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Zujaja Tauqeer,1 Stephanie E Jinno,1,2 Caroline W Chung,1 Mina Massaro-Giordano,1 Vatinee Y Bunya1 1Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 2Drexel University School of Medicine, Philadelphia, PA, USACorrespondence: Vatinee Y Bunya, Tel +1-215-662-8100, Email Vatinee.Bunya@pennmedicine.upenn.eduPurpose: Ocular adverse events have been reported in association with dupilumab, a monoclonal antibody to treat allergic diseases including atopic dermatitis (AD). We describe clinical findings and treatment of dupilumab-related ocular complications.Patients and Methods: Retrospective study of 19 dupilumab-treated AD patients seen for a new ocular complaint. Primary outcomes were specific ocular exam findings (conjunctival injection, corneal fluorescein staining, blepharitis, meibomian gland dysfunction (MGD)), treatments, and follow-up.Results: Nineteen dupilumab-treated AD patients were included. Median age was 47 years (range 18– 73). Over half were women (11/19) and majority were Caucasian (13/19). Symptom onset occurred at a mean of 99 days (range 23– 520 days) from first dupilumab dose. The most common symptoms were redness (63%), tearing (47%), and pruritus (37%). Most common ocular findings were conjunctival injection (75%) and corneal staining (60%). Blepharitis was seen in about a third (30%), and 25% had MGD. Initially, 10% were observed without treatment, while 15% were treated with artificial tears alone. Other treatments included antihistamine drops (20%) and steroid drops alone (15%). In 40% of patients, a combination of steroids and various other topical eye drops were prescribed. Eighty-four percent (16/19) of patients were seen for follow-up. Steroid drops were required at follow-up in 3 out of 4 patients initially treated with antihistamines alone and in two-thirds of patients initially treated with artificial tears only. Mean follow-up period was 88 days (range 5– 369). Dupilumab was discontinued in 31.5% (6/19) of patients; of those who discontinued, 3 restarted it later.Conclusion: Conjunctival injection was the most frequent dupilumab-related ocular symptom and most common exam finding followed by corneal staining. Most patients initially treated with antihistamine drops or artificial tears alone subsequently required steroid drops to control symptoms. Some patients who discontinued dupilumab restarted the medication after achieving adequate control of ocular symptoms.Keywords: dupilumab, atopic dermatitis, conjunctivitis, cornea, dry eye

Background: Dry eye disease (DED) is a prevalent condition affecting over 16 million patients in the USA. DED and the symptoms of ocular discomfort are debilitating and a significant burden on patients. If left untreated, DED can progress to cause severe pathology. Treatment is often initiated by patients without consulting a healthcare professional. This study investigated the safety and efficacy of a novel lipid-containing eye drop (BTC), which might better mimic the components of natural tears. Methods: This was a multicenter, randomized, double-masked, active control, two arm, parallel group study of eye drops in adult subjects with self-reported DED. Subjects were randomly assigned to BTC or control (commercially available non-lipid eye drops; NLED) arm and were followed for 30 days. Assessments using visual analog scale and patient-reported outcomes (PRO) questionnaires, non-invasive tear break up time, slit-lamp examination, and subject-reported ocular symptoms were conducted at baseline and at days 7 and 30. The primary endpoint was change in overall ocular comfort score from baseline to day 30. Results: 158 subjects were randomized, of whom 130 completed the study per protocol (PP). Mean (SD) age was 47.8 (14.14) years. The mean (95% CI) change in overall comfort scores at the 30-day follow-up in the PP population was 21.4 (15.1, 27.7) for the test drop and 10.0 (3.9, 16.1) for the comparator. The mean (95% CI) treatment difference was 11.3 (2.6, 20.1); this met the pre-defined requirements for non-inferiority. There was no significant difference in the proportion of eyes with reported ocular symptoms between the groups. At day 7, the OR (95% CI) was 0.967 (0.528, 1.770) and at day 30 was 1.160 (0.610, 2.203). There were no Grade 3 or higher corneal edema, corneal neovascularization, corneal staining, conjunctival injection, tarsal abnormalities or any other biomicroscopy findings, and no corneal infiltrates observed during the study. Conclusions: The investigational lipid eye drop BTC was noninferior to the commercially available non-lipid comparator in all parameters measured and has the potential to provide an effective therapy for subjects with symptoms of dry eye who would benefit from a lipid-based artificial tear. Trial Registration: NCT03995355 (http://www.clinicaltrials.gov), registered June 24, 2019. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prevalence of dry eye disease (DED) and its associated risk factors in a sample of the Argentine population. Methods: A prospective cross-sectional population-based study was conducted in Argentina during April 2022 through an anonymous electronic survey that included participants aged 12 years old or older. The prevalence of symptomatic DED was evaluated using the Women's Health Study (WHS) dry eye questionnaire. In addition, a list of conditions possibly related to dry eye were evaluated in the questionnaire to assess the prevalence of potential risk factors. A multivariate logistic regression analysis was performed. Results: 10,812 subjects (mean age 44.1 ± 13.9, range 12–94 years old) answered the survey. Overall prevalence of DED was 42.1%. DED prevalence in women was 45.1% (3848 out of 8525) and in men was 30.8% (704 out of 2287). Risk factors were female sex (OR 2.78; p < 0.001), age > 60 years (OR 2.92), rheumatologic disease (OR 2.80, CI 1.62–3.13), use of digital screens for more than 6 h per day (OR 2.62; CI 1.43–2.80), glaucoma topical treatment (OR 2.05; CI 1.20–3.01), dysthyroidism (2.03; CI 1.48–2.51), and sleeping less than 7 h per day (OR 1.92; CI 1.30–2.51). Conclusion: DED was found to be a prevalent condition among Argentine participants, the main risk factors were determined by sex, age, and especially those related to lifestyle in South America. [ABSTRACT FROM AUTHOR]

Objective and subjective dry eye tests. The vision, endothelial cell count, and the pressure inside the eye were all found to be within normal limits after the IPL treatment. Even though the people in our study had glaucoma and had been taking glaucoma medicine for it for a year and the fact that the symptoms last for a long time may also change the results. Also, DED caused by glaucoma medication is complicated, with a lot of different symptoms and signs, even in the same stage. Also, subjective complaints may not match up with clinical signs. The type, amount, and length of anti-glaucoma drugs may have affected the results. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis. Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer's tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition. Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3– 4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= − 0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P 0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P< 0.001). Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). Methods: We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. Results: The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Conclusion: Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients. [ABSTRACT FROM AUTHOR]

Purpose: The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). Methods: This case-control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. Results: HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score (r = -3.50, P = 0.027) and the Schirmer I test score (r = -0.374, P = 0.017) were detected in patients with AIDS. Conclusion: Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified. [ABSTRACT FROM AUTHOR]

To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1β, IL −6, and IL-8 occurred in pemphigus and pemphigoid patients. Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate dry eye disease (DED) in newly diagnosed patients with depressive disorder (MDD). Method: This observational study included 48 MDD patients in Group 1 and 20 healthy controls in Group 2. Psychiatric and ophthalmic examinations, Beck Depression Inventory (BDI), Ocular Surface Disease Index (OSDI), Schirmer's test, tear breakup time (TBUT), Meibomian gland dysfunction (MGD), and ocular staining were conducted. The results were statistically compared. Results: The participants, comprising 32 men and 36 women, had a mean age of 31.08 ± 11.7 years (18–64 years). Group 1 had a mean BDI score of 30.87 ± 8.56, while Group 2 had a score of 1.3 ± 1.3 (p < 0.001). In Group 1, 28 patients were diagnosed with DED, whereas in Group 2, six subjects were diagnosed with DED. The mean Schirmer's results in Group 1 and Group 2 were (mm/5 min) 10.87 ± 2.44 and 12.70 ± 2.3, respectively, and were significantly lower in Group 1 (p < 0.001). The mean OSDI scores in Group 1 (34.95 ± 15.8) were significantly higher compared to Group 2 (3.2 ± 3.1) (p < 0.001). There was no significant difference in mean TBUT between Group 1 (9.41 ± 2.6 s) and Group 2 (9.8 ± 0.61 s) (p > 0.05). Significant correlations were found between BDI scores and Schirmer's results as well as OSDI scores (p < 0.05, p = 0.02, respectively). No statistically significant correlations were found between BDI scores and TBUT or MGD (p > 0.05). Conclusion: DED was found to be more prevalent in the MDD group. The severity of MDD and DED, as indicated by BDI, OSDI, and Schirmer's results, was found to be correlated. It was observed that patients with higher depression scores had more severe dry eye. As a result, we recommend performing ophthalmic examinations in newly diagnosed MDD patients. [ABSTRACT FROM AUTHOR]

