The Severity of Diabetic Retinopathy Corresponds with Corneal Nerve Alterations and Ocular Discomfort of the Patient.

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)-ß, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, 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.

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 Nerve Assessment by Aesthesiometry: History, Advancements, and Future Directions.

The measurement of corneal sensation allows clinicians to assess the status of corneal innervation and serves as a crucial indicator of corneal disease and eye health. Many devices are available to assess corneal sensation, including the Cochet-Bonnet aesthesiometer, the Belmonte Aesthesiometer, the Swiss Liquid Jet Aesthesiometer, and the newly introduced Corneal Esthesiometer Brill. Increasing the clinical use of in vivo confocal microscopy and optical coherence tomography will allow for greater insight into the diagnosis, classification, and monitoring of ocular surface diseases such as neurotrophic keratopathy; however, formal esthesiometric measurement remains necessary to assess the functional status of corneal nerves. These aesthesiometers vary widely in their mode of corneal stimulus generation and their relative accessibility, precision, and ease of clinical use. The development of future devices to optimize these characteristics, as well as further comparative studies between device types should enable more accurate and precise diagnosis and treatment of corneal innervation deficits. The purpose of this narrative review is to describe the advancements in the use of aesthesiometers since their introduction to clinical practice, compare currently available devices for assessing corneal innervation and their relative limitations, and discuss how the assessment of corneal innervation is crucial to understanding and treating pathologies of the ocular surface.

[Clinical profile of corneal sensitivity in diabetic patients: A case-control study]. / Profil clinique de la sensibilité cornéenne chez les patients diabétiques : étude cas-témoins.

PURPOSE: To evaluate the corneal sensitivity of black diabetic patients and identify factors associated with changes in corneal sensitivity. METHODOLOGY: 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. CONCLUSION: Decrease in corneal sensitivity related to diabetes is a complication to be systematically screened for during the ophthalmologic follow-up of diabetic patients.

Evaluating the efficacy and safety of therapeutic interventions for corneal neuropathy: A systematic review.

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.

Comparison of Proparacaine, Tetracaine, and Oxybuprocaine in Corneal Sensitivity Measurement.

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.

New disposable esthesiometer (KeraSenseⓇ) to improve diagnosis and management of neurotrophic keratitis.

PURPOSE: 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.

Clinical application of the Swiss Liquid Jet Aesthesiometer for corneal sensitivity measurement.

CLINICAL RELEVANCE: Corneal sensitivity represents an important indicator for corneal health, its innervation and hence also for ocular disease. It is therefore of great interest from a clinical and research perspective to quantify ocular surface sensation. BACKGROUND: The aim of this prospective cross-sectional cohort study was to clinically test the within-day and day-to-day repeatability of the new Swiss Liquid Jet Aesthesiometer, employing small droplets of isotonic saline solution for repeatability, and correlate with the Cochet-Bonnet aesthesiometer in a cohort of participants of two different age groups, based on participant feedback (psychophysical method). METHODS: Participants were recruited from two equally, large age groups: group A (18-30 years) and group B (50-70 years). The inclusion criteria were healthy eyes, Ocular Surface Disease Index (OSDI) ≤ 13, and no contact lens wear. Mechanical corneal sensitivity threshold measurements with means of liquid jet and Cochet-Bonnet methods were carried out twice during two visits (a total of four measurements), with a stimulus temperature equal to or slightly above the ocular surface temperature. RESULTS: Ninety participants completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). The coefficient of repeatability for the liquid jet method was 2.56 dB within visits and 3.61 between visits. For the Cochet-Bonnet method, it was 2.27 dB within visits and 4.42 dB between visits (Bland Altman with bootstrap analysis). Moderate correlation was observed between the liquid jet and the Cochet-Bonnet method (r = 0.540, p < .001, robust linear regression). CONCLUSIONS: Swiss liquid jet aesthesiometry offers a new examiner independent method for corneal sensitivity measurement with acceptable repeatability and moderate correlation with the Cochet-Bonnet aesthesiometer. It offers a large stimulus pressure range of 100-1500 mbar and a precision of 1 mbar. Stimulus intensity can be tuned more precisely and much smaller sensitivity fluctuations may be potentially detected.

