KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye.

Purpose: The purpose of this study was to elucidate the involvement of potassium two pore domain channel subfamily K member 5 (KCNK5)-mediated potassium efflux in the pathogenesis of dry eye and to unravel the underlying molecular mechanisms. Methods: To induce experimental dry eye in adult wild-type C57BL/6 mice, scopolamine was administered via subcutaneous injection, and the mice were subjected to desiccating stress. To create an in vitro model of dry eye, desiccation stress was applied to the human corneal epithelial cell line (HCE-T). Intracellular potassium concentration was quantified using inductively coupled plasma mass spectrometry. Cellular death was assessed through lactate dehydrogenase assays. Gene expression profiling was conducted through both RNA sequencing and quantitative real-time PCR. Protein analysis was carried out through Western blotting and immunofluorescence staining. Assessment of the corneal epithelial defect area was conducted through fluorescein sodium staining. Tear secretion was quantified using the phenol red cotton thread method. Results: Potassium efflux was observed to further facilitate corneal epithelial pyroptosis. KCNK5 exhibited upregulation in both in vivo and in vitro models of dry eye. The overexpression of KCNK5 was observed to induce potassium efflux and activate the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in vitro. Silencing KCNK5 effectively mitigated pyroptosis in dry eye. Additionally, the overexpression of KCNK5 results in the downregulation of TNF superfamily member 10 (TNFSF10) and subsequent impairment of autophagy. TNFSF10 supplementation could promote autophagy and mitigate pyroptosis in dry eye. Conclusions: The upregulation of KCNK5 mediates TNFSF10 to impair autophagy and induce pyroptosis in dry eye. Consequently, targeting KCNK5 may represent a novel and promising approach to therapeutic intervention in the management of dry eye.

Need to Increase the Number of Intense Pulsed Light (IPL) Treatment Sessions for Patients with Moderate to Severe Meibomian Gland Dysfunction (MGD) Patients.

PURPOSE: To evaluate whether patients with moderate-to-severe meibomian gland dysfunction (MGD) will benefit from increasing the number of intense pulsed light (IPL) treatment sessions. METHODS: Ninety Asian adult with MGD (stages 3-4) were enrolled in this retrospective study. In Group1, 30 patients completed the five-session IPL treatment, 63.33% of which also received meibomian gland expression (MGX). In Group 2, 60 patients received three-session IPL treatment, 60.0% of which also accepted MGX. Both intragroup and intergroup analyses were conducted. RESULTS: The population characteristics, clinical baseline characteristics and therapeutic regimen were comparable between Group1 and Group2. The symptoms and most clinical indices improved after IPL treatment finished in both two groups. No statistical difference was found in any improvement level of all symptomatic and physical indices, including the Ocular surface disease index, tear break-up time, Demodex, corneal staining, meibum quality, meibomian gland expressibility, and MGD stage (all p ≥ 0.05) between the two groups at any time, not only month by month, but also at the terminal visit. However, the response rate of Group1 after the five-session treatment (70.00%) was increased compared to that of Group2 after the three-session treatment (63.33%). CONCLUSIONS: Increasing the number of IPL sessions is beneficial for patients with moderate to severe MGD to increase the response rate of treatment, rather than the improvement level. However, there is no need for patients who respond well to a routine number of IPL treatments to undergo additional IPL sessions.

Berberine ameliorate inflammation and apoptosis via modulating PI3K/AKT/NFκB and MAPK pathway on dry eye.

