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Introduction: Dry eye disease (DED) is a multifactorial condition of the ocular surface (OS) characterized by loss of tear film homeostasis, ocular discomfort, and vision disturbances. Most available ocular lubricants target the aqueous deficiency of the tear, restoring only this layer, leaving the tear lipid stratum deficient, as occurs in most patients with evaporative DED. An innovative propylene glycol-hydroxypropyl guar enriched with a phospholipid nanoemulsion (PG-HPG-PH-N) is indicated to restore deficiencies in both the lipid and aqueous layers of the tear film, and its composition was designed to increase lubricant retention on the OS. The purpose of this study was to evaluate, through the Ocular Surface Disease Index (OSDI) and clinical assessment, the treatment of patients who had DED due to aqueous deficiency arising from mixed or evaporative DED subtypes with a PG-HPG-PH-N ocular lubricant at a reduced frequency of twice a day, in a prospective, multicenter, and single-arm study. Methods: Patients were screened from days − 7 to 0, and from day 1 (baseline and first day of treatment) to day 28 of treatment with this lubricant. After visit 1 (screening visit, days − 7 to 0), designed as pre-treatment OS assessment, patients returned to their research center on days 14 and 28 of treatment for a complete assessment, including anamnesis, the OSDI, corrected visual acuity, tear breakup time (TFBUT), OS staining evaluation, tolerability index, and environmental exposure questionnaire. Results: Seventy patients were enrolled in this study (60 women, 10 men), with a mean age of 45 (range 27–64) years. TFBUT results showed an improvement in tear film stability as vital dyes sodium fluorescein and lysamine green showed a decrease in corneal staining after 14 and 28 days of treatment. No significant adverse events were reported, demonstrating the good tolerability of the lubricant. Conclusions: The PG-HPG-PH-N nanoemulsion can be considered to be a safe and effective ocular lubricant for treating DED due to aqueous deficiency, both mixed and evaporative subtypes. Trial Registration: Brazilian National Research Ethics Commission (ReBEC registration number 16055). [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is a frequently observed condition characterized by ocular discomfort and visual disturbance. It is highly prevalent and impairs patients' quality of life (QoL). This study assessed the benefit of a preservative-free bioprotectant eye drop formulation containing sodium hyaluronate and trehalose (SH-trehalose) with regards to DED, as well as patient satisfaction, through a large-scale real-life survey. Methods: In a multi-center, international, prospective observational study, subjects with DED received SH-trehalose for 84 days. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire-5 items (DEQ-5), and patient satisfaction were assessed at baseline, day 28, and day 84, and clinical evaluations included ocular surface staining, Schirmer test, tear film break-up time (TBUT), and conjunctival hyperemia at baseline and day 84. Results: A total of 312 patients were evaluated, of whom 82.4% were women. The mean age was 57.9 ± 15.2 years. The mean OSDI score at baseline was 41.7 ± 20.6. After 84 days, the mean OSDI score was 27.3 ± 19.8 (p < 0.001). The percentage of patients with a severe OSDI score decreased from 60.3 to 34.5%. The DEQ-5 score significantly (p < 0.001) improved after 28 and 84 days, as did patient satisfaction. Ocular surface staining, Schirmer test, TBUT, and conjunctival hyperemia scores improved significantly (all p < 0.001) for both eyes with SH-trehalose between baseline and day 84. Tolerance of SH-trehalose was good. Conclusions: SH-trehalose significantly improved the clinical signs and symptoms of DED after 84 days. Moreover, it significantly increased patient satisfaction and was well tolerated. Trial Registration: NCT04803240. [ABSTRACT FROM AUTHOR]

Evaporation profiles have a strong effect on tear film thinning and breakup (TBU), a key factor in dry eye disease (DED). In experiments, TBU is typically seen to occur in patterns that locally can be circular (spot), linear (streak), or intermediate to those states. We investigate a two-dimensional (2D) model of localized TBU using a Fourier spectral collocation method to observe how the evaporation distribution affects the resulting dynamics of tear film thickness and osmolarity, among other variables. We find that the dynamics are not simply an addition of individual 1D solutions of independent TBU events, and we show how the TBU quantities of interest vary continuously between spots and streaks in the shape of the evaporation distribution. We also find a significant speedup by using a proper orthogonal decomposition to reduce the dimension of the numerical system. The speedup will be especially useful for future applications of the model to inverse problems, allowing the clinical observation at scale of quantities that are thought to be important to DED but not directly measurable in vivo within TBU locales. [ABSTRACT FROM AUTHOR]

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance. [ABSTRACT FROM AUTHOR]

Introduction: High-tech devices for the assessment of dry eye disease (DED) are increasingly available. However, the agreement between high- and low-tech parameters has been poorly explored to date. Trying to fill these gaps, we conducted a post hoc analysis on a recently published retrospective study on patients with DED receiving both low- and high-tech (Keratograph®) assessments, and treatment with different lubricating eyedrops. Methods: Six clinical questions were defined by the authors, considering literature gaps and their clinical experience, namely: (1) are NIKBUT-i and T-BUT interchangeable parameters? (2) What was the correlation between low- and high-tech parameters in untreated and treated patients with DED? (3) What was the correlation between signs and symptoms at baseline and during/after treatment? (4) Which parameters were better associated with symptoms? And with symptoms change over time? (5) What was the performance of NIKBUT-i and T-BUT in detecting clinically relevant changes? (6) What was the clinical advantage of adding other high- and low-tech parameters, respectively, to NIKBUT-i and T-BUT? Results: Low-tech measures were the best descriptors of the Ocular Surface Disease Index (OSDI) at baseline. In contrast, high-tech assessments demonstrate better performance in detecting changes over time. The distribution of NIKBUT-i data was more dispersed than TBUT both at baseline and follow-up. At a fixed specificity of 80%, the sensitivity in detecting clinically relevant ameliorations of symptoms was 42% for NIKBUT-i and 25% for T-BUT. A battery of high-tech tests could detect 90% of clinical amelioration, compared with 45% with low-tech tests (p < 0.001). Correlation between low- and high-tech parameters in both treated and untreated patients is lacking. Conclusions: Low-tech measures are adequate for diagnostic purposes in DED, whereas high-tech showed better performances at follow-up, particularly when different tests are combined. Overall, poor interchangeability among parameters and agreement with symptoms was reported both with high- and low-tech assessments. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters. Methods: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark–Houwink equation. Results: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose®, Thealoz Duo® Gel, and Hyabak®, and highest (1300 kDa) for Vismed® Multi, Vismed® Gel, and Neovis® Gel. The pH values varied between 5.94 for Treovis® and 8.06 for Systane® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis® and Treovis®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid® to 337.47 mPas·s for Thealoz® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors. Conclusion: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED. [ABSTRACT FROM AUTHOR]

