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Background: The mainstay of dry eye treatment is artificial tear solutions. Contralateral eye comparison of 2 types of artificial tears (Xiloial versus Tearlose) in managing dry eye disease was sought in this study. Methods: This study was a prospective, interventional, contralateral eye comparison of 2 types of artificial tears used for managing dry eye disease. The study participants were categorized into mild (13–22 points), moderate (23–32 points), or severe (33–100 points) ocular surface disease according to the baseline ocular surface disease index (OSDI) questionnaire score. Schirmer I and tear film break-up time (TBUT) tests, as well as detailed slit-lamp examinations, were performed at baseline and at the end of the study. All participants received Xiloial monodose eye drops for the right eye and Tearlose eye drops for the left eye, administered as a single drop 4 times per day. Furthermore, they were instructed to perform lid hygiene every 12 hours per day for both eyes. Results: Thirty-five patients (70 eyes) with a mean ± standard (SD) age of 50.2 ± 13.4 years were included, and 14 (40%) were men. The mean ± SD of the OSDI score was 44.24 ± 22.59 at baseline. Of the 35 patients, 10 (28.6%), 5 (14.3%), and 20 (57.1%) had mild, moderate, and severe ocular surface disease, respectively, according to the baseline OSDI score. Compared to baseline, the mean values of both TBUT and Schirmer I tests improved significantly in both groups (both P < 0.001). In comparing the final mean values between the 2 groups, this improvement was comparable for the Schirmer I test (P = 0.179), but TBUT in Tearlose-instilled eyes improved significantly more than in the fellow eyes (P < 0.001). Conclusions: Both Xiloial and Tearlose eye drops improved tear stability and tear production after a 2 week treatment period in eyes with dry eye disease. This improvement was comparable for tear production, but Tearlose-instilled eyes showed significantly greater improvement in tear stability. Further studies with longer follow-up and larger sample sizes could provide more reliable results as a basis for the clinical use of this TSP-containing lubricant eye drop solution in dry eye disease.

Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far—from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED.

The aim of this study was to evaluate repeatability, reproducibility, and agreement of three commonly used tonometers in animal research (TonoLab, TonoVet, and TonoPEN AVIA) in a cohort of 24 rabbits. Additionally, the impact of sedation on IOP was investigated in 21 New Zealand White rabbits with the TonoVet tonometer. Repeatability was determined using the coefficient of variation (CoV) for two observers. For the TonoLab (6.55%) and TonoVet (6.38%) the CoV was lower than for the TonoPEN AVIA (10.88%). The reproducibility was highest for the TonoVet (0.2 ± 3.3 mmHg), followed by the TonoLab (0 ± 12.89 mmHg) and lowest for the TonoPEN AVIA (− 1.48 ± 10.3 mmHg). The TonoLab and TonoVet showed the highest agreement (r = 0.85, R2 = 0.73). After sedation, a significant IOP reduction (often > 25%) was observed. Our results show that among the three tonometers tested, the TonoVet tonometer is best for use in rabbits while the TonoLab should be avoided. The impact of sedation on IOP was substantial and should be taken into account during experimentation.

Impaired tear production - a common sign of keratoconjunctivitis sicca (KCS) - is associated with qualitative or quantitative tear deficiency. OTX-101 0.09% is a novel, nanomicellar formulation of cyclosporine A approved in the US for increasing tear production in patients with KCS. We present a pooled analysis of the phase 2b/3 and phase 3 studies evaluating the effect of OTX-101 on tear production in a subgroup of patients with keratoconjunctivitis sicca with severely impaired tear production (Schirmer's score5 mm in either eye at baseline).In these randomized, double-masked studies, patients instilled 1 drop OTX-101 or vehicle per eye twice daily for 84 days. Pooled efficacy endpoints included percent (%) of patients with ≥10 mm change from baseline and mean change from baseline in Schirmer's score at day 84. Pooled safety endpoints included adverse event monitoring.Subgroup analyses included 133 and 113 patients receiving OTX-101 and vehicle, respectively. Mean baseline (BL) Schirmer's score ± standard deviation was 2.7 ± 1.2 for OTX-101 and 2.5 ± 1.1 mm for vehicle (OTX-101 administered twice daily for 84 days significantly improved tear production vs vehicle in patients with severely impaired tear production, as evidenced by significantly larger proportion of patients with ≥10 mm increases from baseline and higher mean change from baseline in Schirmer's scores.

Objectives Computer vision syndrome (CVS) is a group of various eye and vision-related problems from prolonged use of mobile devices. Symptoms include dry eyes, blurred vision, eye strain, headache, and also neck and shoulder pain. This study was carried out to analyze the correlation between the exposure time of High Energy Visible (HEV) from mobile devices’ use and the prevalence of evaporative dry eyes in young age. Methods An observational cross-sectional study was done using quota sampling method for 100 High School students. Data collection was performed using questionnaire to identify daily use of mobile devices (hours) and duration for using mobile devices (years). A classification was determined as mild, moderate, and heavy HEV exposure. Evaporative dry eyes were diagnosed using tear break-up time test (TBUT) of less than 10 s for both eyes. Results Ninety-four students participated in this study. A total of 82 students (87.2%) experienced evaporative dry eyes. There were 11 students (11.7%) who had dry eyes with mild exposure, 18 students (19.1%) had dry eyes with moderate exposure, and 53 students (56.4%) had dry eyes with heavy exposure. A chi square analysis showed all HEV exposures have similar risk to the prevalence of dry eyes among High School students (p Conclusions The risk of developing evaporative dry eyes, as one of the symptoms of CVS in young age with normal tear production, could be induced even with minimal exposure to mobile devices.

Liemienieva Anastasiia, Shargorodska Iryna, Rykov Sergiy, Petrovsky Mykola. Experimental Studies and the Search for New Innovative Approaches to Treat Dry Eye Disease. Journal of Education, Health and Sport. 2021;11(05): 294-302. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.05.031 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.05.031 https://zenodo.org/record/5338603 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 15.05.2021. Revised: 21.05.2021. Accepted: 28.05.2021. Experimental Studies and the Search for New Innovative Approaches to Treat Dry Eye Disease Anastasiia Liemienieva1, Iryna Shargorodska2, Sergiy Rykov2, Mykola Petrovsky3 1Kyiv City Clinical Ophthalmological Hospital “Eye Microsurgery Center”, Ukraine 2Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine 3Taras Shevchenko National University of Kyiv, Ukraine Anastasiia Liemienieva ORCID: 0000-0001-7312-1610 Iryna Shargorodska ORCID: 0000-0001-8958-1849 Sergiy Rykov ORCID: 0000-0002-3495-7471 Mykola Petrovsky ORCID: 0000-0003-3267-7123 Abstract Introduction and purpose. The main manifestation of eyelids, tear ducts, and orbits disorders is a dry eye disease considered as a serious disease that affects the quality of life. Nowadays, one in ten people worldwide faces this disease. Increased workload, development of multimedia technologies, hypodynamia, and environmental degradation are the main modern causes of the disease. Material and methods. In this work, we used an experimental model of dry eye in rats with the development of inflammation of the anterior surface of the eye. Alkali burns were used to develop inflammation. A fluorescein test performed immediately after alkaline erosion and on days 1, 5, and 10 after burns revealed a gradual increase in corneal epithelialization and vascularization. Results. One day after induction of inflammation, there was a dramatic and statistically significant increase in tear production in experimental rats. By the seventh day, tear production declined to the control level with a subsequent tendency to decrease tear production. Conclusions. In the group of rats with inflammation of the anterior surface of the eye that received polarized red-light therapy, there was no significant decrease in tear production on day 7, which may be indicative of a possible anti-inflammatory effect of light therapy under these conditions. Keywords: dry eye disease; inflammation of the anterior surface of the eye; fluorescein test; Schirmer test; polarized light; Bioptron-Pailer therapy.

