Eye Score Research Articles

Evaluation of the Performance of an Ocular Surface Modulator Containing ST-Lysyal Versus Hyaluronic Acid Eyedrops in Patients with Dry Eye Disease: A Pilot Study.

Dry eye disease (DED) is a multifactorial condition of the ocular surface, primarily treated with tear substitutes, which do not fully restore natural tear functions. In this pilot study, we tested the hypothesis that T-Lysyal (T-Lys) improves symptoms and signs in patients with DED. Additionally, we provide a literature overview on the effects of T-Lys in ophthalmology and non-ophthalmology conditions to elucidate its mechanisms of action. A double-masked, randomized pilot study was conducted in patients with DED treated with T-Lys or hyaluronic acid (HA) 0.2% combined with tamarind seeds polysaccharide (control group) for 2months. Inclusion criteria were a diagnosis of DED with symptoms lasting ≥ 6months, Symptom Assessment in Dry Eye (SANDE) score ≥ 30, and at least one of the following: fluorescein staining of the cornea (score ≥ 3, NEI scale), conjunctival staining (Lissamine Green, score ≥ 3), or tear breakup time (T-BUT) ≤ 10s. Data from the right eye were used for statistical analysis. A PubMed literature search of T-Lys studies was also performed without publication year restrictions. Twelve patients in the T-Lys group and 15 in the control group completed the study (mean age 67 ± 11years). T-Lys treatment resulted in significant improvements from baseline (V0) to 2months (V2) in symptoms assessed by visual analogue scale (T-Lys: 4.58 ± 2.57mm at V0, 2.92 ± 1.38mm at V2, p < 0.05; control: 5.13 ± 2.29mm at V0, 5.3 ± 2.4mm at V2), T-BUT (T-Lys: 2.58 ± 1.31s at V0, 3.58 ± 1.37s at V2, p < 0.05; control: 3.07 ± 1.43s at V0, 3 ± 1.13s at V2), and corneal staining (T-Lys: 2.16 ± 4.17 at V0, 1.41 ± 3.70 at V2, p < 0.05; control: 1.4 ± 2.19 at V0, 1.4 ± 2.16 at V2). No adverse events were reported. Literature findings supported T-Lys's efficacy in managing both ophthalmology and non-ophthalmology conditions. This study provides the first clinical evidence of T-Lys efficacy in patients with DED, supporting preclinical data and highlighting its potential as a promising ocular surface modulator. The study was registered in the ISRCTN registry for Clinical Studies with no. 13587929.

Hemostatic effect of 3D-printed hip fixators in children with retinoblastoma after intra-arterial chemotherapy: a non-randomized controlled trial

This study aimed to investigate the benefits of using three-dimensional (3D)-printed hip joint fixators after intra-arterial chemotherapy (IAC) by inguinal femoral artery puncture in children with retinoblastoma. Overall, 79 cases of retinoblastoma who had undergone IAC through the femoral artery were selected and divided into an observation group of 50 cases and an intervention group of 29 cases according to the hemostasis method employed. The patients in the observation group were treated with sandbags for hemostasis, while those in the intervention group were given 3D-printed hip joint fixators to help immobilize the hips and sandbags. We used the Face, Legs, Activity, Cry and Consolability scale (FLACC), the Wong–Baker Facial Expression Pain Scale, and self-made questionnaires to evaluate demographics, clinical characteristics, pain, complications, satisfaction, and other indicators of the two groups. There were no significant differences in general data, such as age, gender, height, weight, manual compression time, diseased eye, tumor stage, platelet count, puncture times, pain distribution, and total score, between the groups. There was a positive correlation between FLACC pain and the total Wong–Baker pain score (r = 0.599, p < 0.001). During the 2 h of sandbag compression, sandbags were dislodged in the observation group as many as ten times, which was significantly higher than that in the intervention group (up to four times; p < 0.001). This was correlated with a very high score of satisfaction (92.34 ± 19.96 out of 100). The 3D-printed hip fixator is easy to operate, has a low incidence of complications, and saves time and effort. It effectively reduces the incidence of sandbags falling off after IAC in children with retinoblastoma and does not increase the patient’s pain. It is a method that could improve hemostasis in young children undergoing IAC by inguinal femoral artery.

Comparative Analysis of Patient-reported Outcomes After Cranial Vault Remodeling and Strip Craniectomy With the FACE-Q Craniofacial Module.

