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.

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).

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.

Working principle and relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) evaluation.

PURPOSE: To describe and evaluate relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) for ocular surface sensitivity measurement. METHODS: Characteristics of Liquid Jet (LJ) droplets (consisting of isotonic saline solution) were analysed: vertical and horizontal displacement and speed of LJ droplets were recorded with the aid of the High Speed Photron FASTCAM NOVA S6 camera (stimulus duration: 40 ms). Stimulus mass was assessed for 20 sets of 10 LJs with aid of a microbalance (pressure range of 100-1500 mbar). RESULTS: Because continuous flow LJ disintegrated into droplets in the lower pressure range (<700 mbar), pulsed stimuli were applied in order to obtain similar stimulus characteristics across the applied pressure range. For all measurements, very little variability was observed. Vertical and horizontal displacement did not exceed 0.13 mm in either direction. The mass per shot showed an unexpected cubic dependency on pressure. Up to approximately 700 mbar, LJ speed showed an almost linear relationship. For the pressure range of >700-1500 mbar, variability increased and speed decreased compared to the expected in a linear manner. However, this may be caused by the difficulty of identifying pattern changes of LJ droplets from one high speed image frame to the next with increasing stimulus speed, when determining LJ speed via pixel count. CONCLUSIONS: Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity was shown to deliver fine droplets with a pulsed stimulus mode, in a repeatable manner with precise localisation to the ocular surface. Very little variability was observed in LJ speed and mass for the typical pressure range required for clinical sensitivity measurements.

Traumatic displacement of laser in situ keratomileusis flaps: an integrated clinical case presentation.

BACKGROUND: Traumatic dislocation of laser-assisted in situ keratomileusis (LASIK) corneal flaps is an uncommon postoperative complication that could occur any time after LASIK, and could be visually devastating. We evaluated the visual outcomes, corneal sensation, tear function, and dry eye questionnaire results of patients with traumatic dislocation of LASIK flaps, including one LASIK flap amputation. METHODS: This is a retrospective case series. Seven patients who were diagnosed with traumatic displacement of the LASIK flap and underwent flap replacement surgery between August 2014 and January 2019 were included.Patient's visual acuity, refraction, corneal sensitivity, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH), and ocular surface disease index (OSDI) results were evaluated. RESULTS: The patients' mean age was 35.86 ± 5.84 years, and 42.9 % (3/7) were male. The mean duration from LASIK to trauma was 8.86 ± 2.48 years.The mean preoperative and postoperative six-month corrected distance visual acuity (CDVA) were 0.55 ± 0.34 and 0.02 ± 0.03, respectively. The mean spherical equivalent and astigmatism at six months postoperatively was - 1.0 ± 0.95 D and - 0.5 ± 0.25 D, respectively. The corneal flap was clear and well-positioned at the final follow-up (mean: 28.57 ± 6.9 months). 85.71 % (6/7) of the patients showed worse corneal sensation in the injured eye. Interocular OSDI discrepancy was less in those whose last visit was more than 30 months after the trauma. CONCLUSIONS: Postoperative CDVAat six months was improved, and the refractive data also showed some improvement. The corneal nerve and tear function recovery peaked before 30 months, while the OSDI continued to show a strong trend of improvement beyond 30 months.

Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

BACKGROUND: To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy. METHODS: This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups. RESULTS: 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high. CONCLUSIONS: Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect. TRIAL REGISTRATION: Trial registration NCT03906513 , retrospectively registered on 08 April 2019.

Corneal anesthesia associated with topical application of 2% lidocaine nonophthalmic gel to healthy canine eyes.

OBJECTIVE: To assess the degree and duration of corneal anesthesia induced by topical application of 2% lidocaine gel to the healthy canine eye. ANIMALS: Nineteen adult Beagles free of ocular abnormalities. PROCEDURES: Baseline corneal touch threshold (CTT) was measured bilaterally with a Cochet-Bonnet aesthesiometer. The 2% lidocaine gel (0.1 mL) was applied to one eye, randomly assigned, and the same volume of a lubricant gel was applied to the opposite eye. The CTT measurements were repeated bilaterally within 1 minute, after drug application, and every 5 minutes, until the baseline corneal sensitivity was restored. The potential for local adverse effects was evaluated. RESULTS: Complete desensitization of the cornea (CTT = 0) was achieved one minute after lidocaine gel application and was maintained during 25.3 ± 12.5 minutes. Overall, the corneal sensitivity was significantly decreased for 58.4 ± 16.6 minutes compared with baseline level. Minor and reversible punctate epithelial erosions of the cornea were observed in the two treatment groups and were attributed to the anesthetic effect and the aesthesiometry procedure. CONCLUSIONS: In the current study, the 2% lidocaine gel provided a sustained, deep and well-tolerated corneal anesthesia in ophthalmically normal dogs.

