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Background: This study aims to evaluate the ocular surface health with oculus keratograph 5M (Oculus, Wetzlar, Germany) in patients, 4–6 weeks after the SB surgery. Research design and methods: Adult patients with RRD who underwent SB surgery were enrolled. Subjects with the existence of any concomitant ophthalmologic diseases or topical medications that can affect the ocular surface were excluded. The ophthalmic examination and corneal imaging with oculus keratograph 5M were conducted 4–6 weeks after the surgery, following discontinuation of all topical medications. The ocular surface parameters were compared between the surgical and other eyes. Results: The results showed a statistically significant difference in the ocular surface profile, including the tear meniscus height (TMH), Non-invasive keratograph breakup time (NIKBUT), Meibography, and Redness scores, between the surgical eye and the other eye four to six weeks after the procedure. Conclusion: In this study, we showed convincing evidence of the role of keratography imaging in the objective evaluation of the ocular surface 4–6 weeks after SB surgery. We depicted that SB surgery disturbs the ocular surface homeostasis significantly, which can cause ocular discomfort as well as decrease visual function in patients in the post-up periods. [ABSTRACT FROM AUTHOR]

Introduction: This review examines how mechanisms that are not related to tear dysfunctions may contribute to the development of symptoms of dry eye disease and help to explain why dry eye symptoms do not correlate with signs. Consideration is also given to the significance of tear deficiencies which cannot contribute to an examination of symptom-sign correlation. Areas covered: Tear deficiencies which are not routinely assessed include inflammation, mucin quantity and quality, as well as corneal neuropathy and blink inefficiency. Expert opinion: Tear deficiencies detected in an examination of patients reporting symptoms of dry eye disease become the targets for remedial approaches but not always with satisfactory outcomes. Other possible influences on symptoms could include genetic predispositions, sex, ethnicity, race, health literacy, mental health conditions, lower perceived health-related quality of life, and psychological factors. However, these possible influences cannot be assessed in most dry eye disease clinical settings. Consequently, too often symptoms of dry eye cannot correlate with signs of tear dysfunction that are not identified (and so not treated). Consequently, noncompliance with treatment recommendations may not be relevant to the persistence of symptoms or signs when treatment does not address tear dysfunctions which are difficult to assess. [ABSTRACT FROM AUTHOR]

To examine whether corneal epithelial dendritic cells (CEDC) could serve as an indicator to distinguish obstructive meibomian gland dysfunction (MGD) with or without ocular surface inflammation (OSI). We performed a case-control study on patients with diagnosed obstructive MGD between August 2017 and November 2019. 30 MGD cases and 25 healthy controls were recruited. The classification of MGD patients with and without OSI was based on the tear pro-inflammatory cytokine levels. Compared with the MGD without OSI and the control group, a higher CEDC density was detected in the MGD with OSI subgroup. The presence of >15.6 cells/mm2 CEDC had a sensitivity of 73% and specificity of 75% for the diagnosis of MGD with OSI. OSI is not present in all patients with obstructive MGD. Evaluation of CEDC density in the central cornea may help identify whether MGD is concomitant with OSI. [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]

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]

Dry eye disease (DED) is a multifactorial disorder characterized by loss of tear film homeostasis with an estimated worldwide prevalence of 5% to 50%. In DED, dysfunction of the ocular structures that create and regulate the tear film components—including the lacrimal glands, meibomian glands, cornea, and conjunctiva—causes a qualitative and/or quantitative tear deficiency with resultant tear film instability and hyperosmolarity. This initiates a vicious cycle of ocular surface inflammation and damage that may ultimately impair the quality of life and vision of affected patients. Many factors can contribute to the development of DED, including ocular and systemic diseases, topical and systemic medications, and environmental conditions. Because DED is a chronic disorder, treatment is most often long term and may utilize both pharmacologic and nonpharmacologic interventions to address all etiologic components. The long-term management of DED can be challenging and most often should involve eye care specialist referral. However, primary care clinicians (PCCs) are often the first points of contact for patients with DED and importantly provide initial diagnosis and preliminary patient education about the disease process. Consideration of DED is also vital for the practice of various specialties due to the large number of comorbidities and medications that can contribute to DED pathogenesis and progression. Therefore, it is important that PCCs and clinical specialists be aware of the etiology of DED and its available therapeutic options. This manuscript provides an overview of DED pathophysiology and treatment and discusses specific considerations regarding DED management for PCCs and clinical specialists. Successful management of dry eye disease often requires the use of various pharmacologic and/or nonpharmacologic therapies, as well as environmental and lifestyle modifications, to mitigate the underlying etiologies and restore tear film homeostasis. Primary care clinicians play an essential role in dry eye disease management by establishing a diagnosis, educating patients about the disorder, and providing referrals to eye care specialists for initiation of specialized treatment and long-term follow-up. Primary care clinicians and clinical specialists should consider prescribing medications with fewer ocular surface effects whenever possible in patients at risk for or with existing dry eye disease. [ABSTRACT FROM AUTHOR]

