Sustained corneal nerve loss predicts the development of diabetic neuropathy in type 2 diabetes.

Introduction: This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D). Methods: Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4-7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, <24 fibers/mm2), corneal nerve branch density (CNBD, <21 branches/mm2), and corneal nerve fiber length (CNFL, <16 mm/mm2) persisting for ≥50% of the study duration. Results: A total of 107 participants with a mean duration of T2D of 13.3 ± 7.3 years, aged 54.8 ± 8.5 years, underwent baseline and follow-up assessments over a median duration of 4 years, ranging from 1 to 7 years. The DPN prevalence at baseline was 18/107 (16.8%), and of the 89 participants without DPN at baseline, 13 (14.6%) developed DPN during follow-up. Approximately half of the cohort had sustained corneal nerve damage, and corneal nerve measures were significantly lower in this group than those without sustained damage (p < 0.0001). Sustained corneal nerve damage was associated with the development of DPN (p < 0.0001), a progressive loss of vibration perception (p ≤ 0.05), an increased incidence of burning pain, numbness, or a combination of both (p = 0.01-0.001), and a borderline association with progressive sudomotor dysfunction (p = 0.07). Sustained abnormal CNFL effectively distinguished between participants who developed DPN and those who did not (AUC: 76.3, 95% CI: 65.9-86.8%, p < 0.0001), while baseline and other sustained measures did not predict DPN onset. Conclusion: Sustained abnormal CCM is associated with more severe corneal nerve damage, DPN development, and the progression of neuropathic symptoms and deficits. Regular CCM monitoring may enable the identification of those at greater risk of developing and worsening DPN who may benefit from more aggressive risk factor reduction.

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

PURPOSE: To compare, between Alzheimer's disease (AD) patients and healthy individuals, corneal subbasal nerve plexus (CSNP) parameters and corneal sensitivities. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis.

Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions. Data synthesis was undertaken using RevMan web. Eighteen studies including 958 patients were included. CCM identified an early (1-8 months) and longer term (1-5 years) increase in corneal nerve measures in patients with peripheral neuropathy after pharmacological and surgical interventions. This meta-analysis confirms the utility of CCM to identify nerve regeneration following pharmacological and surgical interventions. It could be utilized to show a benefit in clinical trials of disease modifying therapies for peripheral neuropathy.

Comprehensive assessment of ocular parameters for identifying diagnostic indicators of diabetic peripheral neuropathy.

PURPOSE: To explore variations in systemic and ocular parameters among patients with diabetes, both with and without diabetic peripheral neuropathy (DPN) and to identify sensitive indicators for DPN diagnosis. METHODS: Ninty-five patients with type 2 diabetes mellitus (T2DM) were involved in this cross-sectional study, including 49 without DPN and 46 with DPN. Ocular parameters were obtained using optical coherence tomography angiography (OCTA) and corneal confocal microscopy (CCM). RESULT: Patients with DPN presented with significantly higher HbA1c (p < 0.05) and glycated albumin (GA, p < 0.01) levels, increased prevalence of diabetic retinopathy (DR, p < 0.05), and lower serum albumin (ALB, p < 0.01) and red blood cell (RBC, p < 0.05) levels. Ocular assessments revealed reduced corneal nerve fiber length (CNFL, p < 0.001) and enlarged foveal avascular zone (FAZ) area (p < 0.05) in DPN group. Logistic regression analysis indicated a significant association of presence of DR, RBC, GA, ALB, CNFL and DPN (p < 0.05, respectively). In the binary logistic regression for DPN risk, all three models including the presence of DR and CNFL exhibited the area under the curve (AUC) exceeding 0.8. CONCLUSION: The study establishes a strong correlation between ocular parameters and DPN, highlighting CCM's role in early diagnosis. Combining systemic and ocular indicators improves DPN risk assessment and early management.

Circulating netrin-1 levels are reduced and related to corneal nerve fiber loss in patients with diabetic neuropathy.

