Dry Eye Symptoms Research Articles

Pre and postoperative comparative evaluation of tear film stability and conjunctival impression cytology after phacoemulsification using clear corneal temporal incision

Abstract Introduction: Development of significant dry eye symptoms and visual disturbances after successful cataract surgery remains the common and unsatisfying experience for ophthalmologists. Corneal incision site and surgical technique contribute in ocular surface damage after cataract surgery. To assess the pre and post-operative conjunctival impression cytology and tear film stability after phacoemulsification by clear corneal temporal incision. Methodology: This prospective interventional study was conducted in department of ophthalmology at tertiary care teaching hospital. 72 patients were enrolled and the dry eye assessment was done considering the Schirmer’s test, tear meniscus height, tear breakup time and conjunctival impression cytology; preoperatively and then at 1 week and 4 weeks postoperatively. ANOVA and Post Hoc test were used for statistical analysis and p value of <0.05 was considered significant. Results: Mean age of the patients was 59.86±9.56 years and most of the males were employed while females were mostly homemakers. The overall trend for dry eye tests showed significant (P<0.0001 on ANOVA) increase at 1st week postoperatively, while the significant recovery was achieved by 4th week postoperatively. There was a significant decline (p<0.0001) in goblet cell density (GCD) at 1st week, which was reversed by the 4th week postoperatively. Conclusion: The transient dry eye was seen in the patient’s undergoing phacoemulsification by 1st week postoperatively, which resolved spontaneously but partially with routine postoperative care by the 4th week follow up.

Prevalence of symptomatic dry eye and influencing factors among Chinese adolescents: A cross-sectional study.

Comprehensive research on the impact of various types of refractive errors (RE) and anisometropia on dry eye disease is still lacking. This study aimed to estimate the prevalence rates and potential lifestyle factors related to symptomatic dry eye (SDE) among adolescents in eastern China. A cross-sectional study was performed in 2023, and a stratified cluster sampling technique was used among adolescents in Nantong, China. Demographic information, including sex, age and BMI, were collected. All participants underwent optometric tests, while Ocular Surface Disease Index (OSDI) and self-designed questionnaires were administered. Both univariate and multivariate logistic regression analyses were used to assess associations between SDE and related parameters, and various types of RE and anisometropia were also included in the study. A total of 1,518 participants were enrolled in the study, and the overall prevalence of SDE was 20.3% among adolescents in Nantong, China. Multiple logistic regression analyses showed that high myopia (aOR = 3.42, 95% CI = 1.60-3.36, p = 0.025), frequent use of eye drops (aOR = 2.31, 95% CI = 1.60-3.36, p<0.001), a history of allergic conjunctivitis (aOR = 1.93, 95% CI = 1.09-3.34, p = 0.025), and frequent blinking (aOR = 3.23, 95% CI = 2.31-4.53, p<0.001) were identified as risk factors for SDE. Conversely, male gender (aOR: 0.76, 95% CI: 0.58-0.99, p = 0.043), increased sleep time (6-7 h: aOR = 0.64, 95% CI = 0.46-0.89, p = 0.009; 7-8 h: aOR = 0.64, 95% CI = 0.43-0.95, p = 0.026; >8 h: aOR = 0.43, 95% CI = 0.23-0.82, p = 0.010), and timely intervention when vision decline occurred were protective factors against SDE (aOR = 0.61, 95% CI = 0.43-0.85, p = 0.004). High myopia was found to be independently associated with an increased risk of SDE., while hyperopia, astigmatism, and anisometropia were not independent risk factors for SDE. The identified risk and protective factors may help provide valuable insights for future research and interventions aimed at improving ocular health in adolescents.

Comparison of postoperative cyclosporine 2.0% versus betamethasone 0.1% eye drops following trabeculectomy: A randomized clinical trial.

