Cochet-Bonnet Esthesiometer Research Articles

Evaluation of corneal sensitivity in multiple sclerosis patients.

Purpose:To measure the corneal sensitivity in patients with multiple sclerosis (MS), to compare it with normal values and to study its correlation with different disease characteristics.Methods:Corneal sensitivity of 28 MS patients was compared to corneal sensitivity of 28 age- and gender-matched normal controls. Corneal sensitivity was measured using the Cochet-Bonnet esthesiometer and was correlated to the duration, type and severity indexes of the disease.Results:Corneal sensitivity was comparable between both groups (P = 0.79). No statistically significant correlation was found between corneal sensitivity and the duration of MS (P = 0.55) nor the severity indexes of MS (expanded disability status scale [EDSS] P = 0.52, global multiple sclerosis severity score [MSSS] P = 0.64). Following subgroup analysis, only the primary progressive (PPMS) form of MS had a reduced corneal sensitivity with P = 0.023, while remittent-recurrent (RRMS), secondary progressive (SPMS), and clinically isolated (CIS) forms of MS did not have any reduction in the corneal sensitivity. “ROC curve analysis” showed an area under the curve of 0.48.Conclusion:In the exception of PPMS subtype, MS patients have similar corneal sensitivity in comparison to controls. Cochet-Bonnet esthesiometer does not seem to be a good diagnostic tool or a disease severity marker for patients with MS.

Age and Sex Variation in the Duration of Action and Corneal Touch Threshold (CTT) following Instillation of 0.5% Topical Ophthalmic Proparacaine and Tetracaine Hydrochlorides.

Purpose We investigated the effect of age and sex on corneal touch threshold (CTT) and duration of action following administration of 0.5% topical ophthalmic proparacaine and tetracaine hydrochlorides. Methods A prospective, randomized, subject-masked, crossover study design was used. Two hundred and forty human volunteers were enrolled in the study. Corneal touch threshold (CTT) was determined using a Cochet-Bonnet esthesiometer. CTT was measured every 15 seconds for the first 1-minute and at 5-minute intervals subsequently for a period of 40 minutes after the application of each anesthetic. CTT and duration of action of the ophthalmic solutions were tested for statistical significance using repeated measures ANOVA. Results The total duration of effect was 20 minutes for females and 25 minutes for males for both anesthetics. The total duration of the effect of both solutions decreased with increasing age; however, elderly participants had the longest duration (5 minutes) of the maximal effect (minimum CTT) of the two ophthalmic preparations. There was a significant influence of sex, F (2.39, 569.65) = 2.86, p=0.04; F (3.48, 828.19) = 4.41, p=0.003, and age, F (4.78, 566.18) = 8.97, p < 0.001; F (7.19, 852.56) = 20.55, p < 0.001 on CTT following application of proparacaine hydrochloride and tetracaine hydrochloride, respectively. Conclusion CTT and duration of anesthetic effect after instillation of 1 drop of 0.5% proparacaine hydrochloride and 0.5% tetracaine hydrochloride vary based on sex and age.

Corneal neuropathic pain in irritable bowel syndrome: clinical findings and in vivo corneal confocal microscopy.

Ocular discomfort is a common symptom in central sensitization syndromes. The aim of this study was to evaluate ocular surface discomfort and related corneal changes in patients with irritable bowel syndrome. Twenty-nine patients with IBS (20 female, 9 male, mean age: 45.3 ± 10.1years) and 37 healthy control subjects (25 female, 12 male, mean age: 44.95 ± 9.76years) were included. A detailed ophthalmological examination was performed to all participants including tear break-up time (TBUT) and Schirmer test I with anesthetic (SIT). Ocular discomfort was evaluated using the ocular surface disease index (OSDI) questionnaire and corneal sensation was evaluated with Cochet-Bonnet esthesiometer. Corneal subbasal nerve plexus was evaluated with in vivo corneal confocal microscopy (IVCM). There was no significant difference between the groups for age, gender distribution, and visual acuity. OSDI scores were significantly higher (p = 0.008) and TBUT was significantly reduced in patients with IBS compared to controls (p = 0.001 for right eye, p = 0.014 for left eye). However, there was no significant difference in corneal touch sensation and SIT results between the groups. IVCM revealed that corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length were significantly reduced in patients with IBS (p < 0.001, p < 0.001, and p = 0.023, respectively). Patients with IBS have increased dry eye-associated ocular surface complaints and nerve fiber loss in corneal subbasal nerve plexus. IBS should be remembered in the differential diagnosis, when there is discordance between the level of ocular surface discomfort and dry eye disease associated corneal findings.