Introduction: Patients with dry eye disease (DED) complain of a multitude of symptoms that affect their visual function and quality of life (QoL). This clinical investigation assessed the performance, tolerance, and safety of a novel preservative-free ophthalmic solution containing xanthan gum 0.2% and desonide sodium phosphate 0.025%. Methods: This was an observational, prospective, multicentric, and post-market clinical investigation to assess the effect of three times a day instillation of the study formulation in patients suffering from DED. The primary objective was to achieve a 50% reduction in conjunctival hyperemia index as assessed with the OCULUS Keratograph after 1 month of treatment compared to baseline values. The secondary objectives included patient-reported outcomes, clinical performance, and safety. Results: Thirty patients were enrolled (21 women, 9 men) with a mean age of 61.10 ± 14.53 years. The instillation of the study formulation was associated with a significant reduction in redness scores after 1 month of treatment compared to baseline (mean − 0.51 ± 0.51; p ≤ 0.0001). Although the primary endpoint was not completely met, a 50% reduction in the conjunctival hyperemia index was achieved in 23% of the participants, and 77% showed a reduction of 26% of the same index. In addition, the ophthalmic solution significantly increased tear film break-up time, and a significant reduction of corneal and conjunctival staining with fluorescein was achieved. It also reduced DED symptoms and had a very good safety profile. Conclusions: the study formulation produced a significant improvement in the signs, symptoms, and QoL of patients with mild to moderate DED with a good safety profile after 1 month of treatment. [ABSTRACT FROM AUTHOR]

Dry eye syndrome (DES) is a tear film disorder caused by increased tear evaporation or decreased production. The heavy workload on the eye and the increased usage of digital screens may decrease blink frequency, leading to an increased evaporation rate and an upsurge in the incidence and severity of DES. This study aims to assess the severity of DES symptoms and the risk factors among university students. A cross-sectional study was conducted at Umm AlQura University to evaluate the severity of DES among students and explore its potential association with digital screen use. Validated questionnaires were used to assess the severity of DES and digital screen usage. The study included 457 participants, of which 13% had symptoms suggestive of severe DES. Furthermore, multiple risk factors had a significant association with the severity of DES, including gender, use of monitor filters, monitor and room brightness, and smoking habits. DES symptoms were prevalent among university students, particularly female students. Although there was no significant association with the duration of screen usage and collage distribution. Other factors however, such as the usage of screen monitors and the brightness of both the monitor and the room, were significantly associated with the severity of DES symptoms. [ABSTRACT FROM AUTHOR]

Introduction: To assess the efficacy and safety of the combination of microblepharoexfoliation (MBE), intense pulse light (IPL) and meibomian gland expression (MGX) for treatment of meibomian gland dysfunction (MGD). Methods: This was a prospective, parallel-control trial conducted from April 2022 to January 2023. Participants were assigned to receive either three sessions of MBE-IPL-MGX treatment and home-based therapy (treatment group) or home-based therapy alone (control group). Outcome measures were assessed at baseline and after 2-month follow-up. Results: Seventy eyes of 70 patients were enrolled. MBE-IPL-MGX treatment achieved better improvements than home-based therapy in ocular surface disease index (OSDI) and symptom assessment in dry eye (SANDE) scores, noninvasive tear film break-up time (NIBUT), lipid layer grade (LLG), loss area meibomian gland (LAMG) and meibomian gland yielding secretion score (MGYSS). The mean differences between the two groups were as follows: OSDI (– 11.23 ± 4.68 points, P < 0.001), SANDE (– 24.63 ± 13.41 points, P < 0.001), NIBUT (1.3 ± 1.57 s, P = 0.033), LLG (0.4 ± 0.04 points, P = 0.003), LAMG (– 2.85 ± 1.69%, P = 0.023) and MGYSS (7.5 ± 2.32 points, P < 0.001). In addition, the increment (Δ) of MGYSS after MBE-IPL-MGX treatment was significantly higher in MGD grades 2 and 3 (all P < 0.001). Conclusions: MBE-IPL-MGX treatment is an effective and well-tolerated procedure that improves dry eye symptoms and signs as well as meibomian gland secretions in patients with MGD. In addition, this treatment is recommended for MGD grades 2 and 3. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the efficacy and safety of Quantum Molecular Resonance (QMR) treatment in patients with severe dry eye disease (DED), as well as its effects on aqueous-deficient (ADDE), evaporative (EDE), and mixed (MDE) dry eye. Methods: In this prospective, interventional study, 81 patients were randomly allocated to received four treatment sessions of QMR at 1-week intervals (Rexon-Eye®, Resono Ophthalmic, Trieste, Italy) (QRM group) or tear substitute four times daily, containing 0.15% sodium hyaluronate and 3% trehalose (Thealoz Duo®, Thea Pharma, France) (SH-TH group). Outcome measures included ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), tear breakup time (TBUT), non-invasive breakup time (NIBUT), corneal fluorescein staining (CFS), lipid layer thickness (LLT), tear film osmolarity (OSM), and meibomian gland dysfunction (MGD) grade, which were assessed at baseline and 1-month and 3-month follow-up. Results: The QMR group achieved better improvements than the SH-TH group in OSDI and SANDE questionnaires, NIBUT, LLT, and CFS. The mean differences between the groups were as follows: OSDI (− 12.4 ± 0.25 points, P = 0.01), SANDE (10.6 ± 1.7 points, P = 0.01), NIBUT (2 ± 0.25 s, P = 0.01), LLT (18.7 ± 0.7 nm, P = 0.01), and CFS (1.2 ± 0.1 points, P = 0.02). In subgroups analysis, QMR treatment demonstrated a beneficial role to improve DED symptoms and signs in ADDE, EDE, and MDE. Conclusion: QMR is an effective and well-tolerated treatment that seems to improve DED symptoms and signs in patients with severe DED. However, further studies are needed to confirm this. Trial Registration: ClinicalTrials.gov identifier NCT06119386. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED) is a common tear film disorder caused by decreased tear production or increased tear evaporation. The increased use of computers in the workplace has brought about the development of ocular health concerns, including dry eye disease. Therefore, this study was designed to determine the prevalence of DED associated with computer work and recommend preventing or reducing its development. This study investigated the prevalence of DED among IT students in Dera Ghazi Khan. Methods: A cross-sectional descriptive study was conducted among 327 undergraduate students of the IT department in the district of Dera Ghazi khan over 5 months from September 2021 to January 2022. DED was assessed subjectively with Ocular Surface Disease Index. Data were analysed using SPSS version 21. The quantitative analysis was presented as mean and standard deviation, and qualitative variables were introduced in frequency and percentages. The chi-square test (Fisher’s exact test) was used to study the significance of associations between dependent and independent variables. Results: The mean age of the participants was 20.25 ± 1.305 years (range 17–25). The prevalence of DED among computer programmers was 47.7%. This study showed that gender (p = 0.31), contact lens usage (p = 0.64), and duration of time spent on computer display units (p = 0.47) were not significant determinants of DED among computer programmers. Conclusion: DED is prevalent among IT students, along with different symptoms. However, further studies are required to adequately measure the prevalence of DED during longer exposure time to computer screens and explore environmental risk factors. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. Methods: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including “dry eye syndrome,” “ocular surface disease,” “medical management,” “artificial tears,” “topical immunomodulators,” and “meibomian gland dysfunction.” Results: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. Conclusion: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes. [ABSTRACT FROM AUTHOR]