To investigate the effect of cyclosporine A 2% eye drop following trabeculectomy on intraocular pressure (IOP) and surgical success compared to postoperative steroid drop. Prospective, randomized clinical trial in an institutional setting. Forty patients with primary open-angle glaucoma and candidates for trabeculectomy were included in this study. Standard fornix-based trabeculectomy augmented with mitomycin C was performed for all patients. None of the included subjects had a history of prior laser or intraocular surgery in that eye. All included subjects were randomly assigned to either postoperative cyclosporine A 2% or betamethasone 0.1% eye drops. IOP measured by applanation tonometer and surgical success rate. Seventy-five potentially eligible POAG patients were seen during the study period, and 40 met the study criteria and were randomly assigned to one of the study groups. Patients in the cyclosporine A 2% group had consistently lower IOP, fewer glaucoma medications, and higher success rates for at least 24 months after surgery (P < 0.0001). Complete success was more frequent in the cyclosporine group. Moreover, the cyclosporine A group had more diffuse and elevated bleb with less vascularity in the first 3 months after surgery (P ≤ 0.01). This was paralleled with fewer dry eye signs and symptoms in the cyclosporine group in the first 3 months (P < 0.03). Postoperative cyclosporine A 2% eye drop can be used instead of steroid drops and is associated with improved surgical success and decreased dry eye manifestations.

A Comprehensive Review about Risks of Type-II Diabetes on Ocular Tear Film

Millions of people worldwide suffer from diabetes mellitus (DM), which can lead to systemic issues in a number of organs. Ocular problems, such as dry eye syndrome (DES), are among its less well-known side effects. This review delves into the interactions between diabetes and the composition of tear films, emphasizing alterations in the mucin, aqueous and lipid layer. Dry eye symptoms are exacerbated by induced changes in the components of the tear film in diabetes DM, which lead in decrement in tear production, increment in tear evaporation and tear film instability. Lipid layer is a lubricant, that reduces friction between the ocular surface and the eyelids which promotes high-quality, smooth refractive surface. The lacrimal function unit shields the tear film, preserves the normal function of the ocular surface. The mucin layer is secreted by the conjunctival goblet cells, in hyperglycemia the functionality of the cells are reduced thus, the mucin secretion is also altered which causes instability of the tear film. Diabetic patients can have their tear film integrity assessed with the help of diagnostic methods like Schirmer's Test and Tear Break- Up Time (TBUT). In order to relieve symptoms and maintain ocular health, there should be a complete management of diabetes and the induced tear film disorders.

Alpha-1 antagonist treatment for eyelid retraction in patients with thyroid eye disease-a prospective pilot study.

Sympathetic overstimulation of Müller's muscle is a suggested mechanism underlying upper eyelid retraction in thyroid eye disease (TED). We examined the effect of tamsulosin, an alpha-1 antagonist, on eyelid retraction in patients with TED. A single-centre prospective study. Patients with TED and associated eyelid retraction were treated with oral 0.4 mg/day tamsulosin for 3 months. Upper eyelid margins-to-reflex distance (MRD1), vertical palpebral fissure height (PFH), subjective improvement, signs and symptoms of dry eye, and lubricants use were assessed at baseline and at each subsequent visit. Eleven suitable patients (mean age 47.5 ± 9.68, 8 females) enrolled in the study. Three patients discontinued the drug due to mild adverse effects (dizziness, bradycardia, nausea, and gastrointestinal distress), which resolved immediately upon stopping treatment. The other eight patients tolerated the drug well and reported no side effects. Five patients experienced an objective improvement in eyelid position and subjective improvement in eye discomfort. The mean MRD1 decreased by -1.04 ± 0.81 mm (P = 0.015), and mean PFH decreased by -1.46 ± 1.33 mm (P = 0.039). Mean duration of tamsulosin treatment was 84.63 ± 71.9 days. Patients discontinued the drug due to no improvement in MRD1 (n = 3), referral for eyelid surgery with stable inactive TED (n = 2), treatment with intravenous methylprednisolone due to worsening active TED (n = 2), and patient choice after 5 months of treatment with spontaneous resolution of symptoms (n = 1). Tamsulosin is a safe potential treatment for eyelid retraction in TED and can be used as a temporary alternative therapeutic approach for patients unsuitable for surgery.

