Corneal Subbasal Nerve Research Articles

Association of tear osmolarity and corneal nerves structure in dry eye disease: an in vivo study.

To evaluate the structural changes in corneal sub-basal nerves of dry eye disease (DED) patients with tear hyperosmolarity versus normosmolar tears. A prospective evaluation of the tear film (keratograph 5M), tear osmolarity, and sub-basal corneal nerves (laser scanning in-vivo confocal microscopy) was performed in a cohort of 53 DED patients (106 eyes) diagnosed as per DEWS II criteria. Patients with tear hyperosmolarity (Group 1, n = 48 eyes) were compared with DED patients without tear hyperosmolarity (Group 2, n = 58 eyes). Of 53 patients (27 females), 28 had Sjogren's syndrome, and the rest had meibomian gland dysfunction. There were more SS patients (21 vs 7) and females in Group 1. The two groups were similar in age, TMH, NIBUT, meibomian gland loss, bulbar redness, and corneal staining, except for Schirmer I (p < 0.001), and tear osmolarity (p < 0.001; worse in group 1). The groups did not differ in dendritic cell density, whether immature (53.8 vs. 38) or mature (2.7 vs. 0). The significantly different corneal nerve parameters were nerve fiber length (p = 0.005), density (p = 0.01), and branching density (p = 0.04), with lower values observed in group 1. Only tear osmolarity had a weak negative correlation with corneal nerve fiber length (r, -0.38), density (r, -0.32), and branching (r, -0.28). SS patients with hyperosmolar tears had reduced nerve fiber length and branching compared to SS patients with normosmolar tears. Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length despite similar levels of conjunctival congestion, tear film stability, and meibomian gland loss in DED patients. What is known • Corneal nerves are reduced in density and length in dry eye disease patients. • Laboratory studies have shown fragmentation of corneal nerves on exposure to hyperosmolar solutions. What is new • Tear hyperosmolarity is associated with reduced nerve branching, fiber density, and fiber length in dry eyes compared to normosmolar tears. • The effect is independent of dendritic cell density.

Concurrent Limbal Stem Cell Deficiency and Mild Neurotrophic Keratopathy in Graft-Vs-Host Disease

Purpose: The purpose of this study was to delineate the concurrence of limbal stem cell deficiency (LSCD) and neurotrophic keratopathy in patients with ocular graft-vs-host disease (oGVHD). Methods: Medical records of patients with oGVHD were reviewed. Parameters collected included corneal sensitivity measured by using a noncontact esthesiometer, corneal fluorescein staining score (National Eye Institute grading scale), tear volume (Schirmer I test), and subbasal nerve density and limbal structure assessed by in vivo confocal microscopy. Results: Twenty-eight patients (mean age: 60.8 ± 10.4 years) with oGVHD were included; 50% (n = 14) had partial LSCD (P-LSCD), and 32% (n = 9) had complete LSCD (C-LSCD). Patients with C-LSCD showed significantly reduced total nerve density and branch nerve density compared with those with P-LSCD (P &lt; 0.02, P &lt; 0.04) and no LSCD (P &lt; 0.01, P = 0.02). Dendritic cell density was significantly higher in the C-LSCD group compared with the no LSCD group (P &lt; 0.05). Corneal sensitivity was significantly reduced in patients with C-LSCD compared with those with P-LSCD (P = 0.01) and no LSCD (P &lt; 0.02). Patients with C-LCSD had higher corneal fluorescein staining scores than patients with P-LSCD (P &lt; 0.01) and no LSCD (P = 0.02). Conclusions: This study highlights a significant concurrence of LSCD and neurotrophic keratopathy in patients with oGVHD, underscoring the link between inflammation, neurodegeneration, and loss of stem cell function.

Corneal Sensitivity and Neuropathy in Patients With Ocular Graft-Versus-Host Disease.

