Multifunctional Cerium Oxide Nanozyme for Synergistic Dry Eye Disease Therapy.

Dry eye disease (DED) is a chronic multifactorial ocular surface disease mainly caused by the instability of tear film, characterized by a series of ocular discomforts and even visual disorders. Oxidative stress has been recognized as an upstream factor in DED development. Diquafosol sodium (DQS) is an agonist of the P2Y2 receptor to restore the integrity/stability of the tear film. With the ability to alternate between Ce3+ and Ce4+, cerium oxide nanozymes could scavenge overexpressed reactive oxygen species (ROS). Hence, a DQS-loaded cerium oxide nanozyme was designed to boost the synergistic treatment of DED. Cerium oxide with branched polyethylenimine-graft-poly(ethylene glycol) as nucleating agent and dispersant was fabricated followed with DQS immobilization via a dynamic phenylborate ester bond, obtaining the DQS-loaded cerium oxide nanozyme (defined as Ce@PBD). Because of the ability to mimic the cascade processes of superoxide dismutase and catalase, Ce@PBD could scavenge excessive accumulated ROS, showing strong antioxidant and anti-inflammatory properties. Meanwhile, the P2Y2 receptors in the conjunctival cells could be stimulated by DQS in Ce@PBD, which can relieve the incompleteness and instability of the tear film. The animal experiments demonstrated that Ce@PBD significantly restored the defect of the corneal epithelium and increased the number of goblet cells, with the promotion of tear secretion, which was the best among commercial DQS ophthalmic solutions.

Classification of dry eye disease subtypes.

PURPOSE: The current subclassifications of dry eye disease (DED) are aqueous deficient (ADDE) and evaporative (EDE) forms, but there lacks consistency in the clinical characteristics used to define each of these. This study used clinical data to inform cut-off values for the subclassification of ADDE and EDE, to allow more consistent study of the epidemiology of both DED subtypes. METHODS: The study enrolled 261 residents from the UK, extracted from a cohort with demographics representing the population (mean 42.4 ± 18.7 years, 56 % females). The TFOS DEWS II diagnostic criteria were used to identify those with DED. Meibomian gland loss/drop-out (from meibography), lipid layer thickness (LLT - from interferometry graded on the Guillon-Keeler scale), and tear meniscus height (TMH - Keratograph 5M) along with tear evaporation (Delfin Vapometer) were used to characterise the subclassification. The Dry Eye Risk Factor Survey was used to assess risk factors associated with each DED subtype. RESULTS: Compared to individuals who were not diagnosed with DED, EDE was characterized by signs of meibomian gland loss of > 28 %, LLT grade < 3 and tear evaporation > 46 g/m2/h. In contrast, ADDE was best characterized by a reduced TMH < 0.2 mm. Based on these criteria, the prevalence of ADDE was 6.2 %, EDE was 64.2 %, and 11.1 % exhibited features of both ADDE and EDE, with 18.5 % unclassified despite having a DED diagnosis. Contact lens wear and computer use were risk factors for ADDE (p < 0.05), whereas age was a positive risk factor for EDE (p < 0.01). Meibomian gland loss (occurring in 27.9 %) was the most commonly observed sign in EDE. CONCLUSIONS: Data driven-classification of DED confirms that the evaporative form is most prevalent and identified that in a generalisable UK population, ADDE alone occurs only in approximately 1 in 16 cases of DED.

Efficacy of recombinant human epidermal growth factor plus sodium hyaluronate eye drops in diabetic dry eye post-cataract surgery.