A PEDF peptide mimetic effectively relieves dry eye in a diabetic murine model by restoring corneal nerve, barrier, and lacrimal gland function.

PURPOSE: The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using streptozotocin. METHODS: Mice were treated topically for 3-6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury were measured using Cochet-Bonnet esthesiometer, phenol red cotton thread wetting, fluorescein sodium staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the lacrimal glands were measured. RESULTS: Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion and increased corneal epithelium injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1ß and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide treatment. CONCLUSION: The study demonstrates that topical application of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.

How long does the recovery of corneal sensitivity in different corneal regions take after LASEK?

AIM: 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). CONCLUSION: 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.

Assessment and safety of the new esthesiometer BRILL: Comparison with the Cochet-Bonnet Esthesiometer.

BACKGROUND: Corneal sensitivity can decrease by several ocular conditions, such as dry eye or refractive surgery, which favor ocular epithelial lesions and is measured using an esthesiometer. The study's primary objective was to demonstrate the efficacy and safety of the non-contact esthesiometer BRILL, which delivers air pulses to the corneal surface to assess corneal sensitivity. METHODS: A single-center, prospective, controlled pilot study was carried out in adult patients with healthy eyes and or with pathology. Corneal sensitivity measurements were made in triplicate for both eyes at three consecutive visits. The esthesiometer BRILL was used in all visits, and on the last visit, the contact esthesiometer Cochet-Bonnet was also used. The results of both devices were compared by transforming them into force values. RESULTS: 54 subjects with a mean age of 50.43 (SD 16.55, interval 18-87), 77.78% women, were included. Comparing the forces applied by both esthesiometers in the healthy eyes, in the eyes with pathology in all the groups, and in the dry eyes showed significant differences, p = 0.03603, p = 0.00614, and p = 0.0001, respectively. CONCLUSION: The BRILL esthesiometer proved to be an effective and safe tool for non-contact assessment of corneal sensitivity with operator-independent repeatability. The measurements had a good agreement and comparable range with the Cochet-Bonet aesthesiometer measurements in healthy and dry eyes but with no interchangeable values. This portable device can help ophthalmologists and optometrists to diagnose eye pathologies that cause decreased corneal sensitivity and to assess the efficacy of therapy and disease progression.

Corneal sensitivity in silicone hydrogel and rigid gas permeable contact lens wear.

PURPOSE: The aim of this prospective cross-sectional cohort study was to test the effect of silicone hydrogel (SH) and rigid gas permeable (RGP) contact lens (CL) wear on corneal sensitivity, applying the new Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) and the Cochet-Bonnet (CB) aesthesiometer, based on subject feedback (psychophysical method). METHODS: Participants were recruited for three equally large groups: Group A (SH CL), Group B (RGP CL) and Group C (non-CL wearers). Inclusion criteria were healthy eyes and OSDI ≤ 13. Corneal sensory thresholds were determined twice during two visits, with aid of SLACS and CB. RESULTS: 96 participants completed the study (n = 33 in groups A and C, n = 30 in group B); average age in group A: 27.42 ± 6.83 years, group B: 36.90 ± 9.68 years and group C: 26.06 ± 6.19 years. No statistically significant difference in corneal sensitivity was observed between the three groups for either method (p = 0.302 for SLACS, p = 0.266 for CB; Kruskal-Wallis rank sum test). Higher CSTs were obtained for males than for females in both CL groups with SLACS, and with CB only in the RGP CL group (p = 0.041 in Group A, p = 0.006 in Group B with SLACS; p = 0.041 in Group B with CB; bootstrap analysis with age correction and gender balancing). No correlation was observed between CL comfort and corneal sensitivity for neither method applied (for SLACS r = 0.097 and p = 0.51, for CB r = 0.17 and p = 0.15; robust linear mixed model). CONCLUSIONS: No difference in corneal sensitivity with CL compared to non-CL wear was noted in this study. However, lower levels of corneal sensitivity were observed in the male CL groups, warranting further investigation.

Mercury intoxication and ophthalmic involvement: An update review.

