Associations between Corneal Nerve Structure and Function in a Veteran Population.

Background: We evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in this study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5; Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS; Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). The individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and the Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only the corneal fractal dimension remained significantly related to tear production (ß = -0.26, p = 0.02) and only the corneal nerve fiber area remained significantly related to corneal sensation (ß = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This suggests that using corneal nerve anatomy alone may be insufficient for predicting corneal function.

Efficacy of hydroxypropyl-guar drops in improving tear film index and ocular surface dynamics using two treatment methods under a controlled desiccating environment.

AIM: This study aimed to assess the efficacy of hp-guar eye drops on tear film index and ocular surface dynamics under desiccating conditions using protection and relief treatment modalities. METHODOLOGY: The 12 normal, non-dry eye participants were subjected to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C. The participants were screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST), tear production using the Ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and Schirmer strips. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296 mOsm/L at 40% RH to 285 mOsm/L at 5% RH (p = 0.01). Conflicting responses were seen for osmolarity in protection and relief. Mean tear osmolarity was significantly higher in the protection method in comparison to the relief method (p = 0.005). The mean TFI increased from 557 at 40% to 854 at 5% (p = 0.02). A significant increase in TFI was observed in the relief method in comparison with both 40% (p = 0.001) and 5% (p = 0.04). In the relief method, the mean TFI score went up to 1139 when hp-guar was installed. A significant improvement in ocular comfort was experienced in both the protection (p = 0.041) and relief (p = 0.010) methods at 5% RH. The instillation of hp-guar drops in the relief method resulted in a significant reduction in OST. The mean OST dropped to 33.01 ºC, significantly lower than the recorded OST for both normal (p = 0.040) and dry (p = 0.014) environmental conditions. CONCLUSION: Hp-guar drops significantly improve tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, an improvement in tear production and a decrease in ocular surface temperature were seen. Hp-guar performance could be maximized for the management of exposure to adverse environments by using a treatment protocol that targets the most affected parameters in each group of patients. Using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Evaluation of therapeutic efficacy of Emustil drops for ocular discomfort and tear film osmolarity using different treatment management modes under dry environmental conditions.

BACKGROUND: We aimed to check the efficacy of Emustil (oil in water emulsion) drops on tear film index and ocular surface dynamics in dry environments through protection and relief treatment modalities. METHODS: The subjects were exposed to a dry environment using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the temperature was 21 °C and screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST) and tear production using ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620 and Schirmer strips/phenol red test respectively. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296.8 mOsm/l at 40% RH to 291 mOsm/l at 5%. (p = 0.01). Instillation of Emustil resulted in a significant increase in tear osmolarity in the relief method compared with osmolarity seen at 5% RH when no drop was used. The mean PRT value decreased from 26 ± 9 in normal conditions (40% RH) to 22 ± 4 mm in dry conditions (5% RH). Emustil drops did not induce any significant change in tear production in the PRT test. No significant change was found in OST following exposure to 5% RH. OST did not show a statistically significant change with the emulsion when used for relief (p > 0.05). The mean score of ocular discomfort observed was 70 at 5% RH. Still, the instillation of the oil-in-water emulsion (Emustil) resulted in a noticeable decrease in visual discomfort to 37 (p = 0.00) in protection and 59 in relief (p = 0.05). Emustil drops substantially improved tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, tear production was improved. CONCLUSION: CEC allows for a thorough evaluation of tear film parameters and dry eye treatment protocols in labs, providing greater confidence when applying them to patients. In addition, our study showed that Emustil not only provides protection and relief for dry eyes but also helps to maintain ocular homeostasis in desiccating environments. This indicates a promising potential for improving dry eye treatment protocols.

Measurement of Tear Production and Intraocular Pressure in Clinically Conscious Normal Captive Red Deer (Cervus elaphus).

