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Objectives: To investigate tear function and ocular surface disease (OSD) findings in patients with glaucoma who received antiglaucoma medication in one eye and trabeculectomy surgery in the other eye., Materials and Methods: The patient group included 38 eyes of 19 patients who had undergone trabeculectomy surgery with mitomycin C (MMC) treatment in one eye at least 6 months prior. These eyes were followed up without medication while the fellow eye continued receiving antiglaucomatous medication. The control group comprised 20 eyes of 20 healthy individuals. Demographic data, follow-up period after trabeculectomy, antiglaucoma medications, number of drops per day, and duration of medication were recorded. Tear break-up time (BUT), corneal and conjunctival fluorescein staining, Schirmer II test, and conjunctival impression cytology were performed., Results: A statistically significant difference was observed in BUT, corneal and conjunctival fluorescein staining, Schirmer II test, and Nelson staging levels in both eyes of patients with glaucoma compared to the control group (p=0.05). Although not statistically significant, BUT, Schirmer II test, punctate staining, and Nelson staging results showed improvement with increasing postoperative time., Conclusion: In our patient group, antiglaucoma medications and trabeculectomy surgery with MMC induced OSD to a similar degree. No superiority was observed between trabeculectomy with MMC and antiglaucoma drops in terms of OSD incidence., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Sclerocorneal grafts are procedures considered in cases with extensive corneal and scleral tissue destruction. The study aims to describe sclerokeratoplasty outcomes in severely diseased eyes. We performed a retrospective review of clinical records. Demographic characteristics, medical history, surgical indications, aetiology of perforation, visual outcomes, complications associated with the surgical procedure, and ocular integrity at the end of the follow-up were obtained. Wilcoxon-signed rank tests and Mann-Whitney tests were used to compare complications between groups and outcomes at final follow-up. Survival analysis was performed to analyse vision preservation and global integrity and presented in Kaplan-Meier curves. 40 eyes from 40 patients with a mean age of 48.83 ± 18.85 years and a mean follow-up of 21.13 ± 33.92 months were included in the study. Median corrected visual acuity before and after the procedure remained at 2.8 logMAR. Twenty-seven eyes presented complications. The most common complications were a persistent epithelial defect in 11, hypertension in 10, and perforation in 8 eyes. More than half of the eyes (67.5%) presented with either one or more of all complications after corneoscleral graft. No significant differences were found regarding age, gender, or DM history. Concerning perforation, a significant difference was found between infectious and non-infectious only in the presentation of ocular hypertension (p = 0.048). Vision was preserved in 72.5% of the eyes, with a median survival probability of 4.12 years. Preservation of the ocular integrity was achieved in 85% of the eyes, with a median survival probability of 12 years. Sclerokeratoplasty despite being challenging and technically demanding followed by defiant complications, in some situations such as infectious keratitis and autoimmune diseases, is likely a procedure that salvages the eye and preserves vision., (© 2024. The Author(s).)

Ocular surface disease (OSD) is a frequent disabling challenge among patients with glaucoma who use benzalkonium chloride (BAK)-containing topical glaucoma medications for prolonged periods. In this comprehensive review, we evaluated the prevalence of OSD and its management, focusing on both current and future alternatives. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to assess a) the impact of active ingredients and preservatives on the ocular surface and b) the efficacy of preservative-free (PF) alternatives and adjunctive therapies. BAK-containing glaucoma medications were found to significantly contribute to OSD by increasing corneal staining, reducing tear film stability, and elevating ocular surface disease index (OSDI) scores. Transitioning to PF formulations or those with less cytotoxic preservatives, such as Polyquad ® and SofZia ® , demonstrated a marked improvement in OSD symptoms. In particular, the use of adjunct cyclosporine A, through its anti-inflammatory and enhanced tear film stability actions, was shown to be very beneficial to the ocular surface. Therefore, the most effective management of OSD is multi-factorial, consisting of switching to PF or less cytotoxic medications, adjunct use of cyclosporine A, and early incorporation of glaucoma surgical treatments such as laser trabeculoplasty, trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS).

Purpose: While substantial research has focused on systemic immunomodulatory therapy for ocular cicatricial pemphigoid (OCP), limited data exist on managing associated ocular surface disease (OSD). This study evaluates treatments for OCP-related OSD at our institution., Methods: We conducted a retrospective analysis of patients diagnosed with cicatrizing conjunctivitis at the University of Colorado Hospital from January 1, 2013, to October 31, 2023. Patients with cicatrizing conjunctivitis due to non-OCP conditions were excluded, and disease severity was classified using the Foster Staging System., Results: Our review included 30 patients with OCP, all with at least six months of follow-up. The mean age of symptom onset ( n  = 19) was 62.2 years (SD = 16.4), while the mean age at diagnosis ( n  = 28) was 65.1 years (SD = 12.7). The most common OSD treatments at the last visit were preservative-free artificial tears (87%), topical corticosteroids (43%), autologous serum eye drops (40%), topical antibiotics (30%), and topical immunomodulators (23%). All patients used at least one treatment, with 83.3% on prescription therapies. Patients averaged 3.33 (SD: 1.4) treatments, with 1.7 (SD: 1.2) being prescriptions. Topical immunomodulators had the highest discontinuation rate at 73.1% ( n  = 19/26). Autologous serum eye drops and topical corticosteroids were the least discontinued treatments. Number of total treatments, prescriptions, and procedures sharply increased at stage three OCP., Conclusions: The number of treatments and procedures increased with OCP severity, indicating that advanced OCP often necessitated more intensive OSD management.

Background: Dry eye disease (DED) is a prevalent condition affecting over 16 million patients in the USA. DED and the symptoms of ocular discomfort are debilitating and a significant burden on patients. If left untreated, DED can progress to cause severe pathology. Treatment is often initiated by patients without consulting a healthcare professional. This study investigated the safety and efficacy of a novel lipid-containing eye drop (BTC), which might better mimic the components of natural tears., Methods: This was a multicenter, randomized, double-masked, active control, two arm, parallel group study of eye drops in adult subjects with self-reported DED. Subjects were randomly assigned to BTC or control (commercially available non-lipid eye drops; NLED) arm and were followed for 30 days. Assessments using visual analog scale and patient-reported outcomes (PRO) questionnaires, non-invasive tear break up time, slit-lamp examination, and subject-reported ocular symptoms were conducted at baseline and at days 7 and 30. The primary endpoint was change in overall ocular comfort score from baseline to day 30., Results: 158 subjects were randomized, of whom 130 completed the study per protocol (PP). Mean (SD) age was 47.8 (14.14) years. The mean (95% CI) change in overall comfort scores at the 30-day follow-up in the PP population was 21.4 (15.1, 27.7) for the test drop and 10.0 (3.9, 16.1) for the comparator. The mean (95% CI) treatment difference was 11.3 (2.6, 20.1); this met the pre-defined requirements for non-inferiority. There was no significant difference in the proportion of eyes with reported ocular symptoms between the groups. At day 7, the OR (95% CI) was 0.967 (0.528, 1.770) and at day 30 was 1.160 (0.610, 2.203). There were no Grade 3 or higher corneal edema, corneal neovascularization, corneal staining, conjunctival injection, tarsal abnormalities or any other biomicroscopy findings, and no corneal infiltrates observed during the study., Conclusions: The investigational lipid eye drop BTC was noninferior to the commercially available non-lipid comparator in all parameters measured and has the potential to provide an effective therapy for subjects with symptoms of dry eye who would benefit from a lipid-based artificial tear., Trial Registration: NCT03995355 ( http://www., Clinicaltrials: gov ), registered June 24, 2019., (© 2024. The Author(s).)