Background A great number of sedatives and anaesthetics have been used to perform surgeries or routine ophthalmologic examinations in animals and sometimes the combination of these medicines has more suitable effects than each one alone. Objectives This paper aims to explore the main effects of Medetomidine + Acepromazine, Dexmedetomidine + Acepromazine on intraocular pressure, tear secretion and pupil diameter. Methods To accomplish the aforementioned aim, 32 adult dogs (aged one‐to‐three‐years‐old) were clinically examined. Dogs were divided into four groups consisting of group DA, Dexmedetomidine (5 µg/kg) + Acepromazine (0.05 mg/kg); Group D, Dexmedetomidine (5 µg/kg); Group M, Medetomidine (10 µg/kg); Group MA, Medetomidine (10 µg/kg) + Acepromazine (0.05 mg/kg). The ocular factors including tear production, pupil diameter and intraocular pressure of both right and left eyes were first measured and then recorded in each dog at time T0 (−15 min). Afterwards, the drugs were administered intramuscularly, based on which the ocular factors were re‐measured at T1 (+5 min), T2 (+15 min) and T3 (+20 min). All four groups showed a reduction in intraocular pressure, which was significant in DA, D and M groups. Results Furthermore, there was a fluctuation in the amount of tear secretion in DA and D groups (increase and then decrease), as well as a significant reduction in M and MA groups. Decreasing in pupil diameter also occurred in all four groups, but the reduction was significant only in DA and MA groups. Conclusion According to the results obtained, as the changes caused by the systemic administration of the above drug compounds did not exceed the physiological range, it can be concluded that these combinations could be utilized as suitable sedatives or pre‐anaesthetic compounds in the eye surgeries., This paper aims to explore the main effects of Medetomidine + Acepromazine, Dexmedetomidine + Acepromazine on intraocular pressure, tear secretion and pupil diameter.

Infrared (IR) thermographic assessment of ocular surface temperature (OST) is gaining interest as an adjuvant method to evaluate the ocular surface. It is a quick, non-invasive test that causes minimal, if any, discomfort to patients. The purpose of this article was to summarize research on how OST relates to tear film parameters and dry eye disease (DED). PubMed, Google Scholar, and Scopus searches for specific terms were carried out and eligible articles reviewed. OST of the central cornea is ~34-35°C when measured as a single time-point (typically right after a blink). Dynamically, OST values decrease over time at a rate of ~ −0.01 °C/s in healthy eyes. Single time-point OST values are impacted by temperature, with positive correlations noted with both ambient (1°C↓ results in ~0.16°C↓ in OST) and body (1°C↑ results in ~0.98°C↑ in OST) temperature. Single time-point OST values are also impacted by tear parameters, with negative correlations noted with tear break-up time (TBUT; r=−0.61) and positive correlations with lipid layer thickness (~r=0.50). Dynamically, the rate of OST cooling over the interblink period correlates with various tear parameters including Schirmer’s test scores (r=−0.39), tear meniscus height (r=−0.52) and the rate of tear film break-up (r=−0.74). These data imply that OST decreases more rapidly in individuals with greater tear production, larger tear volumes, and shorter tear break-up times (faster rates of tear film break-up). There are discrepancies in relationships between OST and DED across studies, which is not surprising given that DED encompasses a number of different phenotypic presentations. However, most studies found that OST decreases at a more rapid rate in DED vs. control groups. As such, cooling rate may have utility as a screening tool in DED in combination with established point-of-care tests.

Keratoconjunctivitis sicca, also known as dry eye (DE), is an extremely common and often unrecognized pathological entity. It is characterized by decreased tear production or increased evaporation and manifests with a wide spectrum of signs and symptoms. Due to multifactorial and elusive etiology, it is often a challenge to treat DE syndrome. Ocular surface disorders are also clinically very important to manage especially in terms of visual acuity. A comprehensive understanding of the pathophysiology and etiology of DE disease (DED) leads to more meticulous management and treatment of the pathological process. The present review article after detailed literature review aims to provide information on the definition, epidemiology, classification, causes, diagnostic tests, and medical and surgical management and futures trends of DED.

Purpose. To study the influence of personal protective equipment (PPE) of the respiratory and visual systems on the development and progression of dry eye syndrome (DES) and its relationship with other risk factors for medical workers.Patients and methods. The data of 243 people (male — 22.2 %, female — 77.8 %) were analyzed as part of a multi-center analytical scientific one-step study. Total tear production (Schirmer I test) was studied at the beginning and the end of the working day in persons used PPE of respiratory system (disposable medical face mask, gauze masks or different types of respirators), as well as PPE of the eyes (protective half-closed/closed glasses or protective screens). Risk factors for the development and progression of DES were registered (age, smoking, systemic hormones intake, soft contact lenses), as well as the use of artificial tears.Results. A decrease in the Schirmer I test score at the end of a 7–8 hour work shift was found by an average of 3 mm (from 13 (9; 16) mm to 10 (6; 15) mm, p < 0.001). Statistically significant changes were typical mainly for medical personnel (p < 0.001) with the maximum severity in persons working in outpatient sector. The presence of at least one DES risk factor was found in 30.5 % of patients, two factors — in 3.0 %, and three or more — in 7.0 %. There was no influence of risk factors on the degree of changes in total tear production. Reduced tear production is typical for some PPE of respiratory system (disposable masks and respirators) and the eye (screens and half-closed glasses) (p < 0.001). In people who do not use PPE of the eye, significant changes were detected only in the presence of risk factors.Conclusion. The negative influence of various PPE of the respiratory system and eye on the total tear production was established. The decrease in the results of the Schirmer I test by the end of the working day was 20–25 % of the basic level, regardless of the presence of traditional risk factors for DES. The severity of changes depended on the type of PPE used. The data obtained are particularly relevant during the new COVID-19 coronavirus pandemic and justify the need to establish specific prophylactic measures. One of the possible methods is the preventive use of artificial tears.

The purpose: to evaluate the effectiveness of the Delfanto® in the complex therapy of patients with dry eye syndrome of various etiologies and severity of the clinical course.Patients and methods. 114 patients (228 eyes) with dry eye syndrome of various etiologies were examined: 72 patients with chronic meibomian blepharitis and dysfunction of the meibomian glands (xerosis due to increased evaporation of the tear film), 33 women with perimenopause (a mixed form of xerosis with a predominant decrease in the production of components of the tear film) and 9 persons with Syegren syndrome (xerosis due to a pronounced decrease in tear production). All patients received individually selected tear replacement therapy over the past weeks and the drug was not replaced throughout the study. At the same time, patients with mild and moderate clinical course of SSG for 30 days received Delfanto® at a dosage of 60 mg, and with severe course — 120 mg per day.Results. All patients on the background of complex therapy showed a significant decrease in the severity of subjective manifestations of the dry eye syndrome, an increase in the of the tear film stability and indicators of tear production. At the same time, the dynamics of changes in these parameters of the course of the xerotic process increased as the therapy continued, reaching a maximum by the 30th day. The maximum effect of Delfanto® in the complex therapy of patients with dry eye syndrome was observed in patients with chronic meibomian blepharitis. Moreover, patients with a mild clinical course of cornealconjunctival xerosis were the most susceptible to the therapy.Conclusion. The effectiveness of the complex therapy for patients with dry eye syndrome can be significantly increased by prescribing Delfanto® in a daily dose of 60 mg for mild and moderate xerosis and 120 mg — for severe disease. Delfante® can be recommended for widespread clinical use in complex treatment of patients with various clinical and pathogenetic forms of dry eye syndrome.

Purpose . Development and analysis of effectiveness of predictive clinical-mathematical system of development of dry eye syndrome (DES) after phacoemulsification (PE) of senile cataract (SC). Material and methods . 120 patients (120 eyes) after SC surgery: 52 men and 68 women. Age: from 62 to 83 years (average 69.3±6.4 years). The main selection criteria for study were the absence of objective and subjective signs of DES, the presence of initial or immature SC and optimal conditions for surgery – absence of corneal pathology and mydriasis of 6 mm or more. Standard preoperative examination; 3 months after PE – Schirmer 1 test, tear break-up time, OCT mapping (Avanti RTVue XR, Optovue, USA). The above indicators were selected as potential predictors for development of algorithms for predicting of development of DES after PE of SC. Patients were divided into groups: 1st group consisted of 31 patients (31 eyes) with DES developed after PE, 2nd group consisted of 89 patients (89 eyes) without signs of DES. Results . Based on peculiarities of induced damage to structures of ocular surface in treatment of SC, two algorithms were developed to predict DES after FE of SC, which shown high prognostic characteristics: sensitivity – 80–90% and specificity – 80–87%, allowing to consider them reasonable and informative. Conclusion . The analysis of the developed clinical and mathematical system for predicting the development of DES after PE of SC showed its high efficiency. Application of developed technique in ophthalmic practice is advisable to ensure maximum medical and social rehabilitation of patients with SC.