A Preservative-Free Combination of Sodium Hyaluronate and Trehalose Improves Dry Eye Signs and Symptoms and Increases Patient Satisfaction in Real-Life Settings: The TEARS Study.

Dry eye disease (DED) is a frequently observed condition characterized by ocular discomfort and visual disturbance. It is highly prevalent and impairs patients' quality of life (QoL). This study assessed the benefit of a preservative-free bioprotectant eye drop formulation containing sodium hyaluronate and trehalose (SH-trehalose) with regards to DED, as well as patient satisfaction, through a large-scale real-life survey. In a multi-center, international, prospective observational study, subjects with DED received SH-trehalose for 84 days. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire-5 items (DEQ-5), and patient satisfaction were assessed at baseline, day 28, and day 84, and clinical evaluations included ocular surface staining, Schirmer test, tear film break-up time (TBUT), and conjunctival hyperemia at baseline and day 84. A total of 312 patients were evaluated, of whom 82.4% were women. The mean age was 57.9±15.2 years. The mean OSDI score at baseline was 41.7 ± 20.6. After 84 days, the mean OSDI score was 27.3 ± 19.8 (p < 0.001). The percentage of patients with a severe OSDI score decreased from 60.3 to 34.5%. The DEQ-5 score significantly (p < 0.001) improved after 28 and 84 days, as did patient satisfaction. Ocular surface staining, Schirmer test, TBUT, and conjunctival hyperemia scores improved significantly (all p < 0.001) for both eyes with SH-trehalose between baseline and day 84. Tolerance of SH-trehalose was good. SH-trehalose significantly improved the clinical signs and symptoms of DED after 84 days. Moreover, it significantly increased patient satisfaction and was well tolerated. NCT04803240.

The Effectiveness of E&gt;Eye Intense Regulated Pulse Light Therapy in Treating Evaporative Dry Eye Disease among Southeast Asian Patients

Objective: Since the effectiveness of E&gt;Eye Intense Regulated Pulsed Light (IRPL) therapy in treating evaporative dry eye condition caused by meibomian gland dysfunction (MGD) has not been reported among the Southeast Asian population, this study aimed to retrospectively report the effectiveness of this treatment in addressing evaporative dry eye due to MGD among this population using Tear Check analyzer after three consecutive treatments.Material and Methods: This is a retrospective study involving 71 male and 107 female patients, aged between 28 and 83 with complaints of dry eye symptoms accompanied by clinical signs of MGD who have been treated with E&gt;Eye IRPL. All patients were treated with IRPL in three consecutive treatments where five overlapping flashes of light were administered on the lower lid and temporal part of each eye on day 1, 15, and 45. Improvement in lower meibomian gland loss, Tear Film Stability Evaluation (TFSE), and non-invasive breakup time (NIBUT) were assessed using the Tear Check analyzer at baseline and after the third treatment session.Results: Repeated-measure ANOVA showed that the percentage of lower meibomian gland loss and TFSE score significantly improved post-treatment, indicating recovery of the meibomian gland and improved tear stability. McNemar Change Test also showed that the percentage of patients having NIBUT of lower than 6 seconds has significantly reduced post-treatment.Conclusion: E&gt;Eye IRPL treatment is effective in evaporative dry eye disease caused by MGD among Southeast Asian patients after three consecutive treatments by restoring meibomian gland and tear stability post-treatment.