Objective: To determine the replication kinetics and cytopathic effect (CPE) of feline calicivirus (FCV) in feline corneal epithelial cells (FCEC)., Animals Studied: Seven archived FCV isolates and one archived feline herpesvirus type 1 (FHV-1) isolate, previously obtained from eight domestic short hair cats., Procedures: FCV RNA was extracted for sequencing using Illumina MiSeq, to identify three genomically diverse isolates for further testing. Following reference-based assembly, viral genomes were annotated and assessed. Superficial keratectomies were performed to isolate the corneal epithelium of cats and the cells were cultured in vitro. FCEC were infected with the three chosen FCV isolates and one FHV-1 isolate at two different multiplicity of infection ratios (MOIs, 0.1 and 0.01 PFU/cell) and virus titration was assessed at 0, 2, 6, 12, 24, and 48 h post-infection (hpi). Viral identity was confirmed by RT-qPCR., Results: Three genomically diverse FCV isolates were chosen for further assessment in the FCEC model. All infections of FCEC with FCV led to visible CPE, characterized by epithelial cell rounding and detachment from the plate by 24 hpi, while FHV-1 led to visible CPE within 48 hpi. All three of the FCV isolates replicated effectively in FCEC at both 0.1 and 0.01 MOI, with a peak increase in titer approximately 12-24 hpi., Conclusions: The results support the possible role of FCV as a primary pathogen of the feline ocular surface. FCV replicates in FCEC in vitro, leading to profound CPE., (© 2024 American College of Veterinary Ophthalmologists.)

Purpose: To assess two cases of filamentary keratitis with elevated serum levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies without known rheumatoid arthritis (RA)., Methods: A retrospective chart review was conducted on cases with filamentary keratitis and elevated anti-CCP antibodies between January 2021 and January 2023. Patient demographics, clinical characteristics, and serological test results were reviewed., Results: The first patient, a 77-year-old man, presented with foreign body sensation and eye redness. He reported mild dry mouth but no joint pain or known autoimmune disease, though he had a family history of RA. Schirmer test scores were 7 and 12 mm in the right and left eyes, with an ocular staining score (OSS) of 12 in each eye. His serum anti-CCP antibody level was >2,777 U. Over 3 years of follow-up, he showed no signs of RA development. The second patient, an 84-year-old man, presented with severe burning and light sensitivity but no dry mouth or joint pain. Schirmer test scores were 2 and 3 mm in the right and left eyes, with OSS of 9 and 5, respectively. His serum anti-CCP level was 1330 U. He developed inflammatory arthritis and was diagnosed with RA 16 months after initial presentation., Conclusion: This report suggests that filamentary keratitis with elevated serum anti-CCP antibody levels may indicate early RA. These findings underscore the importance of anti-CCP testing in filamentary keratitis patients, even without typical RA symptoms. Further research is needed to explore the link between anti-CCP antibodies and ocular surface diseases in RA.

Purpose: To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD)., Methods: A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC., Results: 167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16-3.97, p = 0.02)., Conclusion: Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development., (Published by Elsevier Inc.)

Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate prevalence and characteristics of pathological ocular surface findings in healthy patients undergoing cataract surgery using a noninvasive ocular surface workup and a validated questionnaire., Design: Prospective single-centre study (sub-analysis clinical trial no. NCT05754437)., Methods: Healthy patients undergoing senile cataract surgery were screened preoperatively by Oculus Keratograph (K5 M; Oculus GmbH, Wetzlar, Germany) for the evaluation of tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), and meibomian gland dropout. Ocular discomfort symptoms were scored by ocular surface disease index (OSDI) questionnaire., Results: 120 eyes of 120 patients (62 females, 58 males; mean age 73.85 years, range 47-91 years) were included. All patients had at least 1 abnormal finding, while 19 (15.8%; 95% CI [0.09-0.22]) had alterations of all parameters. In detail, 39 patients (32.5%; 95% CI [0.24-0.41]) had pathological TMH (mean 0,15 mm [0.03 SD]), 102 (85%; 95% CI [0.79-0.91]) had pathological NIKBUT (mean 3.64 s [2.63 SD]), 117 (97.5%; 95% CI [0.95-1]) had some degree of gland dropout (mean 1.62 [0.70 SD]), 78 patients (65%; 95% CI [0.56-0.74]) had pathological OSDI scores (mean 28.63 [15.08 SD]). Using TFOS DEWS II criteria, 66 patients (55%; 95% CI [0.42-0.60]) resulted affected by dry eye., Conclusions: This quick noninvasive screening documented the high prevalence of pathological ocular surface parameters in patients without risk factors or previous diagnosis of dry eye who are scheduled for cataract surgery., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ocular graft-versus-host disease (oGVHD) remains a challenging and potentially devastating complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although oGVHD significantly impacts the quality of life of affected survivors, it often goes unrecognized, particularly in the early stages. Targeting all providers in the HSCT community who see patients regularly and frequently for their post-allo-HSCT care, this review and opinion piece introduces the basic concepts of ocular surface pathophysiology, dissects the different stages of clinical presentation of oGVHD, explains why the current diagnostic criteria tend to capture the late disease stages, and highlights the warning signs of early disease development to facilitate prompt referral of oGVHD suspects for ocular specialist care. Along with introducing a comprehensive list of treatment options, this review emphasizes basic therapeutic strategy and options that can be safely and effectively initiated by any care provider. We believe in empowering patients as well as care providers beyond disciplinary boundaries to provide the most cohesive and integrated care in a multidisciplinary approach., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: Antibody-drug conjugates (ADCs) are a relatively recent advance in the delivery of chemotherapeutics that improve targeting of cytotoxic agents. However, despite their antitumor activity, severe ocular adverse effects, including vision loss, have been reported for several ADCs. The nonspecific uptake of ADCs into human corneal epithelial cells (HCECs) and their precursors via macropinocytosis has been proposed to be the primary mechanism of ocular toxicity. In this study, we evaluated the ability of a novel polymer, poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), to decrease the ADC rituximab-mc monomethylauristatin F (MMAF) (RIX) uptake into human corneal epithelial (HCE-T) cells. Methods: HCE-T cells were exposed to increasing concentrations of RIX to determine inhibition of cell proliferation. HCE-T cells were treated with PLL-g-PEG, the macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA), or vehicle. After 30 min of incubation, RIX was added. ADC was detected by fluorescent anti-human immunoglobulin G and fluorescently conjugated dextran as viewed by microscopy. Results: RIX caused dose-dependent inhibition of HCE-T cell proliferation. EIPA significantly reduced RIX uptake and decreased macropinocytosis as assessed by direct quantification of RIX using a fluorescently conjugated anti-human antibody as well as quantification of macropinocytosis using fluorescently conjugated dextran. PLL-g-PEG resulted in a dose-dependent inhibition of RIX uptake with half-maximal inhibitory concentrations of 0.022%-0.023% PLL-g-PEG. Conclusion: The data show PLL-g-PEG to be a potent inhibitor of RIX uptake by corneal epithelial cells and support its use as a novel therapeutic approach for the prevention of ocular adverse events associated with ADC therapy.

