Corneal Subbasal Nerve Density Research Articles

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 < 0.02, P < 0.04) and no LSCD (P < 0.01, P = 0.02). Dendritic cell density was significantly higher in the C-LSCD group compared with the no LSCD group (P < 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 < 0.02). Patients with C-LCSD had higher corneal fluorescein staining scores than patients with P-LSCD (P < 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.

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.

Safety and Efficacy of Human Amniotic Epithelial Stem Cells Eye Dropin Ocular Chronic Graft-Versus-Host Disease

Background Approximately 50% of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) suffer from ocular chronic GVHD (ocGVHD), which causes severe dryness and visual impairment. However, current clinical treatments for ocGVHD, such as artificial tears, immunosuppression therapy, and punctual occlusion, typically offer only limited benefits. Amniotic membrane transplantation (AMT) can significantly alleviate ocular symptoms in patients with ocGVHD, but it is an invasive procedure that is not appropriate for all patients with ocGVHD. Therefore, we designed a clinical trial to demonstrate the safety and efficacy of eye drops containing human amniotic epithelial stem cells (hAESC) in ocGVHD. M ethods Register Number: ChiCTR2200057857. The enrolled eyes received 1*10 6 cells/mL of hAESC eye drops four times daily for one to three treatment cycles (A cycle was defined as two weeks of continuous administration and two weeks without hAESC eye drops). The primary outcome measure is safety following treatment with hAESC eye drops. In addition, other clinical indices, such as the ocular surface disease index (OSDI), NIH score(eye), Schirmer's test, corneal fluorescein staining (CFS) score, fluorescein tear breakup time (FTBUT), and in vivo confocal microscopy (IVCM) were essential parameters. Results ： 19 of the 25 patients included in the study completed at least one round of treatment. The average length of follow-up was 9.4 months. There were no adverse events associated with hAESC. After one round of treatment(n=19), there was a significant decrease in OSDI score (P=0.0003) and eye NIH score (P0.0001), an increase in Schirmer basal secretion score (P=0.0237), and a significant improvement in CFS score (P0.0001), corneal subbasal nerve density(P=0.006), and corneal epithelial cell density(P=0.0349). It also produced statistically significant improvements in FTUBT after two rounds of treatment (n=14) (P= 0.024). After three rounds of treatment (n=11), we observed additional improvements in the OSDI (P=0.0001) and CFS (P0.001) scores. Conclusion ： The findings of this study indicated that hAESC eye drops are safe and effective at alleviating symptoms and signs in patients with ocGVHD, making them a promising therapeutic option for the treatment of ocGVHD.

Evaluation of corneal dendritic cell density and subbasal nerve density in contact lens wearers using IVCM: A systematic review and meta-analysis.

To evaluate the subclinical changes in corneal dendritic cell density (CDCD) and corneal subbasal nerve density (CSND) in asymptomatic contact lens (CL) wearers. Databases including PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for trials and studies reporting the changes of corneal CDCD and CSND in contact lens wearers published until 25 June 2022. PRISMA guidelines as well as recommended meta-analysis practices were followed. Meta-analysis was conducted using RevMan V.5.3 software. After the screening, 10 studies with 587 eyes of 459 participants were included. Seven studies reported the data of CDCD. Compared with the control group, CDCD in the CL wearers was higher (18.19, 95% CI 18.8-27.57, p = 0.0001). Type of in vivo confocal microscopy (IVCM), wear duration, and frequency of lens change were sources of heterogeneity. The difference in CSND between CL wearers and the control group was insignificant, and subgroup analysis did not reveal a source of heterogeneity. Overall, CDCD increased in CL wears, while CSND did not show significant differences. IVCM is a feasible tool to assess subclinical changes in CL wearers.

Decreased corneal subbasal nerve fiber length and density in diabetic dogs with cataracts using in vivo confocal microscopy.