Association between pets and dry eye symptoms: A Chinese national-based study

BackgroundPet-derived allergens are another source of indoor air pollution which could affect human health. However, the association between pet ownership and the risk of dry eye symptoms (DES) remains to be elucidated. MethodsWe conducted a nationwide cross-sectional survey among Chinese residents aged over 12 years from June 20, 2022 to August 31, 2022. The Ocular Surface Disease Index-6 (OSDI-6) questionnaire was utilized to evaluate the presence of DES. Multivariable logistic regression models were used to analyze the associations between pet ownership and DES. Subgroup analyses were conducted based on sex, age, residence and affective disorders, and sensitivity analysis by excluding participants with major ocular diseases. The interactions between pet ownership and other risk factors on DES were explored in the additive scale by calculating the synergy index (SI). ResultsA total of 21,916 subjects replied to the questionnaire. The prevalence of DES was 43.6 % (95 % confidence interval (CI), 43.0 %–44.3 %). Pet ownership was significantly associated with increased risk of DES (Odds ratio (OR): 1.13, 95%CI: 1.05–1.21), especially among the elderly (OR: 1.28, 95%CI: 1.09–1.51) and urban residents (OR: 1.13, 95%CI: 1.04–1.24). The individual effect of allergic rhinitis on DES was 2.59 (95%CI: 1.27–5.53), while the joint effect of pets and allergic rhinitis was 5.26 (95%CI: 1.20–36.74), suggesting a synergistic interaction with a SI of 2.48 (95%CI: 0.25–24.39). Furthermore, the interaction analysis also indicated a synergistic interaction between pet ownership and low health literacy with a SI of 1.12 (95%CI: 0.66–1.87). ConclusionPet ownership was identified as a risk factor for DES. The synergistic interaction of pet ownership and allergic rhinitis suggests shared mechanisms between DES and allergic conditions.

Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial

Denifanstat, an oral fatty acid synthase (FASN) inhibitor, blocks de-novo lipogenesis, a key pathway driving progressive lipotoxicity, inflammation, and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH). This study aimed to examine the safety and efficacy of denifanstat for improving liver histology in individuals with MASH and moderate to advanced fibrosis. This multicentre, double-blind, randomised, placebo-controlled, phase 2b trial was conducted at 100 clinical sites in the USA, Canada, and Poland. After a screening period of up to 90 days, participants aged 18 years and older with biopsy-confirmed MASH and stage F2 or F3 fibrosis were randomly assigned (2:1) to receive either 50 mg oral denifanstat or placebo once per day for 52 weeks. Participants were dynamically allocated to treatment groups via a centrally administered interactive web-based response system and stratified by type 2 diabetes, region, and fibrosis stage. Investigators, patients, and the sponsor were masked to group allocation until database lock. The primary efficacy endpoints were a 2-point or greater improvement in non-alcoholic fatty liver disease activity score (NAS) without a worsening of fibrosis or MASH resolution with a 2-point or greater improvement in NAS without a worsening of fibrosis at week 52, assessed by intention to treat. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04906421, and is closed for enrolment. Of the 1087 individuals screened between June 2, 2021, and June 28, 2022, 168 eligible participants were randomly assigned to receive a dose of 50 mg denifanstat once per day (n=112) or placebo (n=56). All 168 participants (100 female, 68 male) received at least one dose of study treatment. In the ITT population, 42 (38%) of 112 participants in the denifanstat group had a 2-point or greater improvement in NAS without a worsening of fibrosis versus nine (16%) of 56 participants in the placebo group (common risk difference 21·0%, 95% CI 8·1-33·9; p=0·0035). 29 (26%) of 112 participants in the denifanstat group showed MASH resolution with a 2-point or greater improvement in NAS without a worsening of fibrosis compared with six (11%) of 56 participants in the placebo group (common risk difference 13·0%, 0·7-25·3; p=0·0173). The most common treatment-emergent adverse events were COVID-19 (19 [17%] of 112 in the denifanstat group vs six [11%] of 56) in the placebo group, dry eye symptoms (ten [9%] of 112 vs eight [14%] of 56), and alopecia (21 [19%] of 112 vs two [4%] of 56). All adverse events considered to be related to the study drug were of grade 1 or grade 2. None of the serious adverse events (13 [12%] of 112 participants in the denifanstat group vs three [5%] of 56 in the placebo group) were considered drug-related. Treatment with denifanstat resulted in statistically significant and clinically meaningful improvements in disease activity, MASH resolution, and fibrosis. The results of this phase 2b trial support the advancement of denifanstat to phase 3 development. Sagimet Biosciences.