Normal values of tear production (STT) and intraocular pressure (IOP) have not been reported in conscious red deer to date. The objective was to determine the normal range of STT and IOP in clinically healthy, conscious red deer (Cervus elaphus) by utilizing a chute restraint. A total of 60 red deer were examined in this study. Both eyes of all red deer underwent a complete ophthalmic examination, including evaluation of tear production with the Schirmer tear test (STT) and assessment of intraocular pressure (IOP) with rebound tonometry, employing the TonoVet® device. The mean ± standard deviation of STT values were 18.35 ± 4.54 mm/30 s in the right eye and 17.87 ± 4.12 mm/30 s in the left; for both eyes, 18.11 ± 4.33 mm/30 s, with a reference range of 17.33-18.89 mm/30 s. IOP was as follows: 26.96 ± 4.42 mmHg in the right eye and 26.67 ± 3.80 mmHg in the left; for both eyes, it was 26.81 ± 4.11 mmHg, with a reference range of 26.07-27.55 mm/30 s. No statistically significant differences were observed between the IOP and STT values of the right and left eyes. This study provides a reference range for the STT and IOP in healthy red deer, showing that STT determination of tear production, and rebound tonometry to evaluate the IOP methods, are practical methods for ophthalmic examination in deer.

A Phase 2 Trial to Test Safety and Efficacy of ST-100, a Unique Collagen Mimetic Peptide Ophthalmic Solution for Dry Eye Disease.

Objective: Dry eye disease (DED) is a worldwide source of ocular discomfort. This first-in-human phase 2 clinical study determined the efficacy of treating signs and symptoms of DED using an ophthalmic solution of synthesized mimetic of human collagen (ST-100). Design: This double-masked, randomized, study compared high (60 µg/mL) and low (22 µg/mL) dose ST-100 to vehicle utilizing the Ora, Inc. Controlled Adverse Environment (CAE) during a 28-day period. Participants: Participants included males and females ≥ 18 years of age with signs and symptoms of DED for ≥ 6 months that worsened during CAE exposure who were not taking any topical prescription therapeutic. Intervention: Participants applied ST-100 or vehicle placebo topically to both corneas (1 drop) twice daily via a blow-fill-sealed preservative-free container. Main Outcome Measures: The prespecified primary efficacy sign end point was mean change from baseline (CFB) in total corneal fluorescein staining, and the primary symptom end point was mean CFB in ocular discomfort. A secondary prespecified efficacy end point was CFB in unanesthetized Schirmer's test for tear film production. Results: Of 160 subjects in the intent-to-treat population (112 female, 48 male, median age 64), 146 completed the study. Total corneal fluorescein staining CFB improved for high-dose ST-100, with superiority over vehicle when both eyes were considered together (2-sample t test: P = 0.0394). High-dose ST-100 was superior to vehicle in Schirmer's CFB for the study eye (least squares mean difference [confidence interval] = 2.3 [0.6, 4.0], P = 0.0094). For study eyes, the proportion of Schirmer's test responders (CFB ≥ 10 mm, Schirmer's responder rate) was 12.2% for high-dose ST-100 versus 0.0% for vehicle (P = 0.0266). The CFB for ocular discomfort score improved in study eyes for high- and low-dose ST-100 (paired t test, P = 0.0133, P = 0.0151, respectively) but without superiority over vehicle (ANCOVA: P = 0.5696, P = 0.8968, respectively). ST-100 Schirmer's responders also demonstrated total elimination of worsening of corneal fluorescein stain during the stress of CAE sessions. Conclusions: ST-100 significantly improved tear production and related outcomes in DED and was well-tolerated in reducing symptoms. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of intranasal and intramuscular administration of butorphanol and zolazepam-tiletamine combination on intraocular pressure and tear secretion in New Zealand White rabbits.