Aqueous tear assessment in dogs: Impact of cephalic conformation, inter-test correlations, and test-retest repeatability.

OBJECTIVE: To characterize diagnostic findings, test-retest repeatability, and correlations among lacrimal tests in dogs of diverse cephalic conformations. ANIMAL STUDIED: Fifty healthy dogs (25 brachycephalic, 25 nonbrachycephalic). PROCEDURES: A series of diagnostics were performed in each dog, allowing for a 10-minute interval between tests and repeating each test 24 hours later under similar conditions: corneal tactile sensation (CTS), strip meniscometry test (SMT), phenol red thread test (PRTT), endodontic absorbent paper point tear test (EAPPTT), Schirmer tear test-1 without (STT-1) or with nasolacrimal stimulation (NL-STT1), and Schirmer tear test-2 (STT-2). RESULTS: Mean ± SD test values were lower in brachycephalic vs. nonbrachycephalic dogs (except for SMT; 7.4 ± 2.0 mm/5 seconds vs 7.3 ± 2.4 mm/5 seconds), with statistically significant differences noted for CTS (1.8 ± 0.5 cm vs 3.4 ± 0.8 cm), PRTT (37.2 ± 4.0 mm/15 seconds vs 41.1 ± 5.5 mm/15 seconds), STT-1 (20.1 ± 3.4 mm/min vs 23.3 ± 5.7 mm/min), STT-2 (13.0 ± 3.4 mm/min vs 16.9 ± 3.9 mm/min), and NL-STT1 (23.2 ± 3.6 mm/min vs 27.1 ± 5.4 mm/min), and nonsignificant differences for EAPPTT (16.6 ± 2.7 mm/15 seconds vs 17.5 ± 2.9 mm/15 seconds). Nasolacrimal stimulation increased STT-1 values by 18% on average. Correlations among tests were generally weak to moderate (r < .70) except for a strong correlation between STT-1 and NL-STT1 (r = .83, P < .001). Test reliability was good although test-retest repeatability was generally poor to moderate, as depicted by low intraclass correlation coefficients (ICC ≤ 0.75) and wide 95% limits of agreement, except for CTS (ICC = 0.91). CONCLUSIONS: Corneal sensitivity and aqueous tear secretion are lower in brachycephalic dogs. A comprehensive assessment of the ocular surface requires the combination of several diagnostic tests. The nasolacrimal reflex may provide a useful diagnostic and therapeutic tool in dogs.

Corneal hypoesthesia, aqueous tear deficiency, and neurotrophic keratopathy following micropulse transscleral cyclophotocoagulation in dogs.

OBJECTIVE: To describe ocular surface complications following micropulse transscleral cyclophotocoagulation (MP-TSCPC) in dogs. ANIMALS STUDIED: Eighteen dogs treated with MP-TSCPC at two institutions for glaucoma management. PROCEDURES: MP-TSCPC was applied to each eye (avoiding 3 and 9 o'clock positions) with 31.3% duty cycle, 2000-3000 mW energy, and 90-180 seconds duration per hemisphere. Central corneal tactile sensation (CTS) and Schirmer tear test-1 (STT-1) were measured at baseline and ≥2 post-operative visits in each dog. RESULTS: Corneal sensitivity decreased in 16/18 dogs (89%) by an average of 10%-42% (up to 100% in 4 dogs). CTS decline was rapid (≤1 week) and only fully recovered in 50% of dogs within 8-180 days. Patients' age, glaucoma duration, laser energy, and total energy delivered did not affect CTS at any visit. However, brachycephalic dogs had significantly lower CTS and likelihood to recover full sensation compared with nonbrachycephalic dogs. Aqueous tear deficiency (STT-1 < 15 mm/min) occurred in 8/18 dogs (44%) within 7-270 days, and concurrent signs of keratoconjunctivitis sicca were noted in 2/18 dogs (11%). Neurotrophic corneal ulcers developed in 6/18 dogs (33.3%) and required 16-53 days to heal. CONCLUSIONS: Corneal hypoesthesia is a common complication of MP-TSCPC in dogs, and can lead to serious adverse effects such as aqueous tear deficiency and neurotrophic corneal ulcers. Brachycephalic dogs represent a population at higher risk. Close monitoring of ocular surface health is recommended for months following MP-TSCPC in dogs.

