Modified Danzhi Xiaoyao Powder (MDXP) improves the corneal damage in dry eye disease (DED) mice through phagocytosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao Powder (MDXP) is a traditional Chinese medicine formula remedy for treating Dry Eye Disease (DED). It showed the function of dispersing stagnated liver Qi for relieving Qi stagnation and clearing heat, which can be effective in treating conditions such as Dry Eye Disease (DED) and irregular menstruation due to liver depression and fire transformation. AIM OF THE STUDY: This study investigated the mechanism of the effect of MDXP in mice with DED. MATERIALS AND METHODS: A DED model was induced in mice using chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops administered in a dry box for 28 days. After modeling, the MDXP groups were given Chinese medicine with different dosages by gavage for 14 days. The following parameters were recorded in each group: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. Behavioral changes were evaluated by elevating cross-maze and open-field experiments. The levels of inflammatory factors serum tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), fcγR-mediated phagocytosis pathway cell division control protein 42 homolog (CDC42), actin-related protein 2/3 complex subunit 2 (ARPC2), and actin-related protein 3 (ACTR3) were measured by using Enzyme-linked immunoassay (ELISA), immunohistochemical staining, and real-time fluorescent qualitative polymerase chain reaction (RT-qPCR). RESULTS: MDXP increased body mass and lowered body temperature, prolonged tear film break-up time, promoted tear secretion, repaired corneal damage, decreased horizontal and vertical scores, elevated percentage of open arm times and boom opening time percentage, and reduced the expression levels of inflammatory factors of TNF-α, IL-1ß and pathway-related proteins CDC42, ARPC2, and ACTR3 in mice. MDXP also reduced the expression levels of inflammatory factors of TNF-α and IL-1ß in human corneal endothelial cells (HCECs), mouse mononuclear macrophage cells (RAW264.7), and human myeloid leukemia mononuclear cells (THP-1). CONCLUSIONS: MDXP can relieve tension and anxiety, inhibit apoptosis, reduce phagocytosis, reduce the expression of pro-inflammatory factors, repair corneal damage, and improve the symptoms in DED mice. The mechanism of action may be through the fcγR-mediated phagocytosis pathway.

The Anti-Inflammatory Effect of Multi-Wavelength Light-Emitting Diode Irradiation Attenuates Dry Eye Symptoms in a Scopolamine-Induced Mouse Model of Dry Eye.

Dry eye disease is a common condition in patients of all ages, causing discomfort and potential visual problems. Current treatments, including artificial tears and anti-inflammatory drugs, have certain limitations, encouraging research into alternative therapies. We investigated the therapeutic potential of multi-wavelength light-emitting diode (LED) irradiation of mice with dry eye. First, we showed that multi-wavelength LED irradiation was non-toxic to human corneal epithelial cells and improved cell viability. We then used a scopolamine-induced mouse model of dry eye to assess the effects of multi-wavelength LED irradiation on various clinical parameters. This treatment increased the tear volume and reduced corneal irregularity, thus improving dry eye. Histological analysis revealed that multi-wavelength LED irradiation protected against corneal epithelial damage and the associated reduction in epithelial thickness and would thus improve the corneal health of dry eye patients. Multi-wavelength LED irradiation significantly reduced the corneal levels of pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α; the treatment was thus anti-inflammatory. Our results suggest that multi-wavelength LED irradiation may serve as a safe and effective treatment for dry eye, alleviating symptoms, reducing inflammation, and promoting corneal health.