This study aimed to compare the effect of intranasal (IN) and intramuscular (IM) administration of butorphanol and zolazepam-tiletamine (ZT) combination on intraocular pressure (IOP) and tear secretion (TS) in rabbits. Fourteen healthy male New Zealand White rabbits weighing 3.05 ± 0.72 kg, aged between 1 and 2 years old, were included in the study. Animals randomly received 0.5 mg/kg butorphanol and 15 mg/kg ZT combination either with IN or IM administration. IOP and TS were measured at baseline (T0), and followed by 5, 15, 30, 45, and 60 min after drug administration. The sedation variables, the time to onset of sedation, duration of sedation, and sedation scores were also recorded. The route of administration for the butorphanol and ZT combination had no significant effect on the mean IOP (p = .301) and TS (p = .445). Furthermore, there were no significant changes observed in the IOP (p = .472) and TS (p = .348) over time. The time to onset of sedation was earlier in the IN group (4.57 ± 0.79 min) than in the IM group (5.86 ± 0.9 min; p = .0004). The duration of sedation was significantly longer for IM (57.43 ± 3.41 min) compared with IN (45.0 ± 1.91 min; p < .0001). No significant difference in the sedation score was observed between groups at all time points. In conclusion, both IN and IM administration of the butorphanol and ZT combination in rabbits had similar effects on IOP and TS.

Determination of reference values for tear production and intraocular pressure in Pygoscelis penguins of the Antarctic Peninsula.

BACKGROUND: According to the literature review, this is the first study investigating tear production (TP) and intraocular pressure (IOP) in the Pygoscelis penguins living in their natural habitat. The study aimed to establish normal values for standard ocular tests in the genus Pygoscelis, namely, the Adélie (Pygoscelis adeliae), gentoo (Pygoscelis papua), and chinstrap (Pygoscelis antarctica) penguins, in four different islands of Antarctica. Sampling was made by specifically using the left eye of the penguins. The Schirmer's tear test type I (STT-I) and the Tonovet® (rebound tonometer) were used to measure the TP and the IOP, respectively. RESULTS: The mean TP and IOP values of 129 Adélie, chinstrap, gentoo, and 120 adult Adélie, gentoo penguins were determined as 10.2 ± 4.0 mm/min and 38.9 ± 13.2 mmHg, respectively. No statistical difference was detected between the penguin species for the mean IOP values, while the difference was determined in all the locations. However, statistical differences in the mean TP values were determined between all locations. CONCLUSION: The results of this study provide a reference range of Schirmer's tear test (STT) and IOP values in Pygoscelis penguins and show that the IOP is significantly affected by locations. This result can be attributed to the harsh climatic conditions of the Antarctic Peninsula that change very quickly. The described data may help diagnose clinical pathological findings in Pygoscelis penguins. The STT and rebound tonometry appears to be safe and reproducible methods in Pygoscelis penguins, as the results were obtained quickly and were well tolerated by the birds. Based on our results, we propose that similar studies can be initiated in crowded colonies of three penguin species of this genus on the Antarctic Peninsula, the southern Shetland Islands, and other frequently visited islands in Antarctica.

Dry eye syndrome model established in rabbits via mitomycin C injection in the lacrimal gland.

PURPOSE: To develop a new dry eye syndrome (DES) animal model by injecting mitomycin C (MMC) into the lacrimal glands (LGs) of rabbits evaluated by clinical examinations. MATERIALS AND METHODS: A volume of 0.1 mL of MMC solution was injected in the LG and the infraorbital lobe of the accessory LG of rabbits for DES induction. Twenty male rabbits were separated into three groups, the control group, and different concentration of MMC, (MMC 0.25: 0.25 mg/mL or MMC 0.50: 0.5 mg/mL) were tested. Both MMC-treated groups received MMC twice injection on day 0 and day 7. Assessment of DES included changes in tear production (Schirmer's test), fluorescein staining pattern, conjunctival impression cytology, and corneal histological examination. RESULTS: After MMC injection, no obvious changes in the rabbit's eyes were noted by slit-lamp examination. Both the MMC 0.25 and the MMC 0.5 groups revealed decreased tear secretion after injection, and the MMC 0.25 group showed a continuous decrease in tear secretion up to 14 days. Fluorescent staining showed punctate keratopathy in both MMC-treated groups. In addition, both MMC-treated groups demonstrated decreased numbers of conjunctival goblet cells after injection. CONCLUSION: This model induced decreased tear production, punctate keratopathy, and decreased numbers of goblet cells, which are consistent with the current understanding of DES. Therefore, injecting MMC (0.25 mg/mL) into the LGs is an easy and reliable method to establish a rabbit DES model which can apply in new drug screening.