PEDF Gene Deletion Disrupts Corneal Innervation and Ocular Surface Function.

PurposeThe cornea is richly innervated by the trigeminal ganglion (TG) and its function supported by secretions from the adjacent lacrimal (LG) and meibomian glands (MG). In this study we examined how pigment epithelium–derived factor (PEDF) gene deletion affects the cornea structure and function.MethodsWe used PEDF hemizygous and homozygous knockout mice to study effects of PEDF deficiency on corneal innervation assessed by beta tubulin staining, mRNA expression of trophic factors, and PEDF receptors by adjacent supporting glands, corneal sensitivity measured using a Cochet-Bonnet esthesiometer, and tear production using phenol red cotton thread wetting.ResultsLoss of PEDF was accompanied by reduced corneal innervation and sensitivity, increased corneal surface injury and tear production, thinning of the corneal stroma and loss of stromal cells. PEDF mRNA was expressed in the cornea and its supporting tissues, the TG, LG, and MG. Deletion of one or both PEDF alleles resulted in decreased expression of essential trophic support in the TG, LG, and MG including nerve growth factor, brain-derived neurotrophic growth factor, and GDNF with significantly increased levels of NT-3 in the LG and decreased EGF expression in the cornea. Decreased transcription of the putative PEDF receptors, adipose triglyceride lipase, lipoprotein receptor–related protein 6, laminin receptor, PLXDC1, and PLXDC2 was also evident in the TG, LG and MG with the first three showing increased levels in corneas of the Pedf+/− and Pedf−/− mice compared to wildtype controls. Constitutive inactivation of ERK1/2 and Akt was pronounced in the TG and cornea, although their protein levels were dramatically increased in Pedf−/− mice.ConclusionsThis study highlights an essential role for PEDF in corneal structure and function and confirms the reported rescue of exogenous PEDF treatment in corneal pathologies. The pleiotropic effects of PEDF deletion on multiple trophic factors, receptors and signaling molecules are strong indications that PEDF is a key coordinator of molecular mechanisms that maintain corneal function and could be exploited in therapeutic options for several ocular surface diseases.

Assessment of Tactile Sensitivity Threshold Using Cochet-Bonnet Esthesiometer and Semmes-Weinstein Monofilaments and Their Use in Corneal Neurotization.

Although the Cochet-Bonnet esthesiometer (CBE) measures corneal sensitivity, it has heretofore only been tested on the index pulp. Tactile skin sensitivity thresholds are measured with Semmes-Weinstein monofilaments (SWM). This study measured skin sensitivity thresholds in healthy individuals using CBE and SWM, and compared both instruments in territories involved in corneal neurotization. Overall, 27 healthy individuals were tested by a single examiner at 9 territories on the face, neck, forearm, and leg, using 20-thread SWM and CBE with a diameter of 0.12 mm. Both sides were tested. Thresholds were compared for both instruments and between the different territories using Bayesian methods. Mean sensitivity levels for SWM ranged from 0.010 to 1.128 g, while mean sensitivity levels for CBE ranged from 0.006 to 0.122 g. Thresholds measured with SWM were significantly higher than with CBE. Both instruments demonstrated higher thresholds in the leg territory than the forearm. However, the forearm presented higher thresholds than the head territories. No significant differences were found between the head territories themselves. Overall, right-side territories exhibited lower thresholds than left-side territories. We have reported the first mapping of skin sensitivity thresholds using CBE. Thresholds measured with CBE and SWM were coherent. The use of CBE on the skin is particularly relevant to the field of corneal neurotization.