[Combination of acupuncture and medication for dry eye complicated with computer vision syndrome: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of acupuncture, Chinese medication and combination of acupuncture and medication in the treatment of dry eye complicated with computer vision syndrome (CVS). METHODS: A total of 152 patients with dry eye complicated with CVS were randomly divided into an acupuncture-medication group (38 cases, 1 case was removed), an acupuncture group (38 cases, 1 case dropped off), a Chinese medication group (38 cases, 1 case was removed), and a western medication group (38 cases, 1 case dropped off). In the western medication group, sodium hyaluronate eye drop combined with esculin and digitalis glycosides eye drop were used. In the acupuncture group, acupuncture was applied at bilateral Taiyang (EX-HN 5)， Cuanzhu (BL 2), Fengchi (GB 20), Qimen (LR 14) , and Hegu (LI 4) etc., once a day. In the Chinese medication group, Yiqi Congming decoction formula ganule was given orally, one dose a day. In the acupuncture-medication group, acupuncture combined with Yiqi Congming decoction formula granule were used. All groups were treated for 14 d. The non-invasive first tear film break-up time (NIBUT f), non-invasive average tear film break-up time (NIBUT av), tear meniscus height (TMH), ocular surface disease index (OSDI) score, and CVS symptom score were compared between the patients of each group before and after treatment. RESULTS: After treatment, the NIBUT f, NIBUT av, and TMH were increased compared with those before treatment in the patients of the 4 groups (P<0.01); the NIBUT f and NIBUT av in the acupuncture-medication group and the acupuncture group were higher than those in the Chinese medication group and the western medication group (P<0.05), and the TMH in the acupuncture-medication group and the Chinese medication group were higher than those in the acupuncture group and the western medication group (P<0.05). After treatment, the OSDI scores, the various scores and total scores of CVS (except for head symptom score in the western medication group) were decreased compared with those before treatment in the patients of the 4 groups (P<0.01). The OSDI score, total score, eye symptom score, and body symptom score of CVS in the acupuncture-medication group were lower than those in the acupuncture group, the Chinese medication group, and the western medication group (P<0.01, P<0.05), the head symptom score of the acupuncture-medication group was lower than that in the western medication group (P<0.05), and the CVS physical symptom scores and mental cognitive symptom scores of the acupuncture-medication group and the acupuncture group were lower than those in the Chinese medication group and the western medication group (P<0.05). CONCLUSION: Acupuncture has advantages in improving NIBUT f, NIBUT av, and CVS physical symptoms and cognitive symptoms, and the Chinese medication has advantage in improving TMH. The combination of acupuncture and Chinese medication has better effects compared with monotherapy.

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.

Bacillus-Derived Manganese Superoxide Dismutase Relieves Ocular-Surface Inflammation and Damage by Reducing Oxidative Stress and Apoptosis in Dry Eye.

Purpose: We hypothesized that antioxidative enzymes supplementation could be a treatment option for dry eye. We investigated the efficacy of oral administration of Bacillus-derived superoxide dismutase (Bd-SOD) in a murine experimental dry eye (EDE). Methods: In part I, mice were randomly assigned to normal control, EDE, and mice groups that were treated with oral Bd-SOD after induction of EDE (EDE + Bd-SOD group; four mice in each group). Expression of SOD2, a major antioxidant enzyme with manganese as a cofactor, was assessed by immunofluorescence staining. In part II, mice were divided into seven groups (six mice in each group): normal control, EDE, vehicle-treated, topical 0.05% cyclosporin A (CsA)-treated, and oral Bd-SOD-treated (2.5, 5.0, and 10.0 mg/kg Bd-SOD) groups. Tear volume, tear-film break-up time (TBUT), and corneal fluorescein-staining scores (CFS) were measured at zero, five, and 10 days after treatment. Ten days after treatment, 2',7'-dichlorodihydrofluorescein diacetate for reactive oxygen species (ROS), enzyme-linked immunosorbent for malondialdehyde, and TUNEL assays for corneal apoptosis, flow cytometry inflammatory T cells, and histological assessment were performed. Results: Compared to the normal control group in part I, the EDE group showed significantly decreased SOD2 expression by immunofluorescence staining. However, the EDE + Bd-SOD group recovered similar to the normal control group. In part II, ROS, malondialdehyde, and corneal apoptosis were decreased in CsA and all Bd-SOD-treated groups. Corneal and conjunctival inflammatory T cells decreased, and conjunctival goblet cell density increased in CsA-treated and Bd-SOD-treated groups. Compared to the CsA-treated group, the 2.5 mg/kg Bd-SOD-treated group showed increased TBUT and decreased inflammatory T cells, and the 5.0 mg/kg Bd-SOD-treated group showed decreased CFS and increased conjunctival goblet cells. Conclusions: Oral Bd-SOD administration might increase autogenous SOD2 expression in ocular surface tissue in EDE and could be developed as a complementary treatment for DE in the future.

