Exploring novel pharmacological trends: Natural compounds in dry eye disease management.

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.

Effectiveness of cyclosporine nanoemulsion eye drops in patients with mild-to-moderate dry eyes: objective and subjective evaluation.

BACKGROUND: To compare and evaluate objective and subjective clinical parameters between 0.05% cyclosporine nanoemulsion (CsN) and 0.15% hyaluronic acid (HA) administration in patients with mild-to-moderate dry eyes. METHODS: In this prospective, randomized, double-masked, single-center, and placebo-controlled parallel study, patients with mild-to-moderate dry eyes were randomly allocated to be treated with 0.05% CsN or 0.15% HA twice daily. Patients were followed-up at 4, 8, and 12 weeks. Objective and subjective parameters were evaluated during each visit. RESULTS: A total of 35 patients were enrolled in this study. Compared with baseline, tear film break-up time and fluorescein staining scores at 4, 8, and 12 weeks significantly improved in the CsN group. However, the Schirmer I test showed no statistically significant change until week 12. Using the Symptom Assessment in Dry Eye (SANDE) score, both groups gradually showed significant improvement compared with baseline values. However, the Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) showed no statistically significant change during the treatment period. CONCLUSIONS: Both 0.05% CsN and 0.15% HA administration twice a day effectively improved the objective signs and subjective symptoms of patients with mild-to-moderate dry eyes. However, patients treated with 0.05% CsN experienced greater and faster improvement.

Effect of laughter exercise versus 0.1% sodium hyaluronic acid on ocular surface discomfort in dry eye disease: non-inferiority randomised controlled trial.

OBJECTIVE: To assess efficacy and safety of laughter exercise in patients with symptomatic dry eye disease. DESIGN: Non-inferiority randomised controlled trial. SETTING: Recruitment was from clinics and community and the trial took place at Zhongshan Ophthalmic Center, Sun Yat-sen University, the largest ophthalmic centre in China, between 18 June 2020 to 8 January 2021. PARTICIPANTS: People with symptomatic dry eye disease aged 18-45 years with ocular surface disease index scores ranging from 18 to 80 and tear film break-up time of eight seconds or less. INTERVENTIONS: Participants were randomised 1:1 to receive laughter exercise or artificial tears (0.1% sodium hyaluronic acid eyedrop, control group) four times daily for eight weeks. The laughter exercise group viewed an instructional video and participants were requested to vocalise the phrases "Hee hee hee, hah hah hah, cheese cheese cheese, cheek cheek cheek, hah hah hah hah hah hah" 30 times per five minute session. Investigators assessing study outcomes were masked to group assignment but participants were unmasked for practical reasons. MAIN OUTCOME MEASURES: The primary outcome was the mean change in the ocular surface disease index (0-100, higher scores indicating worse ocular surface discomfort) from baseline to eight weeks in the per protocol population. The non-inferiority margin was 6 points of this index score. Main secondary outcomes included the proportion of patients with a decrease from baseline in ocular surface disease index score of at least 10 points and changes in dry eye disease signs, for example, non-invasive tear break up time at eight weeks. RESULTS: 299 participants (mean age 28.9 years; 74% female) were randomly assigned to receive laughter exercise (n=149) or 0.1% sodium hyaluronic acid (n=150). 283 (95%) completed the trial. The mean change in ocular surface disease index score at eight weeks was -10.5 points (95% confidence interval (CI) -13.1 to -7.82) in the laughter exercise group and -8.83 (-11.7 to -6.02) in the control group. The upper boundary of the CI for difference in change between groups was lower than the non-inferiority margin (mean difference -1.45 points (95% CI -5.08 to 2.19); P=0.43), supporting non-inferiority. Among secondary outcomes, the laughter exercise was better in improving non-invasive tear break up time (mean difference 2.30 seconds (95% CI 1.30 to 3.30), P<0.001); other secondary outcomes showed no significant difference. No adverse events were noted in either study group. CONCLUSIONS: The laughter exercise was non-inferior to 0.1% sodium hyaluronic acid in relieving subjective symptoms in patients with dry eye disease with limited corneal staining over eight weeks intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04421300.

Complications and compliance in professionally-managed and self-managed contact lenses compared with non-contact lens wearers.

