Development Of Dry Eye Disease Research Articles

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.Graphical

Analyzing Tear Fluid Composition by Synchronous Fluorescence for Diagnosing Dry Eye Disease and the Role of Phytotherapy Intervention.

Tear fluid gained attention as a representative biological fluid. Its simple and non-invasive collection methods as well as richness of candidate biomarkers made it a potential diagnostic tool for different diseases such as dry eye. Synchronous fluorescence spectroscopy is a highly sensitive analytical tool that results in narrowing and enhanced peak resolution, and has a potential role in disease diagnosis, biomarker identification, and therapeutic monitoring. We applied synchronous fluorescence spectroscopy to monitor variations of tear fluid composition during the development of dry eye disease and to evaluate the potential effects of phytotherapy. Dry eye model was induced in Chinchilla rabbits by instillation of 1% atropine sulfate ophthalmic solution. Then, the tear fluid was collected at 3, 7, and 14days and subjected to synchronous fluorescence spectroscopy. Phytotherapy was achieved by topical instillation of 20µl of water extracts of pomegranate peel or green tea powders. The fluorescence results revealed changes in the structure of tear fluid over time and the eye is subjected to toxification due to oxidative stress. In addition, dry eye disease was found to affect the metabolic/energetic state of the eye. On the other hand, phytotherapy led to enhancement of the metabolic/biosynthesis state due to activation of flavin adenine dinucleotide-associated proteins. There was change in the electrical conductivity of tear fluid proteins. In the case of dry eyes, they became electrical insulators, while in the case of treatment with extracts, their electrical conductivity properties improved. The effects of phytotherapy can be related to the high content of ellagic acid and anthocyanin of pomegranate extract, while in green tea, they are related to catechins and phenolic compounds.

The Association between Ovarian Cancer and the Incidence of Newly Developed Dry Eye Disease: A Nationwide Population-Based Study.

We aim to investigate the potential correlation between the presence of ovarian cancer and the development of dry eye disease (DED) via the usage of the Longitudinal Health Insurance Database (LHID) of Taiwan. A retrospective cohort study was executed, and patients with ovarian cancer were selected according to the diagnostic and procedure codes. One ovarian cancer patient was matched to four non-ovarian cancer participants which served as control group, and a total of 4992 and 19,968 patients constructed the ovarian cancer and control groups, respectively. The primary outcome in the current study is the development of DED according to the diagnostic and procedure codes. Cox proportional hazard regression was utilized to produce the adjusted hazard ratio (aHR) and related 95% confidence interval (CI) of DED between the two groups. There were 542 and 2502 DED events observed in the ovarian cancer group and the control group, respectively. The ovarian cancer group illustrated a significantly higher incidence of DED development than the control group after the adjustment of several confounders (aHR: 1.10, 95% CI: 1.01-1.21, p = 0.040). In the subgroup analysis stratified by age, ovarian cancer patients aged older than 60 years showed a higher incidence of DED compared to the non-ovarian cancer population (aHR: 1.19, 95% CI: 1.08-1.28, p = 0.011). In addition, ovarian cancer patients with a disease duration longer than five years also showed higher incidence of DED formation than the non-ovarian cancer population (aHR: 1.13, 95% CI: 1.04-1.22, p = 0.027). In conclusion, the presence of ovarian cancer is associated with higher incidence of subsequent DED, especially in those older than 60 years and with a disease interval of more than five years.

Immunologic basis for development of keratoconjunctivitis sicca in systemic autoimmune diseases: Role of innate immune sensors

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions.Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye.

Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects.

Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions.

The Utilization of Glucagon-like Peptide 1 Agonists and Risk of Following External Eye Diseases in Type 2 Diabetes Mellitus Individuals: A Population-Based Study.