Background: Diabetes mellitus is associated with increased risk of ocular surface diseases in elderly. We consider neutrophil CD15 as a potential marker of ocular surface damage in type II diabetes mellitus patients., Aim: We aimed to evaluate expression of neutrophil CD15 and correlate it with results of conjunctival impression cytology and routine objective anterior ocular surface tests (TMH, NIBUT, LLT, MGD) in T2DM patients., Materials and Methods: We prospectively enrolled sixty type II diabetes mellitus patients (120 eyes) into a study group. The control group included forty (80 eyes) age- and sex-matched healthy individuals. All patients underwent comprehensive ophthalmological examination, and tear meniscus height test (TMH), noninvasive tear break-up time (NIBUT), lipid layer thickness measurement (LLT), Meibomian gland dysfunction evaluation (MGD), conjunctival impression cytology (CIC) and expression of CD15., Results: Abnormal Nelson's grades of squamous metaplasia (grades 2 and 3) were observed in 50% (60 eyes) of the study group, and 13.8 (11 eyes) of the control group. Fifteen patients with type II diabetes mellitus suffered from grade 3 squamous metaplasia. Nelson's grades of squamous metaplasia have shown a positive correlation with the level of CD15 expression either in the study and control groups (rs = 0.628, p  = <0.0001; rs = 0.746, p  < 0.0001; respectively)., Conclusions: The research shows significantly reduced values of routine objective ocular tests in type II diabetes mellitus patients in comparison to healthy participants older than 60 y.o. Increased CD15 in the peripheral blood is associated with the development of squamous metaplasia and may be used to evaluate the severity of ocular surface damage in type II diabetes mellitus patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This cross-sectional study aimed to investigate the associations between environmental and occupational factors and the prevalence of dry eye symptoms among participants from the Ahsa region of Saudi Arabia., Methods: Participants from urban, rural, and suburban areas seeking medical care at primary health centers were recruited through systematic random sampling. Data on demographics, exposures, and ocular health were captured using a structured questionnaire. Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Impact of Dry Eye on Everyday Life (IDEEL), and Symptom Assessment in Dry Eye (SANDE) questionnaires. Logistic regression analysis examined the relationships between environmental/occupational factors and the prevalence of dry eye symptoms., Results: Key exposures included particulate matter (PM) (60%), low humidity (55%), wind/dust (50%), prolonged computer use (65%), and chemical irritants (45%). These factors were significantly associated with an increased prevalence of dry eye symptoms, with the following odds ratios (ORs): PM (1.85, 95% CI: 1.35-2.52), low humidity (1.45, 95% CI: 1.05-2.00), wind and dust (1.60, 95% CI: 1.20-2.14), prolonged computer use (2.10, 95% CI: 1.55-2.85), and chemical irritants (1.75, 95% CI: 1.30-2.35). All associations were statistically significant (p < 0.05). The use of protective equipment was associated with reduced odds of dry eye symptoms (OR 0.60, 95% CI: 0.42-0.85, p = 0.03)., Conclusion: This study identifies significant associations between specific environmental and occupational exposures and the prevalence of dry eye symptoms. Reducing modifiable exposures through policy, workplace enhancements, and clinical preventative strategies is essential to mitigate the burden of dry eye symptoms related to modern lifestyles and technology., Competing Interests: The author declares no conflicts of interest related to this study., (© 2024 Al-Dossary.)

The authors performed an ex vivo and in vivo evaluation of the ultrastructural effects on the conjunctival epithelial cells of a new multiple-action tear substitute containing cross-linked hyaluronic acid, lipids and trehalose (Trimix ® ), using scanning electron microscopy (SEM) with conjunctival impression cytology. The ex vivo study highlights the persistence and distribution of the product at 5 and 60 min on a monolayer of conjunctival epithelial cells and an increase in microvilli density at the 60 min evaluation. In vivo examination was conducted on three subjects with different grades of ocular surface inflammation, treated with one drop of the product twice daily for thirty days. At the baseline (T 0 ) and twelve hours after the last administration of the tear drop (T 30 ), impression cytology of the upper bulbar conjunctiva for SEM evaluation of conjunctival epithelial cells was carried out. Slit lamp examination (SLE), corneal and conjunctival Fluotest, tear film break-up time (TBUT), and ocular surface disease index (OSDI) questionnaires were also performed to correlate the ultrastructural results with the clinical findings. After 30 days of treatment, a significant improvement in all clinical and symptomatic parameters and in the condition of the ocular surface was detected, with microvillar regeneration and strengthening in all the patients, and a complete restoration in 2/3 of them. The persistence and distribution of the product on the epithelial cells was also noted 12 h after the last administration. The results, therefore, suggest a marked epitheliotropic effect along with a high residence time of the tear substitute.

Ocular surface disease (OSD) is a complex condition that can cause a range of symptoms (e.g, dryness, irritation, and pain) and can significantly impact the quality of life of affected individuals. Iatrogenic OSD, a common finding in patients with glaucoma who receive chronic therapy with topical ocular antihypertensive drugs containing preservatives such as benzalkonium chloride (BAK), has been linked to damage to the ocular surface barrier, corneal epithelial cells, nerves, conjunctival goblet cells, and trabecular meshwork. Chronic BAK exposure activates inflammatory pathways and worsens symptoms, compromising the success of subsequent filtration surgery in an exposure-dependent manner. In eyes being treated for glaucoma, symptomatic treatment of OSD may provide some relief, but addressing the root cause of the OSD often necessitates reducing or, ideally, eliminating BAK toxicity. Strategies to decrease BAK exposure in patients with glaucoma encompass the use of preservative-free formulations or drugs with alternative and less toxic preservatives such as SofZia®, Polyquad, potassium sorbate, or Purite®. Though the benefits of these alternative preservatives are largely unproven, they might be considered when financial constraints prevent the use of preservative-free versions. For patients receiving multiple topical preserved drugs, the best practice is to switch to nonpreserved equivalents wherever feasible, regardless of OSD severity. Furthermore, nonpharmacological approaches, including laser or incisional procedures, should be considered. This review explores the effects of BAK on the ocular surface and reviews strategies for minimizing or eliminating BAK exposure in patients with glaucoma in order to significantly improve their quality of life and prevent complications associated with chronic exposure to BAK., Competing Interests: Declaration of competing interest MYK: Patent royalties: Alcon, SpyGlass Pharma, and New World Medical. Ownership Interest: New World Medical, SpyGlass Pharma, Aurea Medical Consultant: New World Medical, SpyGlass Pharma. CJR: Avellino, Baxis, Bio-Tissue, Celularity, Dompé, Emmecell, Glaukos, Kala, Oyster Point, Sight Sciences, Tarsus, TearLab/Trukera. EM: Alcon, AbbVie, Bausch + Lomb, DMG, Dompé, GlaxoSmithKline, Kala, Novartis, Sanofi, Santen, Shire, Sifi, Sun Pharmaceuticals, Théa, TRB-Chemedica, Ursapharm Arzneimittel, Visufarma. NMR: Consultant for Alderya, Aerie Pharmaceuticals; Alcon Vision, Alimera Sciences, AbbVie, Bausch + Lomb, Belkin, Dompé, Eyepoint Pharmaceuticals, Glaukos, Imprimis, Iridex, Kala Pharmaceuticals, Lumenis, Novartis, Ocular Science, Ocular Therapeutix, Omeros, Rayner, Reichert, Santen, SpyGlass, Tarsus, TearClear, Théa. AG: Consultant for Novartis, Oyster Point, Dompé, AstraZeneca, Oculis, EyeCool Therapeutics. Grant funding: B&L. CB: Alcon, Horus Pharma, Oculis, Santen, Théa., (Copyright © 2024. Published by Elsevier Inc.)

The LipiFlow Thermal Pulsation System received its first marketing clearance for the treatment of meibomian gland dysfunction (MGD) 13 years ago. Since then, the evidence evaluating the effectiveness and safety of LipiFlow as a treatment for MGD has grown significantly. The objective of this comprehensive review was to summarize all clinical reports evaluating the effectiveness and safety of LipiFlow over the past 15 years. The literature was systematically reviewed, and 55 unique articles had subjective (patient-reported outcomes) and objective (meibomian gland function, tear production, and ocular staining) outcomes for extraction. Data were collected from 2101 patients and 3521 eyes treated with LipiFlow. Of these, effectiveness was evaluated in 2041 patients and 3401 eyes, and safety was evaluated in 1448 patients and 2443 eyes. Taken together, the studies demonstrate that a single 12-min treatment with LipiFlow safely improves signs and symptoms of MGD and associated evaporative dry eye disease (DED), and the benefits persist up to 3 years in some cases. The findings are corroborated by multiple meta-analyses and consensus guidelines. While some studies showed that daily eyelid hygiene, warm compress, and/or massage had a similar benefit to a single LipiFlow, these treatments were limited by inconvenience, discomfort, and non-compliance. The majority of studies evaluating safety reported no discomfort or pain associated with LipiFlow treatment, which supports the patient acceptability of LipiFlow therapy. All adverse events (AEs) related to LipiFlow were transient, non-vision-threatening, and did not require treatment. No studies reported serious AEs. The data obtained from 55 studies conducted globally overwhelmingly show that LipiFlow is effective and safe for the treatment of MGD and associated evaporative DED. The conclusions are supported by the diversity of the patient populations (geography, race, disease severity, and diagnosis), the large population treated with LipiFlow, the meta-analyses, and that this review analyzed all published clinical studies to date., (© 2024. The Author(s).)