The debate continues among craniofacial surgeons regarding the effectiveness of strip craniectomy (SC) compared with cranial vault remodeling (CVR) in achieving optimal functional and aesthetic outcomes in patients with single-suture craniosynostosis. This study aimed to compare long-term patient-reported outcomes (PROs) between SC and CVR procedures at a single institution using the validated FACE-Q Craniofacial module. Patients older than or equal to 8 years of age and parents of patients younger than 8 years of age who underwent SC or CVR for single-suture craniosynostosis were eligible. Patients with <2 years of follow-up, lambdoid synostosis, and syndromes were excluded. Primary endpoints were PROs as measured by the FACE-Q, with higher scores indicating increased health-related quality of life. Linear regression was used to control for covariates. Sixty-two participants completed the module (response rate 33.3%). SC was performed in 29 patients (46.8%), and CVR in 33 patients (53.2%). On unadjusted bivariate analysis, SC patients had higher eye (P=0.03) and forehead (P=0.05) scores. On regression analysis, controlling for sex, race, craniosynostosis type, and follow-up, there were no significant differences between operation types in any domain. Metopic and sagittal synostosis were associated with higher Eye (metopic: 17.61, P=0.049; sagittal: 41.44, P<0.001) and Head scores (metopic: 48.12, P=0.001; sagittal: 49.35, P<0.001), and sagittal synostosis was associated with higher Face (38.16, P<0.001), Forehead (55.93, P<0.001), and Nose scores (19.28, P=0.003). From patients' and parents' perspectives at a single institution, SC and CVR were equivalent regarding aesthetics and health-related quality of life.

Quality of life of Retinoblastoma survivors in tertiary care eye hospital in South India.

With the increased survival of retinoblastoma (RB) patients, it is important to evaluate the quality of life (QoL) of RB survivors as well as caregivers to provide comprehensive care to the children and caregivers. This study aims to assess the QoL of survivors of RB, as perceived by parents and the self-report by patients, through a pediatric QoL (PEDs-QoL) questionnaire. The study cohort included 86 RB survivors, 86 age-matched controls, and their primary carers. PedsQL 4.0 generic core scale and structured interview were administered. QoL in physical, social, emotional, and school health was evaluated and correlated with clinical and sociodemographic parameters. The mean age of the RB survivors was 5.7 years with an M:F ratio of 1.1:1. Disease was bilateral in 79% of cases. About 45% (39/86) underwent enucleation, while others received combination therapy (16; 18%), chemotherapy (30; 34%), and radiation (1; 1%). As reported by parents, the QoL of physical health domain of RB survivors was 70.2 SD ± 27.8 and 96.15 ± 13 SD, emotional health was 72.1 ± 27.4 SD and 94.4 ± 12.5 SD, social health was 80.4 ± 24.9 SD and 98.6 ± 6.2 SD; and school health was 71.9 ± 2 6.5 SD and 96.1 ± 12.2 SD. As per the self-report perception, the QoL of physical health was 68.2 ± 27.8 SD and 96.2 ± 13 SD, emotional health was 66.2 ± 28.4 SD and 95.3 ± 12.5 SD, social health was 69.5 ± 24.9 SD and 98.7 ± 6.2 SD, and school health was 63.5 ± 26.5 SD and 95.1 ± 12.2 SD. There was a significant relationship between enucleation and QoL domains, where χ2 = 67.75, degrees of freedom (df) = 36, and P < 0.01. There was a significant association between vision in the better eye (6/18 or better = 8, 6/18-6/60 = 8, 3/60 or worse = 42) and QoL scores (χ2 = 95.36, df = 62, P < 0.01). There was a substantial association between socioeconomic status and QoL domains, where χ2= 88.5, df = 56, P < 0.01. The results of the study showed that the QoL of parents of RB survivors and self-proxy reports were negatively affected in many ways, including physical, social, emotional, and school-related dimensions. Despite the small differences, self-proxy reports indicated a lower QoL than the parents' group. The study findings indicate that there are notable correlations between enucleation and visual acuity less than 6/18, as well as socioeconomic status, with various aspects of QoL domains among individuals who have survived RB.

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

BackgroundTo 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.MethodsIn 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.ResultsA 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.ConclusionsBoth 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.

Corneal hypersensitivity to cold stimuli in symptomatic computer users.