To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20–82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 μL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = −0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common ocular condition with a significant impact on patients' quality of life. Conventional treatments include behavioral changes, tear substitutes, and anti-inflammatory agents; however, recent advances in the understanding of DED pathogenesis have opened the way to the development of novel treatment strategies able to target several pathways involved in the onset and persistence of DED. Literature search was conducted on PubMed and Scopus around the term 'dry eye disease' and others involving its pathophysiology and therapeutic strategy. The primary focus was on recent drugs approved by FDA or under investigation in phase 3 clinical trials. Google and ClinicalTrials.gov were used for obtaining information about the status of FDA approval and ongoing clinical trials. Due to its multifaced pathogenesis, DED management is often challenging, and patients' needs are frequently unmet. Recently, several novel treatments have been either FDA-approved or studied in late-phase trials. These novel drugs target-specific biological components of the ocular surface and reduce inflammation and ocular pain. Additionally, new drug delivery systems allow for increased bioavailability, improve effective dosing, and minimize ocular side effects. These advances in drug therapies show real promise for better management of DED patients. [ABSTRACT FROM AUTHOR]

Background: To investigate the validation of phenol red thread (PRT) test in a Chinese population by evaluating the intraobserver repeatability and interobserver reproducibility, determining correlations between the PRT test and other dry eye disease (DED) parameters including tear meniscus height (TMH) and Schirmer I test, and testing the accuracy of diagnosing DED when using the PRT test alone. Methods: A total of 108 eyes were involved in this prospective and diagnostic study, and were divided into two groups (with and without DED). Each subject underwent a series of ocular surface examinations, including Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH) assessment, PRT test, fluorescein tear breakup time (FBUT), corneal fluorescein staining and Schirmer I test. Results: In the experimental group and the control group, the intra-class correlation coefficients (ICCs) of the repeatability were 0.747 and 0.723, respectively (all P < 0.05). The ICCs of the reproducibility in both groups were 0.588 and 0.610, respectively (all P < 0.05). The PRT test correlated weakly with the Schirmer I test and the tear meniscus height, with Spearman coefficients of 0.385 and 0.306, respectively (all P < 0.05). The PRT test is available to diagnose DED, with an area under the curve of 0.806 and a Youden index of 0.556 at the cutoff point of 8.83 mm. Conclusions: The PRT test can provide patients a comfortable, timesaving and less irritating approach to screening and diagnosing DED compared to Schirmer I test. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to compare the ocular surface temperature in keratoconus eyes with that in normal eyes. Methods: A total of 27 participants were enrolled, with 10 and 17 participants in the keratoconus and control groups, respectively. Participants in the control group underwent an ophthalmic slit lamp examination and ocular thermography, while an additional corneal tomography was performed for those in the keratoconus group. Results: For patients with keratoconus, the mean upper eyelid temperature (UET) was 32.36 ± 1.02 °C, inner canthus temperature (ICT) was 34.25 ± 0.83 °C, outer canthus temperature (OCT) was 33.62 ± 0.96 °C, initial central corneal temperature (initial CCT) was 33.04 ± 1.03 °C, sixth-second CCT (6 s-CCT) was 32.67 ± 1.19 °C, and the mean change in CCT measured within 6 s (change in CCT within 6 s) was 0.36 ± 0.26 °C. For controls, the values for UET, ICT, OCT, initial CCT, 6 s-CCT, and change in CCT within 6 s were 32.35 ± 1.13 °C, 34.14 ± 0.91 °C, 33.51 ± 1.02 °C, 33.22 ± 1.01 °C, 32.99 ± 1.01 °C, and 0.22 ± 0.17 °C, respectively. Except for the change in CCT within 6 s (p = 0.022), no significant differences were observed in UET (p = 0.973), ICT (p = 0.659), OCT (p = 0.697), initial CCT (p = 0.556) or 6 s-CCT (p = 0.310) between the two groups. Conclusion: The keratoconus eyes showed faster changes in CCT and evaporation of tear film after opening the eyes. Therefore, the keratoconus eyes had a higher incidence of dry eye conditions. [ABSTRACT FROM AUTHOR]

To investigate health disparities in racial and ethnic minorities with dry eye. Medical records were reviewed for demographics, socioeconomic factors, treatments, and objective dry eye parameters. Race/ethnicity was self-reported as delineated by the U.S. Census. The reference group comprised of randomly selected White patients, with number equal to the largest minority group. The study included 465 patients (157 Black, 157 White, 85 Asian, and 66 Hispanic). Compared to White (3.2%) patients, larger proportion of minorities used Medicaid or lacked health insurance (Black 8.3%, P =.054; Asian 10.6%, P =.019; Hispanic 18.2%, P <.001). Black and Hispanic patients had lower estimated median household income than Whites (White $98,472, Black $75,554, P <.001; Asian $105,503, P =.088; Hispanic $86,839, P =.030). Prior to presentation, fewer minority patients received prescription treatments or procedures (White 61.8%; Black 30.6%, P <.001; Asian 43.5%, P =.006; Hispanic 43.9%, P =.014). Although at baseline visit minorities had worse mean conjunctival (White, 1.7; Black 2.2, P =.136, Asian 2.4, P =.022; Hispanic 2.6, P =.005) and corneal staining scores (White, 1.6; Black 2.5, P <.001; Asian 2.3, P =.003; Hispanic 2.4, P =.001), no differences were noted at final visit. Minorities presented with worse objective dry eye parameters, and less prior dry eye care. Income and health care access may not fully explain the observed undertreatment at presentation. Differential management by eye care providers and patient attitudes warrant further investigation. [ABSTRACT FROM AUTHOR]

