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Treatment of ocular diseases presents unique challenges and opportunities for the clinician and for the clinical pharmacologist. Ophthalmic pharmaceuticals, typically given as liquids, require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Ocular tissue levels are challenging to obtain in humans, and the clinical pharmacokinetics is typically blood levels, which are primarily related to safety, rather than efficacy. The eye is a closed compartment with multiple physiological barriers with esterases and transporters, but relatively little cytochrome oxidases. Delivery routes include topical, intravitreal, and systemic. Patient dosing involves not only adherence issues common to all chronic diseases, but also performance requirements on eye drop instillation. Therapeutically, ocular diseases and their pharmacological treatments include both those analogous to systemic diseases (e.g., inflammation, infection, and neuronal degeneration) and those unique to the eye (e.g., cataract and myopia)., (© 2024, The American College of Clinical Pharmacology.)

Significance: This is one of the first reports to summarize the enrollment metrics for ophthalmology trials completed in the United States (US)., Purpose: This study aimed to describe US ophthalmology clinical trial enrollment metrics to facilitate planning and budgeting of US Food and Drug Administration-regulated ophthalmological drugs trials., Methods: A GlobalData PLC search was conducted on or before February 27, 2024, to evaluate the clinical trial landscape for completed ophthalmology clinical trials conducted in the US. The primary search contained only the term "ophthalmology," which was restricted to trials that were completed and were conducted within the US. Trials were classified as multicenter when trials included three sites or more, and when the enrollment search resulted in ≥30 multicenter trials for an individual indication, enrollment data were further broken down by Food and Drug Administration trial phase., Result: The search yielded 2229 trials, which analyzed 980 different drugs produced by 854 different sponsors. The most common indications evaluated in US trials were macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. Multicenter trials by indication had an overall median enrollment period range of 4.8 to 35.1 months; number of subjects enrollment, range of 36 to 518 subjects; number of sites utilized, range of 4 to 74 sites; and enrollment rate, range of 0.11 to 4.04 subjects/sites per month. There were 17 indications with ≥30 multicenter trials, which allowed for enrollment metric calculation by trial phase., Conclusions: This study provides sponsors with an understanding of the number of subjects and sites needed to complete a trial while also setting realistic enrollment timelines. Although this work represents the US market, more work is needed to better understand other countries given that country-specific guidelines and subject beliefs may impact enrollment metrics., Competing Interests: Conflict of Interest Disclosure: Andrew D. Pucker has served as consultants to Alcon, Bausch + Lomb, HanAll Biopharma, Essilor, and Euclid Systems over the past year; none of these activities are directly related to the content of this report. Nicole Derthick and Lanita Scott have no conflicts of interest to disclose. All authors were employees of Lexitas Pharma Services during the conduct of this project. Lexitas Pharma Services has an interest in projecting accurate enrollment timelines, although the presented work is unbiased given that Lexitas Pharma Services only benefits from accurate clinical trials data., (Copyright © 2024 American Academy of Optometry.)

Purpose: Sjögren's syndrome (SS) is a common autoimmune disease affecting about four million Americans. Although approximately 1 in 10 patients with clinically-significant aqueous deficient dry eye has underlying SS, widespread underappreciation of SS leads to significant underdiagnosis, delays in diagnosis, and consequent morbidity and mortality. The purpose of this article is to illustrate that in addition to dry eye, SS can cause serious, vision-threatening extraglandular ocular manifestations., Methods: We conducted a narrative review of studies that have examined the dry eye and extraglandular ocular complications of SS., Results: SS-related dry eye is a progressive condition with major negative impact on the quality-of-life of afflicted patients, not only due to symptoms of ocular discomfort but also visual dysfunction. In addition, SS can lead to corneal melt/perforation, uveitis, scleritis, retinal vasculitis, and optic neuritis. A major problem with currently-available SS disease activity measurement instruments is the lack of domains evaluating dry eye-related visual dysfunction. For example, one of the most commonly-used instruments for assessing patient symptoms in SS (the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]) only includes one item (out of three) that addresses the severity of overall dryness, without mention of dry eye symptoms or vision-related quality-of-life. Similarly, no extraglandular ocular complications are included in currently-available SS disease activity instruments (e.g., the EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI])., Conclusions: There needs to be a paradigm shift in which eye care providers and rheumatologists become more familiar with various SS-related extraglandular ocular manifestations. Existing disease activity measurement instruments must incorporate dry eye symptoms, particularly those related to visual dysfunction. An evidence-based screening algorithm for determining which patients with dry eye should be tested for underlying SS may be particularly helpful in preventing delays in diagnosis.