BACKGROUND: Pseudoexfoliative material is being implicated in causing tear film abnormalities, and the aim of the present study was to prove it and to compare with the normal healthy participants. METHODS: A total of 398 eyes of 200 participants were studied, and two groups were formed. The first, pseudoexfoliation syndrome (PEXS) group, included 198 eyes of 100 patients, and the second, age-matched control group, included 200 eyes of 100 participants. Tear film abnormalities were compared in the two groups by tear meniscus height (TMH), Schirmer test I, Schirmer test II and tear film break-up time (TBUT). RESULTS: On comparing the two groups using independent t-test, a significant difference was found in Schirmer test I, Schirmer test II, and TBUT between the PEXS group (Schirmer test I: 23.98 ± 10.68 mm, Schirmer test II: 17.11 ± 8.78 mm, and TBUT: 9.778 ± 5.54 s) and the age-matched control group (Schirmer test I: 27.08 ± 9.58 mm, Schirmer test II: 19.98 ± 8.48 mm, and TBUT: 13.495 ± 5.65 s) (p = 0.003 [Schirmer test I]; p = 0.001 [Schirmer test II]; and p

Purpose To evaluate the optical quality and tear film quality in patients with dry eye syndrome (DES) before and after using an intranasal neurostimulation device to stimulate tear production. Methods Cross-sectional review of 33 eyes in 21 patients with DES who underwent optical quality and tear film analysis as part of their routine dry eye evaluation pre- and post-neurostimulation trial in office. Optical quality was assessed by measuring the objective scattering index (OSI) and modulation transfer function (MTF). The time to blink and mean tear film OSI were used to analyze the tear film. Results Optical quality after the use of the intranasal neurostimulator improved with an average decrease (improvement) in OSI of 0.30±0.68 (P=0.015) and an average increase (improvement) in MTF of 2.12±9.2 (P=0.15). Pre-intranasal neurostimulation OSI had a positive correlation with age (Spearman's rho 0.60, p < 0.001), while MTF had a negative correlation (Spearman's rho -0.38, p = 0.03). Pre-intranasal neurostimulation OSI had a negative correlation with MTF (Spearman's rho -0.85, p < 0.001) and a positive correlation with tear film mean OSI (Spearman's rho 0.85, p

Objective : to assess the effectiveness of tear substitutes in patients suffering from dry eye syndrome (DES). Material and methods . 100 patients with an established diagnosis of mild to moderate DES, averagely aged 42.0 ± 2.1, were divided into three groups: group 1 involving 33 patients (54 eyes, 13 men and 20 women) aged 42.7 ± 2.13 with mild DES, who were treated by low viscosity eye drops, group 2 involving 33 patients (56 eyes, 13 men and 20 women) aged 41.4 ± 2.07 with moderate DES, who were treated by moderate viscosity eye drops and group 3 involving 34 patients (52 eyes, 14 men and 20 women) aged 41.9 ± 2.1 with moderate DES, who were treated by high viscosity eye drops. Treatment results were evaluated after 1 month on the basis of complaints, objective examination data and indicators of the functional tests Results . The complaints (of discomfort, eye strain, fatigue when working with text, eye redness, lacrimation, burning and cramping in the eyes) became less severe, and so did the objective signs of DES. The functional test indicators showed an improvement, too. The best results of the treatment were noted in group 3, where the tear production indicator (Schirmer’s test) increased by 68.1 %. This indicator increased by 66.7 % and 61.5 % in groups 1 and 2, respectively. The LIPCOF test results dropped 3.9 times in group 1 and only 2,3 times in groups 2 and 3. Conclusion . Tear substitutes must be used in DES as the first line of conservative therapy. The improvement of subjective evaluations of the patients and the data of objective research in all three groups is the result of an adequate selection of tear substitutes drugs of a certain degree of viscosity according to the severity of DES.

OBJECTIVE Leopard Geckos (Eublepharis macularius) are popular pets and can be affected by a range of ocular disorders. Our objective was to report ocular findings in a group of healthy captive leopard geckos and to establish reference ranges for commonly performed ocular diagnostic tests. ANIMALS STUDIED Twenty-six healthy male geckos aged 1 year old (n = 4) and >2 years old (n = 22). PROCEDURES All animals underwent ophthalmic examination, corneal esthesiometry, modified Schirmer tear test (mSTT), rebound tonometry, conjunctival bacterial aerobic and fungal culture, and measurement of ocular dimensions. Student's t test was used to compare values of corneal esthesiometry, tonometry and mSTT between groups. Multiple correlations were assessed by Pearson correlation coefficient. RESULTS All animals had a normal ocular examination. Tear production as measured with a mSTT (mean ± SD) technique was 3.1 ± 1.3 mm/min and tonometry values (mean ± SD) were 8.2 ± 1.7 mm Hg. Corneal touch threshold (median, range) was 4.4 cm, 2.5-5.0. Younger animals had a significantly increased corneal sensitivity compared to older animals (P = .0383). Results of culture showed no growth for fungal organism in any animals. Conjunctival bacterial isolation rates were low, with only 7/26 samples positive for nine bacterial species. CONCLUSIONS Leopard geckos are amenable to ophthalmic examination and ocular diagnostic database testing with minimal manual restraint.

Keratoconjunctivitis sicca (KCS) is a multifactorial disease characterized by tear hyperosmolarity, inflammation, and ocular surface damage. Cyclosporine A (CsA) is used as an effective disease-modifying agent to improve the signs and symptoms of KCS by reducing inflammation, which interferes with tear production. This review provides an overview of efficacy, safety, and limitations of currently marketed topical CsA formulations-including CsA ophthalmic emulsion, cationic nanoemulsion, and aqueous nanomicelles-and highlights newer technologies for controlled ocular delivery of CsA and their clinical implications. Long available emulsion formulations of CsA are oil-based and have several limitations, including slow onset of efficacy and low intraocular penetration and bioavailability. Aqueous CsA nanomicelle carriers produce rapid improvement in objective signs of KCS such as corneal and conjunctival staining as early as 4 weeks and have acceptable safety profiles. CsA formulations using semifluorinated alkanes or polyaphrons are currently in clinical development, having recently completed Phase 2 studies. Other carriers for CsA currently in the preclinical phase include microemulsions, polymeric aqueous and lyophilized micelles, and hydrogels; these novel formulations have yet to undergo clinical trials. Formulations that improve tissue availability of CsA may be beneficial in clinical practice by providing faster onset of relief and improving patient adherence.

Hormone replacement therapy (HRT) is used by women to get relief from menopausal symptoms, including dry eyes. However, it is not entirely certain that HRT helps relieve dry eye disease (DED). The focus of this study is to systematically review the literature of the relevant studies to understand and determine the correlation between HRT and DED. Literature was systematically reviewed using Distiller SR. Meta-analysis was conducted using STATA 15.0. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was assessed using statistics. Fixed-effect and random-effects models were computed based on heterogeneity. Subgroups analysis was done by follow-up. Our meta-analysis results indicated significant reduction in dry eye with HRT treatment at 1-month follow-up (SMD = −1.97; CI: −3.83, −0.11), a nonsignificant increase in tear breakup time at 3-month (SMD = −0.91; CI: −3.26, 1.44) and 6-month (SMD = −1.05; CI: −3.91, 1.82) follow-ups. Our meta-analysis results indicated a nonsignificant improvement in DED with HRT treatment at 1-month (SMD = −0.97; CI: −2.35, 0.4), 3-month (SMD = 0.19; CI: −0.91, 1.29), and 6-month (SMD = −0.48; CI: −1.39, 0.43) follow-ups.Overall, nonsignificant improvement in postoperative tear production, as well as tear breakup time, was seen after HRT treatment at follow-ups in dry eye patients. More good-quality randomized control trials are needed to make accurate conclusions.