BACKGROUND: Dry eye syndrome (DES) after diabetic cataract surgery can seriously affect the patient's quality of life. Therefore, effective alleviation of symptoms in patients with this disease has important clinical significance. AIM: To explore the clinical effect of recombinant human epidermal growth factor (rhEGF) plus sodium hyaluronate (SH) eye drops on DES after cataract surgery in patients with diabetes. METHODS: We retrospectively evaluated 82 patients with diabetes who experienced DES after cataract surgery at Tianjin Beichen Hospital, Affiliated Hospital of Nankai University between April 2021 and April 2023. They were classified into an observation group (42 cases, rhEGF + SH eye drops) and a control group (40 cases, SH eye drops alone), depending on the different treatment schemes. The thera-peutic efficacy, dry eye symptom score, tear film breakup time (TFBUT), basic tear secretion score [assessed using Schirmer I test (SIt)], corneal fluorescein staining (FL) score, tear inflammatory markers, adverse reactions during treatment, and treatment satisfaction were compared between the two groups. RESULTS: Therapeutic efficacy was higher in the observation group compared with the control group. Both groups showed improved TFBUT and dry eye, as well as improved SIt and FL scores after treatment, with a more pronounced improvement in the observation group. Although no marked differences in adverse reactions were observed between the two groups, treatment satisfaction was higher in the observation group. CONCLUSION: rhEGF + SH eye drops rendered clinical benefits to patients by effectively ameliorating dry eye and visual impairment with favorable efficacy, fewer adverse reactions, and high safety levels. Thus, this treatment should be promoted in clinical practice.

A novel multi-ingredient supplement significantly improves ocular symptom severity and tear production in patients with dry eye disease: results from a randomized, placebo-controlled clinical trial.

Introduction: Dry eye disease (DED) is multifactorial and characterized by a loss of tear film homeostasis that causes a cycle of tear film instability, tear hyperosmolarity, and inflammation. While artificial tears are the traditional mainstay of treatment, addressing the underlying pathophysiology could relieve symptoms and prevent progression. Increasing evidence indicates a role for oral nutritional supplementation in multiple ophthalmic diseases, including DED. Lutein, zeaxanthin, curcumin, and vitamin D3 have demonstrated protective and anti-inflammatory properties in ocular models. This prospective, randomized, double-blind, parallel, placebo-controlled study evaluated the efficacy and safety of a proprietary blend of lutein, zeaxanthin isomers, curcumin, and vitamin D3 (LCD) as a daily supplement in adult participants with DED. Methods: Participants were randomized to receive one LCD supplement capsule (lutein 20 mg, zeaxanthin isomers 4 mg, curcumin 200 mg curcuminoids, and vitamin D3 600 IU) or placebo per day for 8 weeks (LCD, n=77; placebo, n=78). Primary outcomes were changes in tear volume (Schirmer's test) and ocular symptoms (Ocular Surface Disease Index [OSDI]). Results: The study met its primary endpoints: the LCD group demonstrated significantly better Schirmer's test scores and improvement in overall OSDI score, versus placebo, at Day 56 (p<0.001 for both). Scores for total OSDI, and symptoms and vision domains, significantly improved by Day 14 for LCD versus placebo, (p<0.05 for all) and were maintained to Day 56 (p<0.001). In addition, the LCD group demonstrated significantly improved tear film break-up time (TBUT) and tear film osmolarity, versus placebo, by Day 56 (p<0.001), along with significant improvements in corneal and conjunctival staining (p<0.001 for both), and inflammation (matrix metalloproteinase-9; p<0.001 for each eye). Total Standard Patient Evaluation of Eye Dryness (SPEED) score, and scores for the frequency and severity domains, were significantly improved by Day 14 for LCD versus placebo (p<0.05 for all) and maintained to Day 56 (p<0.001). There was no difference between groups for artificial tear usage. The supplement was well-tolerated. Discussion: Once-daily LCD supplementation significantly improved tear production, stability and quality, reduced ocular surface damage and inflammation, and improved participants' symptoms. LCD supplementation could offer a useful adjunct to artificial tears for patients with DED (NCT05481450).

Systematic review of ocular surface treatments in the setting of thyroid eye disease.