BACKGROUND: Dry eye disease (DED) is a multifactorial disease in ocular surface, and inflammation plays an etiological role. Berberine (BBR) has shown efficacy in treating inflammatory diseases. Yet, there was no adequate information related to the therapeutic effects of BBR for DED. PURPOSE: To detect the effects and explore the potential mechanisms of BBR on DED. STUDY DESIGN: In vitro, in vivo study and network pharmacology analysis were involved. METHOD: The human corneal epithelium cells viability was evaluated with different concentrations of BBR. Dry eye murine model was established by exposing to the desiccating stress, and Ciclosporin (CSA), BBR eye drops or vehicle were topical administration for 7 days. The phenol red cotton tests, Oregon-green-dextran staining and Periodic acid-Schiff staining were performed and evaluated the dry eye after treatment. Inflammation and apoptosis levels of ocular surface were quantified. The potential targets related to berberine and dry eye were collected from databases. The Protein-Protein interaction network analysis and GO & KEGG enrichment analysis were realized by STRING database, Metascape platform and Cytoscape software to find core targets and signaling pathways. The SchrÖdinger software was used to molecular docking and PyMOL software to visualization. Finally, the levels of PI3K/AKT/NFκB and MAPK pathways were detected. RESULT: The data revealed BBR could rescue impaired HCE under hyperosmotic conditions. In addition, BBR eye drops could ameliorate dry eye. And BBR eye drops suppressed the inflammatory factors and CD4+T cells infiltration in conjunctiva. Besides, BBR eye drops protected ocular surface by avoiding the severe apoptosis and decreasing the level of MMP-3 and MMP-9. 148 common targets intersection between BBR and dry eye were found via network pharmacology analysis. Core proteins and core pathways were identified through PPI and GO&KEGG enrichment analysis. Molecular docking displayed excellent binding between BBR and those core targets. Finally, in vivo study verified that BBR eye drops had a therapeutic effect in dry eye by inhibiting PI3K/AKT/NFκB and MAPK pathways. CONCLUSION: The research provided convincing evidence that BBR could be a candidate drug for dry eye.

Novel treatment of chalazion using light-guided-tip intense pulsed light.

We assessed the effectiveness of light-guided-tip intense pulsed light (IPL) with meibomian gland expression (MGX) in chalazion treatment. Ninety-five eyes with chalazion received a light-guided-tip IPL-MGX treatment (IPL-MGX group), and another 95 eyes with chalazion received incision with curettage treatment (Control group). Prior to IPL or incision, as well as 1 month after the final treatment, data were gathered pertaining to the lesion location and size, hyperemia, lesions regression or recurrence, and a comprehensive ophthalmic examination. The total size of the chalazia in the IPL-MGX group was significantly reduced after the final treatment, with an average resolution rate of 70.5%, which is comparable to excision surgery. A significant decrease in chalazion recurrence rate was apparent after treatment in the IPL-MGX group compared with control. Moreover, the IPL-MGX demonstrated significant advancements throughout noninvasive tear film breakup time (NIBUT) as well as meibum grade in comparison to baseline and those in the the Control group. The use of IPL-MGX was found to be an efficient therapy for reducing the size and recurring frequency of chalazia, as well as for improving the meibomian gland function. It may be considered as a first-line treatment for cases of primary or recurrent chalazia with inflammation.

1,5-Dicaffeoylquinic acid from Pseudognaphalium affine ameliorates dry eye disease via suppression of inflammation and protection of the ocular surface.

PURPOSE: Pseudognaphalium affine (P. affine), a medicinal plant, has long been used to treat various diseases due to its astringent and vulnerary effects. These therapeutic benefits are largely attributed to high contents of phytochemicals, such as flavonoids and polyphenols, that have anti-inflammatory and tissue-protective activities. Herein, we investigated the potential of dicaffeoylquinic acids (diCQAs), polyphenols from P. affine, as a novel treatment for dry eye disease (DED). METHODS: We isolated 1,5-, 3,4-, 3,5- and 4,5-diCQAs from the P. affine methanol extract, and tested the effects of diCQA isomers in cultures of human corneal epithelial cells (CECs) under desiccating hyperosmolar stress and in two mouse models for DED: desiccating environmental stress-induced DED and the NOD.B10-H2b mouse model of ocular Sjögren's syndrome. RESULTS: Initial screening showed that, among the diCQAs, 1,5-diCQA significantly inhibited apoptosis and enhanced viability in cultures of CECs under hyperosmolar stress. Moreover, 1,5-diCQA protected CECs by promoting proliferation and downregulating inflammatory activation. Subsequent studies with two mouse models of DED revealed that topical 1,5-diCQA administration dose-dependently decreased corneal epithelial defects and increased tear production while repressing inflammatory cytokines and T cell infiltration on the ocular surface and in the lacrimal gland. 1,5-diCQA was more effective in alleviating DED, as compared with two commercially-available dry eye treatments, 0.05% cyclosporine and 0.1% sodium hyaluronate eye drops. CONCLUSIONS: Together, our results demonstrate that 1,5-diCQA isolated from P. affine ameliorates DED through protection of corneal epithelial cells and suppression of inflammation, thus suggesting a novel DED therapeutic strategy based on natural compounds.