Purpose: Dry Eye Disease (DED) is regarded as the most common ocular surface disease worldwide, entailing symptoms that have a major impact on the physical and psychological well-being of DED patients. In this context, the impact of sleep quality on DED has recently attracted attention. Indeed, although little is known about the mechanisms underlying the relationship between sleep and ocular surface diseases, recent evidence suggests that a reciprocal relationship exists between sleep quality and DED. Aim of the study was to investigate such relationship by means of both survey-based and instrumental analysis in a large population., Patients and Methods: The present cross-sectional study included 1182 DED patients who completed the Insomnia Severity Index (ISI) and the Ocular Surface Disease Index (OSDI) questionnaires. Moreover, tear break-up time (TBUT) and ocular surface staining (OSS) data of included patients were collected by physicians., Results: According to the findings of this study, in DED patients, the severity of dry eye symptoms and signs, assessed by OSDI score, TBUT, and ocular surface staining, is associated with more severe insomnia symptoms. Furthermore, higher severity of DED symptoms seems to be associated with the occurrence of nocturnal awakenings rather than with problems in falling asleep., Conclusions: Present work contributes to the understanding of the complex relationship between DED and insomnia by showing that in a large population of DED patients, the more severe the insomnia, the more severe the DED symptoms and signs., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dario Arnaldi received lecture and consultant fees from Fidia, Bioprojet, Jazz, Bruno, Valea, Italfarmaco and Idorsia. The remaining authors have no conflicts of interest to declare.

Objective: To survey the prevalence of pathogens in shelter-housed cats with active ocular surface disease (OSD)., Animals Studied: A total of 255 shelter-housed domestic cats with evidence of active OSD. No normal, unaffected cats were sampled., Procedure(s): OSD scoring was performed on cats with active OSD. Combined oropharyngeal/conjunctival swabs were submitted for rt-PCR/PCR for feline herpesvirus (FHV-1), feline calicivirus (FCV), Chlamydia spp. (CHL), Bordetella bronchiseptica (BORD), and Mycoplasma spp. (MYC)., Results: Pathogens were detected as follows: 76.4% (195/255) MYC, 57.6% (147/255) FHV-1, 42.7% (109/255) FCV, 26.7% (68/255) CHL, and 5.5% (14/255) BORD. Monoinfections affected 21.1% (54/255) animals, with MYC being the most common monoinfection (12.5%, 32/255), followed by FHV-1 (4.7%, 12/255), followed by CHL (2.4%, 6/255), followed by FCV (1.6%, 4/255), with no animals having a BORD monoinfection. Dual infections affected 36.4% of animals (93/255), with MYC detected in 30.1% (77/255) dual infections and FCV detected in 12.9% (33/255) dual infections. Dual infections with MYC and FCV together were detected in 9.8% (25/255) animals. Many animals (35.3%, 90/255) were found to be affected by 3 or more pathogens, and 7.1% (18/255) animals had no pathogens detected. OSD scores were not influenced by any variable assessed, including the number and type of pathogens detected., Conclusion: MYC, FHV-1, FCV, and CHL were commonly detected in this group of animals with OSD. Both MYC and FCV (alone or in combination with each other) were detected in multiple animals with active OSD, supporting prior evidence that either may independently act as a primary ocular surface pathogen., (© 2024 American College of Veterinary Ophthalmologists.)

Background: Ocular surface (OS) disorders before glaucoma filtration surgery (GFS) have been considered to play a crucial role influencing the surgical outcome. Conversely, the impact of surgery itself on the OS is almost completely overlooked, though evidence suggest that ocular surface disease (OSD) may be induced in patients by GFS. This review analyzes the determinants involved in the OSD development after GFS, the clinical features and related consequences, the main diagnostic hallmarks, as well as the therapeutic strategies for its management., Methods: The PubMed database was utilized for the literature examination. Keywords that were searched included ocular surface disease, glaucoma filtration surgery, filtration bleb, post-surgical management, and quality of life., Results: After GFS, OSD is promoted by peri- and post-operative factors, such as the filtration bleb (FB) development, combined surgical approach with phacoemulsification, the use of antifibrotic agents and the reintroduction of antiglaucoma medications. This particular form of OSD that present similar clinical features to mild to moderate dry eye, can be named as post-glaucoma surgery-OSD (PGS-OSD). PGS-OSD may negatively affect the FB functionality, thus potentially hindering the disease control, and significantly worsen the patient quality of life (QOL)., Conclusions: Clinicians are encouraged to routinely include the OS evaluation after GFS and to consider proper management when the occurrence of PGS-OSD worsen the patient's QOL or exert negative effects to the FB functionality. An outline summarizing the main risk factors and the most appropriate therapeutic options to mitigate the PGS-OSD was proposed to support the routine practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The effectiveness, safety and tolerability of the preservative-free fixed combination of tafluprost and timolol (PF-TTFC) were evaluated over the 24-h in patients with open-angle glaucoma or ocular hypertension showing signs and symptoms of Ocular Surface Disease (OSD) and uncontrolled intraocular pressure (IOP) on prior benzalkonium chloride (BAK) - Latanoprost monotherapy., Methods: In this multi-center, prospective, interventional, non-comparative clinical trial, patients treated with BAK-Latanoprost underwent 24-h IOP measurements (8 am, 11 am, 2 pm, 5 pm, 8 pm, 11 pm, 2 am, 5 am) at baseline and after 3 months from switch to PF-TTFC. Mean 24-h IOP and daytime (8 am-8 pm) vs nighttime (11 pm - 5 am) IOP were compared. Changes in OSD signs and symptoms, quality of life (QoL) and in-vivo corneal confocal microscopy (IVCM) were also evaluated., Results: Thirty-eight patients were analyzed. The mean 24-h IOP significantly decreased after 3 months from 17.8 mmHg (95% CI: 17.1-18.6) to 15.3 mmHg (95% CI: 14.6-16.1, p < 0.001). IOP was significantly reduced both at daytime (p < 0.001) and nighttime (p < 0.001), with better IOP control at night [-2.9 (95% CI: -3.5 to -2.1) mmHg vs -2.3 (95% CI: -2.9 to -1.6) mmHg]. In 20 patients (52.6%), corneal fluorescein staining improved, whereas in 4 patients (10.5%) it worsened. Hyperemia has improved in 24 (63.3%) patients and worsened in 2 (5.3%). Breakup time, Schirmer test and QoL scores showed no changes. At IVCM, the mean corneal wing-cell size was found significantly decreased (p < 0.005)., Conclusion: The switch from BAK-Latanoprost to PF-TTFC significantly reduced IOP over the 24-h and improved OSD signs and symptoms., Competing Interests: FO has served as a consultant and received compensations from AbbVie, Santen SA, Fidia, Visufarma, Thea. LMR has served as a consultant and received compensations from Alcon, AbbVie, iCare, Omikron, Novartis, Santen SA, Fidia, OFFHEALTH, Visufarma, Thea. The authors report no other conflicts of interest in this work., (© 2024 Oddone et al.)

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.

