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.

Lubricating drops for contact lens discomfort in adults.

BACKGROUND: Contact lens discomfort is a symptom-based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe. OBJECTIVES: To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline. Study characteristics All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns. Lubricating drops (including saline) versus no treatment Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37-point scale (lower is better), but the evidence is very uncertain (mean difference [MD] -5.9 points, 95% confidence interval [CI] -3.74 to -8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end-of-day" comfort. The trial that compared saline with no treatment provided no results for the control group. Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low-certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD -0.15 points, 95% CI -0.86 to 0.56; 2 RCTs; 119 participants), depth (MD -0.01 points, 95% CI -0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI -0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low-certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI -0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI -0.39 to 0.39; 1 RCT; 73 participants). No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta-analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low-certainty evidence). Lubricating drops versus saline Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI -4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness. No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. Our meta-analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low-certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks. Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient-reported contact lens (dis)comfort using a validated instrument. Therefore, further well-designed trials are needed to generate high-certainty evidence on patient-reported outcomes as well as on longer-term safety outcomes.

Lubratex eye ointment with polyethylene cover significantly reduces corneal abrasion in ICU patients: a randomized controlled trial.

Corneal abrasion is a frequent complication in critically ill, intubated patients, potentially leading to visual impairment. This study compares the efficacy of three ocular care methods in preventing corneal abrasion among this vulnerable population. We conducted a randomized controlled trial involving 156 intubated adult patients admitted to the ICU. Participants were randomly allocated to one of three intervention groups (n = 52 per group): (1) polyethylene cover only, (2) polyethylene cover with artificial tear drops, and (3) polyethylene cover with Lubratex eye ointment. One eye per patient was randomly assigned as the control, receiving standard ICU eye care. Daily assessments over five days included a standardized dryness and corneal abrasion checklist, graded strip evaluation of eye dryness, and documentation of corneal abrasion incidence. Data were analyzed using descriptive and inferential statistics (SPSS-18). The incidence of corneal abrasion was significantly lower in the group receiving polyethylene cover with Lubratex eye ointment (4%) compared to the polyethylene cover with artificial tears group (36%, p < 0.001) and the polyethylene cover only group (60%, p < 0.001). The combined application of a polyethylene cover with Lubratex eye ointment effectively prevents corneal abrasion in intubated ICU patients. This method demonstrates superior efficacy compared to polyethylene covers used alone or with artificial tears. We recommend its implementation as standard practice for corneal abrasion prophylaxis in this high-risk population.Trial Registration. This study is registered with the Iranian Registry of Clinical Trials (IRCT201506294736N8) and can be accessed at www.IRCT.ir .

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.

The Short-term Effects of Artificial Tears on the Tear Film Assessed by a Novel High-Resolution Tear Film Imager: A Pilot Study.

PURPOSE: The purpose of this study was to investigate the effects of artificial tears (AT) on the sublayers of the tear film assessed by a novel tear film imaging (TFI) device. METHODS: The mucoaqueous layer thickness (MALT) and lipid layer thickness (LLT) of 198 images from 11 healthy participants, 9 of whom had meibomian gland disease, were prospectively measured before and after exposure to 3 different AT preparations (Refresh Plus; Retaine [RTA]; Systane Complete PF [SYS]), using a novel nanometer resolution TFI device (AdOM, Israel). Participants were assessed at baseline and at 1, 5, 10, 30, and 60 minutes after instilling 1 drop of AT during 3 sessions on separate days. Repeated-measures analysis of variances were used for comparisons with P < 0.05 considered significant. RESULTS: For all ATs, the mean MALT was greatest 1 minute after drop instillation, with an increase of 67%, 55%, and 11% above the baseline for SYS, Refresh Plus, and RTA, respectively. The SYS formulation demonstrated the highest percentage increases in mean MALT and LLT at most postdrop time points. The MALT differences were significantly higher in the SYS than in the RTA ( P = 0.014). After 60 minutes, no AT group demonstrated statistically significant changes in MALT or LLT compared with baseline. CONCLUSIONS: We report, for the first time, the effects of AT on MALT and LLT using a high-resolution TFI. A substantial acute mean MALT increase occurs 1 minute after AT instillation with all agents tested, but there were clear differences in response and durability, suggesting the benefits of choosing specific AT according to the needs of each patient.