Introduction: While optical coherence tomography (OCT) measurements of the lower tear meniscus height (LTMH) have been reported in adults, here we obtained LTMH measurements through Fourier Domain OCT in healthy children and compared these with values obtained in healthy adults. Methods: Participants were children 7–17 years of age and a control group of adults 20–40 years of age. Inclusion criteria were no abnormal eye conditions or the use of contact lenses. Candidates who fulfilled the TFOS DEWS II criteria for dry eye disease (DED) were excluded. All subjects underwent LTMH measurement (OCT Spectralis) and tests for non‐invasive tear break‐up time and ocular surface staining. Participants also completed the ocular surface disease index questionnaire. Results: A total of 86 children and 27 adults were included. Mean LTMH values in the children and adult groups were 217.40 ± 71.40 μm and 225.0 ± 54.86 μm, respectively; p = 0.53. However, 59.3% of the children had an LTMH ≤210 μm suggestive of DED, compared with only 33.3% of adults (p = 0.02). For the children, no significant differences in LTMH were observed with sex or for those more or less than 12 years of age. Conclusions: Optical coherence tomography‐derived LTMH measurements were obtained in healthy children. While values were similar in children and adults, a greater proportion of children had an LTMH compatible with a diagnosis of DED. More studies in different paediatric populations are required to establish a complete set of normative LTMH measurements. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a very common ocular condition with a considerable socioeconomic impact affecting patient's visual function and quality of life. Currently, thanks to the better knowledge on DED pathophysiology, therapeutical approaches are focused on the primary core mechanisms of DED. Furthermore, new drugs and compounds are being explored in the light of recent findings concerning unique disease-related pathways. The purpose of this review is to stress DED pathogenesis, addressing its vicious cycle, and highlighting the cutting-edge drug therapy approaches under development. A literature search on the PubMed and Scopus databases was carried out. The database search strategy was formulated around the term 'dry eye disease' and other terms regarding its pathophysiology and therapeutic strategy. Additional search was conducted on ClinicalTrials.gov for unpublished results and ongoing clinical trials. The primary approaches used for DED include lifestyle, environmental changes, tears supplementation, and control of the eyelids and ocular surface inflammation. In selected cases, medical therapy could benefit by technological device-based management. Due to the complexity of DED and the continuous growth of disease prevalence and patients' unmet needs, new therapeutic approaches focused on its pathogenesis are currently under investigation, while others are pending approval. [ABSTRACT FROM AUTHOR]

Purpose: To assess changes in visual function and optical and tear film quality in computer users. Methods: Forty computer workers and 40 controls were evaluated at the beginning and end of a working day. Symptoms were assessed using the Quality of Vision questionnaire (QoV), 5‐item Dry Eye Questionnaire (DEQ‐5) and Symptom Assessment in Dry Eye version II (SANDE II). Tear film quality was evaluated using the Medmont E300 dynamic corneal topography tool to measure the tear film surface quality (TFSQ), TFSQ area and auto tear break‐up time (TBUT). Optical quality was assessed by measuring high, low and total ocular aberrations with a Hartmann–Shack wavefront sensor. Visual performance was assessed by measuring photopic and mesopic visual acuity, photopic and mesopic contrast sensitivity and light disturbance. Results: Poorer DEQ‐5, QoV and SANDE II scores were obtained in computer workers at the end of the working day compared with controls (p ≤ 0.02). Computer workers exhibited a higher (worse) TFSQ and TFSQ area at visit 2 compared with visit 1 (p ≤ 0.04), while no significant differences in TBUT (p = 0.19) or ocular aberrations were observed (p ≥ 0.09). Additionally, both light disturbance (p ≤ 0.04) and mesopic and photopic contrast sensitivity worsened at several spatial frequencies (p ≤ 0.04) throughout the working day in computer workers, while visual acuity remained unchanged (p ≥ 0.07). In contrast, control subjects exhibited no decrease in any variable during the day. Conclusions: While visual acuity remained unchanged, several aspects of visual function and quality of vision decreased over a day of computer use. These changes were accompanied by greater dry eye symptoms and tear film changes, which are likely to have played a fundamental role. The present study provides insight into new metrics to assess digital eye strain. [ABSTRACT FROM AUTHOR]

To evaluate the effect of air pollution on the tear film stability by analyzing the correlation between Air Quality Index (AQI) and Lipid Layer thickness (LLT) in Xuzhou. As a prospective descriptive observational study, 284 patients with meibomian gland dysfunction (MGD), 157 patients with Sjögren's syndrome (SS), and 264 healthy volunteers were included. The tear film lipid layer thickness of the three groups of subjects was measured weekly and compared with the air quality index to analyze the correlation between the two indicators. Logistic regression analysis and linear regression analysis were used to analyze the effect of AQI on the thickness of the tear film lipid layer. The change of LLT with air pollution at different AQI levels was also analyzed. There are obvious seasonal differences in the changes of air pollution index in Xuzhou. Significant differences could be observed in the thickness of the lipid layer of the tear film among the three groups. LLT in the MGD group and SS group decreased with the aggravation of air pollution, while remained unchanged in the control group. There was strong evidence of correlation between LLT of the MGD group (F = 353.494, p < 0.01, adjusted R2 = 0.695) and the SS group (F = 502.404, p < 0.01, adjusted R2 = 0.764) with AQI, while there was minor correlation between LLT with AQI in control group (F = 8.525, p < 0.01, adjusted R2 = 0.046). Air pollution can cause a decrease in the thickness of the tear film lipid layer, thereby affecting tear film stability, leading to the occurrence of dry eye. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine if eyes with unilateral pterygium are more likely to suffer from dry eye symptoms and more prone to have abnormalities in dry eye parameters than healthy eyes. Methods: Forty eyes of 20 patients were enrolled. The eyes that were diagnosed as having pterygium were considered as Group 1 and other healthy eyes of the same patients were defined as Group 2. The existence of dry eye was tested with tear film break-up time, Schirmer-1 test, Oxford scale, and Ocular Surface Disease Index (OSDI) score assessments. Results: Median tear film break-up-time measurement and Schirmer 1 value were lower in Group 1; however, no statistically significant difference was detected (p=0.06 and p=0.308, respectively). Median OSDI score and median Oxford scale score were higher in Group 1; however, no statistically significant difference was detected (p=0.05 and p=0.250, respectively). Conclusion: Between eyes with pterygium and healthy ones, there was difference in dry eye test results. These results may show that there might be a relationship between pterygium and dry eye disease regardless of the genetic background and environmental factors. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the efficacy and safety of LipiFlow® thermal pulsation treatment system compared with lid massage combined warm compress in Chinese patients with meibomian gland dysfunction (MGD). Methods: Patients (n = 100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n = 50 eyes) received a single LipiFlow® thermal pulsation system treatment. In warm compress group, patients (n = 50 eyes) underwent warm compress daily for two weeks after an initial manual lid massage. Patients' symptoms were evaluated using Standard Patient Evaluation for Eye Dryness (SPEED) questionnaire. Safety parameters included best-corrected visual acuity (BCVA), intraocular pressure (IOP) and objective parameters including meibomian glands yielding lipid secretion (MGYLS) number, meibomian glands secretion (MGS) score, lipid layer thickness (LLT), tear-film breakup time (TBUT), corneal fluorescein staining (CFS) were measured and presented from baseline and to 3 months post-treatment. Results: Baseline parameters in both groups were comparable (p > 0.05). SPEED score and TBUT improved in two groups from baseline to 3 months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3 months. CFS showed significant improvement in warm compress group at 1 month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number. Conclusion: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3 months. [ABSTRACT FROM AUTHOR]

Aim To compare the outcomes of autologous platelet rich plasma (PRP) eye drops and inferior silicone punctal plugs in the treatment of moderate to severe dry eye disease (DED). Patients and methods This retrospective non-randomized comparative study included 46 patients with bilateral moderate to severe DED during the period from May 2021 to June 2022. They were divided into two groups, Group I: patients treated with autologous PRP eyedrops and Group II: patients treated with an inferior silicone punctal plug. The mean values of ocular surface disease index (OSDI), Schirmer's test (ST), fluorescein break up time (FBUT), and corneal fluorescein staining (CFS) were calculated for each group at baseline and at 2 weeks, 1 month, and 3 months followup. Mean posttreatment values were compared with baseline in each group. Mean values at baseline and at each follow up visit were compared between the two groups. Any complications were recorded. Results Group I included 50 eyes of 25 patients while group II included 42 eyes of 21 patients. Both groups showed statistically significant improvement in all DED parameters posttreatment compared with baseline (P<0.05). There was no statistically significant difference between the two groups regarding DED parameters at baseline and each follow-up visit (P>0.05). Reported complications were spontaneous loss of the plug in 19 (45.2%) eyes and persistent epiphora in 2 (4.8%) eyes in group II. No complications were noted in group I. The difference in complication rates between the two groups was highly significant (P<0.001). Conclusion Both autologous PRP eyedrops and inferior silicone punctal plugs are effective in the treatment of moderate to severe DED. However, inferior silicone punctal plugs are associated with more complications. [ABSTRACT FROM AUTHOR]