Safety and Efficacy of Oral Hydroxychloroquine in the Treatment of Ophthalmic Disease Associated with Sjögren's Syndrome.

Background: Dry eye disease is common among patients with primary Sjögren's syndrome (pSS). Hydroxychloroquine (HCQ), known for its immunomodulatory effects and minimal adverse effects, has emerged as a pivotal treatment option for pSS. Nonetheless, conflicting evidence exists regarding the therapeutic efficacy of HCQ in managing dry eye disease associated with pSS. Objectives: To evaluate the safety and efficacy of oral hydroxychloroquine in treating dry eye disease associated with pSS. Methods: A prospective randomized controlled study was conducted, enrolling pSS patients with moderate to severe dry eye disease. Participants were randomly assigned to an oral HCQ group and an observation group. Various scales (ESSDAI, ESSPRI, OSDI, and SPEED questionnaire score), dry eye-related tests (OSS score, TBUT, and Schirmer test I), ophthalmology-specific tests (BCVA, SD-OCT RT, field of view, latency and amplitudes for multifocal ERG ring 1 and ring 2), whole body protein levels (serum IgA, IgG, and IgM), and blood glucose were assessed before and after 12 months of treatment. Results: Pairwise comparison of the observed indicator baseline revealed no statistical significance (P > .05). After 12 months, the HCQ group exhibited notable improvements in ESSPRI, serum IgA, and Schirmer test I results compared to the control group (P < .05). Both groups demonstrated significant improvements in BCVA, OSDI, SPEED scores, and dry eye-associated examinations compared to baseline (P < .05). Serum IgG and IgM levels decreased in the HCQ group after 12 months of treatment, but without statistical significance (P > .05). None cases of HCQ retinopathy were reported during follow-up. Conclusions: Oral HCQ was demonstrated safety and efficacy in managing pSS-related dry eye disease. Treatment with Oral HCQ markedly reduced the ESSPRI score, improve patients' systemic dryness symptoms, and greatly decreased blood IgA levels. Combined with topical cyclosporin, HCQ improved Schirmer test I scores and alleviated ocular surface inflammation and dry eye signs and symptoms.

Therapeutic effects of low-color-temperature light-emitting diodes on dry eye.

BACKGROUND: As a new technology for treating dry eye diseases, phototherapy has attracted great attention, but the research on its safety and effectiveness is limited. In this study, the therapeutic effects of low-color-temperature light-emitting diodes on dry eye in humans, rabbits, and rats were investigated. METHODS: In clinical experiments, subjects in both groups read the same paper for 3 h under light sources of two color temperatures: 1900 K (low-color-temperature light-emitting diodes) or 4000 K (artificial fluorescent white light-emitting diodes). The differences in the non-invasive tear film breakup time, tear meniscus height, and conjunctival congestion scores before and after the experiment were compared between the two groups. In animal experiments, corneal epithelial barrier function and tear production of Sprague-Dawley rats and New Zealand white rabbits with dry eye were compared before and after low-color-temperature light-emitting diodes treatment. TUNEL staining and Western blotting were used to detect the apoptosis of corneal and conjunctival cells and the expression of inflammatory factor IL-1ß. RESULTS: Low-color-temperature light-emitting diodes prolonged tear film breakup time in patients with dry eye. Moreover, it increased tear secretion, decreased fluorescein sodium staining scores, corneal and conjunctival cell apoptosis, and inflammatory factor expression in rabbits and rats with dry eye. CONCLUSIONS: Low-color-temperature light-emitting diodes phototherapy can be used as an effective treatment for dry eye, reducing its symptoms and related ocular surface damage in humans, rabbits, and rats.