An Investigation of the Psychosocial Outcomes of Dry Eye Disease Treatment in Children with Computer Vision Syndrome.

Objectives: Computer vision syndrome (CVS) is a common disorder among children and is often associated with dry eye disease (DED). While researchers have shown a higher prevalence of psychopathology in older patients with DED, the impact of CVS-induced DED on the psychological state of children is not well known. This study aimed to evaluate psychological outcomes before and after DED treatment in pediatric patients with CVS-related DED. Materials and Methods: In this study, a total of 38 children (32 girls, 6 boys) with CVS-related DED were evaluated with the Schirmer test, tear break-up time (TBUT), ocular surface disease index (OSDI), and Oxford grading scale at the time of diagnosis and after treatment with artificial tear drops. Additionally, quality of life (QoL) and anxiety and depression symptoms were assessed using self-report scales for children. Results: The mean age and mean daily screen exposure of the patients were 13.95±2.42 years and 5.65±2.31 hours, respectively. After treatment, TBUT and Schirmer test values of the patients increased significantly, while OSDI values decreased (p<0.001 for all). The anxiety and depression scores of the patients decreased, while QoL functionality scores increased (p<0.05 for all) following treatment. There were significant correlations between Schirmer test values and anxiety scores (r=-0.32, p=0.045) and QoL total scores (r=0.38, p=0.016). Conclusion: Enhanced QoL and decreased anxiety and depression scores were associated with improved Schirmer test results, indicating that appropriate DED treatment may mitigate the psychosocial effects of CVS-related DED in pediatric patients.

[Three-component tear substitute as preoperative support in glaucoma surgery]. / Primenenie trekhkomponentnogo slezozamenitelya v meditsinskom soprovozhdenii khirurgii glaukomy.

PURPOSE: This study investigates the effect of preoperative preparation with the three-component tear substitute Stillavit on the outcomes of glaucoma surgery in patients on long-term topical glaucoma therapy. MATERIAL AND METHODS: The study included 63 patients (63 eyes) with glaucoma, among them 30 (30 eyes) were women and 33 (33 eyes) were men. Group 1 consisted of 33 patients (33 eyes) receiving long-term topical antihypertensive therapy with preservatives and tear substitute Stillavit 3 times a day for 1 month as preoperative preparation. Group 2 included 30 patients (30 eyes) receiving similar antihypertensive therapy who were not prescribed preoperative medications. All patients underwent a comprehensive ophthalmological examination and computer tomography of the filtering blebs (FB) on Visante system (Carl Zeiss Meditec, Germany) before surgery, as well as 1 week, 1, 3, and 6 months after surgery. RESULTS: Mean intraocular pressure (IOP) elevation at 6 months postoperatively was significantly higher in the group that did not undergo preoperative preparation with a tear substitute, compared to the group of patients who received the tear substitute Stillavit preoperatively. According to anterior segment optical coherence tomography, a greater number of favorable diffuse FB were noted in the group that received the tear substitute Stillavit in preparation for surgery - 87.9%, while in group 2 (without preparation) - 66.7%. Odds ratio calculation between the two groups revealed that preoperative preparation with the tear substitute Stillavit reduced the odds of IOP elevation to 20 mm Hg or higher at 3 months postoperatively by more than 10 times. CONCLUSION: The use of tear substitute Stillavit in preparation for anti-glaucoma surgery reduces the chances of IOP elevation in the early postoperative period by more than 10 times, which may indicate a reduction in the rate of FB scarring due to the beneficial effect of the drug's components on the precorneal tear film.

Patient-Reported Dry Eye Treatment and Burden of Care.