Comparison of clinical outcomes between intense pulsed light therapy using two different filters in meibomian gland dysfunction: prospective randomized study.

Our study compared treatment efficacy between cut-off and notch filters in intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD) through a prospective, randomized paired-eye trial. Additionally, the efficacy of IPL treatment alone was investigated by restricting other conventional treatments. One eye was randomly selected for an acne filter and the other for a 590-nm filter. Identical four regimens of IPL treatments were administered. The tear break-up time (TBUT), Oxford scale, Sjögren's International Clinical Collaborative Alliance (SICCA) staining score, tear matrix metalloproteinase-9 (MMP-9) expression, tear osmolarity, and Ocular Surface Disease Index (OSDI) questionnaires were evaluated before and after IPL. Meibomian gland (MG) parameters were measured. When combining the results from both filters, the TBUT, SICCA staining score, OSDI score, and upper and lower lid meibum expressibility were improved after IPL. No significant differences were found between the two filters in the TBUT, Oxford scale, SICCA staining score, MMP-9 expression, tear osmolarity, and MG parameters. Although not significant, the acne filter showed better treatment efficacy than that in the 590-nm filter. IPL alone is efficacious in terms of ocular surface parameters, MG function, and subjective symptoms. Regarding filter selection, both acne and 590-nm filters are promising options for MGD treatment.

Intense pulsed-light treatment improves objective optical quality in patients with meibomian gland dysfunction.

BACKGROUND: To evaluate changes in objective optical quality following intense pulsed light (IPL) treatment combined with meibomian gland (MG) expression (MGX) in patients with MG dysfunction (MGD). METHODS: This retrospective cross-sectional study included MGD-related dry eye disease (DED) patients who received IPL treatment between March and December 2021 at Kim's Eye Hospital, Seoul, Republic of Korea. Each patient underwent four sessions of IPL treatment using Lumenis M22 (Lumenis Ltd., Yokneam, Israel) and MGX at three-week intervals. RESULTS: This study included 90 eyes from 45 patients with MGD. The mean age was 52.3 ± 16.1 years (range, 20-75 years), and 53.3% (24/45) of patients were female. Compared with the baseline, all clinical symptoms and signs significantly improved after IPL treatment combined with MGX. All optical quality parameters obtained with an optical quality analysis system (OQAS: Visiometrics, Castelldefels, Spain) have improved significantly over the baseline (p < 0.001). CONCLUSIONS: In patients with MGD, IPL treatment combined with MGX improved the objective optical quality and clinical signs and symptoms of DED.

Efficacy of intense pulsed light therapy on signs and symptoms of dry eye disease: A meta-analysis and systematic review.

This study reviewed the efficacy and safety of intense pulsed light (IPL) for the treatment of dry eye disease (DED). The PubMed database was used to conduct the literature search, which used the keywords "intense pulsed light" and "dry eye disease". After the authors evaluated the articles for relevancy, 49 articles were reviewed. In general, all treatment modalities were proven to be clinically effective in reducing dry eye (DE) signs and symptoms; however, the level of improvement and persistence of outcomes differed amongst them. Meta-analysis indicated significant improvement in the Ocular Surface Disease Index (OSDI) scores post-treatment with a standardized mean difference (SMD) = -1.63; confidence interval (CI): -2.42 to -0.84. Moreover, a meta-analysis indicated a significant improvement in tear break-up time (TBUT) test values with SMD = 1.77; CI: 0.49 to 3.05. Research suggests that additive therapies, such as meibomian gland expression (MGX), sodium hyaluronate eye drops, heated eye mask, warm compress, lid hygiene, lid margin scrub, eyelid massage, antibiotic drops, cyclosporine drops, omega-3 supplements, steroid drops, and warm compresses along with IPL, have been found to work in tandem for greater effectiveness; however, in clinical practice, its feasibility and cost-effectiveness have to be taken into consideration. Current findings suggest that IPL therapy is suitable when lifestyle modifications such as reducing or eliminating the use of contact lenses, lubricating eye drops/gels, and warm compresses/eye masks fail to improve signs and symptoms of DE. Moreover, patients with compliance issues have been shown to benefit well as the effects of IPL therapy is sustained for over several months. DED is a multifactorial disorder, and IPL therapy has been found to be safe and efficient in reducing its signs and symptoms of meibomian gland dysfunction (MGD)-related DE. Although the treatment protocol varies among authors, current findings suggest that IPL has a positive effect on the signs and symptoms of MGD-related DE. However, patients in the early stages can benefit more from IPL therapy. Moreover, IPL has a better maintenance impact when used in conjunction with other traditional therapies. Further research is needed to assess cost-utility analysis for IPL.

