Influence of Environmental Factors with Clinical Signs and Symptoms in the Management of Dry Eye Disease.

Background: This research aims to investigate the influence of environmental factors on the treatment efficacy of ocular lubricants in patients from urban areas with dry eye disease (DED). Methods: A phase IV clinical trial, which included 173 patients from major cities in Mexico, was randomly assigned to use ocular lubricants four times a day for 30 days. Ocular Surface Disease Index (OSDI), noninvasive tear film break-up time (NIBUT), ocular staining, and conjunctival hyperemia (CH) among other factors like weather, and air pollution as covariates were analysed. Results: After 30 days, OSDI score decreased by 14.8 points (p<0.001), and NIBUT increased by 2.9 seconds (p< 0.001), with longer values observed in patients recruited in autumn and winter (additional 1.8 seconds, p< 0.05) compared to those recruited in spring. Patients living in cities with cooler weather and high humidity, but low air quality had higher OSDI and conjunctival stain scores of up to 4.4 and 0.3 points, respectively, as compared to those living in cities with similar pollution and humidity levels but with higher temperatures (p-values= 0.019 and 0.050). Patients with moderate CH had an increase of up to 0.8 points in their corneal stain score (p< 0.010). We also found that ozone levels were related to the predicted changes in OSDI and NIBUT. Conclusion: This study demonstrated the impact of environmental factors on the signs and symptoms of DED and suggests that patients residing in cities with inadequately controlled air pollution can benefit from using ocular lubricants to alleviate their symptoms. Trial Registration: Trial is registered at clinicaltrials.gov (NCT04702776).

Review of Hydroxypropyl Methylcellulose in Artificial Tears for the Treatment of Dry Eye Disease.

Dry eye disease (DED) is a highly prevalent condition, resulting in reduced quality of life, lower participation in social life and impaired work efficiency. Hydroxypropyl methylcellulose (HPMC) is a cellulose-based viscosity-enhancing agent and is one of the most popular therapeutic ingredients in artificial tears. This review aims to evaluate the literature on the efficacy and safety of HPMC used in the treatment of DED. Literature searches were conducted in PubMed and Cochrane CENTRAL. A total of 28 clinical trials from 26 publications are included in this review, including 21 clinical intervention studies evaluating the effect of HPMC treatment over time and seven single instillation studies evaluating the short-term physical and symptomatic effects of HPMC after drop-instillation. The duration of clinical intervention studies ranged from 2 weeks to 5.5 months. DED severity ranged from mild to severe. Drop frequency ranged from two to up to 16 drops per day. HPMC concentration in artificial tears ranged from 0.2% to 0.5%. No major complications or adverse events were reported. Artificial tears containing HPMC were effective at improving symptoms and some signs of DED. However, combination drops with HPMC plus other therapeutic ingredients seem more effective than HPMC alone. HPMC appears to be equally effective or inferior to hyaluronic acid (HA). There is no evidence of superiority or inferiority to either carboxymethylcellulose (CMC) or polyethylene glycol 400/propylene glycol (PEG/PG). No single study explained the choice of drop frequency or HPMC concentration. More well-designed studies are needed to determine an evidence-based standard for HPMC treatment, including drop frequency, concentration and molecular weight for different DED severity and subgroups.

Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease.

Dexamethasone (DEX) is used to treat ocular surface diseases. However, regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side effects. In this study, a novel magnetic nanoparticle (MNP)-micelle (MC) co-delivery system (MMDS) was developed. The MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive properties. To extend its residency, the MMDS was magnetically attracted by an external magnet after instilling, which acted as a precorneal drug-depot enabling a sustainable release of DEX in tears. With combination of magnet treatment, the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva, as well as concurrently reduced the DEX-level in the aqueous humor, when compared with the commercial DEX eye drop treatment. The combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension, commercial DEX eye drops, as well as the MMDS@DEX treatment alone. The present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects, which will be beneficial to the treatments of a wide range of ocular surface diseases.

Overview of 37 Tear Substitutes in Europe Based on Various Physicochemical Parameters.

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

An L-type calcium channel blocker nimodipine exerts anti-fibrotic effects by attenuating TGF-ß1 induced calcium response in an in vitro model of thyroid eye disease.

