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Diquafosol promotes secretion of tear fluid and mucin at the ocular surface and is administered for treatment of dry eye (DE). Tear film lipid layer is secreted from meibomian glands and stabilizes the tear film. We recently showed that diquafosol administration increased lipid layer thickness (LLT) for up to 60 min in normal human eyes. We here evaluated tear film lipid layer in DE patients ( n  = 47) with meibomian gland dysfunction (MGD) before as well as 30, 60, and 90 min after diquafosol administration. One drop of artificial tears or one drop of diquafosol was applied randomly to the eyes of each patient. Diquafosol significantly increased LLT at 30 ( P  < 0.001) and 60 ( P  = 0.042) min and noninvasive tear film breakup time for at least 90 min ( P  < 0.001 at each assessment point). Artificial tears had no such effect. Diquafosol significantly improved the tear interferometric pattern compared with artificial tears ( P  < 0.001 at each assessment point). A single topical administration of diquafosol thus improved LLT and tear film stability in DE patients with MGD, suggesting that diquafosol is a potential treatment not only for aqueous-deficient DE but also for evaporative DE associated with MGD.

This study aimed to compare the clinical efficacy and investigate patients’ preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI ( p  = 0.033 and 0.034, respectively), TBUT ( p  < 0.001 and 0.026, respectively), and corneal ( p  < 0.001 and 0.001, respectively) and conjunctival ( p  = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment ( p  = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients’ preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.

Dry eye disease (DED) after cataract surgery has become a critical concern, and various therapeutic options have been developed. Recently, preservative-free diquafosol ophthalmic solution has been introduced; however, its therapeutic effect on DED after cataract surgery has not been reported. We investigated the efficacy of preservative-free diquafosol in patients with pre-existing DED after cataract surgery. We divided subjects who were diagnosed with DED and scheduled to undergo cataract surgery, into 3 groups (preservative-free diquafosol, group 1; preservative-containing diquafosol, group 2; preservative-free hyaluronate, group 3), and each eye drops was administered 6 times daily after surgery. Tear break up time (TBUT), Ocular Surface Disease Index (OSDI), corneal staining score, lid margin abnormality, and meibum quality improved over time in group 1. Groups 1 and 2 had significantly superior TBUT, meibomian gland dysfunction grade, and meibomian gland expressibility throughout the study period than group 3. Meibum quality of group 1 was significantly better than group 2 at 1 and 3 months after surgery. Preservative-free diquafosol showed better efficacy in treating DED after cataract surgery than preservative-containing diquafosol or preservative-free hyaluronate. Preservative-free diquafosol may serve as a reliable option for the management of patients with pre-existing DED after phacoemulsification.

AimsTo compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in patients with dry eye in China and Singapore.MethodsA total of 497 patients with dry eye (Schirmer's test, 5 mm; fluorescein and RB score, 3 points) from China and Singapore were randomised to receive either diquafosol ophthalmic solution (diquafosol) or sodium hyaluronate ophthalmic solution (HA) at 1:1 ratio. The fluorescein staining scores and rose bengal (RB) subjective symptom scores and tear film breakup time were evaluated before treatment and 2 and 4 weeks after start of treatment.ResultsIn the diquafosol group, changes in fluorescein and RB scores compared with baseline at week 4 or at the time of discontinuation were −2.1±1.5 and −2.5±2.0, respectively. Compared with the HA group, changes in fluorescein score were non-inferior and changes in RB score were superior (p=0.019). In addition, diquafosol and HA improved tear film breakup time by 1.046±1.797 and 0.832±1.775 s, respectively (no significant intergroup difference). Adverse event onset rates were 16.3% (40 of 246 subjects) and 10.0% (25 of 251 subjects) in the diquafosol group and HA group, respectively, with borderline significant intergroup differences (p=0.046), while adverse drug reaction incidence rates were 12.2% (30 of 246 subjects) and 6.0% (15 of 251 subjects), respectively (p=0.019). Only mild adverse drug reactions (>2%) in the form of eye discharge, itching or irritation were observed.ConclusionsDiquafosol improved fluorescein staining score in a manner similar to HA, and significantly improved RB score compared with HA.Trial registration numberNCT01101984.

This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by - 6.60 for CN and - 6.63 for DQ group (all P < 0.0001, P = 0.9739 between groups). TBUT and Schirmer values for CN were significantly improved from the baseline at 4 and 12 weeks (P = 0.0034, P < 0.0001 for TBUT, P = 0.0418, P = 0.0031 for Schirmer test). However, for DQ, TBUT showed significant improvement at 12 weeks only (P = 0.0281). Mean OSDI score differences from the baseline to 12 weeks were improved by - 13.03 ± 19.63 for CN and - 16.11 ± 20.87 for DQ, respectively (all P < 0.0001, P = 0.854 between groups). Regarding drug compliance, the mean instillation frequency of CN was less than that of DQ (P < 0.001). There were no statistically significant intergroup differences in safety evaluation. The level of improvement regarding NEI, TBUT, and OSDI scores were not significantly different between the two treatment groups. However, with regards to the early improvement of TBUT and patient compliance, patients using CN improved faster and with greater adherence to drug usage than did those treated with DQ. KCT0002180 , retrospectively registered on 23 December 2016.