This study reviewed the efficacy and safety of intense pulsed light (IPL) for the treatment of dry eye disease (DED). The PubMed database was used to conduct the literature search, which used the keywords “intense pulsed light” and “dry eye disease”. After the authors evaluated the articles for relevancy, 49 articles were reviewed. In general, all treatment modalities were proven to be clinically effective in reducing dry eye (DE) signs and symptoms; however, the level of improvement and persistence of outcomes differed amongst them. Meta‑analysis indicated significant improvement in the Ocular Surface Disease Index (OSDI) scores post‑treatment with a standardized mean difference (SMD) = −1.63; confidence interval (CI): −2.42 to −0.84. Moreover, a meta‑analysis indicated a significant improvement in tear break‑up time (TBUT) test values with SMD = 1.77; CI: 0.49 to 3.05. Research suggests that additive therapies, such as meibomian gland expression (MGX), sodium hyaluronate eye drops, heated eye mask, warm compress, lid hygiene, lid margin scrub, eyelid massage, antibiotic drops, cyclosporine drops, omega‑3 supplements, steroid drops, and warm compresses along with IPL, have been found to work in tandem for greater effectiveness; however, in clinical practice, its feasibility and cost‑effectiveness have to be taken into consideration. Current findings suggest that IPL therapy is suitable when lifestyle modifications such as reducing or eliminating the use of contact lenses, lubricating eye drops/gels, and warm compresses/eye masks fail to improve signs and symptoms of DE. Moreover, patients with compliance issues have been shown to benefit well as the effects of IPL therapy is sustained for over several months. DED is a multifactorial disorder, and IPL therapy has been found to be safe and efficient in reducing its signs and symptoms of meibomian gland dysfunction (MGD)‑related DE. Although the treatment protocol varies among authors, current findings suggest that IPL has a positive effect on the signs and symptoms of MGD‑related DE. However, patients in the early stages can benefit more from IPL therapy. Moreover, IPL has a better maintenance impact when used in conjunction with other traditional therapies. Further research is needed to assess cost‑utility analysis for IPL. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the study was to compare the efficacy and safety of two concentration of autologous serum (AS) 20% vs 50% in recalcitrant moderate‑to‑severe dry eye patients. Methods: A double‑blind prospective, interventional, and randomized study was done on 44 patients (80 eyes) clinically diagnosed with moderate‑to‑severe dry eye disease (DED) that was refractory to conventional treatment, and all patients were treated with AS20% or AS50% for 12 weeks. We documented Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), OXFORD corneal staining score (OSS), and Schirmer test (ST) at baseline, 2,4,8, and 12 weeks. These parameters were compared in both groups and between the groups by using Student’s t‑test. The study included 11 males and 33 females. Results: Out of 80 eyes, 33 eyes had moderate and 47 had severe DED. The age of patients in AS20% was 44.73 ± 14.37 years, and in AS50% was 46.41 ± 14.47 years. The most common etiology associated with DED was secondary Sjogren syndrome. In moderate DED, both the groups showed significant improvement in both subjective and objective parameters. But in severe DED, the AS20% group failed to show any significant improvement objectively, though subjective improvement was present. Conclusion: In refractory severe DED patients, AS50% is better option for treatment and in moderate DED both concentrations of autologous serum are effective. [ABSTRACT FROM AUTHOR]

Purpose: The use of face masks has been proposed to cause or exacerbate the symptoms of dry eye disease (DED), which has been widely discussed under the term mask-associated dry eye (MADE). However, no studies have systematically investigated tear film parameters during the use of different face masks. Therefore, the objective of the present study was to investigate clinically relevant parameters of the tear film before and during the short-time use of face masks in dry and normal eyes. Methods: In a prospective study, the tear film parameters of 42 DED patients and 42 healthy volunteers were examined while wearing different types of face masks in a randomized order. This included measurements of non-invasive tear break-up time (NIBUT), lipid layer thickness, tear meniscus height, and bulbar redness after 30 min of wearing no mask, a surgical face mask or an FFP2/K95 mask. The equivalence of the means was assessed using the two one-sided t-test (TOST) method. Results: In healthy volunteers' lipid layer thickness, NIBUT and tear meniscus height were not significantly altered by 30 min of surgical or FFP2 mask wear (p > 0.016). The use of either type of mask was significantly associated with decreased bulbar redness (p < 0.001) in healthy eyes. In patients with DED, none of the tear film parameters or bulbar redness were significantly altered by 30 min of mask wear (p > 0.016). Conclusions: Based on these results, the short-term wearing of face masks, regardless of type, did not produce a significant difference in tear film parameters of lipid layer thickness, NIBUT, and tear meniscus in healthy or dry eyes, while bulbar redness was reduced after mask wear only in healthy volunteers. [ABSTRACT FROM AUTHOR]

To describe tear concentrations of IL-1β, Il-6, IL-8, IL-10, IL-17A, IFNγ and TNFα in tears, collected by microcapillaries, and their correlation with symptoms and signs in subjects with dry eye disease (DED) in the DREAM Study. Cytokine levels of patients with moderate to severe DED were determined using a magnetic bead assay. Scores for Ocular Surface Disease Index, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer's test were obtained using standardized procedures. Associations of cytokines with each other and signs/symptoms were assessed with Spearman correlation coefficients (r). Assay results from 131 patient samples from 10 sites with tear volumes ≥ 4 ul were analyzed. Cytokine concentrations did not correlate with each other in a generally acknowledged pro-inflammatory/anti-inflammatory pattern, such as proinflammatory IL-17A and IFNγ were not inversely correlated to anti-inflammatory cytokine IL-10, and cytokines did not correlate with DED symptoms. Lower corneal staining was correlated with higher concentrations of IL-17A (r= −0.24, p = 0.006), IL-10 (r= −0.25, p = 0.005) and IFNγ (r= −0.33, p = 0.0001). Higher concentrations of IFNγ were associated with lower conjunctival staining (r= −0.18, p = 0.03). Higher concentrations of IL-17A were associated with higher TBUT scores (r = 0.19 p = 0.02). Cytokines IL-10, IL-17A and IFNγ were highly correlated with each other but weakly correlated with some DED signs. No key cytokines or definitive expression patterns were identified in this study of moderate to severe DED patients. Further studies addressing various biases, including methodological and sampling biases, and standardization of methodology for inter-laboratory consistency are needed to confirm and establish pathological and clinical relevance of tear cytokines in DED. [ABSTRACT FROM AUTHOR]

Introduction: To analyze outcomes on objective ocular surface parameters and subjective symptoms of serial weekly sessions using the Activa mask in patients with meibomian gland dysfunction (MGD). Methods: This is a prospective study including patients with symptomatic MGD who were treated with four weekly sessions using the Activa mask (SBM Sistemi, Turin, Italy). Noninvasive ocular surface examination was carried out before (T0) and 2 weeks after the last mask session (T1) using Idra (SBM Sistemi, Turin, Italy) for the measurement of: (1) noninvasive break-up time (NIBUT); (2) lipid layer thickness (LLT); (3) tear meniscus height (TMH); (4) meibomian gland loss (MGL) of upper and lower eyelids. The I-Pen tear osmolarity system (I-Med Pharma Inc, Dollard-des Ormeaux, Quebec, Canada) was used to measure tear osmolarity values. Ocular discomfort symptoms were ascertained by means of the ocular surface disease index (OSDI) questionnaire. Results: All 25 patients (11 males, 14 females; mean age 57.1 ± 11.9 years) regularly completed the cycle of four mask sessions. No patients used prohibited medications, and no device-related adverse events were noted. At T1, mean values of NIBUT and LLT increased significantly compared to T0 (respectively from 6.0 ± 1.4 to 6.6 ± 1.2 s, P = 0.043, and from 53.2 ± 17.4 to 65.3 ± 16.3 nm, P < 0.001), while mean values of MGL and tear osmolarity decreased significantly (respectively from 17.1 ± 9.3 to 15.1 ± 8.0%, P = 0.014, and from 307.3 ± 12.2 to 301.5 ± 6.8 mOsm/l, P = 0.005). In parallel, OSDI score reduced significantly from 62.4 ± 11.7 at T0 to 34.5 ± 11.2 at T1 (P < 0.001). Conclusion: Weekly serial sessions using the Activa mask significantly improved objective parameters of the ocular surface as well as subjective ocular discomfort symptoms in patients with recalcitrant MGD. As a further benefit from the treatment, patients were able to avoid the use of concomitant medications, apart from tear substitutes, throughout the study. [ABSTRACT FROM AUTHOR]