Prolonged computer use may result in repeated stimulation of the ocular surface due to ocular dryness, potentially leading to alterations in its sensitivity. This study aimed to evaluate the relationship between ocular symptoms and corneal sensitivity to cold and mechanical stimuli in computer users. Fifty-two young (31 ± 6 years), frequent computer users, including symptomatic and asymptomatic users, participated in this study. Mechanical and cold sensation thresholds were determined at the central cornea of one randomly selected eye of each participant using the UNSW Liquid Jet Aesthesiometer. Ocular surface symptoms and digital eye strain were assessed using the Ocular Surface Disease Index, Ocular Comfort Index, Instant Ocular Symptom Survey, and Computer Vision Syndrome Questionnaire (CVS-Q). Associations between central corneal sensation thresholds and demographic variables, patterns of digital device use, and symptom scores were analyzed using Pearson (r) or Spearman (ρ) correlations and linear regression models. Age (ρ = 0.24), CVS-Q score (ρ = -0.33), CVS-Q dry eye score (ρ = -0.28), and mechanical sensation threshold (ρ = 0.63) were significantly associated with cold sensation threshold (p≤0.04). Conversely, there were no significant relationships with Ocular Surface Disease Index, Ocular Comfort Index, or Instant Ocular Symptom Survey or with other demographic variables (p≥0.34). In multiple linear regression models, age and mechanical sensation threshold were significant predictors of cold sensitivity (p=0.04 and p<0.001, respectively) (adjusted R2 = 0.459). There were no significant correlations between mechanical sensitivity and symptom scores (p≥0.09). Symptoms of digital eye strain, particularly those related to dry eye, were associated with higher corneal cold sensitivity. Corneal hypersensitivity to cold stimuli as a marker of ocular discomfort during computer use requires further investigation.

Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease.

Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German-Austrian-Swiss Consensus (GAS) Grading were analyzed. Systemic GVHD manifestations as well as the prevalence of topical and systemic (immunomodulatory) therapies were assessed. Results: A total of 74 of 95 patients (77.8%) had manifestations of systemic chronic graft-versus-host disease other than ocular GVHD. 68.42% (65/95) of patients were under systemic immunosuppressive therapy with at least one immunosuppressive medication. All patients (95/95) received lid-margin hygiene and phosphate- and preservative-free lubricating eye drops. Twenty-five percent of the cohort (24/95) were treated with autologous serum eye drops (ASEDs). In total, 80% (76/95) of patients required topical steroid therapy to treat acute exacerbation of inflammation at least once; continuous topical steroid therapy was only necessary for a minor part (12%) with refractory chronic inflammation. A total of 92.63% (88/95) were primarily treated with ciclosporin A 0.1% as Ikervis®, of whom at least one third did not continue the therapy because of intolerable side effects during follow-up and received alternative topical formulations. Conclusions: Our data show that patients with ocular cGVHD mostly need topical therapy including anti-inflammatory agents despite systemic immunosuppressive therapy. In our cohort, 80% of patients received topical steroids, and more than 90% received topical ciclosporin A eye drops, which were tolerated by only two thirds of patients due to side effects.

Replacing Inorganic Source of Zinc with Zinc Hydroxy Chloride: Effects on Health Status, Hemato-biochemical Attributes, Antioxidant Status, and Immune Responses in Pre-ruminant Crossbred Calves.

The current research aimed to assess the feasibility of using Zn hydroxy chloride (ZnOHCl) as an alternative to ZnSO4 in pre-ruminant crossbred calves. Twenty-four male crossbred calves (Tharparkar × Holstein Friesian) were categorized into four groups according to body weight and age (body weight 31kg; age 10days). Experimental calves were kept on a similar feeding regimen except that different groups were supplemented with either 0mg Zn/kg DMI (Zn-0), 80mg Zn/kg DMI as ZnSO4 (ZnS-80), 40mg Zn/kg DMI as ZnOHCl (ZnH-40), or 80mg Zn/kg DMI as ZnOHCl (ZnH-80). All the calves were fed for 90days as per ICAR (2013) feeding standard to fulfill their nutrient requirements for growth rate of500g/day. The study observed the influence of different sources and varying levels of Zn supplementation over a 90-day experimental period on health status, hemato-biochemical attributes, antioxidant status, immune responses, and plasma minerals and erythrocyte Zn concentrations. The data was examined using a randomized complete block design (RCBD) with fixed effects of treatment, period, and their interaction. The results indicated that irrespective of the sources and levels of Zn, supplementation did not lead to significant changes in health status as assessed by fecal score, nasal score, ear score, and eye score. Hematological parameters remained unchanged following supplementation with different sources and levels of Zn. Zn-supplemented groups showed higher levels of total protein, globulin, and alkaline phosphates (ALP) compared to the non-supplemented group. However, no significant variations were detected within the Zn-supplemented groups. Zinc supplementation significantly increased total antioxidant capacity (TAC), antioxidant enzyme activity, total immunoglobulin (Ig), immunoglobulin G (IgG), cell-mediated immunity (CMI), and humoral immunity (HI); however, no significant variations were detected among Zn-supplemented groups. Zn supplementation enhanced plasma and RBC Zn concentration without affecting the plasma concentration of other minerals. However, among the Zn-supplemented groups, 80mg Zn/kg DMI as ZnOHCl resulted in the highest RBC Zn concentration. The study results demonstrate that Zn supplementation enhanced biomarkers of zinc status, antioxidant levels, and immune responses in pre-ruminant crossbred calves. Nevertheless, no significant variations were observed between the different Zn sources (ZnSO4 and ZnOHCl) utilized in this study. Research suggests that ZnOHCl could be a feasible alternative to ZnSO4 in the diet of pre-ruminant crossbred calves.