AIMS/INTRODUCTION: Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin-1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin-1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy. MATERIALS AND METHODS: A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN- n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy. RESULTS: Corneal nerve fiber density, branch density, fiber length and serum netrin-1 levels were significantly lower in the DN- and DN+ groups compared with controls (P < 0.001). Netrin-1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin-1 cut-off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76-0.94) for differentiating patients with and without corneal nerve loss. CONCLUSIONS: Serum netrin-1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin-1 could act as a biomarker for small nerve fiber damage in DN.

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

PURPOSE: The 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: The 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.

Value of multi-modality small fiber assessments in a genotypically diverse cohort of transthyretin-related amyloidosis in the early stages of disease.

INTRODUCTION: Transthyretin-related amyloidosis (ATTRv) is a progressive multisystem disorder, predominantly involving the peripheral nerve system (PNS) and heart. Quantification of small fiber damage may help guide treatment decisions, as amyloid deposits frequently affect those fibers early in disease course. Corneal confocal microscopy (CCM) is a promising method to monitor patients with ATTRv, due to similarities between corneal nerves and PNS, as the cornea is innervated by Aδ and C fibers. METHODS: We compared CCM measures from ATTRv patients to a group of healthy individuals, matched by age and gender. We then investigated the correlations between small fiber tests (SFT): CCM, LDI-Flare and CDT, COMPASS-31 and disability scales (RODS and ONLS) in patients. RESULTS: Of 20 patients (6 with V30M), mean age 50.3±15.3Y, 7 female (35%), six (30%) had polyneuropathy and 10 (50%) carpal tunnel syndrome. CDT was abnormal in 9 and LDI-flare in 6 patients. CCM was abnormal in 19 tested patients and significantly reduced when compared to controls (CNFL: 6.31±0.31 vs. 15.21±1.02mm/mm2, p<0.001). Mean COMPASS-31-scores were 22.27±22.84; RODS and ONLS were 38.15±12.33 and 2.05±2.3, with no significant differences between sub-group scores. Disease duration was significantly correlated with ONLS (0.43, p=0.05) and RODS (0.46, p=0.03). There were no significant correlations between measures of disability and SFT. CONCLUSIONS: In a diverse cohort of ATTRv patients, CCM was the most frequent abnormal measurement. CCM can be a useful test to triage patients in the early disease stages and with few or equivocal symptoms.

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.

Investigation of small fiber neuropathy in patients with diabetes mellitus by corneal confocal microscopy.

OBJECTIVES: Corneal confocal microscopy (CCM) is a non-invasive technique that examines the corneal cellular structure. Its use in the detection of small fiber neuropathy is being researched. In our study, we examined the role of CCM in the detection of small fiber neuropathy in diabetic patients, as well as the differences between CCM findings in diabetic patients with and without overt polyneuropathy with neuropathic symptoms. METHODS: 56 Diabetes Mellitus (DM) patients and 18 healthy controls were included in the study. The individuals included in the study were divided into three groups. Patients with diabetes who were found to have polyneuropathy according to electrophysiological diagnostic criteria were classified as Group 1, patients with diabetes and neuropathic symptoms without overt polyneuropathy according to electrophysiological diagnostic criteria were classified as Group 2, and healthy individuals were classified as Group 3. Electrophysiological examination and corneal imaging with CCM were performed in all groups. RESULTS: The CNFD and CNFL values of individuals in the diabetic group were discovered to be lower. CNFD values differ statistically between the groups (p = 0.047). Group 1-Group 3 differs from Group 2-Group 3 (respectively; p = 0.018, p = 0.048). CONCLUSION: Our study demonstrates that CCM can be used in patients with neuropathic symptoms and no polyneuropathy detected in EMG and thought to have small fiber neuropathy. CCM provides an opportunity for early diagnosis in small fiber neuropathy.

In Vivo Corneal Confocal Microscopy for Detecting Corneal Nerve Fiber Changes in Patients with Different Types of Optic Neuritis: A Cross-Sectional Study.