To report a case of secondary bilateral choroiditis in a patient with primary Sjögren's syndrome(pSS). Case report. A 69-year-old woman visited our hospital for consultation due to decreased visual acuity in both eyes for 1 month. At the first visit, best corrected visual acuity (BCVA) was 0.2 and 0.3 in her right and left eyes, respectively. Intraocular pressure values were 15 mmHg and 16 mmHg in her right and left eyes, respectively. Examination revealed edema of the eyelids and conjunctiva,and corneal fluorescence staining was positive. No inflammation in the anterior chamber or vitreous opacities were observed. Bilateral multiple retinal detachments were observed on the posterior fundus, and optical coherence tomography revealed bilateral multiple areas of retinal neuroepithelial detachment, choroidal thickening, and choroidal folds. No abnormal fluorescence leakage was observed on fundus fluorescein angiography or indocyanine green angiography. In addition, systematic manifestations included recurrent bilateral parotid gland enlargement. Labial gland biopsy revealed dilated glandular ducts, scattered interstitial glands, and lymphocytic foci. Salivary gland scintigraphy revealed severe impairment of glandular excretory function. Moreover, blood tests for anti-Ro/SSA and anti-La/SSBantibodies were positive. The patient was diagnosed with primary Sjögren's syndrome. After 2 months treatment with oral prednisolone acetate combined with hydroxychloroquine, her BCVAimproved to 0.8 and 1.0 in the right and left eyes, respectively. The fundus also recovered to normal, and no recurrence was observed during the 1-year follow-up period. The current case highlights that pSS, which usually manifests with dry eye and keratoconjunctivitis, may manifest with chronic choroiditis in both eyes as well. Based on our experience with this case, patients with clinically suspected bilateral choroiditis should be evaluated for pSS. [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]

The Ocular Surface Disease Index (OSDI) is the most frequently used dry eye disease (DED) questionnaire, and the Symptom Assessment iN Dry Eye (SANDE) is the simplest and quickest to apply. We analyze the correlation and level of agreement between these two questionnaires in a large DED heterogeneous population to evaluate their performance and potential interchangeability. Prospective, multicenter longitudinal survey-based study performed on patients diagnosed with DED by 99 ophthalmologists from 20/32 Mexican states. Questionnaires were applied in two consecutive visits to analyze the correlation between OSDI and SANDE to evaluate patients with DED clinically. Level of agreement was evaluated with Bland-Altman analysis, and internal consistency of instruments was evaluated individually and combined with Cronbach's alpha index. 3421 patients studied: 1996 (58.3%) women and 1425 (41.7%) men, aged 49.5 ± 15.4 years; 995 (29.1%) patients had aqueous-deficient, 1086 (31.7%) evaporative, and 1340 (39.2%) mixed DED subtypes. Normalized baseline scores were 53.7 (OSDI) and 54.1 (SANDE). After 36.3 ± 24.4 days between visits, scores were reduced to 25.2 (OSDI) and 21.8 (SANDE) points (p <.001). A positive correlation between questionnaires was found at baseline (R = 0.592; p <.001), follow-up (R = 0.543; p <.001) and change between visits (R = 0.630; p <.001). Using both questionnaires together improved the overall reliability of symptom evaluation at baseline (α = 0.7), follow-up (α = 0.7), and both (α = 0.7), compared to individual application (OSDI α = 0.5, SANDE α = 0.6)—the same improvements applied to all DED subtypes. Bland-Altman analysis revealed a differential bias of -0.41% at baseline and +3.6% at follow-up visits between OSDI and SANDE. We validated the correlation (high precision) between questionnaires in a large-scale population, demonstrating improved reliability (high accuracy) in evaluating DED when used together, challenging their interchangeable use. These results open a venue to improve recommendations toward a more precise and accurate diagnostic and therapeutic evaluation of DED by using OSDI and SANDE concurrently. [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]

Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining. One hundred participants were recruited based on OSDI, TO, TFBUT, TMH, and LLP to be categorised as healthy (Group 1) or EDE (Group 2). Group 2 was divided into Group 2A (mild symptoms), 2B (moderate), and 2C (severe). MGLA, conjunctival hyperemia, and corneal staining were measured. Positive correlation between MGLA, conjunctival hyperemia, and corneal staining were found (all r ≥ 0.221, p ≤ 0.027). Significant differences were found: MGLA between Group 1 vs. 2C and 2C vs. 2A or 2B; conjunctival hyperemia between Group 1 vs. 2A, 2B or 2C; corneal staining between Group 1 vs. 2B or 2C and 2A vs. 2B or 2C (all p ≤ 0.049). Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants. [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]

To study the direct economic burden of dry eye diseases (DED) on Chinese residents and analyze the influencing factors of the direct economic burden of patients with DED. Two hundred and twenty-one Chinese adults with DED who underwent treatment in Wuhan Aier Hankou Eye Hospital were enrolled in this health economics research from January 2018 to August 2018 and followed for at least 1 year. Examination, pharmacological therapy, and nonpharmacological therapy costs were collected to calculate the annual direct economic burden of DED on patients through the outpatient medical record system. Annual direct economic burden caused by DED on each patient was $465.54 ± 303.08. The direct economic burden of female patients in the 40–49 years group was significantly higher than that of male patients (P <.05). Age, number of hospital visits and severity of DED were showed a significant influence on the direct economic burden both in univariate linear regression analysis and multiple linear regression analysis. Subtype of DED was showed a significant influence on the direct economic burden in multiple linear regression analysis after eliminating confounding factors. This study preliminarily analyzed the direct economic burden of Chinese DED patients. Age, number of hospital visits, severity of DED, mixed and evaporative dry eye (EDE) subtypes are shown to be the significant influencing factors of the direct economic burden and sex is a potential influencing factor. [ABSTRACT FROM AUTHOR]

