OBJECTIVE: Diabetic 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.
METHODS: People 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.
RESULTS: Twenty-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).
CONCLUSIONS: Bariatric 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.

Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively.

OBJECTIVE: 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).
CONCLUSIONS: 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.

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35-+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = -0.26, 95% CI: -0.44--0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-β, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients\' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM.

OBJECTIVE: To evaluate the corneal sensitivity of black diabetic patients and identify factors associated with changes in corneal sensitivity.
METHODS: We conducted a cross-sectional comparative case-control study at the National Obesity Center of the Yaounde Central Hospital and the Djoungolo District Hospital from March 1 to July 31, 2022. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer in all diabetic patients over 18 years of age, matched for age and sex to a clinically healthy control population. Data were analyzed using SPSS version 23.0 software. A P-value of less than 5% was considered significant.
RESULTS: A total of 111 diabetic and 111 non-diabetic patients participated in the study. The mean age was 53.46±12.74 years for diabetics and 52.85±11.77 years for non-diabetics (P=0.901). The mean duration of diabetes was 6.4±5.30 years. Corneal sensitivity in diabetics was lower (44.56±9.59mm) compared to non-diabetics (53.59±6.30mm) with a statistically significant difference (P=0.000). Factors associated with decrease in corneal sensitivity in diabetics were duration of diabetes and poor glycemic control.
CONCLUSIONS: Decrease in corneal sensitivity related to diabetes is a complication to be systematically screened for during the ophthalmologic follow-up of diabetic patients.

Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care. Protocol registration: PROSPERO ID: CRD42022348475.

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer\'s corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.

OBJECTIVE: To validate the use, repeatability, and reproducibility of a new, cost-effective, disposable, sterile device (KeraSenseⓇ, Dompè farmaceutici SpA, Milan Italy) compared to Cochet-Bonnet (CB) esthesiometer. Secondly, to identify a simple, safe, rapid, and low-cost test to diagnose neurotrophic keratitis (NK).
METHODS: 16 patients with diagnosis of NK stage I, 25 patients with diabetes mellitus (DM), and 26 healthy subjects were included in the study. Corneal sensitivity (CS) was assessed by CB and KeraSenseⓇ. Repeatability, accuracy, and reproducibility of the novel disposable aesthesiometer were assessed. Specificity, sensitivity, and cut-off value for NK diagnosis were calculated by ROC curve analysis.
RESULTS: All NK patients showed a CS ≤ 40 mm, while none of the healthy patients showed a CS value < 50 mm. Significant agreement was found between CB measurements and the single use esthesiometer evaluations of CS (p < 0.001). Repeatability evaluations of the single use esthesiometer showed 100% agreement between different measurements (p < 0.001). Reproducibility evaluations showed 99.6% concordance between different operators (p < 0.001). A 55 mm value of the single use esthesiometer was adequate to exclude an NK diagnosis, while all NK patients showed a value ≤ 35 mm.
CONCLUSIONS: Corneal hypo/anaesthesia is considered the hallmark of NK. The use of the novel single-use esthesiometer will allow for a diagnostic improvement in NK, sparing time and guaranteeing patients\' safety. Diabetic patients despite normal corneal findings may show impairment of CS, suggesting a preclinical stage of NK, requiring a close follow-up.

OBJECTIVE: The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography and to compare these results with age- and sex-matched healthy individuals.
METHODS: The left eyes of 32 patients who applied for refraction or fundus examination and had a diagnosis of DN by electromyography in their medical history were included in this study. Corneal sensitivity was evaluated using the Cochet-Bonnet esthesiometer (Luneau, Paris) in five zones: central, nasal, superior, temporal, and inferior. The measurements of the patients were compared with the measurements of 32 age- and sex-matched healthy volunteers. Furthermore, the measurements of five corneal zones were compared with each other, and the level of correlation was investigated in each group.
RESULTS: The central corneal sensitivity values were measured as 4.12 ± 1.04 (mm) and 5.92 ± 0.14 (mm) (P < 0.001). While the sensitivity values at the superior, inferior, nasal, and temporal quadrants were detected as 5.85 ± 0.21, 5.85 ± 0.26, 5.94 ± 0.13, 5.93 ± 0.13, and 5.92 ± 0.14 (mm) in the control group, it was measured as 3.67 ± 0.66, 3.67 ± 0.62, 3.67 ± 0.62, and 3.89 ± 0.73 (mm) in the DN group, respectively. The corneal sensitivity values were all found to be significantly lower in the DN group (P < 0.001 for all parameters) at all quadrants as well as the central cornea. Furthermore, a moderate positive correlation between all five zones in the control group and a very strong positive correlation in the DN group were found in terms of the corneal quadrature sensitivity.
CONCLUSIONS: The current study revealed a significant reduction in corneal sensitivity in patients with DN. In both the control group and DN group, all corneal zones showed positive correlations which show the consistency of the measurement in different quadratures. Evaluating corneal sensitivity with a Cochet-Bonnet esthesiometer might serve as a useful screening tool in detecting neuropathy development. By taking the necessary precautions, further damage can be prevented.

OBJECTIVE: To determine the corneal sensitivity recovery period after laser-assisted sub-epithelial keratectomy (LASEK) refractive surgery and investigate the effects of ablation depth on it.
METHODS: In this study examinations were performed on 90 right eyes of 90 people (34 males and 56 females) with an age range of 20-35 and an average of 22.26±3.8 years old. A sensation of 5 corneal regions, including the center and 4 mid-peripheral regions, i.e., nasal, inferior, temporal, and superior, each at a distance of 2 mm from the center of the cornea were measured with a Cochet-Bonnet esthesiometer device in 3-time points including before LASEK, 1 and 3mo after the surgery, respectively. LASEK was performed on individuals with stabilized myopia of -1.00 to -7.00 diopters and astigmatism of less than 2.00 diopters. Furthermore, the individuals were divided into three groups regarding ablation depth.
RESULTS: The highest level of corneal sensitivity before surgery was related to the center of the cornea (59.1±7.76), and the highest level of corneal sensitivity loss was also related to this region. The sensation of all measured corneal regions significantly reduced 1mo postoperatively and returned to their preoperative levels 3mo after surgery (mean of 5 corneal regions in levels of preoperation: 58.2±6.48, 1mo postoperation: 57.3±5.84, 3mo postoperation: 58.2±5.49; P<0.05). A significant relationship was found between ablation depth and corneal sensitivity changes in the center and temporal regions (P<0.05).
CONCLUSIONS: Corneal sensitivity in myopia and low astigmatism decreases after LASEK and reaches the preoperative level within 3mo. The depth of ablation during surgery affected the recovery of corneal sensitivity.