Enzyme histochemical characterization of orbital glands in fetuses of Indian buffalo (Bubalus bubalis).

Background: The orbital glands, viz. lacrimal gland, superficial and deep gland of third eyelid (LG, SGT and HG), are important for normal eye functions. These glands have different functions in various animals. The information about the enzyme histochemical nature of prenatal orbital glands in Indian buffalo seems to be unavailable. Therefore, the study was planned on orbital glands of six full term recently died fetuses from animals with dystocia. Methods: The frozen sections of all these glands were subjected to standard localization protocols for Alkaline Phosphatase (AKPase), Glucose 6 phosphatase (G-6-Pase), Lactate dehydrogenase (LDH), Succinate dehydrogenase (SDH), Glucose 6 phosphate dehydrogenase (G-6-PD), Nicotinamide Adenine Dinucleotide Hydrogen Diaphorase (NADHD), Nicotinamide Adenine Dinucleotide Phosphate Hydrogen diaphorase (NADPHD), Dihydroxy phenylalanine oxidase (DOPA-O), Tyrosinase, non-specific esterase (NSE) and Carbonic anhydrase (CAse). Results: The results revealed a mixed spectrum of reaction for the above enzymes in LG, SGT and HG which ranged from moderate (for LDH in SGT) to intense (for most of the enzymes in all three glands). However, DOPA-O, Tyrosinase and CAse did not show any reaction. From the present study, it can be postulated that the orbital glands of fetus have a high activity of metabolism as it has many developmental and functional activities which were mediated with the higher activity of the enzymes involved.

The development of the normal Schirmer tear test results during the dog's first year of life.

OBJECTIVE: To evaluate the relationship between lacrimation and age in a homogeneous group of healthy beagle dogs during the first year of life. MATERIALS AND METHODS: Schirmer tear test I (STT I) was performed at an interval of 12-15 days in both eyes of 16 clinically healthy beagle dogs (eight males and eight females) from 94 to 361 days of age. Three different quadratic polynomial regression equations were estimated for the variation in lacrimation: (1) for the entire period (19 observations), (2) for observations 1-4 (days 94-136), and (3) for observations 5-19 (days 150-361). RESULTS: By fitting quadratic regression equations to different phases of tear production during the dog's first year of life, it was possible to see that with each day of life, lacrimation increased 0.08 times (8%). From days 94 to 136, however, lacrimal production fell 1.1 times with each day of life. From day 150 to 361, production increased by 0.02 (2%) each day of life. In addition, there was a positive significant and moderate linear correlation between body weight and STT I values (p = .01). CONCLUSION: In dogs, during the first year of life, STT I data distribution is parabolic in shape. Age significantly affected tear production. STT I decreased at approximately 108-121 days of age and increased thereafter. Body weight was a significant factor for STT I in young dogs. The establishment of this normal pattern of lacrimation is important for both clinical practitioners and laboratory studies.

Diagnostic Tests Used During the Ocular Examination.

This article provides a review of the required ocular tests during the ophthalmologic examinations of canine and feline patients. Knowledge of medications affecting ocular parameters and awareness of available instrumentation and test materials is essential for accurate diagnoses.

An eye on the Shih Tzu dog: Ophthalmic examination findings and ocular surface diagnostics.