To determine whether there is a difference in corneal sensitivity and corneal subbasal nerve plexus (CSNP) morphology in cataractous dogs with diabetes mellitus (DM) versus without DM. Twenty six domestic dogs with cataracts of various breeds presented for phacoemulsification, 13 with DM and 13 without DM. The inclusion criteria for the study were dogs with bilateral cataracts and no clinical evidence of corneal disease. The diabetic group had documented hyperglycemia and was currently treated with insulin. The non-diabetic group had no evidence of DM on examination and bloodwork. Complete ophthalmic examination, corneal esthesiometry, and in vivo confocal microscopy of the CSNP was performed for both eyes of each dog. The CSNP was evaluated using a semi-automated program and statistically analyzed. The mean (±SD) CSNP fiber length was significantly decreased in diabetic (3.8 ± 3.0 mm/mm2 ) versus non-diabetic (6.7 ± 1.9 mm/mm2 ) dogs. Likewise, the mean (±SD) fiber density was significantly decreased in diabetic (8.3 ± 3.1 fibers/mm2 ) versus non-diabetic (15.5 ± 4.9 fibers/mm2 ) dogs. The corneal touch threshold was significantly reduced in diabetic (2.1 ± 0.8cm) versus non-diabetic (2.8 ± 0.4cm) dogs. There was a non-significant trend towards subclinical keratitis in diabetic (9/13) versus non-diabetic (4/13) dogs. Morphological and functional abnormalities of the CSNP were present in dogs with DM, including decreased fiber length, fiber density, and corneal sensitivity. These findings are consistent with diabetic neuropathy and could contribute to clinically significant corneal complications after cataract surgery.

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

We sought to investigate alterations in the corneal subbasal nerve plexus and endothelium in patients with Behçet's disease (BD). This cross-sectional study included 64 patients with BD and 30 age- and gender-matched healthy control subjects. Those with BD were classified as having ocular or non-ocular disease. All subjects underwent a corneal endothelial and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). The differences among groups were analyzed using the Kruskal-Wallis test followed by Dunn's multiple comparison procedure. The mean age of study participants was 35.7 ± 10.2years (16-58) in the ocular BD group, 39.6 ± 14.9years (11-66) in the non-ocular BD group, and 34.1 ± 11.2years (21-55) in the control group. No statistical significance was found in terms of age (p = 0.259) or sex (p = 0.560) between groups. The mean endothelial cell density determined with IVCM was 2124.9 [Formula: see text] 417.4 cells/mm2 (1811-3275) in the ocular group and 2546 [Formula: see text] 335 cells/mm2 (1798-3280) in the control group (p = 0.000). In the ocular group, the mean density of the subbasal nerve plexus was significantly lower (p = 0.004), and nerve tortuosity was significantly higher (p = 0.002). Ocular BD could be responsible for changes in the corneal layers, especially endothelial and corneal nerve structures. Nerve density and tortuosity differences could be inflammatory indicators for BD.

Influences of SMILE and FS-LASIK on Corneal Sub-basal Nerves: A Systematic Review and Network Meta-analysis.

To compare postoperative corneal sub-basal nerve density and number between small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). A search was made in PubMed, EMBASE, and the Cochrane library for prospective comparative studies. The analysis was divided into two parts: network meta-analysis and traditional meta-analysis of the studies directly comparing two surgical groups. Stata 16 (Stata Corporation) and Rev-Man 5.4 (Cochrane) software were used to analyze the data. Twelve studies (n = 775) were included. In the network meta-analysis, the SMILE group showed a significant increase compared with the FS-LASIK group in corneal nerve density at 1 month postoperatively (mean: 4.23; 95% CI: 0.06 to 8.39, P < .05), and in the number of corneal nerve trunks at 6 months postoperatively (mean: 13.25; 95% CI: 10.20 to 16.30, P < .05). In the traditional meta-analysis, the SMILE group showed significant improvement compared with the FS-LASIK group in corneal nerve density at 1 (weighted mean difference [WMD]: -2.05, 95% CI: -3.11 to -1.00, P < .05) and 3 (WMD: -0.90, 95% CI: -1.30 to -0.50, P < .05) months postoperatively, and in the number of corneal nerve trunks (WMD: -2.52, 95% CI: -4.91 to -0.14, P < .05) and corneal nerve branches (WMD: -2.80, 95% CI: -3.41 to -2.19, P < .05) at 1 month postoperatively. The corneal nerve injury in the FS-LASIK group was worse than that in the SMILE group. The corneal nerve recovery in the SMILE group was better at 3 months postoperatively. However, there was no significant difference in corneal nerve density and number between the two groups at 6 months postoperatively. [J Refract Surg. 2022;38(4):277-284.].