Effectiveness of rb-bFGF Eye Drops for Post-Cataract Surgery Dry Eye and Observation of Changes in Tear Secretion and Corneal Damage in Patients.

Objective: Dry eye syndrome after cataract surgery is a common complication that may affect the patient's visual comfort and quality of life. Because the surgery may affect the secretion and quality of tears in the eye, resulting in dry and uncomfortable eyes.This study aimed to investigate the therapeutic effects of recombinant bovine basic fibroblast growth factor (rb-bFGF) eye drops on dry eye syndrome after cataract surgery and to analyze its impact on tear secretion and corneal injury. Methods: This is a retrospective study. A total of 126 patients (126 eyes) with dry eye syndrome after cataract surgery were treated between January 2021 and October 2022. patients were randomly divided into a study group (64 patients, 64 eyes) and a control group (62 patients, 62 eyes). Both groups were treated with sodium hyaluronate eye drops, while the study group received rb-bFGF eye drops for four weeks in addition to the sodium hyaluronate eye drops. The clinical efficacy, results of tear secretion test (SIT), tear film break-up time (BUT), corneal fluorescein staining, corneal topography examination, oxidative stress indicators, ocular surface disease index (OSDI) score, and drug adverse reactions were compared between the two groups. Results: The study group exhibited a significantly higher total effective treatment rate (96.88%) compared to the control group (85.48%), suggesting the enhanced efficacy of rb-bFGF eye drops. Moreover, the study group demonstrated extended tear secretion length and tear film break-up time, indicating improved tear film stability and ocular surface health. Additionally, the study group showed reduced corneal fluorescein staining score and improved corneal surface regularity index, indicative of enhanced corneal integrity and smoothness. Notably, tear superoxide dismutase levels were elevated, while lipid peroxide levels were lowered in the study group, underscoring the potential antioxidative effects of rb-bFGF. The study group also exhibited a lower OSDI score, suggesting reduced ocular discomfort and improved quality of life. Although the study group had a slightly higher incidence of adverse reactions (9.38%) compared to the control group (8.06%), the difference was not statistically significant. Particularly significant is the statistical significance highlighting the heightened total effective treatment rate in the study group, indicating the potential of rb-bFGF eye drops in promoting favorable therapeutic outcomes. Conclusion: rb-bFGF eye drops are safe and effective in treating dry eye syndrome after cataract surgery. They can help regulate tear secretion, repair corneal damage, and improve dry eye symptoms. Despite the retrospective design and relatively small sample size of this study, further randomized controlled trials and larger sample size may be needed to verify the robustness of the results, but this study is important for guiding the treatment strategy and optimizing patient care for dry eye after cataract surgery.

Medication Rules and Mechanism of Topical Traditional Chinese Medicine for Meibomian Gland Dysfunction-Related Dry Eye Disease.

Objective: To summarize the use of traditional Chinese medicine in the treatment of meibomian gland dysfunction-related dry eye disease through data mining. Additionally, it aims to explore the signaling pathways and mechanisms of critical drugs used in the treatment of this condition through network pharmacology analysis. Methods: Clinical trial literature on the topical application of traditional Chinese medicine for meibomian gland dysfunction-related dry eye disease in the past 20 years was collected from Chinese academic databases (Zhiwang, Wanfang Data, and Weipu). Association rule analysis and clustering analysis were performed using IBM SPSS. Active ingredients and target sites of critical drugs were obtained from the TCSMP and BATMAN-TCM databases. Disease target sites were sourced from databases such as DrugBank and OMIM. The drug-disease intersecting target genes were used to construct a protein-protein interaction (PPI) network in the String database. Common target genes were subjected to GO function and KEGG signaling pathway enrichment analyses using the DAVID platform. The molecular docking of active ingredients and key targets was validated using AutoDock Vina (1.1.2). Results: A total of 93 Chinese herbal medicines in 56 prescriptions were collected. The critical drugs identified were flos chrysanthemi, flos lonicerae japonicae, fructus forsythiae, radix scrophulariae, radix rehmanniae recens, and radix ophiopogonis. There were 63 active ingredients and 905 potential targets. Key targets identified through PPI analysis included AKT1, TP53, TNF, EGFR, IL6, VEGFA, IL1B, INS, EGF, and CXCL8. GO function analysis revealed processes such as positive regulation of expression, positive regulation of cell proliferation, negative regulation of apoptosis, and inflammatory reactions. The main signaling pathways identified were the MAPK signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interactions. Molecular docking indicated relatively strong binding activity between the small molecules of the active ingredients and the target proteins. Conclusions: The critical drugs analyzed in this study potentially exert therapeutic effects on meibomian gland dysfunction-related dry eye disease by regulating related biological processes such as anti-inflammation and repairing the corneal epithelial barrier. These findings provide a theoretical basis for future research and development of new drugs and subsequent experimental investigations.