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening autoimmune disorder. Orbital tissue fibrosis leading to intractable complications remains a troublesome issue in TED management. Exploration of novel therapeutic targets and agents to ameliorate tissue fibrosis is crucial for TED. Recent work suggests that Ca2+ signaling participates in tissue fibrosis. However, whether an alteration of Ca2+ signaling has a role in fibrogenesis during TED remains unclear. In this study, we aimed to investigate the role of Ca2+ signaling in the fibrogenesis process during TED and the potential therapeutic effects of a highly selective inhibitor of the L-type calcium channel (LTCC), nimodipine, through a TGF-ß1 induced in vitro TED model. METHODS: Primary culture of orbital fibroblasts (OFs) were established from orbital adipose connective tissues of patients with TED and healthy control donors. Real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing were used to assess the genes expression associated with LTCC in OFs. Flow cytometry, RT-qPCR, 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay, wound healing assay and Western blot (WB) were used to assess the intracellular Ca2+ response on TGF-ß1 stimulation, and to evaluate the potential therapeutic effects of nimodipine in the TGF-ß1 induced in vitro TED model. The roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 1 (STAT1) in fibrogenesis during TED were determined by immunohistochemistry, WB, flow cytometry and co-immunoprecipitation assay. Selective inhibitors were used to explore the downstream signaling pathways. RESULTS: LTCC inhibitor nimodipine blocked the TGF-ß1 induced intracellular Ca2+ response and further reduced the expression of alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 (Col1A1) and collagen type I alpha 2 (Col1A2) in OFs. Besides, nimodipine inhibited cell proliferation and migration of OFs. Moreover, our results provided evidence that activation of the CaMKII/STAT1 signaling pathway was involved in fibrogenesis during TED, and nimodipine inhibited the pro-fibrotic functions of OFs by down-regulating the CaMKII/STAT1 signaling pathway. CONCLUSIONS: TGF-ß1 induces an LTCC-mediated Ca2+ response, followed by activation of CaMKII/STAT1 signaling pathway, which promotes the pro-fibrotic functions of OFs and participates in fibrogenesis during TED. Nimodipine exerts potent anti-fibrotic benefits in vitro by suppressing the CaMKII/STAT1 signaling pathway. Our work deepens our understanding of the fibrogenesis process during TED and provides potential therapeutic targets and alternative candidate for TED.

MEIBO (perfluorohexyloctane): a novel approach to treating dry eye disease.

Dry eye disease (DED) or keratoconjunctivitis sicca (KCS) is a multifactorial disease that classically develops due to the hyperosmolarity of the tear film. Categorically divided into two types, based on decreased production and increased evaporation of the tear film, DED begins with a spectrum of nonspecific symptoms like pruritus, redness, burning and discomfort, progressively leading to stringy mucus eye discharge, photophobia, twitching, visual fluctuations, and punctate epithelial lesions. This disease has numerous treatment options, including medications, artificial tear inducers, and surgical manoeuvres that prevent water loss from the tear film. However, each of these treatment options has its limitations. The Food and Drug Administration (FDA) has approved another intervention, Meibo (perfluorohexyloctane), as a choice of management for dry eye disease. With its shielding action on the ocular surface, Meibo (perfluorohexyloctane) reduces desiccation stress-induced ocular damage, making it highly specific for treating DED. Available in an eye drop formulation of perfluorohexyloctane (PFHO), these drops can reduce saline evaporation by up to 80%. The methods we used for this analysis are literature searches from PubMed, Medline and Google Scholar. This study aims to scour varying differentials of DED, its aetiology, general interventions, the latest refinements, and clinical efficacy, safety, and trials associated with Meibo (perfluorohexyloctane) in the management of DED.

Association between insulin-like growth factor-1 and ocular surface parameters in obese prepubertal boys.