The inter-eye difference in corneal sensitivity in patients with infectious ulcers as measured with the Cochet-Bonnet esthesiometer

Background: The purpose of this study was to quantify the inter-eye difference in corneal sensations in patients with infectious corneal ulcers using the Cochet-Bonnet esthesiometer (CBE). Material and methods: Patients with unilateral corneal ulcers of at least 1.5 mm of the clear cornea in all quadrants meeting the study criteria were identified and enrolled. The clinical features with their etiologies were noted. The corneal sensations were measured with CBE in all four quadrants. Patients were further sub-categorized based on the surface area and the “time to heal” of the ulcers for further correlation and analysis. Results: This was a cross-sectional study conducted at a tertiary care center. The study included 35 patients, with the majority (30 patients, 85.7%) diagnosed with fungal etiology. The average corneal sensations in the ulcer and the normal eyes were 52.29 mm and 57.36 mm, respectively. The inter-eye differences were 3.93 mm (p = 0.06) and 6.55 mm (p = 0.04) among patients with an average surface area of ≤ 10 mm 2 and > 10 mm 2 , respectively. Patients who took up to 30 days and > 30 days to had inter-eye differences in a sensation of 0.71 mm (p = 0.04) and 6.14 mm (p = 0.05), respectively. Conclusions: The mean corneal sensations in all quadrants were less significant in the infectious ulcer eyes than normal eyes. Infectious ulcers with a surface area of > 10 mm2 had greater inter-eye differences in their corneal sensitivities. Patients who took a longer time to heal of > 30 days showed a significant and greater inter-eye difference in their corneal sensitivities.

Pigment Epithelium-Derived Factor Peptide Promotes Corneal Nerve Regeneration: An In Vivo and In Vitro Study.

PurposeTo investigate the potential of a pigment epithelium-derived factor (PEDF) peptide 44-mer to promote nerve regeneration in a rabbit corneal nerve injury model to demonstrate its neurotrophic ability in cultivated mouse trigeminal neuron cells.MethodsSubconjunctival or intrastromal injection of 44-mer on the cornea was performed in a rabbit model of corneal nerve injury created by corneal epithelial debridement. Immunocytochemical analysis (44-mer, anti-tubulin III, SMI312, CD11b, and α-SMA) and in vivo confocal microscopy were performed. Corneal sensation was estimated using a Cochet-Bonnet corneal esthesiometer. Primary cultivated mouse trigeminal neurons were used to examine the in vitro neurotrophic ability of 44-mer. The cellular morphology and the immunocytochemical staining with anti-tubulin III and SMI312 in different concentrations of 44-mer were compared, and a quantitative assessment of neurite outgrowth was performed.ResultsImmunohistochemical staining showed the retention of 44-mer in the corneal stroma for at least 7 days after a single dose of corneal intrastromal injection and promoted corneal nerve regeneration revealed by in vivo confocal microscopy. Corneal esthesiometer demonstrated gradual recovery of the corneal sensation in 44-mer-treated eyes with a lower corneal touch threshold than wounded vehicles and closer to baseline at 3 weeks after corneal injury (P < 0.001). In vitro studies showed a dose-dependent neurotrophic effect of 44-mer in cultivated trigeminal neuron cells.ConclusionsThe 44-mer showed in vivo and in vitro corneal neurotrophic abilities. Our results suggest that intrastromal injection of 44-mer into the corneal stroma may have a potential role in treating diseases related to corneal nerve damage.

Ocular surface diabetic disease: A neurogenic condition?

