Influencing factors of self-management ability among dry eye patients in west China.

AIM: To investigate the current situation and influencing factors of self-management ability in dry eye patients in west China. METHODS: A total of 265 patients clinically diagnosed with dry eye received a convenience survey questionnaire at West China Hospital of Sichuan University. All participants completed the rating scale of health self-management skill for adults (AHSMSRS), Huaxi Emotional-Distress Index (HEI), e-health literacy scale (e-HEALS) and Brief Illness Perception Questionnaire (Brief-IPQ). A generalized linear model was employed to establish a multivariate linear model with demographic data, psychological state, e-HEALS, and illness perception as independent variables and health self-management skill score as the dependent variable. RESULTS: The mean score for health self-management skill was 165.58±15.79. Multivariate analysis revealed that advanced age, better illness perception and improved psychological state were associated with better health self-management ability among dry eye patients. Furthermore, the health self-management ability of patients with a disease duration less than 1y was found to be higher compared to those with a disease duration exceeding 1y. CONCLUSION: The health self-management ability of dry eye patients in west China is relatively high. Age, duration of disease, illness perception and psychological state are the influencing factors on the health self-management ability of dry eye patients.

Psychometric validation of the Chinese version of the dry eye-related quality-of-life score questionnaire.

AIM: To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire (DEQS-CHN) among Chinese patients with dry eye. METHODS: This study involved 231 participants, including 191 with dry eye disease (DED) comprising the dry eye disease group, and 40 healthy participants forming the control group. Participants were required to complete the DEQS-CHN, and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I test. To assess the internal consistency and retest reliability, Cronbach's α and the intraclass correlation coefficient (ICC) were employed. Content validity was assessed by item-level content validity index (ICV) and an average scale-level content validity index (S-CVI/Ave). Construct validity was assessed by confirmatory factor analysis. The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire. Discriminative validity was evaluated through non-parametric tests, with receiver operating characteristic (ROC) curve serving as conclusive indicators of the questionnaire's distinguishing capability. RESULTS: The Cronbach's α coefficients for frequency and degree of ocular symptoms, impact on daily life, and summary score were 0.736, 0.704, 0.811, 0.818, 0.861, and 0.860, respectively, and the ICC were 0.611, 0.677, 0.715, 0.769, 0.711, and 0.779, respectively. All I-CVI scores ranged from 0.833 to 1.000, with an S-CVI/Ave of 0.956. Confirmatory factor analysis results exhibited a well-fitting model consistent with the original questionnaire [χ 2/df=2.653, incremental fit index (IFI)=0.924, comparative fit index (CFI)=0.924, Tucker-Lewis index (TLI)=0.909, and root mean square error of approximation (RMSEA)=0.065]. There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire (r 2=0.588). The dry eye group demonstrated significantly higher scores compared to the control group, and the area under the curve (AUC) value was 0.8092. CONCLUSION: The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.

Short-term effects of ophthalmic topical 0.01% atropine on the ocular surface, pupil size, and subsequent subjective quality of vision in young myopic Chinese adults.

Background: Daily use of low concentrations of atropine is recommended for children undergoing myopia control therapy. While the benefits of controlling myopia progression have been confirmed, the potential unwanted side effects on the ocular surface, pupil size, and quality of vision following the administration of 0.01% atropine have not been investigated. Objective: This single-arm, self-control study aimed to investigate the short-term effects of 0.01% atropine topical eye drop (He Eye Hospital Co., Ltd., Shenyang, China) on pupil size and subjective quality of vision in participants with myopia. Each 3 mL vial of eye drops contains atropine (0.01%), sodium chloride (0.9%), and benzalkonium chloride (0.005%) in an aqueous solution. Methods: Thirty-three adults (66 eyes) were recruited for the study. The mean age of the participants recruited for this study was 24.91 ± 3.36 years. This study is registered with Clinical Trials.gov (NCT06071260). Assessments were performed at baseline and 10 h, 14 h, and 18 h following the administration of 0.01% topical atropine drop (TAD). Mesopic pupil diameter (MPD), photopic pupil diameter (PPD), higher order aberration (HOA), non-invasive tear breakup time (NITBUT), tear meniscus height (TMH), tear film lipid layer (TFLL), and Redness score (RS). Subjective assessments included the quality of vision (QoV) and the ocular surface disease index (OSDI) questionnaires. Results: Following the use of 0.01% atropine, PPD significantly increased at all the time points (p < 0.001); MPD increased significantly at 10 h and 14 h (p < 0.001 and p < 0.05, respectively). A decrease in TMH and an increase in the OSDI questionnaire scores were observed up to 10 and 14 h, respectively, after using atropine (p < 0.001). Glare (p = 0.004 at 10 h and p = 0.003 at 14 h), blurred vision (p < 0.0001 at 10 h and p = 0.035 at 14 h), and focusing difficulties (p < 0.0001 at 10 h and p < 0.0001 at 14 h) were significantly higher at both 10 h and 14 h after using atropine. No significant changes were observed in the HOA, NITBUT, and RS scores (all p > 0.05) at all time points. Conclusion: Decreased TMH, dry eye symptoms, and visual symptoms will likely persist overnight but often diminish within 18 h after using 0.01% atropine eye drops.