Purpose of Review: The purpose of this article is to review the available strategies to successfully identify and manage ocular surface disease (OSD) pre, intra and post-cataract surgery., Recent Findings: Cataract surgery and OSD have an intricate relationship: the surgical procedure can induce or exaggerate OSD symptoms, while OSD can negatively impact surgical refractive outcomes and increase the rate of postoperative complications., Summary: Improving the health and stability ocular surface is the key to enhance post cataract surgery refractive outcomes and avoid complications. This is pivotal for patients affected by severe OSD, but is also important for patients with minimal signs or symptoms. A correct diagnosis and a stepwise approach are the keys to improve the quality of life of such patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Maintenance of internal homeostasis is a sophisticated process, during which almost all organs get involved. Liver plays a central role in metabolism and involves in endocrine, immunity, detoxification and storage, and therefore it communicates with distant organs through such mechanisms to regulate pathophysiological processes. Dysfunctional liver is often accompanied by pathological phenotypes of distant organs, including the eyes. Many reviews have focused on crosstalk between the liver and gut, the liver and brain, the liver and heart, the liver and kidney, but with no attention paid to the liver and eyes. In this review, we summarized intimate connections between the liver and the eyes from three aspects. Epidemiologically, we suggest liver-related, potential, protective and risk factors for typical eye disease as well as eye indicators connected with liver status. For molecular mechanism aspect, we elaborate their inter-organ crosstalk from metabolism (glucose, lipid, proteins, vitamin, and mineral), detoxification (ammonia and bilirubin), and immunity (complement and inflammation regulation) aspect. In clinical application part, we emphasize the latest advances in utilizing the liver-eye axis in disease diagnosis and therapy, involving artificial intelligence-deep learning-based novel diagnostic tools for detecting liver disease and adeno-associated viral vector-based gene therapy method for curing blinding eye disease. We aim to focus on and provide novel insights into liver and eyes communications and help resolve existed clinically significant issues., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Dupilumab-associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response and to learn more about the effect of dupilumab on conjunctival goblet cells (GC)., Methods: This prospective study included dupilumab-treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht. Patients were examined by an ophthalmologist and a dermatologist before start (baseline), and after 4 and 28 weeks of dupilumab treatment. Ophthalmological examination was assessed by the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. DAOSD was defined as an increase in UTOPIA score of ≥3 points from baseline. To quantify conjunctival GCs and to investigate the percentage of Cytokeratin 19 (CK19)-CD45-Mucin 5 AC (MUC5AC)+ cells, conjunctival impression cytology samples were analysed., Results: Ocular surface disease (OSD) was present in 91.3% (n = 63/69) patients at baseline. DAOSD was observed in 28.9% (n = 20/69) patients, in whom GC numbers remained stable and the percentage of CK19-CD45-MUC5AC+ cells decreased at onset of DAOSD compared with baseline. After 28 weeks of dupilumab treatment, DAOSD was seen in 14.5% (n = 10/69) patients. Of the 85.5% (n = 59/69) patients without DAOSD or with controlled DAOSD at Week 28, 40.7% (n = 24/59) patients received anti-inflammatory ophthalmic drugs., Conclusions: Ocular surface disease is common in moderate-to-severe AD patients before starting dupilumab. During treatment with dupilumab DAOSD severity improves with early ophthalmic treatment. The decrease in percentage of CK19-CD45-MUC5AC+ cells during dupilumab treatment suggests an impairment of the GC function due to dupilumab treatment., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Ocular surface diseases are becoming more prevalent worldwide. Reasons for this include the ongoing population ageing and increasing use of digital displays, although ophthalmologists have a wide selection of tools, which can be implemented in the evaluation of the ocular surface health, methods, which enable the in-depth study of biological functions are gaining more interest. These new approaches are needed, since the individual responses to ocular surface diseases and treatments can vary from person to person, and the correlations between clinical signs and symptoms are often low. Modern mass spectrometry (MS) methods can produce information on hundreds of tear proteins, which in turn can provide valuable information on the biological effects occurring on the ocular surface. In this review article, we will provide an overview of the different aspects, which are part of a successful tear proteomics study design and equip readers with a better understanding of the methods most suited for their MS-based tear proteomics study in the field of ophthalmology and ocular surface., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Ocular cytology specimens are small, with limited options for a repeat biopsy. Appropriate handling of these specimens and triaging for ancillary testing can be taxing. In this article, the author reviews a selection of potentially challenging diagnoses and current common practices and methods used in diagnosing ocular diseases by cytology. The majority of cytology specimens submitted for evaluation of ocular diseases can be divided into 3 major categories: surface epithelial corneal and conjunctival cytology samples, intraocular fluids from the anterior (aqueous fluid) or posterior (vitreous fluid) chambers of the eye, and intraocular fine-needle aspiration specimens. The clinical findings, testing, and cytologic features of ocular surface epithelial infections, inflammations and neoplasia are discussed; and challenges in processing and diagnosing intraocular infections, chronic uveitis, and vitreoretinal lymphoma are reviewed. Novel molecular testing in the cytologic diagnosis and classification of uveal melanoma also is explored. Cytology evaluation of corneal epithelial and stromal cells, anterior chamber and vitreous samples, and fine-needle aspiration biopsies can provide detailed diagnostic findings to aid in the treatment and follow-up of patients with ocular diseases., (© 2020 American Cancer Society.)

Background: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. Methods: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. Results: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. Conclusion: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively. [ABSTRACT FROM AUTHOR]

Purpose: To assess changes in symptoms and ocular surface signs following a bilateral sutureless treatment of dehydrated amniotic membrane (dAM) under a specialised bandage contact lens (sBCL) in patients with moderate-to-severe dry eye disease (DED). Patients and Methods: In this prospective pre-post interventional study, 35 patients diagnosed with moderate-to-severe DED, with an Ocular Surface Disease Index (OSDI) score > 30 on current treatment, were enrolled. Assessments were conducted at baseline (day − 30), after 30 days run-in with no additional treatment (day 0 – control), and 30 days post sBCL+dAM treatment (day 30 – treatment). Intervention involved two successive bilateral 4-5 day sutureless applications of dAM (17mm diameter, with a 6 mm central aperture, Omnigen® VIEW) under an 18mm sBCL (OmniLenz®). Symptomatology and ocular signs were measured using OSDI, Dry Eye Questionnaire-5 (DEQ-5), Symptom Assessment iN Dry Eye (SANDE), and other ocular surface health indicators including non-invasive breakup time, corneal and conjunctival staining, and lid wiper epitheliopathy length and width (LWE). Results: While symptomatology remained stable during the 30-day no-treatment run-in, 1-month post-dAM treatment, there was a significant reduction in OSDI scores (from 55.8 to 32.3, p< 0.001), DEQ-5 (from 14.6 to 10.0, p< 0.001), SANDE frequency (from 65.2 to 43.6, p< 0.001), and SANDE severity (from 59.8 to 41.1, p< 0.001). Additionally, there was a notable decrease in the width of LWE staining, from grade 2 (50– 75% of the lid wiper) to grade 1 (25– 50% of the lid wiper) (p=0.011). Conclusion: A bilateral 8– 10-day treatment duration with dAM applied with sBCL demonstrated a 31 to 42% improvement in symptomatology and a decrease in ocular surface signs of mechanical stress. This innovative bilateral treatment approach offers a promising treatment modality for patients with refractory moderate-to-severe DED. [ABSTRACT FROM AUTHOR]