A 65-year-old male presented to the Ophthalmology clinic with painless loss of vision in his right eye. Over the previous week the right eye's vision had progressed from being blurry to complete loss. Three weeks prior to presentation he had begun treatment with pembrolizumab for urothelial carcinoma. Ophthalmological assessment and subsequent imaging prompted further investigation, and a temporal artery biopsy confirmed a diagnosis of giant cell arteritis. This case demonstrates a rare, yet serious, condition of biopsy-confirmed giant cell arteritis in the setting of pembrolizumab treatment for urothelial carcinoma. In addition to reporting a vision threatening side effect of pembrolizumab we emphasise the need for vigilant care of patients on this drug as symptomatology and laboratory results may be inconspicuous. [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]

To enquire whether patients with dry eye symptoms also report dry skin, whether their perception could be corroborated with objective measurement, and whether dry eye disease might be suspected based on patients' complaints. This cross-sectional study included 50 subjects, 25 with and 25 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms. Ocular signs were assessed by monitoring conjunctival hyperemia, ocular surface staining, meibomian gland expression, tear film lipid layer thickness, tear break-up time, lid parallel conjunctival folds, Schirmer test, and meibometry. Skin dryness was assessed by noting patients' self-perception of their facial skin dryness and measured by sebumeter. Subjects without dry eye symptoms had self-reported oilier facial skin than those with dry eye symptoms (p <.001). Sebumetry scores measured on the forehead and cheek were significantly higher in subjects without dry eye symptoms than dry eye subjects (p =.003). After adjustment for age and gender in a logistic regression analysis, dry eye was independently and significantly associated with dry skin (AOR 0.69, p =.040), higher LIPCOF score of both eyes (AOR 2.28, p =.028), lower sebumetry score of the forehead (AOR 0.98, p =.041) and cheek (AOR 0.98, p =.041), and shorter TBUT score after gland expression (AOR 0.90, p =.018). This study showed that ocular dryness was subjectively and objectively positively correlated to facial skin dryness. Patients reliably described their skin condition. People with dry facial skin also had drier eyes. [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]

Dry eye disease (DED) and other inflammatory ocular disorders have been reported to be associated with decreased corneal endothelial cell density (CECD), however the mechanism of underlying endothelial cell loss remains unknown. We conducted a comprehensive literature search of English-written publications on dry eye disease, corneal endothelial cell loss, Sjögren's syndrome, and Graft Vs Host Disease (GVHD), to review the effects of DED and other inflammatory ocular surface conditions on CECD. A total of 78 studies were included in our study. Loss of corneal neurotrophic support, cytotoxic stress, and a heightened immune response, all of which may occur secondarily to a common causative agent such as inflammation, are major contributors to reduced CECD. More studies are needed to determine how the interrelated pathways of altered corneal nerve function and upregulated expression of inflammatory activity influence corneal endothelial cell loss. [ABSTRACT FROM AUTHOR]

The objective of this meta-analysis was to identify whether headache increase the risk of dry eye disease (DED). PubMed, Web of Science, Cochrane Library and EMBASE databases were searched for relevant studies. The odds ratio (OR) of DED in all-cause headache was calculated via Stata software. To explore the source of heterogeneity, subgroup and sensitivity analyses were conducted. Funnel plots and Egger's test were performed to assess publication bias. This meta-analysis included 11 studies. Pooled analysis indicated that all-cause headache was related to a higher risk of DED (OR = 1.586, 95% CI : 1.409–1.785, I2 = 89.3%, p <.001). Migraine headache, tension headache and cluster headache were all related to a higher risk of DED (OR = 1.503, 95% CI: 1.369–1.650, I2 = 81.8%, p <.001; OR = 1.610, 95% CI: 1.585–1.635, p <.001; OR = 2.120, 95% CI: 1.104–4.073, p =.024), respectively. The risk of DED in case–control studies was slightly higher than in cross-sectional studies and cohort study (OR = 1.707, 95% CI: 1.291–2.258, I2 = 85.0%, p <.001; OR = 1.600, 95% CI: 1.590–1.610, I2 = 0.0%, p <.001; OR = 1.440, 95% CI: 1.096–1.893, p =.009), respectively. Subgroup analysis in territory type showed that all-cause headache in America, Europe, Asia and Oceania were all related to a higher risk of DED. This study indicates that headache is related to a higher risk of DED, especially in the migraine patients. These results suggest that headaches should be regarded as an independent risk factor for DED. In this meta-analysis, 11 studies (one cohort study, four case–control studies and six cross-sectional studies) covering 3,575,957 individuals were included. Pooled analysis indicated that all-cause headache was related to a higher risk of dry eye (OR = 1.586, 95% CI: 1.409–1.785, I2 = 89.3%, p <.001). These results suggest that headaches should be regarded as an independent risk factor for dry eye. [ABSTRACT FROM AUTHOR]