Objectives: Ocular surface reactions (OSR) have been associated with dupilumab for atopic dermatitis (AD) treatment. However, the association of dupilumab-associated OSR (DA-OSR) for nasal polyps (CRSwNP) treatment has not been studied. We evaluated DA-OSR for CRSwNP treatment using the FDA Adverse Event Reporting System (FAERS)., Methods: FAERS was queried for any general ocular reactions (DA-GOR) from 2019Q1 to 2022Q4. DA-OSR were subcategorized from DA-GOR and compared between treatment groups (CRSwNP, asthma, AD). Logistic regression was used to predict DA-OSR. Disproportionality analysis (DPA) of DA-OSR was performed using OpenVigil., Results: There were 60,198 total observations, of which 5344 were treated for CRSwNP. The prevalence of DA-GOR and DA-OSR was greatest for AD (15.3%, 7.8%), followed by CRSwNP (12.2%, 6.7%) and asthma (9.2%, 3.5%). The most commonly reported OSRs were dry eyes (35.9%), conjunctivitis (15.7%), and increased lacrimation (11.0%). The reported odds ratio (ROR) of CRSwNP-treated DA-OSR was 0.84 (0.73-0.97; p = 0.015), compared to 1.29 (1.20-1.40; p < 0.001) for AD and 0.66 (0.59-0.73; p < 0.001) for asthma. For CRSwNP treatment, the DA-OSR ROR was 0.97 (0.90-1.03; p = 0.3) for men and 0.78 (0.73-0.83, p < 0.001) for older adults (age > 50). ROR in the DPA for DA-OSR was 12.5 (12.2-12.8; p < 0.001) for any indication and 0.58 (0.53-0.64; p < 0.001) for CRSwNP treatment only., Conclusions: While there are limitations to FAERS, this study confirms the association between dupilumab and OSR for AD treatment, and does not support an association between dupilumab and OSR for CRSwNP treatment. Younger adults experience more DA-OSR in CRSwNP treatment without a specific predilection for sex., Level of Evidence: IV Laryngoscope, 134:2602-2608, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The use of povidone-iodine for ocular surface asepsis is widespread for intravitreal injections. They became frequent procedures, leading to serial exposure of patients' eyes to iodinated solutions. In this study, we investigate the changes in the ocular surface in patients submitted to repeated use of povidine for intravitreal injection of anti-VEGF asepsis, analyzing Ocular Surface Disease Index, non-invasive break up time, blinking quality, lipid layer, meniscus height and osmolarity., Methods: This case-control study included 34 individuals (68 eyes), 14 males, 20 females aged 48 to 94. Inclusion criteria were individuals who received application of 2% povidone-iodine eyedrops for intravitreal injections treatment with the non-treated contralateral eye used as control. Ocular surface examinations were performed at a single occasion. A pre-intravitreal injection asepsis protocol with povidone-iodine was applied. All statistical analysis was performed using the STATA® 18.0 Software and a p-value = 0.05 was considered as the statistical significance value in all tests., Results: The median number of IVIs in treated eyes was 12 (range 6-20). The results in treated eyes compared with untreated eyes were respectively : median OSDI 16 (IQR 6-39) and 12.5 (IQR 8-39) (p = 0.380); mean NIBUT 10.30 (SD ± 2.62) and 10.78 (SD ± 2.92) ( s, p = 0.476); median blinking quality 100 (IQR 100) and 100 (IQR 100 ) (%, p = 0.188); median lipid layer 87 (IQR 77-90) and 86 (IQR 74-100) (nm, p = 0.451); median meniscus height 0.22 (IQR 0.19-0,31) and 0.24 (IQR 0.20-0.27) (mm, p = 0.862), median Meibomian gland atrophy 33 (IQR 24-45) and 31.5 (IQR 25-39) (%, p = 0.524); and mean osmolarity 306.6 (SD ± 21.13) and 313.8 (SD ± 29) (mOsm, p = 0.297). There was no statistically significant relationship between the repetitive use of 2% iodinated solution and signs or symptoms compatible with dry eye syndrome in this group of patients., Conclusions: The findings suggest that 2% povidone iodine is a safe and efficacious agent for ocular surface antisepsis during intravitreal injections, not leading to substantial ocular surface modifications. This conclusion supports the continued use of povidone iodine in routine ophthalmic procedures without increased risk of inducing dry eye syndrome., (© 2024. The Author(s).)

Introduction: Although affecting an estimated 35% of the population, Dry Eye is not well understood by patients and the medical community. As a result, both in research and clinical settings, diagnostic and treatment protocols tend to be non-specific, ad hoc, and inadequate, with a narrow industry-driven focus. The purpose of this convening was to propose a research roadmap that orients Dry Eye researchers toward a comprehensive patient-centered approach to diagnosing and treating Dry Eye, Meibomian gland dysfunction (MGD), and related comorbidities with a goal of improving clinical outcomes for Dry Eye/MGD patients., Methods: Sixteen participants, including Dry Eye/MGD patients, caregivers, and patient advocates together with a group of experts in Dry Eye, MGD and other fields identified gaps in research on Dry Eye and MGD diagnostic and treatment approaches (age range 20-80; male to female ratio of 7:11; patients: 7). During a 2-day virtual convening, participants were assigned to topic-specific focus-group sessions to discuss and develop research questions pertaining to Dry Eye and MGD. The research questions were compiled into a proposed patient-centered roadmap for Dry Eye and MGD research. Two additional participants contributed to the proposed roadmap following the convening., Results: The focus groups identified over 80 patient-centered research questions important to patients and other stakeholders and compiled these into a proposed research roadmap., Conclusion: The convened stakeholders aim to establish a cohesive and comprehensive patient-centered approach to treating Dry Eye, Meibomian Gland Dysfunction, and comorbidities. The research roadmap will serve as a reference for researchers, educational institutions, clinicians, and others evaluating diagnostic and treatment protocols in Dry Eye and MGD., Competing Interests: All authors received honoraria from PCORI for their participation in this work. Natalia A. Warren, Diana Adelman, Deidre A. Rector, and Claire Toland reported receiving additional financial support for their extended contributions. Dr. Steven L. Maskin reported owning >5% of MGDinnovations, Inc, a corporation receiving patent-based royalties (patent numbers: 9510844, 10159599, and 11110003) from a licensing agreement with Katena Products. The authors report no other conflicts of interest in this work., (© 2024 Warren et al.)

Background: Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. Purpose: This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. Methods: The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. Results: While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. Conclusion: This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice.

Changes in the bacterial flora in the gut, also described as gut microbiota, are readily acknowledged to be associated with several systemic diseases, especially those with an inflammatory, neuronal, psychological or hormonal factor involved in the pathogenesis and/or the perception of the disease. Maintaining ocular surface homeostasis is also based on all these four factors, and there is accumulating evidence in the literature on the relationship between gut microbiota and ocular surface diseases. The mechanisms involved are mostly interconnected due to the interaction of central and peripheral neuronal networks, inflammatory effectors and the hormonal system. A better understanding of the influence of the gut microbiota on the maintenance of ocular surface homeostasis, and on the onset or persistence of ocular surface disorders could bring new insights and help elucidate the epidemiology and pathology of ocular surface dynamics in health and disease. Revealing the exact nature of these associations could be of paramount importance for developing a holistic approach using highly promising new therapeutic strategies targeting ocular surface diseases., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID)., Design: Retrospective cohort study., Participants: Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020., Methods: Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development., Main Outcome Measures: The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated., Results: Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53-0.65), 0.74 (95% CI, 0.68-0.81), and 1.99 (95% CI, 1.88-2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28-7.36] to 11.80 [95% CI, 10.40-13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57-3.75; 95% CI, 2.17-4.34), male sex (OR, 1.38; 95% CI, 1.26-1.50), Asian descent (OR, 3.12; 95% CI, 2.70-3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02-1.55) were associated with POSID development., Conclusions: This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study explores the relationship between acquired punctal stenosis (PS) and ocular surface disease (OSD), assessing causal mechanisms and clinical impacts, utilizing a combination of a comprehensive literature review and a detailed analysis of a patient cohort from a tertiary care center., Methods: Data from 213 PS patients at Sheba Medical Center were retrospectively analyzed, evaluating various OSD symptoms and treatment effectiveness through standardized clinical assessments and statistical tests., Results: Predominantly older and female, many patients exhibited bilateral PS. OSD symptoms were found in 35.2% of all patients. Treatments like punctoplasty with stents significantly alleviated symptoms. Significant associations between treatment modalities and symptom improvement were identified., Conclusions: PS and OSD have acomplex, bidirectional relationship that complicates treatment outcomes. This study underscores the need for thorough diagnostic approaches and personalized treatments to improve PS management. Further research is essential to deepen understanding of PS-OSD interactions and develop effective therapies.