Introduction: Approximately 85% of patients with thyroid eye disease experience ocular surface symptoms. Although corneal exposure plays a role in inducing inflammatory changes to the ocular surface, multiple studies reveal more complexity to the abnormal tear film composition and parameters in thyroid eye disease patients including those who do not have proptosis or increased corneal exposure. Currently, a majority of cases of thyroid associated dry eye symptoms are given treatments intended for ocular surface disease arising from different etiologies. Methods: Medline via Ovid, Cochrane CENTRAL, PubMed, and Google Scholar were systematically searched for articles evaluating the efficacy of treatments for dry eye symptoms in patients with thyroid eye disease. Articles were from all geographic regions and dates ranged from inception until October 2023. Results: Seven papers ultimately met inclusion criteria and were included in this review. These papers revealed that multiple topical and non-topical treatment modalities address dry eye symptoms in thyroid eye disease and improve subjective and objective ocular surface parameters. However, due to the few studies that exist and due to disparities in sample size and study design, no overwhelming best practices were identified that could influence clinical practice. Conclusion: This systematic review identifies the current treatments that exist and highlights the clear unmet need for a large population suffering with dry eye symptoms. Ideally, further well-designed investigations into this area would target topical, non-invasive modalities to develop first line options for thyroid eye disease patients.

Sicca syndrome as complication of COVID-19 infection: A case report.

Several reports of suspected oral and ocular manifestations of coronavirus disease 2019 (COVID-19) has prompted investigations into ocular signs, symptoms, and transmission (5).11.2% of patients with COV19 infection had ocular symptoms, including ocular pain, conjunctivitis, dry eye, and floaters, meanwhile, many studies had documented oral symptoms such as dry mouth and dysgeusia in these patients. Our case reported a 39-year-old male, presented with symptoms of dry mouth and dry eye lasting more than 3 months. The patient had recovered from (PCR-confirmed) COVID-19 which lasted 10 days, 4 months ago. The physical examination was normal. Ocular findings include conjunctival hyperemia and superficial punctate keratitis. The anti-nuclear antibody (ANA) was weekly positive at 1/80. Schirmer test considered positive. He continued on 200 mg/day of hydroxychloroquine, along with tear drops until now with remission. Sicca symptoms may be a sequel of COVID-19 infection, and physicians should be aware of this sequel. The sequela of this infection is not understood, with limited data in the literature. Future prospective cohort studies are needed to reveal the impact of these features on oral health.

The Utilization of Topical Insulin for Ocular Surface Diseases: A Narrative Review.

Various etiologies, including diabetic keratopathy (DK), dry eye disease (DED), and neurotrophic keratopathy (NK), can disrupt corneal homeostasis, exacerbating corneal epithelial defects. Topical insulin has emerged as a promising therapy for promoting corneal wound healing and addressing underlying pathologies. This review systematically evaluates the efficacy of topical insulin across different corneal disorders. A literature review was conducted across the PubMed, Google Scholar, and Scopus research databases. The search resulted in a total of 19 articles, consisting of clinical trials, retrospective studies, and case reports. In DK, topical insulin accelerates corneal wound healing post-vitreoretinal surgery with lower concentrations showing higher outcomes when compared to conventional therapy, possibly due to improved epithelial stem cell migration. In comparison, the dry-eye disease results are inconclusive regarding patient-reported outcomes and corneal staining. For NK, topical insulin accelerates corneal wound healing and restores corneal nerve sensation. Other persistent epithelial defect (PED) etiologies that have been treated with topical insulin are infection, immune-mediated, mechanical and chemical trauma, and chronic ocular surface alterations. Although individual mechanisms for the benefits of topical insulin for each of these etiologies have not been studied, the literature demonstrates that topical insulin is efficacious for PEDs regardless of etiology. Future clinical trials need to be conducted to further evaluate optimal dosing, duration, and use of topical insulin for the restoration of the corneal surface.

[Changes in the precorneal tear film at various stages of keratoconus]. / Izmenenie prekorneal'noi sleznoi plenki pri razlichnykh stadiyakh keratokonusa.