OBJECTIVES: Dry eye is a common condition that can decrease the quality of life. This survey-based study of persons with dry eye investigated self-reported treatments (initial, current), out-of-pocket expenses, time spent on self-management, sources of care, and sources of information about their condition. METHODS: Online dry eye newsletters and support groups were emailed a link to an electronic survey asking members to participate. Survey respondents were not required to answer every question. RESULTS: In total, 639 persons with self-reported dry eye responded (86% women, 14% men [n=623]; mean ± SD age, 55 ± 14 years [n=595]). Artificial tears were the most reported intervention (76% initially, 71% currently). The median (interquartile range) out-of-pocket treatment cost annually was $500 ($200-$1,320 [n=506]). In addition, 55% (n=544) estimated 5 to 20 min daily on self-management; 22% spent an hour or more. Ophthalmologists provided most dry eye care (67%, n=520). Only 48% (n=524) reported that their primary source of dry eye information came from their eye care clinician. CONCLUSIONS: Artificial tears are the primary treatment for dry eye. Ophthalmologists provide most dry eye care, but half of patients report that their eye care provider is not their primary source of information. Almost one fourth of patients spend an hour or more daily on treatments.

The impact of Demodex blepharitis on patient symptoms and daily life.

SIGNIFICANCE: Patients with Demodex blepharitis have a considerable symptomatic burden that negatively impacts their daily activities and well-being. Despite chronic manifestations of and problems associated with blepharitis that resulted in multiple visits to eye care providers, Demodex blepharitis remained underdiagnosed or misdiagnosed. PURPOSE: This study aimed to evaluate the effect of Demodex blepharitis on patients' daily activities and well-being. METHODS: This prospective, multicenter, observational study recruited 524 patients with Demodex blepharitis from 20 U.S. ophthalmology and optometry practices. Demodex blepharitis was diagnosed based on the presence of the following clinical manifestations in at least one eye: >10 collarettes on the upper lashes, at least mild lid margin erythema of the upper eyelid, and mite density of ≥1.0 mite/lash (upper and lower combined). Patients were asked to complete a questionnaire related to their symptoms, daily activities, and management approaches. RESULTS: The proportion of patients who experienced blepharitis symptoms for ≥2 years was 67.8%, and for ≥4 years, it was 46.5%. The three most bothersome symptoms ranked were "itchy eyes," "dry eyes," and "foreign body sensation." Overall, 77.4% of patients reported that Demodex blepharitis negatively affected their daily life. One-third (32.3%) of patients had visited a doctor for blepharitis at least two times, including 19.6% who visited at least four times. Despite having clinical manifestations of Demodex blepharitis confirmed by an eye care provider, 58.7% had never been diagnosed with blepharitis. Commonly used management approaches were artificial tears, warm compresses, and lid wipes. Among those who discontinued their regimen, 45.9% had discontinued because of either tolerability issues or lack of effectiveness. Among contact lens wearers, 64.3% of the patients either were uncomfortable wearing contact lenses or experienced vision changes "sometimes" or "frequently." CONCLUSION: Demodex blepharitis results in a significant negative impact on daily activities, creating a psychosocial and symptomatic burden on patients.

Carrageenan films as promising mucoadhesive ocular drug delivery systems.

Polymer mucoadhesive films being developed for use in ophthalmology represent a new tool for drug delivery and are considered an alternative to traditional dosage forms. Due to their mucoadhesive properties, carrageenans (CRGs) are widely used in various forms for drug delivery. In this study, films based on CRGs of various structural types (κ/ß, κ, x, and λ) for use in ophthalmology were studied. The films were loaded with the active substance echinochrome (ECH), a sea urchin pigment used in ophthalmology. Spectral data showed that ECH remained stable after its incorporation into the CRG films and did not oxidize for at least six months. Hydrophilic CRG films with a thickness of 10-12 µm were characterized in terms of their swelling and mucoadhesive properties. The rheological properties of solutions formed after film dissolution in artificial tears were also assessed. κ- and κ/ß-CRG films with ECH exhibited pseudoplastic behavior after rehydrating films with an artificial tear solution. The CRG-loaded films had different swelling characteristics depending on the structure of the CRG used. The films based on highly sulfated CRGs dissolved in artificial tears, while the films of low-sulfated κ/ß-CRG exhibited limited swelling. All studied ECH-loaded films exhibited mucoadhesive properties, which were evaluated by a texture analyzer using mucous tissue of the small intestine of the pig as a model. There was a slight prolongation of ECH release from CRG films in artificial tears. The effect of CRG/ECH on the epithelial cell lines of the outer shell of the human eye was investigated. At low concentrations, ECH in the composition of the CRG/ECH complex had no cytotoxic effect on corneal epithelial and conjunctival human cells. The use of ECH-containing films can prevent the drug from being immediately washed away by tears and help to retain it by increasing viscosity and having mucoadhesive properties.