This study was done to observe the safety and effect of Xiaoyaosan (XYS) on the stimulated depressive disorder (DD) related dry eye disease (DED) in mice. Normal control (NC) group, Vehicle group, and drug treatment groups, including Sertraline Hydrochloride (SH), XYS low-dose (XYS-LD), medium-dose (XYS-MD), and high-dose (XYS-HD), were established. The drug quality of XYS was assessed by high-performance liquid chromatography (HPLC). XYS toxicity in kidney and liver was assessed with Hematoxylin & Eosin (H&E) staining. Serum enzyme-linked immunosorbent assay (ELISA) and body weights were used to evaluate the depression status of mice. Tear production, corneal sensitivity, Oregon Green Dye (OGD) staining, and corneal confocal microscopy were used to assess ocular surface changes. H&E staining was also used to assess pathological cornea and lacrimal gland changes. HPLC results showed that XYS complied with Chinese drug quality standards. The drug treatment groups observed no drug toxicity reactions in the liver and kidney. SH and XYS groups improved DD-related serological indices as compared with Vehicle. Body weight was enhanced in mice with XYS groups compared to Vehicle and SH. Mice with XYS treatments showed increased tear production and corneal sensitivity, decreased corneal OGD staining scores, improved morphology, and decreased inflammatory cell infiltration in the cornea and lacrimal gland. In conclusion, XYS had no drug toxicity, improved serological indices, and ocular surface pathological changes in DD-related DED mice. XYS is safe and may have a therapeutic effect on DD-related DED. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial chronic condition with a broad spectrum of symptoms that can affect daily activities and quality of life. New treatment approaches that target more systematically distinct parts of the pathophysiology would present new potential to effectively regulate signs and symptoms of DED. In this review, a comprehensive list of device-based treatments has been provided, according to their mechanism of action. Given the variability and complexity of DED, adjuvant treatments should be considered as a boost for patients who do not respond to first-line therapy. Most of those devices primarily target meibomian glands, using heat or mechanical energy to restore normal meibum flow. Although several treatments have been discussed in this review, further studies are needed to identify new options, evaluate current therapies in randomized clinical trials more extensively, and identify which subtypes of DED could benefit from any given therapy. [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]

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]

Objectives. This study aimed to evaluate visual display terminal (VDT)-related digital eye strain (ES) and dry eye disease (DED) symptoms in subjects whose work was changed to teleworking (TW) during the coronavirus pandemic. Methods. A digital self-reported survey was conducted on subjects in TW, including demographics, medical history, VDT time and ES-related symptoms before and during the pandemic and DED (dry eye questionnaire 5 [DEQ-5] questionnaire). Results. A total of 1797 questionnaires were analyzed. Mean age was 40.5 (SD 11.1) years, and 69.9% were female. The mean number of TW weeks was 10.2 (SD 3.0). The total VDT total hours increased from 7.4 (SD 3.3) to 9.5 (SD 3.3) (p < 0.001). All ES symptoms presented a significant increase (p < 0.001). The mean DEQ-5 score was 8.3 (SD 4.9). The oldest group presented lower values, and women had a higher score (p < 0.001). Additionally, 28.6% of the subjects were classified with severe DED, and the variables associated with a logistic regression model were total VDT hours, female gender, refractive surgery, rosacea, depression, previous DED, keratoconus and blepharitis. Conclusions. The number of VDT hours seemed to be a relevant factor for increase in ES symptoms and a high prevalence of DED during the pandemic period. [ABSTRACT FROM AUTHOR]

To evaluate the short- (within 90 min) and long-term (after 21 days of treatment) effects of an artificial tear containing carbomer, hyaluronic acid, glycerol, and medium-chain triglycerides in patients with mild-to-moderate dry eye symptoms. Subjects received the tested artificial tears in the right eye and control artificial tears in the left eye and were assessed 10, 30, 60, and 90 min after instillation in the short-term study phase. They received the study product in both eyes in the long-term phase. Non-invasive break-up time (NIBUT), tear lipid layer pattern, tear evaporation, and tear film objective optical dynamics (TFOOD) were measured in controlled environmental conditions. In total, 32 patients (10 males, mean age 42 ± 11 years) were enrolled. During the short-term phase, NIBUT increased significantly in the right eyes at all time points compared with baseline (all p < 0.05). Conversely, in the left eyes, NIBUT increased significantly at 10 and 30 min (p < 0.05). The tear evaporation values increased at 10 min and decreased at 30 and 60 min (p < 0.05) in the right eyes, while they increased only at 10 min (p < 0.05) in the left eyes. Compared with baseline, the TFOOD was significantly more stable at all time points in the right eyes (p < 0.05), while it was more stable at 10 and 30 min in the left eyes (p < 0.05). In the long-term phase, treated eyes showed a significant increase in NIBUT values, a significant reduction of tear evaporation, a significant improvement of tear lipid layer pattern, and a more stable TFOOD compared with baseline (all p < 0.05). Symptoms, measured with the Ocular Surface Disease Index questionnaire, were also significantly reduced compared with baseline (p < 0.05). The tested product increased tear film stability and reduced tear evaporation, normalizing lipid layer pattern and reducing symptoms in the short- and long-term observation. [ABSTRACT FROM AUTHOR]