The functional and structural evaluation of small fibers in asymptomatic carriers of TTR p.Val50Met (Val30Met) mutation

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients’ family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

Characteristics of Corneal Subbasal Nerves in Different Age Groups: An in vivo Confocal Microscopic Analysis.

PurposeTo determine the normative characteristics of corneal subbasal nerves in different age groups using laser scanning in vivo confocal microscopy (IVCM).Patients and MethodsThis descriptive observational study recruited healthy subjects (aged 20–60 years) from Siriraj Health-Screening Center. Excluded were individuals who had abnormal ocular symptoms, previous ocular surgery, a history of any diseases related to systemic and/or corneal neuropathy, or abnormal corneal sensitivity. Corneal IVCM (HRT3/Rostock Corneal Module) was performed at the central cornea to analyze the subbasal nerve plexus. The corneal nerve characteristics, comprising the number and density of nerves (main nerve trunks, branches, and total nerves) were analyzed using the NeuronJ program, and the corneal nerve tortuosity was graded. The correlations between the subbasal nerve density, tortuosity and age were then analyzed.ResultsEighty subjects were enrolled, with twenty in each of four age groups (20–30, >30–40, >40–50, and >50–60 years). Overall, the mean number and density of main nerve trunks were 27.93±0.81/mm2 and 11.22±0.30 mm/mm2, respectively. As of the nerve branches, the average number and density were 103.56±2.37/mm2 and 9.15±0.30 mm/mm2, respectively. The total nerve density was 20.37±0.39 mm/mm2. There were no significant differences between subbasal nerve parameters of the four age groups. It is noteworthy that 65% of the subjects aged over 40 years revealed high-grade nerve tortuosity.ConclusionThe corneal subbasal nerve numbers and densities were not significantly different among a healthy population aged 20–60 years. However, there was a trend towards high tortuosity of the corneal nerve in people aged over 40 years.

The relationship between corneal subbasal nerve density and corneal sensitivity in patients with Fuchs endothelial corneal dystrophy.

Purpose:The aim of this study was to investigate the association between alterations in corneal subbasal nerve plexus and tactile corneal sensitivity in patients with Fuchs’ endothelial corneal dystrophy (FECD).Methods:This retrospective, cross-sectional study included 24 (10 M/14 F) patients with FECD and 25 age- and sex-matched (10 M/15 F) healthy subjects as controls. Subjects with FECD were classified as having early (grades 1 and 2) and late (grades 3 and 4) disease. All subjects underwent central corneal tactile sensitivity measurements with the Cochet–Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). Association between corneal nerve plexus density and corneal sensitivity alterations were evaluated using the Mann–Whitney U test and the Spearman correlation test.Results:Compared to healthy subjects (mean age = 60.4 ± 7.5 years), patients with FECD (mean age = 60.6 ± 8.0 years) had worse central corneal sensitivity scores (5.9 ± 0.1 cm vs. 4.2 ± 0.8 cm; P < 0.001), reduced corneal nerve fibers (3.4 ± 1.3 nerves/frame vs. 5.0 ± 0.9 nerves/frame; P < 0.001) and lower corneal subbasal nerve plexus densities (2229.4 ± 364.3 μm/mm2 vs. 1901.6 ± 486.8 μm/mm2; P = 0.050). Patients with late stage FECD demonstrated lower subbasal nerve densities as compared to those with early disease (2204.3 ± 313.1 μm/mm2 (range = 1523–2552 μm/mm2); 1397.1 ± 227.4 μm/mm2 (range = 1120-1834 μm/mm2); P < 0.001). In the FECD group, subbasal nerve density was found to be directly correlated with corneal sensitivity scores (r = 0.457, P = 0.025).Conclusion:Progressive loss of the corneal subbasal nerve plexus appears to be a consistent feature of FECD. Reduction of the corneal nerve plexus parallels the decrease in corneal sensitivity in this patient population.

Corneal nerve structure in patients with primary Sj\xf6gren\u2019s syndrome in China

BackgroundThe aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren’s syndrome in China.MethodsThis was a case control study of 22 dry eye disease (DED) patients with primary Sjögren’s syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study.ResultsSS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P < 0.001 and P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = − 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = − 0.534, P = 0.013 and r = − 0.487, P = 0.025, respectively).ConclusionsSjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.