The combination of keratoconus (KC) with signs of dry eye disease (DES) has been described in numerous scientific publications. At the same time, there is a relationship between KC stage and an increase in the severity of DES symptoms, however, there is still no common understanding of the severity of xerotic process depending on the clinical course of keratectasia. PURPOSE: This study assesses the changes in the state of the precorneal tear film in KC relative to the stages of the disease. MATERIAL AND METHODS: The study included 50 patients (100 eyes) with bilateral non-operated KC from subclinical to stage IV. The following methods were used for a comprehensive assessment of the condition of the tear film: biomicroscopy of the anterior segment of the eye using vital dyes, functional tests (Norn, Schirmer, Jones tests), tearscopy of the lipid layer of the tear film with software processing of the results, OCT-meniscometry, as well as filling out the OSDI questionnaire by patients. RESULTS: The following significant changes were revealed as the KC stage progressed: an increase in the area of staining of the ocular surface with vital dyes, a decrease in the results of the Norn functional test and OCT-meniscometry, an increase in the areas of smaller thickness of lipids and areas of their complete absence according to tearscopy, as well as an increase in scores of the OSDI questionnaire. CONCLUSION: A comprehensive assessment of the condition of the tear film in KC indicates the relationship and the strengthening of the signs of DES as keratectasia progresses, and can be considered as justification for the need to prescribe tear replacement and reparative therapy that improves the condition of the ocular surface and stabilizes the precorneal tear film.

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

BACKGROUND: Dry 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. METHODS: This 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. RESULTS: At 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. CONCLUSIONS: Cenegermin 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 REGISTRATION: NCT03982368; registered May 23, 2019.

The severity of dry eye symptoms and risk factors among university students in Saudi Arabia: a cross-sectional study.

Dry eye syndrome (DES) is a tear film disorder caused by increased tear evaporation or decreased production. The heavy workload on the eye and the increased usage of digital screens may decrease blink frequency, leading to an increased evaporation rate and an upsurge in the incidence and severity of DES. This study aims to assess the severity of DES symptoms and the risk factors among university students. A cross-sectional study was conducted at Umm AlQura University to evaluate the severity of DES among students and explore its potential association with digital screen use. Validated questionnaires were used to assess the severity of DES and digital screen usage. The study included 457 participants, of which 13% had symptoms suggestive of severe DES. Furthermore, multiple risk factors had a significant association with the severity of DES, including gender, use of monitor filters, monitor and room brightness, and smoking habits. DES symptoms were prevalent among university students, particularly female students. Although there was no significant association with the duration of screen usage and collage distribution. Other factors however, such as the usage of screen monitors and the brightness of both the monitor and the room, were significantly associated with the severity of DES symptoms.

Visual, ocular surface, and extraocular diagnostic criteria for determining the prevalence of computer vision syndrome: a cross-sectional smart-survey-based study.

Background: The American Optometric Association defines computer vision syndrome (CVS), also known as digital eye strain, as "a group of eye- and vision-related problems that result from prolonged computer, tablet, e-reader and cell phone use". We aimed to create a well-structured, valid, and reliable questionnaire to determine the prevalence of CVS, and to analyze the visual, ocular surface, and extraocular sequelae of CVS using a novel and smart self-assessment questionnaire. Methods: This multicenter, observational, cross-sectional, descriptive, survey-based, online study included 6853 complete online responses of medical students from 15 universities. All participants responded to the updated, online, fourth version of the CVS questionnaire (CVS-F4), which has high validity and reliability. CVS was diagnosed according to five basic diagnostic criteria (5DC) derived from the CVS-F4. Respondents who fulfilled the 5DC were considered CVS cases. The 5DC were then converted into a novel five-question self-assessment questionnaire designated as the CVS-Smart. Results: Of 10 000 invited medical students, 8006 responded to the CVS-F4 survey (80% response rate), while 6853 of the 8006 respondents provided complete online responses (85.6% completion rate). The overall CVS prevalence was 58.78% (n = 4028) among the study respondents; CVS prevalence was higher among women (65.87%) than among men (48.06%). Within the CVS group, the most common visual, ocular surface, and extraocular complaints were eye strain, dry eye, and neck/shoulder/back pain in 74.50% (n = 3001), 58.27% (n = 2347), and 80.52% (n = 3244) of CVS cases, respectively. Notably, 75.92% (3058/4028) of CVS cases were involved in the Mandated Computer System Use Program. Multivariate logistic regression analysis revealed that the two most statistically significant diagnostic criteria of the 5DC were ≥2 symptoms/attacks per month over the last 12 months (odds ratio [OR] = 204177.2; P <0.0001) and symptoms/attacks associated with screen use (OR = 16047.34; P <0.0001). The CVS-Smart demonstrated a Cronbach's alpha reliability coefficient of 0.860, Guttman split-half coefficient of 0.805, with perfect content and construct validity. A CVS-Smart score of 7-10 points indicated the presence of CVS. Conclusions: The visual, ocular surface, and extraocular diagnostic criteria for CVS constituted the basic components of CVS-Smart. CVS-Smart is a novel, valid, reliable, subjective instrument for determining CVS diagnosis and prevalence and may provide a tool for rapid periodic assessment and prognostication. Individuals with positive CVS-Smart results should consider modifying their lifestyles and screen styles and seeking the help of ophthalmologists and/or optometrists. Higher institutional authorities should consider revising the Mandated Computer System Use Program to avoid the long-term consequences of CVS among university students. Further research must compare CVS-Smart with other available metrics for CVS, such as the CVS questionnaire, to determine its test-retest reliability and to justify its widespread use.