Introduction: An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog®, Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph®) assessments. Methods: This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score. Results: Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15 days (6.4 ± 3.6 vs 5.4 ± 3.7 s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45 days (6.8 ± 2.6 vs 5.6 ± 2.3 s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage. Conclusion: These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3–6 months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests. [ABSTRACT FROM AUTHOR]

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis. [ABSTRACT FROM AUTHOR]

Many candidate drugs for dry eye disease (DED) have been assessed over the years in pursuit of demonstrating efficacy in both signs and symptoms. However, patients with DED have very limited treatment options for management of both signs and symptoms of DED. There are several potential reasons behind this including the placebo or vehicle response, which is a frequent issue observed in DED trials. A high magnitude of vehicle response interferes with the estimation of a drug's treatment effect and may lead to failure of a clinical trial. To address these concerns, Tear Film and Ocular Surface Society International Dry Eye Workshop II taskforce has recommended a few study design strategies to minimize vehicle response observed in DED trials. This review briefly describes the factors that lead to placebo/vehicle response in DED trials and focuses on the aspects of clinical trial design that can be improved to mitigate vehicle response. In addition, it presents the observations from a recent ECF843 phase 2b study, wherein the study design approach consisted of a vehicle run-in phase, withdrawal phase, and masked treatment transition, and led to consistent data for DED signs and symptoms and reduced vehicle response post randomization. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the applicability of lower lid margin thickness (LLMT) measurements in adults with and without meibomian gland dysfunction (MGD) by optical coherence tomography (OCT) and keratograph. Methods: This is a cross-sectional, observational study. A hundred and eight volunteers aged 20 to 79, including 68 MGD patients and 40 normal subjects, were recruited. Using OCT and keratograph to measure the LLMT from the posterior lash line to anterior edge or outer edge of the tear meniscus was separately performed two times by the same person. Results: The mean age of normal and MGD subjects was 50.5 ± 14.2 years and 55.8 ± 15.5 years, respectively. The LLMT with OCT and keratograph in MGD patients was significantly greater than that in normal subjects (1.06 ± 0.27 and 1.03 ± 0.25 mm vs. 0.90 ± 0.20 and 0.86 ± 0.16 mm, respectively). In both normal and MGD subjects, the tear meniscus height and LLMT with OCT were both greater than that with keratograph (P < 0.05), and intraclass correlation coefficient (ICC) demonstrated a good agreement in the LLMT measurements between two devices (ICC = 0.83 and 0.79, respectively). Additionally, the LLMT in MGD patients was appeared to be positively correlated with meiboscore (rs = 0.37, P = 0.002). Conclusions: The OCT and keratograph were two reliable tools in the LLMT measurements, which may have potential applications for diagnosis and evaluation of MGD. Furthermore, we found that the LLMT measured by OCT was greater than that measured by keratograph. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED), Meibomian gland dysfunction (MGD), and Sjögren's syndrome dry eye disease (SS-DED) are eye dryness conditions that show significant overlap in various symptoms of ocular discomfort. The aim of this study was to qualitatively explore the patient experience and evaluate content validity of the newly developed Dry Eye Disease Questionnaire (DED-Q). Methods: Semi-structured interviews were conducted with 61 US adults who reported experiencing ocular symptoms due to their physician-confirmed primary diagnosis of DED (n = 21), MGD (n = 20), or SS-DED (n = 20). The open-ended concept-elicitation phase was followed by cognitive debriefing (CD) of the DED-Q to evaluate participants' understanding and relevance of the instructions, items, response options, and recall periods. Interviews were also conducted with eight specialist healthcare professionals to assess clinical relevance of the concepts included. Verbatim interview transcripts were analyzed using thematic analysis in ATLAS.ti v8 software. Results: A total of 29 symptoms and 14 impacts on quality of life were reported across participant interviews. Primary ocular symptoms reported included eye dryness (n = 61/61; 100%), eye irritation (n = 55/61; 90%), eye itch (n = 54/61; 89%), burning sensation (n = 52/61; 85%), and foreign body sensation (n = 51/61; 84%). The most impacted aspects of daily life were using digital screens (n = 46/61; 75%), driving (n = 45/61; 74%), working (n = 39/61; 64%), and reading (n = 37/61; 61%). CD findings showed most participants had good understanding of DED-Q items and confirmed most concepts were relevant to the lived experience of their condition. Aside from few minor changes to the items and examples to facilitate more accurate interpretation, the proposed instruction wording was modified for various symptom and impact modules to encourage participants to focus only on dry eye vision problems. Conclusions: This research identified multiple prevalent symptoms and impacts of DED, MGD, and SS-DED, most of which were similar across the conditions. The DED-Q was confirmed to be a content-valid PRO measure suitable for use in clinical studies to assess the patient experience of DED, MGD, and SS-DED. Future work will focus on evaluating the psychometric properties of the DED-Q for use as an efficacy endpoint in clinical trials. Plain English summary: Dry Eye Disease (DED), Meibomian Gland Dysfunction (MGD), and Sjögren's Syndrome Dry Eye Disease (SS-DED) are conditions related to dryness of the eye. There is no suitable patient-reported outcome (PRO) measure available for use across the three conditions. Interviews were conducted with 61 participants with any of the three conditions to understand the symptoms they experience and their impact on daily life. The findings were used to refine the content of a new PRO measure, the Dry Eye Disease Questionnaire (DED-Q). To evaluate the suitability of the DED-Q, participants were also asked to complete each item of the DED-Q during the interview and share their understanding of the item wording, response options and the recall period. Interviews were also conducted with eight healthcare professionals (HCPs). The main symptoms reported by the patients across three conditions were eye dryness, eye irritation, eye itch, burning sensation, and foreign body sensation. The symptoms caused difficulties in performing activities such as using digital screens, driving, working, and reading. Almost all participants demonstrated good understanding of the items on the DED-Q and found them to be relevant to their experience of their condition. The HCPs also confirmed that the concepts covered in the DED-Q were relevant to assess the participant experience across these conditions. Next steps will involve a more detailed analysis of the measurement properties of the DED-Q to confirm its usefulness in supporting primary or secondary endpoints in clinical trials. [ABSTRACT FROM AUTHOR]

Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing). Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, large-scale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD. [ABSTRACT FROM AUTHOR]

Purpose: To assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM). Methods: Eighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer's I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested. Results: The T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups. Conclusion: Patients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations. [ABSTRACT FROM AUTHOR]

Background: We investigated the safety and efficacy of short-term treatment with topical low-dose hydrocortisone sodium phosphate 0.335% (PFH) in patients with moderate to severe primary Sjögren syndrome (SS)-related dry eye disease (DED). Methods: A retrospective single-centre interventional study. All patients received PFH for 6 days with a pulsed posology: three times daily for 2 days, twice daily for 2 days, and once daily for 2 days. This scheme was repeated for 3 consecutive months and then alternated for 3 months. Data were collected at baseline, 3 months, and 6 months of follow-up. Results: A total of 40 SS patients were enrolled. Conjunctival hyperaemia and corneal-conjunctival stain significantly improved (p < 0.001). Ocular Surface Disease Index score reduced significantly between baseline and 3 months and between baseline and 6 months (p < 0.001). The tear film osmolarity lowered significantly in each eye from baseline to 3 months and from baseline to 6 months (p = 0.002 and p = 0.037, respectively). Comparing results at 3 and 6 months, the Ocular Surface Disease Index score (p = 1.000), the frequency of lacrimal substitutes installation (p = 0.632), and tear film osmolarity (right eye p = 0.518, left eye p = 1.000) did not change significantly. Intraocular pressure did not change during the study period. Conclusion: PFH eye drops with a pulsed posology improve signs and symptoms, not affecting the intraocular pressure in SS-related DED. Therefore, this pulsed treatment is safe and efficacious. [ABSTRACT FROM AUTHOR]

Purpose: There are only a few epidemiological studies of dry eye syndrome (DES) in populations with a common academic background. in this study, the prevalence of DES and associated factors were evaluated separately in men and women physical education and sports science graduates. Study design: Cross-sectional survey. Methods: A questionnaire about the diagnosis of DES and associated factors was mailed to 9507 graduates of the Faculty of Health and Sports Science, Juntendo University. The questions covered subjective DES using Schaumberg et al.'s questionnaire and the prevalence of diagnosed DES. Associated factors, age, sex, smoking, alcohol consumption, body mass index, daily screen viewing time, and contact lens (CL) use were analyzed. Results: A total of 2048 valid responses were received. The prevalence of diagnosed DES was 2.9% in men and 9.3% in women. For subjective DES, the prevalence was 14.8% in men and 39.8% in women. The odds ratio for DES was high in men and women who used CLs and women whose daily screen viewing time was ≥ 4 h. Conclusion: Both diagnosed and subjective DES were highly prevalent in men and women of all ages, particularly among those in their 20 and 30s. CL use was associated with DES in both men and women. Measures to deal with the factors that can be corrected might have a positive effect on the ocular health and quality of life of physical education and sports science graduates. [ABSTRACT FROM AUTHOR]

Introduction: To assess the effectiveness and safety of intranasal tear neurostimulation in the treatment of dry eye disease. Methods: We performed a meta-analysis of four databases from their inception to October 2022 without language restrictions. Randomized controlled trials and non-randomized controlled trials meeting the inclusion criteria were included in this review and were quality appraised. The risk of bias was evaluated by two independent reviewers using the Cochrane Collaboration Tool and Methodological Index for Non-Randomized Studies. The random-effect model or fixed-effect model was adopted to estimate the pooled effect sizes. Results: Fifteen published studies consisting of 17 clinical trials with a total of 901 patients were analyzed. Schirmer II test scores were significantly higher after intranasal tear neurostimulation in patients with dry eye disease (mean difference = 14.12 mm, 95% confidence intervals (8.93, 19.31), P < 0.001). Intranasal tear neurostimulation increased the meibomian gland areas (mean difference = − 251.79 μm2, 95% confidence intervals (− 348.34, − 155.23), P < 0.001), but no significant difference was found in meibomian gland perimeters before and after stimulation (mean difference = 3.72 mm, 95% confidence intervals (− 22.14, 29.59), P = 0.78). All adverse events were mild or moderate, and no serious adverse events were reported. Conclusions: This meta-analysis provides promising evidence for the controversial effectiveness of intranasal tear neurostimulation in the treatment of dry eye disease, along with useful information for guiding intranasal tear neurostimulation in future clinical trials. Trial Registration: This meta-analysis was registered on the Prospective Register of Systematic Reviews (PROSPERO) (CRD42021284214). [ABSTRACT FROM AUTHOR]

Introduction: This study sought to compare the efficacy of OC-01 (varenicline solution) nasal spray for treatment of dry eye disease (DED) in postmenopausal women (PM+) versus women who were not postmenopausal (PM−). Methods: This was a post hoc subgroup analysis of data integrated from two prior randomized controlled clinical trials, ONSET-1 and ONSET-2. Women randomized to treatment with OC-01 (varenicline solution) nasal spray 0.03 mg or vehicle control (VC) whose self-reported menopausal status (PM+ versus PM−) was known were included. Outcomes included the treatment difference (the OC-01 [varenicline solution] nasal spray change from baseline [CFB] minus VC CFB) in Schirmer test score (STS, mm) with anesthesia and the eye dryness score (EDS) measured on a 100-mm visual analog scale (0 = no discomfort, 100 = maximal discomfort). Least-squares mean treatment differences were derived from analysis of covariance (ANCOVA) models. Results: Overall, 449 female participants in the ONSET-1 and ONSET-2 trials randomized to the OC-01 (varenicline solution) nasal spray 0.03 mg or VC groups were included in this analysis. The treatment–menopausal status interaction terms in the STS and EDS ANCOVA and logistic regression models were not statistically significant (p > 0.05), indicating consistency of treatment effect between the PM− and PM+ groups. The treatment difference in STS was similar in the PM− and PM+ groups (6.7 and 5.5 mm, respectively). The treatment difference in EDS was similar in the PM− and PM+ groups (− 5.5 and − 4.1, respectively). Conclusions: OC-01 (varenicline solution) nasal spray demonstrated similar efficacy in promoting natural tear production and improving symptoms in both PM− and PM+ groups. As menopausal-related hormonal changes may be associated with more severe DED, these results may support OC-01 (varenicline solution) nasal spray as an effective treatment for DED in women regardless of presenting menopausal status. Trial Registration: Post hoc subgroup analysis of data integrated from ONSET-1 (ClinicalTrials.gov identifier NCT03636061) and ONSET-2 (ClinicalTrials.gov identifier NCT04036292). [ABSTRACT FROM AUTHOR]