Dry eye disease due to meibomian gland dysfunction treated with Pinggan Yuyin Qingre formula: a stratified randomized controlled trial.

OBJECTIVE: To observe the clinical efficacy on improving the quality of meibum in patients suffer from dry eye disease (DED) due to meibomian gland dysfunction (MGD) with hyperactivity ofdue todeficiency pattern after being treated with Pinggan Yuyin Qingre formula (, PGYYQR). METHODS: Totally 120 patients who met the inclusion criteria were included and stratified into three levels according to the level of MGD (1-3), and patients in each level was randomly allocated into the treatment group and control group according to a 1∶1 ratio. Both groups were treated with sodium hyaluronate eye drops, and the treatment group was also given PGYYQR granules. Both groups were treated continuously for eight weeks. The score of the properties of meibomian gland (MG) secretion, the score of the palpebral margins, the average noninvasive tear breakup time (NITBUTav), lipid layer thickness (LLT), and Traditional Chinese Medicine (TCM) syndrome efficacy were compared between the two groups after treatment. RESULTS: A total of 116 cases were included in the statistical analysis. The differences were statistically significant in the score of the properties of MG secretion, the score of the palpebral margins, and NITBUTav between the two groups after treatment, the treatment group was superior to the control group; there was no evidence of a difference in LLT. In terms of TCM syndrome efficacy, the total effective rate was 84.7% in the treatment group and 50.9% in the control group, with the statistically significant difference. None of the included cases had adverse reactions. CONCLUSIONS: PGYYQR is effective in improving the quality of meibum, and the tear film stability which thereby relieving the ocular symptoms in MGD-related DED patients with hyperactivity ofdue todeficiency pattern.

Vitamin D and eye: Current evidence and practice guidelines.

Vitamin D is a steroid hormone that has widespread role in human physiology, not only in the maintenance of calcium homeostasis but also in immunomodulation, cellular differentiation, and proliferation. The immunomodulatory effects of vitamin D are well known and are applicable to the ocular surface immune cells and structural cells. The role of vitamin D in ocular surface conditions such as dry eye disease (DED), keratoconus (KC), and post-surgical outcomes has received widespread and well-deserved attention. Vitamin D supplementation is shown to improve DED clinically as well as in experimental models. The anti-inflammatory properties may be crucial in the treatment of ocular surface conditions such as DED and KC. Vitamin D plays a multifaceted role in corneal wound healing with its anti-inflammatory and extracellular matrix remodeling properties. In this review, we discuss how to approach patients with DED and those undergoing refractive surgery with the available basic and clinical knowledge on the role of vitamin D in these conditions. We aim to highlight the importance of clinically harnessing vitamin D-mediated natural immuno-inflammatory modulation in combination with currently available standard of care strategies to reduce the morbidity and disease duration associated with ocular surface diseases.

Omega-3 fatty acids supplements for dry eye - Are they effective or ineffective?