PurposeTo investigate clinical and inflammatory changes in the ocular surface of insulin-dependent type I diabetic patients. MethodsTwo hundred and nine eyes of 106 patients with diagnosis of type I diabetes were recruited in a prospective observational study. Ocular surface clinical assessment, corneal sensitivity and tear film stability tests were performed to evaluate ocular surface system function. Ocular Surface Disease Index (OSDI) questionnaire was administered to all enrolled subjects. Conjunctival impression cytology specimens were also collected to detect neuromediators and inflammatory molecules. Duration of disease, HbA1c levels and diabetic retinopathy stage were recorded. ResultsCorneal sensitivity assessed by Cochet-Bonnet esthesiometer was reduced in patients with more chronic disease, higher HbA1c levels and proliferative diabetic retinopathy. Tear break-up time (TBUT) was reduced in subjects with long-standing diabetes or with more severe retinopathy. OSDI questionnaire scores showed direct correlation with increased HbA1c values. Significant increase of NPY, STAT-5 and ICAM-1 was found in diabetic patients compared to healthy controls. A direct correlation between NPY concentration and ICAM-1 values in patients with type I diabetes was demonstrated. ConclusionsPatients with long-standing type I diabetes showed chronic inflammation of the ocular surface, due to neurogenic dysregulation of para-inflammatory homeostatic mechanisms. These patients with ocular surface system failure complained of ocular discomfort but had modest reduction of corneal sensitivity and no signs of neurotrophic keratopathy. Disease duration, increased HbA1c levels and severe diabetic retinopathy appear the most critical factors.

Feasibility and variability of corneal esthesiometry in Hermann's tortoises (Testudo hermanni) depending on age and body weight

ABSTRACT Background Hermann's tortoise is one of the most popular reptiles kept as pet which underlines the importance to reinforce the information needed to provide advanced and adequate veterinary care in exotic animal species. Therefore, the purpose of this study, performed in Testudo hermanni, was to evaluate corneal touch threshold (CTT) and its feasibility according to age and body weight. Methods Fifty-one healthy tortoises were classified in 2 groups (≤2 years [young; n = 25] and 8–10 years [subadult; n = 26]). Central CTT was measured by means of a Cochet-Bonnet esthesiometer and defined as the filament length required to elicit a blink in at least 3/5 applications. CTT feasibility according to body weight was also evaluated by diving the individuals in weight groups consisting of “lighter” ( Results Mean CTT was 5.99 cm for the whole population (90% CI: 5.87–6.11), being 5.98 cm for young (90% CI: 5.81–6.15) and 6 cm for all subadult (90% CI: 6.00–6.00) tortoises, and 5.98 cm for lighter (90% CI: 5.84–6.13) and 6 cm for all heavier (90% CI: 6.00–6.00) tortoises. No statistical differences were detected between age and weight groups (P = 0.159 and P = 0.159, respectively). Three animals presented unilateral faint fluorescein uptake postesthesiometry (3/51; 2.9%) that resolved spontaneously within 48 hours. Conclusions and clinical relevance Cochet-Bonnet esthesiometer was a safe means of confirming high corneal sensitivity in all tortoises, which was high regardless of age. Increasing filament lengths would ultimately be required to determine the true corneal sensitivity scope of Testudo hermanni.