aime E Dickerson Jr9,101Private Practice, Philadelphia, PA, USA; 2Schwartz Laser Eye Center, Scottsdale, AZ, USA; 3Loh Ophthalmology Associates, Miami, FL, USA; 4Cleveland Eye Clinic, Brecksville, OH, USA; 5Rosenberg School of Optometry, University of the Incarnate Word, San Antonio, TX, USA; 6LASIK San Antonio, Kerrville, TX, USA; 7Gordon Schanzlin New Vision Institute, La Jolla, CA, USA; 8Kannarr Eye Care, Pittsburg, KS, USA; 9Sight Sciences, Menlo Park, CA, USA; 10North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA Correspondence: Jaime E Dickerson Jr, Email [email protected] Purpose: To evaluate dry eye disease (DED) signs and symptoms six months after a single treatment with Localized Heat Therapy (LHT) (TearCare, Sight Sciences) for patients previously treated for six months with cyclosporine (0.05%) ophthalmic emulsion (CsA) BID (Restasis, Allergan). Setting: Nineteen ophthalmic and optometric practices in 11 US states. Design: Multicenter, cross-over, six month extension to the SAHARA randomized, controlled trial (RCT). Included patients were those randomized to CsA in Phase 1 of the SAHARA RCT. Methods: This was the second phase of the SAHARA RCT in which, following the 6-month endpoint, all patients that had been randomized to CsA discontinued CsA and were treated with LHT and subsequently followed for an additional six months. Outcome measures at 12 months for CsA patients crossed over to LHT included TBUT, OSDI and MGSS. Results: One hundred and sixty-one patients (322 eyes) were analyzed. Mean (SD) baseline TBUT prior to CsA was 4.4 (1.2) seconds, 5.6 (2.6) at 6 months which improved to 6.6 (3.2) and 6.1 (2.8) seconds (both P < 0.001) at 9 and 12 months (3, 6 months post LHT). Mean (SD) OSDI was 50.0 (14.9) at baseline and 34.2 (21.5) after CsA. With LHT at 6 months, this improved to 30.0 (20.6) and 31.0 (19.5) at 9 and 12 months (P = 0.162 vs month 6, P < 0.0001 vs baseline). MGSS was 7.1 (3.2) at baseline, 13.3 (8.2) at the end of CsA treatment which improved to 17.4 (8.8) and 16.1 (9.0) at 9 and 12 months; both P < 0.001. Conclusion: SAHARA showed 6-month superiority of LHT to CsA in clinical signs and non-inferiority in symptom scores. This extension shows that patients treated with CsA for 6 months can achieve meaningful additional improvement in signs and symptoms lasting for as long as 6 months following a single LHT treatment without the need for topical prescription therapy. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to evaluate multi-symptom relief of dry eye manifestations with the use of propylene glycol-hydroxypropyl-guar (PG-HPG) nanoemulsion lubricant eye drops, among subjects with dry eye disease (DED). Methods: This was a post-marketing, prospective, single-arm study conducted in the USA. Subjects aged ≥ 18 years, with tear breakup time (TBUT) ≤ 10 s for both eyes, dry eye questionnaire-5 (DEQ-5) "watery eyes" symptom score 1–4, symptoms of burning/stinging, sore and tired eyes as determined by impact of dry eye on everyday living—symptom bother (IDEEL-SB) questionnaire, and IDEEL-SB score 16–65 were included. Subjects were required to complete IDEEL-SB and DEQ-5 at days 0, 14 ± 2, and 28 ± 2, and self-administer one drop of PG-HPG four times daily for 28 ± 2 days. Primary endpoints were change from baseline at day 28 in symptoms of sore, stinging/burning, and tired eyes on IDEEL-SB; and symptom of watery eyes on DEQ-5. Other endpoints evaluated were corneal staining and TBUT at baseline and day 28 ± 2; symptom relief (5-point Likert scale) at day 28 ± 2, and safety. Results: Of 119 subjects enrolled, 95 completed the study (mean ± SD age 61.2 ± 13.0 years; female 69.5%). Mean IDEEL-SB scores reduced significantly from baseline at day 28 for symptoms of aching/sore eyes (change from baseline − 1.0 ± 1.1), burning/stinging eyes (change from baseline − 1.1 ± 0.9), and tired eyes (change from baseline − 1.1 ± 1.0) (all p < 0.0001). Mean DEQ-5 score for watery eye symptoms significantly reduced from baseline at day 28 (change from baseline − 0.9 ± 1.0, p < 0.0001). Corneal staining at day 28 was comparable to baseline. TBUT improved from baseline to day 28. On a Likert scale, more than 50% of subjects reported relief from symptoms of sore, stinging, and burning eyes. Three (3.1%) subjects reported treatment-emergent adverse events (non-ocular). Conclusions: PG-HPG nanoemulsion lubricant eye drops significantly improved multiple dry eye symptoms in subjects with DED over 28 days, with no new safety concerns. Trial Registration: ClinicalTrials.gov Identifier, NCT05056155. [ABSTRACT FROM AUTHOR]