Efficacy and safety of a lipid-containing artificial tear compared with a non-lipid containing tear: a randomized clinical trial.

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

Efficacy of Topical Cyclosporine Combined with Punctal Plugs in Treating Dry Eye Disease and Inflammation

Purpose To evaluate the effect of punctal plugs combined with cyclosporine eye drops on dry eye disease (DED) and ocular surface inflammation. Methods In a clinical trial, 73 patients were randomly allocated into three groups: punctal plug group, combination therapy group, and cyclosporine group. At the baseline and four weeks after treatment, the Schirmer I test score, fluorescein tear film break-up time (FBUT), ocular surface staining score and dry eye symptoms were assessed. Tear samples were collected to detect the level of inflammatory factors (interleukins, matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor alpha (TNF-α)). In an animal experiment, a New Zealand rabbit dry eye model was induced. The rabbits were randomly divided into control group, punctal plug group, and combination therapy group (n = 6). Conjunctival goblet cell density, protein level of MMP-9 in conjunctiva and mRNA levels of inflammatory factors in conjunctiva and cornea were measured before and after treatment. Results In combination therapy group of the clinical trial, the following results were observed: significant improvement in Schirmer I test scores and FBUT compared to the cyclosporine group and punctal plug group, respectively; a decrease in the tear levels of IL-6, IL-1, and MMP-9 compared to the punctal plug group; and a decrease in the tear levels of IL-1α, IL-6, and IL-17 compared to the baseline (all p < 0.05). In the animal experiment, rabbits in combination therapy group had a higher goblet cell density (p < 0.01) and lower mRNA levels of IL-16 (p < 0.05), IL-17 (p < 0.05), and MMP-9 (p < 0.01) in conjunctiva and that of MMP-9 (p < 0.01) in cornea compared to punctal plug group. Conclusion Cyclosporine eye drops combined with degradable punctal plugs is a more optimized clinical treatment strategy for DED compared with degradable punctal plugs or cyclosporine eye drops alone, considering the influence of comprehensive clinical efficacy and ocular surface inflammation.

Effectiveness and safety of a novel crosslinked hyaluronate canalicular gel occlusive device for dry eye.

To evaluate the effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared with a commercially available hydrogel canalicular plug (Form Fit). 5 sites in the United States. Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). Adults (≥22 years) with the Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of "not applicable," patent lacrimal drainage system, and bilateral corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was noninferiority of the mean within subject change from baseline to month 3 in Schirmer score for patients receiving filler compared with plugs. The key secondary effectiveness endpoint was noninferiority of the proportion of patients with filler achieving improvement from baseline to month 3 in OSDI by a minimal clinically important difference. Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear breakup time, and safety. 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was noninferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.

Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance.

The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology. We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS). Ten predictors, such as "vitality," "immunomodulating drugs," sensory symptoms," and "ethnicity," remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13). Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.

Mesenchymal Stem Cells-Derived Exosomal miR-223-3p Alleviates Ocular Surface Damage and Inflammation by Downregulating Fbxw7 in Dry Eye Models.