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDEand unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.

Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial

BackgroundDry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy.MethodsThis was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren’s DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance.ResultsAt week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; −1.47 to 3.32, P = 0.078; b.i.d.: 2.31; −0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P < 0.025) observed in the b.i.d. group. Only cenegermin t.i.d. yielded statistically significant (P < 0.025) reductions in SANDE scores versus vehicle, which were sustained up to the end of follow-up (P value range, 0.002–0.008). Eye pain, primarily mild and transient, was the most frequently observed treatment-emergent adverse event with cenegermin. Similar results were observed in patients with Sjögren’s DED.ConclusionsCenegermin was well tolerated and although this study did not meet its primary endpoint, significant improvement in patient-reported symptoms of dry eye was observed through follow-up. Larger studies evaluating cenegermin in patients with DED are warranted.Trial registrationNCT03982368; registered May 23, 2019.

REM sleep breathing: Insights beyond conventional respiratory metrics.

Breathing and sleep state are tightly linked. The traditional approach to evaluation of breathing in rapid eye movement sleep has been to focus on apneas and hypopneas, and associated hypoxia or hypercapnia. However, rapid eye movement sleep breathing offers novel insights into sleep physiology and pathology, secondary to complex interactions of rapid eye movement state and cardiorespiratory biology. In this review, morphological analysis of clinical polysomnogram data to assess respiratory patterns and associations across a range of health and disease is presented. There are several relatively unique insights that may be evident by assessment of breathing during rapid eye movement sleep. These include the original discovery of rapid eye movement sleep and scoring of neonatal sleep, control of breathing in rapid eye movement sleep, rapid eye movement sleep homeostasis, sleep apnea endotyping and pharmacotherapy, rapid eye movement sleep stability, non-electroencephalogram sleep staging, influences on cataplexy, mimics of rapid eye movement behaviour disorder, a reflection of autonomic health, and insights into cardiac arrhythmogenesis. In summary, there is rich clinically actionable information beyond sleep apnea encoded in the respiratory patterns of rapid eye movement sleep.

Comparing the effectiveness of oral montelukast versus cetirizine in the management of allergic rhino-conjunctivitis and its effect on quality of life among children: A randomized, double-blind clinical trial

Background: Allergic rhino-conjunctivitis (AR) is a common disorder in children, which causes significant morbidity and impact on learning and day-to-day activities. Objectives: To compare effectiveness of montelukast versus cetirizine in AR and its effect on the quality of life (QoL) among children aged 6-12 years, attending Asthma Clinic, Faculty of Medicine, University of Ruhuna, Sri Lanka. Method: This was a randomized, double-blind, parallel-group trial; 'Group A' was given montelukast with a cetirizine dummy; 'Group B' was given cetirizine with a montelukast dummy. Primary endpoint was to compare improvement of nasal, eye and night symptom scores. Secondary endpoint was to compare the QoL between the groups. Total symptoms were assessed at baseline, one month, two months and three months. Results: There were 176 children (62.5% boys) with a mean age of 8.82 ± 1.79 years. Fifteen children were lost to follow-up, 7 from the montelukast and 8 from the cetirizine group. There was a significant reduction in all symptoms (p&lt;0.05) every month in both treatment groups. Whilst montelukast group had more improved day and night symptom scores than cetirizine group, statistically significant improvement was seen only in the 3rd month (t-4.10 p &lt;0.001). Mean QoL score showed no significant difference between the two groups at onset (montelukast 9.01±9.4 and cetirizine 15.9 ± 10.4; t-0.369; p=0.712). Both groups showed a statistically significant improvement in all domains of QoL by completion of treatment (p&lt;0.05). Upon completion, the montelukast group showed a significantly better QoL than the cetirizine group. Conclusions: Both cetirizine and montelukast showed remarkable improvement in the symptoms and better QoL in children. Study outcomes in all clinical domains and QoL were more significantly improved in montelukast group than in cetirizine group when treatment was continued for 3 months.