Diquafosol ophthalmic solution 3 % (Diquas ® ) is a P2Y 2 receptor agonist that promotes tear fluid and mucin secretion and is currently approved in Japan and South Korea for the treatment of dry eye. In randomized, double-blind, multicentre trials in patients with dry eye, significantly greater improvements in fluorescein and rose bengal staining scores were seen with diquafosol ophthalmic solution 3 % than with placebo, and diquafosol ophthalmic solution 3 % was noninferior to sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the fluorescein staining score and more effective than sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the rose bengal staining score. The efficacy of diquafosol ophthalmic solution 3 % in the treatment of dry eye was maintained in the longer term, with improvements also seen in subjective dry eye symptoms, and was also shown in a real-world setting. Diquafosol ophthalmic solution 3 % also demonstrated efficacy in various specific dry eye disorders, including aqueous-deficient dry eye, short tear film break-up time dry eye, obstructive meibomian gland dysfunction, dry eye following laser in situ keratomileusis surgery and dry eye following cataract surgery, as well as in contact lens wearers and visual display terminal users. Diquafosol ophthalmic solution 3 % was generally well tolerated in patients with dry eye, with eye irritation the most commonly reported adverse event. In conclusion, diquafosol ophthalmic solution 3 % is a useful option for the treatment of dry eye.

The ongoing pandemic has led to an urgent need for novel drug discovery and potential therapeutics for Sars-CoV-2 infected patients. Although Remdesivir and the anti-inflammatory agent dexamethasone are currently on the market for treatment, Remdesivir lacks full efficacy and thus, more drugs are needed. This review was conducted through literature search of PubMed, MDPI, Google Scholar and Scopus. Upon review of existing literature, it is evident that marine organisms harbor numerous active metabolites with anti-viral properties that serve as potential leads for COVID-19 therapy. Inorganic polyphosphates (polyP) naturally found in marine bacteria and sponges have been shown to prevent viral entry, induce the innate immune response, and downregulate human ACE-2. Furthermore, several marine metabolites isolated from diverse sponges and algae have been shown to inhibit main protease (Mpro), a crucial protein required for the viral life cycle. Sulfated polysaccharides have also been shown to have potent anti-viral effects due to their anionic properties and high molecular weight. Likewise, select marine sponges produce bromotyrosines which have been shown to prevent viral entry, replication and protein synthesis. The numerous compounds isolated from marine resources demonstrate significant potential against COVID-19. The present review for the first time highlights marine bioactive compounds, their sources, and their anti-viral mechanisms of action, with a focus on potential COVID-19 treatment.

Dry eye disease (DED) is a prevalent and disabling condition. Artificial tears are commonly used but often inadequate for moderate-to-severe cases. Secretagogues such as pilocarpine, cevimeline, and diquafosol offer potential alternatives, though their comparative effectiveness remains unclear. To evaluate the safety and efficacy of these secretagogues versus artificial tears in adults with DED, we searched CENTRAL, PubMed, Scopus, LILACS, ClinicalTrials.gov, and WHO ICTRP without language restrictions. Randomized controlled trials (RCTs) comparing secretagogues to artificial tears were eligible. Data extraction and synthesis were conducted using Covidence and the Cochrane RoB 2 tool, and 19 RCTs (n = 2697) were included. Fifteen were analyzed quantitatively; however, only eight trials evaluating diquafosol were suitable for meta-analysis, as data for pilocarpine and cevimeline were insufficient for quantitative synthesis. GRADE was used to assess evidence certainty. PROSPERO registration: CRD42020218407. Diquafosol significantly improved rose bengal staining at 4 weeks and OSDI scores and TBUT in post-cataract patients at 4 and 12 weeks. However, it increased mild adverse events (RR, 1.81; 95% CI, 1.15–2.84). Evidence for pilocarpine and cevimeline was limited. Diquafosol 3% shows greater efficacy than artificial tears in post-cataract DED but with more side effects. Further research is needed for other secretagogues.

The mucus layer of the nasopharynx and bronchial epithelium has a barrier function against inhaled pathogens such as the coronavirus SARS-CoV-2. We recently found that inorganic polyphosphate (polyP), a physiological, metabolic energy (ATP)-providing polymer released from blood platelets, blocks the binding of the receptor binding domain (RBD) to the cellular ACE2 receptor in vitro. PolyP is a marine natural product and is abundantly present in marine bacteria. Now, we have approached the in vivo situation by studying the effect of polyP on the human alveolar basal epithelial A549 cells in a mucus-like mucin environment. These cells express mucins as well as the ectoenzymes alkaline phosphatase (ALP) and adenylate kinase (ADK), which are involved in the extracellular production of ATP from polyP. Mucin, integrated into a collagen-based hydrogel, stimulated cell growth and attachment. The addition of polyP to the hydrogel significantly increased cell attachment and also the expression of the membrane-tethered mucin MUC1 and the secreted mucin MUC5AC. The increased synthesis of MUC1 was also confirmed by immunostaining. This morphogenetic effect of polyP was associated with a rise in extracellular ATP level. We conclude that the nontoxic and non-immunogenic polymer polyP could possibly also exert a protective effect against SARS-CoV-2-cell attachment; first, by stimulating the innate antiviral response by strengthening the mucin barrier with its antimicrobial proteins, and second, by inhibiting virus attachment to the cells, as deduced from the reduction in the strength of binding between the viral RBD and the cellular ACE2 receptor.

Abstract Context In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH). Objective This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function. Methods Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks (“peak”) and 4 weeks (“trough”) after the third dose of burosumab. Results All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal. Conclusion The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.