To assess corneal sensitivity changes in patients with ocular graft-versus-host disease using a non-contact and Cochet-Bonnet esthesiometer. In addition, we evaluate the association between corneal sensitivity and subbasal nerve changes and epitheliopathy in these patients. In this retrospective study, the clinical data and images were evaluated for 36 patients (19 female, 17 male) who fulfilled the inclusion criteria. The analyzed data included demographic and ocular surface parameters, including best-corrected visual acuity, corneal sensitivity with non-contact (mbar) and Cochet-Bonnet (cm) esthesiometer, corneal fluorescein staining (CFS) and symptoms scores, tear volume (Schirmer-I test, mm/5'), and subbasal nerve density (μm/mm2; assessed with in vivo confocal microscopy). The mean age of the study cohort was 59.9 ± 10.5 years. The mean corneal sensitivity assessed by Cochet-Bonnet and non-contact esthesiometer was 5.9 ± 0.3 cm and 7.3 ± 2.0 mbar, respectively. The ocular surface parameters included a corneal fluorescein staining (CFS) score, as per the National Eye Institute grading scheme, of 6.9 ± 3.5, and a Schirmer-I test result of 7.5 ± 6.2 mm/5 minutes.. Total corneal subbasal nerve density was inversely associated with CFS scores (r = -0.74; P < 0.001). Moreover, similar correlations between CFS scores and main trunk (r = -0.62; P < 0.001) and branch (r = -0.59; P < 0.001) nerve densities were observed. A significant correlation was found between reduced corneal sensitivity and higher CFS scores (r = 0.66; P < 0.001). Higher pressures were correlated with lower total (r = -0.83; P < 0.001), main trunk (r = -0.62; P < 0.001), and branch (r = -0.72; P < 0.001) nerve densities. The univariate analysis showed that corneal sensitivity loss (assessed with non-contact esthesiometer) was correlated with advanced age of the patients (P = 0.049) and inversely associated with total (P < 0.001), main trunk (P < 0.001), and branch (P < 0.001) nerve densities. In addition, sensitivity loss was inversely associated with punctal occlusion (cauterization (P = 0.001) or plug placement (P < 0.001). The multivariate analysis adjusted for age and punctal occlusion confirmed the associations in the univariate analysis. In this study, we observed that corneal sensitivity loss was associated with reduced main trunk, branch, and total nerve density in patients with ocular graft-versus-host disease. In addition, a significant correlation was observed between reduced corneal nerve density, corneal sensitivity, and severity of epitheliopathy.

Deep-learning based analysis of in-vivo confocal microscopy images of the subbasal corneal nerve plexus’ inferior whorl in patients with neuropathic corneal pain and dry eye disease

PurposeTo evaluate and compare subbasal corneal nerve parameters of the inferior whorl in patients with dry eye disease (DED), neuropathic corneal pain (NCP), and controls using a novel deep-learning-based algorithm to analyze in-vivo confocal microscopy (IVCM) images. MethodsSubbasal nerve plexus (SNP) images of the inferior whorl of patients with DED (n = 49, 77 eyes), NCP (n = 14, 24 eyes), and controls (n = 41, 59 eyes) were taken with IVCM and further analyzed using an open-source artificial intelligence (AI)-based algorithm previously developed by our group. This algorithm automatically segments nerves, immune cells, and neuromas in the SNP. The following parameters were compared between groups: nerve area density, average nerve thickness, average nerve segment tortuosity, junction point density, neuroma density, and immune cell density. Results160 eyes of 104 patients (63 % females), aged 56.8 ± 15.4 years, were included. The mean nerve area density was significantly lower in the DED (P = 0.012) and NCP (P < 0.001) groups compared to the control group. The junction point density was lower in the NCP group compared with control (P = 0.001) and DED (P = 0.004) groups. The immune cell density was higher in the DED group compared with controls (P < 0.001). ConclusionsDeep-learning-based analysis of IVCM images of the corneal SNP inferior whorl distinguished a decreased mean nerve area density in patients with DED and NCP compared with controls and an increased immune cell density in patients with oGVHD- and SS-associated DED. These findings suggest that the inferior whorl could be used as landmark to distinguish between patients with DED and NCP.

