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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.

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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.

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Ocular surface inflammatory disorders, such as dry eye, are becoming increasingly prevalent. Developing new treatment strategies targeting harmful bacteria could provide significant therapeutic benefits. The purpose of this study was to characterize the common ocular pathogen Staphylococcus aureus and the rarer endophthalmitis-associated species Enterococcus faecalis isolated from the ocular surface of dry eye disease patients in Norway. Together the 7 isolates (5 S. aureus and 2 E. faecalis) comprise the complete set of members of each species isolated in our previous study of the ocular microbiome of 61 dry eye sufferers. We aimed to investigate the pathogenic potential of these isolates in relation to ocular surface health. To this end, we used whole genome sequencing, multiplex PCR directed at virulence genes and antibiotic susceptibility tests encompassing clinically relevant agents. The E. faecalis isolates showed resistance to only gentamicin. S. aureus isolates displayed susceptibility to most of the tested antibiotics, except for two isolates which showed resistance to trimethoprim/sulfamethoxazole and three isolates which were resistant to ampicillin. Susceptibilities included sensitivity to several first-line antibiotics for treatment of ocular infections by these species. Thus, treatment options would be available if required. However, spontaneous resistance development to gentamicin and rifampicin occurred in some S. aureus which could be a cause for concern. Whole genome sequencing of the isolates showed genome sizes ranging from 2.74 to 2.83 Mbp for S. aureus and 2.86 Mbp for E. faecalis, which is typical for these species. Multilocus sequence typing and phylogenetic comparisons with previously published genomes, did not suggest the presence of eye-specific clusters for either species. Genomic analysis indicated a high probability of pathogenicity among all isolates included in the study. Resistome analysis revealed the presence of the beta-lactamase blaZ gene in all S. aureus isolates and the dfrG gene in two of them; while E. faecalis isolates carried the lsa(A) gene which confers intrinsic resistance to lincosamides and streptogramin A in this species. Screening for virulence factors revealed the presence of various pathogenicity associated genes in both S. aureus and E. faecalis isolates. These included genes coding for toxin production and factors associated with evading the host immune system. Some of the identified genes (tst, hylA & hylB) are suggested to be linked to the pathophysiology of dry eye disease. Lastly, the presence of specific S. aureus virulence genes was confirmed through multiplex PCR analysis.

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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.

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Contact lens (CL) use is growing rapidly, with a current estimate of over 100 million wearers worldwide. Vast improvements in materials and designs have occurred over the past decades with advancements in the understanding of ocular surface health with CL wear. However, the potential impact of CL on neural structures and function of the ocular surface, particularly in relation to the richly innervated cornea, remain poorly understood. Problems with sensation such as CL discomfort and conditions that may be associated with lens wear including dry eye disease also remain pervasive. This narrative review discusses the findings from studies involving soft or rigid CL wearers, assessed with c linical techniques designed for examining the neural integrity of the cornea, namely in vivo confocal microscopy and esthesiometry. While the collective findings remain equivocal in terms of the changes in corneal nerve morphology and function with conventional CL wear, more specialised CLs, namely orthokeratology lenses, which mechanically manipulates the structure of the cornea seem to produce more prominent changes in nerve distribution and sensitivity reduction. Given the intricate relationship between neural and immune mechanisms in maintaining balanced ocular surface health, the potential links between these structural and functional findings with parainflammation and neuroinflammation, as well as clinical issues including CL discomfort and dry eye disease, are also explored.

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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).

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A 37-year-old, never-smoker, pregnant woman diagnosed with Graves' disease who had stable thyroid eye disease (TED) before pregnancy presented with aggravated proptosis and eyelid swelling at 13 weeks of pregnancy. Despite the administration of local triamcinolone and 3 cycles of corticosteroid pulse therapy from 25 to 28 weeks, the patient's visual acuity decline necessitated postpartum orbital decompression surgery. Although TSH receptor antibody (TRAb) levels decreased during the mid- to late term of pregnancy, the TED worsened. This finding suggests that factors other than anti-TSH receptor antibodies may have a significant effect on disease severity.