Background: Dry eye is one of the most common ophthalmic conditions and can significantly impact quality of life. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye. We sought to conduct a systematic review and meta-analysis to estimate the prevalence and incidence of dry eye and MGD in Central and South America and to identify factors associated with disease burden. Methods: Data sources Ovid MEDLINE and Embase. Study selection: A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case–control studies, and interventional studies were excluded. Data extraction and synthesis: The review was based on a protocol registered on PROSPERO (CRD42021256934). Risk of bias was assessed in duplicate using a risk of bias tool designed for the purposes of descriptive epidemiological studies. Data were extracted by one investigator and verified by another for accuracy. Prevalence of dry eye and MGD were grouped based on study participant characteristics. Main outcomes and measures: Prevalence and incidence of dry eye and MGD in Central and South America. Summary estimates from meta-analysis with 95% confidence intervals (CI). Results: Fourteen studies (11,594 total participants) were included. The population prevalence of dry eye was 13% (95% CI, 12%-14%) in Brazil and 41% (95% CI, 39%-44%) in Mexico based on one study each. Meta-analyses suggested that dry eye prevalence was 70% among indoor workers (95% CI, 56%-80%; I2, 82%; 3 studies), 71% among students (95% CI, 65%-77%; I2, 92%; 3 studies), and 83% in general ophthalmology clinics (95% CI, 77%-88%; I2, 88%; 2 studies). MGD prevalence ranged from 23% among indoor workers (95% CI, 16%-31%; 1 study) to 68% in general ophthalmology clinics (95% CI, 62%-72%; 1 study). No studies reported incidence of dry eye or MGD. Conclusions: This systematic review and meta-analysis demonstrated considerable variation in the published prevalence of dry eye and MGD among the general population and subpopulations in Central and South America. Local and subpopulation estimates of dry eye disease burden may be valuable to assist needs assessments and implementation of measures to mitigate the condition. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess how Romanian medical students suffer from dry eye disease symptoms, establish the prevalence and severity of dry eye (DE) symptoms and identify potential risk factors. Methods: An analytical, cross-sectional study was conducted on students from "Carol Davila" University of Medicine, Romania, after the final examination period of July 2022. The OSDI score (Ocular Surface Disease Index©) was applied in an online survey. The study adopted the standards used by other authors, who defined symptomatic DED as an OSDI score greater than 12. The chi-square test was used to establish statistical significance at a cutoff value of p < 0.05. The predictive model was created using linear logistic regression analysis. The goodness of fit of the logistic regression model was assessed using the Hosmer-Lemeshow test. When the severity outcome had a nominal categorical form, multinomial regression analysis with normal subjects as a reference was performed. The distribution of the severe type of symptomatology across sex categories and years of study was analyzed using a nonparametric test (Independent-Samples Kruskal-Wallis Test). Results: A total of 274 answers were received from 81.4% females and 18.6% males with a response rate of 35.58%. The mean age was 22.7 years ± 1.66 with an age range between 20 and 25 years old. Using the OSDI score, we established that the overall prevalence of DE symptoms was 83.6% (95%CI: 79.6%, 88%), with an 85.2% (95%CI: 80.5%, 89.8%) prevalence in females and 76.5% (95%CI: 65%,88%) in males. The severe form of DE was the most prevalent, regardless of the study year or sex. Increased screen time (p-value < 0.05) and non-smokers (p-value < 0.05) were proven risk factors. The predictive model which includes the explanatory variables (sex, contact lens wearers, smoking, oral contraceptives, screen time) proved an 84.7% predictability for symptomatic DE and was able to better predict the dependent variable than the intercept model only (p-value < 0.05). Smoking (p = 0.002) and screen time (p = 0.009) preserved their significance in the multinominal regression as well. Conclusions: This is the first study to report the epidemiology of DE symptoms among Romanian medical students. OSDI revealed a high prevalence of symptomatic DE in medical students. Screen time, although not the only factor, likely plays a role in exacerbating the disease. This information can be used to inform healthcare policies, establish occupational health guidelines, and implement preventive measures for individuals in similar high-stress academic or professional environments. [ABSTRACT FROM AUTHOR]

Introduction and aim: Recently, an increased use of video display terminals has been observed in workplace environments, as a result of the evolution of communication technologies and new information-sharing strategies. It has led to an increased prevalence of computer-related ocular disorders, such as computer vision syndrome, dry eye disease, refractive errors and convergence insufficiency. In this review we describe problems associated with these disorders and propose preventive methods. Material and methods: With the use of specific keywords, the databases of the PubMed, Science Direct, and Google Scholar were searched for relevant original papers. Analysis of the literature. The listed disorders might have similar symptoms, such as eye burning, itching, blurred vision, and tearing, and their severity correlates with the time of exposure to video display units. However, there are preventive measures, which can help in decreasing the negative effects of computers on our vision, such as adequate viewing distance, proper workspace lighting, eyeglasses with anti-glare coating, taking 5-minutes breaks after every 30 minutes, or following the 20-20-20 rule. Concusion: Prolonged usage of the video display terminals is connected to many ocular disorders, and in today's world, it is very important to remember actions that can be undertaken to minimize the risk. [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]

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 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]

Purpose: A randomized clinical trial was run to evaluate the effectiveness of a preservative-free 0.4% sodium hyaluronate eye drop (LOF) in different dosage schemes to alleviate signs and symptoms of dry eye disease (DED).Methods: A total of 116 subjects with mild-to-moderate DED were included, and 111 completed the study (from which 67.6% were female and 65.3% were users of oral contraceptives). Patients were randomly assigned to instill a drop of LOF either 2 (BID), 4 (QID) or 6 (6TD) times a day (at least 3 hours apart) for 30 days. The clinical parameters and symptom endpoints were Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), ocular surface staining, and conjunctival hyperemia. Other parameters evaluated were chemosis, best corrected visual acuity, and the incidence of adverse events (AE).Results: There was a significant reduction in OSDI scores by day 30 in all groups. The recovery of the OSDI score back to normal values was observed in 51.4% of patients treated (50%, 48.6%, and 55.6% in BID, QID, and 6TD, respectively, p = 0.822). Similar improvement was observed for TBUT, 50.5% of patients increased this variable to > 10 seconds (39.5%, 51.4%, and 61.1%, p = 0.175), and for ocular surface staining, ≥ 72% showed Grade 0. There were no significant differences among posology groups regarding ocular surface staining, conjunctival hyperemia, or any safety parameters. No overall improvement in OSDI and TBUT to normal values was noted for 31 patients (21 were female and 71.4% users of contraceptive drugs).Conclusion: The ophthalmic use of preservative free LOF, 2, 4 or 6 times a day, may alleviate clinical parameters and symptoms in 50% of patients with mild-to-moderate DED after a one-month treatment. This improvement seemed to be less ubiquitous in patients within reproductive age and using oral contraceptives.Trial Registration: This trial is registered at clinicaltrials.gov (NCT0704531). [ABSTRACT FROM AUTHOR]