Ocular surface pain has been traditionally lumped under the umbrella term 'dry eye' (DE) but is now understood as its own entity and can occur in the absence or presence of tear dysfunction. Identifying patients at risk for the development of chronic ocular surface pain, and factors contributing to its severity are important in providing precision medicine to patients. In this review, we discuss factors linked to the presence and severity of ocular surface pain, including eye-related features, systemic characteristics, and environmental findings. We discuss corneal nerves, whose anatomic and functional integrity can be characterized through in vivo confocal microscopy images and testing of corneal sensitivity. We review systemic diseases that are comorbid with ocular surface pain, including physical and mental health diagnoses. Finally, we identify environmental contributors, including air pollution, previous surgeries, and medications, associated with ocular surface pain. Intrinsic and extrinsic factors contribute to ocular surface pain and must be considered when evaluating an individual patient. These factors can inform the suspected etiology of the pain, and guide management decisions such as tear replacement or medications targeting nerve pain. [ABSTRACT FROM AUTHOR]

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To evaluate the effect of dry eye disease (DED) on the central corneal thickness and anterior corneal surface irregularity parameters using Scheimpflug tomography. In this study, the central corneal thickness and topometric indices of the anterior corneal surface were compared between the right eyes of 43 subjects with dry eye (DE group) and the right eyes of 35 non-dry eye individuals (NDE group). The central corneal thickness (CCT) and the topometric indices of the anterior corneal surface, including IVA, IHA, ISV, and IHD, were measured using the Pentacam HR (Pentacam-HR, Oculus, Wetzlar, Germany). Dry eye was diagnosed using a symptom questionnaire, TBUT, and Schirmer’s test without anesthesia. The mean ISV, IVA, IHA, and IHD were 17.02 ± 3.43, 0.114 ± 0.04, 5.82 ± 4.82, and 0.011 ± 0.01 in the DE group and 14.65 ± 3.10, 0.086 ± 0.03, 3.70 ± 3.23, and 0.007 ± 0.00 in the NDE group, respectively. All of the above corneal irregularity indices were significantly higher in the DE group (P<0.05). The mean CCT was 531.19 μ (±34.88 μ) and 540.66 μ (±27.13 μ) in the DE and NDE group, respectively. Based on linear regression analysis, ISV, IVA, IHA, and IHD had a significant association with DED (P<0.05), while CCT had no significant association with DED (P=0.148). DED significantly increases corneal surface irregularity, but it has no significant effects on CCT measured by the Pentacam. [ABSTRACT FROM AUTHOR]

Background. Osmolarity is used to detect symptoms of dry eye disease (DED) and can be measured using TearLab™ and I-Pen® systems. Objectives. To investigate the correlation between osmolarity measurements using the TearLab™ and I-Pen® systems in subjects with a high body mass index (BMI). Materials and methods. Thirty male subjects with a high BMI (27-48 kg/m2; 23.3 ±2.1 years old) participated in this study. The control group consisting of 30 healthy males (24.9 kg/m2; 22.9 ±2.1 years old) was also enrolled. Osmolarity measurements were recorded from the right eye using the TearLab™ and I-Pen® systems, and interviews were conducted to determine ocular surface disease index (OSDI) scores. Results. The OSDI (p = 0.042), TearLab™ (p < 0.001) and I-Pen® (p < 0.001) scores were significantly higher in the study group than in the control group. In the study group, OSDI scores ranged from 2 to 16 (median 8.0, interquartile range (IQR) 6.8), while it was from 0 to 10 (median 6.3, IQR 4.1) in the control group. The TearLab™ osmolarity scores were in the range of 278-309 mOsm/L in the study group, whereas the I-Pen® osmolarity measurements were in the range of 294-336 mOsm/L in the study group, compared with 263-304 mOsm/L and 278-317 mOsm/L in the control group, respectively. In the study group, there was a strong correlation between the TearLab™ and I-Pen® osmolarity scores (r = 0.934; p = 0.001). In addition, strong correlations were found between the BMI and both TearLab™ (r = 0.736; p = 0.001) and I-Pen® (r = 0.707; p = 0.001) scores, as well as between the OSDI scores and both TearLab™ (r = 0.731; p = 0.001) and I-Pen® measurements (r = 0.666; p = 0.001). Conclusions. Osmolarity measurements using the I-Pen® system were significantly higher than those recorded using the TearLab™ system in subjects with a high BMI. The I-Pen® measurements showed large variations in osmolarity scores and were highly unreliable in correctly identifying normal eyes compared to the TearLab™ system. Also, a strong correlation was found between the osmolarity scores obtained from the TearLab™ and I-Pen® systems. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye is a component of computer vision syndrome (CVS) which is affected by the duration of using a visual display terminal (VDT), such as playing online games. Purpose: To analyze the correlation between the duration spent playing online games and the degree of dry eye complaints and quality of life. Methods: This research is cross-sectional research conducted on students of the General Practitioner Study Program, Faculty of Medicine, Universitas Nusa Cendana, Kupang, Indonesia, who play online games through Zoom meetings and WhatsApp with a total sampling method on 47 respondents. Data was acquired through online game playing duration questionnaire and dry eye related quality of life score (DEQS) questionnaire. The inclusion criteria in this research was an active medical student of the Universitas Nusa Cendana, Kupang, Indonesia, who had a habit of playing online games and had good literacy skills. This research used eta square statistical analysis. Results: From the 47 acquired samples, the most prominent acquired sample was male (70.2%). DEQS score that was acquired was vary. The lowest score 0-10 is was present on 25.53% of samples, score 11-74 was present on 72.34% of samples and the highest score (75) is present on 2.1% of samples. Impaired quality of life score was found on dry eye range (31-75). There was no significant correlation between the duration spent online playing games and the degree of dry eye complaints (p = 0.693). There was significant correlation between degree of dry eye complaint and quality of life (p = 0.000). Conclusions: The duration of spent online playing games has no effect on the degree of dry eye complaints. The degree of dry eye complaints can affect the quality of life. [ABSTRACT FROM AUTHOR]