This scoping review examined the relationship between Dry Eye Disease (DED) and Uveitis. We searched Pubmed, Embase, and LILACS databases for articles in which at least one patient had DED and uveitis concomitantly. The search produced 2381 records, and 24 studies were included in the qualitative synthesis. We concluded that DED and uveitis of any etiology could appear concomitantly in patients of any age. However, both diseases seem to coexist more frequently in middle-aged women and cases of anterior uveitis. Therefore, it is crucial that ophthalmologists actively look for the coexistence of ocular surface abnormalities, especially in patients with these characteristics. Future studies should establish and quantify the risk factors and pathophysiological mechanisms of this coexistence to achieve an early diagnosis of both etiologies and comprehensive management of these patients. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial disorder with recognized pathology, but not entirely known pathomechanism. It is suggested to represent a continuum with neuropathic corneal pain with the paradox that DED is a pain-free disease in most cases, although it is regarded as a pain condition. The current paper puts into perspective that one gateway from physiology to pathophysiology could be a Piezo2 channelopathy, opening the pathway to a potentially quad-phasic non-contact injury mechanism on a multifactorial basis and with a heterogeneous clinical picture. The primary non-contact injury phase could be the pain-free microinjury of the Piezo2 ion channel at the corneal somatosensory nerve terminal. The secondary non-contact injury phase involves harsher corneal tissue damage with C-fiber contribution due to the lost or inadequate intimate cross-talk between somatosensory Piezo2 and peripheral Piezo1. The third injury phase of this non-contact injury is the neuronal sensitization process with underlying repeated re-injury of the Piezo2, leading to the proposed chronic channelopathy. Notably, sensitization may evolve in certain cases in the absence of the second injury phase. Finally, the quadric injury phase is the lingering low-grade neuroinflammation associated with aging, called inflammaging. This quadric phase could clinically initiate or augment DED, explaining why increasing age is a risk factor. We highlight the potential role of the NGF-TrkA axis as a signaling mechanism that could further promote the microinjury of the corneal Piezo2 in a stress-derived hyperexcited state. The NGF-TrkA-Piezo2 axis might explain why female sex represents a risk factor for DED. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. Methods: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. Results: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. Conclusions: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. Trial Registration: ClinicalTrials.gov, NCT03688802. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) after cataract surgery is associated with various risk factors, while causing a wide range of heterogeneous symptoms including decreased quality of vision. This systematic review and meta-analysis aimed to determine the prevalence and characteristics of DED after cataract surgery. We searched PubMed and EMBASE and included studies on patients with DED after cataract surgery, between January 2011 and June 2020. Study-specific estimates (DED prevalence rates after cataract surgery in patients without preexisting DED) were combined using one-group meta-analysis in a random-effects model. We included 36 studies published between 2013 and 2020. We included nine of these in the meta-analysis of DED prevalence after cataract surgery. Overall 37.4% (95% CI 22.6–52.3; 206/775) of patients without preexisting DED developed DED after cataract surgery. The risk factors for DED after cataract surgery included age, female sex, systemic diseases, systemic medications, psychiatric conditions, preexisting DED, meibomian gland dysfunction, preservatives in eye drops, surgery techniques, and lifestyle. DED severity peak occurred 1 day postoperatively and persisted for at least 1–12 months following cataract surgery; therefore, consistent follow-up for DED is warranted for at least 1 month after cataract surgery. Topical administration of preservative-free diquafosol tetrasodium solution and preoperative meibomian gland treatment were effective in preventing and treating DED following cataract surgery. As more than one-third of patients develop DED after cataract surgery, careful DED management and treatment is needed after cataract surgery to improve satisfaction and vision quality. [ABSTRACT FROM AUTHOR]

Background and purpose: Corneal fluorescein staining is one of the most important diagnostic tests in dry eye disease (DED). Nevertheless, the result of this examination is depending on the grader. So far, there is no method for an automated quantification of corneal staining commercially available. Aim of this study was to develop a software-assisted grading algorithm and to compare it with a group of human graders with variable clinical experience in patients with DED. Methods: Fifty images of eyes stained with 2 µl of 2% fluorescein presenting different severity of superficial punctate keratopathy in patients with DED were taken under standardized conditions. An algorithm for detecting and counting superficial punctate keratitis was developed using ImageJ with a training dataset of 20 randomly picked images. Then, the test dataset of 30 images was analyzed (1) by the ImageJ algorithm and (2) by 22 graders, all ophthalmologists with different levels of experience. All graders evaluated the images using the Oxford grading scheme for corneal staining at baseline and after 6–8 weeks. Intrarater agreement was also evaluated by adding a mirrored version of all original images into the set of images during the 2nd grading. Results: The count of particles detected by the algorithm correlated significantly (n = 30; p < 0.01) with the estimated true Oxford grade (Sr = 0,91). Overall human graders showed only moderate intrarater agreement (K = 0,426), while software-assisted grading was always the same (K = 1,0). Little difference was found between specialists and non-specialists in terms of intrarater agreement (K = 0,436 specialists; K = 0,417 non-specialists). The highest interrater agreement was seen with 75,6% in the most experienced grader, a cornea specialist with 29 years of experience, and the lowest was seen in a resident with 25,6% who had only 2 years of experience. Conclusion: The variance in human grading of corneal staining - if only small - is likely to have only little impact on clinical management and thus seems to be acceptable. While human graders give results sufficient for clinical application, software-assisted grading of corneal staining ensures higher consistency and thus is preferrable for re-evaluating patients, e.g., in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The PERSPECTIVE study evaluated, in routine clinical practice, the effectiveness, tolerability and safety of cyclosporine A (CsA) 0.1% cationic emulsion (CE) in controlling severe keratitis in adults with dry eye who remained insufficiently controlled despite artificial tear (AT) use. Methods: A prospective, multicenter, observational study was conducted at 44 ophthalmology clinics across Finland, Germany, Norway, Sweden and the UK. Adults treated with ATs for severe keratitis and dry eye received CsA 0.1% CE therapy (1 drop in both eyes at bedtime) and were followed up at weeks 4, 12 and 24 and at month 12. Primary endpoint was mean [standard deviation (SD)] change from baseline in corneal fluorescein staining (CFS; Oxford Grade Scale) at month 12 following CsA 0.1% CE initiation. Secondary endpoints examined ocular sign and symptom severity and adverse events (AEs). Results: The full analysis set included 472 adults (75.9% female). Mean (SD) age was 61.9 (15.41) years. Mean (SD) CFS score was significantly reduced from baseline [2.56 (1.10)] at month 12 [1.10 (SD 1.13); P < 0.0001]. CFS score reductions were statistically significant from week 4, with further incremental decreases reported at study visits through month 12 (P < 0.0001). Severity of eyelid and conjunctival erythema was significantly reduced from baseline at week 4 and maintained through month 12 (P < 0.001). Tear film breakup time increased significantly from baseline at all study visits through month 12 (P < 0.001). Ocular symptom severity was significantly reduced from baseline at all study visits through month 12 (P < 0.001). Overall, 101 treatment-related AEs were reported. Most were mild/moderate (83.6%) and resolved by month 12 (73.3%). Conclusions: In routine clinical practice, CsA 0.1% CE provided statistically significant reductions in dry eye signs and symptoms. Improvements were seen at week 4 and maintained over 12 months. Treatment tolerability was good and consistent with previous CsA 0.1% CE clinical studies. Trial registration: EU PAS register number: EUPAS 22376. [ABSTRACT FROM AUTHOR]