Purpose: To evaluate effectiveness of omega-3 fatty acid supplements in relieving dry eye symptoms and signs in symptomatic visual display terminal users (VDT). Methods: A randomized controlled study was done; eyes of 470 VDT users were randomized to receive four capsules twice daily for 6 months (O3FAgroup), each containing 180 mg of eicosapentaenoic acid and 120 mg docosahexaenoic acid. The O3FA group was compared with another group (n = 480) who received four capsules of a placebo (olive oil) twice daily. Patients were evaluated at baseline, 1, 3, and 6 months, respectively. The primary outcome was improvement in omega-3 index (a measure of EPA and DHA ratio in RBC membrane). Secondary outcomes were improvement dry eye symptoms, Nelson grade on conjunctival impression cytology, Schirmer test values, tear film breakup time (TBUT), and tear film osmolarity. Means of groups (pre-treatment, 1, 3, and 6-months) were compared with repeated measure analysis of variance. Results: At baseline, 81% patients had low omega-3 index. In the O3FA group, a significant increase in omega-3 index, improvement in symptoms, reduction in tear film osmolarity, and increase in Schirmer, TBUT, and goblet cell density was observed. These changes were not significant in the placebo group. Improvement in test parameters was significantly (P < 0.001) better in patients with low omega3 index (<4%) subgroup. Conclusion: Dietary omega-3 fatty acids are effective for dry eye in VDT users; omega-3 index appears to be the predictor to identify potential dry eye patients who are likely to benefit from oral omega-3 dietary intervention.

Dry Eye Disease: What Is the Role of Vitamin D?

Dry eye disease (DED) is a multifactorial condition resulting from reduced tear secretion from the lacrimal glands, increased tear water evaporation or the production of poor-quality tears. Such tear instability can lead to inflammation and damage of the ocular surface, as well as to abnormal nociception. Historically, tear substitutes and corticosteroids have been the bastion of DED therapy, but a substantial number of patients still suffer from residual symptoms even after being treated with traditional treatments. Aiming to find safe and effective alternative therapies, recent efforts have been focused on the role of vitamin D in the cellular physiology of the eye. Possibly because of its positive effect in modulating the immune and inflammatory responses, the systemic supplementation of vitamin D seems, indeed, to be an effective therapeutic strategy, especially, but not only, for patients affected by DED that does not respond to conventional treatments. In this context, this review focuses on the literature reporting on the pathogenesis and treatment of DED, with a special emphasis on the recent investigations reporting on the potential role of the systemic administration of vitamin D as a therapeutic approach in the management of such condition.

Evaluating the efficacy of Quantum Molecular Resonance (QMR) electrotherapy in mixed-type dry eye patients.

PURPOSE: To evaluate the efficacy and safety of the low-power, high-frequency electrical current treatment administered by the Rexon-Eye device, in a cohort of patients affected by mixed-type dry eye disease (DED) of medium to severe level. PATIENTS AND METHODS: In this prospective, non-randomized, interventional clinical study, eighteen mixed type DED patients were treated. Treatment was a specific type of electrotherapy, Quantum Molecular Resonance (QMR®), administered by means of the Rexon-Eye® device (Resono Ophthalmic, Sandrigo, Italy) with a protocol of one 20-min session per week, for 4 weeks. Patients were examined at baseline and one month after the last treatment, utilizing the Ocular Surface Disease Index (OSDI) questionnaire and clinical signs: non-invasive tear break-up time (NIBUT), Oxford staining, meibum quality, meibography, meibomian gland expressibility, tear meniscus height (TMH), Schirmer's test, ocular inflammation expressed by MMP-9 concentration. RESULTS: Subjective benefit in OSDI was reported (p = 0.013). Improvement was also observed in NIBUT (p < 0.001), Oxford staining (p = 0.002), expressible meibomian glands number (p = 0.001) and meibum quality (p < 0.001). A remarkable benefit was present in inflammation, as evidenced by the reduction of MMP-9 (p = 0.003). Changes, although not statistically significant, were also present in TMH (p = 0.076) and Schirmer's test (p = 0.675), whereas no change was observed in meibography score. No adverse event was reported. CONCLUSION: In this mixed-type DED patients' cohort, Rexon-Eye proved to be effective and safe in improving subjective and objective ocular parameters, as well as capable to normalize inflammatory markers.

Effect of oral vitamin D supplementation on dry eye disease patients with vitamin D deficiency.

