The severity of dry eye symptoms and risk factors among university students in Saudi Arabia: a cross-sectional study.

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

Vectored Thermal Pulsation as a Treatment for Meibomian Gland Dysfunction: A Review Spanning 15 Years.

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.

PLL-g-PEG Polymer Inhibits Antibody-Drug Conjugate Uptake into Human Corneal Epithelial Cells In Vitro.

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.

Sutureless Dehydrated Amniotic Membrane (Omnigen) Application Using a Specialised Bandage Contact Lens (OmniLenz) for the Treatment of Dry Eye Disease: A 6-Month Randomised Control Trial.

Background and Objectives: Dry Eye Disease (DED) is a chronic condition characterised by tear film instability and ocular surface disruption, significantly impacting patients' quality of life. This study aimed to provide top-level clinical evidence for the long-term efficacy of dehydrated amniotic membrane (dAM, Omnigen®) delivered via a specialised bandage contact lens (sBCL, OmniLenz) for managing moderate-to-severe DED. Materials and Methods: This randomised controlled trial (NCT04553432) involved 93 participants with moderate-to-severe DED, randomised to receive a 1-week bilateral treatment of either dAM (17 mm diameter with 6 mm central 'window') applied under a sBCL or sBCL alone. Participants were assessed at baseline and followed up at 1, 3, and 6 months post-treatment. Outcomes included changes in symptomatology, tear film and ocular surface measurements, and in vivo confocal microscopy imaging of corneal nerve parameters and corneal dendritic cell (CDC) counts. Results: The dAM-sBCL group demonstrated a 65% reduction in OSDI scores at 6 months (p < 0.001), with 88% of participants showing improvement at 1 month. Corneal staining was significantly reduced in both groups. dAM-sBCL provided significant improvements in corneal nerve parameters at 1 month, with sustained positive trends at 3 months. Additionally, dAM-sBCL significantly reduced mature CDC counts, suggesting an anti-inflammatory effect. Conclusions: Treatment with dAM-sBCL for just 1 week significantly and rapidly improved dry eye symptoms as well as ocular surface signs for at least 3 months. It also enhanced corneal nerve health while reducing activated/mature corneal inflammatory cell numbers, presenting a safe and promising new treatment for moderate-to-severe DED.

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review.

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.

24-Hour Evaluation of the Effectiveness and Tolerability of Preservative-Free Tafluprost-Timolol Fixed Combination in Open-Angle Glaucoma or Ocular Hypertensive Patients Previously Treated with Preserved Latanoprost.

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.

Prevalence of dry eye disease in the low vision population at the University of Colorado

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. (AU)

Engaging Stakeholders to Develop a Roadmap for Dry Eye and MGD PCORI-Funded Research.

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.

Crystalline keratopathy following long-term netarsudil therapy.

Purpose: This case report highlights a possible association between netarsudil use and crystalline keratopathy. Observations: Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment. Conclusions and importance: Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.

Using 2% PVPI topical solution for serial intravitreous injections and ocular surface findings: a case control study.

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.

Detection of Mycoplasma spp. and feline calicivirus in cats with ocular surface disease.

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.

Neurotrophic keratopathy: General features and new therapies.

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.

Association Between Acquired Punctal Stenosis and Ocular Surface Disease: the Egg and the Chicken Story.

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.

A novel method of evaluating the non-invasive tear film break-up time and progression of corneal opacification in dogs using imaging video.

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.

Topical Insulin for Ocular Surface Disease.

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.

Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.

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).

A Preservative-Free Approach - Effects on Dry Eye Signs and Symptoms After Cataract Surgery.

Purpose: To compare the effect of treatment with preservative-free dexamethasone, NSAIDs and trehalose/hyaluronic acid eye drops with the preservative benzalkonium chloride containing dexamethasone and NSAIDs after cataract surgery in dry versus non-dry eyes. Patients and Methods: In this prospective randomized intervention study, dry eye tests were performed before and 6 weeks after cataract surgery. Patients were considered as having dry eye, SDE (sign of dry eye), if at least one of the following dry eye tests were abnormal; corneal fluorescein staining (CFS), non-invasive keratograph breakup time (NIKBUT) or tear osmolarity. Patients with SDE were randomly assigned to one of two groups. Group 1 patients were treated with dexamethasone and bromfenac eye drops with the preservative benzalkonium chloride (BAC). Group 2 patients were treated with preservative-free dexamethasone and preservative-free diclofenac, as well as a preservative-free lubricant with trehalose and hyaluronic acid both before and after surgery. Patients with normal tear film status acted as the control group (group 3) and received same treatment as group 1. Results: A total of 215 patients were enrolled six weeks after surgery, the number of patients with SDE decreased significantly in groups 1 and 2 (p <0.001). Subjective symptoms and objective measures including osmolarity, NIKBUT, CFS, and tear film thickness (TFT) improved after surgery, tear production remained unchanged, while corneal sensitivity and meibomian gland dysfunction (MGD) parameters worsened. In the control group with normal tear-film status, SDE increased significantly after the surgery (p <0.001). There were no statistically significant differences in tear film parameters between the three groups after surgery. Conclusion: After cataract surgery, patients with mild to moderate dry eyes may experience improved tear film status and reduced symptoms. However, we found no additional beneficial effect on dry eye parameters with treatment with preservative-free dexamethasone, NSAIDs, and lubricants compared to preservative-containing eye drops.

How gut microbiota may impact ocular surface homeostasis and related disorders.

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.

Understanding Ocular Surface Disease in Glaucoma: A Comparative Analysis of Symptoms and Objective Parameters.

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.

Safety and Tolerability of KIO-101 Eye Drops in Healthy Volunteers and Patients with Ocular Surface Disease-A Phase I Study.

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.