Multimodal Approach in Dry Eye Disease Combining In Vivo Confocal Microscopy and HLA-DR Expression.

The purpose of this study was to determine the association between corneal images provided by in vivo confocal microscopy (IVCM) with clinical parameters and conjunctival expression of HLA-DR antigen in patients with dry eye disease (DED). Two hundred fourteen eyes of 214 patients with DED were analyzed, consisting of 2 groups of patients - 63 with autoimmune dry eye disease (AIDED) and 151 with non-autoimmune dry eye disease (NAIDED). Patients underwent a full clinical examination, including symptom screening, using the Ocular Surface Disease Index (OSDI) questionnaire, and objective analysis of DED signs by Schirmer's testing, tear break-up time (TBUT), Oxford's test, and IVCM corneal imaging. The IVCM scoring criteria were based on corneal sub-basal nerve density (ND), nerve morphology (NM), and inflammatory cell (IC) density. Quantification of conjunctival HLA-DR antigen was performed by flow cytometry. The total IVCM score (T-IVCM) as well as the IVCM-IC subscore (sc) were positively correlated with HLA-DR levels with r = 0.3, P < 0.001 and r = 0.3, P < 0.01, respectively in the total population of patients with DED. The IVCM-NDsc was negatively correlated with TBUT in patients with AIDED (r = -0.2, P < 0.05) and with the Schirmer's test in patients with NAIDED (r = -0.24, P < 0.05). However, the IVCM-NMsc was positively correlated with the Oxford score only in patients with AIDED (r = 0.3, P < 0.05). The proposed IVCM scoring system showed significant correlations with clinical parameters along with conjunctival HLA-DR quantification in patients with DED. The IVCM grading score represents an interesting point of commonality among clinical parameters, imaging, and molecular investigation of the ocular surface.

Remission of corneal and peripheral neuropathy after bariatric surgery in people with diabetes

PurposeDiabetic peripheral neuropathy can be detected using non-invasive in vivo confocal microscopy of the cornea (IVCM) and such abnormalities may precede the development of clinical neuropathy. The current study aimed to assess any progression or remission of corneal and peripheral neuropathy in patients with type 2 diabetes undergoing bariatric surgery. MethodsPeople with known type 2 diabetes for at least five years and listed for bariatric surgery were recruited. Participants were assessed before, and 12, 26, and 52 weeks following bariatric surgery. IVCM and corneal sensitivity measurements were performed. A modified total neuropathy score (mTNS) was obtained from neuropathy questionnaire, clinical assessment and biothesiometry. ResultsTwenty-nine participants (M:F, 11:18) with mean BMI of 44.7 ± 6.4 kg/m2, and 11 ± 7.6 years duration of diabetes, were assessed. Corneal sub-basal nerve fibre length (CNFL), displayed an increase from a baseline mean of 12.20 ± 1.00 to 17.48 ± 0.92 mm/mm2 at 52 weeks (p < 0.0001). Corneal sensitivity threshold displayed a decrease over time, thus corneal sensitivity improved, falling from a mean of 1.11 ±0 .15 to 0.62 ± 0.11 (mBAR) (p < 0.0001). Clinical neuropathy scores demonstrated significant improvements from baseline, displaying a decrease in average mTNS score from 3.29 ± 0.68 to 0.76 ± 0.30 (p < 0.0001). A significant inverse relationship was shown between CNFL and sensitivity (β coefficient = −0.047, p < 0.001), and CNFL and mTNS (β coefficient = −0.178, p < 0.001). ConclusionBariatric surgery led to an improvement in metabolic control of diabetes and weight loss, along with improvement in corneal nerve microstructure, corneal sensitivity, and neuropathic symptoms, suggesting a reversal of both small and large fibre neuropathy.