The protective effect of vitamin A palmitate eye gel on the ocular surface during general anaesthesia surgery: a randomized controlled trial

PurposeTo investigate the change in tear production associated with general anesthesia and the protective effect of vitamin A palmitate eye gel on the ocular surface during general anesthesia.MethodsThis double-blind, randomized clinical trial included patients undergoing non-ophthalmic surgery under general anesthesia who randomly received vitamin A palmitate eye gel and taping for one eye (Group A, n = 60) or taping alone for the other eye (Group B, n = 60). Symptom assessment in dry eye (SANDE) score, tear film break-up time (TBUT), corneal fluorescein staining (CFS) score, and Schirmer tear test I (STT-1) were analyzed under a hand-held slit lamp before anesthesia (T0), 0.5 h postoperatively (T1), and 24 h postoperatively (T2).ResultsAt 0.5 h postoperatively, an increase in CFS score was observed in both groups (P < 0.05 in Group A and P < 0.01 in Group B), and the participants in Group A had less corneal abrasions than those in Group B. STT-1 significantly increased in Group A (P < 0.05), while it significantly decreased in Group B (P < 0.001). The changes between the two groups were statistically significant (P < 0.001). At 24 h postoperatively, both CFS score and STT-1 almost returned to baseline levels in the two groups. In both groups, the SANDE score and TBUT showed little change at 0.5 h and 24 h postoperatively (all P > 0.05).ConclusionVitamin A palmitate eye gel effectively protected the ocular surface and aqueous supplementation during general anesthesia.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2100052140) on 20/10/2021.

Frequency of dry eye syndrome in patients with multiple sclerosis: A cross-sectional case-control study

Introduction: Demyelination of the nerve fibers of the central nervous system is a main pathology of multiple sclerosis (MS), in which inflammation plays a major role. Studies have shown that inflammation is the leading cause of dry eye disorder. To investigate the association between inflammation and both diseases, we aimed to estimate the prevalence of dry eye syndrome (DES) in MS patients and its correlation with the severity of the disease and disability status. Methods: We enrolled 100 MS patients randomly and 100 healthy controls. DES was evaluated by Dry Eye questionnaire and Scoring System (DESS), tear break-up time (TBUT), tear meniscus height (TMH), and Schirmer 1 &amp; 2 tests in subjects. Furthermore, the leading disability in MS was assessed by a clinician (neurology professor) using the related questionnaire (Expanded Disability Status Scale). Results: According to the TBUT, THM, and Schirmer tests, the number of subjects with abnormal results was significantly higher in the MS group than in the control group. The severity of DES measured by the DESS was also higher in the MS group compared to control group. Also, there was a significant relationship between increasing disability and abnormal dry eye tests, especially in MS patients with EDSS scores&gt;4. Conclusion: The present study highlights the importance of considering dry eye disorder in MS patients as a possible consequence of inflammation. Also, our results suggested a significant relationship between dry eye disorder and the EDSS scores.

Diamond Bur Microblepharoexfoliation Combined with Intense Pulse Light and Meibomian Gland Expression for Evaporative Dry Eye: A Short-term Controlled Clinical Trial.

To assess the efficacy and safety of the combination of microblepharoexfoliation (MBE), intense pulse light (IPL) and meibomian gland expression (MGX) for treatment of meibomian gland dysfunction (MGD). This was a prospective, parallel-control trial conducted from April 2022 to January 2023. Participants were assigned to receive either three sessions of MBE-IPL-MGX treatment and home-based therapy (treatment group) or home-based therapy alone (control group). Outcome measures were assessed at baseline and after 2-month follow-up. Seventy eyes of 70 patients were enrolled. MBE-IPL-MGX treatment achieved better improvements than home-based therapy in ocular surface disease index (OSDI) and symptom assessment in dry eye (SANDE) scores, noninvasive tear film break-up time (NIBUT), lipid layer grade (LLG), loss area meibomian gland (LAMG) and meibomian gland yielding secretion score (MGYSS). The mean differences between the two groups were as follows: OSDI (- 11.23 ± 4.68 points, P < 0.001), SANDE (- 24.63 ± 13.41 points, P < 0.001), NIBUT (1.3 ± 1.57s, P = 0.033), LLG (0.4 ± 0.04 points, P = 0.003), LAMG (- 2.85 ± 1.69%, P = 0.023) and MGYSS (7.5 ± 2.32 points, P < 0.001). In addition, the increment (Δ) of MGYSS after MBE-IPL-MGX treatment was significantly higher in MGD grades 2 and 3 (all P < 0.001). MBE-IPL-MGX treatment is an effective and well-tolerated procedure that improves dry eye symptoms and signs as well as meibomian gland secretions in patients with MGD. In addition, this treatment is recommended for MGD grades 2 and 3.