Purpose: To compare the performance and safety of 2 tear substitutes containing sodium hyaluronate (SH); one containing 0.15% SH and polyethylene glycol (PEG) 8000, and the other containing 0.18% SH. Methods: In this multicenter, randomized, investigator-masked, noninferiority trial, 83 patients with moderate or severe dry eye disease underwent a 2-week washout, and were then randomly assigned (1:1) to receive SH plus PEG tear substitute (n = 45) or comparator SH tear substitute (n = 38) 3-6 times daily for 3 months. The primary performance endpoint was the change from baseline in the ocular surface fluorescein staining (OSFS) score on day 28 in the per-protocol (PP) population, according to the 15-point Oxford Scheme, with a noninferiority margin of 2. Results: Both groups improved significantly in terms of signs and symptoms. Among the 78 patients without major protocol deviations (the PP population), the OSFS score decreased by 2.9 ± 2.0 on day 28 from 5.4 ± 1.3 at baseline in the SH plus PEG group and by 2.3 ± 2.2 from 5.2 ± 1.4 in the comparator group (95% confidence interval of the difference: -1.2 to 0.3), demonstrating noninferiority. On day 90, the improvement in OSFS scores was significantly greater in the SH plus PEG group (P = 0.0002). The safety profiles were satisfactory in both groups. Conclusion: SH plus PEG tear substitute was noninferior to SH tear substitute in the studied population and may provide additional benefits in the long term. ClinicalTrials.gov ID: NCT02975102. [ABSTRACT FROM AUTHOR]

To determine the metabolic activity, and cytokine expression over time from immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. HCECs were cultured and expanded in DMEM/F-12 with 10% FBS. The cells were exposed to either normal media (295 mmol/kg) or hyperosmolar media (500 mmol/kg) for 0.25, 3, 6, and 12 hours. After each exposure duration, metabolic activity was quantified using alamarBlue, and a panel of pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, IFN-γ, and IL-17A) was quantified using multiplexed electrochemiluminescence (Meso Scale Diagnostics, Rockville, MD). Metabolic activity of the HCEC exposed to hyperosmolar conditions was significantly reduced at the 3-, 6-, and 12-hour mark compared to the control (all p < 0.01). There was no significant difference in cytokine expression between the hyperosmolar media and control at the 0.25- and 3-hour mark for all cytokines (all p ≥ 0.28). The difference in cytokine expression between the hyperosmolar media and the control was significant for IL-1β, IL-4, IL-6, IL-8, IL-12p70, IL-13, and TNF-α at the 6-hour mark (all p ≤ 0.02). No significant change in cytokine expression between the hyperosmolar media and control was noted for IL-2, IL-10, IL-17A, and IFN-γ (all p ≥ 0.74) at the 6-hour mark. Hyperosmolar stress reduced cell metabolic activity and increased expression of IL-1β, IL-4, IL6, IL8, IL-12p70, IL-13, and TNF-α over a 6-hour period in an immortalized HCEC line. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease is common after refractive procedures due to tear film instability. There are several causative factors for tear film instability, but the state of individual components of the tear film is not assessed much in published literature. This article quantifies the lipid layer thickness (LLT) of the tear film using surface interferometry before and after the small incision lenticule extraction (SMILE) refractive procedure. Objectives: This study aimed to evaluate the effects of femtosecond SMILE on the postoperative stability of the LLT of the tear film. Design: This was a prospective, interventional, non-case–control study. Methods: A total of 160 eyes of 80 patients were enrolled in the study. The follow-up period was 6 months after surgery. A noninvasive surface interferometer was used to measure the thickness of the lipid layer before surgery and was repeated at 3 and 6 months after surgery. The main outcome measure was the change in average LLT at 3 and 6 months after SMILE and its statistical significance. Results: There were 48 women and 32 men. Age ranged from 21 to 42 years (mean = 27 ± 6.4). Mean LLT at baseline was [oculus dextrus (OD) = 53.38 (±7.24) nm; oculus sinister (OS) = 52.21 (±6.95) nm], at 3 months [OD = 54.38 (±5.75) nm; OS = 53.26 (±5.70)], and at 6 months [OD = 53.31 (±5.66) nm; OS = 52.39 (±5.94)]. Mean LLT showed mild improvement at 3 months after surgery (OD = 53.38–54.38 mm, p = 0.0417; OS = 52.21–53.26 mm, p = 0.0398). There was no significant change in LLT from the baseline before surgery to levels 6 months after surgery (p = 0.8914 OD; p = 0.7368 OS). Conclusion: The SMILE refractive procedure did not alter the LLT that remained stable and adequate at 6 months postoperative follow-up. [ABSTRACT FROM AUTHOR]

Background: To compare the Ocular surface disease index (OSDI) score, Schirmer I test (SIT), fluorescein break up time (FBUT) and fluorescence staining (FLCS) score of dry eye patients at different ages.Methods: 90 eyes of 90 patients with mild to moderate dry eye from September 2020 to September 2021 were retrospectively included and were divided into young group (20-39 years, n = 29), middle-age group (40-59 years, n = 30), and elder group (> 60 years, n = 31). Patients were given a 28-day topical lubricating ocular surface and repair-promoting drugs combined with local physical therapy. Patients were followed up at 7, 14 and 28 days. The OSDI score, SIT, FBUT and FLCS score were examined.Results: There were differences between the OSDI score in three groups at each time point (all P < 0.001). SIT were different among the three groups (F = 350.61, P < 0.001), and a time effect was found (F = 80.87, P < 0.001). SIT at 14 and 28 days after treatment in middle-age and elder groups were lower than young group (all P < 0.001). SIT at 7, 14 and 28 days in elder group were lower than middle-age group (all P < 0.001). FLCS score was lower at 28 days than other time points (all P < 0.001).Conclusion: Dry eye patients are given a 28-day topical lubricating ocular surface and repair-promoting drugs combined with local physical therapy, which can promote tear secretion, film stability, and the recovery of corneal integrity. Age affects the treatment effect of mild to moderate dry eye, among which tear secretion is the most significant. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) has been used as a topical treatment for various ocular surface diseases including dry eye disease (DED). Several CsA formulations are available as solutions or emulsions. This review describes the development and the preclinical testing of a cationic oil-in-water emulsion of CsA (CE-CsA) in terms of pharmacodynamics, pharmacokinetics, and ocular tolerance. Due to the cationic charge, CE electrostatically interacts with the negatively-charged ocular surface, improving its residence time. Compared to other CsA formulations, CE-CsA and CE itself were found to reduce the signs and symptoms of DED, by restoring tear film stability and properties, and inhibiting the expression and secretion of pro-inflammatory factors. No delay in wound healing nor ocular toxicity were observed using CE formulations. these findings indicate that the type of vehicle can significantly affect the performance of eye drops and play an ancillary role in DED treatment. CE appears as a promising strategy to deliver drugs to the ocular surface while maintaining its homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the efficacy and safety of a new-generation intense pulsed light (IPL) device in improving the symptoms and signs of meibomian gland dysfunction (MGD)-related dry eye, and compare it with a traditional IPL device. Methods: This multicenter randomized controlled trial enrolled 132 patients with MGD-related dry eye from two centers. Patients were randomly assigned into the new-generation IPL (Eyesis) group or traditional IPL (E-Eye) group, and then blinded to receive treatment on days 0 and 7. Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear breakup time (TBUT), corneal fluorescein staining (CFS), Schirmer test, and meibomian gland signs were evaluated on days 0, 7, and 14. The primary outcome was defined as the effective rate of treating MGD at day 14. Any adverse events were recorded for safety assessment. Intergroup comparisons and non-inferiority analysis were performed. p values less than 0.05 were considered statistically significant. Results: Basic information showed no significant difference between treatment groups. The intergroup difference of the effective rate was − 1.7% in the left eye and 1.6% in right eye, verifying the non-inferiority of the Eyesis device (p = 0.927). Significant improvements in OSDI, TBUT, Schirmer test, TMH, CFS, and meibomian gland signs were observed in Eyesis group on days 7 and 14 (all p < 0.05). Compared to the E-Eye group, the Eyesis group achieved more significant improvements in OSDI, TBUT, Schirmer test, TMH, and meibum quality (all p < 0.05). There was no significant difference in the incidences of adverse events between groups (p = 1.000). Conclusions: The new-generation IPL was effective and safe in relieving the symptoms and signs of MGD-related dry eye, exhibiting a non-inferior effective rate compared to the traditional IPL. Additionally, Eyesis showed more clinical benefits over E-Eye in alleviating symptoms, increasing tear film stability and improving meibomian gland function. [ABSTRACT FROM AUTHOR]