OBJECTIVE: To characterize the ocular surface parameters and determine the prevalence of ocular pathology in Shih Tzu dogs. ANIMAL STUDIED: Fifty Shih Tzu dogs (28 male, 22 female). PROCEDURES: Each dog underwent a complete ophthalmic examination (recording any pathology) and a series of diagnostics, allowing for a 10 min-interval between tests: intraocular pressure (IOP), blink rate, palpebral fissure length (PFL), corneal tactile sensation (CTS), Schirmer tear test and nasolacrimal reflex without (STT-1, NL-STT1) and with topical anesthesia (STT-2, NL-STT2), tear ferning, strip meniscometry test (SMT), tear film breakup time (TFBUT), and punctate fluorescein staining (PFS) of the cornea. RESULTS: Mean ± SD test values were as follows: IOP (17.9 ± 3.7 mmHg), blink rate (2.4 ± 1.4 blinks/min), PFL (23.8 ± 1.8 mm), CTS (1.8 ± 0.7 cm), STT-1 (22.0 ± 5.5 mm/min), NL-STT1 (24.2 ± 4.7 mm/min), STT-2 (16.9 ± 6.5 mm/min), NL-STT2 (18.5 ± 7.5 mm/min), SMT (7.5 ± 3.5 mm/5 s), TFBUT (5.3 ± 2.4 s), tear ferning (1.3 ± 0.7), and PFS (1.6 ± 0.6). PFL was significantly greater in male vs. female Shih Tzus (p< .001). Age was negatively correlated with TFBUT results (r = -0.31, p = .027). Lagophthalmos was observed in 82% eyes. Ocular surface pathology was common, including adnexal abnormalities (100% eyes with caruncular trichiasis and medial lower lid entropion) and corneal opacification (27% pigmentation, 20% fibrosis, 12% neovascularization). CONCLUSIONS: Qualitative tear film deficiency (low TFBUT), along with several anatomical abnormalities that promote ocular irritation and reduce globe protection, together help explain the concerningly high prevalence of ocular surface disease in the Shih Tzu breed. Prophylactic measures (e.g., medial canthoplasty, topical lubrication) could be considered to improve ocular health in Shih Tzus.

Ocular surface physiology and aqueous tear secretion in cats of diverse cephalic conformations.

OBJECTIVE: To describe normative ocular surface and aqueous tear testing data for cats of various cephalic conformation. ANIMALS STUDIED: Fifty-three healthy adult cats (11 British Shorthair, 11 Burmese, 10 Devon Rex, 10 Scottish Fold, and 11 Sphynx). PROCEDURES: Blink rate, corneal tactile sensation (CTS), and Schirmer tear test with or without topical anesthesia (STT-1, STT-2) and with nasolacrimal stimulation (NL-STT1, NL-STT2) were assessed. Palpebral fissure length (PFL) and skull morphology were measured, and cephalic index (CI) and craniofacial ratio (CFR) calculated. RESULTS: Mean ± SD test results were as follows: blink rate (5.0 ± 2.3 blinks/min), CTS (3.2 ± 0.7 cm), STT-1 (11.2 ± 4.3 mm/min), STT-2 (6.7 ± 3.6 mm/min), NL-STT1 (13.4 ± 5.7 mm/min), NL-STT2 (13.5 ± 5.2 mm/min), and PFL (2.0 ± 0.2 cm). Corneal sensitivity did not differ significantly among breeds (p = .152) but was negatively correlated with body weight (r = -.32, p = .019). STT-1 significantly differed among breeds (p < .001) and was lowest in Sphynx cats (8.7 ± 4.3 mm/min). A positive correlation was detected between STT-1 values at 30 and 60 s (r = .98; p < .001). The nasolacrimal reflex significantly increased STT in anesthetized and unanesthetized eyes (approximately +100% and +20%, respectively; p ≤ .002). STT-1 tended to be higher in intact versus neutered cats (p = .062). Age did not impact any test result (p ≥ .085). CONCLUSIONS: Normative data described here serve as a baseline for future studies assessing ocular surface disease in multiple feline breeds. Unlike dogs, brachycephalic cats did not have lower CTS or STT-1 than non-brachycephalic cats.

