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.

[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.

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.

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.

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.

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.

Scleral Lenses for Managing Dry Eye Disease in the Absence of Corneal Irregularities: What Is the Current Evidence?

Scleral lenses (SLs) are large-diameter rigid contact lenses that are a mainstay treatment for eyes with corneal irregularities. In recent years, there has been increased interest in the role of managing dry eye disease (DED) with SLs, as many patients with DED have reported symptomatic relief with SL wear. The role of SLs for DED management when there are associated corneal irregularities is supported by individual case reports and studies. This has prompted practitioners to begin advocating using SLs in DED cases, even in the absence of associated corneal irregularities and other ocular surface diseases (OSDs). There have also been discussions on potentially placing SLs earlier in the treatment hierarchy of DED, where it currently sits at a more advanced level of intervention (Step 3) in the TFOS DEWS II Report. This review will present the currently available, albeit sparse, evidence that supports and suggests this practice, as well as ancillary evidence supporting the purported benefits of SL wear in DED. The advantages of SL wear, such as corneal healing, absence of tear evaporation and contact lens dehydration, and improved visual acuity with associated increased wear comfort, and how this will benefit DED patients will be explored. Conversely, the challenges associated with fitting SLs in DED patients, including increased midday fogging, poor wettability, and subjective patient satisfaction, will also be presented, as well as a discussion on the key considerations for SL fitting in this population. Overall, while more research is needed to support the use of SLs in DED patients without associated corneal irregularities and other forms of OSD, the use of these lenses may prove to have a potentially wider role given their reported ancillary benefits in these populations.

Customized Scleral Lenses: An Alternative Tool for Severe Dry Eye Disease-A Case Series.

Purpose: Dry eye disease (DED) is a multifactorial condition significantly impacting patients' quality of life (QoL). This study aims to present a case series highlighting the effectiveness of customized scleral lenses in managing severe DED and improving patient outcomes. Methods: This case series includes three patients with severe DED refractory to conventional treatments. Customized scleral lenses were fitted for each patient, and clinical outcomes were evaluated over a period of two months. Assessments included best-corrected visual acuity (BCVA), slit-lamp examination findings, and corneal National Eye Institute (NEI) scores. Results: All three patients demonstrated significant improvements in BCVA, reductions in ocular symptoms, and enhanced ocular surface health. Patient 1, with secondary Sjögren's syndrome and suspected mucous membrane pemphigoid, showed resolution of conjunctival hyperemia and epithelial defects. Patient 2, with graft versus host disease, exhibited resolution of punctate keratitis and the absence of thread mucus. Patient 3, post-oncologic surgery, achieved complete resolution of keratoconjunctivitis sicca and the restoration of vision. Conclusions: Customized scleral lenses are a useful therapeutic option for severe DED, providing significant symptomatic relief and enhancing patients' quality of life. Their use should be considered in refractory cases to optimize ocular surface health and visual outcomes.

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.

Dry eye disease adverse reaction of pharmacological treatment for early-stage breast cancer.

Breast cancer is the most prevalent cancer worldwide. With advancements in breast cancer diagnosis and treatment, the prognosis of patients with early-stage cancer has significantly improved. Enhancing the long-term quality of life of patients after antineoplastic therapy, including visual quality, has become a crucial research focus. This review aims to comprehensively summarize dry eye disease adverse reaction resulting from pharmacotherapy for early-stage breast cancer. Through a review of the relevant literature, this study explored the etiology, clinical features, and potential therapeutic strategies for drug-induced dry eye disease in breast cancer treatment. A thorough understanding of the medication-induced dry eye disease adverse reaction aid clinicians in monitoring and managing patients' ocular health more effectively, facilitating early diagnosis and intervention, preventing complications, and ensuring optimal visual protection for patients undergoing breast cancer treatment.

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).

The efficacy of vitamin D supplementation in dry eye disease: A systematic review and meta-analysis.