Corneal nerve fiber morphology following COVID-19 infection in vaccinated and non-vaccinated population

To examine corneal subbasal nerve changes in patients who received vaccination against SARS-CoV-2 virus and underwent COVID-19 infection compared to infected non-vaccinated patients and healthy controls. Twenty-nine eyes of 29 vaccinated patients (mean age: 36.66 ± 12.25 years) within six months after PCR or Ag test proven COVID-19 infection and twenty-eight eyes of 28 age-matched infected, non-vaccinated patients (mean age: 42.14 ± 14.17 years) were enrolled. Twenty-five age-matched healthy individuals (mean age: 47.52 ± 18.45 years) served as controls. In vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module, Germany) was performed in each group. Corneal subbasal nerve plexus morphology and corneal dendritic cells (DC) were evaluated. Significantly higher corneal nerve fiber density (P < 0.001), nerve branch density (P < 0.001), nerve fiber length (P < 0.001), total branch density (P = 0.007), nerve fiber area (P = 0.001) and fractal dimension (P < 0.001) values were observed in vaccinated patients after COVID-19 infection compared to the non-vaccinated group. Significantly higher DC density was observed in the non-vaccinated group compared to the control group (P = 0.05). There was a statistically significant difference in the size of mature DCs (P < 0.0001) but the size of immature DCs did not differ significantly among the 3 groups (P = 0.132). Our results suggest that SARS-CoV-2 vaccination may have a protective effect against the complications of COVID-19 disease on the corneal subbasal nerve fibers.

Co-existence of Neurotrophic Keratopathy in Eyes With Limbal Stem Cell Deficiency

PurposeTo investigate whether neurotrophic keratopathy is present in limbal stem cell deficiency (LSCD) by measuring corneal sensation and characterizing corneal subbasal nerve plexus. DesignProspective, cross-sectional “case-control” comparative study. MethodsForty-six eyes with LSCD and 14 normal eyes were recruited from 2019 to 2022. Corneal sensation was measured using a Cochet-Bonnet esthesiometer and subbasal nerve plexus was imaged using in vivo confocal microscopy (IVCM) at the central cornea and 4 limbal regions. Subbasal nerve density (SND, number of nerve/mm2), subbasal nerve length (SNL, total length of nerve/mm2) and subbasal nerve branch density (SNBD, number of branch/mm2) were quantified. LSCD was graded to stage 1, 2 and 3 using a previously established staging method` consisting of clinical scores, basal cell density, central corneal epithelial thickness and SNL. ResultsThe mean (±SD) cornea sensation in the central cornea and limbus were 29.2 ± 21.5 and 33.6 ± 15.1 mm in the LSCD group and 57.6 ± 5.8 and 54.3 ± 4.7 mm in the control group, respectively (all P < 0.001). In sectoral LSCD, the sensation in the affected regions (29.1 ± 17.6 mm) decreased significantly compared to the unaffected regions (41.4 ± 18.2 mm, P < 0.001). Central corneal SND, SNL and SNBD were reduced by 84.6%, 82.6%, and 89.2%, respectively in LSCD compared to the control (all P < 0.05). The central corneal sensation negatively correlated with the severity of LSCD (rho = -0.64, P < 0.0001) and positively correlated with SND, SNL, and SNBD (rho=0.63, 0.66, and 0.56, respectively; all P < 0.001). ConclusionsCorneal sensation was reduced in eyes with LSCD. The degree of corneal sensation reduction positively correlated with the severity of LSCD. This finding demonstrated the co-existence of neurotropic keratopathy in LSCD.

Three-Dimensional Reconstruction of Subbasal Nerve Density in Eyes With Limbal Stem Cell Deficiency: A Pilot Study.