Clinical ophthalmic parameters of the Quaker parrot (Myiopsitta monachus).

PURPOSE: Ophthalmic diagnosis in many avian species remains hindered by a lack of normative values. This study aimed to establish normal ophthalmic parameters for select diagnostic tests in clinically normal Quaker parrots. METHODS: Ninety-six captive Quaker parrots aged 8-18 years underwent ophthalmic examination to include assessment of neuro-ophthalmic reflexes, phenol red thread test, rebound tonometry, fluorescein staining, palpebral fissure length measurements, slit lamp biomicroscopy, indirect ophthalmoscopy, and ocular ultrasound biometry. RESULTS: Menace response, dazzle reflex, and direct pupillary light reflex were present for all Quaker parrots. Tear production (mean ± SD) was 13.3 ± 4.0 mm/15 s and intraocular pressure (IOP, mean ± SD) was 10.6 ± 1.4 and 6.0 ± 1.3 mmHg in the D and P rebound tonometer calibration settings, respectively. For IOP measurement, D and P calibration settings were not interchangeable, with the lesser variation of the D setting preferred in the absence of a gold standard. Ultrasound measurement of the anterior chamber depth increased with age and males had longer axial globe and vitreous lengths. Incidental adnexal and ocular lesions, identified in 36/96 (37.5%) of Quaker parrots, did not statistically affect the created reference data. CONCLUSIONS: This work provides reference values and clinical findings to assist with monitoring the health of wild populations and maintaining the health of captive Quaker parrots.

Lacrimal Gland Histopathology and Secretory Function in Sjögren's Syndrome Mice Model Treated with Moringa oleifera Lam. Leaf Extract.

BACKGROUND: The pathogenesis of Sjögren's syndrome involves the activation of NF- κB, producing proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1α, IL- 1ß, IL-6, IL-17, and interferon-γ. Through oxidative stress, they will cause necrosis and apoptosis of lacrimal gland cells, resulting in impaired secretory function or reduced tear production. Moringa oleifera leaf extract is known to have strong anti-inflammatory and antioxidant activities. OBJECTIVE: To determine the effect of Moringa oleifera leaf extract on lacrimal gland histopathology and secretory function in Sjögren's syndrome mice model. METHODS: The experimental study had a post-test only control group design with 32 eight-week-old male mice of the BALB/c strain divided into four groups, negative control (C-), which was not induced by SS, positive control (C+), treatment 1 (T1), and treatment 2 (T2) induced by Sjögren's syndrome by immunizing with the 60-kD Ro antigen (SSA) as much as 100 µg. After 42 days, the T1 group was given dexamethasone 1.23 mg/kg BW/day orally for 14 days, whereas T2 was given dexamethasone 1.23 mg/kg BW/day and Moringa oleifera leaf ethanol extract 200 mg/kg BW/day orally for 14 days. At the end of the study, lacrimal gland histopathology and secretory function (tear production) were examined. Statistical analysis using F ANOVA/Kruskal-Wallis was followed by partial difference test with the Least Significant Difference post hoc test/Mann-Whitney. Significant if p < 0.05. RESULTS: The comparison of lacrimal gland histopathology in T1 (p = 0.044) and T2 groups (p = 0.020) obtained significant results (p < 0.05) when compared to C+. However, the comparison of tear production in T1 (p = 0.127) and T2 groups (p = 0.206) was not significant (p > 0.05) when compared to the C+ group. CONCLUSION: The administration of Moringa oleifera leaf extract 200 mg/kg BW for 14 days could significantly improve lacrimal gland histopathology but was not effective in increasing tear production in Sjögren's syndrome mice model.