Human intoxication after mercury exposure is a rare condition that can cause severe damage to the central nervous, respiratory, cardiovascular, renal, gastrointestinal, skin, and visual systems and represents a major public health concern. Ophthalmic involvement includes impaired function of the extraocular muscles and the eyelids, as well as structural changes in the ocular surface, lens, retina, and optic nerve causing a potential irreversible damage to the visual system. Although, there are many pathways for poisoning depending on the mercury form, it has been suggested that tissue distribution does not differ in experimental animals when administered as mercury vapor, organic mercury, or inorganic mercury. Additionally, visual function alterations regarding central visual acuity, color discrimination, contrast sensitivity, visual field and electroretinogram responses have also been described widely. Nevertheless, there is still controversy about whether visual manifestations occur secondary to brain damage or as a direct affectation, and which ocular structure is primarily affected. Despite the use of some imaging techniques such as in vivo confocal microscopy of the cornea, optical coherence tomography (OCT) of the retina and optic nerve, and functional tests such as electroretinography has helped to solve in part this debate, further studies incorporating other imaging modalities such as autofluorescence, OCT angiography or adaptive optics retinal imaging are needed. This review aims to summarize the published structural and functional alterations found in the visual system of patients suffering from mercury intoxication.

Characteristics of the ocular surface in neurotrophic keratitis induced by trigeminal nerve injury following neurosurgery.

PURPOSE: To analyse and quantify ocular surface parameters in patients with unilateral neurotrophic keratitis (NK) induced by trigeminal nerve injury post-neurosurgery. METHODS: The study included 26 unilateral NK patients who had undergone neurosurgery, and 20 matched normal controls. Demographic and clinical characteristics of all participants were collected and analysed. Slit-lamp examination, Cochet-Bonnet aesthesiometry, Keratograph 5 M, and LipiView interferometer were performed on both eyes of 17 mild NK patients. For nine moderate/severe NK patients, sub-basal nerve density was measured by in vivo confocal microscopy. RESULTS: Of the 26 patients, nine had acoustic neuroma, nine had trigeminal neuralgia, and eight had neoplasms. Facial nerve paralysis was observed in one of the 17 mild NK eyes (5.9%) and seven of the nine moderate/severe NK eyes (77.8%). Compared to contralateral and normal control eyes, 26 NK eyes showed significantly reduced sensitivity in five corneal regions (P < 0.05). Corneal sensitivity in moderate/severe NK eyes was significantly lower than in mild NK eyes (P < 0.05). Moderate/severe NK eyes had poor visual acuity, and their sub-basal nerve density was lower than that of the controls. The onset of the moderate/severe NK was from 0.5 to 24 months (median [Q1, Q3], 1 [0.5, 2.5] months) after neurosurgery. For the mild NK eyes, the number of total blinks, the first non-invasive tear breakup time (NITBUT) and average NITBUT were significantly lower than contralateral and normal control eyes (P < 0.05), and the number of partial blinks and partial blinking rate were significantly higher than the other two control groups (P < 0.05). CONCLUSIONS: Patients with NK induced by trigeminal nerve injury following neurosurgery had decreased corneal sensitivity to various degrees accompanied by increased partial blinks and shortened NITBUT. The severity of NK is related to the severity of the corneal sensory impairment. Facial nerve paralysis can worsen the clinical progression of NK. Trial registration Chinese Clinical Trial Registry (ChiCTR2100044068, Date of Registration: March 9, 2021).

Prevalence and Severity of Dry Eye Disease Symptoms Among Diabetics: A Nationwide Survey.