Corneal subbasal nerve parameters have been previously reported using 2-dimensional scans of in vivo laser scanning confocal microscopy (IVCM) in eyes with limbal stem cell deficiency (LSCD). This study aims to develop and validate a method to better quantify corneal subbasal nerve parameters and changes from reconstructed 3-dimensional (3D) images. IVCM volume scans from 73 eyes with various degrees of LSCD (mild/moderate/severe) confirmed by multimodal anterior segment imaging including IVCM and 20 control subjects were included. Using ImageJ, the scans were manually aligned and compiled to generate a 3D reconstruction. Using filament-tracing semiautomated software (Imaris), subbasal nerve density (SND), corneal nerve fiber length, long nerves (>200 μm), and branch points were quantified and correlated with other biomarkers of LSCD. 3D SND decreased in eyes with LSCD when compared with control subjects. The decrease was significant for moderate and severe LSCD ( P < 0.01). 3D SND was reduced by 3.7% in mild LSCD, 32.4% in moderate LSCD, and 96.5% in severe LSCD. The number of long nerves and points of branching correlated with the severity of LSCD ( P < 0.0001) and with declining SND (R 2 = 0.66 and 0.67, respectively). When compared with 2-dimensional scans, 3D reconstructions yielded significant increases of SND and branch points in all conditions except severe LSCD. 3D analysis showed a 46% increase in long nerves only in mild LSCD ( P < 0.01). This proof-of-concept study validates the use of 3D reconstruction to better characterize the corneal subbasal nerve in eyes with LSCD. In the future, this concept could be used with machine learning to automate the measurements.

Corneal innervation changes ın Alzheimer's: implications for sensory dysfunction.

To compare, between Alzheimer's disease (AD) patients and healthy individuals, corneal subbasal nerve plexus (CSNP) parameters and corneal sensitivities. Twenty-two patients who were followed up with Alzheimer's disease (Alzheimer's group) and 18 age- and gender-matched healthy individuals (control group) were included in this cross-sectional study. CSNP parameters, including nerve fiber length (NFL), nerve fiber density (NFD), and nerve branch density (NBD), were evaluated using in vivo confocal microscopy. Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. The results were compared between the two groups. In the Alzheimer's group, NFL was 12.2 (2.4) mm/mm2, NFD was 12.5 [3.1] fibers/mm2, and NBD was 29.7 [9.37] branches/mm2. In the control group, NFL was 16.5 (2.0) mm/mm2, NFD was 25.0 [3.13] fibers/mm2, and NBD was 37.5 [10.9] branches/mm2. All three parameters were significantly lower in the Alzheimer's group compared to the control group (p < 0.001, p < 0.001, and p = 0.001, respectively). Similarly, corneal sensitivity was significantly lower in the Alzheimer's group (55.0 [5.0] mm) compared to the control group (60.0 [5.0] mm) (p < 0.001). We determined that, in AD, corneal sensitivity decreases significantly, in parallel with the decrease in corneal nerves. Changes in the corneal nerve plexus and a decrease in corneal sensitivity may be used in the early diagnosis and follow-up of AD. In addition, ocular surface problems secondary to these changes should also be kept in mind.

Associations between Corneal Nerve Structure and Function in a Veteran Population.

Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (β = -0.26, p = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function.

Bilateral Pattern Electroretinogram Abnormalities in Patients with Herpes Zoster Keratitis and Conjunctivitis.

Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment.

Corneal subbasal nerve plexus reinnervation and stromal cell morphology with different cap thicknesses in small incision lenticule extraction

PurposeThe corneal cap thickness is a vital parameter designed in small incision lenticule extraction (SMILE). The purpose was to investigate the changes in corneal subbasal nerve plexus (SNP) and stromal cells with different cap thicknesses and evaluate the optimized design for the surgery.MethodsIn this prospective, comparative, non-randomized study, a total of 108 eyes of 54 patients who underwent SMILE were allocated into three groups with different corneal cap thicknesses (110 μm, 120 μm or 130 μm group). The SNP and stromal cell morphological changes obtained from in vivo corneal confocal microscopy (IVCCM) along with their refractive outcomes were collected at 1 week, 1 month, 3 months and 6 months postoperatively. One-way analysis of variance (ANOVA) was used to compare the parameters among the three groups.ResultsThe SNPs in the three groups all decreased after surgery and revealed a gradual increasing trend during the 6-month follow-up. The values of the quantitative nerve metrics were significantly lower in the 110 μm group than in the 120 μm and 130 μm groups, especially at 1 week postoperatively. No difference was detected between the 120 μm and 130 μm groups at any time point. Both Langerhans cells and keratocytes were activated after surgery, and the activation was alleviated during the follow-up.ConclusionsThe SMILE surgeries with 110 μm, 120 μm or 130 μm cap thickness design achieved good efficacy, safety, accuracy and stability for moderate to high myopic correction while the thicker corneal cap was more beneficial for corneal nerve regeneration.