To review and summarize information on meibomian gland dysfunction (MGD) epidemiology in Africa. A systematic search of online databases was conducted for literature/studies on MGD in Africa. Meta-analysis was conducted to estimate the prevalence of MGD in Africa. Meta-regression was used to explore sources of heterogeneity. Twelve studies conducted in five countries were included in the review. All studies were hospital-based studies. Nine studies were included in the meta-analysis; the total sample size was 4963 and participants' age range was 17–96 years. The overall prevalence estimate of MGD in Africa was 45.9% (95% CI: 27.6–64.1%). Prevalence of MGD among males and females were each pooled from three studies and in urban and rural setting from 6 and 3 studies, respectively. Prevalence of MGD among males and females were 56.0% (95% CI: 22.4–89.5%) and 58.9% (95% CI: 28.5–89.4%) respectively; in urban and rural settings were 42.8% (95% CI: 21.1–64.5%) and 65.7% (95% CI: 25.7–95.7%), respectively. There was no association of MGD with sex (p =.872) and with study setting (p =.231). There is a paucity of evidence on MGD prevalence in Africa, emphasizing the need for epidemiological studies to enhance our understanding of region-specific differences in MGD in Africa. The pooled estimate from hospital-based studies, however, suggests a substantial MGD burden in Africa. Epidemiological studies are needed to assess if this translates to a high disease burden within the general African population. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common disorder that remains challenging from a clinical perspective. Unstable or deficient tear film is a major factor contributing to DED and the inability to resolve the loss of tear film homeostasis that accompanies DED can result in a vicious circle of inflammation and treatment-refractory disease. Recently recognized as a multifactorial disease, the main etiological subtypes of DED are aqueous-deficient and evaporative which exist on a continuum, although evaporative dry eye (EDE) is the more frequent classification. Although attaining greater recognition in recent years, there is currently no consensus and no clear recommendation on how to manage EDE. Clarity on the early diagnosis and treatment of EDE may facilitate the avoidance of progression to chronic inflammation, permanent damage to the ocular surface, and treatment-refractory disease. The purpose of this review was to identify current best practice for management of EDE in order to help clinicians in providing accurate diagnosis and optimized treatment. We summarize recent literature considering the role of the lipid layer on tear film stability, the importance of its composition and of its dynamic behavior, and the link between its malfunction and the insurgence and maintenance of tear film-related diseases. We have provided an assessment of the best management of lipid-deficient EDE based upon an understanding of disease pathophysiology, while indicating the flow of current treatments and possible future evolution of treatment approaches. Lipid containing eye drops may be considered as a step closer to natural tears from artificial aqueous tears because they more closely mimic the aqueous and lipid layers and may be used in combination with other management approaches. As a next step, we recommend working with a wider expert group to develop full guidelines to enable patient-centered management of EDE. Dry eye is a multifactorial disease of variable presentation with the tendency to become a chronic disease for which it is essential to identify and treat the main pathogenic mechanisms involved and tailor the treatment to the individual patient. Early intervention is needed to prevent the vicious cycle of DED and may require a multi-faceted management approach. EDE is not just a problem of MGD but can be the result of anything affecting blinking, mucin spreading, aqueous layer volume and content. Lipid-containing eye drops may provide significant relief of symptoms by improving the lipid layer and its spreading ability and, as such, are an appropriate component of the overall management of lipid-deficient EDE; natural lipid-containing eye drops should be the preferred treatment. [ABSTRACT FROM AUTHOR]

To investigate the role and mechanism of melatonin-loaded polymer polyvinyl caprolactam–polyvinyl acetate–polyethyleneglycol graft copolymer micelles (Mel-Mic) in dry eye disease (DED). In vitro, the apoptosis and reactive oxygen species (ROS) generation in human corneal epithelial cells (HCECs) were analyzed by immunostaining and flow cytometry. The effect of Mel-Mic on autophagy and mitophagy was evaluated by immunostaining and western blots. PINK1 knockdown was analyzed by small interfering RNA. In vivo, sodium fluorescein staining, tear secretion test, and periodic acid-Schiff staining were used to determine whether Mel-Mic can alleviate the severity of DED. Small molecule antagonists were pretreated to investigate whether melatonin type 1 and/or 2 receptors (MT1/MT2) mediate the effects of Mel-Mic. Mel-Mic improved the solubility and biological activities of Mel in aqueous solutions. Treatment with Mel-Mic decreased the apoptosis of HCECs exposed to hyperosmotic medium, accompanied by downregulation of cleaved Caspase-3 and upregulation of Bcl-2. In addition, Mel-Mic application suppressed ROS overproduction, rescued mitochondrial function, and decreased the level of oxidative stress associated biomarkers (COX-2 and 4-HNE) in HCECs. Interestingly, HCECs treated with Mel-Mic exhibited increased levels of mitophagy markers (PINK1, PARKIN, Beclin 1, and LC3B) and restored impaired mitophagic flux under hyperosmolarity. While PINK1 knockdown largely abolished its protective effects. In vivo, compared to vehicle group, topical Mel-Mic-solution-treated mice showed significantly improved clinical parameters, increased tear production, and decreased goblet cells loss in a dose-dependent manner. Also, transmission electron microscopic assay revealed increased autophagosome number in the corneal epithelium of Mel-Mic group. Moreover, luzindole, a nonselective MT1/MT2 antagonist, but not 4-P-PDOT, a selective MT2 antagonist, blocked the protective effect of Mel-Mic. Our findings demonstrated that Mel-Mic ameliorates hyperosmolarity-induced ocular surface damage via PINK1-mediated mitophagy and may represent an effective treatment for DED possibly through acting MT1 receptor. [ABSTRACT FROM AUTHOR]

Growing evidence emphasizes the role of inflammation and oxidative stress in the pathogenesis of Dry Eye Syndrome (DES). Concordantly, the importance of agents targeting the inflammatory cascade and oxidative stress in the treatment is also progressively increasing. Herein, the study has investigated the protective effects and underlying mechanism of allyl isothiocyanate (AITC) on the ocular surface in a benzalkonium chloride (BAC)-induced dry eye rat model. A total of twenty-one Wistar albino rats were used to form the following three groups: Control, BAC, BAC + AITC. DES was established by topical application of BAC (four times daily for two weeks) in two groups, of which one group was treated with AITC (10 mg/kg BW daily oral dosage) for four weeks. Rats were monitored by dry eye diagnostic tests during the study period, and eventually, corneal tissues were used to evaluate for histopathologic analyzes and inflammatory and oxidative status. A significant improvement was observed in various histopathologic and ophthalmologic findings, including tear volume, tear film integrity, ocular surface damage, ocular inflammatory signs, corneal thickness, and edema through AITC supplementation. AITC prominently balanced the inflammatory status and oxidative stress by lowering key proinflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, and IL-8) and increasing the activities of antioxidant enzymes (SOD, GSH-Px). Also, levels of protective tear proteins, including Muc1, Muc4, and Muc5 were recovered with AITC supplementation. AITC alleviates clinical and histopathologic signs related to DES. Antioxidative and anti-inflammatory properties of AITC play a significant role in the mechanism of action. [ABSTRACT FROM AUTHOR]