PURPOSE: Vitamin D (VD) is a vitamin with anti-inflammatory and immunomodulatory effects. Several studies have shown that VD deficiency is associated with the incidence and severity of dry eye disease (DED) in humans. This meta-analysis compared signs and symptoms in patients with DED before and after VD supplementation. METHODS: Ten databases (PubMed, Cochrane, Web of science, Ovid, Embase, Scopus, CNKI, CSTJ, Wanfang, Sinomed) and four clinical trials registry websites (ISRCTN, CT, ICTRP, ICH GCP) were searched for studies on the efficacy of VD supplement in patients with DED that were published up to 2023 January. A total of 8 studies with 439 cases were included. Two reviewers independently assessed the quality of the literature and extracted data to calculate standard mean differences (SMD) for the Schirmer's test (SH test), tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS, Oxford Scale, 0-5), lid hyperemia, ocular surface disease index (OSDI), and visual analogue pain scale (VAS). RESULTS: The analysis showed that VD supplementation improved tear production (SMD 1.43, 95% CI 0.81, 2.05, p = 0.000) and tear film stability (SMD 1.19, 95% CI 0.83, 1.55, p = 0.000) and reduced lid hyperemia (SMD -0.71, 95% CI -1.09, -0.32, p = 0.000) and OSDI (SMD -1.10, 95% CI -1.45, -0.74, p = 0.000), which is effective in alleviating the signs and symptoms of DED. CONCLUSIONS: VD supplementation could be an adjuvant treatment to alleviate the signs and symptoms of dry eye in the future. However, further studies regarding its most appropriate administration and dosage need to be conducted.

Dry eye disease in systemic lupus erythematosus: a cross sectional study.

AIM: To explore ocular surface manifestations of dry eye disease (DED) and its influencing factors in systemic lupus erythematosus (SLE) patients. METHODS: Ophthalmological examinations were conducted in SLE patients (n=43) and controls (n=41), including Ocular Surface Disease Index (OSDI), objective scatter index (OSI), tear meniscus height (TMH), lipid layer thickness (LLT), non-invasive Keratograph tear breakup time (NIKBUT), corneal fluorescein score (CFS), Schirmer I test. DED was diagnosed according to the Tear Film and Ocular Surface Society Dry Eye Workshop II Criteria. SLE patients were further divided into DED group and non-DED group, the disease activity, clinical manifestations and laboratory investigations were compared between the two groups. The disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Receiver operative characteristic (ROC) curve and multiple-factor binary logistic regression were performed. RESULTS: SLE patients showed higher OSDI [9.1 (2.8-15.9) vs 6.3 (2.2-7.5), P=0.035], higher OSI [1.67 (1.09-2.60) vs 0.96 (0.87-1.60), P=0.001], higher CFS [1 (0-2) vs 0 (0-1), P=0.001], lower LLT [65 (42-100) vs 100 (79.5-100), P=0.010], and lower NIKBUT [8.03 (4.02-9.73) vs 9.67 (5.26-12.71), P=0.030] than controls. The 32.6% of SLE patients had DED, which was higher than 12.2% of healthy controls. DED group showed higher SLEDAI-2K score [9.7±6.1 vs 5.4±3.4, P=0.025], higher anti-cardiolipin antibody (ACL) [8.7 (3.5-13.2) vs 3.6 (2.0-6.9), P=0.035], and higher proportion of patients with cutaneous eruption [42.9% vs 6.9%, P=0.015] than non-DED group. According to multiple-factor binary logistic regression analysis, the SLEDAI-2K score (OR=1.194, P=0.041) and cutaneous eruption (OR=7.094, P=0.045) could be consider as risk factors for DED in SLE patients. The ROC curve of the combined factors including age, disease duration, SLEDAI-2K score, ACL, and cutaneous eruption was analyzed, with a sensitivity of 0.786, a specificity of 0.793, and an area under curve of 0.820. CONCLUSION: Ocular surface affection is frequent in SLE patients, and patients with high disease activity and cutaneous eruption show increased risk of DED.

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.

Effect of Periodontitis on Dry Eye Disease Signs and Symptoms: A Cross-sectional Study.

PURPOSE: Gingivitis and periodontitis are oral disorders characterised by chronic inflammation, impacting the supportive structures around teeth due to bacterial accumulation. While the role of inflammation in both periodontitis and dry eye disease (DED) has been established individually, their potential association remains unclear. This study aimed to investigate the association between periodontitis and the manifestation of signs and symptoms related to DED in patients aged 18-40. MATERIALS AND METHODS: A cross-sectional study was conducted involving healthy controls, DED patients with or without periodontitis, and patients with periodontitis without DED. Ophthalmic and oral examinations were performed, and demographic, ocular, and systemic disease data were collected. Statistical analysis was conducted using ANOVA and chi-squared tests. RESULTS: A total of 684 participants were included in the study. Significant elevations in tear osmolarity levels, increased Ocular Surface Disease Index scores (OSDI), and decreased tear break-up time (TBUT) and Schirmer (ST-I) values were observed in DED patients with periodontitis compared to individuals with DED but without periodontitis, as well as control and periodontitis groups. Furthermore, higher neutrophil-to-lymphocyte ratios (NLR) were found in DED patients with periodontitis. CONCLUSION: The findings suggest an association between periodontitis and the severity of signs and symptoms related to DED. The study highlights the importance of interdisciplinary approaches in understanding the systemic implications of periodontal disease and its potential impact on ocular health.