The glucagon-like peptide 1 (GLP-1) agonist showed anti-hyperglycemic and anti-inflammatory effects, which may retard the risk of external eye disease. The protective effect of GLP-1 agonist and dry eye disease (DED) was found, while the relationship between GLP-1 agonist and other corneal diseases was not clear. Herein, we aim to evaluate the association between the usage of GLP-1 agonists and the development of the following external eye disease in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan was conducted. The T2DM patients were divided into those with GLP-1 treatment and those without GLP-1 treatment and matched with a 1:2 ratio. The main outcomes were the development of dry eye disease (DED), superficial keratitis, and infectious keratitis. The Cox proportional hazard regression was adopted to produce the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) of external eye diseases between groups. There were 115, 54, and 11 episodes of DED, superficial keratitis, and infectious keratitis in the GLP-1 group. Another 280, 168, and 31 events of DED, superficial keratitis, and infectious keratitis were recorded in the control group. The GLP-1 group demonstrated a significantly lower incidence of DED (aHR: 0.853, 95% CI: 0.668-0.989, p = 0.0356) and superficial keratitis (aHR: 0.670, 95% CI: 0.475-0.945, p = 0.0107) compared to the control group. In the subgroup analyses, the correlation of GLP-1 agonist and DED development was more prominent in patients younger than 60 years old (p = 0.0018). In conclusion, the GLP-1 agonist treatments are significantly associated with a lower incidence of subsequent DED and superficial keratitis, while the relationship was not significant between GLP-1 agonist usage and infectious keratitis.

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease.

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

Restoration of Meibomian Gland Functionality with Novel Mesenchymal Stem Cell-Derived Product “Derived-Multiple Allogeneic Proteins Paracrine Signaling (d-MAPPS)”: A Case Report

Abstract Meibomian gland dysfunction (MGD) results in the increased tear film osmolarity and leads to the development of dry eye disease. Results obtained in several experimental and clinical studies suggested that mesenchymal stem cells (MSCs) could promote repair and regeneration of injured meibomian glands. We recently developed a new biological product “derived-Multiple Allogeneic Proteins Paracrine Signaling (d-MAPPS)” which activity was based on the effects of immunosuppressive and trophic factors secreted by MSCs. Herewith, we report a case of MGD treated by d-MAPPS containing eye drops, demonstrating therapeutic potential of d-MAPPS in regeneration of injured meibomian glands and in the attenuation of MGD. D-MAPPS containing eye drops significantly attenuated MGD-related symptoms (foreign body sensation, burning, pain in the eye and eye fatigue) and remarkably improved quality of life. The analysis of meibomian glands demonstrated restoration of meibomian gland morphology, structure and function, after the 3-weeks of d-MAPPS based therapy. MGD patient did not report any adverse effects related to the d- MAPPS administration, indicating that d-MAPPS containing eye drops were safe for intraocular application.

Dry Eye Disease following LASIK, PRK, and LASEK: An Observational Cross-Sectional Study.

Dry eye disease is the most frequent non-refractive postoperative complication following refractive surgery. This prospective study investigated the development of dry eye disease after three common refractive laser surgeries: laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and laser-assisted sub-epithelial keratectomy (LASEK). Patients who underwent uneventful refractive surgery in a single private medical center between May 2017 and September 2020 were included. Ocular surface disease was graded according to the Dry Eye Workshop severity (DEWS) classification. Patients were examined 6 months following refractive surgery. The analysis included 251 eyes of 137 patients: 64 eyes (36 patients) after LASEK, 90 eyes (48 patients) after PRK, and 97 eyes (53 patients) after LASIK. At 6 months post-surgery, the DEWS score was higher for the LASIK than the PRK and LASEK groups (p = 0.01). For the total cohort, severe DEWS score (grades 3 and 4) at 6 months post-surgery was correlated with female gender (p = 0.01) and to the amount of refractive correction (p < 0.001), but not to age (p = 0.87). In conclusion, LASIK surgery and female gender were associated with dry eye. Patients, particularly those with high myopia, should be counseled about the risk of developing dry eye after refractive surgeries.

Dry eye among medical students before and during COVID-19.