aimi,5 Yahya Al-Najmi61Ophthalmology Department, King Faisal Medical Complex, Taif, Saudi Arabia; 2Ophthalmology Department, Alhada Military Hospital, Taif, Saudi Arabia; 3Ophthalmology Department, Jeddah Eye Hospital, Jeddah, Saudi Arabia; 4Ophthalmology Department, Asir Central hospital, Abha, Saudi Arabia; 5Ophthalmology Department, College of Medicine, Majmaah University, Majmaah, Saudi Arabia; 6Ophthalmology Department, Saggaf Eye Center, Jeddah, Saudi ArabiaCorrespondence: Yahya Al-Najmi, Ophthalmology Department, Saggaf Eye Center, Abdullah Salman St., Al Faiha'a Dist., P.O. Box: 31903, Jeddah, 21418, Saudi Arabia, Tel +966 564844281, Email [email protected] Purpose: To estimate the prevalence and determinants of Ocular Surface Disease Index (OSDI) score based dry eye disease (DED) among the adult urban population of four cities located at high altitudes in Southwest Saudi Arabia.Methods: This cross-sectional survey was held in 2023. OSDI questionnaire was used to collect the responses of the adult participants. The score was further graded into none, mild, moderate, and severe DED to estimate age-sex-adjusted DED prevalence. The OSDI score was correlated to demographic (age group, gender, education, occupation, city) and risk factors like smoking and co-morbidities.Results: Of the 401 adults, 388 (response rate of 97.8%) participated. The age-sex-adjusted prevalence of mild, moderate, and severe DED was 21.7%, 13.1%, and 32%, respectively. The median ODSI score was 22.9 [Interquartile range (IQR) 10.4; 47.9)]. The score was significantly higher in females (Mann–Whitney U-test P = 0.038), residents of Taif city (KW P = 0.05), those with primary/middle school education (Kruskal–Wallis P = 0.004), comorbidities like hypertension, asthma (KW P < 0.001) and risk factors like past refractive surgeries, arthritis (KW P = 0.013). Education status (P < 0.001) [B = − 9.0 95%] and presence of comorbidity (P = 0.022), [B = − 0.823] were significant predictors of DED.Conclusion: The prevalence of DED and severe grade was high. The level of education and presence of comorbidities significantly influenced DED in the adult urban Saudi population of cities at high altitudes. [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]

Background: The neutrophil-to-lymphocyte ratio (NLR) and immunoglobulin A (IgA) level are commonly used as biomarkers for inflammation. Patients with type 2 diabetes (T2D) may experience an imbalance of tear film and inflammation, which can result in dry eye disease (DED). This study aimed to assess the levels of IgA and explore its correlation with the NLR as potential inflammatory biomarkers for dry eye disease in patients with T2D. Methods: A retrospective study was conducted at the cornea clinic and diabetes centre of King Abdulaziz Medical City (Jeddah, Saudi Arabia). The study included patients with DED and the number of available T2D-DED patients determined the sample size. Neutrophil, lymphocyte, IgA and CRP (C-reactive protein) laboratory values were obtained from medical records and correlational analyses were performed. Results: The study included 85 patients with an average age of 54 ± 14.4 years for the DED group (n=32) and 62 ± 13.9 years for the T2D-DED group (n=53). The age difference between the two groups was statistically significant (p 0.0001). The NLR values of the T2D-DED and DED groups were 3.203 ± 0.66 and 2.406 ± 0.46, respectively, with no significant difference (p<0.285). Similarly, there were no significant differences in neutrophil and lymphocyte values between the two groups. The IgA levels showed no significant variation between T2D-DED and DED groups (p<0.364). Spearman’s correlation analysis in the DED group showed a significant negative correlation between IgA and lymphocyte (p=0.011; r= - 0.471) values and significant positive correlations between IgA and neutrophil (p=0.014; r=0.309) and NLR (p=0.052; r= - 0.283) values. In the T2D-DED group, a significant correlation was found between IgA and CRP values (p=0.032; r=0.33). Conclusion: Although diabetic patients may exhibit higher levels of NLR and IgA that correlate with disease severity, our study did not find significant differences in NLR and IgA values between the two groups. These findings may guide future research and enhance understanding of the disease’s underlying mechanisms. [ABSTRACT FROM AUTHOR]

A 69-year-old woman with bilateral primary open-angle glaucoma who underwent cataract extraction with intraocular lens implantation and excisional goniotomy with the Kahook Dual Blade (KDB; New World Medical, Rancho Cucamonga, CA, USA) in both eyes one year prior was referred for evaluation of significant visual acuity loss and pain in the left eye. On initial examination, intraocular pressure in the left eye was 3 mmHg and slit lamp examination revealed normal anterior chamber depth. Gonioscopy revealed a cyclodialysis cleft that was confirmed by anterior segment optical coherence tomography. Prominent chorioretinal folds suggestive of long-standing hypotony maculopathy were observed during fundoscopic examination. The cyclodialysis cleft, thought to be created inadvertently during the KDB goniotomy, resolved after three sessions of argon laser photocoagulation and the patient's symptoms and visual acuity partially improved. [ABSTRACT FROM AUTHOR]