Capsaicin-induced pain sensitivity in short tear break-up time dry eye

PurposeTo evaluate transient receptor potential vanilloid 1 (TRPV1)-mediated pain sensitivity in patients with short tear break-up time (TBUT) dry eye (DE) by using the capsaicin stimulus test. MethodsThis prospective cross-sectional comparative study included 22 eyes of 22 patients with short TBUT DE and 11 eyes of 11 non-DE control subjects. Patients were divided into two groups based on response to standard DE treatments: 10 non-responders (intractable DE) and 12 responders (responsive DE). Mechanical touch (M-touch) and mechanical pain (M-pain) were measured using a Cochet-Bonnet esthesiometer. Capsaicin-induced pain (C-pain) and C-pain duration (C-pain DT) were measured using a capsaicin stimulus test. Psychological distress was also assessed. ResultsM-touch sensitivity was similar among all three groups. M-pain sensitivity was higher in the responsive DE group than in the intractable DE and control groups (P < .001). C-pain sensitivity was lower (P < .001) in the intractable DE group than in the responsive DE and control groups, and C-pain DT was shorter (P = .006) in the intractable DE group than in the responsive DE group. Psychological distress was higher in the intractable DE group than in the control group (P < .001). ConclusionsPatients with intractable short TBUT DE were less sensitive to the effects of capsaicin than patients with responsive short TBUT DE and controls. Altered neural activation may contribute to the development of DE symptoms in the short TBUT DE subjects. The capsaicin stimulus test may be used to better understand pain sensitivity in short TBUT DE patients.

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.

Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats.

PurposeTo examine the effect of 3% diquafosol ophthalmic solution (DQS) on ocular surface disorders in diabetic model rats maintained in a continuous airflow condition.MethodsGoto–Kakizaki (GK) rats, a spontaneous model of type 2 diabetes, were exposed to constant airflow for 8 weeks. After the establishment of the animal model in this environment, DQS or saline was instilled six times a day into GK rat eyes for 6 weeks. Schirmer’s test was performed before and after 6-week instillations. Corneal fluorescein staining was scored at 2-, 4-, and 6-week instillations. Touch thresholds for the cornea were also determined using a Cochet–Bonnet esthesiometer before and after 6-week instillations.ResultsThe mean Schirmer’s test score after instillation of DQS was twice higher than that recorded for saline alone. DQS significantly decreased corneal staining scores at 4- and 6-week instillations. No changes in touch thresholds were observed before and after 6-week instillations.ConclusionThese results suggest that DQS improves corneal epithelial damage by stimulating tear secretion without influencing corneal sensation in diabetic keratopathy. Thus, DQS may have potential for treatment of diabetic patients with dry eye.

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.

Corneal Neurotization: A Review of Pathophysiology and Outcomes.

The objective of this study is to provide a systematic review of the clinical outcomes of corneal neurotization and present the pathophysiology of corneal wound healing, neurotrophic keratopathy, and corneal neurotization. A literature review of published articles and meeting abstracts between December 2008 and February 2019 in the English language with the terms "corneal neurotization," "corneal neurotisation," "corneal reinnervation," and "neurotrophic keratopathy" was performed. Reported clinical data before and after corneal neurotization, and surgical techniques, were collected and analyzed. A total of 54 eyes that underwent corneal neurotization were identified. Final Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity improved to 0.85 (standard deviation [SD] = 0.65) from 1.25 (SD = 0.71) with a mean improvement of 0.41 (SD = 0.55; p < 0.0001). Central corneal sensation measured using Cochet-Bonnet esthesiometer improved from 2.18 mm (SD = 0.4) to 40.10 mm (SD = 18.66) with a mean filament length change of 38.00 mm (SD = 18.95; p < 0.0001). The median time to the reported maximal sensation return was 8 months (interquartile range 6-10). The most common reported limitation to visual recovery was corneal scarring (31.5%). Children (ages 0-17 years) as compared with adults (ages 18-82 years) had significantly greater final central corneal sensation esthesiometry readings, central corneal sensation return, and improvement in the logMAR best-corrected visual acuity (p < 0.011). Neurotrophic keratopathy disturbs the homeostatic balance of trophic factors and trigeminal nerve reflexes needed to support ocular surface health and corneal healing. Corneal neurotization can significantly improve corneal sensation and visual acuity and should be considered for the treatment of refractory neurotrophic keratopathy, especially in pediatric populations.