A randomized controlled study evaluating outcomes of intense pulsed light and low-level light therapy for treating meibomian gland dysfunction and evaporative dry eye.

Purpose: This randomized, controlled, blinded study evaluates the efficacy of intense pulsed light (IPL) therapy with low-level light therapy (LLLT) in the treatment of meibomian gland dysfunction (MGD) and evaporative dry eye (EDE) compared to a control group. Methods: Hundred patients with MGD and EDE were randomized into control (50 subjects, 100 eyes) and study group (50 subjects, 100 eyes). The study group underwent three sittings of IPL with LLLT 15 days apart and were followed up 1 month and 2 months after the last treatment sitting. The control group underwent sham treatment and was followed up at the same intervals. The patients were evaluated at baseline and 1 month and 3 months (post 1st treatment) for dry eye. Schirmer's test and tear breakup time (TBUT), OSDI, meibomian gland expression, and meibography. Results: The study group showed significant improvement in OSDI scores (P < 0.0001) compared to the control group and a significant improvement in TBUT (P < 0.005) compared to the control group. There was no change in schirmer's test and an improvement in the meibomian gland expression but not significant. Conclusion: The results show that a combined therapy of IPL with LLT is effective in treating MGD with EDE compared to controls, and repeated treatment sessions have a cumulative effect on the disease outcomes.

The Approach of Intense Pulsed Light Treatment in Patients with Different Severities of Meibomian Gland Dysfunction.

PURPOSE: To make appropriate therapeutic decisions of intense pulsed light (IPL) for meibomian gland dysfunction (MGD) patients. METHODS: Sixty patients with MGD stage 2-3 were enrolled in IPL Group1 and Self-hygiene Group; 110 patients with MGD stage 3-4 were included in IPL + MGX Group and IPL Group2. Patients in IPL groups received IPL treatment once a month for three times. Meibomian gland expression (MGX) was combined with IPL treatment in IPL + MGX Group. Meibomian gland (MG) functions, MGD stage, associated ocular-surface indexes, and response rate were evaluated. RESULTS: Population characteristics and clinical conditions were comparable between groups. In patients with MGD stage 2-3, both IPL Group1 and Self-hygiene Group improved in MG functions, ocular surface disease index (OSDI) and tear break-up time (TBUT). No statistical difference was found in improvements. Posttreatment response rate was 64.3-66.7% in two groups. In patients with MGD stage 3-4, IPL + MGX Group achieved better improvements in MG expressibility and higher response rate (75.5%) than IPL Group2 (63.3%). Referring to IPL treatment, no statistical difference in MG functions and OSDI improvements was found among MGD patients with different ages, genders, and IPL energy exposure. Patients with higher Fitzpatrick scale improved more in MG expressibility. CONCLUSION: Self-eyelid hygiene is cost-effective for milder MGD stages. Combining MGX with IPL is necessary in more severe stages. Adult patients with all age and different genders can benefit from IPL treatment. Patients with darker skin can benefit more in expressiblity.

The Effects of Lycium chinense, Cuscuta chinensis, Senna tora, Ophiopogon japonicus, and Dendrobium nobile Decoction on a Dry Eye Mouse Model.

Background and objective: Dry eye disease (DED) is a relatively common disorder associated with abnormal tear film and the ocular surface that causes ocular irritation, dryness, visual impairment, and damage to the cornea. DED is not a life-threatening disease but causes discomfort and multifactorial disorders in vision that affect daily life. It has been reported that all traditional medicinal plants exhibit anti-inflammatory effects on several diseases. We hypothesized that the decoction ameliorated ocular irritation and decreased cytokine expression in the cornea. This study aimed to investigate the molecular mechanisms of DED and discover a therapeutic strategy to reduce corneal inflammation. Material and Methods: We used a DED mouse model with extraorbital lacrimal gland (ELG) excision and treated the mice with a decoction of five traditional medicines: Lycium chinense, Cuscuta chinensis, Senna tora, Ophiopogon japonicus, and Dendrobium nobile for 3 months. The tear osmolarity and the ocular surface staining were evaluated as indicators of DED. Immunohistochemistry was used to detect the level of inflammation on the cornea. Results: After treatment with the decoction for three months, epithelial erosions and desquamation were reduced, the intact of corneal endothelium was maintained, and tear osmolarity was restored in the eyes. The IL-1ß-associated inflammatory response was reduced in the cornea in the DED model. Conclusions: These data suggested that a mixture of traditional medicines might be a novel therapy to treat DED.