PURPOSE: Optic neuritis (ON), a demyelinating disease of the central nervous system, is often a precursor manifestation of neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS). Reduced corneal nerve fiber counts have been found in patients with NMOSD or MS. This study aimed to observe and compare the corneal subbasal nerve plexus in patients with three types of ON and controls without ON using in vivo corneal confocal microscopy (IVCM). METHODS: Data were analyzed for 77 eyes of 48 patients with ON, grouped according to seropositivity for anti-aquaporin-4 IgG, myelin oligodendrocyte glycoprotein antibody, or no seropositivity, and 35 healthy eyes in the control group. Corneal parameters were quantified based on IVCM images. Visual function indicators were recorded, following which their correlations with IVCM parameters were analyzed. RESULTS: Significant differences in IVCM parameters were detected among the different groups. Reductions in corneal nerve fiber counts were negatively correlated with visual acuity. Corneal nerve fibers were significantly more damaged in the affected eye than in the unaffected eye in patients with ON. CONCLUSION: IVCM revealed corneal nerve fiber loss of varying degrees, depending on the type of ON. This indicates that, although ON primarily affects the central nervous system, peripheral nerves, such as the trigeminal nerve, which innervates the corneal subbasal nerve plexus may also be damaged in affected patients.

High-resolution nerve ultrasound and corneal confocal microscopy in taxane-induced polyneuropathy.

BACKGROUND AND PURPOSE: The role of high-resolution nerve ultrasound (HRUS) and corneal confocal microscopy (CCM) in the early detection of taxane-induced polyneuropathy (TIPN) is unclear. The present prospective longitudinal controlled observational pilot study estimates the role of HRUS and CCM in the early diagnosis of TIPN in breast cancer patients. METHODS: Fifteen breast cancer patients receiving paclitaxel and 15 healthy age matched controls were included. Visits before and 3 weeks, 8 weeks and 6 months after treatment included clinical examination, the total neuropathy score, nerve conduction studies (NCS), monocular CCM including corneal nerve fibre length, density and branching and HRUS of bilateral median, ulnar, radial, tibial, peroneal and sural nerves. Patients were compared between different visits and to healthy controls. RESULTS: Total neuropathy score increased from 2.2 at baseline to 5.8 (p < 0.001) at week 8. NCS showed a decreased sensory amplitude in the sural, radial, ulnar and median nerve after 6 months (p < 0.001). HRUS revealed a significant increase of cross-sectional area in the sural nerve (p = 0.004), the median nerve (p = 0.003) at the carpal tunnel and the ulnar nerve in the forearm (p = 0.006) after 6 months. CCM showed no changes at different visits. CONCLUSIONS: Corneal confocal microscopy and HRUS do not detect early signs of TIPN during the paclitaxel treatment period. HRUS and NCS might detect congruent signs of an axonal, predominantly sensory polyneuropathy after 6 months. The clinical examination remains the most sensitive tool in the early detection of TIPN in breast cancer patients.

Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively. METHODS: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 µm2 ). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 µm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls. RESULTS: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03). DISCUSSION: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.

Analysis of the ocular surface functional unit in episodic migraine.

AIM: Migraine is a chronic neurovascular disease that affects the trigeminovascular system. The purpose of this study was to evaluate corneal subbasal nerve fibers, dendritic cells and to measure tear film parameters in migraine. PATIENTS AND METHODS: 87 eyes of 44 patients suffering from migraine with a mean age of 33.23 ± 11.41 years were included in our study. 25 age-matched controls (mean age of 30.16 ± 12.59 years; P = 0.162) were recruited. The corneal subbasal plexus and the dendritic cells (DC) were analyzed using in vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module; Heidelberg Engineering GmbH), and the tear film was imaged using LacryDiag (Quantel Medical, France). RESULTS: Regarding the subbasal nerve fibers of the cornea, none of the examined parameters differed significantly in migraine patients from controls. We found a significant increase in the corneal DC density (P < 0.0001) and DC area (P < 0.0001) in migraine patients compared to healthy volunteers. DC density showed a positive correlation with the monthly attack frequency (r = 0.32, P = 0.041) and the DC area a negative correlation with corneal nerve branch density (r = -0.233, P = 0.039), nerve fiber length (r = -0.232, P = 0.04) and total branch density (r = -0.233, P = 0.039). Using LacryDiag a significant loss of Meibomian gland area could be detected on the superior eyelid (P = 0.005) in migraine. CONCLUSIONS: Our results suggest the presence of neuroinflammation in the cornea of migraine patients affecting the peripheral trigeminal system. Dendritic cells surrounding the subbasal plexus may be involved in the activation and modulation of pain in migraine.