Impact of acute conjunctivitis on ocular surface homeostasis in dogs.

OBJECTIVE: To investigate the effects of acute conjunctivitis on tear film characteristics and corneal sensitivity in dogs. ANIMALS STUDIED: Eight female spayed Beagle dogs (1.5-2 years old, 7.5-10 kg). PROCEDURES: On two consecutive days, one randomly selected eye in each dog received 1 or 375 mg/mL histamine solution to induce mild or severe conjunctivitis, while the contralateral eye served as control. Diagnostic tests were performed in the following order: fluorescein instillation and repeated tear collection over 20 minutes (to determine tear volume [TV] and turnover rate [TTR] by fluorophotometry), Schirmer tear test-1 (STT-1), tear ferning, corneal esthesiometry, and tear film breakup time (TFBUT). RESULTS: Results are presented as median values for severe conjunctivitis, mild conjunctivitis, and control eyes. Eyes with severe conjunctivitis had significantly higher STT-1 (24, 19.5, 17.5 mm/min; P = .002) and significantly lower TFBUT (10.5, 13.5, 15.5 s; P = .002), but no changes were noted in corneal tactile sensation (2, 2.5, 2.5 cm) or tear ferning (grades 2, 2, 2.5). Severe conjunctivitis significantly increased TV by nearly 10-fold (631, 97, 65 µL) initially (reflex tearing), although basal TV returned rapidly (<5 minutes) in all eyes (46, 58, 48 µL). Finally, there was a nonsignificant trend for higher reflex TTR in the conjunctivitis vs control eyes (68, 58, 43%/min). CONCLUSIONS: Experimentally induced conjunctivitis increases tear quantity and decreases tear quality in dogs, but has no impact on corneal sensitivity. Changes in tear film dynamics could affect ocular pharmacology (eg, precorneal retention time), although homeostasis of lacrimal volume and drainage is rapidly restored.

Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice.

Aging impacts the ocular surface and reduces intraepithelial corneal nerve (ICN) density in male and female mice. Many researchers use retired breeders to study naturally aged female mice. Yet, the impact of parity and the length of time since breeders were retired on age-related changes in the intraepithelial corneal nerves is not known. Here we study 2 month (M) nulliparous (NP) females as well as 9M, 10M, and 11M NP and multiparous (MP) female mice to determine whether parity impacts the age-related decline seen in corneal axon density; 9M male mice are also included in these assessments. After showing that parity attenuates age-related loss in axon density, we also assess the impact of parity on corneal epithelial cell proliferation and find that it impacts cell proliferation and axon density normalized by cell proliferation. Stromal nerve arborization is also impacted by aging with parity enhancing stromal nerves in older mice. qPCR was performed on 20 genes implicated in ICN density using corneal epithelial RNA isolated from 10M NP and MP mice and showed that NGF expression was significantly elevated in MP corneal epithelium. Corneal sensitivity was significantly higher in 9M MP mice compared to NP mice and increased sensitivity in MP mice was accompanied by increased nerve terminals in the apical and middle cell layers. Together, these data show that parity in mice attenuates several aspects of the age-related decline seen on the ocular surface by retaining sensory axons and corneal sensitivity as mice age.

Ocular Examinations and Investigation of Intraocular Pressure, Tear Production, Central Corneal Thickness, and Corneal Touch Threshold in a Captive Flock of Atlantic Puffins (Fratercula arctica).