Outcome measures used to assess efficacy of dry eye therapeutics have not been consistently applied in clinical settings, nor have they been shown to correlate with functional outcomes. We propose that corneal staining, a clinically meaningful dry eye parameter, should be used as a standard objective outcome measure across all clinical trials evaluating dry eye treatments. We justify this based on evidence regarding its relationship to vision and vision related quality-of-life. In addition, corneal staining has been shown to correlate with ocular surface inflammation, a well elucidated aspect of dry eye pathophysiology and an active area in therapeutics research. No one outcome measure explored herein correlates perfectly to this heterogenous disease. However, there is mounting evidence showing the correlation between corneal staining and functional visual indices. We hope that future clinical trials will standardize corneal staining as a measure to determine the efficacy of interventions and justify their clinical utility. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED), a multifactorial condition of the tear film and ocular surface, is one of the leading reasons for patients seeking eye care. Despite the multiple toxic ingredients of eye make-up products and their long-term application close to the ocular surface, few studies have analyzed their role in initiating and worsening DED. Females and the elderly experience the highest prevalence of DED and may be particularly vulnerable to the effects of eye make-up. The multifactorial nature of DED and common mechanisms behind several ocular surface diseases make it difficult to link a particular ingredient-driven mechanism to DED. Therefore, here, we list potential responses to eye cosmetics that may be involved in DED development. The first part of this review introduces the anatomy of the eye and DED, the second section explains the classification of eye cosmetic products, and the final part discusses the undesired effects under physical, pathogenic, and chemical insults. [ABSTRACT FROM AUTHOR]

Propose: We aimed to investigate the prevalence and risk factors of dry eye syndrome (DES) among a population-based cohort study.Methods: This cross-sectional study was conducted on 475 subjects (184 men and 291 women) enrolled in the Study Group for Environmental Eye Disease at July 2013. Using the ocular surface disease index (OSDI), we measured the DES severity and defined DES as OSDI score ≥13. Current symptoms of DES and possible risk factors such as body mass index, occupations, comorbidities, exercise, smoking and drinking status were assessed by multivariate logistic regression.Results: Prevalence of DES was significantly higher in women (52.6%) than in men (41.9%) (p <.001). Compared to white-collar workers, blue-collar workers and unemployed persons showed significantly higher DES prevalence and severity. Compared to those with low BMI (<23.0 kg/m2), people with extremely high BMI (≥30.0 kg/m2) had significantly higher odds ratio (OR) of having DES after fully adjusted for sex, age, hypertension, diabetes, menopausal status, hormone replacement therapy, occupation, and lifestyle factors (OR: 2.83, 95% confidence interval: 1.04–7.71).Conclusions: We found some novel factors which have been unknown to the relationship with DES through the five years observation of the cohort. The positive associations of unemployment status, blue-collar work, alcohol habit, and obesity with DES suggests a person's comprehensive condition, not individual factors, contribute significantly in developing DES. Further studies will be helpful to understand the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: There are no clinical studies directly comparing anionic and cationic emulsions of cyclosporine for the treatment of dry eye disease (DED). We therefore conducted a literature review to evaluate the efficacy and safety of these different formulations. Methods: A literature search was performed in Embase and Medline from January 1999 to May 2019 to identify publications that evaluated clinical outcomes with either cyclosporine anionic or cationic emulsion in patients with moderate-to-severe or severe DED. Results: Thirteen publications met criteria. In patients with moderate-to-severe disease, evidence demonstrated improvement in the signs of DED with both formulations. However, improvement in symptoms was not consistently demonstrated. Studies specifically in severe DED were only identified with the cationic emulsion and showed improvement in the objective signs of DED. There were no obvious differences in tolerability between products. Conclusions: Both formulations are effective for the treatment of moderate-to-severe DED and are well tolerated. [ABSTRACT FROM AUTHOR]

Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions. Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis. Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile. This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues. [ABSTRACT FROM AUTHOR]

Purpose: The meibomian glands are located in the tarsal plate of the upper and lower eyelid and are responsible for the production of a lipid-rich secretion, the meibum, which forms the outer component of the tear film. Meibomian gland dysfunction results in excessive evaporation of the tear film and is the leading cause of dry eye disease (DED). Despite the high prevalence of DED, the etiology of meibomian gland dysfunction is only basically understood. In addition, the molecular mechanisms of meibomian gland maturation and physiological function are currently the focus of research. Methods: A systematic literature search was performed using the main scientific databases, including all relevant published articles up to September 2020. Results: This article provides an overview of the current state of knowledge about meibomian gland stem cells, cell surface marker expression and PPARγ signaling, as well as the pathological causes of meibomian gland dysfunction. Conclusion: Androgen deficiency, hyperkeratinization, PPARγ signaling and inflammatory reactions including neutrophil extracellular traps (NETs) seem to be key factors within the pathological processes of the meibomian gland. [ABSTRACT FROM AUTHOR]