Purpose: We report the clinical efficacy of sequential applications of 0.3% and 0.15% unpreserved hyaluronic acid (HA) for the treatment of dry eye disease (DED). Study design: Randomized clinical trial. Methods: Patients over 19 years of age with DED level 2 or higher, corneal fluorescein staining (CFS) score > 1, and tear break-up time (TBUT) < 10 s were included. Seventy-six patients were randomly assigned to the 0.15% HA group, 0.3% HA group, or combination group. Each group applied two drops of 0.15% or 0.3% HA, or a single drop of both 0.3% and 0.15% HA. Patients were evaluated using the ocular surface disease index (OSDI), CFS and conjunctival fluorescein stain score, TBUT, and blurring/discomfort after application at baseline, 4 weeks, and 8 weeks. Results: The combination group had the greatest improvement in CFS score from baseline to 8 weeks, compared with the 0.15% and 0.3% HA group (p < 0.001). The combined CFS-OSDI responder rates of the combination group (CFS score = 0 and OSDI ≥ 50% improvement at 8 weeks) were significantly higher than those of the 0.15% and 0.3% groups (p = 0.037). At 4 and 8 weeks, blurring after application in both the 0.3% and combination groups was significantly higher than in the 0.15% group, despite no difference between the 0.3% and combination groups. There were no differences in CFS and conjunctival staining score, TBUT, or OSDI within the three groups at baseline, 4 weeks, and 8 weeks. Conclusions: Sequential application of 0.3% and 0.15% HA improved symptoms/signs in moderate to severe DED patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and safety of a vectored thermal pulsation system (Lipiflow®) in the treatment of dry eye disease resulting from meibomian gland dysfunction (MGD). Methods: We searched for randomized clinical trials (RCTs) in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, and ClinicalTrials.gov up to 4 January 2021. The subjective symptoms, objective tests of dry eye, meibomian gland function, and the incidence of adverse events were evaluated. Results: Ten qualified RCTs incorporating 761 patients were analyzed. In the comparison of Lipiflow® treatment and lid hygiene, the subgroup with inconsistent units of randomization and analysis showed that the Lipiflow® treatment brought slight improvement in corneal fluorescein staining (mean difference (MD), − 0.42; 95% CI, − 0.75 to − 0.1), significant improvements in ocular surface disease index (OSDI) score (MD, − 7.4; 95% CI, − 11.06 to − 3.74), Standard Patient Evaluation of Eye Dryness (SPEED) score (MD, − 2.7; 95% CI, − 3.95 to − 1.45), meibomian glands yielding liquid secretion (MGYLS) (MD, 1.3; 95% CI, 0.78 to 1.82), and meibomian glands yielding secretion score (MGYSS) (MD, 4.09; 95% CI, 1.18 to 6.99). Meanwhile, significant improvements were detected in OSDI score, SPEED score, MGYLS, and MGYSS with patients who received Lipiflow® treatment compared with those who received nontreatment. The adverse events were comparable in the two control groups. Conclusions: Lipiflow® treatment can improve the subjective and objective outcomes of MGD and does not increase the incidence of adverse events. The improper choice of units of analysis may be the leading cause of heterogeneity, which should be noted in the design of future ophthalmology research. Additional well-designed, large-scale RCTs are required to reach a firmer conclusion. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a complex, progressive and multifactorial condition that is commonly seen in clinical practice and can be challenging to accurately diagnose. Untreated or suboptimally managed dry eye can progress to severe, chronic disease which may become resistant to treatment. Symptoms include ocular irritation and visual impairment. Patients frequently report negative consequences regarding quality of life (QoL), productivity and psychological wellbeing. Certain lifestyle factors (e.g. use of screen-based devices, air conditioning) can induce or exacerbate symptoms of DED, leading to progressive and debilitating complications. Exposures to such triggers are likely to have increased significantly during the ongoing COVID-19 pandemic with people across the globe living with heightened levels of stress/anxiety while being forced to adapt most aspects of their daily lives (from work and education through to social activities) to accommodate social distancing, primarily through the use digital technologies. This review aims to provide a concise and practical overview of current understanding regarding DED, highlighting proposals for refined diagnostic categories and therapeutic terminologies that are designed to improve identification and management of dry eye as well as reduce or slow disease progression. Finally, the findings of a European survey are shared to illustrate the impact of the COVID-19 pandemic on the lives of people with DED. The survey was conducted during the first lockdown period (March–September 2020) and explored issues relating to psychological wellbeing, QoL and engagement with healthcare services. The results demonstrate the ways in which the pandemic amplified the impact of dry eye on daily life and may be valuable in enhancing understanding among clinicians of the challenges faced by people with DED, which extend beyond the signs and symptoms of disease. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our research was to investigate the reliability and clinical applicability of a modern tear film imaging tool by comparing the inter- and intragrader difference. The further goal was to compare the non-invasive tear break-up time (NIBUT) measured with the LacryDiag® device with traditional tear film break-up time (TBUT). Methods: Comprehensive ophthalmological examination was performed, including LacryDiag® (Quantel Medical, France) (lower tear meniscus height measuring (LTMH), superior and inferior eyelid meibography (MeibS MeibI), interferometry (INT), NIBUT), slit lamp examination, and TBUT. Two independent, well-trained graders selected and analyzed the LTMH, MeibI, MeibS, and INT. The second grader reanalyzed the data 1 month later. Intra- and inter-examiner reliabilities were evaluated using intraclass correlation coefficients (ICC), while for categorical variable, Cohen's kappa statistics were provided. The Bland-Altman plot was used for visualization of the agreement between measurements. Results: Fifty healthy volunteers were examined. For LTMH both the inter- and intragrader variabilities were excellent. Between two graders, the ICC of MeibI was poor; however, between two graders, the ICC of MeibS was good, and the intragrader variability in MeibI and MeibS was excellent. For the INT, both intra- and intergrading were in fair and moderate agreement, although the intragrader agreement was higher. Comparing the NIBUT and TBUT, the agreement was slight. Conclusion: Based on our results, examination of a patient during follow-up should be performed by the same examiner, because of the slight agreement. The LacryDiag® is a non-invasive, easy-to-use device, which can examine the tear film and save the recordings for easier follow-up. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to assess the intraexaminer repeatability of Non-invasive Keratograph Break-Up Time (NIKBUT) obtained using the Oculus Keratograph 5M (K5M), given its relevance as a homeostasis marker in Dry Eye Disease (DED). Methods: In total, 80 healthy volunteers aged between 30 and 89 years participated. Measurements were classified according to age, sex and the presence or not of DED. Repeatability was evaluated by the calculation of within-subject standard deviation (Sw), coefficient of repeatability (CoR) and coefficient of variation (CoV). Moreover, the Passing–Bablok regression method was applied. Results: Sw, CoR and CoV coefficients showed low repeatability in all groups with values between 3.57 and 7.14; 9.90 and 19.79; and 51.90 and 65.49, for each coefficient, respectively. No statistically significant differences were found in the NIKBUT measurements between healthy and DED patients (p = 0.188). Groups with more DED risk had better repeatability. Passing–Bablok regression also confirmed a lack of agreement between the maximum and minimum NIKBUT measurement. Conclusion: NIKBUT measurement has low intraexaminer repeatability even when considering sex, age and DED diagnosis. Nevertheless, not only is this low repeatability due to the device, but also it is largely due to the intrinsic variability of the tear film. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have examined the patient experience regarding the diagnosis and management of dry eye disease (DED). The current study explored the ways in which the DED diagnostic pathway differs for those living with and without Sjögren's syndrome (SS), to identify aspects that influence the patient experience and associated quality of life (QoL). Methods: An observational/descriptive, non-interventional, retrospective, self-reported online survey was conducted among adults living in France, Spain and Italy who were diagnosed with DED (with/without SS), were using topical DED treatments (≥ 6 months), and were not contact lens users. Recruitment was via an online database for non-SS participants and through local patient advocacy groups for SS respondents. Results: The analysis included 827 respondents; 416 (50.3%) had SS and 82% were female. The mean age was 55 (SD 11; range 16–99) years. The mean age at diagnosis was 46 (SD 12; range 13–78) years and 50 (SD 10; range 21–73) years for SS and non-SS groups, respectively (p < 0.0001). The mean time to diagnosis was extended for SS participants [32 (SD 62) months] versus non-SS individuals [8.6 (SD 28) months (p < 0.0001)] and was associated with reduced QoL scores (r = 0.113; p = 0.0169). More SS participants (31%) consulted ≥ 4 healthcare professionals (HCPs) before DED diagnosis, versus non-SS individuals (6%) (p < 0.0001). Diagnosing clinician varied for SS respondents according to country, probably due to differences in healthcare systems/structures. More SS participants viewed their condition as a handicap than a discomfort, reporting greater QoL impact (p < 0.0001). Conclusions: Patient experiences in DED diagnosis vary substantially when comparing SS and non-SS individuals. Time to diagnosis significantly impacts QoL for SS patients, who see more HCPs ahead of DED diagnosis. The number of HCPs consulted before diagnosis and perceptions of DED are important for both groups. Country-specific variations highlight opportunities to improve consistency and efficiency across DED diagnostic pathways. These data should be considered alongside existing evidence from high-quality sources (e.g. clinical records). [ABSTRACT FROM AUTHOR]