Effect of Intense Pulsed Light Therapy in Dry Eye Disease Caused by Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to systematically evaluate the effect of intense pulsed light (IPL) therapy in patients harboring dry eye disease caused by meibomian gland dysfunction (MGD) based on qualified studies. METHODS: The electronic databases, including PubMed, Cochrane, and Embase, were searched using keywords to identify available publications updated to November 2021. Relative risk or weighted mean difference combined with 95% confidence interval was used to synthesize the outcomes of included studies. The meta-analysis included 15 randomized controlled trials with 1,142 patients (2,284 eyes). RESULTS: The results revealed that IPL could significantly decrease the ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED), artificial tear usage, tear film lipid layer, meibomian gland quality (MGQ), meibomian gland expression (MGX), and corneal fluorescein staining (CFS) while increase tear break-up time (TBUT) and noninvasive tear break-up time (NIBUT) compared with sham. Compared with MGX, IPL+MGX markedly decreased the SPEED, CFS, and tear meniscus height (TMH), but with increased TBUT. Compared with MGX, IPL showed significant effect in increasing the OSDI and TBUT, but decreasing the TMH and NIBUT. However, no significant differences were seen between IP+MGX and MGX in OSDI, MGQ, and MGX, nor between IPL and MGX in OSDI, SPEED, and TBUT. CONCLUSION: We identified that the application of IPL alone or IPL combined with MGX elicited superior clinical effect for improving the eye function and symptoms in the treatment of MGD-related dry eye disease, which is considered available for wide clinical application.

Combination treatment with intense pulsed light, thermal pulsation (LipiFlow), and meibomian gland expression for refractory meibomian gland dysfunction.

PURPOSE: To evaluate the clinical efficacy and safety of combination treatment with intense pulsed light (IPL), LipiFlow thermal pulsation, and manual meibomian gland expression (MGX) for patients with refractory meibomian gland dysfunction (MGD). METHODS: A total of 23 eyes from 23 patients who underwent combination treatment with IPL, LipiFlow, and MGX for refractory MGD were included in the study. All patients were followed up for 12 months after the first treatment. All patients were examined prior to treatment and underwent three sessions of IPL, LipiFlow, and MGX, a subsequent three sessions of IPL and MGX, and six subsequent sessions of MGX. Patients were examined 10 weeks, 6 months, and 12 months after the first treatment. The ophthalmologic examination included ocular surface disease index (OSDI), non-invasive tearfilm break-up time (NIBUT), lipid layer thickness (LLT), meibomian gland expressibility (MGE), meibomian gland morphology (meiboscore), and tear meniscus height (TMH). RESULTS: OSDI, NIBUT, LLT, and MGE significantly improved with treatment, which was maintained during the follow-up period. TMH and meiboscore remained unchanged throughout follow-up. No serious adverse events occurred during follow-up. CONCLUSIONS: Combination therapy with IPL, LipiFlow, and MGX was clinically effective and safe for the treatment of refractory MGD. Combination treatment could be considered for patients with insufficient improvement despite conventional MGD treatments, including IPL treatment with MGX.

Efficacy of Artificial Tears Based on an Extract of Artemia salina Containing Dinucleotides in a Rabbit Dry Eye Model.

