in this study. Slit-lamp biomicroscopy and in vivo laser confocal microscopy were performed. Images of owl’s eye cells in the endothelial cell layer were arranged and mapped into subconfluent montages. Montage images of owl’s eye cells were then superimposed on a slit-lamp photo of the corresponding coin-shaped lesion. Degree of concordance between the confocal microscopic images and slit-lamp photos was evaluated.

Results

In both eyes, a two-dimensional reconstruction map of the owl’s eye cells was created by computer software using acquired confocal images; the maps showed circular patterns. Superimposing montage images of owl’s eye cells onto the photos of a coin-shaped lesion showed good concordance in the two eyes.

Conclusions

This study suggests that there is an association between owl’s eye cells observed by confocal microscopy and coin-shaped lesions observed by slit-lamp biomicroscopy in patients with CMV corneal endotheliitis. The use of in vivo laser confocal microscopy may provide clues as to the underlying causes of CMV corneal endotheliitis.     

Investigation of anterior segment structures of the eye in Behçet’s disease using in vivo confocal microscopy

Graefe's Archive for Clinical and Experimental Ophthalmology - We sought to investigate alterations in the corneal subbasal nerve plexus and endothelium in patients with Behçet’s...     

The pathogenic role of transforming growth factor-β2 in glaucomatous damage to the optic nerve head

In patients with primary open angle glaucoma (POAG), the optic nerve head (ONH) shows characteristic cupping correlated with visual field defects. The progressive optic neuropathy is characterized by irreversible loss of retinal ganglion cells (RGC). The critical risk factor for axonal damage at the ONH is an elevated intraocular pressure (IOP). The increase in IOP correlates with axonal loss in the ONH, which might be due to an impaired axoplasmatic flow leading to the loss of RGCs. Damage to the optic nerve is thought to occur in the lamina cribrosa (LC) region of the ONH, which is composed of characteristic sieve-like connective tissue cribriform plates through which RGC axons exit the eye. The cupping of the optic disc, and the compression and excavation of LC are characteristic signs of glaucomatous ONH remodelling. In ONH of POAG patients a disorganized distribution and deposition of elastic fibers and a typical pronounced thickening of the connective tissue septae surrounding the optic nerve fibers is found.Transforming growth factor (TGF)-β2 could be one of the pathogenic factors responsible for the structural alterations in POAG patients as the TGF-β2 levels in the ONH of glaucomatous eyes are elevated as well as in the aqueous homour. TGF-β2 leads to an increased synthesis of extracellular matrix (ECM) molecules mediated by connective tissue growth factor and to an impaired ECM degradation in cultured ONH astrocytes. Bone morphogenetic protein (BMP)-4 effectively antagonizes the effects of TGF-β2 on matrix deposition. The BMP antagonist gremlin blocks this inhibition, allowing TGF-β2 stimulation of ECM synthesis. Overall, the ECM in the ONH is kept in balance in the OHN by factors that augment or block the activity of TGF-β2.     

The role of protein tyrosine phosphorylation in the cell–cell junctions and intercellular permeability of post-confluent bovine corneal epithelial cells

PurposeTo evaluate the role of protein tyrosine phosphatase (PTP) in controlling the integrity of cell–cell junction and intercellular permeability in postconfluent bovine corneal epithelial cells.MethodsConfluent cultures of bovine corneal epithelial cells were treated with different concentrations of general phosphate inhibitors andsodium orthovanadate for varying periods. An MTS assay was used to confirm no cellular death under the treatment profile. Immunocytochemical (ICC) analysis was performed to demonstrate protein tyrosine phosphorylation after treatment with sodium orthovanadate, and the effect of sodium orthovanadate on junctional proteins such as p120, α-catenin, occludin, ZO-1, and ZO-2. Western blot analysis was used to analyze the changes in p120, α-catenin, occludin, ZO-1, and ZO-2 after treatment. Paracellular permeability was evaluated by transepithelial electrical resistance (TER).ResultsDuring the whole course of treatment, no significant cellular death was noticed. Dose- and time-dependent effects of sodium orthovanadate on protein tyrosine phosphorylation were confirmed by ICC. ICC also demonstrated the dose- and time-dependent effect of sodium orthovanadate on the disruption of p120, α-catenin, occludin, ZO-1, and ZO-2. However, results of Western blot analysis showed no change in the expression levels of p120, α-catenin, occludin, ZO-1, and ZO-2. Dose- and time-dependent increase of paracellular permeability was evaluated by TER.ConclusionInhibition of protein tyrosine phosphatase activity can increase protein tyrosine phosphorylation. A dose- and time-dependent release of cell–cell contacts and increased transepithelial permeability were found in postconfluent culture of bovine corneal epithelial cells.