Dry eye is a multifactorial disease of the ocular surface. It showed an increased incidence during the pandemic situation, which may be due to long hours of exposure to electronic gadgets. We aimed to find the prevalence of dry eye disease among medical students during the coronavirus disease 2019 (COVID-19) pandemic and pre-pandemic periods. This was a cross-sectional study conducted in a tertiary care teaching institute. This was an institution-based, cross-sectional study conducted among medical students. A modified Ocular Surface Disease Index (OSDI) questionnaire was used to find the severity and prevalence of dry eye disease. Considering 95% confidence interval (CI) and prevalence as 50%, the calculated sample size was 271. Online responses were collected and entered in an Excel sheet. The Chi-square test, univariate and multivariate logistic regression were used for statistical analysis. Data were collected from 271 medical students; the prevalence of dry eye disease was 41.5 and 55.19 during the pre-pandemic and pandemic periods, respectively. There was a significant rise in dry eye disease cases during the pandemic when compared to pre-pandemic period (P < 0.05). The odds of getting dry eye disease were 1.7 times more during the pandemic than pre-pandemic. The lockdown situation during the pandemic forced people to use electronic gadgets for work, recreation, and academics. Prolonged screen time predisposes to the development of dry eye disease.

An insight on the eye bacterial microbiota and its role on dry eye disease.

The human ocular surface hosts a bacterial assemblage that integrates a diverse and complex microbiome. This bacterial microbiota is part of a healthy eye and plays a protective role in it. However, this ocular bacterial assemblage may alter the ocular surface inflammation response and can influence the development and progression of dry eye disease. For this reason, the present review describes the changes generated on the ocular surface by bacterial assemblages during the development of dry eye disease. Likewise, the interaction of this microbiota with the other inflammatory factors that influence the development of this disease is analyzed, as well as the use of treatments focused on modifying the bacteria on the ocular surface.

The relationship between sedentary behavior and dry eye disease

PurposeSedentary behavior (SB) has been linked with low-grade systemic inflammation, which could play a role in the development of dry eye disease (DED). This cross-sectional study aims to investigate the association between SB and DED. MethodsWe assessed 48,418 participants from the population-based Lifelines cohort (58% female, 18–96 years). Women's Health Study (WHS)-defined DED was the primary outcome. SB was assessed using the Marshall Sitting Questionnaire. The relationship between DED and SB was analyzed using logistic regressions, corrected for age, sex, BMI, smoking status, demographics, and 48 comorbidities. Any potential modifying effect of physical activity (PA) was also assessed, and the analyses were repeated excluding the most computer-intensive domains, investigating SB independent from screen exposure. ResultsWHS-defined DED was present in 9.1% of participants. Greater SB was associated with an increased risk of DED (odds ratio (OR) 1.015 per hour/day, 95%CI 1.005–1.024, P = 0.004). The association between SB and DED was only significant for those with less than WHO-recommended PA (OR 1.022, 95%CI 1.002–1.042, P = 0.027), and not in participants meeting WHO's recommendation (OR 1.011, 95%CI 0.999–1.023, P = 0.076). Lastly, when excluding computer-related sitting, the relationship between SB and DED was attenuated, and no longer significant (OR 1.009, 95%CI 0.996–1.023, P = 0.19). ConclusionsGreater sedentary time was tied to an increased risk of DED, especially for those with lower PA levels than WHO recommendations. However, as there was no significant association when computer-intensive sitting time was excluded, screen use could explain the observed relationship and should be noted as a possible key confounder.

Predictive significance of genetic analysis of the development of dry eye disease of different origin

The aim of the study was to determine the prognostic significance of a panel of polymorphic gene markers in the development of dry eye syndrome in patients with primary Sjögren's syndrome and rheumatoid arthritis over a five-year follow-up period. Patients with a verified diagnosis of PSS and RA without signs of DED were examined (n=35 and n=42, respectively). The control group included 82 volunteers without AID and DED. The observation period was 5 years. Every year all study subjects underwent an ophthalmological clinical and functional examination. Dry eye disease had developed in groups of patients with AID with predisposing genotypes of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22. The peak of DED development in these patients was in the third year of the follow-up. As a result of ROC analysis, it was found that the sensitivity and specificity of determining the predisposing genotypes of polymorphic markers of the THBS1, MUC1, TRIM21, STAT4, PTPN22 genes was 68 and 87%, respectively (p<0.0001). Genetic research methods are essential for minimally invasive early diagnosis of dry eye disease, and can subsequently become the basis for a personalized approach to its treatment.