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PURPOSE: This study examines the impact of dry eye on screen reading, with an emphasis on glare and visual comfort for patients. POPULATION AND METHODS: We recruited ten patients with dry eye and nine healthy controls. Clinical signs of dry eye were quantified to determine the quality of the tear film and corneal aberrations. Questionnaires related to quality of life and light sensitivity were administered. All participants underwent a screen reading test under five different levels of brightness. RESULTS: Patients with dry eye presented with more significant ocular inflammation (Oxford score) and reduced tear breakup time (BUT; DED: 4.1s, CO: 11.8s; W=90, P<0.001) compared to the control population. Patients also exhibited impaired quality of life (OSDI score: CO: 15.044±9.16, DED: 38.150±18.66, P=0.004) and increased light sensitivity (Glare test: CO: 96.56±65.5 arc.min, DED: 204.1±82.5 arc.min, W=15, P=0.013; VLSQ score: CO: 16.44±4.85, DED: 22.0±6.34, P=0.049). Reading tests did not show a significant difference between the groups (CO: 155±23.3 words/min and DED: 149±28.0, F=1.935, P=0.169). Brightness did not influence reading speed (F=1.308, P-value=0.275). A correlation was observed between reading speed and the OSDI quality of life questionnaire (R=-0.7, P=0.043). CONCLUSION: Although screen brightness did not have a significant impact on reading speed, glare proved to be a major issue for patients with dry eye. The associations between clinical manifestations of dry eye and reading performance emphasize the importance of comprehensive management of this condition. The results suggest that dry eye can influence both quality of life and screen reading, highlighting the need for dedicated approaches to improve the visual comfort of patients.

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The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events.

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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.

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Dry eye disease (DED) is an ocular condition characterized by altered tear film homeostasis, resulting in symptoms like tear film instability, hyperosmolarity, inflammation, and neurosensory abnormalities. It affects visual acuity and quality of life and is influenced by age, gender, and environmental factors. The first line of treatment consists of dynamically developing artificial tears, gels, and eyelid sprays, which can be supplemented with natural ingredients for enhanced efficacy. Other therapeutic steps include auto-logous serum tears, anti-inflammatory and immunosuppressive eyedrops, or oral tablets. Management also targets Meibomian gland dysfunction and the ocular surface micro-biome. This article explores various therapeutic approaches, including natural compounds and complementary strategies. Natural compounds, such as vitamins, and herbal substances (e.g., trehalose), offer promising benefits in enhancing tear film stability and ocular surface protection. Apitherapeutic products like manuka honey and propolis exhibit antibacterial and anti-inflammatory properties. Additionally, human tissue-derived solutions, such as auto-logous serum tears and amniotic membrane extracts, hold the potential for ocular surface regeneration. Other strategies, including polyherbal eye drops, liposomal eyelid sprays, and microbiome-supporting solutions offer alternative therapeutic avenues. Moreover, patient education, lifestyle modifications, and interdisciplinary collaboration play crucial roles in DED management, emphasizing the importance of holistic care approaches.

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In today's globalized society, ophthalmologists can examine people of different ethnicities regardless of where they live. The frequency of disease-causing genes varies according to a patient's ethnic background. We explain genetic findings for Japanese patients with inherited eye diseases. Ocular genetics has made great advances over the past 30 years. For example, detecting mutations at nucleotide position 11778 in mitochondrial DNA was useful in the genetic diagnosis of Leber's hereditary optic neuropathy (LHON). I evaluated the genotype-phenotype relationship in cases of corneal dystrophy and inherited retinal dystrophy (IRD). I identified the entire exon sequence of the eyes shut homolog (EYS) gene in patients with autosomal recessive retinitis pigmentosa (RP). EYS gene mutations are the most frequent cause of autosomal recessive RP. RPGRIP1 may be a common causative gene with early-onset severe retinal dystrophy, including Leber congenital amaurosis. However, some genes have complex structures that are difficult to analyze, including the OPN1LW/OPN1MW gene cluster in blue cone monochromacy and the IKBKG/NEMO genes in incontinentia pigmenti. This review will also present two cases with uniparental disomy, a case of IRD with double mutations, and a case with RP complicated with LHON-like neuropathy. Precise understanding of the effects of genetic variants may reveal differences in the clinical characteristics of patients with the same variant. When starting genome medicine, accurately diagnosing the patient, making accurate prediction, determining the genetic pattern, and providing genetic counseling are important. Above all, that both the doctors and patients understand genetic diseases correctly is important.

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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.