Evaluation of differences in quality of life in patients with chronic graft-versus-host disease

Objective: To evaluate the status of, differences in, and factors influencing quality of life (QoL) in patients with chronic graft-versus-host disease (GVHD). Methods: From September 2021 to February 2023, a cross-sectional study of 140 patients with chronic GVHD was conducted at our center. Symptom burden was assessed by the Lee Symptomatology Scale (LSS), and QoL was assessed by the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36) (version 1) and five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L). Results: Data from 140 respondents, including 32 (22.9%) with mild chronic GVHD, 87 (62.1%) with moderate chronic GVHD, and 21 (15.0%) with severe chronic GVHD, were analyzed. Of the respondents, 61.4% were male, and the median transplantation age was 34 (15-68) years. The primary diagnoses were acute myeloid leukemia (50.0%), acute lymphoblastic leukemia (20.0%), and myelodysplastic syndrome (15.0%). The common chronic GVHD-affected organs included the skin in 74 patients (52.9%), the eyes in 57 patients (40.7%), and the liver in 50 patients (35.7%). Among the whole cohort, the eye (20.48±23.75), psychological (16.13±17.00), and oral (13.66±20.55) scores were highest in the LSS group. The physiological function (36.07±11.13), social function (36.10±10.68), and role-emotional functioning (38.36±11.88) scores were lowest in the SF-36 group. The EQ-5D index was 0.764. The total LSS scores for mild, moderate, and severe chronic GVHD were 6.51±6.15, 10.07±5.61, and 20.90±10.09, respectively. The SF-36 physical component scores (PCSs) were 43.12±6.38, 40.73±7.14, and 36.97±6.97, respectively, and the mental component scores (MCSs) were 43.00±8.47, 38.90±9.52, and 28.96±9.63, respectively. The EQ-5D values were 0.810±0.124, 0.762±0.179, and 0.702±0.198, respectively. The multivariate analysis showed that the overall symptom burden (β=-0.517), oral symptom burden (β=-0.456), National Institute of Health (NIH) criteria for the eyes (β=-0.376), and nutrition-related symptom burden (β=-0.211) were significantly negatively correlated with the PCS. The NIH score (β=-0.260) was negatively correlated with the MCS score. Oral symptom burden (β=-0.400), joint/fascia NIH criteria (β=-0.332), number of involved systems (β=-0.253), overall NIH criteria (β=-0.205), and number of immunosuppressants taken (β=-0.171) were significantly negatively correlated with the EQ-5D score (all P<0.05). Medium to strong correlations were found between the EQ-5D score and the SF-36 score (|r|=0.384-0.571, P<0.001). Conclusions: The QoL of patients with chronic GVHD is impaired, and the more severe the disease, the poorer the QoL. Overall symptom burden, severity of eyes, and oral symptom burden were the most important factors affecting QoL.

Usefulness of the Simple Coma Scale, a Simplified Version of the Glasgow Coma Scale.

The Glasgow Coma Scale (GCS) is the most commonly used consciousness rating scale worldwide. Although it is a sensitive and accurate way of assessing a patient's level of consciousness, it is time-consuming and requires training. We designed the Simple Coma Scale (SCS) as a simplified version of the GCS. In this study, we examined whether the SCS could predict favorable neurogenic outcomes at discharge, survival, and GCS scores in patients with traumatic brain injury (TBI). We analyzed the data of 1,230 patients registered in the Japan Neurotrauma Data Bank (Project 2015) between April 2015 and March 2017. In the SCS, eye, verbal, and motor scores are given based on a 3-point scoring system, with similar wording ("Normal," "Something Wrong," and "None") used for all scores. The SCS is based on a 7-point scale. The Glasgow Outcome Scale was used to assess the outcomes. For the receiver operating characteristic (ROC) curves with the objective variable of good prognosis at discharge in the SCS and GCS, the area under the curve (AUC) for the SCS was 0.740 (95% confidence interval [CI]: 0.711-0.769), and that of the GCS was 0.757 (95% CI: 0.729-0.786). For ROC curves with survival as the objective variable, the AUC of the SCS was 0.751 (95% CI: 0.724-0.778), and that of the GCS was 0.764 (95% CI: 0.737-0.791). The SCS, similar to the GCS, may predict good prognosis and survival at discharge. Further analyses will continue to examine the usefulness and practicality of the SCS.