A highly selective inhibitor of discoidin domain receptor-1 (DDR1-IN-1) protects corneal epithelial cells from YAP/ACSL4-mediated ferroptosis in dry eye.

BACKGROUND AND PURPOSE: This study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed the potential of specific DDR inhibitors as a therapeutic strategy for dry eye by exploring the underlying mechanism. EXPERIMENTAL APPROACH: Dry eye was induced in Wistar rats by applying 0.2% benzalkonium chloride (BAC), after which rats were treated topically for 7 days with DDR1-IN-1, a selective inhibitor of DDR1. Clinical manifestations of dry eye were assessed on Day-7 post-treatment. Histological evaluation of corneal damage was performed using haematoxylin and eosin (H&E) staining. In vitro, immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress (HS) were treated with varying doses of DDR1-IN-1 for 24 h. The levels of lipid peroxidation in dry eye corneas or HS-stimulated HCECs were assessed. Protein levels of DDR1/DDR2 and related pathways were detected by western blotting. The cellular distribution of acyl-CoA synthetase long chain family member 4 (ACSL4) and Yes-associated protein (YAP) was evaluated using immunohistochemistry or immunofluorescent staining. KEY RESULTS: In dry eye corneas, only DDR1 expression was significantly up-regulated compared with normal controls. DDR1-IN-1 treatment significantly alleviated dry eye symptoms in vivo. The treatment remarkably reduced lipid hydroperoxide (LPO) levels and suppressed the expression of ferroptosis markers, particularly ACSL4. Overexpression or reactivation of YAP diminished the protective effects of DDR1-IN-1, indicating the involvement of the Hippo/YAP pathway in DDR1-targeted therapeutic effects. CONCLUSIONS AND IMPLICATIONS: This study confirms the significance of DDR1 in dry eye and highlights the potential of selective DDR1 inhibitor(s) for dry eye treatment.

Multifunctional cerium oxide nanozymes with high ocular surface retention for dry eye disease treatment achieved by restoring redox balance.

Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. STATEMENT OF SIGNIFICANCE: • PBA-functionalized bPEI-g-PEG-based cerium oxide (Ce@PB) nanozymes were designed and fabricated. • The Ce@PB nanozymes have superoxide dismutase (SOD) and catalase (CAT) enzyme-like activity scavenging excessive intracellular reactive oxygen species (ROS). • The Ce@PB nanozymes demonstrate extended retention on the ocular surface and can effectively treat dry eye disease.

Evaluation of Dry Eye Parameters Among Electronic Cigarette Smokers.