The study aimed to investigate the correlation between insulin-like growth factor 1 (IGF-1) and ocular surface parameters in obese prepubertal boys. Thirty obese prepubertal boys and 30 age- and gender-matched healthy controls underwent physical measurements, laboratory tests, and ocular surface assessments. The obese group showed lower IGF-1 levels (P = 0.001), reduced Schirmer I tear test (SIT) (P <0.001), and higher meibomian gland scores (meiboscore) compared to controls (P = 0.015). Bivariate analysis revealed a positive association between IGF-1 and SIT (r = 0.677, P < 0.001), and a negative association with between IGF-1 and meiboscore (r = - 0.487, P < 0.001). Multiple regression analysis indicated that IGF-1 (P < 0.001) and triglycerides (P = 0.028) independently influenced SIT. Logistic analysis showed a significant association between decreased IGF-1 and higher meiboscore values (OR 0.994, 95% confidence interval 0.988-1.000; P = 0.033). CONCLUSION: The findings suggest that reduced IGF-1 in obese prepubertal boys is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. This implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on. WHAT IS KNOWN: • Obese children exhibit decreased levels of IGF-1, and this reduction in IGF-1 is associated with cardiovascular metabolic complications related to obesity. • Ocular surface tissues might act as targets for hormones, might experience local effects of these hormone. WHAT IS NEW: • In prepubertal obese boys, the decrease in IGF-1 is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. • This finding implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on.

Silk-Derived Protein-4 versus vehicle control in treating patients with moderate to severe dry eye disease: a randomized clinical trial.

PURPOSE: In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface. DESIGN: Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study. METHODS: In the first cohort (N=305), patients were randomized 1:1:1:1 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed two times per day (BID), while in the second cohort patients were randomized 1:1 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N=151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study. RESULTS: SDP-4 (1%) significantly increased TBUT vs the vehicle control (P<0.05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED (P<0.05). All treatment groups were well tolerated with a 2.6% total discontinuation rate. CONCLUSIONS: To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP-4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation.

Effects of social support on vision-related quality of life in older adults with dry eye disease: the chain mediating role of illness perception and coping style.

Objective: This study explored the effects of social support, illness perception, coping style, and vision-related quality of life (VRQOL) in older patients with dry eye disease (DED) using a chain mediation model. Methods: A total of 407 patients with DED from a tertiary hospital in Wuxi, Jiangsu Province, China, between June and December 2023 were selected as participants. A demographic questionnaire, the Social Support Rating Scale, the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, and the National Eye Institute Visual Functioning questionnaire-25 were all given to them to complete. IBM SPSS (version 27.0) was used for data analysis, and Model 6 of the PROCESS Macro was used to test the predicted chain mediation model. Results: The positive association between social support and VRQOL demonstrated the mediation role of illness perception and coping style. Social support affected VRQOL via three pathways: illness perception (effect = 0.190), confrontational coping style (effect = 0.103), and a combination of illness perception and confrontational coping style (effect = 0.067), accounted for 23.60%, 12.80%, and 8.32% of the total effect, respectively. Conclusion: Social support in older patients with DED can significantly and positively predict the VRQOL. In addition to the independent mediating effect of illness perception and confrontational coping style, a chain-mediating effect exists between social support and VRQOL. The study serves as a valuable strategy for healthcare professionals to prevent and intervene in VRQOL for older patients with DED in the future.

Prevalence of dry eye in people over 50 years old in Beichen district, Tianjin city: a cross-sectional population-based survey.

BACKGROUND: A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. METHODS: A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. RESULTS: According to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p < 0.001). Furthermore, the severity of DED was more severe in women (p = 0.006). The associated risk factors were age, female, depression, smoking, insomnia, and glaucoma. On the other hand, 53.6% of these populations were diagnosed as asymptomatic DED, and the morbidity was higher in males (p = 0.007). CONCLUSIONS: The prevalence of DED in China was relatively high, which was associated with aging, female(sex), depression, smoking and sleep problems. Hence, it is crucial for clinicians and caregivers to be aware of the existence of asymptomatic DED within the susceptible population.

Extraocular Muscle Enlargement in Thyroid Eye Disease Using Volumetric Analysis.

BACKGROUND AND OBJECTIVES: It is commonly taught that thyroid eye disease (TED) causes enlargement of the extraocular muscles (EOMs) in the following descending order: inferior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus (LR), superior oblique (SO) and inferior oblique (IO). However, with recent literature challenging this notion, we aimed to compare EOM volumes in our cohort of TED patients.  Methods: We conducted a retrospective, non-randomized case-control study. Twenty-eight orbits from 28 unique patients with TED who had high-resolution CT scans were compared to 31 normal orbits, all from a single academic institution. Orbital soft tissues were manually segmented using ITK-SNAP 3.8.0 (http://itksnap.org), and soft tissue volumes of the control and TED orbits were compared using independent-sample t-tests. RESULTS: Of the TED orbits, 54% of SR/levator palpebrae superioris complex volumes (SRC) and 50% of IR volumes were greater than two standard deviations above the normal orbit average. Compared to controls, the mean SRC volume in TED subjects was 2.3 times enlarged, followed by the IR (2.1 times), SO (1.8 times), MR (1.7 times), LR (1.6 times), IO (1.6 times), and orbital fat (1.4 times) (p < 0.01 for all).  Conclusions: Our findings suggest that contrary to previous teaching, the SRC may be the most severely affected in TED.