PURPOSE: To test the impact of professional management of soft contact lens wear on symptoms and ocular complications. METHODS: Subjective symptoms and ocular complications of soft CL users who did not seek professional follow-up care (self-managed, SM), were compared to users who were prescribed CLs and their care professionally managed in optometry practices (PM), and to a control group of non-CL wearers. Habitual visual acuity, subjective dry-eye symptoms, and corneal abnormalities were assessed in all participants. CL wearers filled-out a usage habits questionnaire, and their CL fit was assessed. Outcomes were compared using Kruskal-Wallis and Chi Squared tests. RESULTS: The SM, PM, and non-CL wearers cohorts included 127 (mean age:24.3±5.1, median:23, range:16-45 years,104 female), 132 (mean age:25.5±6.2, median:23, range:18-43 years,103 female), and 56 (mean age:22.3±3.5, median:21, range:18-39 years,36 female) participants, respectively. Meibomian gland dysfunction grade (p = 0.004, p<0.0001), limbal redness (both p = 0.04), corneal neovascularization (both p = 0.003), and papillary conjunctivitis (p<0.0001,p = 0.005) were significantly worse in SM CL wearers compared with both the non-CL wearers and PM CL wearers, respectively. Conjunctival staining was significantly worse in the SM cohort compared with the PM cohort (p = 0.01). 38.6% of the SM compared with 22.8% of the PM CL wearers, had an inappropriate refractive correction (p = 0.006). SM CL wearers wore CLs significantly more years (mean and median 1 year,p = 0.008), for more daily hours (mean and median of 2 hours,p<0.00001), and tended to nap or sleep with their CLs compared with the PM CL wearers (47 vs. 29,p = 0.02). The cohorts did not differ in their subjective symptoms. CONCLUSIONS: Complications are significantly more prevalent in SM CL wearers compared with PM CL wearers, and SM CL wearers tend to wear CLs with incorrect powers, and are less compliant with napping or sleeping with the CLs compared with PM CL wearers. These findings emphasize the importance of fitting, patient education and follow-ups in CL wearers.

Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK.

OBJECTIVE: The chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample. DESIGN: Cross-sectional study. SETTING: Community-dwelling cohort. PARTICIPANTS: Twins from the TwinsUK cohort PRIMARY AND SECONDARY OUTCOME MEASURES: We compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing. RESULTS: In N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance. CONCLUSION: Our findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS.

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#shorts Síndrome do olho seco | Coisa de Homem

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Allogeneic serum-based eye drops may give better results than autologous drops in Sjögren's syndrome dry eye.

PURPOSE: Sjögren's syndrome (SS) may cause severe dry eye symptoms. One of the therapeutic option known for almost 40 years are autologous serum eye drops (ASEDs). Due to the presence of many pro-inflammatory factors in the autologous serum of SS patients, the use of allogeneic serum is often considered a better option. In our facility almost one-fifth of the patients using allogeneic serum-based eye drops (alloSEDs) suffered from autoimmune diseases, including SS. The study aim was to compare the effectiveness of both ASEDs and alloSEDs in SS patients. METHODS: From the group of SS patients using alloSEDs, five female SS patients aged 39-73 years were selected. They had the longest history of the use of the product. The analysis was based on OSDI forms and internal questionnaires which compared the effects of ASEDs and alloSEDs application. The patients used alloSEDs for a period of 5-28 months. All had previously used ASEDs for at least 2 years. RESULTS: For all five patients the mean OSDI after application of ASEDs and before introducing alloSEDs was 68.71, while the mean OSDI after the use of alloSEDs was 30.49. CONCLUSION: In SS the treatment results are better with alloSEDs than with ASEDs. Almost all SS patients who applied both autologous and allogeneic drops reported better effects with the latter as also confirmed by the study cases.

M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye.

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

S100A9-TLR4 axis aggravates dry eye through the blockage of autophagy.

This research focused on how upregulation of S100A9 contributed to the pathogenesis of the dry eye disease (DED) and whether S100A9 served as a promising therapeutic target in DED. Public single-cell RNA sequencing (scRNA-seq) data of a lacrimal gland excision (LGE) murine DED model was analyzed. LGE model was established and expression of protein was measured through immunofluorescence and Western blot. DED-related signs were evaluated through tear secretion and fluorescent staining. TUNEL was performed to detect the level of cell death. Briefly, S100A9 was recognized as a highly variable gene in the DED group. LGE model was successfully established, and S100A9 showed a time-dependent increase in the corneal epithelia. Autophagic blockage was predicted by the scRNA-seq data in DED, and further verified by decrease of LC3B-II/LC3B-I and increase of SQSTM1 and p-mTOR/mTOR, while S100A9 inhibitor paquinimod (PAQ) reversed the changes. PAQ also downregulated TLR4, and inhibition of TLR4 also alleviated autophagic blockage in DED. Finally, signs of DED, chronic corneal inflammation and cell death got a remission after either inhibition of S100A9 or TLR4. In general, we deduced a S100A9-TLR4-Autophagic blockage pathway in the pathogenesis of DED.