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Purpose: To evaluate the use of meibography as an objective measure of the effects of incision & curettage (I&C) chalazion surgery on meibomian gland loss and morphology as well as dry eye syndrome. Methods: This prospective, interventional clinical study included adult patients with a primary chalazion which persisted despite conservative treatment. All patients underwent I&C surgery. The following parameters were compared both preoperatively and 21 days postoperatively: meibography, tear breakup time (TBUT), Schirmer test, meibum expression, tear meniscus height, meibomian gland dysfunction (MGD) grading, and the Ocular Surface Disease Index (OSDI). Results: Thirty eyelids were enrolled in the study. The mean age ± SD was 40.56 ± 13.94 years. Meibography demonstrated a significant decrease in meibomian gland loss (P = 0.00) and improvement in morphology. The most common meibomian gland pathology preoperatively noted was morphological signs of atrophy that included fluffy areas and tortuous glands. Both of these findings improved postoperatively (P = 0.04 and P = 0.02, respectively). There were a significant change in MGD grading and a significant decrease in meibum expression score postoperatively (P = 0.00). TBUT and tear meniscus height also improved significantly (P = 0.00 and P = 0.003, respectively). The OSDI score improved significantly as well (P = 0.00). Conclusion: While incision and drainage surgery is a time-honored, standard treatment for chalazion, meibography now demonstrates a global improvement in the meibomian glands, not just the ones involved with the chalazion. In addition to the improvements in the clinical and dry eye syndrome parameters improvements, meibography findings demonstrate that early I&C surgery restores the meibomian glands architecture significantly. [ABSTRACT FROM AUTHOR]

Introduction: DE-089C is a newly developed long-acting formulation of diquafosol ophthalmic solution with less frequent administration (three times daily) than the currently approved and clinically used diquafosol ophthalmic solution (six times daily), hereinafter referred to as DQS. DE-089C is desirable for achieving better patient adherence in clinical practice for dry eye therapy. The objective of this study was to confirm the efficacy and safety of DE-089C in patients with dry eye compared to placebo. Methods: This randomized, multicenter, double-masked, placebo-controlled, parallel-group phase 3 study was conducted in Japan. Patients with aqueous-deficient dry eye satisfying Schirmer's test I results ≤ 5 mm/5 min were included. A total of 337 patients with dry eye were randomized in an equal ratio to treatment with DE-089C or placebo ophthalmic solution, three times daily for 4 weeks. The primary endpoint for efficacy was change in fluorescein corneal staining score from baseline to week 4. The incidence of adverse drug reactions was investigated for safety evaluation. Results: The background characteristics of patients in the two groups were similar. Primary endpoint of change in fluorescein corneal staining score at week 4 in the DE-089C group was significantly improved compared with the placebo group (least squares mean difference − 0.51, 95% CI − 0.754 to − 0.269, P < 0.0001). The secondary endpoint of the Lissamine green conjunctival staining score was also significantly improved in the DE-089C group compared to that in the placebo group, while other secondary endpoints were not achieved in this study. Commonly (incidence ≥ 1%) reported adverse drug reactions in the DE-089C group were eye irritation (3.6%) and eye discharge (1.8%) with mild severity, and the incidences of these two events were not higher than those in previous clinical studies on DQS. Conclusion: The efficacy and safety of DE-089C administered three times daily at half the dosage of DQS in patients with dry eye were confirmed in this study. Trial Registration: Japan Pharmaceutical Information Center ID, JapicCTI-205177. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of prolonged surgical face mask wearing on dry eye symptoms and tear film break-up time (T-BUT) in health care professionals. Materials and methods: A total of 33 health care professionals were included in the present cross sectional prospective study. In addition to a complete ophthalmological examination T-BUT measurements were performed twice for all participants in the morning (8 am) and in the afternoon (5 pm). The subjects also filled-in the ocular surface disease index (OSDI) questionnaire twice, before and after wearing the face mask, on the same day. Results: Sixty-six eyes of 33 participants (17 female and 16 male) were evaluated. The mean age was 33.6 ± 7.55 (24–48) years and mean total duration with mask on between the two evaluations was 514 ± 12.5 (495–526) minutes. The mean T-BUT was 9.3 ± 1.0 (3–16) seconds at 8 am and 8.3 ± 1.5 (3–14) seconds at 5 pm (p = 0.01). The mean OSDI score was 20.1 ± 8.3 (0–68.75) at 8 am and 27.4 ± 10.4 (0–81.25) at 5 pm (p < 0.01). Conclusion: Use of a surgical mask for the entire work-day was seen to worsen T-BUT and increase dry eye symptoms in healthy individuals. Ophthalmologists should be aware of the possibility of worsening of dry eye symptoms with the prolonged use of surgical face masks and consider modifications if necessary. [ABSTRACT FROM AUTHOR]

Purpose: To assess the potential additive effects of short‐term display use and contact lens (CL) wear on the ocular surface and tear film. Methods: Thirty‐four healthy volunteers (20.87 ± 2.33 years old) participated in this study. Participants' dry eye symptoms, ocular surface, tear film and pupil size were assessed before and after executing a 20‐min reading task on a computer and a smartphone with and without CL wear, or with CL wear and artificial tear instillation. Measurements included the Ocular Surface Disease Index (OSDI) questionnaire; 5‐item Dry Eye Questionnaire (DEQ‐5); tear meniscus height (TMH); noninvasive keratograph break‐up time (NIKBUT); bulbar conjunctival redness (BR) and pupil size. Results: Higher symptoms were reported after reading on both displays with and without CLs (p ≤ 0.001) for short periods. BR was higher and NIKBUT shorter after reading on the computer regardless of wearing CLs (p ≤ 0.02 and p ≤ 0.02, respectively), while TMH increased for all conditions (p ≤ 0.02) except for CL computer reading (p = 0.23). Reading with CLs did not lead to greater signs of dry eye (BR, NIKBUT) and symptoms compared with reading unaided (p > 0.05), although a smaller increase in TMH was observed when reading on the computer with CLs (p = 0.005). Artificial tear instillation during CL wear led to a smaller increase in symptoms (p ≤ 0.02), a smaller increase in BR (p ≤ 0.04) and a decrease in NIKBUT (p = 0.02) compared to reading without correction. Conclusions: Disposable CL wear had no additive effects on signs and symptoms of dry eye when using digital devices for short periods. The instillation of artificial tears is an effective strategy for reducing the impact of display use in CL wearers. [ABSTRACT FROM AUTHOR]

Dry eye is one of the most common ocular surface diseases in the world and seriously affects the quality of life of patients. As an immune-related disease, the mechanism of dry eye has still not been fully elucidated. The cGAS-STING pathway is a recently discovered pathway that plays an important role in autoimmune and inflammatory diseases by recognizing dsDNA. As an important signal to initiate inflammation, the release of dsDNA is associated with dry eye. Herein, we focused on the pathophysiology of the immune-inflammatory response in the pathogenesis of dry eye, attempted to gain insight into the involvement of dsDNA in the dry eye immune response, and investigated the mechanism of the cGAS-STING pathway involved in the immune-inflammatory response. We further proposed that the cGAS-STING pathway may participate in dry eye as a new mechanism linking dry eye and the immune-inflammatory response, thus providing a new direction for the mechanistic exploration of dry eye. [ABSTRACT FROM AUTHOR]