Introduction  The emergence of electronic cigarettes as the "healthier" version of smoking has been popular, especially among young adults. However, knowledge about the potential effects of e-cigarettes on ocular structures is scarce. Objective  To compare the mean change in dry eye parameters between e-cigarette smokers and non-smokers and to correlate between dry eye parameters with device power output. Methodology A cross-sectional, single-visit study was conducted involving 85 e-cigarette smokers and 85 non-smokers. All participants were evaluated on dry eye parameters, including the Ocular Surface Disease Index (OSDI) score, tear meniscus height (TMH), tear break-up time (TBUT), cornea fluorescein staining, and Schirmer's I test. The mean change in dry eye parameters was compared between e-cigarette smokers and non-smokers. The correlation between dry eye parameters with device power output was analyzed. Results Specifically, 32.94% of e-cigarette smokers were found to have a TMH <0.2 mm, compared to only 5.88% of non-smokers (p<0.001). A significant change in mean TBUT was found between the e-cigarette smokers (10.41+2.65 seconds) and non-smokers (12.66+3.14 seconds, p<0.001). The lower mean Schirmer's I test was found among e-cigarette smokers (12.75+7.24 mm, p<0.001). No significant change in the median OSDI score and corneal fluorescein staining. The OSDI score and device power output were found to have a significant positive correlation (p=0.003). There was a significant association between dry eye signs and device power output, including TMH (p=0.047), TBUT (p=0.002), Schirmer's I test (p<0.001), and corneal fluorescein staining (p<0.001). Conclusion Electronic cigarette smokers are prone to develop dry eyes. Concern should be raised on the risk of electronic cigarette use on ocular health, and regulation on e-cigarette ban should be revisited.

Evidence-Based Strategies for Warm Compress Therapy in Meibomian Gland Dysfunction.

AIM: Despite promising results from technological therapies like intense pulsed light application, warm compress therapy is a mainstay in meibomian gland dysfunction (MGD). However, applying warm compresses (WC) to the eyelids is palliative rather than curative and not always dispensed with specific instructions. The range of eyelid warming treatments available and lack of clear directives for use creates uncertainty for patients accustomed to explicit dosage information. This report examines data from clinical studies across the past 20 years to identify effective protocols for three types of WC-hot towel, microwavable eye mask, and self-heating eye mask (EM). METHOD: Literature search for studies on WC and MGD published between 2004 and 2023 in English was conducted. Studies wherein hot towel, microwavable EM, and self-heating EM were used in a treatment arm were included and those wherein they served only as control or were used in conjunction with another intervention were excluded. 20 resulting studies were separated into 3 groups: 5 on temperature profiles of WC, 6 with single application of WC, and 9 with repeated applications. Study methods and outcomes were tabulated, and a qualitative review was performed, attending to WC protocol and efficacy, as indicated by measures of tear film, meibomian gland health, and dry eye questionnaires. RESULTS: Data from the aforementioned studies revealed that each method can achieve target eyelid temperature of 40 °C. A single application of WC-ranging from 5 to 20 min-can significantly improve tear quality, while repeated applications significantly relieve symptoms associated with dry eyes from MGD and, in most studies, significantly improve meibomian gland health. Hot towels, however, require frequent reheating to maintain eyelid temperatures above 40 °C, rendering them relatively ineffective in longitudinal studies. Microwavable EM retain heat well across 10 min and were found to improve tear break-up time and/or meibomian gland score. Self-heating EM have variable activation times and were typically applied for longer periods, showing benefits akin to microwavable EM in short-term studies. Studies monitoring compliance indicate greater deviation from protocol with higher application frequencies or longer-term use. Evidence suggests superior heat retention and therapeutic effects on specific contributing factors in MGD (such as Demodex) with moist-heat compress. CONCLUSION: Considering decreased patience adherence to therapy with increased usage frequencies, and balancing needs to provide succinct instructions for various compress types, an advisable strategy is for patients to apply a moist-heat generating EM (microwavable or self-heating) to each eye for at least 10 min, prepared according to manufacturer's instructions.

Remarkable improvement of symptoms and signs of severe dry eye treated by ocular immersion hydrotherapy.

Key Clinical Message: Traditional treatment options are often insufficient in treating severe dry eyes caused by systemic diseases. This case demonstrates that ocular immersion hydrotherapy significantly alleviated symptoms and ocular surface inflammation in ocular graft-versus-host disease. Based on these findings, we propose it as a promising option for managing severe dry eye disease. Abstract: This case report investigates the efficacy of ocular immersion hydrotherapy (OIH) in treating severe dry eye secondary to ocular graft-versus-host disease (oGVHD). A 35-year-old female with a history of acute myeloid leukemia-M2 and subsequent hematopoietic stem cell transplantation (HSCT) developed high-intensity oGVHD unresponsive to conventional treatments, including topical corticosteroids and lubricants. We introduced OIH, utilizing sterilized swimming goggles filled with intraocular irrigating solutions, providing a moist microenvironment for the ocular surface. Symptoms were significantly relieved after treatment. Corneal filaments and epithelial defects were significantly reduced, and in vivo confocal microscopy (IVCM) demonstrated resolution of inflammation and reappearance of corneal nerves. This case indicates that OIH could be a promising therapeutic approach for severe dry eye conditions arising from oGVHD, particularly for patients refractory to traditional treatments. Further studies are warranted to elucidate the long-term benefits and mechanisms of OIH in oGVHD management.