CLINICAL RELEVANCE: Dry eye disease (DED) and vitamin D deficiency are both common clinical entities. Vitamin D has been reported to play a significant role in ocular surface homeostasis. BACKGROUND: This study aimed to determine the therapeutic effect of oral vitamin D supplementation in dry eye disease patients with vitamin D deficiency. METHODS: A randomized, controlled study was completed in 100 patients with dry eye disease and concurrent vitamin D deficiency (< 20 ng/ml). Participants were randomly allocated to 8 weeks of oral vitamin D supplementation with both groups receiving conventional dry eye treatment with artificial tears. Schirmer's, tear break-up time (TBUT) and osmolarity tests were measured before and after eight weeks of treatment. RESULTS: The mean age of participants was 36.8 ± 8.56 years in the treatment group (n: 50) and 34.8 ± 10.13 year in the control group (n: 50). After eight weeks of treatment the mean differences in Schirmer's, TBUT and tear osmolarity were 2.38 ± 1.55 mm, 3.95 ± 1.48 s and -16.9 ± 6.28 mOsm/L, respectively in the treatment group, and 0.7 ± 0.86 mm, 0.92 ± 1.57s and -3.34 ± 2.0 mOsm/L respectively in the control group (p < 0.001 for all parameters). The treatment group demonstrated a more significant improvement than the control group in Schirmer's, TBUT and osmolarity values (p < 0.001). CONCLUSION: Vitamin D supplementation as an adjuvant to routine dry eye treatment improves ocular surface hemostasis parameters, results in better tear stability and a more improved tear osmolarity in patients with vitamin D deficiency.

Therapeutic Effects of Acer palmatum Thumb. Leaf Extract (KIOM-2015E) on Benzalkonium Chloride-Induced Dry Eye in a Mouse Model.

We determined the effects of two extracts from Acer palmatum Thumb. leaves (hot water extract KIOM-2015EW and 25% ethanol extract KIOM-2015EE) in a benzalkonium chloride (BAC)-induced dry eye mouse model. Dry eye was induced by 0.2% BAC for 2 weeks, followed by treatment three times (eye drop) or once (oral administration) daily with KIOM-2015E for 2 weeks. Treatment with both KIOM-2015EE and KIOM-2015EW resulted in a marked increase in tear volume production for the 4 days of treatment. The Lissamine Green staining score, TUNEL-positive cells, and inflammatory index were significantly decreased after 2 weeks. Topical KIOM-2015EE administration exhibited a greater improvement in decreasing the ocular surface staining scores, inflammation, dead cells, and increasing tear production in a dose-dependent manner compared with the other groups. Furthermore, KIOM-2015E significantly reduced the phosphorylation of NF-κB, which was activated in the BAC-treated cornea. Topical administration was much more effective than oral administration for KIOM-2015E and KIOM-2015EE was more effective than KIOM-2015EW. Application of KIOM-2015E resulted in clinical improvement, inhibited the inflammatory response, and alleviated signs of dry eye. These results indicate that KIOM-2015E has potential as a therapeutic agent for the clinical treatment of dry eye.

Dry Eye Subtypes in the Dry Eye Assessment and Management (DREAM) Study: A Latent Profile Analysis.

Purpose: Dry eye disease (DED) is a heterogeneous condition with poorly characterized subtypes. The DREAM study was a large multicenter randomized clinical trial that did not find omega-3 to be more effective than placebo in treating symptomatic DED. We performed secondary analysis of DREAM data to characterize DED subtypes and their omega-3 response. Methods: A total of 535 patients with moderate-to-severe DED were randomized to omega-3 or placebo treatment for one year. We used latent profile analysis to identify subtypes based on baseline Ocular Surface Disease Index, tear break-up time (TBUT), anesthetized Schirmer's test, corneal and conjunctival staining, and meibomian gland dysfunction (MGD). We evaluated omega-3's effect for each subtype using generalized linear regression. Results: Five clinically meaningful DED subtypes were identified. They differed significantly in sex (P < 0.001) and race (P = 0.02). Subtype 1 had the most severe DED signs yet milder symptoms and was associated with more Sjögren's syndrome (21%, P < 0.001). Subtype 2 had the mildest DED signs except MGD. Subtype 3 had the most severe symptoms, out of proportion to DED signs. Subtype 4 had relatively milder symptoms and MGD. Subtype 5 had severe MGD and TBUT and was associated with rosacea (29%, P = 0.04). Omega-3 was not significantly more beneficial than placebo for any subtype. Conclusions: Five clinically meaningful DED subtypes differed significantly in demographics, symptoms, signs, and systemic disease associations. Omega-3 was not significantly more effective than placebo for any subtype. Translational Relevance: T3 translational research identifying subtypes in the DREAM study can improve DED clinical classification and targeted management.