Changes in conjunctival mononuclear phagocytes and suppressive activity of regulatory macrophages in desiccation induced dry eye.

PURPOSE: To evaluate the effects of dry eye on conjunctival immune cell number and transcriptional profiles with attention to mononuclear phagocytes. METHODS: Expression profiling was performed by single-cell RNA sequencing on sorted conjunctival immune cells from non-stressed and C57BL/6 mice subjected to desiccating stress (DS). Monocle 3 modeled cell trajectory, scATAC-seq assessed chromatin accessibility and IPA identified canonical pathways. Inflammation and goblet cells were measured after depletion of MRC1+ MΦs with mannosylated clodronate liposomes. RESULTS: Mononuclear phagocytes (monocytes, MΦs, DCs) comprised 72% of immune cells and showed the greatest changes with DS. Distinct DS induced gene expression patterns were seen in phagocytes classified by expression of Ccr2 and [Timd4, Lyve1, Folr2 (TLR)]. Expression of phagocytosis/efferocytosis genes increased in TLF+CCR2- MΦs. Monocytes showed the highest expression of Ace, Cx3cr1, Vegfa, Ifngr1,2, and Stat1 and TLF-CCR2+ cells expressed higher levels of inflammatory mediators (Il1a, Il1b, Il1rn, Nfkb1, Ccl5, MHCII, Cd80, Cxcl10, Icam1). A trajectory from monocyte precursors branched to terminate in regulatory MΦs or in mDCs via transitional MΦ and cDC clusters. Activated pathways in TLF+ cells include phagocytosis, PPAR/RXRα activation, IL-10 signaling, alternate MΦ activation, while inflammatory pathways were suppressed. Depletion of MRC1+ MΦs increased IL-17 and IFN-γ expression and cytokine-expressing T cells, reduced IL-10 and worsened goblet loss. CONCLUSIONS: Dryness stimulates distinct gene expression patterns in conjunctival phagocytes, increasing expression of regulatory genes in TLF+ cells regulated in part by RXRα, and inflammatory genes in CCR2+ cells. Regulatory MΦs depletion worsens DS induced inflammation and goblet cell loss.

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.

Effect of posterior chamber phakic refractive lens implantation on the ocular surface and tear film.