Adverse effects of meteorological factors and air pollutants on dry eye disease: a hospital-based retrospective cohort study.

Although previous studies have suggested that meteorological factors and air pollutants can cause dry eye disease (DED), few clinical cohort studies have determined the individual and combined effects of these factors on DED. We investigated the effects of meteorological factors (humidity and temperature) and air pollutants [particles with a diameter ≤ 2.5 µ m (PM2.5), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO)] on DED. A retrospective cohort study was conducted on 53 DED patients. DED was evaluated by Symptom Assessment in Dry Eye (SANDE), tear secretion, tear film break-up time (TBUT), ocular staining score (OSS), and tear osmolarity. To explore the individual, non-linear, and joint associations between meteorological factors, air pollutants, and DED parameters, we used generalized linear mixed model (GLMM) and Bayesian kernel machine regression (BKMR). After adjusting for all covariates, lower relative humidity or temperature was associated with a higher SANDE (p < 0.05). Higher PM2.5, O3, and NO2 levels were associated with higher SANDE and tear osmolarity (p < 0.05). Higher O3 levels were associated with lower tear secretion and TBUT, whereas higher NO2 levels were associated with higher OSS (p < 0.05). BKMR analyses indicated that a mixture of meteorological factors and air pollutants was significantly associated with increased SANDE, OSS, tear osmolarity, and decreased tear secretion.

Preservatives and ocular surface disease: A review.

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.

Benchmarking four large language models' performance of addressing Chinese patients' inquiries about dry eye disease: A two-phase study.

Purpose: To evaluate the performance of four large language models (LLMs)-GPT-4, PaLM 2, Qwen, and Baichuan 2-in generating responses to inquiries from Chinese patients about dry eye disease (DED). Design: Two-phase study, including a cross-sectional test in the first phase and a real-world clinical assessment in the second phase. Subjects: Eight board-certified ophthalmologists and 46 patients with DED. Methods: The chatbots' responses to Chinese patients' inquiries about DED were assessed by the evaluation. In the first phase, six senior ophthalmologists subjectively rated the chatbots' responses using a 5-point Likert scale across five domains: correctness, completeness, readability, helpfulness, and safety. Objective readability analysis was performed using a Chinese readability analysis platform. In the second phase, 46 representative patients with DED asked the two language models (GPT-4 and Baichuan 2) that performed best in the in the first phase questions and then rated the answers for satisfaction and readability. Two senior ophthalmologists then assessed the responses across the five domains. Main outcome measures: Subjective scores for the five domains and objective readability scores in the first phase. The patient satisfaction, readability scores, and subjective scores for the five-domains in the second phase. Results: In the first phase, GPT-4 exhibited superior performance across the five domains (correctness: 4.47; completeness: 4.39; readability: 4.47; helpfulness: 4.49; safety: 4.47, p < 0.05). However, the readability analysis revealed that GPT-4's responses were highly complex, with an average score of 12.86 (p < 0.05) compared to scores of 10.87, 11.53, and 11.26 for Qwen, Baichuan 2, and PaLM 2, respectively. In the second phase, as shown by the scores for the five domains, both GPT-4 and Baichuan 2 were adept in answering questions posed by patients with DED. However, the completeness of Baichuan 2's responses was relatively poor (4.04 vs. 4.48 for GPT-4, p < 0.05). Nevertheless, Baichuan 2's recommendations more comprehensible than those of GPT-4 (patient readability: 3.91 vs. 4.61, p < 0.05; ophthalmologist readability: 2.67 vs. 4.33). Conclusions: The findings underscore the potential of LLMs, particularly that of GPT-4 and Baichuan 2, in delivering accurate and comprehensive responses to questions from Chinese patients about DED.