Mask Associated Dry Eye Section (MADE) in Healthcare Workers: A Cross-sectional Study

Introduction: The Coronavirus disease-19 (COVID-19) pandemic mediated by Severe Acute Respiratory Syndrome-CoV2 (SARSCoV2), made the use of face masks mandatory to check the spread of the disease. With the increased use of face masks, more people started presenting to the ophthalmologist with symptoms of dry eye. The proposed mechanism of dry eye was attributed to air blowing upwards from behind the mask into the eyes, especially in loose fitting masks. This air leads to rapid evaporation of tears and disturbance of homeostasis of the tear film. Aim: To measure self reported symptoms of dry eye and to establish mask use as a risk factor for the development of Dry Eye Disease (DED) in healthcare workers in a Tertiary Care Hospital. Materials and Methods: This cross-sectional, observational study was conducted at Nilratan Sircar (NRS) Medical College and Hospital for a duration of three months from December 2021 to February 2022. The study was conducted on 146 participants. An online survey was conducted using Google Forms, sent via email to hospital employees working in different departments of the hospital. All healthcare workers employed at NRS Medical College and Hospital who wore a face mask during duty hours and were willing to participate in the study were included. The Ocular Surface Disease Index (OSDI) questionnaire was used and modified by adding “while wearing a facemask” to the end of each question. To establish face mask use as a causative agent for development of DED, a few other questions related to face mask usage were included in the survey. The data was tabulated in Microsoft Excel and analysed with Statistical Package for Social Sciences (SPSS) version 24. Results: The mean age of the study population was 27.4±8.28 years. The mean hours of wearing a mask was 6.38 ±3.04 hours. N95 face mask was the most common type of mask used. The study population included 100 doctors, 14 nursing staff, 18 optometrists, eight group D staff (sweepers and ward attendants), and six dieticians. The mean OSDI score was 14.24. Increased usage of face masks, in particular surgical, more hours of reading significantly correlated with higher incidence of DED. Conclusion: This study showed that increased hours of face mask use in particular surgical was associated with development of DED. To encourage more people to wear face masks, all possible problems arising from face mask use should be promptly identified and dealt with.

Prolactin Inducible Protein, but Not Prolactin, Is Present in Human Tears, Is Involved in Tear Film Quality, and Influences Evaporative Dry Eye Disease.

PurposeDecreased production of the aqueous component of the tear film is an important cause of the development of dry eye disease (DED). Tear production is influenced by hormones and hormone-like factors. Prolactin (PLR), a multifunctional pituitary gland hormone, is regularly present in the lacrimal gland of rats and rabbits. In humans, serum PLR concentration correlates with tear quality. To gain deeper insights of possible effects of PRL, prolactin receptor (PRLR) and prolactin inducible protein (PIP), we analyzed the three proteins in the human lacrimal apparatus and in reflex tears of healthy volunteers as well as patients suffering from DED.MethodsGene expression of PRLR and PIP was analyzed by RT-PCR in cadaveric human lacrimal gland and ocular surface tissues, immortalized human corneal epithelial cells (HCE and hTEPI) and human Meibomian gland epithelial cells (HMGECs). At the protein level, the expression and localization of PRL, PRLR and PIP in formalin-fixed paraffin sections of the lacrimal apparatus were studied by immunohistochemistry. In addition, tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the concentration of PRL and PIP.ResultsRT-PCR analyses revealed gene expression of PRLR and PIP in human tissue samples of cornea, lacrimal glands, and eyelids, whereas only PIP, but not PRLR, was detectable in immortalized corneal epithelial cells. Immunohistochemistry revealed for the first time the expression and localization of PRL, PRLR, and PIP in human tissues of the lacrimal apparatus and at the ocular surface. PRL and PRLR were detectable in corneal epithelium, lacrimal glands, and Meibomian glands. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers.ConclusionPRL, PRLR, and PIP are found in the lacrimal apparatus and on the ocular surface. PIP, but not PRL, is present in human tears and appears to be involved in the physiology of tear film quality. Our clinical data revealed that PIP may affect tear quality, but further functional analyses are needed to fully elucidate the effects of PRL and PIP-associated factors in tear secretion as well as in the connection of DED.