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.

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.

Rosmarinic acid-grafted gelatin nanogels for efficient diquafosol delivery in dry eye disease therapy.

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.

Detection of Subclinical Neurotrophic Keratopathy by Noncontact Esthesiometry.

INTRODUCTION: This study aimed to analyze corneal sensitivity with a new noncontact and handheld esthesiometer (Brill Engines, Spain) in patients with dry eye disease (DED) and patients on hypotensive drops, and to compare it with healthy subjects. METHODS: A total of 31 patients (57 eyes) with DED, 23 patients (46 eyes) with glaucoma, and 21 healthy patients (33 eyes) were recruited. In all patients, corneal sensitivity was measured. Subsequently, a keratography test (Keratograph 5M, Oculus) was carried out to measure tear meniscus height (TMH), non-invasive breakup time (NIBUT), bulbar redness (Jenvis scale), and corneal staining (CS, Oxford scale). Both corneal sensitivity and ocular surface parameters were compared between DED, glaucoma, and healthy subjects. Linear mixed models were constructed to utilize data from both eyes of patients. An alpha level of 0.05 was considered statistically significant. RESULTS: The mean age was 56.1 ± 16.1 years in the DED group, 69.5 ± 11.7 years in the glaucoma group, and 37.190 ± 11.677 years in the control group. After adjustment for age and sex, corneal sensitivity was significantly reduced in DED and glaucoma vs control group (P = 0.02 and P = 0.009, respectively). NIBUT was lower in DED and glaucoma groups (P < 0.001 and P = 0.001, respectively). Redness and CS values were higher in the DED group (P = 0.04 and P = 0.001, respectively). TMH was lower in the glaucoma group (P = 0.03). CONCLUSIONS: Corneal sensitivity measured with a novel noncontact esthesiometer was reduced in DED and glaucoma groups compared to controls. In clinical practice, this esthesiometer could be an easy-to-use device to screen for patients with subclinical neurotrophic keratopathy.

Sutureless Dehydrated Amniotic Membrane (Omnigen) Application Using a Specialised Bandage Contact Lens (OmniLenz) for the Treatment of Dry Eye Disease: A 6-Month Randomised Control Trial.

Background and Objectives: Dry Eye Disease (DED) is a chronic condition characterised by tear film instability and ocular surface disruption, significantly impacting patients' quality of life. This study aimed to provide top-level clinical evidence for the long-term efficacy of dehydrated amniotic membrane (dAM, Omnigen®) delivered via a specialised bandage contact lens (sBCL, OmniLenz) for managing moderate-to-severe DED. Materials and Methods: This randomised controlled trial (NCT04553432) involved 93 participants with moderate-to-severe DED, randomised to receive a 1-week bilateral treatment of either dAM (17 mm diameter with 6 mm central 'window') applied under a sBCL or sBCL alone. Participants were assessed at baseline and followed up at 1, 3, and 6 months post-treatment. Outcomes included changes in symptomatology, tear film and ocular surface measurements, and in vivo confocal microscopy imaging of corneal nerve parameters and corneal dendritic cell (CDC) counts. Results: The dAM-sBCL group demonstrated a 65% reduction in OSDI scores at 6 months (p < 0.001), with 88% of participants showing improvement at 1 month. Corneal staining was significantly reduced in both groups. dAM-sBCL provided significant improvements in corneal nerve parameters at 1 month, with sustained positive trends at 3 months. Additionally, dAM-sBCL significantly reduced mature CDC counts, suggesting an anti-inflammatory effect. Conclusions: Treatment with dAM-sBCL for just 1 week significantly and rapidly improved dry eye symptoms as well as ocular surface signs for at least 3 months. It also enhanced corneal nerve health while reducing activated/mature corneal inflammatory cell numbers, presenting a safe and promising new treatment for moderate-to-severe DED.