Eye infection risks from Pseudomonas aeruginosa via hand soap and eye drops.

Eye infections from bacterial contamination of bulk-refillable liquid soap dispensers and artificial tear eye drops continue to occur, resulting in adverse health outcomes that include impaired vision or eye enucleation. Pseudomonas aeruginosa (P. aeruginosa), a common cause of eye infections, can grow in eye drop containers and refillable soap dispensers to high numbers. To assess the risk of eye infection, a quantitative microbial risk assessment for P. aeruginosa was conducted to predict the probability of an eye infection for two potential exposure scenarios: (i) individuals using bacteria-contaminated eye drops and (ii) contact lens wearers washing their hands with bacteria-contaminated liquid soap prior to placing the lens. The median risk of an eye infection using contaminated eye drops and hand soap for both single and multiple exposure events (per day) ranged from 10-1 to 10-4, with contaminated eye drops having the greater risk. The concentration of P. aeruginosa was identified as the parameter contributing the greatest variance on eye infection risk; therefore, the prevalence and level of bacterial contamination of the product would have the greatest influence on health risk. Using eye drops in a single-use container or with preservatives can mitigate bacterial growth, and using non-refillable soap dispensers is recommended to reduce contamination of hand soap. Given the opportunistic nature of P. aeruginosa and its ability to thrive in unique environments, additional safeguards to mitigate bacterial growth and exposure are warranted.IMPORTANCEPseudomonas aeruginosa (P. aeruginosa) is a pathogen that can persist in a variety of unusual environments and continues to pose a significant risk for public health. This quantitative microbial risk assessment (QMRA) estimates the potential human health risks, specifically for eye infections, associated with exposure to P. aeruginosa in bacteria-contaminated artificial tear eye drops and hand soap. This study applies the risk assessment framework of QMRA to evaluate eye infection risks through both consumer products. The study examines the prevalence of this pathogen in eye drops and soap, as well as the critical need to implement measures that will mitigate bacterial exposure (e.g., single-use soap dispensers and eye drops with preservatives). Additionally, limitations and challenges are discussed, including the need to incorporate data regarding consumer practices, which may improve exposure assessments and health risk estimates.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Immediate Impact on Tear Osmolarity Following the Application of Different Ocular Lubricants in Patients Experiencing Moderate Dry Eye Symptoms.

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy. METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface's tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED. RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance. CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

Efficacy and Safety of Artificial Tears Containing Lipidure and Hypromellose for the Treatment of Moderate Dry Eye Disease in Contact Lens Wearers.

Background and Objectives: Dry eye disease (DED) affects 5-50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety of novel Respilac artificial tears containing lipidure and hypromellose (HPMC) with the widely used Nextal artificial tears, which are also HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers. Materials and Methods: In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED, and wearing CL were randomly assigned to the Respilac (n = 15) or Nextal group (n = 15). Patients self-administrated one drop of Respilac or Nextal in both eyes three times daily for 21 days. Changes in the endpoint (visual analogue scale (VAS) score for ocular tolerability, symptom assessment in dry eye (SANDE) score, non-invasive first break-up time (NIF-BUT) results, tear analysis value, meibography results, and CL tolerability results were assessed, comparing treatment groups and time-point evaluations. Adverse events (AEs) were also recorded and evaluated. Results: VAS scores decreased with time (p < 0.001) in both groups, showing no statistically significant difference among them (p = 0.13). Improvements were also detected from screening to end-of-treatment, which were indicated by the SANDE scores for severity and frequency (p < 0.001) and by tear analysis results (p < 0.001) with no observed difference between the Nextal and Respilac arms. NIF-BUT, meibography, and CL tolerability values were shown to be non-significantly affected by treatment and time. There were no AEs detected in this study cohort. Conclusions: Respilac was confirmed to be effective, safe, and well-tolerated. Lipidure-based ophthalmic solution was shown not to be inferior to the currently used Nextal, however, showing improvements in DED symptoms. Within the existing literature, our study is one of the first to report that MPC plus HPMC-containing eye drops are an effective option for the treatment of moderate dry eye disease and desiccation damage prevention in contact lens wearers.