The role of Meibomian glands on the development of dry eye disease in patients with unilateral pseudoexfoliation

To evaluate the Meibomian glands and presence of dry eye in patients with unilateral pseudoexfoliation. The study included 32 patients with clinical pseudoexfoliation (PEX) in one eye and 30 controls. Schirmer and tear film break-up time (TBUT) tests were performed, along with a detailed ophthalmological examination, meibography and evaluation of areas of meibomian gland loss. Subjective symptoms were evaluated using the ocular surface disease index (OSDI). Schirmer test results for eyes with or without PEX were similar (10.438±4.47mm and 11.563±4.35mm, respectively), vs. 15.967±9.75mm in the control group. While measurements of TBUT were found to be similar in both eyes of the patient group (6.188±2.66s in eyes with PEX and 6.250±1.87s in eyes without PEX), this was 8.233±2.66s in the control group. Schirmer and TBUT test results were found to be significantly lower in both eyes of patients with unilateral pseudoexfoliation compared to control eyes. The rate of meibomian gland loss in the upper and lower eyelids in the patient group was found to be significantly higher than in the control group. Similarly, meiboscores of both eyelids in the control group were significantly lower than those in patient group; however, there were no differences between patient eyes with or without pseudoexfoliation. The patients with unilateral pseudoexfoliation had a significant loss of meibomian gland area in both eyes compared to the control group, and their meiboscore was higher. It should be considered that meibomian gland loss may be one of the causes of dry eye in patients with pseudoexfoliation.

Autophagy Protects Ocular Surface Against Overactivated Inflammation by Degrading Retinoic Acid-Induced Gene-I in Human Conjunctival Epithelial Cells.

Purpose: To evaluate the pathological role of autophagy in dry eye diseases by detecting the autophagic degradation of RIG-I, a master RNA-sensing receptor in cells. Methods: RNA-sequencing analysis and qPCR analysis of the expression level of genes related to IFN-I signaling pathway was used to evaluate the inflammatory level of cells overexpressed with RIG-I or empty vector, which was further confirmed by WB analysis. Chemical treatment (3-methyladenine, chloroquine, NH4Cl, rapamycin, torin 1 or trehalose) or gene knockdown was used to modulate autophagy. When the autophagy level was regulated, the autophagic degradation of RIG-I and its pathological role in dry eye diseases were determined by detecting the protein level of RIG-I and the level of cell inflammation. Results: Cells that overexpressed RIG-I showed increased expression of genes involved in the IFN-I signaling pathway compared with cells transfected with an empty vector. Inhibition of autophagy leaded to the accumulation of RIG-I in HCECs, combined with the aggravation of the RIG-I-mediated IFN-I signaling pathway. Contrarily, promoting the autophagic degradation of RIG-I by trehalose treatment could alleviate IFN-I signaling pathway. Conclusions: Autophagy could protect the ocular surface against IFN-I signaling pathway by degrading RIG-I in HCECs. This process may restrict the overactivation of inflammation in the pathological development of dry eye disease.

IGFBP-3 Regulates Mitochondrial Hyperfusion and Metabolic Activity in Ocular Surface Epithelia during Hyperosmolar Stress.