Jonathan Lilley,1 Erin C O’Neil,1 Vatinee Y Bunya,1 Kennedy Johnson,1 Gui-Shuang Ying,2 Peiying Hua,2 Mina Massaro-Giordano1 1Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 2Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Mina Massaro-GiordanoDepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA, 19104, USATel +1 215-662-9393Email mina@pennmedicine.upenn.eduPurpose: To assess the efficacy and safety of an intranasal tear neurostimulator (ITN) device in Sjögren syndrome (SS) patients.Methods: This was a two-visit prospective, randomized, controlled, same-day crossover study in participants with SS. Inclusion criteria were assessed at a baseline screening visit and included an Ocular Surface Disease Index (OSDI) score ≥ 13, and a Schirmer with anesthesia ≤ 10 mm/5 min (in at least one eye), with a cotton swab stimulation induced increase of ≥ 4 mm in the same eye. Participants returned for the application visit, where they received intranasal and extranasal applications of the ITN in random sequence, separated by at least 60 min. Schirmer scores were measured in both eyes after each application and compared to baseline values. Generalized linear models were performed to compare the change in Schirmer scores from baseline, and generalized estimating equations were used to account for correlations from repeated measurements in the same eye and measurements from two eyes of the same patient.Results: Fifty-five participants were screened and 35 were enrolled (all female), ranging in age from 31 to 72 years (mean, 57 years). The baseline OSDI score ranged from 14 to 91 (mean, 50.5), and the baseline Schirmer score had a mean (SD) of 6.4 (3.5) ranging from 0 to 20 (mm/5min). Improvement in Schirmer scores was significantly greater for intranasal device application (13.5 mm/5min, 95% CI: 10.4, 16.5) compared to extranasal device application (0.8mm/5min, 95% CI: − 0.9, 2.4) (p< 0.0001). The effects of the intranasal device application were significant regardless of the participant’s baseline Schirmer score and systemic SS medication usage (p< 0.05).Conclusion: Intranasal application of the ITN device significantly increased tear production in a subset of SS patients compared to baseline and was more effective than extranasal application. While production of the ITN device was recently discontinued, our findings suggest that other therapies that neurostimulate the lacrimal function unit may be effective in a subset of SS patients.Keywords: Sjögren syndrome, intranasal tear neurostimulation, tear production

The purpose of the current study was to investigate the effects of two commonly used sedation protocols in dogs, acepromazine (ACP) and acepromazine–methadone (ACP–MET) combination, on tear production measured by the Schirmer Tear Test (STT) 1. We hypothesized that both sedation protocols cause a reduction in canine tear production for a variable time. Fifteen client-owned dogs were recruited for the study. Each dog was subjected to sedation twice, 2–3 weeks apart, and they were randomly allocated to one of two groups receiving ACP (0.015 mg kg−1) or ACP–MET (0.010 mg kg−1 and 0.2 mg kg−1) intramuscularly. In both eyes, tear production was measured 15 min before sedation (T0) and 20 min (T20 m), 40 min (T40 m), 1 h (T1), 2 h (T2), 4 h (T4) and 8 h (T8), after drug administration. Two-way repeated measures ANOVA, followed by the Bonferroni post hoc test (p &lt, 0.05), showed a significant effect of time (p &lt, 0.0001) and treatment (p &lt, 0.0001). A significant decrease in tear production at T20 m, T40 m, T1 and T2 compared to T0 was observed in the ACP experimental protocol, while in the ACP + MET protocol, this reduction persisted until T8. Comparing the two experimental protocols, no statistically significant differences were observed at T0 or T20 m, and STT 1 values were statistically lower in the ACP + MET than the ACP protocol at the other data points. In the ACP + MET group, at T40 m, 100% of dogs showed STT 1 readings lower than 15 mm/min. This finding is clinically relevant as it can predispose dogs to corneal injuries. The major reduction in tear production due to the ACP + MET protocol proves the need for adequate corneal hydration, particularly to discourage its use in animals with altered tear production. The data obtained provide important information helping clinicians to better manage the drug’s effects on tear production.

Given the abundance of chickens in Italy, it is important for veterinarians to know the normal state of chickens’ eyes in order to identify any ophthalmic pathological changes. The aim of this study was to determine the normal values of select ocular parameters and to evaluate conjunctival microflora in two Italian chicken breeds. Sixty-six healthy chickens underwent a complete ophthalmic examination, which included a phenol red thread test (PRTT) for the evaluation of tear production and the assessment of intraocular pressure by rebound tonometry. B-mode ultrasound biometric measurements and conjunctival microflora identification were also performed in twenty-seven chickens. Mean PRTT was 23.77 ± 2.99 mm/15 s in the Livorno breed and 19.95 ± 2.81 mm/15 s in the Siciliana breed. Mean intraocular pressure was 14.3 ± 1.17 mmHg in the Livorno breed and 14.06 ± 1.15 mmHg in the Siciliana breed. Reference ranges for morphometric parameters were reported in the two breeds. Twenty-three chickens (85.18%) were bacteriologically positive. Chlamydia spp. antigen was detected in 14.81% of chickens. No positive cultures were obtained for fungi. Normal reference range values for selected ophthalmic parameters were obtained in clinically healthy chickens, which could facilitate accurate diagnosis and better management of ophthalmic diseases in these animals.

Particulate matter 2.5 (PM2.5) may aggravate dry eye disease (DED). Corni Fructus (CF), which is fruit of Cornus officinalis Sieb. et Zucc., has been reported to have various beneficial pharmacological effects, whereas the effect of CF on the eye is still unknown. Therefore, in this study, we investigated the effect of oral administration of water extract of CF (CFW) on the eye, hematology, and biochemistry in a DED model induced by topical exposure to PM2.5. Furthermore, the efficacy of CFW compared with cyclosporine (CsA), an anti-inflammatory agent, and lutein, the posterior eye-protective agent. Sprague-Dawley rats were topically administered 5 mg/mL PM2.5 in both eyes four times daily for 14 days. During the same period, CFW (200 mg/kg and 400 mg/kg) and lutein (4.1 mg/kg) were orally administered once a day. All eyes of rats in the 0.05% cyclosporine A (CsA)-treated group were topically exposed to 20 μL of CsA, twice daily for 14 days. Oral administration of CFW attenuated the PM2.5-induced reduction of tear secretion and corneal epithelial damage. In addition, CFW protected against goblet cell loss in conjunctiva and overexpression of inflammatory factors in the lacrimal gland following topical exposure to PM2.5. Furthermore, CFW markedly prevented PM2.5-induced ganglion cell loss and recovered the thickness of inner plexiform layer. Meanwhile, CFW treatment decreased the levels of total cholesterol and low-density lipoprotein cholesterol in serum induced by PM2.5. Importantly, the efficacy of CFW was superior or similar to that of CsA and lutein. Taken together, oral administration of CFW may have protective effects against PM2.5-induced DED symptoms via stabilization of the tear film and suppression of inflammation. Furthermore, CFW may in part contribute to improving retinal function and lipid metabolism disorder.