The incidence and prevalence of dry eye disease (DED) after cataract surgery is greatly underestimated. The severity of dry eye symptoms has been reported to peak 7 days after cataract surgery and may persist for months, significantly affecting patients' quality of life (QoL). The importance of considering surgical outcomes not only in terms of visual acuity, but also in terms of the patients' QoL, necessitates the assessment and evaluation of the ocular surface by the cataract surgeon prior to the procedure. This narrative review, drafted by the P.I.C.A.S.S.O. (Italian Partners for the Correction of Ocular Surface Alterations) board, analyses the physiopathology of post-cataract surgery DED and highlights the pre-, intra- and postoperative risk factors that may alter ocular surface homeostasis; it proposes a practical comprehensive algorithm for the prevention, treatment and management of DED associated with cataract surgery. Particular attention needs to be paid to the pre- and intraoperative risk factors to reduce the incidence of postoperative dry eye and to improve cataract surgery outcome. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is a multifactorial disorder of the ocular surface. The current phase II study was performed to assess the safety and dose regimen of a recently developed topical estradiol formulation for the treatment of DED.Methods: A total of 104 postmenopausal women suffering from moderate-to-severe DED were included. Topical 17-β-estradiol-3-phosphate eye drops were administered in three different dosage groups (group 1, 0.05% twice daily; group 2, 0.1% morning, vehicle in the evening; group 3, 0.1% twice daily) and vehicle twice daily as control group for a total period of 3 months. Clinical signs including Schirmer's test and corneal staining were assessed at baseline and at days 14, 30, 60, and 90. Symptoms of DED were measured using the symptom assessment in dry eye (SANDE) test at the same time points. Safety was assessed via frequency of adverse events.Results: Schirmer's test II wetting distance significantly increased in all four groups from baseline to day 90 without significant difference between groups (group 1, + 5.6 ± 6.7 mm/5 min; group 2, + 3.7 ± 4.2 mm/5 min; group 3, + 4.8 ± 4.5 mm/5 min; group 4, + 4.0 ± 5.3 mm/5 min). Statistical significance versus baseline was reached earlier in the treatment groups versus the control group. Corneal staining was significantly reduced after the 3-month treatment period with no significant difference between treatment groups. Staining of the inferior cornea, however, showed a significantly more pronounced decrease in the highest dose group compared to vehicle (p = 0.0463). Symptoms score as assessed with the SANDE test decreased at the end of the treatment period in all four groups. Estradiol eye drops showed a favorable safety profile.Conclusion: Our results show that both estradiol eye drops and vehicle are safe and reduce signs and symptoms in postmenopausal women with moderate-to-severe DED. Although the study failed to reach the primary outcome to demonstrate a significant difference between the estradiol eye drops and vehicle in Schirmer's test, improvement occurred earlier in the active groups compared to the control group. The data of the current study will serve as a basis for a larger phase III study to establish a potential therapeutic effect of topical estradiol eye drops.Clinical Trial Registration: Clinicaltrials.gov registry NCT03821415. [ABSTRACT FROM AUTHOR]