(1) Background: Artemia salina is a brine shrimp containing high concentrations of dinucleotides, molecules with properties for dry eye treatment. For this reason, the purpose of the study was to evaluate the effect of the artificial tears based on an extract of Artemia salina in a rabbit dry eye model. (2) Methods: A prospective and randomized study was carried out. Twenty rabbits were divided into 4 groups (n = 5, each group): healthy rabbits, dry eye rabbits, dry eye rabbits treated with hypromellose (HPMC), and dry eye rabbits treated with Artemia salina. Dry eye was induced by the topical instillation of 0.2% benzalkonium chloride. The measurements were performed before and after the treatment for 5 consecutive days. (3) Results: The topical instillation of artificial tears containing Artemia salina showed beneficial effects on tear secretion, tear break-up time, corneal staining, the density of Goblet cells, heigh of mucin cloud secreted by these cells, and mRNA levels of IL-1ß and MMP9 in conjunctival cells. Compared with the HPMC, there was a statistically significant improvement (p < 0.05) with the Artemia salina in all the variables under study, except for the conjunctival hyperemia, density of Goblet cells, and mRNA levels of IL-6. (4) Conclusions: The potential of artificial tears based on Artemia salina as a secretagogue agent for dry eye treatment was confirmed, opening the door for future clinical trials and studies to extrapolate the findings for dry eye patients.

Inhibition of Aberrant α(1,2)-Fucosylation at Ocular Surface Ameliorates Dry Eye Disease.

Fucosylation is involved in a wide range of biological processes from cellular adhesion to immune regulation. Although the upregulation of fucosylated glycans was reported in diseased corneas, its implication in ocular surface disorders remains largely unknown. In this study, we analyzed the expression of a fucosylated glycan on the ocular surface in two mouse models of dry eye disease (DED), the NOD.B10.H2b mouse model and the environmental desiccating stress model. We furthermore investigated the effects of aberrant fucosylation inhibition on the ocular surface and DED. Results demonstrated that the level of type 2 H antigen, an α(1,2)-fucosylated glycan, was highly increased in the cornea and conjunctiva both in NOD.B10.H2b mice and in BALB/c mice subjected to desiccating stress. Inhibition of α(1,2)-fucosylation by 2-deoxy-D-galactose (2-D-gal) reduced corneal epithelial defects and increased tear production in both DED models. Moreover, 2-D-gal treatment suppressed the levels of inflammatory cytokines in the ocular surface and the percentages of IFN-γ+CD4+ cells in draining lymph nodes, whereas it did not affect the number of conjunctival goblet cells, the MUC5AC level or the meibomian gland area. Together, the findings indicate that aberrant fucosylation underlies the pathogenesis of DED and may be a novel target for DED therapy.

IGFBP-3 Mediates Metabolic Homeostasis During Hyperosmolar Stress in the Corneal Epithelium.

Purpose: The insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional secretory protein with well-known roles in cell growth and survival. Data in our laboratory suggest that IGFBP-3 may be functioning as a stress response protein in the corneal epithelium. The purpose of this study is to determine the role of IGFBP-3 in mediating the corneal epithelial cell stress response to hyperosmolarity, a well-known pathophysiological event in the development of dry eye disease. Methods: Telomerase-immortalized human corneal epithelial (hTCEpi) cells were used in this study. Cells were cultured in serum-free media with (growth) or without (basal) supplements. Hyperosmolarity was achieved by increasing salt concentrations to 450 and 500 mOsM. Metabolic and mitochondrial changes were assessed using Seahorse metabolic flux analysis and assays for mitochondrial calcium, polarization and mtDNA. Levels of IGFBP-3 and inflammatory mediators were quantified using ELISA. Cytotoxicity was evaluated using a lactate dehydrogenase assay. In select experiments, cells were cotreated with 500 ng/mL recombinant human (rh)IGFBP-3. Results: Hyperosmolar stress altered metabolic activity, shifting cells towards a respiratory phenotype. Hyperosmolar stress further altered mitochondrial calcium levels, depolarized mitochondria, decreased levels of ATP, mtDNA, and expression of IGFBP-3. In contrast, hyperosmolar stress increased production of the proinflammatory cytokines IL-6 and IL-8. Supplementation with rhIGFBP-3 abrogated metabolic and mitochondrial changes with only marginal effects on IL-8. Conclusions: These findings indicate that IGFBP-3 is a critical protein involved in hyperosmolar stress responses in the corneal epithelium. These data further support a new role for IGFBP-3 in the control of cellular metabolism.

Role of Choline in Ocular Diseases.

Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.

Comparison of intense pulsed light and near-infrared light in the treatment of dry eye disease: a prospective randomized study.