Aim: To study the intraocular pressure (IOP) and tear production changes in uncomplicated pregnant women at term pregnancy and immediate postpartum. Materials and methods: The patients admitted in the Department of Obstetrics and Gynaecology for delivery were included in the study. A total of 106 participants who were at term uncomplicated pregnancy were selected according to the inclusion and exclusion criteria. They were subjected to type 1 Schirmer's testing and intraocular pressure measurement by Perkin's tonometer before and after delivery. Result: There was no significant pre- and postdelivery IOP difference between the different age groups (

OBJECTIVE To assess the response to topical and/or systemic pilocarpine in dogs with neurogenic dry eye. METHOD Medical records of dogs diagnosed with dry eye between 2015 and 2018 were reviewed. Cases were excluded if STT values were decreased bilaterally, if dogs were lost to follow-up, or if surgical measures (parotid duct transposition) were undertaken within thirty days of presentation. Dogs were on treatment with topical pilocarpine (0.1%, every 6 hours) and/or oral pilocarpine (starting dose 2%, one drop per 10 kg every twelve hours). RESULTS Eleven cases were included in the study, seven females and four males with mean age of 10 years. Seven cases had xeromycteria, two cases had facial nerve paralysis, and one case had Horner's syndrome. Seven cases (63.6%) had successful outcome following pilocarpine treatment, return to normal STT (15-25mm/minute), in an average of 24 ± 5.1 days. Of these cases, five had both systemic and topical treatment, one had just topical treatment, and one had just systemic treatment. The average time to normal tear production on treatment with topical pilocarpine ± systemic was 23 days (range 9-48 days). The number of systemic drops until a positive response varied between individuals from 0.8drops/10kg to 7drops/10kg. CONCLUSION Pilocarpine treatment (topical ± systemic) is an effective therapy for unilateral dry eye disease in cases suspected to be neurogenic in origin. Most cases responded within 30 days. Side effects included topical irritation to the ophthalmic solution and systemic effects from oral pilocarpine, such as diarrhea and regurgitation.

Clinical data on new directions in combined treatment of neurotrophic keratitis, including anti-inflammatory therapy are presented.Purpose. To compare the effectiveness of bromfenac 0.09 %, nepafenac 0.1 % and indomethacin 0.1 % eye drops in the treatment of neurotrophic keratitis (NK).Materials and methods. 22 NK patients, aged 34 to 78, were divided into three groups. Group I received bromfenac 0.09 %, group II, nepafenac 0.1 %, and group III, indomethacin 0.1 %. Ophthalmic tests included visometry, biomicroscopy, corneal sensitivity determination, as well as diagnostic tests to determine indicators of tear production (Schirmer test, Norn test, LIPCOF test), and measuring lacrimal meniscus height.Results. Between visits V2 and V3, patients of group III showed an increase in conjunctival irritation to an average of 2.3 points, while groups I and II revealed the condition of the conjunctiva at 0.9 and 1.1 points, respectively. The lesion area was evaluated in points (max = 20) and averaged on V1 6.8 points in group I, 5.9 points in group II and 7.2 points in group III. Keratopathy in group I which was estimated at 3.8 points before V2, dropped to 1.4 points by V3. In group III it was 1.7 points by V3. In group II, keratopathy showed only 4.1 points by V3. The average Norn test on the day of treatment showed 2.7 seconds in group I, 2.5 seconds in group II, and 3.1 seconds in group III. No significant increase in Schirmer's test results in all groups was recorded.Conclusion. The use of non-steroidal anti-inflammatory eye drops of various groups — bromfenac 0.09%, nepafenac 0.1 % and indomethacin 0.1 % — gave a positive result in NK therapy. However, bromfenac 0.09% instillations administered once a day produce a higher anti-inflammatory effect then the same quantity of nepafenac 0.1% and indomethacin 0.1 % instillations.

Periorbital burns generate contraction and distortion of periorbital soft tissue, causing eyelid malfunction, further contributing to loss of vision from corneal scarring or perforation. We present our multidisciplinary algorithm to restore vision in patients with burn-related bilateral corneal blindness with light perception. Chart review was performed for four consecutive burn patients requiring periocular reconstruction and keratoprosthesis. Initial treatment included globe coverage with eyelid releases and grafts. Strategy of corneal replacement was determined by eyelid position and function and sufficiency of tear production. All patients were corneal blind with light perception only and cicatricial ectropion. The eye with better visual prognosis was reconstructed. Eyelid reconstruction procedures consisted of lid releases with full-thickness skin graft (FTSG) or split-thickness skin graft (STSG). Two patients regained adequate lid function and underwent standard keratoprosthesis placement. Two underwent mucous membrane grafts followed by keratoprosthesis. All patients experienced improved postoperative vision in their reconstructed eye. Corneal injury due to periocular burns can lead to blindness. Early involvement of ophthalmology, protective measures, and early ectropion release are critical. For severe burns, a multidisciplinary approach, where adequate globe protection is followed by keratoprosthesis placement, can effectively restore vision in patients with burn-related corneal blindness.

Objective To analyze the relationship between dry eye symptoms and modern dry eye tests, including the Schirmer I test, lipid layer thickness (LLT), and blinking pattern by LipiView interferometer. Design Cross-sectional study. Participants 115 dry eye outpatients. Methods Dry eye symptoms were quantified by questionnaire scores, such as Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness (SPEED). LLT, complete, and incomplete blinking rate were recorded by the LipiView interferometer. Results 115 patients (229 eyes, mean age = 60.5 ± 13.6 years) were enrolled in this study. The mean value of the SPEED and OSDI scores was 9.5 and 10.2, respectively. A total of 44.3% of all subjects had severe dry eye syndrome (SPEED, OSDI ≥ 10). LLT (mean = 71.2 nm) was inversely correlated with both the SPEED and OSDI (p = 0.003 and 0.004, respectively). The incomplete-to-complete ratio of blinking rate (i/c ratio) was correlated with both the SPEED and OSDI (p = 0.0048 and 0.0234, respectively). Patients with LLT less than 69 nm were more likely to have severe dry eye syndrome. There was no significant relationship between the Schirmer I test and the SPEED or OSDI. However, LLT was inversely related to the Schirmer I test (linear regression, p = 0.0002, r = −0.1857). Conclusions LLT and the i/c ratio were significantly correlated to dry eye symptoms. Eyes with thinner LLT are more likely to have better aqueous tear production. The role of the reciprocal influence between each tear component in the maintenance of tear function warrants further investigation.

Common age-related changes in the human eye contribute to the development of dry eye, including decreases in aqueous tear production. Although the infiltration of lymphocytes into the lacrimal glands occurs with age, age-related increases in tear production have also been observed in mice; however, the mechanisms underlying this increase remain unclear. We herein demonstrated that increases in tear production were not dependent on body weight gain or systemic conditions, such as insulin resistance, using aged mice and high-fat diet-fed mice. The results obtained also showed that senescence-associated T (SA-T) cells accumulated in the lacrimal glands of aged mice, particularly females. Expression levels of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) in whole lacrimal glands and epithelial cells isolated from lacrimal glands were significantly higher in aged mice than in young mice. The expression levels of adiponectin and one of its receptors, AdipoR2, also increased in the lacrimal glands of aged mice, but not in those of high-fat diet-fed mice. Collectively, the present results indicate that PPARγ and adiponectin-mediated signaling contribute to age-related increases in tear production in mice and have potential as therapeutic targets for the treatment of dry eye in humans.

Purpose To determine whether reliance on eyelid margin vascularization as a diagnostic criterion for meibomian gland dysfunction (MGD) results in underdiagnosis of MGD in individuals with dark skin pigmentation. Patients and methods This cross-sectional study enrolled consecutive cornea clinic patients in Buffalo, New York. Eyelid margin vascularization was graded qualitatively from slit-lamp photos. Skin pigmentation was quantified from digital photos using red/green/blue (RGB) pixel analysis and dichotomized using the RGB median. MGD was defined as abnormal quantity or quality of meibum or increased pressure required to express meibum. Additional testing included infrared meibography, Schirmer's testing, and a dry eye questionnaire. Sensitivity of MGD diagnosis by visualization of vascularization, compared to diagnosis by expression of meibum, was estimated with and without stratification by skin pigmentation. Results Among 47 participants, 15-79 years old, meibomian gland truncation/dropout, abnormal tear production, and dry eye symptoms affected individuals of all skin pigmentations. Eyelid margin vascularization was less common in subjects with dark (n=21%) compared to light pigmentation (65%; p=0.002), although the prevalence of MGD assessed via clinical evaluation did not vary significantly between those groups. Use of eyelid margin vascularization alone was not sensitive (33%) for MGD diagnosis. The sensitivity was 17% when limited to those with dark pigmentation. Conclusion Our findings highlight the importance of gland expression and suggest limiting reliance on eyelid margin vascularization for MGD diagnosis, especially in those with dark eyelid skin pigmentation.