Ocular examinations were completed on a group of 10 Atlantic puffins (Fratercula arctica), 5 males and 5 females that ranged in age from 8 months to older than 30 years. The exams consisted of intraocular pressure/rebound tonometry, tear production/phenol red thread test, central corneal thickness/ultrasound pachymetry, and corneal sensitivity/esthesiometry. On ocular examination, there were no corneal abnormalities observed. Bilateral cataracts were diagnosed in 8 puffins, 6 of which were considered incipient, focal subcapsular opacities. One bird had hypermature cataracts and was removed from the study and excluded from data analysis; the other birds had no evidence of ophthalmic pathology that would interfere with diagnostic results (n = 9). All results for 9 birds were included in the study, with the exception of 1 puffin's tear production, which was too low for accurate assessment and was excluded from data analysis. There were no significant differences between right and left eye measurements for intraocular pressure, corneal thickness, and corneal sensitivity. The median intraocular pressure for both eyes (OU) was 13 mm Hg with an interquartile range [IQR] of 12-15 mm Hg. The median corneal thickness OU was 241 µm, IQR 233-248 µm. The median corneal sensitivity OU was 1.13 cm, IQR 0.81-1.50 cm. There was a significant difference between right and left eye measurements for tear production (right eye median, 7.5 mm/15 s, IQR 6.5-9.3 mm/15 s; and left eye median, 5.0 mm/15 s, IQR 4.0-7.3 mm/15 s) (P= .03), with the right eye producing more tears than the left. However, 1 puffin was determined to be an outlier, and when removed, there was no longer a significant difference (OU median, 7.0 mm/15 s, IQR 4.6-8.0 mm/15 s) (P = .38). There was no significant difference between sex and intraocular pressure, tear production, and corneal sensitivity. However, there was a significant difference between sex and corneal thickness (P = .02), with males (left eye median, 249 µm, IQR 241-249 µm) having thicker corneas than females (left eye median, 236 µm, 234-238 µm). Although sample size precluded statistical testing, there appeared to be an association between opacities and increasing age. There were no associations between age and intraocular pressure, tear production, or corneal thickness. There was a moderate correlation between age and corneal sensitivity, with older birds showing decreased corneal sensitivity (r = -0.57). Although the sample size of 9 birds was small, these findings provide preliminary ranges for ocular parameters of Atlantic puffins.

Relationship between corneal sensitivity and diabetic retinopathy among diabetics attending a Nigerian Teaching Hospital.

PURPOSE: To determine the relationship between corneal sensitivity and diabetic retinopathy among diabetics attending Lagos University Teaching Hospital, compared to their age-sex-matched non-diabetics, with a view to proposing its use as a screening tool for diabetic retinopathy. METHODS: The study was a hospital-based comparative cross-sectional study among diabetics aged 25-65 years and their age-sex-matched non-diabetics at Lagos University Teaching Hospital, Lagos, Nigeria. Interviewer-based questionnaire was administered. Corneal sensitivity was assessed with Cochet-Bonnet aesthesiometer. Dilated fundoscopy examination was carried out using slit-lamp bio-microscope with 78D lens and binocular indirect ophthalmoscope. RESULTS: A total of 120 diabetics and 120 age- and sex-matched non-diabetics were enrolled into the study. Among the diabetics, the mean corneal sensitivity was 52.6 ± 6.9 mm, which was statistically lower than among non-diabetics - 58.2 ± 3.0 mm (p-value < 0.05). Twenty-one percent of the diabetic respondents had diabetic retinopathy. The mean cornea sensitivity was statistically lower among diabetics who had developed diabetic retinopathy compared to those with no diabetic retinopathy (48.9 ± 7.3 vs. 55.3 ± 5.4, p < 0.05). The sensitivity and specificity of the aesthesiometer for proliferative diabetic retinopathy at 55 mm cut-off were 100% and 58%, respectively. CONCLUSION: Cornea sensitivity was significantly lower among diabetics with retinopathy compared to those without retinopathy. Also, the degree of cornea sensation loss among diabetics reduced significantly with severity of diabetic retinopathy. Larger validity studies need to be conducted to further assess the use of corneal aesthesiometer as a screening tool for diabetic retinopathy among non-ophthalmologists and other cadres of health workers.

[The effect of the tear film on the results of a direct assessment of the sensitivity of the cornea]. / Vliyanie sleznoi plenki na rezul'taty pryamoi otsenki chuvstvitel'nosti rogovitsy.