PURPOSE: To compare the efficacy of intense pulsed light (IPL) and near-infrared light (NIL) treatments in alleviating symptoms and signs of dry eye disease (DED). METHODS: Patients diagnosed with DED at the Peking University Third Hospital Eye Center from January 2019 to October 2019 were randomized to undergo either NIL therapy combined with meibomian gland expression (MGX; NIL Group) or IPL combined with MGX (IPL Group). Treatments were performed three times at 1-month intervals. DED signs and symptoms were evaluated before every treatment. We compared the clinical improvement within and between the groups. Additional comparisons were made according to the meibomian gland (MG) dropout grade. RESULTS: A total of 260 eyes of 130 patients (mean age, 49.68 ± 18.01 years) were included. The dryness and total symptom scores and the MG expressibility and secretion quality (upper and lower eyelids) significantly improved after the three treatments in both groups (p < 0.05). However, IPL had superior efficacy in improving blurred vision, photophobia, burning, increased secretions and the total symptom score at 2 months in patients with more severe MG dropout. CONCLUSIONS: Both IPL and NIL treatments were effective in the treatment of DED, but IPL provided greater symptom improvement, particularly in patients with severe MG dropout. NIL can be a new therapeutic option for the treatment of DED.

The Risks of Corneal Surface Damage in Aqueous-Deficient Dry Eye Disease: A 17-Year Population-Based Study in Taiwan.

PURPOSE: To investigate the epidemiologic characteristics and risk of corneal surface damage in patients with aqueous-deficient dry eye disease (DED) in Taiwan. DESIGN: Retrospective, population-based cohort study. METHODS: We used claims data in the Taiwan National Health Insurance Research Database from 1997 to 2013 of patients with DED, defined according to diagnoses, drug codes, and clinical follow-up. A comparison cohort without DED was selected through propensity score matching. The main outcome measures were corneal surface damage, including corneal erosion, corneal ulcers, or corneal scars. RESULTS: Patients with DED had a significantly higher rate of corneal surface damage (hazard ratio [HR]: 2.70; 95% confidence interval [CI] 2.38-3.06, P < .001), especially higher in patients aged <18 years (HR 6.66; 95% CI 3.58-12.41) than in older patients and in women (HR 2.98; 95% CI 2.57-3.46) than in men (HR 2.22; 95% CI 1.78-2.77), compared to those in the non-DED cohort. DED with diabetes mellitus (P = .002), rheumatoid arthritis (P = .029), or systemic lupus erythematosus (P = .005) was positively associated with corneal surface damage. The overall prevalence of DED was 7.85%, higher among women (10.49%) than men (4.92%), and increased with age (0.53%, 3.94%, 10.08%, and 20.72% for ages <18, 18-39, 40-64, and >65 years, respectively). The prevalence increased gradually during the study period. CONCLUSIONS: The younger age group (<18 years) had the highest risk of corneal surface damage in aqueous-deficient DED. Other predisposing factors included female sex, diabetes, and autoimmune diseases. To improve clinical care, special attention is required for patients with DED with these risk factors.

Hyperglycemia-induced severe mitochondrial bioenergetic deficit of lacrimal gland contributes to the early onset of dry eye in diabetic mice.

Dry eye and diabetic keratopathy represent the major diabetic complications in ocular surface. Here we found that diabetic mice exhibited the early onset of reduced tear secretion and lacrimal gland weight compared to the symptoms of diabetic keratopathy. Considering to the high bioenergetic needs in lacrimal gland and cornea, we hypothesized that hyperglycemia may cause different severity of mitochondrial bioenergetic deficit between them. Through the measurement of oxygen consumption rate (OCR) and basal extracellular acidification rate (ECAR), we found the apparent alterations of mitochondrial bioenergetic profiles in diabetic lacrimal gland and cornea, accompanied with the mtDNA damage and copy number reduction, as well as the reduced glutathione content. Comparative analysis revealed that mouse lacrimal gland cells exhibited 2-3 folds higher of basal, ATP production, maximal OCR and basal ECAR than corneal epithelial cells in normoglycemia. However, the differences were slightly significant or even not detected in hyperglycemia. Accordingly, the mitochondrial bioenergetic metabolism of lacrimal gland was more compromised than that of corneal epithelium in diabetic mice. Through the administration of mitochondrial-targeted antioxidant SkQ1, the severity of dry eye and diabetic keratopathy was significantly attenuated with the improved mitochondrial function. These results indicate that the susceptibility of mitochondrial bioenergetic deficit in diabetic lacrimal gland may contribute to the early onset of dry eye, while mitochondria-targeted antioxidant possesses therapeutic potential for diabetic dry eye and keratopathy.