Objectives: To determine if patients treated with multiple intravitreal injections for neovascular age-related macular degeneration are more likely to suffer from dry eye and meibomian gland dysfunction. Materials and Methods: Sixty eyes of 30 patients were enrolled. One eye of each patient was treated with multiple monthly intravitreal injections for neovascular AMD (Group 1) and the fellow healthy eye received no treatment (Group 2). The presence of dry eye was evaluated using tear film break-up time, Schirmer 1 test, the Oxford scale, and Ocular Surface Disease Index (OSDI). The loss rate of meibomian glands was evaluated by meibography and was graded and scored (meiboscore) from grade 0 (no loss of glands) to grade 3 (loss of >2/3 of total meibomian glands) for each eyelid. Results: Group 1 had lower mean Schirmer 1 and tear film break up-time measurements and higher mean OSDI score than Group 2, but the differences were not statistically significant (p=0.257, p=0.113, and p=0.212, respectively). Mean Oxford scale scores and meiboscore of the upper eyelids showed no statistically significant difference between the groups (p=0.594, p=0.663, respectively). The meiboscore of the lower eyelids was significantly higher in Group 1 (p=0.048). Conclusion: Multiple factors such as povidone-iodine and the preservatives in topical eye drops may cause inflammation leading to ocular surface damage in patients treated with multiple intravitreal injections. As the treatment requires repeated injections, exposure to these factors might worsen the ocular surface inflammation. The possibility of dry eye and meibomian gland dysfunction should be considered in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the correlation of Meiboscale with symptom score (Ocular Surface Disease Index [OSDI]) and meibomian gland dysfunction (MGD) sign score.Methods: We performed a cross-sectional hospital-based study of 53 patients of primary MGD who filled the OSDI questionnaire form and underwent complete ocular examination. The MGD sign score was calculated in both eyes using the sum of six grading systems proposed by Arita et al. in 2016. The participants underwent imaging of the upper and lower eyelids of both eyes (212 eyelids) by specular microscope. The area of meibomian gland loss (MGL) was visually assessed and scored using the Meiboscale photographic card. Correlation between these three values - OSDI score, sign score, and MGL score based on Meiboscale - was calculated using Spearman's correlation analysis and Jonckheere-Terpstra (J-T) test. Correlation coefficient rs > 0.5 was considered clinically significant.Results: Associations between MGL score and OSDI score, as well as between OSDI and sign score were statistically significant, but not clinically significant (rs = 0.3684, P < 0.001 and rs = 0.41179, P < 0.001, respectively). The association between MGL score and MGD sign score was statistically as well as clinically significant (rs = 0.8392, P < 0.001). J-T test revealed large effect size (P < 0.001, r-effect = 0.93).Conclusion: The Meiboscale card had not been tested for utility in the Indian outpatient setting yet. Meiboscale can be used for reliable assessment and grading of MGD, and has clinical utility similar to the sum of six MGD sign scores. Additionally, assessment of symptoms using OSDI or a similar questionnaire is also recommended. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to identify changes in tear film function and meibomian gland function in children after congenital/developmental cataract surgery.Methods: This study enrolled 16 eyes of 16 congenital/developmental cataract patients (mean age: 8.05 ± 1.43 years) who underwent cataract surgery and 16 eyes of 16 normal volunteers (mean age: 8.31 ± 2.18 years). Clinical assessments were conducted preoperatively and at 1 week, 1, 3 and 6 months postoperatively. Symptom questionnaires, non-invasive tear film break-up time, tear meniscus height, corneal fluorescein staining, lid margin abnormality, meibomian gland expressibility, and meibography were assessed.Results: The ocular symptom score was significantly higher in congenital/developmental cataract patients compared to normal controls during the 5 visits (P = 0.009). And the average non-invasive tear film break-up time was significantly lower in congenital/developmental cataract patients compared to normal controls (P = 0.017). The first non-invasive tear film break-up time and average non-invasive tear film break-up time were lowest at 1 month postoperatively compared to baseline levels (P = 0.008 and P = 0.012, respectively). The lid margin score of the upper eyelid was significantly higher in congenital/developmental cataract patients compared to normal controls at 1 week postoperatively (P = 0.027). The meibum expressibility score decreased significantly during the 5 visits (P = 0.024). No significant difference was observed in meibomian gland tortuosity, meibomian gland width, meibomian gland area and meibomian gland length between the congenital/developmental group and normal controls preoperatively and at 6 months postoperatively (P > 0.05).Conclusion: Tear film stability and meibomian gland function are worsened transiently after congenital/developmental cataract surgery without accompanying meibomian gland morphological changes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association and application value of rheumatoid factor (RF) in diagnosis of dry eye among patients with common autoimmune diseases. Patients and Methods: A retrospective case-control study was conducted from Jan 1st 2019 to Dec 31st 2020, and 117 patients with common autoimmune diseases were enrolled. The concentrations of serum RF were detected. The receiver operating characteristics (ROC) curve was plotted to evaluate the values of RF in diagnosis. Results: Compared with no dry eye patients, patients with dry eye (n = 59, 50.43%) had higher levels of RF (P < 0.001). Moreover, Pearson's correlation analysis showed that RF levels were negatively correlated with Schirmer-I tear test (P = 0.004) and invasive tear film break-up time (P = 0.002), respectively. The statistically significant threshold value (cut-off points) of the RF levels for dry eye was 21.4 (IU/mL), and the areas under the curve (AUC) of RF was 0.73 (95% confidence interval [CI]: 0.639– 0.821; P < 0.001) (sensitivity = 78%; specificity = 58.6%) for dry eye among patients with common autoimmune diseases. Conclusion: Serum levels of RF may be an independent factor for dry eye among patients with common autoimmune diseases, and they may have a high significant value and clinical application value. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence of dry eye disease (DED) and Meibomian gland dysfunction (MGD) in a very old population. Methods: The Ural Very Old Study (UVOS), a population‐based cohort study performed in rural and urban Bashkortostan/Russia, included 1526 (81.1%) out of 1882 eligible individuals aged 85+ years. The participants underwent a detailed medical and ophthalmological examination including Schirmer´s test, slit‐lamp based assessment of the Meibomian glands and an interview. Results: The study included 1493 (97.8%) individuals with available information about DED (mean age: 88.3 ± 2.9 years). Schirmer´s test was ≤5 mm in 388 individuals (34.3%; 95% confidence interval (CI): 31.5, 37.1), and the mean score of subjective dry eye symptoms was 7.52 ± 2.14 (median: 6; range: 6–18; 95%CI: 7.41, 7.63). An MGD grade 1, 2, 3 and 4 was diagnosed in 367 (31.4%), 309 (26.4%), 89 (7.6%) and 39 (3.3%) eyes, respectively. The prevalence of DED diagnosis definition #2 (dry eye score ≥8, Schirmer´s test ≤5 mm) and definition #4 (dry eye score ≥7, Schirmer test ≤5 mm, MGD grade 1+), were 164/1132 (14.5%; 95%CI: 12.4, 16.5), and 167/1131 (14.8%; 95%CI: 12.7, 16.8), respectively. In multivariate analysis, higher DED prevalence was associated with female sex (odds ratio (OR): 2.36; 95%CI: 1.18, 4.71; p = 0.02), rural region of habitation (OR: 2.72; 95%CI: 1.10, 6.70; p = 0.03), longer axial length (OR: 1.30; 95%CI: 1.04,1.62; p = 0.02), higher hearing loss score (OR: 1.03; 95%CI: 1.01, 1.05; p = 0.001) and lower self‐reported salt consumption (OR: 0.64; 95%CI: 0.54, 0.75; p < 0.001). Conclusions: In this population‐based recruited very old study sample aged 85+ years, higher DED prevalence (dry eye score ≥8, Schirmer´s test <5 mm; mean: 14.5%) and MGD prevalence (any grade:68.8%) was associated with female sex, rural region of habitation, longer axial length, higher hearing loss score and lower salt consumption. [ABSTRACT FROM AUTHOR]