Our previous study indicated that exosomes derived from mouse adipose-derived mesenchymal stem cells (mADSC-Exos) alleviated the benzalkonium chloride (BAC)-induced mouse dry eye model. However, the specific active molecules in mADSC-Exos that contribute to anti-dry eye therapy remain unidentified. In this study, we aimed to investigate the efficacy and mechanisms of miR-223-3p derived from mADSC-Exos in dry eye models. Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to determine miR-223-3p derived from mADSC-Exos that exerted anti-inflammatory effects on hyperosmolarity-induced mouse corneal epithelial cells (MCECs). The therapeutic efficacy of miR-223-3p was evaluated in mice with dry eye induced by either BAC or scopolamine (Scop). Mice were randomly assigned to 5 groups: sham, model, miR-223-3p overexpression, miR-223-3p knockdown, and 0.1% pranoprofen (positive group). Post-treatment, the severity of dry eye symptoms, and the pro-inflammatory cytokine levels were assessed. The effect of miR-223-3p on silencing the target gene was verified using ELISA and dual luciferase reporter assays. The mADSC-Exos that knocked out miR-223-3p did not reduce interleukin (IL)-6 content. Supplementing with miR-223-3p could restore the reduction of IL-6. The miR-223-3p effectively ameliorated ocular surface damage and decreased pro-inflammatory cytokines or chemokines in both BAC- and Scop-induced mouse dry eye models. Furthermore, miR-223-3p inhibited cell apoptosis. F-box and WD repeat domain-containing 7 (Fbxw7) was the potential direct target of miR-223-3p. The miR-223-3p suppressed the 3'-untranslated region of Fbxw7. The Fbxw7 knockdown suppressed hyperosmolarity-induced inflammation in MCECs. The mADSC-derived exosomal miR-223-3p mitigates ocular surface damage and inflammation, indicating its potential as a promising treatment option for dry eye.

Mineralocorticoid receptor expression and the effects of the mineralocorticoid receptor antagonist spironolactone in a murine model of graft-versus-host disease

PurposeThe topical administration of spironolactone, a mineralocorticoid receptor antagonist (MRA) improves dry eye symptoms in patients with ocular graft-versus-host disease (GVHD); however, the detailed mechanism remains unclear. This study aimed to investigate the effects of spironolactone eyedrops on the ocular surface using a chronic GVHD (cGVHD) mouse model and to determine the expression of the mineralocorticoid receptor (MR). MethodsA cGVHD mouse model was established by allogeneic bone marrow transplantation (BMT) from B10.D2 mice to BALB/c mice. Subsequently, cGVHD mice were treated with either 0.005 % spironolactone or vehicle eyedrops. The eyelids, cornea and conjunctiva of the recipients were analyzed at 4-week intervals post-BMT in both groups. ResultsSigns of ocular GVHD, such as corneal epithelial damage, depletion of meibomian glands, and inflammatory cell infiltration onto the ocular surface, were significantly decreased in cGVHD mice treated with spironolactone eyedrops. The expression of the MR NR3C2 in the corneal and conjunctival epithelia was significantly increased in cGVHD mice. HSP47+NR3C2+ MR-expressing fibroblasts, CD45+NR3C2+ MR-expressing leukocytes, and CD4+NR3C2+ MR-expressing T cells infiltrated the ocular surface tissue of cGVHD mice significantly more than that of syngeneic controls. ConclusionsMR expression is increased in epithelial cells, fibroblasts, and T cells in a murine cGVHD model, whereas MRA and spironolactone eyedrops could attenuate the severity of ocular GVHD. These findings suggest that MR signaling partially contributes to the development of ocular GVHD in this mouse model.

Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC50, SMS2 = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t1/2, cornea = 1.11 h; t1/2, meibomian glands = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Efficacy of 100% autologous platelet-rich plasma and 100% autologous serum in dry eye disease: a randomised controlled trial

ObjectiveThe 0bjective is to compare treatment effects between undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) in patients with moderate-to-severe dry eye disease (DED).Methods and analysisA single-centre, randomised, double-masked,...

Response predictors of a topical corticosteroid-based regimen for dry eyes: A real-life study.