A Comparison of the Intrarectal and Intramuscular Effects of a Dexmedetomidine, Ketamine and Midazolam Mixture on Tear Production in Cats: A Randomized Controlled Trial.

Cats are often easily stressed and uncooperative. The use of sedative agents in the feline species is widely used to perform even minor clinical and diagnostic procedures. The aim of this study is to assess the impact on tear film production of the intrarectal route (IR) administration of a mixture of dexmedetomidine, ketamine and midazolam in comparison with the intramuscular (IM) one. A group of twenty cats were involved in a randomized and blinded clinical trial. A clinical and ophthalmological examination was conducted on the cats. The IR group received dexmedetomidine 0.003 mg kg-1, ketamine 4 mg kg-1 and midazolam 0.4 mg kg-1; the IM group received dexmedetomidine 0.003 mg kg-1, ketamine 2 mg kg-1 and midazolam 0.2 mg kg-1. A Shirmer tear test I (STT- I) was conducted 1 h before sedation and 2', 10', 20', 30', 40', and 80' post drug administration. The reaction to STT-I administration was also evaluated. The IM group has a lower mean tear production than the IR group for all time points evaluated. Cats in the IM group showed less reaction to STT-I administration. This study may suggest that the effect of sedative agents administered by the IR route has a lower incidence on tear production than the IM one. The use of eye lubricant is recommended in any case.

OC-01 (Varenicline Solution) Nasal Spray Demonstrates Consistency of Effect Regardless of Age, Race, Ethnicity, and Artificial Tear Use.

Purpose: To evaluate OC-01 [varenicline solution nasal spray (VNS)] tear production and symptom outcomes in patients with dry eye disease by age, gender, race, ethnicity, and artificial tear use status. Patients and Methods: Adults ≥22 years of age diagnosed with dry eye disease, with Ocular Surface Disease Index score ≥23, corneal fluorescein staining score ≥2 in ≥1 region or ≥4 for all regions, and baseline Schirmer Test Score (STS) ≤10 mm, with no restrictions on eye dryness score (EDS). Efficacy was assessed using integrated data from ONSET-1 and ONSET-2 [vehicle control (VC), n=294; OC-01 VNS 0.03 mg, n=308]. Subgroups included age (≤55, 56-65, >65 years), gender (male, female), race (White, Black or African American), ethnicity (Hispanic or Latino, Not Hispanic or Latino), and artificial tear use (yes, no). Analysis of covariance models, with the covariates treatment, study site, and baseline severity measures, were used to calculate treatment-VC differences. Consistency of effect among subgroups was evaluated by conducting interaction tests. Results: Consistency of treatment effect across subgroups was observed for all endpoints, with P value for all treatment-subgroup interaction terms >0.05. For % of patients with ≥10mm improvement in STS and least squares (LS) mean change from baseline in STS and EDS, there was improvement in tear production across demographic group categories. Artificial tear use did not change STS or EDS outcomes with OC-01 VNS. Conclusion: OC-01 VNS improved tear production and patient-reported symptom outcomes across a broad range of patients by age, gender, race, and ethnicity, and regardless of artificial tear use status at baseline. OC-01 VNS demonstrated a consistent benefit across an extensive range of patients with dry eye disease.

Influence of anaesthetics on aqueous tear production in dogs: a systematic review.