A Novel Scoring System for Humane Endpoints in Mice with Cecal Ligation and Puncture-Induced Sepsis.

Animal-based research is essential to the study of sepsis pathophysiology, diagnostics, and therapeutics. However, animal models of sepsis are often associated with high mortality because of the difficulty in predicting imminent death based on premortem assessment of the animals. The use of validated visual scoring would allow researchers to systematically identify humane endpoints but visual approaches require high interobserver agreement for accurate results. The objective of this study was to establish a scoring system for mice undergoing cecal ligation and puncture (CLP)-induced sepsis based on 3 visual parameters: respiratory status, activity and response to stimulus (ASR), and eye appearance, with scores ranging from 0 to 3. In the first study, we evaluated interobserver agreement. Veterinary and investigative staff assessed 283 mice with CLP and had substantial to near-perfect agreement for all 3 parameters as evaluated using weighted Cohen κ statistic. The second study assessed the ability of the scoring system and temperature to predict death. The scoring system and subcutaneous transpond- ers were used to monitor C57BL/6J mice (n = 80, male and female) until death or for 7 days after CLP. Results showed that the scoring system discriminates between surviving (n = 26) and nonsurviving (n = 54) septic mice. The scoring system was accurate in predicting death, with an AUC of 0.8997. The sensitivity and specificity of the ASR parameter were 96% and 92%, respectively, and for the eye parameter were 94% and 73%. A sum of the ASR and eye scores that was 5 or more was also predictive of death. Temperature was a quantitative predictor, with sensitivity and specificity of 93% and 92%, respectively. This scoring system refines the CLP model by allowing identification of humane endpoints and avoidance of spontaneous death.

A Novel Dual Kinase Inhibitor for the Treatment of Chronic Graft Vs. Host Disease

Chronic Graft vs. Host Disease (cGvHD) remains a major debilitating and potentially fatal sequelae of allogeneic hematopoietic cell transplantation. Corticosteroids remain the initial therapy of clinically significant cGvHD. Since 2017 three targeted therapies have been approved for steroid refractory cGVHD, ruxolitinib, a JAK 1/2 inhibitor, is approved post one or two previous therapies. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and belumosudil, a ROCK2 inhibitor, are both approved after two previous lines of therapy. We tested RR- RR-1752 a single digit nM dual ROCK/AURK inhibitor in a mouse model of severe cGVHD. BALB/c recipient mice were preconditioned with 7.5 Gy TBI, 8 hours later they received 10 7 T-cell depleted (TCD) C57BL/6 bone marrow cells alone (Group A, n=7) or 10 7 TCD C57Bl bone marrow cells plus 10 6 splenocytes (Groups B, n=8 and C, n=8). Beginning day 7 post cell infusion animals received either oral vehicle control (groups A and B) or vehicle with 1.0 mg/kg RR-1752 (Group C) daily. Body weight, alopecia score and eye score were monitored 3×/week through day 56 or until termination. All animals in groups B and C developed signs and symptoms of chronic graft vs. host disease. Animals in group A exhibited 20% weight loss through seven days post irradiation and cell infusion but began to recover to baseline and recovered weight to 90% of baseline. Animal weights in groups B and C dropped to less than 80% at day seven post irradiation, but only recovered to 80.38% +/- 10.18 (Group B) and 87.11% +/- 7.90 (Group C) on day 14 and then declined to 74.10% +/- 4.19 in Group B and 80.23% +/- 7.35 in Group C by day 28 (Figure 1). Animals in Group A had no significant change in eye score or alopecia. In contrast all animals in groups B and C showed signs of cGvHD. Eye showed moderate effects in Group B and mild changes in group C, while alopecia scores were moderate in both groups B and C. All animals in group A survived through day 56, median survival in group B was 16.5 days, as compared to 38 days in group C (Figure 2). In a separate study in normal mice, RR-1752 given at 1.0 mg/kg/day for 2 weeks showed no negative effects on hemoglobin, hematocrit, platelets, total WBC, or neutrophils, and only a mild decrease in lymphocytes. Using a model for cGVHD, exhibiting weight loss, alopecia, and ocular changes, we demonstrated that RR-1752 1.0 mg/kg/day slows mouse body weight loss, increases survival and shows trends to ameliorate ocular toxicity. The dose tested did not ameliorate the alopecia in the cGVHD mice. Further studies are ongoing to assess higher dose levels and dose schedule effects in the severe cGVHD mouse model. Additional studies to compare effects on cGVHD to ruxolitinib and belumosudil and in combination with those standard of care therapies need to be conducted.