The purpose of this review is to delve into the clinical and research understanding of the pathophysiology and presentation of Sjögren's-related keratoconjunctivitis sicca in order address the diagnostic and management challenge that it represents, as well as to provide a basis for appreciating the pharmacotherapies designed to treat the ophthalmic symptoms of Sjögren's disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of a preservative free sodium hyaluronate/chondroitin sulfate ophthalmic solution (SH/CS-PF) in patients with dry eye disease (DED). Methods: This was a randomized phase IV, multicentric, prospective, double-blind clinical trial. Intent-to-treat (ITT) and per-protocol (PP) analyses were performed. Patients were assigned to receive either SH/CS-PF, Systane® Ultra (PEG/PG) or Systane® Ultra PF (PEG/PG-PF) for 90 days. A total of 326 patients were included in the ITT, and 217 in the PP analysis. Efficacy endpoints were goblet cell density, Nelson's grades (conjunctival impression cytology), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), and Schirmer's test. Other parameters included were tolerability, measured by the ocular symptomatology; and safety, measured through corneal staining, intraocular pressure, visual acuity and adverse events. Results: In the ITT, there was a significant increase in mean goblet cell density in all treatments compared with their baseline (28.4% vs 21.4% and 30.8%), without difference between arms (p =.159). Eyes exposed to SH/CS-PF, PEG/PG and PEG/PG-PF showed Grade 0-I squamous metaplasia (85.5%, 87.9% and 93.2%, respectively). Similar improvements were observed for TBUT (1.24 ± 2.3s vs 1.27 ± 2.4s and 1.39 ± 2.3s) and OSDI scores at day 90 (−8.81 ± 8.6 vs −7.95 ± 9.2 and −8.78 ± 9.8), although no significant intergroup difference was found. Schirmer's test also presented improvement compared to baseline (1.38 ± 4.9 vs 1.50 ± 4.7 and 2.63 ± 5.9), with a significantly higher variation for PEG/PG-PF. There were no significant differences between treatments for any tolerability and safety parameter, nor between ITT and PP analyses for any outcome. Conclusions: The topical application of SH/CS-PF is as effective, safe and well tolerated as that of PEG/PG or PEG/PG-PF. The results suggest that SH/CS-PF may lead to normalization of clinical parameters and symptom alleviation in patients treated for DED. [ABSTRACT FROM AUTHOR]

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Purpose: To determine the feasibility of non-invasive tear break-up time (NIBUT) assessment using the Handheld tear lipid layer thickness assessment instrument and compare it with the standard tear break-up time (TBUT) test and other dry eye tests. Subjects and methods: 108 subjects were enrolled, 56 with and 52 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms. Ocular signs were assessed by NIBUT, TBUT, lipid layer thickness (LLT), lid-parallel conjunctival folds (LIPCOF), conjunctival hyperemia, and corneal staining. Results: Median NIBUT and TBUT, and other clinical test values significantly differed among the dry eye symptoms group and control group. NIBUT yielded the most significant difference between the groups (NIBUT: 7 sec vs. 17.5 sec, p <.001, Z = 5.94; TBUT: 5 sec vs. 10 sec, p <.001, Z = 4.38; LLT: p =.007; LIPCOF: p <.001, conjunctival hyperemia: p <.047, corneal staining: p <.010). Spearman's test showed a significant correlation between NIBUT and TBUT (p <.001), NIBUT and LLT (p =.001), NIBUT and LIPCOF (p =.019), NIBUT and conjunctival hyperemia (p =.002), and NIBUT and corneal staining (p =.012) in the dry eye symptoms group. NIBUT did not significantly differ among the three measurements in both groups of patients (p =.061, p =.096), while TBUT values did in the control group (p <.001). Short NIBUT values were the main predictors and indicators of dry eye complaints (AOR = 0.87, p <.001), superior to TBUT (AOR = 0.88, p =.008) and other tests even after adjustment for age and gender. Conclusion: NIBUT measured by Handheld instrument is a simple, accessible, practical, and, most of all, reproducible and objective method that might allow NIBUT assessment on a regular basis. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film and accompanied by symptoms such as ocular discomfort and visual disturbance. DED is one of the most common reasons for seeking medical care in the United States and across the world. Despite this, there are a limited number of pharmacologic therapies for the treatment of DED in the United States and Europe. This review examines the different pivotal trials for DED medications and the impact the vehicle in each trial. In recent clinical trials, the vehicle of the active formulation of the medication is often used as the active comparator. A literature review of published dry eye clinical trials was performed to identify the pivotal clinical trials of DED medications and to compare treatment effect and further understand the impact of the vehicle on clinical trial outcomes. The pivotal clinical trials for the currently approved treatments for dry eye have widely varying study designs. The variations include differences in inclusion criteria, outcome measures and efficacy endpoints, and whether or not the use of concomitant artificial tears is allowed. These differences make it difficult for accurate comparisons to be made between DED medications. Each trial demonstrated that the vehicle alone has some beneficial effect on signs and symptoms of dry eye disease. This review discusses the varying trial designs and vehicles used in the pivotal studies for the four approved dry eye medications in the United States and Europe, as well as novel vehicles under development and clinical trial recommendations. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film. Epidemiological studies suggest it occurs more frequently in women than men. The aim of this retrospective analysis was to determine whether patients with DED show gender-specific differences in symptoms and signs. A retrospective analysis of 107 patients was conducted at the Department of Ophthalmology of the University of Düsseldorf – Germany. After completing the OSDI questionnaire, the patients underwent objective refraction and were asked about the following symptoms: burning, itching, foreign body sensation, epiphora, sticky eyes, pain, red eyes and swollen eyelids. Furthermore, they underwent an evaluation of the following signs: lipid layer thickness, non-invasive break-up-time (NI-BUT), conjunctival hyperemia, lid parallel conjunctival folds, meibography, Schirmer test and tear meniscus height, ocular surface staining, expressibility of meibomian glands. Of the 107 patients (56.2 ± 17.3 years) 75 were women and 32 men. Women reported significantly more often eyelid swelling (p =.03) and showed a tendency to complain more about red eyes (p =.051), while men tended to complain more often about epiphora (p =.053). In an age-matched sample taken from the cohort, significant differences were found for OSDI-scores (p =.025) showing women reporting more symptoms compared to men, while men showed more conjunctival hyperaemia (p =.004) than women. Women showed a significant thicker lipid layer (p =.0009) in the full cohort, but not in the age-matched sample (p =.43). Although the majority of the investigated parameters did not show gender-specific differences, women reported higher OSDI scores. These findings could be explained by an increased frequency of neuropathic symptoms or ocular surface sensitivity in women or higher resilience of men to consult an ophthalmologist. Sex may have an effect on the clinical characteristics of DED, but further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to assess the pooled prevalence of meibomian gland dysfunction (MGD) and evaluate its risk factors by gender, age, and ethnicity. Methods: Articles were searched reporting the prevalence of MGD from PubMed, Scopus, Web of Science, and Embase databases. Results: The estimated pooled prevalence of MGD was 0.358 (95% CI 0.26–0.46; I2: 99.57%). The prevalence of MGD was 0.358 (95% CI 0.24–0.50) in clinical and 0.359 (95% CI 0.22–0.52) in population-based studies. Men were more prone to MGD than women (OR: 1.24, 95% CI 1.01–1.52, p = 0.034). The rate of MGD was between 21.2% and 29.5% in Africans and Caucasians, to 71.0% in Arabs, and 67.5% in Hispanics. Conclusion: MGD is a quite prevalent disorder with an estimated pooled prevalence of 35.8%. Men are more prone to MGD than women. There is a large variation between studies in terms of quality, sample size, age ranges, diagnostic criteria, and ethnicity. [ABSTRACT FROM AUTHOR]