Relation Between Corneal Dendritic Cell Density and Tear Film Stability in Patients with Epidemic Keratoconjunctivitis Associated Dry Eye.

PURPOSE: To clarify the ocular surface features of patients with recent history of epidemic keratoconjunctivitis (EKC) and the relation between corneal dendritic cells (DCs) and ocular discomfort. METHODS: Normal controls (NC) and dry eye (DE) patients without EKC were recruited. Patients with recent EKC history (onset >4 weeks, but <20 weeks) were recruited as EKC + DE group (with dry eye) or EKC-DE group (without dry eye). Ocular surface disease index (OSDI) questionnaire, tear film parameters including lipid layer thickness, first tear break-up time (fBUT), average tear break-up time (aBUT), tear meniscus height and Schirmer I test, meibomian gland parameters, and in vivo corneal confocal microscopy were evaluated. RESULTS: 50 subjects in the NC group, 83 patients in the DE group, 76 patients in the EKC + DE group, and 38 patients in the EKC-DE group were included. Compared with the NC, DE, and EKC-DE groups, the EKC + DE group represented higher OSDI, lid margin, and meibum score (p < 0.05). In the EKC + DE group, the tear volume (10.5 ± 3.7 mm) was significantly higher than in the DE group (8.1 ± 2.8 mm, p < 0.001). The DC density in the EKC + DE group (29.98 ± 15.38 cells/image) was significantly higher than in NC, DE, and EKC-DE groups (4.68 ± 4.05 cells/image) (p < 0.001). The DC density was positively correlated with OSDI, lid margin, and meibum score (all p < 0.01) while inversely correlated with fBUT, aBUT (all p < 0.001) in the EKC + DE group. CONCLUSIONS: Corneal DC density significantly correlates to ocular discomfort and tear film instability in patients with recent EKC history who suffer from DE without aqueous tear deficiency.

Evaluation of Microvascular Complications in Kidney Recipients With Posttransplant Diabetes Mellitus.

CONTEXT: The paucity of data on microvascular complications in patients with posttransplant diabetes (PTDM) is an obstacle to developing follow-up algorithms. OBJECTIVE: To evaluate diabetic microvascular complications in patients with long-standing PTDM. METHODS: In patients with ≥5-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM), diabetic peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument, the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy tests were performed using heart rate variability. Nephropathy screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy was evaluated by fundus examination and photography, and optical coherence tomography. RESULTS: This study included 41 patients with PTDM and 45 NDM patients. The median follow-up was 107.5 months in the PTDM group. Peripheral neuropathy was significantly higher in the PTDM group than in the NDM group (P = .02). In the PTDM patients with peripheral neuropathy, corneal nerve fiber density examined by CCM was significantly lower than in PTDM patients without neuropathy (P = .001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (P = .001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (P = .001). Retinopathy was observed in 19.5% of patients in the PTDM group and in none of the NDM patients (P < .001). Renal functions were similar between the study groups. CONCLUSION: Cardiac autonomic neuropathy and diabetic retinopathy can affect patients with PTDM at a high rate. Diabetic retinopathy is a threat to the vision of PTDM patients. Diabetic peripheral neuropathy can be detected early in PTDM patients by CCM.

Corneal Confocal Microscopy Identifies Structural Small Fibre Abnormalities in an Adolescent with Type 1 Diabetes and Impaired Awareness of Hypoglycaemia.