Background: Environmental and epidemiological factors increase the risk of dry eye in Saudi Arabia, but most studies have limited generalizability. Objective: To determine the prevalence of dry eye disease (DED) among adults across Saudi Arabia and the associated risk factors. The secondary objective was to estimate the economic burden of DED by calculating lubricant usage and its annual costs. Methods: This cross-sectional study invited adults from across Saudi Arabia to complete a questionnaire that collected data regarding demographics, symptoms related to DED, previous diagnosis of DED, use of contact lenses, and use of eye lubricants. Results: A total of 2042 responses were received, of which 784 (38.4%) respondents had previously been diagnosed with DED and 752 (36.8%) were symptomatic but undiagnosed. Between the DED diagnosed and symptomatic-undiagnosed groups, a significant difference was found in terms of age (P < 0.001), gender (P = 0.002), presence of diabetes mellitus (P = 0.004), smoking status (P = 0.007), duration of electronic screen use (P = 0.05), number of ocular complaints (P < 0.001), and frequency of lubricants use (P < 0.001). Between the DED-diagnosed and non-DED groups, significant differences were found in terms of age (P < 0.001), gender (P < 0.001), presence of diabetes mellitus (P = 0.001), allergy (P = 0.001), autoimmune disease (P = 0.005), smoking status (P < 0.001), and history of refractive surgery (P < 0.001). The mean estimated annual cost of using lubricating agents was SAR 328.2 ± 210.3 (USD 87.5 ± 56.1), and this was significantly higher in the diagnosed group (P = 0.01) than the symptomatic-undiagnosed group. Conclusions: The prevalence of DED is high among adults in Saudi Arabia. High-risk population include elderly, female, and using electronic screens for >2 hours/day. [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]

On the other hand, Giannaccare et al. [[192]] conducted a study on patients with MGD having subjective symptoms (OSDI>= 13) and at least one clinical sign of MGD, such as terminal ductal obstruction, plugging of the meibomian glands, turbid secretions, inflammation and swelling of the eyelid margins, or poor meibum secretions. One RCT [[423]] and two observational studies [[429]] assessed improvements in meibomian gland orifices and surrounding findings and report that minocycline oral administration can improve meibomian gland orifices and surrounding findings in patients with MGD and meibomitis. Additionally, Ibrahim et al. [[279]] show that meibomian gland acinar density, shortest and longest acinar diameter, and inflammatory cell density were significantly associated with BUT, fluorescein staining score, Rose Bengal staining, decreased lipid expression from the meibomian gland orifices, meibomian gland dropout, and ocular surface tear evaporation rate. In 22 patients without atrophy of the meibomian gland, after treatment with the cleansing agent, meibography indicated significant improvements in the meibomian gland orifices/surrounding findings (eyelid margin vascularity), quality of meibum, and BUT. [Extracted from the article]

Dry eye disease (DED) is a common ocular condition, but the diagnosis relative to other ocular conditions and the evaluation of severity of the condition has often been difficult. This challenge can be due to clinical signs and symptoms not always correlating with each other. An understanding of the various components which create the condition, as well as the diagnostic measures used to evaluate these components, is useful to the clinician working with DED patients. This review paper will discuss traditional diagnostic options, diagnostic imaging, and Advanced Point of Care testing capabilities to determine the severity level of dry eye disease more adequately. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye disease (DED) is a common ocular problem that worsens patients' quality of life. This study aimed to assess DED prevalence and risk factors among medical students at the University of Tabuk. Patients and Methods: This is an analytical, cross-sectional, survey-based study. An online questionnaire was distributed by email to all medical students at the University of Tabuk. A self-administered McMonnies questionnaire was used in the assessment. Results: We included 247 medical students who completed the questionnaire. Most participants were females (71.3%) and were < 25 years old (85.8%). DED prevalence rate was 18.2% (95% CI=13.61% to 23.61%). Furthermore, DED was found to be significantly associated with the presence of irritation of eyes when waking up from sleep (OR=19.315), sleeping with partially opened eyes (OR=19.105), redness and irritation of the eyes when swimming in chlorinated fresh water (OR=7.863), and having prescription eyedrops or other dry eye treatments (OR=3.083). Conclusion: Our study at the University of Tabuk found that 18.2% of medical students had dry eye disease and identified the associated risk factors. Early diagnosis and treatment are crucial to prevent complications due to the high prevalence of DED. [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]

Objectives: To assess the prevalence of dry eye disease (DED) in the Uyghur population in Hotan, Xinjiang, and to identify risk factors associated with this disorder. Methods: Between January and September of 2020, 5,121 Uyghur subjects aged 18 − 98 years from 105 villages were selected and studied cross-sectionally using a whole-group random sampling method in the Hotan area, Xinjiang, China. The Ocular Surface Disease Index questionnaire was used to collect subjective symptoms of DED and examine tear-film break-up times. The break up time and Schirmer's test were used to collect objective signs, to determine the prevalence of DED and its risk factors. Results: A total of 5,121 subjects aged 18 − 98 years were recruited from the Uyghur population in the Hotan region of Xinjiang, China, for eye examinations and questionnaire surveys. A total of 40.6% (2,078/5,121) were diagnosed with DED, of which 38.3% were male and 41.9% were female. The prevalence of DED was the highest in subjects ≥ 65 years of age, with 47.8% in males and 53.3% in females. The lowest occurrence was in subjects 18 − 44 years of age, with 32.5% in males and 33.7% in females. Older age, tea drinking, and staying awake late were risk factors affecting the severity of DED prevalence (p < 0.05), but there was no significant difference in sex, presence of diabetes, or presence of hypertension (p > 0.05). Conclusion: The prevalence of DED in the study population was 40.6%, and its prevalence was higher in females, when compared with males. The prevalence of dry eye also increased with age, and at an advanced age, female sex, smoking, staying awake late, and not exercising were risk factors for DED. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effectiveness of subconjunctival application of a novel sirolimus liposomal formulation for the treatment of dry eye. Methods: A randomized, triple-blind, Phase II clinical trial. Thirty-eight eyes of 19 patients were included. Nine patients (18 eyes) assigned to the sham group (Sham) and 10 patients (20 eyes) to sirolimus-loaded liposomes group (Sirolimus). The treatment group received three doses of subconjunctival liposome-encapsulated sirolimus and the sham group received three doses of liposomal suspension without sirolimus. Subjective (Ocular Surface Disease Index, OSDI) and measured (corrected distance visual acuity, conjunctival hyperemia, tear osmolarity, Schirmer's test, corneal/conjunctival staining and matrix metalloproteinase-9) variables were measured. Results: Sirolimus-entrapped liposomes-treated group OSDI scores changed from 62.19 (± 6.07) to 37.8 (± 17.81) (p=0.0024), and conjunctival hyperemia from 2.0 (± 0.68) to 0.83 (± 0.61) (p< 0.0001); Sham group with OSDI scores from 60.02 (± 14.2) to 36.02 (± 20.70) (p=0.01), and conjunctival hyperemia from 1.33 (± 0.68) to 0.94 (± 0.87) (p=0.048). All the other evaluated outcomes only showed significant differences in the sirolimus group: corneal/conjunctival staining score (p=0.0015), lipid layer interferometry (p=0.006), and inferior meibomian gland dropout (p=0.038). No local or systemic adverse effects regarding the medication itself were reported, and the administration route was well accepted. Conclusion: Our findings suggest that sub-conjunctival sirolimus-loaded liposomes are effective in reducing both signs and symptoms of dry eye in patients with poorly controlled moderate-to-severe DED, while avoiding other topical administration adverse effects. Further investigation with a larger sample size is required to determine long-term effects. [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]