OBJECTIVE: To evaluate the tear production, intraocular pressure, and central corneal thickness in healthy white‐tailed deer (Odocoileus virginianus) and assess for seasonal variability. ANIMALS STUDIED: Nineteen healthy fawns (3‐10 days old) and 8 healthy adult white‐tailed deer (164‐280 days old) were studied. PROCEDURES: All fawns were manually restrained for the study, while adult animals were immobilized with an intramuscular injection of combined xylazine (2.2 mg/kg), tiletamine (1 mg/kg), and zolazepam (1 mg/kg). Tear production (STT‐1) was evaluated in both eyes of all fawns. Intraocular pressure (applanation and rebound tonometry) and central corneal thickness (ultrasound pachymetry) were determined in both eyes of all fawns and adult deer. RESULTS: Mean ± SD tear production in fawns was 12.32 ± 4.46 mm/min. Mean ± SD IOP values in the fawns were 16.21 ± 4.97 mm Hg (TonoPen®) and 14.05 ± 5.03 mm Hg (TonoVet®). In adult deer, mean ± SD IOP values were 15.57 ± 2.88 mm Hg with TonoPen® and 12.87 ± 2.57 with TonoVet®, and TonoPen® significantly overestimated the IOP, compared to TonoVet® (P

Purpose. To study the dynamics of tear production and morphometric parameters of cornea after phacoemulsification of senile cataract (SC) at different postoperative terms. Material and methods. 123 patients (123 eyes) aged from 62 to 83 years were examined after phacoemulsification of SC. All patients were divided into 2 groups depending upon the level of tear production (TP): 1st group – 61 patients with normal and insufficiently lowered TP, 2nd group consisted of 62 patients with moderate and severe TP suppression. Besides standard examination methods, all patients underwent Schirmer’s – 1 test, tear breakup time (TBUT), cornea OCT, corneal endothelial cell density (CECD) before operation and on the 1st, 10th , 20th and 30th postoperative day. Results. Indices of TBUT, corneal epithelium and stromal thickness (CET and CST), CECD turned out to be lower in the eyes of patients from the second group in comparison with the 1st. Conclusion. The conducted research showed that postoperative changes of CET occur 4 times and CST 1,5 times more often in patients with moderate and severe decrease of TP rather than in eyes with normal TP. The recovery of TP on the final stage of research was found 2.6 times less in eyes of patients from the 2nd group in comparison with the 1st, which can be the evidence of possible neurotrophic corneal disorders in patients with reduced TP.

Dry eye disease (DED) is a commonly diagnosed disorder in small animals. It has been historically described as a quantitative or qualitative deficiency in tear production; however, the pathogenesis of the disease is much more complex than previously recognised. Ocular inflammation is the hallmark of DED, reflected in early nonspecific conjunctivitis and later in dramatic changes of the ocular surface. Prompt recognition of the disease, accurate diagnostics and appropriate treatment are paramount in preserving the ocular surface integrity and the patient's comfort. Part 1 discussed the aetiopathogenesis of the condition and described the clinical signs. This second article looks at diagnostics and treatment of ocular surface disorders in dogs.

Dry eye disease (DED) is a commonly diagnosed disorder in small animals. It has been historically described as a quantitative or qualitative deficiency in tear production; however, the pathogenesis of the disease is much more complex than previously recognised. Ocular surface disorders in people are currently investigated as a dysfunction of what is termed the ‘lacrimal functional unit’, consisting of the ocular surface, including Meibomian glands and conjunctiva, in addition to lacrimal glands, eyelids and sensory and motor innervation. A loss of homeostasis of the tear film leads to the vicious cycle of increased osmolarity and inflammation, with dreadful consequences for the ocular surface in both dogs and humans. Ocular inflammation is the hallmark of DED, reflected in early nonspecific conjunctivitis and later in dramatic changes of the ocular surface. Prompt recognition of the disease, accurate diagnostics and appropriate treatment are paramount in preserving the ocular surface integrity and the patient's comfort. This article discusses the aetiopathogenesis of the condition, and describes the clinical signs, while the second article will look at diagnostics and treatment of ocular surface disorders in dogs.

The aim of this study was to compare the Shirmer tear test (STT) and Standardized endodontic absorbent paper point tear test (PPTT) in ferrets and establish normal ophthalmic parameters for PPTT. A total of 66 eyes from 33 healthy ferrets (17 males and 16 females) aged 10 to 120 months were included in the study. Measurement for STT was 7.4 ± 1.9 mm/min and 12.6 ± 2.4 mm/min for PPTT. There were no significant differences between values obtained from left and right eyes (P = 0.29) or between age groups (P = 0.16), however there was a significant difference between sexes (P = 0.03). The results from this study can both serve as useful parameters for ophthalmologic evaluation in ferrets but less variable results, and therefore more precise measurements can be obtained using PPTT than STT.

The aim is to evaluate the effectiveness of Stillavit in the treatment of dry eye syndrome (DES) and its effect on the density of conjunctival goblet cells and the functional parameters of tear production. Methods. There were analyzed treatment results of 18 patients (36 eyes) with DES at the age of 48 to 80 years (average 60.6 ± 1.3 years) including 17 women and 1 male before and after 1 and 3 months after Stillavit prescription. In all patients in addition to a standard ophthalmological examination the results of Schirmer I, Norn, as well as the LIPCOF test were evaluated and the density of conjunctival goblet cells was examined. Results. After 1 and 3 months there was a significant improvement in the results of the Norn test: from 5.17 ± 0.22 seconds to 7.18 ± 0.17 seconds which indicated an increase in the stability of the tear film. After 3 months there was a significant increase in the density of conjunctival goblet cells, improvement in the Schirmer sample: from 9.26 ± 0.89 to 11.7 ± 0.6 mm (t = 2.28, p < 0.05) and LIPCOF test (t = 2.18, p < 0.05) which indicated an increase in tear production and a significant decrease in the inflammatory process and edema of the conjunctiva. Conclusion. Treatment of DES with the use of Stillavit leads after 3 months to a significant increase in the density of conjunctival goblet cells, increases tear production and stability of the tear film.

Currently, there are many studies on the effectiveness of ointment ophthalmological medicines. Ophthalmic ointments are unique because they have a multi-component action mechanism. On the one hand, the action of the medicinal substance itself is prolonged due to the ointment base, and on the other hand, due to the structural features of the conjunctival cavity mucosa, these medicinal substances are very rapidly absorbed. In the treatment of ocular surface pathology, including as meibomiitis, barley and chalazions, local therapy and ointment forms are preferred. The purpose of the study was the investigation the antibacterial eye ointment effectiveness of domestic production Oftocipro — a fluoroquinolone derivative for the treatment of acute and chronic eyelid and conjunctiva diseases. During the study patients were divided into 2 groups with acute and chronic inflammatory diseases of the eyelids and conjunctiva in the acute stage. It is known that chronic pathological processes are often stopped in longer periods. This fact was a prerequisite for assessing the effectiveness of Ontocipro with a comparative analysis of the dynamics of subjective (patient complaints) and objective (biomicroscopy, tear production tests) indicators characterizing the severity of the inflammatory process. The study has showed a high drug efficacy, when it is applied topically 3–4 times a day. The average time to relieve the inflammatory process was 3–7 days. The possibility of using the drug Oftocipro locally, when it is applied to the eyelid area, without affecting the conjunctival cavity, allows to minimize the impact area due to the ointment base and limit the risk of side effects in the form of a violation of the natural conjunctival microflora. Considering high level of tolerance and low allergenicity of the drug Oftotsipro, it can be recommended for widespread use for the treatment of acute and chronic blepharoconjunctivitis, barley and chalazion in the acute stage, as well as meibomiitis.