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Purpose: Orbital steroid injections offer a potential therapeutic avenue for managing Thyroid Eye Disease (TED). This study aimed to assess the effectiveness and potential systemic impacts of a single deep orbital triamcinolone injection in TED patients. Methods: In a prospective investigation conducted from January 2021 to March 2023, patients diagnosed with TED were enrolled. Inclusion criteria encompassed a Clinical Activity Score (CAS) of ≥3, extraocular muscle inflammation, and upper eyelid retraction. A total of 1 mL of triamcinolone acetonide (40 mg/mL) was administered posterior to the orbital septum at both the medial and lateral aspects of both the upper and lower eyelids. Parameters, including CAS, margin-reflex distances (MRD1 and MRD2), intraocular pressure (IOP), ocular motility (Hess area ratio [HAR%]), exophthalmometry, extraocular muscle size, and blood and urinary indices, were evaluated before and at 2 and 4 weeks after a single injection. Results: Analysis included 28 patients (23 women, 5 men; mean age (SD): 38.7 (11.1) years), representing 56 eyes. Following the injection at 4 weeks, the mean CAS and MRD1 significantly decreased by 2 points and 0.8 mm, respectively. There was a 4.5% increase in HAR%, and extraocular muscle size decreased by 4 to 15.3 mm². Neutrophil count, C-reactive protein, and thyroid antibodies significantly decreased. No severe adverse ophthalmic or systemic effects, including IOP increases or liver damage, were observed. Conclusion: Bilateral single orbital triamcinolone injections provided relief from TED symptoms through both direct effects on orbital soft tissue and systemic effects by decreasing antibody reactions.

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PURPOSE: To evaluate the reliability and validity of Turkish translation of the 5-item Dry Eye Questionnaire (T-DEQ-5) and to compare it with the Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal staining, and Schirmer test results. METHODS: The linguistic validation procedures adopted internationally, including forward translations, backward translation into English, examination of the translation quality, and a pilot test on 10 subjects, were employed. The translated and validated questionnaire was applied to 25 subjects two-time points (second time within three days) to evaluate the intra-test reliability. One hundred subjects were recruited for the study. They underwent an ophthalmic examination, including Schirmer tests, TBUT, and ocular surface staining (OSS) after completing OSDI questionnaire. Receiver operating characteristics (ROC) were assessed to determine sensitivity and specificity of the T-DEQ-5. RESULTS: The mean age of subjects was 45.7 ± 16.2 years, with 65 % being female. Overall, the test-retest reliability was excellent with an intra-class correlation coefficient value of 0.95 (95 % CI 0.90-0.98, p < 0.001). The Cronbach's alpha reliability coefficient was 0.90, which demonstrated a strong level of internal consistency of the T-DEQ-5. Using ROC analysis to compare the results of the T-DEQ-5 with those of the OSDI, the area under the curve was found 0.95, with an optimal cut-off threshold of 6, resulting in 81 % sensitivity and 91 % specificity. Establishing the diagnosis based on a positive OSDI (≥13) and at least one positive sign (TBUT and/or OSS) yielded a sensitivity of 95 % and a specificity of 87 % at the cut-off threshold of 6. CONCLUSION: The Turkish version of the DEQ-5 is a valid and reliable questionnaire and capable of differentiating patients with dry eye.

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Dry eye disease (DED) is a multifactorial aging disorder leading to tear film insufficiency and instability. Yet, an important knowledge gap lingers in understanding senescence-associated ocular pathogenesis, due to limited in vitro translational lacrimal gland (LG) models. Consequently, this remains a major roadblock to discover effective therapies for the restoration of tear film secretion. Herein, the authors reported the magnetic bioassembly of two LG organoid platforms to recapitulate functional and aging states. Using a proof-of-concept approach, porcine primary LG cells were assembled into organoids via a magnetic 3D bioprinting (M3DB) platform. This platform could form reproducible LG organoids with epithelial hallmarks (AQP5+) and exhibit epithelial secretory functions (lysozyme activity). DNA damage-induced senescence and cell death was induced with etoposide, and LG organoid hypofunction and senescence-associated pathogenesis were observed. To confer DNA protection against aging, a novel gene therapy with Box A domain of high-mobility group box-1 (HMGB1-Box A) previously established by our group, was applied here to prevent LG cellular senescence for the first time. HMGB1-Box A transfection prevented LG organoids from senescence-associated pathogenesis at the transcriptomic, metabolomic and proteomic levels. Thus, M3DB platforms could generate functional and DNA damage-induced senescence LG organoids, and this latter damage could be prevented with HMGB1-Box A gene therapy.

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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.

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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.

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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.

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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.