Evaluation of Two Artificial Tears Containing Hyaluronic Acid for Post Cataract Surgery Dry Eye Disease: A Randomized Controlled Trial.

INTRODUCTION: This study compared the efficacy of hydroxypropyl guar (HPG)/hyaluronic acid (HA) and carboxymethylcellulose (CMC)/HA lubricant eye drops for post-cataract surgery dry eye disease (DED). METHODS: This was a prospective, open-label, assessor-masked, parallel, randomized controlled study. Seventy patients with DED who underwent cataract surgery were randomized in a 1:1 ratio to receive 1-2 drops of HPG/HA or CMC/HA lubricant four times daily for 3 weeks. Efficacy assessments included changes from baseline in corneal fluorescein staining (CFS) score, Ocular Surface Disease Index score, Schirmer's test score (without anesthesia), tear break-up time, and central corneal sensitivity at weeks 1 and 3. RESULTS: There were 35 patients in each group. The HPG/HA group demonstrated superior improvements in CFS scores (expressed as means and standard deviations) to the CMC/HA group at week 1 ( - 1.0 [1.7] vs. - 0.1 [1.7], p = 0.039) and demonstrated comparable results at week 3 ( - 1.6 [1.8] vs. - 1.3 [1.9], p = 0.552). No statistical differences were observed in other secondary outcomes between groups at weeks 1 and 3 (p > 0.05). Only one adverse event was reported in this study, which occurred in the HPG/HA group. The AE of ocular hypertension was mild, deemed unrelated to the study treatment, and resolved within a week. CONCLUSIONS: The HPG/HA lubricant eye drops resulted in greater CFS scores at 1 week after treatment compared with CMC/HA drops. The HPG/HA and CMC/HA drops were safe and well tolerated. GOV IDENTIFIER: NCT06221345.

The relationship between sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty.

Purpose: The study aimed to investigate the correlation between the change of sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty(ICPP). Methods: Eighteen girls with ICPP and 18 age-matched normal girls participated in this study, all of the participants had undergone physical measurements, laboratory tests, imaging examination and ocular surface assessments. Results: The Objective Scatter Index (OSI) in the ICPP group was significantly higher than in the control group (P = 0.031), girls with ICPP showed slightly lower MNITBUT compared to the normal control group, although this difference was not statistically significant. Bivariate analysis revealed a positive association between estradiol and OSI (r=0.383, P=0.021), Additionally, in the study population, both Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were negatively correlated with Mean noninvasive tear breakup time (MNITBUT) (r=-0.359, P=0.031)(r=-0.357, P=0.032). Conclusion: In comparison with the normal control group, alterations in the OSI were observed in girls with ICPP. This alteration may be associated with an elevation in estrogen levels. Although there was a slight non-significant decrease in NITBUT in ICPP girls, the negative correlation between LH and FSH with MNITBUT suggests new perspective for further investigation.

Reversible cerebral vasoconstriction syndrome due to teprotumumab: two case reports.

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome (RCVS) involves cerebral vasculature constriction and dilation. While the exact pathophysiology of RCVS is still not fully understood, there are multiple etiological factors suggested to be implicated in triggering RCVS. We report two RCVS cases potentially linked to teprotumumab. Case 1: A 59-year-old female with Graves' eye disease (GED) developed leg weakness and headache after initiating teprotumumab, and neuroimaging studies revealed multifocal cerebral vasospasm (CVS). Verapamil mitigated vasospasm and the patient overall improved. Case 2: A 71-year-old female with GED developed thunderclap headache two months after starting teprotumumab, with subarachnoid hemorrhage (SAH) and CVS revealed on neuroimaging studies. The patient improved on verapamil and was discharged without deficits. CONCLUSIONS: The temporal correlation between teprotumumab initiation and RCVS's symptom onset raises concern for the potential involvement of teprotumumab in triggering RCVS via disrupting cerebrovascular modulation. Further research is needed to investigate this proposed association.

Diquafosol Improves Corneal Wound Healing by Inducing NGF Expression in an Experimental Dry Eye Model.