The Association between Meibomian Gland Atrophy and Corneal Subbasal Nerve Loss in Patients with Chronic Ocular Graft-versus-host Disease

ABSTRACT Purpose: To investigate the association between meibomian gland (MG) loss and corneal subbasal nerve plexus density in patients with chronic graft-versus-host disease (GVHD) related dry eye disease (DED). Materials and Methods: This cross-sectional study included 22 adult patients with severe DED secondary to chronic GVHD. Control group comprised age- and sex-matched 28 healthy subjects with no evidence of ocular disease. All subjects underwent tear breakup time (TBUT), corneal staining, Schirmer I test without anesthesia, quantitative MG drop-out assessment using infrared meibography and corneal subbasal nerve density measurements with in vivo confocal microscopy (IVCM) (ConfoScan4, Nidek, Japan). One eye per patient was included for statistical purposes. Mann–Whitney U test and one-way multivariate ANOVA test were used for comparative analyses. Results: Compared to healthy subjects (mean age = 26.9 ± 13.5 years (range = 20–44 years)), patients with chronic GVHD (mean age = 29.6 ± 12.6 years (range = 19–45 years)) had worse meibography scores (p < .001), reduced corneal subbasal nerve plexus densities (p < .001), lower TBUT scores (p = .012), lower Schirmer I values (p = .001) and higher corneal staining scores (p = 003). Meiboscores in the GVHD and control groups were 2.9 ± 1.1 (range = 1–4) vs. 0.7 ± 0.4 (range = 0–2) for the superior (p < .001), and 3.2 ± 1.2 (range = 2–4) vs. 0.5 ± 0.3 (range = 0–2) for inferior (p < .001) eyelids, respectively. Corneal subbasal nerve densities of patients with GVHD did not reveal a correlation with meiboscores (r = 0.030; p = .709 for the inferior and r = 0.268; p = .075 for the superior eyelids) but showed a weak correlation with Schirmer I test values (r = 0.268; p = .014). Conclusions: Patients with chronic GVHD are at high risk for developing DED and MG dysfunction. In the setting of chronic GVHD-related DED, MG loss does not appear to be a significant factor for corneal subbasal nerve damage.

Effect of herpes simplex keratitis scar location on bilateral corneal nerve alterations: an in vivo confocal microscopy study

AimsTo evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM).MethodsCentral and peripheral corneal subbasal nerve density (CSND)...

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Changes in Corneal Subbasal Nerves after Punctal Occlusion in Dry Eye Disease

ABSTRACT Purpose To evaluate corneal subbasal nerve plexus by in vivo confocal microscopy (IVCM) following punctal occlusion in patients with moderate to severe dry eye disease (DED). Materials and Methods Patients with grade 3 or 4 severity of DED based on Delphi Panel dry eye severity grading scheme were enrolled in the study. Permanent inferior punctal occlusion was performed. A comprehensive ophthalmic evaluation, including Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal fluorescein staining, conjunctival Rose bengal staining, Schirmer’s test, and corneal sensation by Cochet-Bonnet esthesiometry, were performed at baseline, and 1 and 3 months after punctal occlusion. Furthermore, density and number of corneal subbasal nerves were evaluated by IVCM. Results Forty-one eyes of 23 patients with a mean age of 46.3 ± 9.0 years were enrolled. Corneal fluorescein staining, Rose bengal staining, and TBUT significantly improved at 3 months following punctal occlusion (p < .015). Corneal esthesiometry significantly increased at both postoperative visits (p < .03), and OSDI scores improved only at 3-month follow-up (p < .005). Nerve density and total number significantly increased 3 months after punctal occlusion (p < .045). Baseline nerve density had significant correlations with TBUT, fluorescein staining, Rose bengal staining (p < .012), but not with esthesiometry, Schirmer scores, or OSDI scores (p > .329). Conclusions Corneal subbasal nerve density and total number increased following punctal occlusion in patients with moderate to severe DED. These findings were associated with improvements in corneal sensation, and signs and symptoms of DED. This emphasizes the effect of punctal occlusion in regeneration of corneal subbasal nerve plexus.