The lacrimal glands produce the aqueous component of the pre-ocular tear film, which is essential for ocular health and optimal vision. This review explores its history, current understanding, and recent advances, and scope for future research. It traces the evolution of human knowledge about the source of tears across several millennia, with specific emphasis on the individuals who made seminal contributions to this field. It provides a detailed update on the morphology, microscopic structure, innervation, vascular supply, and imaging modalities of both the main and accessory lacrimal glands. The review also summarizes the recent advances in lacrimal gland regeneration and repair for the treatment of dry eye disease, particularly the role of mesenchymal stem cells. Lastly, the review gazes into the future of lacrimal gland research, which aims at translating the existing laboratory knowledge into clinical application, with the possibility of transplanting in vitro cultivated lacrimal constructs or the use of cell-based therapies for in situ repair of diseased human lacrimal glands. The lacrimal glands produce the aqueous component of the pre-ocular tear film, which is essential for ocular health and optimal vision. This review explores its history, current understanding, recent advances, and scope for future research. The authors reviewed the major studies discussing the history of lacrimal glands and their anatomical description, including microscopic anatomy, innervation patterns, imaging, and ongoing translational research. The review traces the evolution of human knowledge about the source of tears across several millennia, with specific emphasis on the individuals who made seminal contributions to this field. It provides a detailed update on the morphology, microscopic structure, innervation, vascular supply, and imaging modalities of both the main and accessory lacrimal glands. The review also summarizes the recent advances in lacrimal gland regeneration and repair for the treatment of dry eye disease, particularly the role of mesenchymal stem cells. Lastly, the review gazes into the future of lacrimal gland research, which aims at translating the existing laboratory knowledge into clinical application, with the possibility of transplanting in vitro cultivated lacrimal constructs or the use of cell-based therapies for in situ repair of diseased human lacrimal glands. Knowledge about the lacrimal glands in health and disease has improved tremendously since its discovery in the mid-eighteenth century. Today we stand at the cusp of exploring potential regenerative approaches for the treatment of lacrimal gland damage in dry eye disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of age, gender and body mass index (BMI) on the levels of tear film neuromediators and corneal nerve parameters in healthy individuals. Methods: Twenty-six healthy subjects were screened for any neurological deficits. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Corneal nerve fibers were imaged using confocal microscopy and assessed by automated image analysis software. Associations between the clinical variables were analyzed using Pearson or Spearman correlation. Univariate general linear regression was performed to examine the independent relationship between age, BMI and gender of the subjects with concentrations of substance P, CGRP and corneal nerve fiber parameters. Results: Fifteen (58%) of the study participants were male. The mean age of the study cohort was 36 ± 12 years (range, 21–59) with an average BMI of 25 ± 4 kg/m2. The median [IQR] concentrations of substance P and CGRP was 715 [372–1463] pg/mL and 38 [15–74] ng/mL respectively. Moderate but significant positive correlations were found between the concentration of substance P and corneal nerve fiber density (r = 0.467, P =.016), nerve fiber length (r = 0.528, P =.006) and nerve fractal dimension (rs = 0.614, P =.002). There was a significant age-dependent reduction in the concentration of substance P (−6% pg/mL per year, P =.001) and CGRP (−8% ng/ml per year, P <.001). Corneal nerve fiber density (−0.171 no./mm2 per year, P =.029) and nerve fractal dimension (−0.001 per year, P =.021) showed reductions with advancing age. Gender and BMI did not influence any of the measurements. Conclusions: The concentrations of substance P and CGRP in tears, as well as corneal nerve fiber density and nerve fractal dimension, are significantly reduced with advancing age. Age should be considered when evaluating patients for diagnosis and follow-up of corneal neuropathy or ocular surface disorders. [ABSTRACT FROM AUTHOR]