Dry eye disease (DED) is caused by inflammation and damage to the corneal surface due to tear film instability and hyperosmolarity. Various eye drops are used to treat this condition. Each eye drop has different properties and mechanisms of action, so the appropriate drug should be used according to clinical phenotypes. This study aims to compare the therapeutic mechanisms of cyclosporine A (CsA) and diquafosol tetrasodium (DQS). An experimental in vivo/in vitro model of DED using hyperosmolarity showed decreased cell viability, inhibited wound healing, and corneal damage compared to controls. Treatment with cyclosporine or diquafosol restored cell viability and wound healing and reduced corneal damage by hyperosmolarity. The expression of the inflammation-related genes il-1ß, il-1α, and il-6 was reduced by cyclosporine and diquafosol, and the expression of Tnf-α, c1q, and il-17a was reduced by cyclosporine. Increased apoptosis in the DED model was confirmed by increased Bax and decreased Bcl-2 and Bcl-xl expression, but treatment with cyclosporine or diquafosol resulted in decreased apoptosis. Diquafosol increased NGF expression and translocation into the extracellular space. DED has different damage patterns depending on the progression of the lesion. Thus, depending on the type of lesion, eye drops should be selected according to the therapeutic target, focusing on repairing cellular damage when cellular repair is needed or reducing inflammation when inflammation is high and cellular damage is severe.

Development of a dry eye index as a new biomarker of dry eye disease.

PURPOSE: To evaluate signs and symptoms in patients diagnosed with dry eye disease (DED), divided into dry eye (DE) groups, in order to find a new biomarker that allows an accurate diagnosis, management and classification of DED. METHODS: This cross-sectional, observational study included 71 DED subjects. Subjective symptoms, visual quality and DE signs were assessed using the Ocular Surface Disease Index (OSDI), the Quality of Vision (QoV) questionnaire, best corrected distance visual acuity (VA), functional visual acuity (FVA), contrast sensitivity (CS), high- and low-order corneal aberrations (HOA and LOA, respectively), tear break-up time (TBUT), Meibomian Gland Dysfunction (MGD), Schirmer test, corneal staining, lid wiper epitheliopathy (LWE) and meibography. Participants were classified into three groups based on dryness severity using a cluster analysis, i.e., mild (N = 17, 55.8 ± 15.4 years), moderate (N = 41, 63.5 ± 10.6 years) and severe (N = 13, 65.0 ± 12.0). A new Dry Eye Severity Index (DESI) based on ocular surface signs has been developed and its association with symptoms, visual quality and signs was assessed. Comparisons between groups were made using Kruskal-Wallis and Chi-squared tests. Spearman correlation analysis was also performed. RESULTS: The DESI was based on three tests for DE signs: TBUT, Schirmer test and MGD. The DESI showed significant differences between different pairs of groups: Mild Dryness versus Moderate Dryness (p < 0.001), Mild Dryness versus Severe Dryness (p < 0.001) and Moderate Dryness versus Severe Dryness (p < 0.001). The DESI was significantly correlated with age (rho = -0.30; p = 0.01), OSDI score (rho = -0.32; p = 0.007), QoV score (rho = -0.35; p = 0.003), VA (rho = -0.34; p = 0.003), FVA (rho = -0.38; p = 0.001) and CS (rho = 0.42; p < 0.001) Also, significant differences between the severity groups were found for OSDI and QoV scores, VA, FVA, CS and MGD (p < 0.05). CONCLUSIONS: The DESI has good performance as a biomarker for the diagnosis, classification and management of DED.

Tolerability of Current Treatments for Dry Eye Disease: A Review of Approved and Investigational Therapies.

Dry eye disease (DED) is a common, multifactorial ocular disease impacting 5% to 20% of people in Western countries and 45% to 70% in Asian countries. Despite the prevalence of DED and the number of treatment approaches available, signs and symptoms of the disease continue to limit the quality of life for many patients. Standard over-the-counter treatment approaches and behavior/environmental modifications may help some cases but more persistent forms often require pharmacological interventions. Approved and investigational pharmaceutical approaches attempt to treat the signs and symptoms of DED in different ways and tend to have varying tolerability among patients. While several pharmacological approaches are the standard for persistent and severe disease, mechanical options provide alternate treatment modalities that attempt to balance efficacy and comfort. Newer approaches target the causes of DED, utilizing novel delivery methods to minimize irritation and adverse events. Here, we review approved and investigational approaches to treating DED and compare patient tolerability.