Alterations in the Ocular Surface and Corneal Subbasal Nerve Plexus Following Various Retinal Surgical Procedures: A One-Year Confocal Microscopy Prospective Study.

To evaluate the effects of retinal surgery on the ocular surface and corneal subbasal nerve plexus (SNP). Ninety-eight patients undergoing 23-gauge pars plana vitrectomy for various vitreoretinal disorders were prospectively studied. We collected detailed operative and perioperative data, measuring dry eye syndrome (DED) severity and Ocular Surface Disease Index (OSDI) scores before surgery and at postoperative intervals. In vivo confocal microscopy (IVCM) quantified SNP and dendritic cell (DC) densities. Fifty-three patients were analyzed. Post-surgery, OSDI scores rose from a baseline of 5.5 ± 3.5 to 12.24 ± 6.5 at one month, later reducing to 7.8 ± 4.0 after a year. DED severity increased from 0.6 ± 0.6 initially to 1.6 ± 0.6 at three months, returning to near baseline (0.9 ± 0.6) one year after surgery. DC densities increased notably by the third (58.85 ± 75.6 cells/mm²) and ninth (59.95 ± 86 cells/mm²) postoperative months, especially in patients undergoing combined phacoemulsification, vitrectomy, and C3F8 gas tamponade. SNP parameters, particularly nerve fiber density and length, showed significant declines one month post-surgery, not recovering to baseline levels within a year. Fiber density dropped from 19.06 ± 8.3 fibers/mm² preoperatively to 4.68 ± 4.8 fibers/mm² at one month, partially recovering to 10.64 ± 8.2 fibers/mm² at twelve months. Fiber length decreased from 13.31 ± 3.2 mm/mm² to 6.86 ± 3.4 mm/mm² at one month, later improving to 9.81 ± 4.5 mm/mm² at twelve months, notably in patients with silicone oil (SiO2) tamponade. Retinal surgery, especially when combined with phacoemulsification and C3F8 or SiO2 tamponade, significantly affects ocular surface integrity and SNP density, with these changes lasting up to a year. Expanded studies with more patients and longer follow-up, using finer 25- and 27-gauge vitrectomy tools, are recommended to confirm and extend these findings.

Structural and functional changes of binocular corneal innervation and ocular surface function after unilateral SMILE and tPRK

AimsTo evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures.Methods34...

Topical Insulin for Ocular Surface Disease.

Background: Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. Purpose: This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. Methods: The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. Results: While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. Conclusion: This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice.

Corneal nerves and amyotrophic lateral sclerosis: an in vivo corneal confocal imaging study.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27months. In vivo corneal confocal microscopy, assessing the sub-basal nerve plexus of the cornea, has been proposed as a potential biomarker for ALS. We aimed to determine whether the assessment of corneal nerves using in vivo confocal microscopy can serve as an imaging biomarker for ALS. A single-centre prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. The corneal sub-basal nerve plexus was analysed using in vivo confocal microscopy. An automated algorithm (ACCMetrics) was used to evaluate corneal parameters: nerve fibre density, nerve branch density, nerve fibre length, nerve fibre area, nerve total branch density, nerve fibre width, and nerve fractal dimension. Twenty-two patients with ALS and 30 controls were included. No significant differences were found between ALS and control groups for all corneal parameters (p > 0.05). Corneal sensitivity did not differ between groups, and no correlation was identified between corneal nerve parameters and ALS disease duration, severity and rate of progression (p > 0.05). The present study does not support the use of in vivo corneal confocal microscopy as an early diagnostic or prognostic tool for ALS. Further research, especially longitudinal investigations, is needed to understand any potential corneal innervation changes as ALS progresses.