To evaluate changes in dry eye-related parameters after posterior chamber phakic refractive lens (PC-PRL) implantation. This prospective study included 21 highly myopic patients (39 eyes) who underwent PC-PRL implantation at Lanzhou Huaxia Eye Hospital between January 2021 and June 2022, with a 3-month postoperative follow-up. In addition to routine preoperative examinations, dry eye assessments were conducted preoperatively and at 1 week, 1 month, and 3 months postoperatively. These assessments included the Ocular Surface Disease Index (OSDI) questionnaire score, non-invasive first tear break-up time (NIF-BUT), non-invasive average tear break-up time (NIA-BUT), tear meniscus height (TMH), meibomian gland loss (MGL) rate, and Schirmer I test (SIt). Repeated measures ANOVA was used to compare the differences in parameters across different time points, with pairwise comparisons conducted using the LSD-t test. After grouping, the Student's t-test was applied to compare normally distributed data, while the Mann-Whitney U test was used for non-normally distributed data. Categorical data were analyzed using the chi-square test. A total of 21 patients (39 eyes) were included, comprising 10 males (19 eyes) and 11 females (20 eyes), aged 19 to 49 years (33.76 ± 7.87). All patients completed the 3-month follow-up. Significant differences in OSDI scores were observed pre- and post-surgery (P = 0.008), with a peak at one week post-surgery (P < 0.001), then stabilizing at one and three months post-surgery. Postoperative NIF-BUT and NIA-BUT significantly decreased (P < 0.001 for both) but returned to preoperative levels within three months. There were no significant changes in TMH, MGL, or SIt postoperatively (P > 0.05). Significant differences in dry eye parameters were observed between the dry eye and control groups before and after surgery (P < 0.001). PC-PRL implantation impacts tear film stability on the ocular surface after surgery, leading to varying degrees of dry eye symptoms in patients. After surgery, all dry eye parameters return to their preoperative levels within three months.

Unveiling senescence-associated ocular pathogenesis via lacrimal gland organoid magnetic bioassembly platform and HMGB1-Box A gene therapy.

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

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment.

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1ß, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1ß and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1ß and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Overview of 37 Tear Substitutes in Europe Based on Various Physicochemical Parameters.

INTRODUCTION: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters. METHODS: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark-Houwink equation. RESULTS: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose®, Thealoz Duo® Gel, and Hyabak®, and highest (1300 kDa) for Vismed® Multi, Vismed® Gel, and Neovis® Gel. The pH values varied between 5.94 for Treovis® and 8.06 for Systane® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis® and Treovis®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid® to 337.47 mPas·s for Thealoz® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors. CONCLUSION: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED.

The lifestyle and nutritional factors for dry eye disease in depression population: a retrospective case-control study.

Background: We aim to evaluate lifestyle and nutritional factors that lead to dry eye disease (DED) in a depressed population using data from the Taiwan BioBank (TWB). Methods: A retrospective case-control study was conducted, and patients with depression based on a questionnaire were selected as the depression group. Each patient in the depression group was matched by age and sex to two individuals without depression, and a total of 3,754 and 7,508 patients constituted the depression and non-depression groups, respectively. Based on the questionnaire, the primary outcome was the presence of DED. Additionally, the chi-square test and interaction test were applied to survey the effect of lifestyle and nutritional factors on DED in the depression and non-depression groups. Results: There were 822 (21.90%) and 958 (12.76%) DED patients in the depression and non-depression groups, respectively, and the incidence of DED was significantly higher in the depression group (p < 0.001). In terms of lifestyle and nutritional factors in the depression population, a higher rate of chronic pain and a sedentary lifestyle were observed than in the patients with depression without DED (both p < 0.05). According to the interaction test, the chronic pain (p = 0.0227) and sedentary lifestyle (p = 0.0002) were significant risk factors for DED presence in the depression group than in the non-depression group, while the persistent coffee consumption (p = 0.0005) and tea consumption (p = 0.0003) were significant protective factors for the DED exclusively for the depression group and not for the non-depression group. Conclusion: The depression population could be significantly benefited from physical activity, coffee intake and tea intake regarding DED development compared to the general population.

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 SANDE and 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.

Analyze interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels in dry eye and the therapeutic effect of cyclosporine A.

BACKGROUND: Dry eye is a common eye disease. Artificial tears supplements are widely used for the treatment of dry eyes. However, multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears, which may affect the therapeutic effect. AIM: To analyze the characteristics of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A. METHODS: A total of 124 dry eye patients treated at The First People's Hospital of Xining from April 2020 to April 2022 were selected as the observation group, while 20 healthy individuals served as the control group during the same period. Levels of inflammatory markers, including IL-1ß, IL-6, and TNF-α, were analyzed. The observation group was further divided into a study group and a control group, each consisting of 62 patients. The control group received artificial tears, whereas the study group received a combination of artificial tears and cyclosporine A. Inflammatory markers, Schirmer's test (SIT), tear break-up time (TBUT), corneal fluorescein staining (CFS), National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) scores, and adverse events (AEs) were compared between the two groups. RESULTS: The observation group exhibited significantly elevated serum levels of IL-1ß, IL-6, and TNF-α in comparison to the healthy group. Following treatment, the study group demonstrated substantial reductions in IL-1ß, IL-6, and TNF-α levels relative to the control group. Moreover, after treatment, the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group. Additionally, significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia, foreign body sensation, fatigue, red eye, and burning sensation within the study group. Furthermore, post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group (P < 0.05). It is noteworthy that significant AEs were reported in both groups throughout the treatment period. CONCLUSION: Cyclosporine A combined with artificial tears is effective in treating dry eye, yielding enhanced outcomes by improving SIT and TBUT levels, reducing CFS scores, and ameliorating vision-related quality of life.