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to <10 s), and Group 3 (≥ 10 s). The Schirmer's tear Test 1 (STT-1) results of the included patients were also divided into three groups: Group 1 (< 5 mm/min), Group 2 (5 to <10 mm/min), and Group 3 (≥ 10 mm/min). The corneal opacity grades are divided into four scores, ranging from 0 to 3. The corneal opacity grade score (COS) of 0 indicates a completely clear cornea or only a trace of opacity. COS of 1, 2, 3 indicate the presence of a prominent corneal opacity that does not interfere with the visualization of the fine iris details, the opacity obscures the visibility of the iris and lens details and severe obstruction of the intraocular structure visibility, respectively. The mean difference in COS during the follow-ups for each group of NIBUT were 0.61 ± 0.92 ( n  = 28), 0.10 ± 0.32 ( n  = 10), 0.19 ± 0.40 ( n  = 16). The NIBUT groups were significantly correlated with COS ( p -value = 0.073) at a 10% level of significance. Post-hoc test at a 10% level of significance revealed significant correlations between Groups 1 and 2 ( p -value = 0.041) and between Groups 1 and 3 ( p -value 0.104). Although the TFBUT and STT-1 groups did not show any significant correlation with COS. Eyes with NIBUT of <5 s were found to have a significantly higher chance of increased COS compared with eyes with NIBUT of >5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Han, Yang, Choi and Kim.)

Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy., Methods: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non-AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology., Results: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL-12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non-AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome., Conclusions: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: To evaluate the prevalence of diagnosed dry eye syndrome, meibomian gland dysfunction, and blepharitis amongst the low vision population., Methods: A retrospective analysis was conducted on patients seen in the University of Colorado Low Vision Rehabilitation Service between the dates of 12/1/2017 and 12/1/2022. 74 ICD-10 codes were used to identify patients as having dry eye syndrome or not having dry eye syndrome. Data was further analyzed to determine the prevalence of blepharitis and meibomian gland dysfunction using 29 blepharitis and 9 meibomian gland dysfunction ICD-10 codes. Data were also analyzed to determine the age and sex of the patients with diagnosed dry eye syndrome., Results: The percentage of patients with a diagnosis of dry eye syndrome by an eyecare provider was 38.02 %. The prevalence of dry eye syndrome by age group was 3.57 % for 0-19 years, 14.35 % for 20-39 years, 29.07 % for 40-59 years, 43.79 % for 60-79 years, and 46.21 % for 80 and above. The prevalence of meibomian gland dysfunction and blepharitis was 11.90 % and 9.1 % respectively. Dry eye syndrome prevalence amongst males was 31.59 % and 42.47 % for females., Conclusion: This study demonstrates that dry eye syndrome in the low vision population is a significant co-morbidity occurring in over a third of patients in the University of Colorado Low Vision Rehabilitation Service. These findings are meaningful as ocular comfort should not be overlooked while managing complex visual needs., Competing Interests: Conflicts of interest The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Ocular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid inflammatory markers are lacking. New knowledge may help guide research into ocular surface disease biomarkers and therapeutics., Methods: In this prospective twin cohort study, healthy individuals were recruited from a population-based registry. Tear fluid was collected with the Schirmer test strips was submerged in phosphate buffered saline and stored at -80° before undergoing 27-cytokine multiplex immunoassay analysis. Broad-sense heritability (h 2 ) of cytokine concentrations was analyzed., Results: 90 participants (23 monozygotic and 22 dizygotic twin pairs) were included. Data availability allowed for heritability analysis of 15 cytokines, and a h 2 >50% was seen for 10 cytokines. A statistical power of >80% was achieved for heritability analyses of the cytokines interferon gamma induced protein 10 (h 2  = 94.8%), eotaxin (89.8%), interleukin 7 (86.6%), interleukin 1β (82.2%) and monocyte chemoattractant protein 1 (68.2%)., Conclusions: The tear fluid concentration of several analyzed cytokines was found to be highly heritable. A considerable amount of the inter-individual variation observed for the concentration of certain tear fluid cytokines can be linked to hereditary factors that cannot easily be modified by changing factors in the environment of patients. This suggests that a higher success in ocular surface disease drug discovery may be anticipated for drugs that have targets in specific populations, and points to the importance of emphasizing known preventive measures of ocular surface disease and examinations of close relatives of patients with ocular surface disease, such as dry eye disease., Competing Interests: Declaration of competing interest The authors have no commercial relations with the suppliers of diagnostic devices or therapeutics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To report the outcomes of a novel microwave heating device (Blepha EyeBag ® ) used serially for the treatment of meibomian gland dysfunction (MGD)., Patients and Methods: This prospective single center study was conducted at University Magna Graecia of Catanzaro. Patients were instructed to apply the compress twice daily for 15 days and once per day every two days, as reported in the package insert. Outcome measures were i) ocular surface disease index (OSDI) score, ii) tear meniscus height (TMH), iii) non-invasive keratograph break-up time (NIKBUT) (first and average), iv) meiboscore, v) bulbar redness. Evaluations were performed at baseline (T0) after 15 days (T1) and after 45 days of therapy (T2)., Results: Overall, 19 patients with MGD (8 males, 11 females; mean age 64.58 ± 9.72 years) were included. The mean value of OSDI score showed a significant decrease from 28.16 ± 17.46 at T0 to 13.69 ± 7.62 at T2 (p=0.008). The mean value of NIKBUT first significantly increased from 6.67 ± 3.51 seconds (s) at T0 to 10.46 ± 4.64 at T2 (p=0.0121); in parallel, the mean value of NIKBUT average increased significantly from 11.09 ± 4.15 s at T0 to 14.95 ± 4.85 at T2 (p=0.0049). No significant differences were detected at each time point for bulbar redness, meiboscore and TMH. Throughout the entire study, no adverse events were recorded., Conclusion: The microwave-heated eye bag treatment is both safe and effective for treatment of MGD, being able to significantly ameliorate both patient-reported symptoms and tear film stability., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Rossi et al.)

Exposure to air pollutants, especially in the case of particulate matter (PM), poses significant health risks throughout the body. The ocular surface is directly exposed to atmospheric PM making it challenging to avoid. This constant exposure makes the ocular surface a valuable model for investigating the impact of air pollutants on the eyes. This comprehensive review assembles evidence from across the spectrum, from in vitro and in vivo investigations to clinical studies and epidemiological studies, offering a thorough understanding of how PM 10 and PM 2.5 affect the health of the ocular surface. PM has been primarily found to induce inflammatory responses, allergic reactions, oxidative stress, DNA damage, mitochondrial impairment, and inhibit the proliferation and migration of ocular surface cells. In toto these effects ultimately lead to impaired wound healing and ocular surface damage. In addition, PM can alter tear composition. These events contribute to ocular diseases such as dry eye disease, blepharitis, conjunctivitis, keratitis, limbal stem cell deficiency and pterygium. Importantly, preexisting ocular conditions such as dry eye, allergic conjunctivitis, and infectious keratitis can be worsened by PM exposure. Adaptive responses may partially alleviate the mentioned insults, resulting in morphological and physiological changes that could be different between periods of short-term and long-term exposure. Particle size is not the only determinant of the ocular effect of PM, the composition and solubility of PM also play critical roles. Increasing awareness of how PM affects the ocular surface is crucial in the field of public health, and mechanistic insights of these adverse effects may provide guidelines for preventive and therapeutic strategies in dealing with a polluted environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Dry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients' quality of life. The association between air pollution and the risk of dry eye disease remains uncertain., Methods: Data on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution., Results: Among the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 μg/m 3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 μm (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 μm (PM2.5) showed a significant association with DED outpatient visits in males and the 19-59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season., Conclusion: The noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xia, Yang, Sun, Huang, Huang, Zhang and Yao.)