The effect of combination therapy with intravitreal bevacizumab and topical timolol-dorzolamide eye drops on diabetic macular edema: a double-blind randomized controlled trial.

BACKGROUND: The mainstay of treatment in diabetic macular edema (DME) is intravitreal administration of anti-vascular endothelial growth factors (anti-VEGFs). Aqueous depressants may enhance the effects of anti-VEGF agents by prolonging their clearance via aqueous outflow. PURPOSE: To compare the anatomical and functional outcomes of treatment with intravitreal bevacizumab (IVB) and topical timolol-dorzolamide versus IVB alone. METHOD: In this randomized placebo-controlled clinical trial, patients with center-involving DME (ci-DME) and best corrected visual acuity (BCVA) of 20/30 or less were enrolled and randomly allocated to two treatment arms. One group received three monthly IVB injections and timolol-dorzolamide eye drops twice a day (IVB + TD group); the other group received three monthly IVB injections and artificial tear drops as placebo (IVB group). Patients underwent ophthalmic evaluations and macular optical coherence tomography scans at baseline and 1 month after the third injection. RESULT: Forty-six eyes from 46 patients with ci-DME were recruited. There was no intergroup difference regarding age, gender distribution, diabetic retinopathy stage, glycemic indices, BCVA, central macular thickness (CMT), or intraocular pressure at baseline. BCVA was significantly improved in the IVB + TD group (0.46 ± 0.18 to 0.36 ± 0.18 logarithm of the minimum angle of resolution [logMAR], p = 0.002), in contrast to IVB group (0.40 ± 0.17 to 0.35 ± 0.22 logMAR, p = 0.113). Similarly, the IVB + TD group showed a significant reduction in CMT (p < 0.001), unlike the IVB group (p = 0.086); and the CMT change in the former was greater than in the latter (- 0.57 ± 57.67 vs. - 25.52 ± 68.02 µm, p = 0.033). CONCLUSION: Our findings support the short-term effectiveness of topical timolol-dorzolamide as adjunctive therapy to IVB injections in managing center-involving DME in terms of anatomical and visual outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT05083689 (October 19, 2021).

Ocular surface changes following computer use in post-LASIK patients.

PURPOSE: To assess the impact of computer use on the ocular surface of individuals after laser in situ keratomileusis (LASIK). METHODS: The dry eye symptoms and ocular surface of 18 post-LASIK young individuals and 18 controls were evaluated before and after performing a 30-min task on a computer without (Visit 1) and with (Visit 2) initial instillation of artificial tears. Symptoms were assessed using the Ocular Surface Disease Index (OSDI), Symptom Assessment in Dry Eye questionnaire version two (SANDE II) and Computer Vision Syndrome Questionnaire (CVS-Q). The ocular surface was assessed by measuring corneal higher order aberrations, tear meniscus height (TMH), conjunctival redness, blink rate and incomplete blinking, lipid layer thickness (LLT) and non-invasive keratograph break-up time (NIKBUT). RESULTS: SANDE II scores were >0 after the computer task in both groups (p ≤ 0.01). SANDE II and CVS-Q scores did not differ between LASIK and controls (p ≥ 0.43). Greater bulbar-temporal conjunctival redness, TMH and LLT and shorter NIKBUT were found after computer use in the LASIK group (p ≤ 0.04), whereas no changes were observed in the controls (p ≥ 0.20). Lower SANDE II and CVS-Q scores were reported at Visit 2 compared with Visit 1 in both groups (p ≤ 0.01). Likewise, no worsening of dry eye signs was observed at Visit 2 (p ≥ 0.11). CONCLUSIONS: Ocular symptoms reported during computer use were comparable between the groups. However, a worsening of dry eye signs was mostly observed in post-LASIK individuals. The instillation of artificial tears was effective in preventing the effects of computer use on the ocular surface in post-LASIK patients.

In Vitro Evaluation of Soft Contact Lens Wettability With a Nonmodified Commercial Videokeratoscope.