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.

Genomics of Staphylococcus aureus and Enterococcus faecalis isolated from the ocular surface of dry eye disease sufferers.

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

The effect of type 2 diabetes mellitus on lid wiper epitheliopathy and ocular surface parameters.

Introduction: This cross-sectional study was conducted to investigate the impact of type 2 diabetes mellitus(DM) and its duration on indicators such as lid wiper epitheliopathy(LWE), and to assess the significance of LWE for early diagnosis of dry eye disease(DED) in DM patients. Methods: A total of 137 subjects with ocular surface disease index(OSDI) score ≥13 were divided into the non-DM group, the short-term DM group (duration <5 years), and the mid-to-long-term DM group(duration ≥5 years). Evaluations were conducted for LWE, OSDI, lipid layer thickness (LLT), partial blinking rate (PBR), fluorescein tear breakup time (FTBUT), corneal fluorescein staining score (CFS), eyelid margin score, and meibomian gland dropout (MGd). Results: The upper-LWE score and total LWE score in the mid-to-long-term group were higher than those in the non-DM group (p = 0.008 and p = 0.031, respectively). The lower-LWE scores were more severe than upper-LWE scores in the non-DM and short-term groups (p = 0.001 and p = 0.045, respectively).The confirmed diagnosis rate of DEWSII dry eye with LWE as the primary diagnostic indicator was significantly higher than that which utilize FTBUT<5s as the primary diagnostic indicator(p < 0.05). Compared to the non-DM group, the LLT was thinner and the MGd was more severe in the mid-to long-term group. The upper-LWE score was moderately positively correlated with the MGd, and the lower LWE score was moderately negatively correlated with LLT. Conclusion: LWE, LLT, and MGd worsen with the progression of diabetes. Additionally, changes in LWE may precede the FTBUT, indicating that LWE could be considered as an important indicator for early diagnosis of DED in diabetic patients.

A machine learning approach to predicting dry eye-related signs, symptoms and diagnoses from meibography images.

Purpose: To use artificial intelligence to identify relationships between morphological characteristics of the Meibomian glands (MGs), subject factors, clinical outcomes, and subjective symptoms of dry eye. Methods: A total of 562 infrared meibography images were collected from 363 subjects (170 contact lens wearers, 193 non-wearers). Subjects were 67.2 % female and were 54.8 % Caucasian. Subjects were 18 years of age or older. A deep learning model was trained to take meibography as input, segment the individual MG in the images, and learn their detailed morphological features. Morphological characteristics were then combined with clinical and symptom data in prediction models of MG function, tear film stability, ocular surface health, and subjective discomfort and dryness. The models were analyzed to identify the most heavily weighted features used by the algorithm for predictions. Results: MG morphological characteristics were heavily weighted predictors for eyelid notching and vascularization, MG expressate quality and quantity, tear film stability, corneal staining, and comfort and dryness ratings, with accuracies ranging from 65 % to 99 %. Number of visible MG, along with other clinical parameters, were able to predict MG dysfunction, aqueous deficiency and blepharitis with accuracies ranging from 74 % to 85 %. Conclusions: Machine learning-derived MG morphological characteristics were found to be important in predicting multiple signs, symptoms, and diagnoses related to MG dysfunction and dry eye. This deep learning method illustrates the rich clinical information that detailed morphological analysis of the MGs can provide, and shows promise in advancing our understanding of the role of MG morphology in ocular surface health.

Immediate sequential changes in the tear film lipid layer following eyelid massage in dry eye syndrome: A comparative control study.