Attempts to find clinical application for esthesiometry are associated with studying sensitivity disorders that occur in various diseases (diabetes mellitus, keratitis of various etiologies, corneal erosion, dry eye syndrome), as well as after surgical interventions. PURPOSE: To evaluate the influence of the tear film on the results of direct assessment of corneal sensitivity. MATERIAL AND METHODS: The study was conducted in a group of 20 healthy volunteers. Criteria for inclusion in the group: absence of any ocular and general systemic diseases in the anamnesis, normal indicators of tear production and stability of the tear film according to Schirmer and Norn tests. The process of testing involved a specially designed device that was used to exert a dosed force by jets of air on the frontal corneal surface and the pressure was recorded at the moment of tactile sensations and at the breakup time of tear film, as an indicator of its biomechanical stability. RESULTS: A strong correlation have been found between the pressure of the air stream at the moment of getting tactile sensations and at the breakup of the tear film (R=0.91, p=0.0094). The obtained data indicate that the biomechanical resistance of the lacrimal film is a significant factor preventing the correct assessment of the results of direct corneal esthesiometry in the range of values close to conditionally normal sensitivity. CONCLUSION: In this regard, in their current technical implementation, modern esthesiometers can only be used for monitoring (not for diagnosis!) of pathological processes by analyzing relative (compared to each other) - rather than absolute - sensitivity measures (optimally in combination with analysis of the structural changes in the corneal nerves based on laser confocal microscopy).

Relationship between corneal sensitivity, corneal thickness, corneal diameter, and intraocular pressure in normal cats and cats with congenital glaucoma.

OBJECTIVE: To determine the effect of feline congenital glaucoma (FCG) on corneal sensitivity, and relationships between corneal sensitivity, central corneal thickness (CT), and corneal diameter (CD). ANIMALS AND PROCEDURES: Corneal sensitivity (estimated by corneal touch threshold [CTT] using Cochet-Bonnet esthesiometry); CT using ultrasonic pachymetry; intraocular pressure (IOP) using rebound tonometry; and maximal horizontal CD were measured in 16 normal and 14 FCG cats, both males and females, aged 7 months-3.5 years. All procedures complied with an Institutional Animal Care and Use Committee-approved protocol. Data were analyzed by linear regression: paired Student's t tests for between-eye comparisons, and unpaired Student's t tests for comparisons between groups. Relationships between parameters were evaluated by Pearson correlation coefficients and linear mixed effects modeling. For statistical tests, with the exception of values that were Benjamini-Hochberg adjusted for multiple comparisons, P-values < 0.05 were considered significant. RESULTS: Mean CTT and CT values were lower in FCG eyes relative to normal eyes, but differences were not statistically significant. Mean CD was significantly larger in FCG eyes relative to normal eyes, and there was a significant negative correlation between CD and CTT in FCG (r = -0.8564, corrected P = 0.005). These associations were confirmed in linear mixed effects models. CONCLUSIONS: Eyes with FCG have significantly larger CDs when compared with normal eyes, and larger CDs correlated with decreased corneal sensitivity in this group. Further studies are warranted to explore the effect of buphthalmos and corneal enlargement on corneal sensitivity and innervation in feline subjects with chronic glaucoma.

The Effects of Rebamipide 2% Ophthalmic Solution Application on Murine Subbasal Corneal Nerves After Environmental Dry Eye Stress.

Rebamipide ophthalmic solution is a mucin secretagogue which is an important therapeutic agent in the treatment of dry eye. It has been noted that dry eye in office workers is associated with a decrease in secretory mucin. This study aimed to evaluate the effects of 2% rebamipide ophthalmic solution in mice subjected to environmental dry eye stress (EDES), which mimics the conditions of office workers. Thirty eyes from thirty BALB/c mice (eight-week-old males) were divided into three treatment groups: artificial tear (vehicle), 2% rebamipide ophthalmic solution, and 0.1% hyaluronic acid (HA) ophthalmic solution. After four days of pretreatment, mice were exposed to EDES for three days. The corneal subbasal nerve and inflammatory cells were then examined using in vivo confocal microscopy. Following EDES exposure, the lissamine green staining score was significantly lower and corneal sensitivity was more preserved in the 2% rebamipide group than in the HA group. In addition, the subbasal nerve fiber density was significantly higher and the DC density was significantly lower in the 2% rebamipide group than in the HA group. Overall, the topical rebamipide ophthalmic solution showed more favorable therapeutic effects when compared to the HA ophthalmic solution in a mouse model of EDES, likely owing to its anti-inflammatory and neuroprotective effects.

The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses.