INTRODUCTION: Diabetes mellitus (DM) microvascular complications can impair corneal sensitivity and lacrimal gland functioning, leading to dry eye disease (DED). Hence, this study aimed to measure the prevalence and severity of DED symptoms, and the related risk factors, among the Saudi diabetic population. METHODS: This is a retrospective, cross-sectional, survey-based study which targeted Saudi adults (20 years and older) previously diagnosed with type 1 or type 2 DM. It was conducted in eight primary healthcare centers (PCHs) scattered around eight different provinces of Saudi Arabia (SA). The prevalence and severity of DED were measured by the Ocular Surface Disease Index (OSDI). RESULTS: The total study population was 389 subjects, of which 182 (46.8%) were males and 207 (53.2%) were females. The overall prevalence of DED was 51.7%. Among those, 20.3% of patients had mild dryness, 11.1% had moderate dryness, and 20.3% had severe dryness. Glycosylated hemoglobin (HbA1c) levels of 6.5% or higher proved to be an independent risk factor for the development of DED symptoms, 3.6-folds higher for HbA1c levels of 6.5% to 9% (AOR=3.573; p=0.001), and 2.3-folds higher for HbA1c levels higher than 9% (AOR=2.293; p=0.013). The long duration of diabetes did not show a significant association with manifesting DED symptoms (p=0.263). CONCLUSION: Half of the diabetic population complained of DED symptoms, compared to one-third of the previously studied general Saudi population. Patients with mild to moderate HbA1c elevation were more likely to report DED symptoms than those with severe elevation, which could be related to impaired corneal sensation. Therefore, a routine ophthalmological examination is recommended.

Evaluation of Corneal Alterations After Short-Term Silicone Hydrogel Contact Lens Use by Confocal Microscopy.

Objectives: To evaluate the corneal subbasal nerve morphology, corneal sensitivity, and anterior segment alterations in short-term silicone hydrogel contact lens (SiHCL) users by confocal microscopy. Materials and Methods: The study included 25 right eyes of 25 male volunteers aged 25-30 years who had never used SiHCLs before. ocular surface disease index (OSDI), tear break-up time, Schirmer test, tear meniscus area, strip meniscometry tube, corneal sensitivity, and corneal subbasal nerve morphology were evaluated before and after 1 month of CL use. Results: OSDI was 10.6±1.1 before CL use and 17.2±1.2 after 1 month of CL use (p<0.01). Schirmer test distance was 16.3±2.3 mm before and 14.3±1.9 mm after 1 month of CL use (p>0.05). Tear film break-up time was 7.1±0.4 s before and 6.2±0.3 s after CL use (p>0.05). The tear meniscus area was 0.026±0.002 mm2 before and 0.024±0.001 mm2 after 1 month of CL use (p>0.05). Strip meniscometry tube results were 5.4±0.9 mm before and 4.9±0.8 mm after 1 month of CL use (p>0.05). Corneal sensitivity values were 3.2±0.4 mm before and 2.95±0.3 mm after 1 month of CL use (p>0.05). Dendritic cell density evaluated by confocal microscopy was 14.84±3.1 cells/mm2 before and 32.57±4.2 cells/mm2 after 1 month of CL use (p<0.01). Subbasal nerve tortuosity was 0.92±0.2 before and 1.03±0.2 after 1 month of CL use (p>0.05). Subbasal nerve density was measured as 4726±310 pixels/frame before and 4570±272 pixels/frame after 1 month of CL use (p>0.05). Conclusion: After a month of SiHCL use, no significant changes were observed in tear secretion, corneal sensitivity, tear meniscus volume, subbasal corneal nerve density, reflectivity, or tortuosity, while a significant increase was found in OSDI and dendritic cell density.

Corneal Nerve Changes Observed by In Vivo Confocal Microscopy in Patients Receiving Oxaliplatin for Colorectal Cancer: The COCO Study.

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings.

Corneal nerves and their role in dry eye pathophysiology.

As the cornea is densely innervated, its nerves are integral not only to its structure but also to its pathophysiology. Corneal integrity depends on a protective tear film that is maintained by corneal sensation and the reflex arcs that control tearing and blinking. Furthermore, corneal nerves promote epithelial growth and local immunoregulation. Thus, corneal nerves constitute pillars of ocular surface homeostasis. Conversely, the abnormal tear film in dry eye favors corneal epithelial and nerve damage. The ensuing corneal nerve dysfunction contributes to dry eye progression, ocular pain and discomfort, and other neuropathic symptoms. Recent evidence from clinical studies and animal models highlight the significant but often overlooked neural dimension of dry eye pathophysiology. Herein, we review the anatomy and physiology of corneal nerves before exploring their role in the mechanisms of dry eye disease.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

PURPOSE: To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). METHODS: Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. RESULTS: The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. CONCLUSIONS: The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.