Establishing the normal range of corneal sensitivity in an Indian Population using the Cochet–Bonnet esthesiometer

Background: The human cornea is the most densely innervated tissue, and the corneal sensitivity is a measure of its function and an indicator of the integrity of the protective mechanism. Corneal sensitivity plays a vital role in the protection and maintenance of corneal health and is known to vary with race, age, region, climate, environment, and the time of the day. The study was aimed to quantify and establish the range of corneal sensations in different age groups in an Indian population using the Cochet–Bonnet Esthesiometer (CBE). Materials and Methods: This was a cross-sectional study done at a tertiary care center in South India, between January and April 2018. One hundred and fifty patients (30 patients stratified by age into five groups) were enrolled after informed consent. The corneal sensations were measured using CBE by a single examiner in a specified period of a day over five regions and the data analyzed. Results: The average measured corneal sensitivity was 58.36 (21–30 years), 57.96 (31–40 years), 56.43 (41–50 years), 56.40 (51–60 years), and 54.84 (>60 years) mm, respectively. The frequency of having maximal measurable sensations (60 mm) in all the tested regions dropped with increasing age from 46.67% to 16.67%. All regions showed a sensitivity drop with an increase in age, the maximum in the nasal quadrant and the least drop in the central region. No statistically significant difference in the corneal sensitivity was found between the genders. Conclusions: An inverse linear correlation between the corneal sensitivity and age was evident. The central and the superior regions are the most and least sensitive regions of the cornea, respectively, in our study population. The varied pattern of change in corneal sensations in different populations highlights the importance of establishing normal ranges of corneal sensitivity in patients from different ethnic and geographical backgrounds.

Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.

SUMMARYWe focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 µg/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other’s effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics.

Ocular Surface, Meibomian Gland Alterations, and In Vivo Confocal Microscopy Characteristics of Corneas in Chronic Cigarette Smokers.

To evaluate the ocular surface, meibomian gland alterations, and in vivo confocal microscopy (IVCM) parameters through correlation with nicotine dependency level (NDL) and duration of smoking (DS) in chronic smokers. This cross-sectional study included 50 eyes of 50 chronic smokers, and 50 eyes of 50 age- and gender-matched healthy nonsmokers. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet esthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index (OSDI) questionnaire were performed consecutively. Basal epithelial cell, keratocyte, and endothelial cell density, the percentage of endothelial polymegethism/pleomorphism, and subbasal nerve plexus were evaluated using IVCM. Meibomian gland density was evaluated with a meibography unit. The Fagerström test was used to measure NDL, and DS was recorded. In the chronic smokers group, the basal epithelial cell density, anterior and posterior keratocytes, endothelial cell density, and long and total subbasal nerve numbers were lower, and LG staining, meiboscore, and OSDI scores were higher, compared with the control group, whereas other parameters were similar. The percentage of polymegethism was higher and the percentage of pleomorphism was lower in the chronic smokers group. In the correlation analysis, no significant relationship was found between the DS, NDL and ocular surface, and IVCM findings. Decreased corneal basal epithelium, anterior and posterior keratocytes, endothelial cell density, meibomian gland density, and subbasal nerve numbers were found in chronic smokers. The results of the study show that smoking has an adverse effect on ocular surface parameters.

Neuroprotective Effect of Citicoline Eye Drops on Corneal Sensitivity After LASIK.

To evaluate the accelerator role of a topically administered neuroprotective eye drop (citicoline) on the recovery of corneal sensitivity after laser in situ keratomileusis (LASIK). In this prospective, controlled study, 78 eyes of 78 patients (mean age: 26.8 ± 7.6 years) were enrolled in the study group and their eyes were treated with topical citicoline three times a day for 1 month postoperatively. Seventy-eight eyes of 78 patients (mean age: 26.1 ± 7.4 years) were randomly selected as the control group and their eyes were treated with lubricant hyaluronic acid (0.15%) eye drops three times a day for 1 month. Corneal sensitivity was assessed in both groups using a Cochet-Bonnet esthesiometer at baseline and 1, 2, 3, 4, 6, 8, and 12 weeks after the LASIK procedure. Corneal sensitivity at 1, 2, 3, 4, and 6 weeks after LASIK was significantly better in the citicoline group than the control group (P < .05 for all). Differences between the groups at 8 and 12 weeks after LASIK were not significant (P > .05). Topically administered citicoline eye drops had beneficial effects in the early recovery of corneal sensitivity during the first 6 weeks after LASIK, suggesting that citicoline may play a significant role in accelerating corneal reinnervation. [J Refract Surg. 2019;35(12):764-770.].