Efficacy and Safety of Processed Amniotic Fluid (pAF) Drops for the Treatment of Ocular Chronic Graft-Versus-Host Disease

Background: Ocular graft-versus-host disease (GVHD) affects more than 50% of patients with chronic GVHD and can lead to debilitating dry or painful eyes, impaired activities of daily living and poor quality of life. Management is mainly supportive, through control of surface inflammation, lubrication, and control of drainage and evaporation. Amniotic fluid (AF) is a rich source of nutrients, cytokines, and growth factors that has antimicrobial and immunomodulatory activities and may have reparative and regenerative roles in human disease. Investigators at the University of Utah developed protocols to collect AF from full-term pregnant women, process and sterile filter AF to separate cytokines and growth factors from residual cells and debris contained in the no-cellular fraction of AF, and treat patients with different conditions. We report the treatment effects and safety of processed AF (pAF) for the treatment of ocular GVHD. Methods: In this randomized, double-blinded, placebo-controlled phase II trial (NCT# 03298815), patients age ≥ 18 years diagnosed within 5 years after allogeneic hematopoietic transplant with ocular GVHD causing dry eye symptoms requiring lubricant drops &amp;gt;3x/day, punctal plugs, thermally cauterized puncta or special eyewear to relieve pain; or inability to work because of ocular symptoms; or loss of vision due to keratoconjunctivitis sicca were enrolled. Patients with any other chronic GVHD treated with &amp;gt;3 lines of therapy beyond corticosteroids with or without calcineurin inhibitors or sirolimus; or had a difference in dryness between both eyes of &amp;gt;2 points by the International Dry Eye WorkShop (DEWS) 2007 report; or were not willing to discontinue the use of medicated lubricant eye drops prior to randomization were excluded. Randomization was performed within participants, with one eye receiving one drop of pAF and the other eye saline treatment (placebo) twice daily for 30 days. In patients wearing scleral lenses, the eye drops were applied prior to lens insertion in the morning and after removal at night. Patients were allowed to resume their medicated eye drops after the 30-day treatment period. The primary objectives were to determine the day 30 overall response (complete and partial response) and safety of pAF. Response type to treatment is defined in Table 1. Key secondary objectives included longitudinal changes in visual acuity and the corneal surface, and patient-reported outcomes. Results: All fifteen patients' eyes were randomized to either pAF or saline treatment. The median age was 61 years (range, 35-72). At enrollment, six patients wore scleral lenses. The median baseline FACT-G score was 88 (range, 58-104). Baseline eye characteristics by treatment are shown in Table 2. Baseline NIH CC eye scores were similar between pAF and saline-treated eyes. The saline-treated group had more eyes with DEWS score 3 (n=7) compared to the pAF group (n=2). All 15 patients completed treatment. The overall response at day 30 in the pAF and saline-treated groups was 25% and 50%, respectively, p=0.38. All responding eyes had a partial response. No treatment-related serious ocular adverse events were observed. Two minor events occurred in the pAF treated eye group, including a change in eyelid position (n=1) and stinging after study drop application (n=1). There was no significant change in visual acuity and corneal surface staining between treatment groups at 30, 60, and 100 days. There was no significant change in the FACT-G score at 30, 60, and 100 days, and there was no significant difference in patient reported eye pain between pAF vs. saline-treated eyes over time (p=0.21). Conclusion: In this study, the primary endpoint of safety was met as there were few adverse events. One quarter of pAF-treated eyes responded. These findings justify evaluating pAF for ocular GVHD in a larger study. Limitations of this study included restricting patients to pAF application to twice a day and the study design of randomizing eyes within each subject as several patients had mild asymmetric disease between the two eyes. Other challenges included having delayed ocular assessments and/or altered perceptions of quality of life due to the COVID19 pandemic.