Corneal Sub-Basal Nerve Plexus Regeneration Pattern following Implantable Collamer Lens Implantation for Myopia: A Prospective Longitudinal In Vivo Confocal Microscopy Study.

Implantable Collamer Lens (ICL) surgery has increasingly been adopted for myopia correction in recent decades. This study, employing in vivo confocal microscopy (IVCM), aimed to assess the impact of corneal incision during ICL surgery on the corneal sub-basal nerve plexus (SNP) and adjacent immune dendritiform cells (DCs). In this longitudinal study, eyes from 53 patients undergoing ICL surgery were assessed preoperatively and postoperatively over a twelve-month period. Quantification of seven SNP parameters was performed using ACCMetrics V.2 software. Ultimately, the final analysis was restricted to one eye from each of the 37 patients who completed a minimum of three months' postoperative follow-up. Preoperative investigations revealed a positive correlation of DC density with patient age and a negative association with corneal nerve fiber density (CNFD). Additionally, both DCs and CNFD were positively linked to spherical equivalent refraction (SER) and inversely related to axial length (AL). Intriguingly, preoperative DC density demonstrated an indirect relationship with both baseline and postoperative CNFD changes. Post-surgery, an initial surge in DC density was observed, which normalized subsequently. Meanwhile, parameters like CNFD, corneal nerve fiber length (CNFL), and corneal nerve fractal dimension (CNFrD) initially showed a decline following surgery. However, at one-year follow-up, CNFL and CNFrD displayed significant recovery, while CNFD did not return to its baseline level. This study thus delineates the regeneration pattern of SNP and alterations in DC density post-ICL surgery, highlighting that CNFD in the central cornea does not completely revert to preoperative levels within a year. Given these findings, practitioners are advised to exercise caution in older patients, those with high myopia, or elevated preoperative DCs who may undergo delayed SNP regeneration.

Corneal reinnervation in patients with severe neurotrophic keratopathy secondary to herpes zoster ophthalmicus after treatment with autologous serum tear drops.

To study potential corneal reinnervation and recovery of corneal sensation in patients with severe neurotrophic keratopathy (NK) secondary to herpes zoster ophthalmicus (HZO) after treatment with topical autologous serum tears (AST). Four cases of HZO with severe NK were followed clinically and by serial laser in vivo confocal microscopy (IVCM, HRT3/RCM, Heidelberg Engineering) before and during treatment with 20% AST drops eight times a day. Two masked observers reviewed the IVCM images and assessed corneal nerve alterations. At baseline, all patients had complete loss of corneal sensation. In addition, IVCM showed complete lack of the subbasal corneal nerve plexus in all patients. All four patients were refractory to conventional therapies and were treated with AST drops. All patients demonstrated significant nerve regeneration by IVCM within 3-7 months of treatment. The total nerve density increased to a mean ± SEM of 10,085.88±2,542.74 μm/mm2 at the last follow up. Corneal sensation measured by Cochet-Bonnet esthesiometry improved to a mean ± SEM of 3.50±1.30 cm. Interestingly, 3 of 4 patients developed stromal keratitis with ulceration within weeks of corneal reinnervation, which was reversed by adding topical steroids. Autologous serum tears are effective in restoring corneal subbasal nerves and sensation in patients with severe NK secondary to HZO. However, this group of patients may require concurrent topical immunomodulation and antiviral therapy while on AST to prevent stromal keratitis.

Corneal confocal microscopy detects damage to the subbasal corneal nerve plexus in patients with chronic inflammatory demyelinating polyneuropathy

Corneal confocal microscopy detects damage to the subbasal corneal nerve plexus in patients with chronic inflammatory demyelinating polyneuropathy