To examine the effectiveness and identify clinical response predictors of a short corticosteroid-based regimen consisting of topical preservative-free 0.1% dexamethasone (Monopex®, Théa Laboratories) in conjunction with artificial tears (AT) for dry eyes in a real-life clinical setting. Patients were recruited from the Norwegian Dry Eye Clinic and were allowed to use ATs of their own choice in addition to the prescribed 14-day topical dexamethasone course. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire (DEQ-5), Schirmer test (ST), fluorescein tear film break-up time (FBUT), ocular surface staining (OSS), meibum expressibility (ME), meibum quality (MQ), number of expressible meibomian glands among the central eight glands in the lower lids (NMG) and intraocular pressure (IOP) were measured at baseline and at 1-month follow-up. The average values of clinical parameters from both eyes were used for analyses. A paired t-test and a significance value of p < 0.05 were used for statistical analyses. Associations between sex, age, baseline values and the changes after the intervention (Δ) were explored using linear regression. A total of 167 patients (124 women, mean age 54 years ±17 (standard deviation)) were included. One month after initiation of intervention, OSDI and DEQ5 scores improved from 39.5 ± 22.1 to 31.4 ± 21.3 (p < 0.001) and from 12.6 ± 4.2 to 11.0 ± 4.6 (p < 0.001), respectively. OSS improved from 2.2 ± 1.4 to 1.8 ± 1.5 (p < 0.001), NMG increased from 4.8 ± 2.2 to 5.1 ± 2.2 (p < 0.05), while IOP decreased from 12.9 ± 3.3 to 12.4 ± 3.5 mmHg (p < 0.05). Significant associations were found between the change in symptoms and objective measures of DED (ΔOSDI, ΔDEQ5, ΔOSS, ΔFBUT, ΔNMG, ΔMQ) and their respective baseline values (OSDI, DEQ5, OSS, FBUT, NMG, MQ). The remaining tests did not show statistically significant changes. Improvement in dry eye symptoms and signs were observed following a short course of topical, preservative-free 0.1% dexamethasone treatment in combination with AT. Individuals exhibiting more pronounced symptoms and signs witnessed the most profound improvements with the treatment regimen, suggesting that poor baseline parameters may serve as response predictors of the treatment regimen. While the real-life data presented herein are valuable, the conclusions are limited by the inherent biases of a non-controlled study.

Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease.

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers' recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device.

Dry eye disease and spondyloarthritis: expanding the spectrum of systemic inflammatory disorders associated with ocular surface disease. Data from the international AIDA Network Spondyloarthritis Registry.

Dry eye disease (DED) is a condition associated with a myriad of systemic disorders. According to recent preliminary data, axial spondylarthritis (axial-SpA) could represent a new entity associated with DED. Therefore, this study aimed to assess DED in patients with axial SpA by performing quantitative and qualitative specific tests to investigate the potential association between DED and ocular surface damage in patients with axial-SpA and to identify potential variables associated with DED. A total of 71 patients with axial-SpA who fulfilled the Assessment of SpondyloArthritis International Society (ASAS) classification criteria and 19 healthy controls were enrolled in this study. Both the patients and the controls underwent a complete ocular assessment aimed at evaluating the tear film and ocular surface, which included the Schirmer test, tear break-up time (TBUT), fluorescein staining, and lissamine green staining. The Ocular Surface Disease Index (OSDI) questionnaire was administered to all patients. DED symptoms were reported in 46 (64.8%) patients and three (15.8%) healthy controls (p = 0.0004). The odds ratio for receiving a diagnosis of axial-SpA based on the presence of dry-eye-related symptoms was 9.2 (95% C.I. 2.72-42.52, p = 0.001). The Schirmer test values of < 6 mm/5 min were observed in 31 (43.7%) patients with axial-SpA and two (10.5%) healthy controls (p = 0.013); a TBUT of <5 s was observed in 34 (47.9%) patients with axial-SpA and six (31.6%) healthy controls. The median OSDI score was found to be 22.9 (IQR = 29.35) among the patients with axial-SpA and 0.0 (IQR = 4.69) among the healthy controls (p = 0.009). The fluorescein and lissamine green staining of the ocular surface indicated a significantly higher Oxford Grading Scale in the patients with axial-SpA than in the healthy controls. Patients with axial-SpA often complain of eye dryness, which may be quantified with the self-administered OSDI questionnaire and objectively assessed through the tests commonly used for the diagnosis of DED. Patients suspected of having axial-SpA should routinely be asked about dry eye symptoms and evaluated for potential corneal and conjunctival damage.