OBJECTIVE: To compare the efficacy and duration of effect of three local anesthetics on corneal sensitivity when administered subconjunctivally in horses. ANIMALS STUDIED: Eight healthy adult horses. PROCEDURE: A randomized, masked, crossover study design was used, with a two-week washout period between trials. The subconjunctival space of the randomly selected eye was injected with 0.2 mLs of bupivacaine (0.5%), lidocaine (2%), mepivacaine (2%), or saline. All horses received each medication once. The contralateral eye served as a control. The corneal touch threshold (CTT) was measured in both eyes with a Cochet-Bonnet esthesiometer prior to sedation with xylazine, after sedation, and at 10-min intervals after subconjunctival injection until corneal sensitivity returned to baseline. The total time of decreased CTT and the maximum decrease in CTT were compared for each medication using a general linear mixed model (P < 0.05). RESULTS: Total time of decreased CTT was 105.0 min for bupivacaine, 103.8 min for lidocaine, 138.8 min for mepivacaine, and 7.5 min for saline. All local anesthetics decreased CTT longer than saline (P < 0.001) and mepivacaine decreased CTT longer than lidocaine (P = 0.04). The mean minimum CTT was 1.67 cm for bupivacaine, 1.42 cm for lidocaine, and 0.73 cm for mepivacaine, which were all significantly less (P < 0.001) than saline (4.73 cm). No evidence of corneal toxicity was noted with any treatment. CONCLUSION: Subconjunctival injections of lidocaine, bupivacaine, and mepivacaine effectively and safely reduce corneal sensitivity in eyes of healthy horses for 1.5-2 h, and may be useful for providing perioperative analgesia for equine corneal procedures.

Corneal sensitivity and tear production in 108 horses with ocular disease.

PURPOSE: To compare corneal sensitivity and tear production in horses with keratitis to horses with other ocular disease. METHOD: Retrospective medical record review was used to identify equine patients presented during a 1-year period for an ocular complaint who had Schirmer Tear Test (STT) or Corneal Touch Threshold (CTT) measured. Variables studied included patient age and sex; affected eye; category of presenting ocular complaint (keratitis vs. other ocular complaint); STT; and CTT. Patients with a complaint of ulcerative keratitis, immune-mediated keratitis, and stromal abscess were categorized in the keratitis group. Patients with a complaint of uveitis, as well as lid, lens, or retinal disease, were categorized in the group having other ocular disease. For patients presenting more than once in 2013, only the first visit at which STT or CTT was measured was included. For patients with bilateral disease, STT and CTT of both eyes were averaged. RESULTS: A total of 108 patients were included, 45 with keratitis and 63 with other ocular disease. Average age was 13.65 years, with more males (77) than females (31). Adjusted for age, STT in affected eyes did not differ significantly between the two groups (keratitis = 29.92 mm/min; other ocular disease = 27.96 mm/min), but CTT was significantly lower in patients with keratitis (33.78 mm) than in patients with other ocular disease (40.10 mm). CONCLUSIONS: Corneal sensitivity may be decreased in patients with keratitis. It is not known whether this is a cause or an effect of corneal disease.

Reduced Corneal Innervation in the CD25 Null Model of Sjögren Syndrome.

Decreased corneal innervation is frequent in patients with Sjögren Syndrome (SS). To investigate the density and morphology of the intraepithelial corneal nerves (ICNs), corneal sensitivity, epithelial cell proliferation, and changes in mRNA expression of genes that are involved in autophagy and axon targeting and extension were assessed using the IL-2 receptor alpha chain (CD25 null) model of SS. ICN density and thickness in male and female wt and CD25 null corneas were assessed at 4, 6, 8, and 10/11 wk of age. Cell proliferation was assessed using ki67. Mechanical corneal sensitivity was measured. Quantitative PCR was performed to quantify expression of beclin 1, LC3, Lamp-1, Lamp-2, CXCL-1, BDNF, NTN1, DCC, Unc5b1, Efna4, Efna5, Rgma, and p21 in corneal epithelial mRNA. A significant reduction in corneal axon density and mechanical sensitivity were observed, which negatively correlate with epithelial cell proliferation. CD25 null mice have increased expression of genes regulating autophagy (beclin-1, LC3, LAMP-1, LAMP-2, CXCL1, and BDNF) and no change was observed in genes that were related to axonal targeting and extension. Decreased anatomic corneal innervation in the CD25 null SS model is accompanied by reduced corneal sensitivity, increased corneal epithelial cell proliferation, and increased expression of genes regulating phagocytosis and autophagy.