A comparison of the effects of different cap thicknesses on corneal nerve destruction after small incision lenticule extraction.

To evaluate the features of corneal nerve destruction after small incision lenticule extraction (SMILE) with different cap thicknesses (100 and 120μm). Nine consecutive patients (18 eyes) received SMILE with a 120-μm cap thickness and nine patients (18 eyes) with a 100-μm cap thickness were recruited. Confocal microscopy was used to evaluate the density and microscopic morphological changes of central corneal subbasal nerves preoperatively and at postoperative week 1. The postoperative corneal subbasal nerve densities decreased significantly in both 120μm and 100μm groups. No statistical difference was detected in reduction of subbasal nerve density between two groups (P = 0.299). The number of subbasal nerve fibers significantly decreased in both groups. The reductions were not significantly different between two groups (P = 0.293). Using a 120-μm cap thickness during SMILE preserves no more central corneal subbasal nerve fibers compared to a 100-μm cap thickness.

In Vivo Evaluation of Corneal Nerves and Epithelial Healing After Treatment With Recombinant Nerve Growth Factor for Neurotrophic Keratopathy

To evaluate the renewal of corneal nerve structure and function in patients with neurotrophic keratopathy (NK) treated with recombinant human nerve growth factor (rhNGF) eye drops. Prospective, interventional, before-and-after case series. This study included 18 patients with NK with a persistent epithelial defect or corneal ulcer, treated with topical rhNGF, and age-matched healthy controls. Patients underwent clinical examination with corneal fluorescein staining, Schirmer 1 tear test, assessment of corneal sensitivity with the Cochet-Bonnet esthesiometer, and morphologic examination of the nerves by invivo confocal microscopy (IVCM) at baseline and at 4 and 8weeks of treatment. IVCM analysis was used to assess corneal sub-basal nerve density, number of nerve branches, and the diameter of nerve fibers. A complete resolution of the epithelial defect was observed in all patients within 8weeks. Schirmer 1 test showed a significant improvement of tear film secretion. Change from baseline in corneal sensation was significant (P < .001) but did not approach that of healthy controls. After 8weeks of treatment, there was a significant increase in the mean nerve density in affected eyes as compared to baseline (P= .007) as well as in the number of nerve branches (P= .008) and nerve fiber diameter (P= .007). Topical treatment with rhNGF was effective in promoting complete corneal healing of persistent epithelial defects and corneal ulcers in patients with NK. This was associated with an improvement of corneal sensitivity and an increase of sub-basal nerve density, diameter, and number of nerve branches, indicating improvement in structure and function of corneal nerves.

Corneal Reinnervation and Sensitivity Recovery after Pterygium Excision.

Purpose To evaluate changes in corneal sensitivity and subbasal nerve density after pterygium excision. Methods This prospective trial included 22 eyes with nasal primary pterygium and 18 controls. Corneal sensitivity was evaluated using a Cochet–Bonnet esthesiometer in the nasal, superior, temporal, inferior, and center quadrants of the cornea before surgery and 10 days, 1 month, and 3months after surgery. The central cornea was analyzed using in vivo confocal microscopy (IVCM) before surgery and 1 and 3 months after surgery. Subbasal nerve density and other nerve parameters were analyzed using NeuronJ. Nerve tortuosity was evaluated and graded in individual IVCM scans. The tear film break-up time (TBUT) test and Schirmer's test were performed before surgery, as well as 1 and 3 months after surgery. All the same tests were performed in the controls. Results All affected eyes showed a significant increase in corneal sensitivity in the nasal corneal quadrant after surgery when compared with preoperative data (F = 37.3; P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (F = 37.3; P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (F = 37.3; P < 0.01). Compared with controls, pterygium patients demonstrated decreased corneal subbasal nerve density (Conclusion Pterygium patients demonstrated deteriorated corneal subbasal nerve fibers when compared with healthy controls in terms of nerve length, nerve trunks, and nerve branches. Therefore, pterygium excision improves corneal sensitivity and increases corneal subbasal nerve density.

Clinical and in vivo confocal microscopic features of neuropathic corneal pain

AimsTo describe clinical and in vivo confocal microscopy (IVCM) features of neuropathic corneal pain (NCP) without clinically visible signs.MethodsProspective, observational study of 27 eyes of 14 patients who had continuous...