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.

Clinical Characteristic and Tear Film Biomarkers After Myopic FS-LASIK: 1-Year Prospective Follow-up.

PURPOSE: To assess the long-term (1-year) effect of myopic femtosecond laser-assisted in situ keratomileusis (FSLASIK) on clinical characteristics and tear film biomarkers. METHODS: Eighty eyes from 80 patients who underwent FSLASIK were evaluated. Ocular surface symptoms and signs were evaluated using specific questionnaires and tests. The corneal nerves and dendritic cells were examined using in vivo confocal microscopy. Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. Tear inflammatory cytokines and neuropeptides were evaluated using Luminex immunoassay. These examinations were performed preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Seventy-three participants completed all follow-up visits. Following FS-LASIK, ocular symptoms and signs (except Schirmer I test) worsened at 1 month but corneal and conjunctival stainings improved by 3 months. The numbers of dendritic cells and activated dendritic cells increased at the 3-month postoperative visit and recovered to preoperative levels by the 6-month visit. Ocular symptoms and corneal sensitivity recovered to preoperative levels at the 12-month visit. Tear break-up time and corneal nerve morphology were not recovered to preoperative status at the 12-month visit. Interleukin (IL)-1ß, IL-17A, tumor necrosis factor-α, and substance P tear levels significantly increased at all postoperative visits compared to preoperative levels. Corneal staining scores positively correlated with tear IL-1ß and IL-17A levels, whereas corneal nerve morphology positively correlated with corneal sensitivity and negatively correlated with substance P levels. CONCLUSIONS: Although most clinical variables improved at 12 months postoperatively, some tear inflammatory cytokines and substance P remain altered beyond 12 months, indicating that ocular homeostasis is not completely recovered. [J Refract Surg. 2024;40(8):e508-e519.].

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.

[Practical Application of Intelligent Vision Measurement System Based on Deep Learning].

To comprehensively assess the true visual function of clinical dry eye patients and the comprehensive impact of blinking characteristics on functional vision of the human eye, an intelligent vision measurement system has been designed and developed to detect and analyze blinks from the side. The system employs deep learning keypoint recognition technology to analyze eyelid features from a lateral perspective. It presents the data of identified key points for the upper and lower eyelids in a line chart format and annotates the trough of each blink. By setting benchmark values, the system automatically calculates the proportion of complete and incomplete blinks in the tested individuals. The results indicate that the system is stable in performance and accurate in measurement, successfully achieving the anticipated design objectives. It thereby provides reliable technical support for future clinical applications.

Improvement in signs and symptoms of severe dry eye disease after dual therapy with high-potency steroids and 0.05% cyclosporine.

OBJECTIVE: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED). MATERIALS AND METHODS: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences. RESULTS: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment (p = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals (p = .003 and .005). The sign score in the control group remained unchanged (all p > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p < .05). The high-potency steroid group had more favourable symptom (p = .035) and sign (p < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom (p = .025) and sign (p = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p > .05). CONCLUSIONS: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.

High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.

Health impact of screen addiction: A cross-sectional comparative study.

Background Prevalence-based, non-comparative studies have been done to assess psychological and physical consequences of social media and gaming addiction. However, similar studies are lacking for binge-watching, especially in India. We compared the physical and psychological health impact between screen addicted and healthy screen users, by minimizing bias due to confounding factors. Methods We did this cross-sectional comparative study among 120 participants (60 cases and 60 matched controls) consisting of gamers, social media users and binge-watchers, who were recruited from schools and colleges of Mumbai based on their scores on the Digital Addiction Scale (DAS). Levels of depression, anxiety and stress; sleep quality; and dry eye disease were assessed using pre-validated scales such as DASS-21, Pittsburgh Sleep Quality Index (PSQI), and Ocular Surface Disease Index (OSDI), respectively, while the other variables were assessed using a self-designed questionnaire with a content validity ratio (CVR) >0.65. Results The mean (SD) age of the participants was 19.3 (3.2) years, one-third were women; 68% were from medical colleges and 16% each from engineering colleges and high schools. The prevalence and scores of depression, anxiety and stress; poor sleep quality; and dry eye disease; and prevalence of loneliness, aggression and musculoskeletal pain in the wrist, thumb, neck and back were significantly higher in the screen addicted group (p<0.05). Conclusions There was a significant difference in the prevalence and levels of physical and psychological health impact between screen addicted and healthy screen users.