Prolonged Duration Topical Corneal Anesthesia With the Cationic Lidocaine Derivative QX-314

PurposeTopical corneal local anesthetics are short acting and may impair corneal healing. In this study we compared corneal anesthesia and toxicity of topically applied N-ethyl lidocaine (QX-314) versus the conventional local anesthetic, proparacaine (PPC).MethodsVarious concentrations of QX-314 and 15 mM (0.5%) PPC were topically applied to rat corneas. Corneal anesthesia was assessed with a Cochet-Bonnet esthesiometer at predetermined time points. PC12 cells were exposed to the same solutions to assess cytotoxicity. Repeated topical corneal administration in rats was then used to assess for histologic evidence of toxicity. Finally, we created uniform corneal epithelial defects in rats and assessed the effect of repeated administration of these compounds on the defect healing rate.ResultsQX-314 (15 mM) and PPC (15 mM) caused similar total duration (114 ± 17 and 87 ± 16 minutes, respectively; P = 0.06) of anesthesia. The depth of anesthesia was similar between these low-dose groups at 15 minutes after application (1.8 ± 0.3- and 2.0 ± 0.8-cm filament lengths). QX-314 (100 mM) provided more prolonged corneal anesthesia (174 ± 13 minutes; P < 0.0001), with improved depth at 15 minutes (0.7 ± 0.3-cm filament length; P = 0.007). All tested concentrations of QX-314 demonstrated similar or less toxicity than 0.5% PPC.ConclusionsTopical administration of QX-314 is effective for corneal anesthesia and demonstrates no histologic signs of local toxicity in a rodent model. In higher concentrations, QX-314 provides more than twofold the duration of anesthetic effect than does 0.5% PPC.Translational RelevanceOur study reveals a clinically relevant compound providing prolonged duration topical corneal anesthesia.

Progesterone Application to the Rat Forehead Produces Corneal Antinociception.

PurposeOcular pain and discomfort are the most defining symptoms of dry eye disease. We determined the ability of topical progesterone to affect corneal sensitivity and brainstem processing of nociceptive inputs.MethodsProgesterone or vehicle gel was applied to the shaved forehead in male Sprague Dawley rats. As a site control, gel also was applied to the cheek on the side contralateral to corneal stimulation. Corneal mechanical thresholds were determined using the Cochet-Bonnet esthesiometer in intact and lacrimal gland excision–induced dry eye animals. Eye wipe behaviors in response to hypertonic saline and capsaicin were examined, and corneal mustard oil-induced c-Fos immunohistochemistry was quantified in the brainstem spinal trigeminal nucleus.ResultsProgesterone gel application to the forehead, but not the contralateral cheek, increased corneal mechanical thresholds in intact and lacrimal gland excision animals beginning <30 minutes after treatment. Subcutaneous injection of the local anesthetic bupivacaine into the forehead region before application of progesterone prevented the increase in corneal mechanical thresholds. Furthermore, progesterone decreased capsaicin-evoked eye wipe behavior in intact animals and hypertonic saline evoked eye wipe behavior in dry eye animals. The number of Fos-positive neurons located in the caudal region of the spinal trigeminal nucleus after corneal mustard oil application was reduced in progesterone-treated animals.ConclusionsResults from this study indicate that progesterone, when applied to the forehead, produces analgesia as indicated by increased corneal mechanical thresholds and decreased nociceptive responses to hypertonic saline and capsaicin.