Dry eye disease (DED) is a multi‑factorial ocular surface condition driven by compromised ocular lubrication and inflammation which leads to itching, dryness, and vision impairment. The available treatment modalities primarily target the acquired symptoms of DED including tear film supplements, anti‑inflammatory drugs, mucin secretagogues, etc., However, the underlying etiology is still an area of active research, especially in regard to the diverse etiology and symptoms. Proteomics is a robust approach that has been playing major role in understanding the causative mechanism and biochemical changes in DED by identifying the changes in protein expression profile in tears. Tears are a complex fluid composed of several biomolecules such as proteins, peptides, lipids, mucins, and metabolites secreted from lacrimal gland, meibomian gland, cornea, and vascular sources. Over the past two decades, tears have emerged as a bona‑fide source for biomarker identification in many ocular conditions because of the minimally invasive and simple sample collection procedure. However, the tear proteome can be altered by several factors, which increases the complexity of the approach. The recent advancements in untargeted mass spectrometry‑based proteomics could overcome such shortcomings. Also, these technological advancements help to distinguish the DED profiles based on its association with other complications such as Sjogren’s syndrome, rheumatoid arthritis, diabetes, and meibomian gland dysfunction. This review summarizes the important molecular profiles found in proteomics studies to be altered in DED which have added to the understanding of its pathogenesis. [ABSTRACT FROM AUTHOR]

Lacrimal and meibomian glands contribute to the aqueous and lipid components of tear film, respectively. Their evaluation remains central to diagnosing and managing dry eye disease (DED). The review discusses the differences and reliability of various diagnostic tests and commercially available devices used for DED diagnosis. Slit‑lamp‑based techniques are direct palpebral lobe and tear flow assessment, Schirmer test, meibum quality and expressibility, and evaluation of tear meniscus height. Non‑invasive tear meniscus height (TMH), tear break‑up time (TBUT), lipid layer thickness (LLT), and meibography are machine‑based diagnostic tests. The structure–function correlation of the tear‑producing glands gives more comprehensive details than either information alone. Many devices are available in the market, which make DED diagnosis an easy feat, but the tests should be interpreted keeping in mind the intra‑observer and inter‑observer repeatability. Also, the tear film displays a huge variability as per the environmental conditions and impact of blinking. Hence, the examiner should be well versed with the techniques and repeat the test two to three times to obtain an average reading, which is more reliable. The recommended sequence of tests for diagnosing DED is a dry eye questionnaire, TMH, LLT, NIBUT (FBUT if non‑invasive test is unavailable but should be performed after osmolarity), tear osmolarity, meibography, and ocular surface staining. Invasive tests such as Schirmer should be performed after the non‑invasive tear film diagnostic testing. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial chronic ocular surface inflammatory condition. Disease severity has been directly related to the immuno‑inflammatory status of the ocular surface. Any perturbation in the orchestrated functional harmony between the ocular surface structural cells and immune cells, both resident and trafficking ones, can adversely affect ocular surface health. The diversity and contribution of ocular surface immune cells in DED have been of interest for over a couple of decades. As is true with any mucosal tissue, the ocular surface harbors a variety of immune cells of the innate‑adaptive continuum and some of which are altered in DED. The current review curates and organizes the knowledge related to the ocular surface immune cell diversity in DED. Ten different major immune cell types and 21 immune cell subsets have been studied in the context of DED in human subjects and in animal models. The most pertinent observations are increased ocular surface proportions of neutrophils, dendritic cells, macrophages, and T cell subsets (CD4+; CD8+; Th17) along with a decrease in T regulatory cells. Some of these cells have demonstrated disease‑causal association with ocular surface health parameters such as OSDI score, Schirmer’s test‑1, tear break‑up time, and corneal staining. The review also summarizes various interventional strategies studied to modulate specific immune cell subsets and reduce DED severity. Further advancements would enable the use of ocular surface immune cell diversity, in patient stratification, i.e. DED‑immunotypes, disease monitoring, and selective targeting to resolve the morbidity related to DED. [ABSTRACT FROM AUTHOR]