Purpose: Inhibitors of dihydroorotate dehydrogenase (DHODH) have been found to be potent anti-inflammatory agents. Recently, a topical formulation (KIO-101 eye drops) of a DHODH inhibitor has been developed. The aim of the present study was to evaluate the safety and tolerability of KIO-101 eye drops in Healthy Volunteers (HVs) and patients with conjunctival hyperemia., Methods: The study was carried out in a double-masked, placebo-controlled, randomized, parallel-group design with two parts. In part I, HVs received single and multiple instillations (four times daily for 12 consecutive days) of KIO-101 eye drops in ascending doses of 0.05%, 0.15%, and 0.30%, respectively. Part II was conducted in patients with conjunctival hyperemia who received 0.15% KIO-101 eye drops twice daily for 12 consecutive days. Ophthalmic and systemic safety examinations were performed on all participants. In part II, ocular hyperemia grading and an ocular surface disease index (OSDI) questionnaire were performed., Results: 24 HVs participated in part I and 21 patients in part II. KIO-101 eye drops were well tolerated in all subjects. No serious adverse events (SAEs) occurred, and all AEs that were reported were transient and considered mild to moderate. In the highest dose cohort (0.30%), epistaxis occurred in two subjects after multiple instillations. In part II, after 12 days treatment with 0.15% KIO-101, conjunctival hyperemia decreased by -1.1 ± 0.27 points in the treatment and -0.6 ± 0.79 points in the placebo group ( p = 0.0385). OSDI decreased from 47.9 ± 18.7 to 27.6 ± 19.13 points in the treatment group, while in the placebo group, a change from 41.3 ± 12.08 to 27.3 ± 18.63 points occurred., Conclusions: A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia.

Purpose: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients., Methods: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging., Results: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05)., Conclusion: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words)., (© 2024. The Author(s).)

Background Glaucoma is a progressive optic neuropathy that may result in irreversible visual impairment and can diminish quality of life. Lowering intraocular pressure (IOP) through topical eyedrops is usually the primary approach to managing glaucoma. However, long-term treatment poses a risk to ocular surface health, leading to ocular surface disease (OSD). Preservative-containing eyedrops are implicated in OSD development due to their detrimental effects on the tear film and goblet cell density. OSD symptoms may impact patient compliance due to local side effects. This study aims to assess OSD in glaucoma patients receiving topical treatment, quantify symptoms and objective ocular surface parameters, and compare them to a control group not using topical glaucoma medications. Methodology Patients diagnosed with primary open-angle glaucoma receiving topical treatment and a control group were included in this study. To assess OSD, patients completed the Ocular Surface Disease Index (OSDI) questionnaire to evaluate symptoms and underwent objective measurements of ocular surface parameters using a keratograph. These parameters included assessments of bulbar redness and non-invasive keratograph tear break-up time (NIKTBUT). Results A cohort of 92 patients was subjected to examination, comprising 66 individuals diagnosed with glaucoma and 26 controls. Within the glaucoma patient subset, the mean number of IOP-lowering drugs administered was 2.42 ± 0.18, with 22.7% exclusively utilizing preservative-free eye drops. Our investigations unveiled a substantial prevalence of OSD symptoms, manifesting not only within the glaucoma cohort but also among the control group, with 72.7% and 53.8%, respectively (p = 0.224), reporting moderate-to-severe symptoms (OSDI > 23). Remarkably, OSDI scores exhibited higher values among female participants (p = 0.039) and glaucoma patients using prostaglandins (p<0.001) and were negatively correlated to the number of IOP-lowering drugs used (-0.448; p < 0.001). Furthermore, employing keratograph assessment, we discerned heightened bulbar redness (1.86 ± 0.07) in the glaucoma group compared to the control group (1.58 ± 0.07; p = 0.008). Glaucoma subgroup analyses further unveiled higher bulbar redness among glaucoma patients employing carbonic anhydrase inhibitors (p = 0.035) and applying medication preservatives (p = 0.045) but lower among individuals using beta-blockers (p = 0.018). However, the NIKTBUT did not show significant variance between the two groups (glaucoma group: 10.19 ± 0.85 seconds; control group: 10.96 ± 1.37 seconds; p = 0.499). Conclusions Our study revealed a significant prevalence of OSD in our sample, with the OSDI questionnaire showing limited specificity. The notable increase in bulbar redness pointed to an elevated prevalence of OSD among glaucoma patients, emphasizing the considerable impact of preservatives on ocular surface damage. Recognizing the potential damage to the tear film and ocular surface is crucial for glaucoma experts, who must employ comprehensive therapeutic strategies to mitigate symptoms, advocating for the preferential use of preservative-free medications, when possible, for optimizing long-term treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Romano et al.)

Background: Corneal perforation is an ophthalmic emergency. The conventional management of corneal perforation can be associated with severe complications especially in patients with ocular surface disease. Endothelial keratoplasty has been suggested as an alternative surgical technique for the management of corneal perforations. We present a case series of nine patients with corneal perforation and ocular surface disease managed with secondary patch endothelial keratoplasty., Methods: This is a retrospective case series of nine patch endothelial keratoplasties performed between 2016 and 2022 at a quaternary eye hospital in Australia. The surgical technique is similar to conventional endothelial keratoplasty except descemetorhexis was not performed., Results: A total of 9 cases were treated during the review period. Eight of the nine cases had an improvement in visual acuity. One case failed to achieve corneal tectonic objective., Conclusion: Patch endothelial keratoplasty is a safe secondary procedure for the management of corneal perforations in patients with ocular surface disease., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patient expectations for cataract surgery are continuously increasing, and dry eye disease (DED) represents a major cause of patient dissatisfaction in eye surgery. The present opinion paper aims to provide useful insights to improve the entire pathway of a patient undergoing cataract surgery, from the preoperative setting to the postoperative one. The available evidence from main clinical trials published on this topic is presented in association with experience-based points of view by the authors. Ocular surface disease (OSD) is common in patients presenting for cataract surgery, and more than half of these patients have DED and meibomian gland dysfunction (MGD), even in the absence of symptoms. Therefore, there is a need to encourage preoperative assessments for the risk of DED development or worsening in all patients as a routine approach to cataract surgery. New all-in-one diagnostic machines allow for fast and noninvasive screening of the ocular surface status. Once a preoperative diagnosis of DED/OSD is reached, ocular surface optimization should be obtained before surgery. In the case of unresolved OSD, the decision to delay surgery should be considered. The surgical procedure can be optimized by avoiding large incisions, limiting microscope light intensity and exposure, and avoiding an aspirating speculum or preserved eye drops. Postoperatively, the continued avoidance of preserved agents is advisable, as well as a limited exposure to epitheliotoxic antibiotics and nonsteroidal anti-inflammatory drugs. Short-term, preservative-free, soft corticosteroids may be useful for patients with extensive or persistent inflammation.

We aim to summarize the current evidence of Vascular endothelial growth factors (VEGF)s in external eye diseases and determine whether serum and plasma VEGF levels are associated with tear and ocular surface tissues. A systematic search of PUBMED and EMBASE was conducted using PRISMA guidelines between October 2022 and November 2023, with no restriction on language or publication date. Search terms included relevant MESH terms. These studies were evaluated for quality, and an assessment of the risk of bias was also carried out. Extracted data were then visually represented through relevant tables or figures. The initial literature search yielded 777 studies from PUBMED, 944 studies from EMBASE, and 10 studies from manual searches. Fourteen eligible studies were identified from 289 articles published from 2000 to 2023 in the English language or with English translations, including rabbit models, murine models, and human-derived samples. Most studies were retrospective in nature and case-control studies. Various common external eye diseases, such as dry eye disease (DED) and allergic eye disease were investigated. Despite limitations and small sample sizes, researchers have found elevated tissue levels of the VEGF in the vascularized cornea, especially in animal models, but there is no evidence of clear changes in the tear concentrations of VEGF in DED and allergic eye disease. Tear VEGF is associated with corneal vascularization. Anti-VEGF therapies may have the potential to manage such conditions.

Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE.