A Possible Reciprocal Relationship Between Myopia and Dry Eye Disease in Japanese Teenagers.

Purpose: To investigate the relationship between dry eye disease (DED) and myopia in Japanese teenagers. Methods: This clinic-based, retrospective, cross-sectional study assessed DED condition in 10- to 19-year-old teenagers presenting at Japanese eye clinics. They included 106 high myopic patients (HM; mean age, 16.4 ± 2.2 years), 494 mild myopic patients (15.0 ± 2.6 years) and 82 non-myopic teenagers (NM; 13.8 ± 2.6 years). Subjective refraction and anisometropia were measured. Myopia grade was classified as HM (≤ -6.00 D), MM (> -6.00 D, < -0.50 D), or NM (≥ -0.5 D). The presence of DED-related symptoms including dryness, irritation, pain, fatigue, blurring and photophobia were assessed through a questionnaire. Tear film break-up time (BUT) and fluorescein corneal staining were investigated. Comparison among three groups and regression analysis of myopic error and other variables were conducted. Results: Anisometropia and astigmatic error were greatest in the HM group compared with the other groups (p < 0.001). The HM group reported less photophobia (p < 0.001) and less pain (p = 0.039) compared with the NM group. Regression analysis revealed that myopic error was correlated with astigmatic error (ß = -0.231, p <0.001), anisometropia (ß = -0.191, p <0.001), short BUT (ß = -0.086, p = 0.028) and the presence of diagnosed DED (ß = -0.112, p = 0.003). Dryness (ß = -0.127 p = 0.004), photophobia (ß = 0.117, p = 0.002) and pain (ß = 0.084, p = 0.034) correlated with myopic error. Conclusion: This study associated clinical findings of DED in HM teenagers. The present results suggest DED might be associated with myopia, possibly in a reciprocal relationship.

Efficiency of Combining Heated Eye Mask with Intense Pulsed Light Therapy as a Treatment Option for Evaporative Dry Eye Disease.

Background and objectives: The study aimed to establish the efficiency of combining the Posiforlid heated eye mask with intense pulsed light therapy (IPL), as a treatment strategy for evaporative dry eye disease. Materials and methods: This study included 110 patients, respectively 220 eyes, diagnosed with evaporative dry eye disease, patients between 18 and 86 years old, divided into two study groups. The first one, the control group, consisted of 73 patients treated with IPL therapy, and the second of 37 patients, who underwent IPL therapy associated with Posiforlid heated eye mask. Subjective evolution was assessed using an eye fitness test (EFT) regarding symptomatology. Objective assessment of the ocular surface was performed by tear film stability evaluation (TFSE), non-invasive first break-up time (NIFBUT), non-invasive average breakup time (NIABUT), ocular surface inflammatory evaluation (OSIE), measuring of the central tear meniscus height (CTMH) and thinnest tear meniscus height (TTMH). The assessment was performed at the beginning of the IPL treatment, during the IPL sessions, at the end of the IPL treatment, and afterward, at 3, 6, and 12 months. Results: Tear film stability has increased in both study cases, but no statistically significant difference was observed between the two groups studied. For the control group, tear film stability evaluation (TFSE) started from 310.56 ± 389.54 at baseline (time 1 presentation) to 114.40 ± 122.90 after 12 months, and for the heated mask group, from 391.11 ± 456.45 (time 1 presentation) to 97.38 ± 105.98 after 12 months. NIABUT increased from 10.72 ± 4.90 seconds to 14.79 ± 3.72 seconds in the control group, and from 11.11 ± 5.08 seconds to 15.84 ± 2.26 seconds in the second group. OSIE decreased, as expected, from 7.18 ± 7.93 percent in the control group to 2.24 ± 2.38 percent after 12 months and from 7.42 ± 7.77 percent to 2.47 ± 2.50 percent in the Posiforlid group. Although significantly lower, there was no significant difference between the two studied groups. No statistically significant changes were registered in the studied quantitative parameters. Using the EFT test, great improvements were registered regarding symptomatology, with a score increasing from 29.99 ± 8.60 to 39.10 ± 5.08 in the control group and from 27.35 ± 9.24 to 38.35 ± 4.62 in the other group. Again, the same statistical result was registered on this variable. Conclusions: The improvement of tear film stability, ocular surface inflammatory condition, and subjective symptoms during IPL therapy sessions and the first year of observation after the completion of the treatment was not necessarily increased by the additional use of a heated eye mask. Abbreviations: IPL = intense pulsed light therapy, EFT = eye fitness test, NIFBUT = non-invasive first break-up time, NIABUT = non-invasive average break-up time, OSIE = ocular surface inflammatory evaluation, TFSE = tear film stability evaluation, CTMH = central tear meniscus height, TTMH = thinnest tear meniscus height, DED = dry eye disease, MGD = meibomian gland dysfunction, SD = standard deviation.