PURPOSE: To evaluate a new in vitro technique for measuring soft contact lens wettability using a nonmodified commercial videokeratoscope, the Medmont E300. To this end, the capability of different artificial tears containing hyaluronic acid (HA) to improve soft contact lens wettability in vitro was investigated. METHODS: An experimental in vitro study was conducted to assess the wetting properties of three artificial tears containing different concentrations of HA (0.1%, 0.2%, and 0.3%) on soft contact lenses. A saline solution was used as the control. For each solution, 15 hydrogel (Ocufilcon D) contact lenses and 15 silicone-hydrogel (Somofilcon A) contact lenses were evaluated. The in vitro wettability of the lenses was measured using the Medmont E300 with a self-developed technique, which involved measuring the tear film surface quality (TFSQ) mean, TFSQ area, TFSQ central, and TFSQ inferior. RESULTS: Compared with the saline solution, all the concentration of HA (0.1%, 0.2%, and 0.3%) improved the in vitro wettability of both soft contact lenses by decreasing their TFSQ mean and TFSQ area ( P <0.05). Regression models revealed an exponential relationship between contact lens wettability and the concentration of HA for both soft contact lenses ( R >0.5, P <0.05). Furthermore, the hydrogel contact lens presented a wetter surface than the silicone-hydrogel contact lens ( P <0.05). CONCLUSIONS: The measurement of in vitro wettability of soft contact lenses with a nonmodified Medmont E300 seems to be a useful technique to evaluate the wetting properties of contact lens products.

Safety and efficacy of combined acupuncture (body and intradermal acupuncture) for dry eye disease: study protocol for a pilot, single-centre, assessor-blinded, randomised, artificial tear drop-controlled trial at Naju Dongshin University Korean Medicine Hospital.

INTRODUCTION: The prevalence of dry eye disease (DED) has been consistently increasing yearly. However, the radical therapy has not yet been established. This study is to confirm the superiority of acupuncture over artificial tear drops (ATDs) in patients with DED. METHODS AND ANALYSIS: This study is a single-centre, investigator-initiated, assessor-blinded, parallel randomised controlled trial. 30 participants will be enrolled. Over a period of 4 weeks, the experimental group would receive two kinds of acupuncture three times a week. First, body acupuncture would be performed on bilateral BL2, GB14, TE23, EX-HN5 and ST1 for 15 min. Thereafter, intradermal acupuncture would be performed on the same acupoints for 4 hours. On the other hand, the control group would apply the provided ATD at least four times a day. As a rescue medication for severe DED symptoms, both groups can additionally apply ATD. The frequency of ATD use would be recorded during the trial. The primary outcomes are the Ocular Surface Disease Index and tear film break-up time. The secondary outcomes are subjective symptom Visual Analogue Scale, quality of life, Schirmer I test, tear lactoferrin level, treatment satisfaction and safety. The outcomes would be mostly assessed at visits 1, 13 and 14. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of Naju Dongshin University Korean Medicine Hospital (Approval No. NJ-IRB-23-5). The obtained results will be disseminated through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: KCT0008563.

Review of clinical outcomes of a cationic emulsion tear substitute in patients with dry eye disease.

First-line options for the treatment of dry eye disease (DED) rely on artificial tears (ATs), among which cationic emulsion (CE)-based ATs have been developed in order to mimic the healthy tear film for an improved restoration of the ocular surface homeostasis. In this review, we describe the outcomes reported in several studies, assessing the mode of action, ocular tolerance and clinical performance of a CE-based AT. Pilot studies have revealed that CE-based ATs can increase the volume and stability of the tear film while limiting its evaporation rate. Larger studies have demonstrated that CE-based ATs play a significant role in the improvement of both objective and subjective DED parameters, including superior efficacy on DED symptoms compared to several other available AT formulation types. Concomitantly, CE-based ATs have been shown to help patients to prevent or recover from corneal defects associated with refractive surgery. These positive outcomes on ocular surface epithelia are likely due to the combination of unique rheological behaviour and intrinsic anti-inflammatory properties. Based on all clinical findings, CE-based ATs represent a valuable treatment option for patients with various etiologies of DED including evaporative forms and would deserve evaluation of benefits in other surgical intervention types triggering DED.