Efficacy of Cordyceps cicadae (Ascomycota) Mycelium Supplementation for Amelioration of Dry Eye Symptoms: A Randomized, Double-Blind Clinical Pilot Study.

Dry eye disease (DED), a multifactorial inflammatory ocular surface disorder, affects up to 50% of individuals over 50 years old worldwide and is one of the most common reasons for seeking ophthalmologic care. Generally, topical eye drops or oral drugs are administered to treat DED; however, the use of preservatives in eye drops or the adverse effects of oral drugs are disadvantageous for long-term therapy. Cordyceps cicadae, a traditional Chinese medicinal fungus, possesses anti-inflammatory effects without evident toxicity and is obtainable at low price. Our previous study demonstrated that C. cicadae mycelium effectively ameliorates dry eye symptoms in the benzalkonium chloride (BAC)-induced mouse dry eye model by increasing tear volume and tear film breakup time (TBUT). However, the effects of C. cicadae mycelium for human dry eye amelioration remains unknown. Thus, the present study investigated the mitigation of dry eye conditions and related discomforts through oral supplementation of fermented C. cicadae mycelium. A total of 70 healthy individuals were recruited and randomly allocated to receive a daily oral dose of 1,050 mg preparation in sachet containing either freeze-dried C. cicadae mycelium powder with 0.3 mg of adenosine and 1.5 mg of HEA per gram or placebo for 90 days. The participants were subjected to anthropometric measurements, dry eye questionnaires (DEQ), Schirmer's tests, intraocular pressure (IOP) measurements, tear film breakup time (TBUT) tests, tear osmolality measurements, and tear electrolyte analysis prior to and right after completion of the study. The results showed a significantly increased TBUT as well as a significant decrease in tear osmolarity, in parallel with the decrease of tear electrolytes, especially Na+ and Cl ions. Although significant increase of tear volume was not observed, the increased TBUT suggests mitigation of dry eye through improvement of tear quality. Therefore, C. cicadae mycelium supplementation may be used for dry eye alleviation as a novel therapeutic intervention.

Topical Omega-3 Fatty Acids Eyedrops in the Treatment of Dry Eye and Ocular Surface Disease: A Systematic Review.

Dry eye is a common inflammatory condition of the ocular surface. While oral omega-3 supplementation for its treatment has been extensively studied, recent large-scale studies have cast doubt on their efficacy. However, efficacy of topical omega-3 has yet to be reviewed. We performed a systematic search of PubMed, Embase, and Cochrane databases for all studies evaluating topical omega-3 in dry eye. Five human and five animal studies were included. Of the five human studies, two were on dry eye disease (DED), one was on contact lens discomfort, and two were on patients undergoing corneal collagen crosslinking. In humans, there is promising evidence for improved ocular surface staining and tear break-up time compared to controls, equivocal evidence for improvements to ocular surface symptoms and meibomian gland dysfunction, and no effect on increasing tear production. Data from animal models largely agree with these findings, and further reveal decreased inflammatory cytokines and monocyte infiltration. Our review suggests that topical omega-3 is a promising treatment for dry eye, but also points to the paucity of evidence in this field. Further trials in humans are required to characterize effects of topical omega-3 and optimize its dosage.

Can Nutrition Play a Role in Ameliorating Digital Eye Strain?

Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.