OBJECTIVE: The aim of this systematic review is to summarize outcomes of studies focused on the effects of opioids, injectable sedative and anaesthetic drugs and inhalant anaesthetics on tear production in dogs. This manuscript complements the systematic review describing the effect of anaesthetics on intraocular pressure in dogs (Pierce-Tomlin et al. 2020). Databases used A detailed search of scientific references has been performed. PubMed, Web of Science, Science Direct and Google Scholar databases were used to search for sources using free text terms 'Dog' or 'Canine', 'Anaesthesia' or 'Anaesthetic' or 'Sedative' or 'Opioid' or the name of used opioids, sedative and anaesthetic drugs and 'Tear' or 'Schirmer' or 'Lacrimation'. The time frame searched was from 1960 to October 2021. Any published manuscripts that were concerned with sedative or anaesthetic drugs administered systemically in the dog and tear production were evaluated. CONCLUSIONS: Low doses of α2-adrenoceptor agonists, neuroleptics, benzodiazepines, opioids, propofol or alfaxalone administered alone have no clinically significant effect on aqueous tear production in healthy dogs measured by the Schirmer tear test I (STT-I). Intramuscular injection of ketamine increases STT-I values. Higher doses of α2-adrenoceptor agonists and combinations of anaesthetics, including inhaled anaesthetics, always clinically significantly decrease tear production.

A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1).

PURPOSE: Dry eye disease (DED) symptoms can negatively impact quality of life (QoL). AR-15512, a transient receptor potential melastatin 8 (TRPM8) agonist, was evaluated as a potential therapy for DED. METHODS: In a Phase 2b study, patients with DED were randomized 1:1:1 to 0.0014% AR-15512, 0.003% AR-15512, or vehicle twice daily for 12 weeks. Eligibility criteria included DED signs and symptoms of prespecified severity levels. Outcomes assessed were DED signs (Schirmer score ± anesthetic, ocular surface staining, hyperemia), symptoms (Ocular Discomfort [ODS-VAS], Symptoms Assessment iN Dry Eye [SANDE], Eye Dryness-VAS, Ocular Pain-VAS), QoL-VAS, and adverse events. Co-primary endpoints were changes from baseline in ODS-VAS and anesthetized Schirmer score at Day 28. RESULTS: 0.003% AR-15512 (n = 122) was associated with early and sustained improvements in unanesthetized Schirmer score (Days 1 and 14, p < 0.0001), as well as improvements in ocular surface staining (Days 14 and 84, p ≤ 0.0365) and hyperemia (Day 84, p < 0.0215). Statistically significant improvements in symptoms were observed for the 0.003% concentration on SANDE (Days 14, 28, and 84, p ≤ 0.0254), ODS-VAS (Day 84, p = 0.0281), Eye Dryness-VAS (Day 84, p = 0.0302), and multiple QoL measures (Days 14, 28, and 84, p < 0.05). There were no significant differences between active and vehicle groups for the co-primary endpoints. The most common adverse events were burning and stinging upon instillation. CONCLUSIONS: Although predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related QoL.

Effect of light intensity on the tear production, central corneal thickness, and intraocular pressure in broiler chickens.

OBJECTIVE: The objective of the present study was to examine the effect of different light intensities on tear production, corneal thickness, and intraocular pressure in broilers. ANIMALS STUDIED: Both eyes of 72 male broilers were evaluated in this study. MATERIALS AND METHODS: Broilers were divided into the following three groups: low light intensity (n = 24, 5 lux), moderate light intensity (n = 24, 20 lux), and high light intensity (n = 24, 80 lux). The eyes of all birds (n = 72) underwent a complete ophthalmic examination, which included the Schirmer tear test (STT-I), intraocular pressure (IOP), and the central cornea thickness measurement (CCT). The effect of light intensity on the Schirmer test, intraocular pressure, and central corneal thickness values was examined at eye and animal level (right and left eyes separately and cumulatively/no distinguishing left or right) by using one-way ANOVA. RESULTS: At the animal level, without discrimination of left and right eye measurements, statistically significant differences were found between 5-20 and 20-80 lux groups on IOP measurements (p < .05). The difference in CCT measurements between the 5 and 20 lux groups was statistically significant (p < .05), and the corneal thickness of the 5 lux group animals was found to be statistically significant and higher than the 20 lux group (p < .05). CONCLUSIONS: In conclusion, light intensity has an influence on eye health in broilers. Present results may attribute to the future studies as a reference value for broilers raised under different light intensities.