In the eye, hyperosmolarity of the precorneal tear film triggers inflammation and the development of dry eye disease (DED), a highly prevalent condition that causes depression and disability in severe forms. A member of the insulin-like growth factor (IGF) family, the IGF binding protein-3 (IGFBP-3), is a pleiotropic protein with known roles in growth downregulation and survival. IGFBP-3 exerts these effects by blocking IGF-1 activation of the type 1 IGF-receptor (IGF-1R). Here, we examined a new IGF-independent role for IGFBP-3 in the regulation of mitochondrial and metabolic activity in ocular surface epithelial cells subject to hyperosmolar stress and in a mouse model of DED. We found that hyperosmolar stress decreased IGFBP-3 expression in vitro and in vivo. Treatment with exogenous IGFBP-3 induced an early, transient shift in IGF-1R to mitochondria, followed by IGFBP-3 nuclear accumulation. IGFBP-3 nuclear accumulation increased protein translation, blocked the hyperosmolar-mediated decrease in oxidative phosphorylation through the induction of mitochondrial hyperfusion, and restored corneal health in vivo. These data indicate that IGFBP-3 acts a stress response protein in ocular surface epithelia subject to hyperosmolar stress. These findings may lead to the development of first-in-class therapeutics to treat eye diseases with underlying mitochondrial dysfunction.

Occupational ocular health problems among marble workers at Shaq El Tho’ban industrial area in Egypt

Eye health of the working population is an essential condition for productivity. Marble industry is processed at large scale at Shaq El Tho’ban area where much dust, crushed pieces of stone, and fluctuating temperatures are endangering employees’ health generally and eye health specifically. The objectives of this study were assessing the prevalence of the most common ocular health problems associated with marble industry and investigating the impact of the working environment and occupational risk factors on the oculo-visual status of marble workers. A cross-sectional study was conducted among 250 workers, working at Shaq El Tho’ban area in Egypt during the period from August 2020 to September 2021, using a semi-structured questionnaire and eye examination comprised of full ocular history, visual acuity testing (unaided/aided), slit lamp examination, ophthalmoscopy, and Schirmer’s type I and tear break up time tests. The current study showed that gritty sensation (65.2%) and eye dryness (51.2%) were the commonest symptoms complained. By examination, conjunctival hyperemia (59.6%) was the most prevalent finding. By performing dry eye tests, dry eye was diagnosed in 60.4% and 51.2% of workers by Schirmer’s test and tear break up time test respectively. The study’s results indicated that age, working category, smoking, and diabetes had significant impact on development of ocular symptoms, while working duration, diabetes, smoking, ocular symptoms, and ocular foreign body had significant impact on development of dry eye disease. Implementation of engineering control measures, proper designing, and supply of eye PPE together with adequate health education to all workers about occupational health risks and preventive measures are recommended.

The role of meibomian gland dysfunction on the development of dry eye disease in patients with facial nerve palsy.

To investigate whether meibomian gland dysfunction is the cause of dry eye in facial nerve palsy and to identify the possible relationship between the grades and durations of facial nerve palsy and meibomian gland dysfunction. This prospective observational study included 63 patients with unilateral facial nerve palsy. Facial nerve function and severity were assessed using the House-Brackmann grading system. Unaffected contralateral eyes were used as the control group. The following parameters were compared: tear breakup time, Schirmer 1 test score, area and density scores for corneal fluorescein staining, eyelid abnormality, meibomian gland expression, meibography scores, and areas of meibomian gland loss. A Pearson correlation analysis was performed between the grades and durations of facial nerve palsy and meibomian gland dysfunction. The eyes affected by facial nerve palsy demonstrated significantly lower tear breakup time (p<0.001) and significantly higher values for corneal fluorescein staining (p<0.001), Schirmer 1 test score (p=0.042), lid abnormality score (p<0.05), meibomian gland expression level (p=0.005), meibography scores (p<0.05), and areas of meibomian gland loss (p<0.05). The grade and duration of facial nerve palsy significantly correlated with meibomian gland dysfunction (p<0.05). Meibomian gland dysfunction has a significant contribution to the development of dry eye disease after facial nerve palsy. Furthermore, a strong correlation was observed between the grades and durations of facial nerve palsy and meibomian gland dysfunction.