Corneal perforations in eyes with dry eye disease (DED) are difficult to manage due to the interplay of several factors such as the unstable tear film, surface inflammation, and the underlying systemic disease affecting the wound healing process, and the eventual outcome. A careful preoperative examination is required to identify the underlying pathology, and status of ocular surface and adnexa, rule out microbial keratitis, and order appropriate systemic workup in addition to assessing the perforation itself. Several surgical options are available, which include tissue adhesives, multilayered amniotic membrane grafting (AMT), tenon patch graft (TPG), corneal patch graft (CPG), and penetrating keratoplasty (PK). The choice of procedure depends upon the size, location, and configuration of the perforation. In eyes with smaller perforations, tissue adhesives are effective treatment modalities, whereas AMT, TPG, and CPG are viable options in moderate‑sized perforations. AMT and TPG are also preferable in cases where the placement of a bandage contact lens may be a challenge. Large perforations require a PK, with additional procedures such as tarsorrhaphy to protect the eyes from the associated epithelial healing issues. Conjunctival flaps are considered in eyes with poor visual potential. The management of the acute condition is carried out in conjunction with measures to improve the tear volume bearing in mind the chances of delayed epithelialization and re‑perforation in these cases. Administration of topical and systemic immunosuppression, when indicated, helps improve the outcome. This review aims to facilitate clinicians in instituting a synchronized multifaceted therapy for the successful management of corneal perforations in the setting of DED. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) which affects millions of people worldwide is an ocular surface disease that is strongly associated with pain, discomfort, and visual disturbances. Altered tear film dynamics, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities are the key contributors to DED pathogenesis. The presence of discordance between signs and symptoms of DED in patients and refractoriness to current therapies in some patients underpin the need for studying additional contributors that can be modulated. The presence of electrolytes or ions including sodium, potassium, chloride, bicarbonate, calcium, and magnesium in the tear fluid and ocular surface cells contribute to ocular surface homeostasis. Ionic or electrolyte imbalance and osmotic imbalance have been observed in DED and feed‑forward interaction between ionic imbalances and inflammation alter cellular processes in the ocular surface resulting in DED. Ionic balances in various cellular and intercellular compartments are maintained by dynamic transport via ion channel proteins present in cell membranes. Hence, alterations in the expression and/or activity of about 33 types of ion channels that belong to voltage‑gated channels, ligand‑gated channels, mechanosensitive ion channel, aquaporins, chloride ion channel, sodium– potassium–chloride pumps or cotransporters have been investigated in the context of ocular surface health and DED in animal and/or human subjects. An increase in the expression or activity of TRPA1, TRPV1, Nav1.8, KCNJ6, ASIC1, ASIC3, P2X, P2Y, and NMDA receptor have been implicated in DED pathogenesis, whereas an increase in the expression or activity of TRPM8, GABAA receptor, CFTR, and NKA have been associated with resolution of DED. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a complex disorder of the ocular surface with a loss of tear film homeostasis, causing an imbalance in the tear–air interface and leading to ocular discomfort, pain, and vision issues. Immune control issues are a primary factor in dry eye disorder’s origin, progression, and management. The aim of managing DED is to reduce symptoms and improve the life quality of those affected. Despite the diagnosis, up to half of the patients do not get proper care. The scarcity of successful treatments for DED is worrisome, and it is of increasing importance to comprehend the root causes and create more effective therapies to alleviate the distress of those afflicted with the disorder. Therefore, the role of the immune system in the initiation and progression of DED has become the research focus. This paper reviews the current insight into the immune response in DED, the existing treatment methods, and ongoing research to search for better treatments. [ABSTRACT FROM AUTHOR]

Evaporative dry eye (EDE) due to meibomian gland dysfunction (MGD) is one of the common clinical problems encountered in ophthalmology. It is a major cause of dry eye disease (DED) and of ocular morbidity. In EDE, inadequate quantity or quality of lipids produced by the meibomian glands leads to faster evaporation of the preocular tear film and symptoms and signs of DED. Although the diagnosis is made using a combination of clinical features and special diagnostic test results, the management of the disease might be challenging as it is often difficult to distinguish EDE from other subtypes of DED. This is critical because the approach to the treatment of DED is guided by identifying the underlying subtype and cause. The traditional treatment of MGD consists of warm compresses, lid massage, and improving lid hygiene, all measures aimed at relieving glandular obstruction and facilitating meibum outflow. In recent years, newer diagnostic imaging modalities and therapies for EDE like vectored thermal pulsation and intense pulsed light therapy have emerged. However, the multitude of management options may confuse the treating ophthalmologist, and a customized rather than a generalized approach is necessary for these patients. This review aims to provide a simplified approach to diagnose EDE due to MGD and to individualize treatment for each patient. The review also emphasizes the role of lifestyle modifications and appropriate counseling so that patients can have realistic expectations and enjoy a better quality of life. [ABSTRACT FROM AUTHOR]

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

Dry eye disease (DED) is prevalent in all age groups and is known to cause chronic ocular discomfort and pain, and greatly affects the quality of life. Patients with ocular surface disease (OSD) may also have reduced tear secretion due to lacrimal gland damage, thus leading to aqueous deficient DED. Even with conventional management modalities such as lubricating eyedrops, topical corticosteroids, autologous serum eyedrops, or punctal plugs, many patients continue to suffer from debilitating symptoms. Contact lenses are increasingly being used in OSD providing surface hydration, protection from environmental insults, mechanical damage from abnormal lids, and as a modality for constant drug delivery to the ocular surface. This review describes the role of soft lenses and rigid gas‑permeable scleral lenses in the management of DED associated with OSD. The efficacy of contact lenses, lens selection, and optimal lens fit are reviewed for specific indications. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study was to compare the efficacy of sodium hyaluronate (SH) and carboxymethyl cellulose (CMC) eye drops in treating mild to moderate dry eye disease in terms of relief of symptoms, mean change in tear film breakup time, Schirmer’s test, and impression cytology of conjunctiva from baseline. Methods: An observational study was carried out during a 2‑year period in our tertiary referral hospital. The study consisted of 60 patients randomly allotted to two groups to receive SH and CMC eye drops for an 8‑week period. Ocular surface disease index, tear film breakup time, and Schirmer’s test were performed at baseline visit and 4 and 8 weeks of treatment, and impression cytology of conjunctiva was performed at baseline and 8 weeks. Results: Significant improvement in patient symptoms, tear film breakup time, and Schirmer’s test from baseline was seen in both SH and CMC groups at 8 weeks posttreatment, whereas impression cytology of conjunctiva in both groups did not show significant improvement at 8 weeks of treatment. Data analysis using unpaired t‑test showed comparable results. Conclusion: Both CMC and SH demonstrated equal efficacy in treating mild to moderate dry eye disease. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous‑deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one‑third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long‑term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well‑being of affected individuals. This review discusses the various etiologies of ADDE, highlights a pathophysiology‑based approach for evaluating underlying contributors, outlines various diagnostic tests, and reviews treatment options. We present the current standards and discuss ongoing research in this field. Through this review, we propose a treatment algorithm that would be useful for an ophthalmologist in diagnosing and managing individuals with ADD. [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]