Purpose: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. Study design: Crowdsourced observational study. Methods: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of ≥ 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. Results: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4%), followed by hyaluronic acid 0.1% (33.1%) and diquafosol sodium 3% (18.7%). Risk factors (odds ratio [95% confidence interval]) for no eye drop use were age (0.97 [0.97–0.98]), body mass index (1.04 [1.01–1.07]), brain disease (0.38 [0.15–0.98]), collagen disease (0.30 [0.13–0.68]), mental illness other than depression and schizophrenia (0.65 [0.45–0.93]), cataract surgery (0.12 [0.02–0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34–0.88]), current (0.47 [0.38–0.57]) or past (0.58 [0.43–0.77]) contact lens use, >8 h screen exposure time (1.38 [1.05–1.81]), <6 h (1.24 [1.01–1.52]) and >9 h (1.34 [1.04–1.72]) sleep time, and water intake (0.97 [0.94–0.98]). Conclusion: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment. [ABSTRACT FROM AUTHOR]

Purpose: To translate and validate a Spanish-language adaptation of the 5-Item Dry Eye Questionnaire for the Mexican population. Methods: Based on the MAPI Institute guidelines, the linguistic validation procedures consisted of four steps. Every step was reviewed by the committee. The translated validated questionnaire was applied to 25 Mexican subjects. The questionnaires were completed by the same subjects at three time points, 8 h apart on the same day and then 3 days later. Sensitivity and specificity of the DEQ-5 to predict DE signs was subsequently estimated in 200 patients see in the Asociación para Evitar la Ceguera ophthalmology clinic. Results: During the forward translation step analysis, the committee decided to change the severity scale, as the words "constantly" and "frequently" are synonymous in Spanish, so it was modified by changing "constantly" to "always" for better understanding. Overall, the intra-test intra-class correlation coefficient from tests administered on the same day was 0.9 (95% CI 0.77–0.95, p = 0.0005). The intra-test intra-class correlation coefficient from tests administered 3 days apart was 0.9 (95% CI 0.88–0.97, p = 0.0005). When applying the questionnaire to 200 patients seen in an eye clinic, we found a sensitivity of 76% and a specificity of 31% for a DEQ-5 score of ≥ 6, against 2 or more positive signs of dry eye. Conclusion: MAPI methodology proved to be a reliable strategy for the transcultural Dry Eye Questionnaire for translation from English to Spanish for the Mexican population. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye disease (DED) is a multifactorial disease of the ocular surface that leads to symptoms of discomfort and reduces quality of life. Several studies have shown an association with depression. We investigated the prevalence of depressive symptoms and their severity in DED patients and examined whether depressive symptoms correlate with signs, symptoms, or subtypes of DED or with psychological factors (resilience, premorbid personality, and subjective well-being).Methods: This cross-sectional study (n = 64, mean age 56.72, 70% women) was conducted at the Dry Eye Clinic of the Department of Ophthalmology, University Hospital Düsseldorf. Psychological assessment included the Beck Depression Inventory, revised version (BDI-II); World Health Organization Well-Being Index (WHO-5); 13-item Resilience Scale (RS-13); and Munich Personality Test (MPT). DED parameters were assessed by the Ocular Surface Disease Index (OSDI), Schirmer test (ST), tear film break-up time (TBUT), and corneal fluorescein staining (CFS). As the reference for the BDI-II depression score, we used standard values from a German sample of healthy individuals (n = 582, 66% women). Multivariate logistic regression analysis was performed to investigate the effects of various parameters on depressive symptoms. Associations between variables were examined by Pearson or Spearman correlation tests.Results: Among all participants, 61% had depressive symptoms (25% minimal, 14% mild, 17% moderate, and 5% severe). The mean BDI-II score (11.95, ± 8.46) was significantly higher than in the healthy reference group (p < .0001). It was not correlated with the severity of signs or symptoms of DED or with its subtypes, but it was significantly negatively correlated with resilience (p < .0001) and subjective well-being (p < .0001). Depressive symptoms were negatively correlated with the premorbid personality trait extraversion (p = .036) and frustration tolerance (p < .0001) and positively correlated with premorbid neuroticism (p = .001), isolation tendencies (p = .014), and esoteric tendencies (p = .001).Conclusions: Depressive symptoms of all degrees of severity are common in DED patients, but they are not associated with the severity of signs or symptoms of DED. Subjective well-being, resilience, and premorbid personality do not correlate with the signs or symptoms of DED, but they do correlate with depressive symptoms. [ABSTRACT FROM AUTHOR]

Preclinical models of human diseases are critical to our understanding of disease etiology, pathology, and progression and enable the development of effective treatments. An ideal model of human disease should capture anatomical features and pathophysiological mechanisms, mimic the progression pattern, and should be amenable to evaluating translational endpoints and treatment approaches. Preclinical animal models have been developed for a variety of human ophthalmological diseases to mirror disease mechanisms, location of the affected region in the eye and severity. These models offer clues to aid in our fundamental understanding of disease pathogenesis and enable progression of new therapies to clinical development by providing an opportunity to gain proof of concept (POC). Here, we review preclinical animal models associated with development of new therapies for diseases of the ocular surface, glaucoma, presbyopia, and retinal diseases, including diabetic retinopathy and age-related macular degeneration (AMD). We have focused on summarizing the models critical to new drug development and described the translational features of the models that contributed to our understanding of disease pathogenesis and establishment of preclinical POC. [ABSTRACT FROM AUTHOR]