Dry eye disease (DED) is a multifactorial disease that manifests in patients with a variety of symptoms and signs such as ocular pain, visual issues, rapid tear evaporation and/or decreased tear production. It is a global health problem and is the leading cause of optometry and ophthalmology clinic visits. The mainstay therapy for DED is artificial tears (ATs), which mimics tears and improves tear stability and properties. ATs have been found to improve symptoms and signs of disease in all DED subtypes, including aqueous deficient DED and evaporative DED. However, given the heterogeneity of DED, it is not surprising that ATs are not effective in all patients. When AT fails to relieve symptoms and/or signs of DED, it is critical to identify the underlying contributors to disease and escalate therapy appropriately. This includes underlying systemic diseases, meibomian gland dysfunction, anatomical abnormalities and neuropathic dysfunction. Thus, this review will discuss the benefits and limitations of ATs and review conditions when escalation of therapy should be considered in DED.

This study was performed to investigate the effects of cyclopentolate on ultrasonographic parameters of eye structures, intraocular pressure (IOP), tear production, and pupil size in normal donkeys. Sixteen eyes of eight clinically healthy adult donkeys (2–2.5 years old) weighing 295 ± 34 kg (mean ± standard deviation) were used in this study. Cyclopentolate hydrochloride 1% was instilled in a randomly selected eye and the other eye received normal saline drops as a control. The effect of cyclopentolate was evaluated by ultrasonography. Additionally, changes in IOP and tear production were evaluated for 2 hours post-instillation by tonometry and Schirmer tear test (STT), respectively. Vertical and horizontal pupil diameters were recorded pre-instillation (0), and 15, 30-, 45-, 60-, and 120-minutes post-instillation. After cyclopentolate 1% instillation, iridocorneal angle and width of the entry of ciliary cleft were significantly increased as observed by ultrasonography. IOP was significantly increased starting from 30 minutes till 60 minutes post-instillation of cyclopentolate 1%. Non-significant alteration in the STT was observed in the cyclopentolate-treated eyes compared to the control eyes. Both vertical and horizontal pupil diameters began to significantly increase 30 minutes after cyclopentolate 1% instillation compared to the control saline group. In conclusion, cyclopentolate 1% could be used as a potent cycloplegic drug in donkeys without systemic or ocular side effects.

Simple Summary The general anesthesia or sedation reduces both the tear production and the stability of tear film that protect corneal surface, predisposing itself to the exposure keratopathy. The aim of the present study was to evaluate the effects of intramuscular dexmedetomidine (DEX) on canine tear production, measured by standardized Schirmer Tear Test 1 (STT-1) strips, for the 8 h following sedation, in dogs. A significant effect of time on canine tear production was found, highlighting that dexmedetomidine sedative protocol significantly affects tear production in dogs. It is recommended to treat the canine eyes with tear substitutes to protect ocular surface health and the welfare of the dogs. The ocular lubrication should be performed during and up to 12 h after sedation. The present report could provide preliminary information to better understand the effect of DEX on the tear film dynamics. Abstract Tear film provides lubrication and protection to the ocular surface. The sedation reduces tear production, often leading to perioperative exposure keratopathy. The aim of the present study was to report the effects of intramuscular dexmedetomidine on canine tear production, measured by STT-1, for an experimental period of 8 h after sedation. Ten dogs who underwent sedation for routine radiologic assessment were recruited for the study. In all animals, tear production in right and left eyes was measured 15 min before sedation (T0: basal values) and 20 min (T20), 1 h (T1), 2 h (T2), 4 h (T4) and 8 h (T8) after drug administration. Analysis of variance and post hoc Bonferroni test (p < 0.05) were performed. A significant effect of time on canine tear production was found. The tear production returned to basal values at T8. So, it is recommended to treat the canine eyes with tear substitutes during and up to 12 h after sedation.

The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally (n = 15, 25 eyes) or transcutaneously (n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer&rsquo, s I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (Pan troglodytes) were anesthetized using either tiletamine-zolazepam (TZ; 2 mg/kg) combined with medetomidine (TZM; 0.02 mg/kg), or, TZ alone (6mg/kg). Tear production was lower (P = 0.03) with TZM (5.63 ± 6.22 mm/min; n = 16) than with TZ (11.13 ± 4.63 mm/min; n = 8). Mean IOP, measured using rebound tonometry in an upright body position (n = 8) was 18.74 ± 3.01 mm Hg, with no differences between right and left eyes. However, positioning chimpanzees in left lateral recumbency (n = 27) resulted in higher IOP in the dependent (left) eye (24.77 ± 4.49 mm Hg) compared to the nondependent (right) eye (22.27 ± 4.65 mm Hg) of the same animal (P < 0.0001). These data indicate medetomidine anesthesia markedly lowers tear production in chimpanzees, and that body position should be taken into consideration when performing rebound tonometry.

This study is aimed at comparing the effects of tea tree oil (TTO) shampoo with regular eyelid shampoo on the treatment of meibomian gland dysfunction (MGD) signs and symptoms.Double-masked randomized clinical trial METHODOLOGY: Forty patients with MGD were treated by daily eyelid scrubbing with TTO shampoo in one eye and regular eyelid shampoo in the other one. Before treatment and then after 1 and 3 months, the effect on ocular surface symptoms, tear production and stability, and conjunctival and eyelid signs of the 2 eyes were compared.Plugging and capping of meibomian gland orifices, foamy tear, glands expressibility, 5-Item Dry Eye Questionnaire score (DEQ5), and tear breakup time were improved more significantly in TTO shampoo-treated eyes (capping P = .050, plugging and glands expressibility P = .001, others P.001). In spite of improvement in both eyes, scores of meibum quality, conjunctival hyperemia, corneal and conjunctival staining, and Schirmer1 test value showed no statistically significant difference between the eyes (P = .06, .187, .192, .19, respectively). Moreover, eyelid margin telangiectasia resolved only in TTO shampoo-treated eyes (P.001). Trichiasis and distichiasis changed in neither group (P.99). Furthermore, ocular surface irritation during scrubbing was more common with TTO shampoo (P = .002).TTO shampoo was found to be more efficient than regular eyelid shampoo in controlling MGD signs and symptoms although ocular surface irritation during its application was more frequent.

Purpose To investigate long-term correlations between Matrix Metalloproteinase-9 (MMP-9) testing and dry eye (DE) parameters. Additionally, to evaluate variability in MMP-9 results over time and with anti-inflammatory treatment. Methods Retrospective cohort study of DE patients with equal MMP-9 testing results (positive or negative) in both eyes and a minimum of 6 months of follow up. Our main outcome measure was to examine whether initial MMP-9 status affected change in DE parameters over time. Secondarily, we evaluated the frequency of MMP-9 status change over time and examined whether MMP-9 status change was impacted by treatment. Results 67 patients (76% female) fit the inclusion criteria. Mean age was 63 years with a mean follow up of 10.6 months. The majority (37/67, 55%) had concomitant systemic immune disease. MMP-9 testing was positive in both eyes in 39 individuals (58%) and negative in both eyes in 27 (42%) individuals. Of all DE parameters, initial MMP status predicted change in tear production. Individuals in the MMP-9 positive group had a greater decrease in production from baseline to final visit compared to the negative group (−2.6 vs 2.1, P = 0.013). In those initially MMP-9 positive, the frequency of becoming MMP-9 negative was higher in eyes treated with anti-inflammatory therapy compared to artificial tears (22.9% vs 3.3%, P = 0.106). However, only Lifitegrast 5% showed statistical significance compared to artificial tears (31.3% vs 3.3%, P = 0.044). Conclusions Eyes with detectable MMP-9 had significantly decreased tear production over time compared to those without detectable MMP-9. Anti-inflammatory treatment more frequently normalized MMP-9 compared to PFATs.