Ocular surface disease (OSD) associated with topical glaucoma drugs is a common issue impacting treatment adherence. We aimed to identify conjunctival transcriptomic changes in glaucoma and dry eye patients, comparing them to healthy controls. Bulbar conjunctival specimens were collected via impression cytology from 33 patients treated for glaucoma, 9 patients with dry eye, and 14 healthy controls. RNA extraction and bulk RNA sequencing were performed, followed by bioinformatics analysis to detect gene dysregulation. Ingenuity pathways analysis (IPA) identified pathways and biological processes associated with these transcriptomic changes. Sequencing analysis revealed 200 modified genes in glaucoma patients compared to healthy individuals, 233 differentially expressed genes in dry eye patients versus controls, and 650 genes in treated versus dry eye samples. In glaucoma patients, 79% of altered pathways were related to host defense, while dry eye patients showed a 39% involvement of host response, 15% in cellular proliferation and integrity, and 16% of mitochondrial dysfunction. These findings were validated through qRT-PCR. Glaucoma patients showed an intensified conjunctival immune response as a potential cause of OSD, whereas in dry eye patients, in addition to the immune response, other mechanisms such as mitochondrial dysfunction or reduced cellular proliferation were observed.

Purpose: This study evaluated the ocular surface disease (OSD), especially dry eye disease (DED) parameters by combining qualitative and quantitative tools, including tear matrix metalloproteinase 9 (MMP-9), in patients with Graves' disease (GD) with and without Thyroid eye disease (TED)., Patients and Methods: A total of 17 active TED, 16 inactive TED, 16 GD without ophthalmopathy, and 16 healthy controls were included. All patients were assessed with CAS, ophthalmometry, qualitative tear MMP-9, Ocular Surface Disease Index (OSDI), ocular surface staining, Schirmer test, meibography, tear meniscus height, conjunctival hyperemia, and non-invasive tear film break-up time. Patients were classified into three subtypes of DED: aqueous tear deficiency, meibomian gland dysfunction (MGD) and mixed dry eye., Results: Inactive TED was shown to be an associated factor with DED (odds ratio 14, confidence interval 2.24-87.24, p=0.0047), and presented more DED than healthy controls (87.5% versus 33.3%, p=0.0113). MGD was also more prevalent among these subjects than in healthy control (62.5% versus 6.7%; p=0.0273). No significant differences were found in other ophthalmological parameters, except for more intense conjunctival redness among active TED than GD without ophthalmopathy (p=0.0214). Qualitative MMP-9 test was more frequently positive in both eyes among active TED than in other groups (p < 0.0001)., Conclusion: Patients with GD were symptomatic and presented a high prevalence of ocular surface changes and DED, particularly the subgroup with inactive TED. Tear MMP-9 detection was associated with active TED suggesting a relationship between ocular surface changes and the initial inflammatory phase of ophthalmopathy., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Riguetto et al.)

Purpose: To elucidate risk factors for meibomian gland disease (MGD) and understand associated changes in meibography and in relation to ocular surface disease., Patients and Methods: As part of the standard workup for ocular surface disease at a tertiary academic center, 203 patients received an ocular history and lifestyle questionnaire. The questionnaire included detailed inquiries about ocular health and lifestyle, including makeup use, cosmetic eyelid procedures, screen time, and contact lens habits. Subjects also took the standardized patient evaluation of eye dryness (SPEED) II questionnaire. Meibomian gland (MG) dropout and structural changes were evaluated on meibography and scored by three independent graders using meiboscores. Statistical analysis was conducted to identify significant risk factors associated with MG loss., Results: This retrospective, cross-sectional study included 189 patients (378 eyes) with high-quality images for grading, and the average age was 67 years (77% female). Patients older than 45 years had significantly more dropout than younger patients (p < 0.01). Self-reported eye makeup use did not significantly impact MG loss. Patients with a history of blepharoplasty trended toward higher meiboscores, but the difference was not statistically significant. Self-reported screen time did not affect meiboscores. Contact lens use over 20 years was associated with significant MG loss (p < 0.05). SPEED II scores had no relationship to meiboscores (p = 0.75)., Conclusion: Older age is a significant risk factor for MG loss. Any contact lens use over 20 years also impacted MG dropout. Highlighting the incongruence of symptoms to signs, SPEED II scores showed no relationship to the structural integrity of MGs., Competing Interests: Dr. Farid, Dr. Smith, and Dr. Knezevic are consultants for Johnson & Johnson Vision. Dr. Lee reports personal fees from Cloudbreak Therapeutics, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Kim et al.)

Purpose: To evaluate diacerein (interleukin-1β inhibitor) efficacy on ocular surface disease (OSD)., Patients and Methods: This prospective observational study included patients who received diacerein for osteoarthritis and had dry eye (DE). The primary outcome was corneal staining score. Secondary outcomes were ocular surface disease index (OSDI) score, tear breakup time (TBUT), tear osmolarity (Osm), Schirmer's test results, interleukin-1α (IL-1α), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1Ra) levels in tears. All measurements were done at baseline and 2-month follow-up visits. Linear mixed models were used to examine the effect of all parameters, and log-transformed models were used for IL-1α, IL-1β, and IL-1Ra analyses., Results: Thirty-four patients (31 females and 3 males) were enrolled. The corneal staining score improved by 1.29 points (P=0.022, 95% confidence interval [95% CI] 0.19 to 2.40) after 2 months, and the OSDI score improved by 17.2 points (P<0.001, 95% CI 10.82 to 23.58) but TUBT decreased by 0.66 seconds (P=0.021, 95% CI 0.10 to 1.22). No significant differences were observed in the tear Osm and Schirmer's test. IL-1Ra demonstrated no statistical difference, IL-1α was significantly increased by 80% (P=0.260), and IL-1β was significantly decreased by 99.21% (P<0.001)., Conclusion: Diacerein can improve corneal staining and decrease IL-1β levels in tears, which reflects better DE symptoms. Diacerein may be a promising alternative treatment for patients with OSD and osteoarthritis., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Treewipanon et al.)

Purpose: RCI001, a novel therapeutic candidate for the treatment of ocular inflammatory diseases, have demonstrated remarkable anti-inflammatory and antioxidant effects in various ocular experimental models. This study was to evaluate the effects of RCI001 on intraocular pressure (IOP) and compare them with those of corticosteroids in experimental mouse models., Methods: Experimental mice were randomly divided into naïve, phosphate-buffered saline (PBS), 0.1% dexamethasone (DEX-1), and 1% RCI001 (RCI) groups, and each reagent was pipetted into the right eye of the mouse at 10 μL thrice daily for 5 weeks. In addition, 20 μL of 0.1% dexamethasone was injected subconjunctivally into the right eye once weekly for 5 weeks in the DEX-2 group. The IOP was measured under anesthesia at baseline and twice weekly for 5 weeks. The △IOP (%) was defined as the change in IOP from baseline [△IOP (%) = (IOP week 5 -IOP baseline )/IOP baseline × 100%]. The anterior segments were clinically and histologically examined., Results: There was no significant increase in IOP and △IOP (%) [values by week 3 (day 21) in any of the groups]. However, IOP and △IOP (%) in the DEX-2 group tended to increase slightly after day 10 compared with baseline. Compared with baseline IOP values, the DEX-1 group showed a statistically significant increase in IOP at weeks 4 and 5, and the DEX-2 group at week 5. The △IOP (%) of the DEX-1 and DEX-2 groups (%) at week 5 were 38.2% ± 5.8% and 38.4 ± 4.6%, respectively. However, the IOP in the RCI group did not increase significantly until week 5. The RCI group did not show notable corneal changes, such as epithelial defects or stromal opacities, at week 5. In addition, hematoxylin and eosin (H&E) staining of corneas in the RCI group revealed healthy corneal epithelial, stromal, and endothelial integrity., Conclusion: Long-term use of RCI001 did not induce significant IOP elevation or ocular surface changes, whereas topical corticosteroids significantly increased the IOP. Therefore, RCI001 may be an effective anti-inflammatory agent with a low risk of drug-induced IOP elevation., Competing Interests: DHK invented a patent for the topical use of RCI001 for the treatment of various ocular diseases (Republic of Korea: 10-1816277/US: 10/675294). YHK was chief executive officer of RudaCure, the company developing RCI001. YK was an employee at RudaCure. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Ku, Yoo, Kim and Kim.)