Topical Tacrolimus in Anterior Segment Disorders in Ophthalmology: A Review.

The purpose of this study is to emphasize topical tacrolimus's role in treating anterior segment diseases in ophthalmology. The present study analyzed research papers and publications from international databases, including Pubmed, MedLine, Google Scholar, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and Scopus to highlight the significance and advantages of topical application of tacrolimus and its efficacy in treating allergic eye disorders, immune-mediated diseases, and other ocular surface disorders. Tacrolimus and cyclosporine are the two most commonly used topical immunosuppressants in ophthalmology. Tacrolimus is a selective calcineurin inhibitor administered for the prevention and treatment of allograft rejection in solid organ transplant recipients and has a similar mechanism of action to cyclosporine. Management of immune-mediated inflammatory anterior segment requires intense immunosuppression and studies have shown that tacrolimus is ten to hundred times more effective than cyclosporine. Abbreviations: IL-2 = interleukin-2, FDA = Food and Drug Administration Agency, GvHD = graft versus host disease, (Ig)E = immunoglobulin E, SAC = seasonal conjunctivitis, PAC = perennial allergic conjunctivitis, VKC = vernal keratoconjunctivitis, AKC = allergic keratoconjunctivitis, GPC = giant papillary conjunctivitis, PKC = phyctenular keratoconjunctivitis, DED = dry eye disease, TBUT = tear break up time.

The shared mechanism and potential diagnostic markers for premature ovarian failure and dry eye disease.

Premature ovarian failure (POF), which is often comorbid with dry eye disease (DED) is a key issue affecting female health. Here, we explored the mechanism underlying comorbid POF and DED to further elucidate disease mechanisms and improve treatment. Datasets related to POF (GSE39501) and DED (GSE44101) were identified from the Gene Expression Omnibus (GEO) database and subjected to weighted gene coexpression network (WGCNA) and differentially expressed genes (DEGs) analyses, respectively, with the intersection used to obtain 158 genes comorbid in POF and DED. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of comorbid genes revealed that identified genes were primarily related to DNA replication and Cell cycle, respectively. Protein-Protein interaction (PPI) network analysis of comorbid genes obtained the 15 hub genes: CDC20, BIRC5, PLK1, TOP2A, MCM5, MCM6, MCM7, MCM2, CENPA, FOXM1, GINS1, TIPIN, MAD2L1, and CDCA3. To validate the analysis results, additional POF- and DED-related datasets (GSE48873 and GSE171043, respectively) were selected. miRNAs-lncRNAs-genes network and machine learning methods were used to further analysis comorbid genes. The DGIdb database identified valdecoxib, amorfrutin A, and kaempferitrin as potential drugs. Herein, the comorbid genes of POF and DED were identified from a bioinformatics perspective, providing a new strategy to explore the comorbidity mechanism, opening up a new direction for the diagnosis and treatment of comorbid POF and DED.