Impaired awareness of hypoglycaemia (IAH) is present in around 25-40% of individuals with type 1 diabetes mellitus (T1DM). Herein, we present a case of an adolescent with T1DM and IAH who had worse corneal nerve parameters compared to a T1DM adolescent without IAH. Small fibre abnormalities detected by corneal confocal microscopy in an objective easy-to-perform non-invasive test might be a surrogate indicator of underlying autonomic dysfunction in T1DM and IAH.

Corneal characteristics of Mongolian population with type 2 diabetic peripheral neuropathy in inner Mongolia, China: an assessment using corneal confocal microscopy.

OBJECTIVE: To quantify corneal nerve fiber parameters in a Mongolian population with diabetic peripheral neuropathy (DPN) by corneal confocal microscopy. METHODS: This study conducted a comprehensive evaluation of 114 participants from Hulunbuir between January 2020 and December 2021. The participants included healthy controls, Mongolian and Han patients with type 2 diabetes mellitus. Demographic, medical, and laboratory data were collected, and neuropathy was evaluated by confocal corneal microscopy. And compare various parameters between Han and Mongolian were performed using SPSS software. RESULTS: The average waist circumference of Mongolian diabetic patients was larger than that of Han diabetic patients (P < 0.05). The mean HbA1c of Mongolian was 9.30 (8.15, 10.30) %, and that of Han was 8.30 (7.20, 9.40) % (P = 0.023). The average values of Corneal Nerve Fiber Density (CNFD), Corneal Nerve Fiber Length (CNFL) and corneal nerve branch density (CNBD) in Mongolian diabetic patients were significantly lower than those in Han diabetic patients (P < 0.05). The correlation coefficient between CNFL and age was - 0.368. ROC results show that CNBD has a certain diagnostic value for DPN in Mongolian patients with type 2 diabetes and the optimal cut-off point value is 24.99(no./mm2), the sensitivity is 80.0%, and the specificity is 77.8%. CONCLUSION: The corneal confocal microscopy could possibly represent a promising adjuvant technique for the early diagnosis and assessment of PDN in Mongolian T2DM patients.

Corneal confocal microscopy demonstrates varying degrees of neurodegeneration in atypical parkinsonian disorders.

OBJECTIVE: We have used corneal confocal microscopy (CCM) to identify corneal nerve loss as a potential marker of neurodegeneration in participants with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). METHODS: Patients with PD (n = 19), PSP (n = 11), MSA (n = 8) and healthy controls (n = 18) underwent neurological assessment and CCM. RESULTS: Corneal nerve fibre density was significantly lower in participants with PD (p = 0.005), PSP (p = 0.005) and MSA (p = 0.0003) compared to controls. Corneal nerve branch density was significantly lower in participants with PD (p = 0.01) and MSA (p = 0.019), but not in participants with PSP (p = 0.662), compared to controls. Corneal nerve fibre length was significantly lower in participants with PD (p = 0.002) and MSA (p = 0.001) but not in participants with PSP (p = 0.191) compared to controls. CONCLUSION: CCM detects corneal nerve loss in participants with PD and MSA and to a lesser extent in PSP compared to healthy controls.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Retinal nerve fibre layer thinning and corneal nerve loss in patients with Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive, genetically heterogeneous, pleiotropic disorder caused by variants in genes involved in the function of the primary cilium. We have harnessed genomics to identify BBS and ophthalmic technologies to describe novel features of BBS. CASE PRESENTATION: A patient with an unclear diagnosis of syndromic type 2 diabetes mellitus, another affected sibling and unaffected siblings and parents were sequenced using DNA extracted from saliva samples. Corneal confocal microscopy (CCM) and retinal spectral domain optical coherence tomography (SD-OCT) were used to identify novel ophthalmic features in these patients. The two affected individuals had a homozygous variant in C8orf37 (p.Trp185*). SD-OCT and CCM demonstrated a marked and patchy reduction in the retinal nerve fiber layer thickness and loss of corneal nerve fibers, respectively. CONCLUSION: This report highlights the use of ophthalmic imaging to identify novel retinal and corneal abnormalities that extend the phenotype of BBS in a patient with syndromic type 2 diabetes.