The frequency and structure of ophthalmopathology in workers of the Novokuznetsk Metallurgical Combine (NMC) have been studied. In total 1911 workers of NMC have been examined. The control group comprised 1801 people working in hazardous industrial conditions. The experimental group consisted of employees dealing with management, engineering center, accounting (110 people). Their work was not connected with the impact of unfavorable factors of metallurgical production. In the control group, the hazard classes ranged from 3.2 to 3.4. The difference between the classes of hazard impact consisted in an increase of the intensity of the hazardous factors exposure. In the structure of conjunctival diseases we have diagnosed chronic conjunctivitis (198.3 ‰), chronic blepharoconjunctivitis (109.4 ‰), pinguecula (266.7 ‰) and pterygium (7.2 ‰) in metallurgical workers. Pengucules in the control group of workers was not only more often than in engineers, but also larger, often located in the inner and outer corner of the eye, and was detected in workers under 30–35 years. The workers of the main shops suffered more severely from the function of tear production and the stability of the pre-corneal tear film. The miners suffered from the highest frequency of cataract development — 301 ‰. Thus, a high incidence of inflammatory and dystrophic diseases of the eyelids and conjunctiva, cataracts in metallurgy has been established. An increase in the frequency of ophthalmopathology was noted with an increase in the length of service under harmful conditions of metallurgical production. The authors suggest the term “metallurgy ophthalmopathy”, which includes manifestations of chronic conjunctivitis and / or blepharoconjunctivitis against the background of unstable precorneal film and frequent formation of posterior-subcapsular opacities of the lens.

Neuromodulation is a novel approach that utilizes electrical signals, pharmaceutical agents, or other forms of energy to modulate abnormal neural function through neurostimulation. Neurostimulation is a novel technique that uses electrical currents to stimulate the nervous system. During the recent few decades, neuromodulation has gained significant attention, in particular for the treatment of chronic neurological diseases, due to its success in treating patients unresponsive to conventional pharmacological therapies. Dry eye disease (DED) is a chronic, multifactorial disease that affects millions of people worldwide. Recent data have demonstrated that neurosensory abnormalities contribute to the pathogenesis of DED. Current mainstays of dry eye therapy include lubrication, tear retention, and anti-inflammatory therapies, among others. The recent development of intranasal neurostimulation therapy for DED utilizes the nasolacrimal reflex as an alternative pathway, not only to increase tear production via increased lacrimation, but also to target other tear film components, such as mucin and meibum secretion, promoting tear film homeostasis. This review aims to describe the different types of neuromodulation devices available and their application for non-ocular diseases, as well as to review recent advances and literature on ocular neurostimulation.

Vinod Burade,1 Rishit Zalawadia,1 Alpesh Patel,1 Abayomi Ogundele2 1Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India; 2Sun Pharmaceutical Industries, Inc, Princeton, NJ, USACorrespondence: Abayomi OgundeleSun Pharmaceutical Industries, Inc, Princeton, NJ, USATel +1 (609) 720-5389Email Abayomi.Ogundele@sunpharma.comIntroduction: Cyclosporine ophthalmic solution 0.09% (CsA 0.09% sol) is approved to increase tear production in patients with keratoconjunctivitis sicca. This study evaluated the efficacy of CsA 0.09% sol vs cyclosporine ophthalmic emulsion 0.05% (CsA 0.05% eml) vs ciclosporin ophthalmic emulsion 0.1% (CsA 0.1% eml) in a NOD mice model.Methods: Mice were randomized and administered placebo, CsA 0.09% sol twice daily, CsA 0.05% eml twice daily, CsA 0.09% sol once daily, or CsA 0.1% eml once daily in the conjunctival sac of both eyes for 60 days. Tear volume was measured with phenol red threads at baseline and 4 hours after treatment every 15 days. On day 58, the corneal surface was observed under a slit-lamp after staining with 3% lissamine green administered into the inferior lateral conjunctival sac. On day 61, mice were euthanized, globes excised, sliced into 4 μm sections in 3 areas per section, and stained. Total number of stained goblet cell/μm was counted, and the sum per eye was averaged. Lacrimal gland tissues were removed and interleukin (IL) 1-β cytokine levels estimated.Results: Groups comprised 11 mice each, including an untreated normal and untreated diseased control group (7 groups total). CsA 0.09% sol twice daily significantly increased tear volume on day 30, 45, and 60 vs CsA 0.05% eml (P< 0.05, < 0.001, < 0.001, respectively) and vs CsA 0.1% eml on day 60 (P< 0.05); CsA 0.09% sol once daily significantly increased tear volume on day 45 vs CsA 0.05% eml (P< 0.05). Goblet cell density significantly increased with CsA 0.09% sol twice daily vs placebo and NOD control (P< 0.01 both). There was no significant difference in corneal staining and IL-1β levels with CsA 0.09% sol.Conclusion: Sixty-day treatment with CsA 0.09% sol showed comparatively improved preclinical results vs CsA 0.05% eml and CsA 0.1% eml.Keywords: cyclosporine A, goblet cell density, keratoconjunctivitis sicca, preclinical, tear production

Background Sjogren syndrome (SS) is an autoimmune disease which involves the nervous system in about 20% of SS cases, whilst in 25-92% neurological symptoms may precede the onset of sicca syndrome. Methods A 65-year-old male came to our observation due to a 7-month history of near-syncope episodes, constipation, hypohidrosis, fatigue and asthenia. Past history revealed hypothyroidism due to Hashimoto's thyroiditis, under treatment with levothyroxine. Physical examination showed: temperature 36.5 °C, blood pressure 90/60 mmHg and respiration rate 20 breaths per minute. The ECG revealed sinus bradycardia with 55 beats per minute (bpm) and right bundle-branch block (RBBB). Laboratory exams showed: lymphocytopenia (WBC 9008/μL, with 90% granulocytes and 3% lymphocytes); CRP (0.3 mg/dL), ESR (20mm/hr). In order to investigate endocrine disorders, hormone tests were also performed, showing: euthyroidism (FT3 2.0 pg/mL, FT4 12.6 pg/mL, TSH 1.685 µUI/mL, Ab anti-thyroglobulin 1630.0 UI/mL, Ab anti-thyreoperoxidase 592.5 UI/mL), hypogonadotropic hypogonadism (LH 1.6 mIU/mL, FSH 2.7 mIU/mL, prolactin 15.9 ng/mL, testosterone 133 ng/dL) and normal adrenocortical function (serum cortisol 8 am 17.5 µg/dL, aldosterone 6.8 pg/dL, ACTH 8.5 pg/mL). Brain-MRI showed anterior pituitary hypoplasia. Results In order to assess a potential autonomic neuropathy, deep breathing test (E/I 1.02) , lying to standing test (R/R’ 0.95) and orthostatic hypotension tests (at 120 seconds systolic reduction was >20 mmHg and diastolic reduction >10 mmHg) were performed, all resulting pathological. ECG Holter monitoring revealed sinus bradycardia, with a mean heart rate of 55 bpm and RBBB. Holter blood pressure 24-hour monitoring showed a diurnal hypotensive profile. The echocardiogram revealed a mild mitral and tricuspid insufficiency. A paraneoplastic syndrome was also excluded by total body-CT with mean of contrast and tumor markers, which resulted normal. On a further assessment, the patient reported a 3-month history of worsening dry mouth and persistent dehydrated tongue. Signs of anisocoria in response to light stimulation, were observed as well. Tests for autoimmune diseases showed ANA (1:320 speckled pattern), Ro/SS-a (>240U/l) and La/SS-b (162 U/ml) antibodies. Though symptoms such as dry eyes were not reported, “Shirmer test” revealed an insufficient tear production in both eyes (RE 5 mm, LE 3 mm). The patient was discharged with the diagnosis of autonomic neuropathy most likely due to primary Sjögren’s syndrome and started therapy with Prednisone 25 mg/die and Hydroxychloroquine 200 m/bid o.d. After one month, he reported a significant improvement in symptoms such as asthenia, fatigue and dry mouth. Orthostatic hypotension symptoms were also significantly decreased and no further near-syncopal events occurred. Conclusion This case underlines the clinically importance of dys-autonomic symptoms, antecedent to the onset of sicca syndrome, and highlights the favorable response to immune-modulating therapy in the treatment of autonomic dysfunction arising from SS. Disclosures F. Masini None. K. Gjeloshi None. F. Danzo None. E. Pinotti None. L. Monaco None. G. Cuomo None.