Background/Purpose: Meibomian glands are sebaceous glands that release meibum onto the ocular surface; enhancing the quality and quantity of meibum secretions has been proven to improve signs and symptoms of evaporative dry eye (EDE) and meibomian gland dysfunction (MGD). This study aimed to evaluate and compare the efficacy of a heated eye mask (HEM) and eyelid massage device EyePeace (EP) in alleviating signs and symptoms of evaporative dry eye. Methods: Forty dry eye participants were recruited in a prospective, contralateral-eye trial study. After undergoing 10 min of HEM therapy, eyelid massage therapy was applied to one eye by the device. The efficiency was assessed at four time points: baseline (0 min), 5 min (5 min), 15 min (15 min), and 30 min (30 min). Non-invasive breakup time (NITBUT), redness score (RS Score), tear meniscus height (TMH), tear-film lipid layer (TFLL), endothelial cell count (ECC), meibomian gland expressibility (MGEx), meibomian gland quality (MGQ), conjunctivocorneal staining (CS), ocular surface temperature (OST), best corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT) flat-axis keratometry value (K1), and steep-axis keratometry value (K2), were examined. Results: Baseline clinical measurements did not have statistically significant differences between the groups (all p > 0.05). After 30 min, a comparison was made between the HEM group and EP + HEM group, revealing significant changes only in the primary outcomes, TFLL (2.18 ± 0.45 versus 2.40 ± 0.50; p < 0.05), and MGEx grades (0.68 ± 0.53 versus 0.98 ± 0.70; p < 0.05). Improvements in NITBUT and TMH were sustained until 5 min and 15 min after using EP + HEM. No significant changes were observed in RS Score, MGQ, OST, CFS, BCVA, IOP, ECC, K1, K2, and CCT (all p > 0.05) at all test time points. Conclusion: The application of a heated eye mask followed by a gentle massage using EyePeace on the eyelids can have a sustained improvement in the tear film lipid layer and meibomian gland expressivity score but not clinically significant, and does not pose any significant immediate impact on the cornea.Trial registration number: NCT06158997.

Comparison of upper eyelid pressure and ocular surface parameters in dry eye disease and benign essential Blepharospasm: A cross-sectional study.

PURPOSE: To compare the upper eyelid pressure (UEP) and ocular surface parameters between dry eye disease (DED) and DED coexisting with benign essential blepharospasm (BEB), exploring which parameters could assist in distinguishing between DED and BEB, as potential risk factors for DED with BEB. METHODS: All enrolled participants diagnosed with DED or DED coexisting with BEB were initially subjected to ocular surface disease index (OSDI) determination. Subsequently, the upper eyelid pressure was recorded using an innovative eyelid pressure measurement device, followed by a series of ocular surface examinations. The two groups were compared using the independent t-test and Mann-Whitney U test. A logistic regression analysis was performed to identify which parameters can predict the onset of blepharospasm. RESULTS: The BEB group achieved a higher upper eyelid pressure (101.9 ± 23.5mN vs 88.4 ± 18.1mN, P = 0.009), lower number of total blink (6.2 ± 4.2 vs 7.1 ± 4.1, P = 0.016), higher corneal fluorescein staining score (4.0 ± 1.9 vs 3.0 ± 1.7, P = 0.046), higher partial blink rate (0.9 ± 0.2 vs 0.5 ± 0.4, P = 0.000) and the lower grade of meibum expressibility (1 (1, 2) vs 2 (1, 3), P = 0.000) and meibum quality (1 (1, 1) vs 1 (1, 1), P = 0.033) compared with the DED group. The upper eyelid pressure (OR = 1.123), partial blink rate (OR = 0.014) and the grade of meibum expressibility (OR = 10.804) showed significant associations with BEB (P < 0.05). CONCLUSION: Despite similar OSDI scores, DED coexisting with BEB exhibited higher upper eyelid pressure, lower corneal fluorescein staining score, lower partial blink rate, more total blinks, lower grades of meibum expressibility, and lower meibum quality compared to DED alone. Among these, higher upper eyelid pressure, lower partial blink rate, and worse grade of meibum expressibility were identified as risk factors for BEB in DED.