Diquafosol Improves Corneal Wound Healing by Inducing NGF Expression in an Experimental Dry Eye Model.

Dry eye disease (DED) is caused by inflammation and damage to the corneal surface due to tear film instability and hyperosmolarity. Various eye drops are used to treat this condition. Each eye drop has different properties and mechanisms of action, so the appropriate drug should be used according to clinical phenotypes. This study aims to compare the therapeutic mechanisms of cyclosporine A (CsA) and diquafosol tetrasodium (DQS). An experimental in vivo/in vitro model of DED using hyperosmolarity showed decreased cell viability, inhibited wound healing, and corneal damage compared to controls. Treatment with cyclosporine or diquafosol restored cell viability and wound healing and reduced corneal damage by hyperosmolarity. The expression of the inflammation-related genes il-1ß, il-1α, and il-6 was reduced by cyclosporine and diquafosol, and the expression of Tnf-α, c1q, and il-17a was reduced by cyclosporine. Increased apoptosis in the DED model was confirmed by increased Bax and decreased Bcl-2 and Bcl-xl expression, but treatment with cyclosporine or diquafosol resulted in decreased apoptosis. Diquafosol increased NGF expression and translocation into the extracellular space. DED has different damage patterns depending on the progression of the lesion. Thus, depending on the type of lesion, eye drops should be selected according to the therapeutic target, focusing on repairing cellular damage when cellular repair is needed or reducing inflammation when inflammation is high and cellular damage is severe.

Multifunctional Cerium Oxide Nanozyme for Synergistic Dry Eye Disease Therapy.

Dry eye disease (DED) is a chronic multifactorial ocular surface disease mainly caused by the instability of tear film, characterized by a series of ocular discomforts and even visual disorders. Oxidative stress has been recognized as an upstream factor in DED development. Diquafosol sodium (DQS) is an agonist of the P2Y2 receptor to restore the integrity/stability of the tear film. With the ability to alternate between Ce3+ and Ce4+, cerium oxide nanozymes could scavenge overexpressed reactive oxygen species (ROS). Hence, a DQS-loaded cerium oxide nanozyme was designed to boost the synergistic treatment of DED. Cerium oxide with branched polyethylenimine-graft-poly(ethylene glycol) as nucleating agent and dispersant was fabricated followed with DQS immobilization via a dynamic phenylborate ester bond, obtaining the DQS-loaded cerium oxide nanozyme (defined as Ce@PBD). Because of the ability to mimic the cascade processes of superoxide dismutase and catalase, Ce@PBD could scavenge excessive accumulated ROS, showing strong antioxidant and anti-inflammatory properties. Meanwhile, the P2Y2 receptors in the conjunctival cells could be stimulated by DQS in Ce@PBD, which can relieve the incompleteness and instability of the tear film. The animal experiments demonstrated that Ce@PBD significantly restored the defect of the corneal epithelium and increased the number of goblet cells, with the promotion of tear secretion, which was the best among commercial DQS ophthalmic solutions.

Management of Dry Eye Disease for Intraocular Lens Power Calculation in Cataract Surgery: A Systematic Review.

Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the tear film is lost. As the prevalence of both diseases increases with age, there is a high prevalence of DED among patients who are candidates for cataract surgery. In recent years, cataract surgery has evolved from vision restoration surgery to refractive surgery. To achieve good surgical outcomes, it is necessary to minimize postoperative refractive error in intraocular lens (IOL) power calculation, which requires accurate preoperative keratometry measurements. A stable tear film is important for the accuracy and reproducibility of keratometry measurements, and DED may have a deleterious effect. In this study, original articles that focused primarily on findings related to this topic were evaluated. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Although appropriate DED diagnoses were not presented in the articles evaluated in this review, it was confirmed that the clinical signs of DED, particularly the shortening of the tear film break-up time (TBUT), negatively impact IOL power calculations. Improvement in these clinical signs might mitigate the negative effects on these calculations.

Effects of a Long-Acting Diquafosol Ophthalmic Solution on the Ocular Surface, Tolerability, and Usability in Dry Eye Disease.

INTRODUCTION: This study aimed to investigate the tolerability of high-viscosity diquafosol tetrasodium (DQS) ophthalmic solution (DIQUAS LX; DQSLX) and examine its usability and effect on clinical findings in patients with dry eye disease (DED). METHODS: This interventional retrospective study included 66 eyes of 66 patients with DED who switched from conventional DQS to DQSLX ophthalmic solution. Tear function assessments (tear film breakup time [BUT], keratoconjunctival vital staining [VS] score), evaluations of DED symptom relief, and a four-item usability questionnaire ("comfort upon instillation," "irritation upon instillation," "eye mucus discharge," "convenience of instillation frequency") assessed using a visual analog scale from 0 (worst) to 10 (best) were administered 4 weeks after switching to DQSLX. Factors associated with drug tolerability were assessed using multiple regression analysis. RESULTS: The symptoms improved by 64.2% after switching to DQSLX. The BUT value, VS score, and the questionnaire items "comfort upon instillation" and "convenience of instillation frequency" were significantly improved after switching to DQSLX. DQSLX tolerability was reported as acceptable in 56 (84.8%) and unacceptable in 10 (15.2%) patients. Overall, DQSLX tolerability was significantly associated with "comfort upon instillation" and "convenience of instillation frequency" and tended to be associated with a VS score ≥ 1. DQSLX tolerability depended on symptom and VS score improvements and absence of excessive "eye mucus discharge" in patients with a VS score ≥ 1 (39 patients), but on "comfort upon instillation" and absence of excessive "eye mucus discharge" in patients with a VS score = 0 (27 patients). CONCLUSION: The high-viscosity DQSLX ophthalmic solution was generally considered acceptable in the study population. However, drug tolerability seemingly differed between patients with DED with and without epithelial damage. The former were affected by improvements in symptoms and clinical findings, whereas the latter were affected by comfort upon instillation. TRIAL REGISTRATION: University Hospital Medical Information Network identifier, UMIN000051390.

Development and evaluation of hot-melt-extruded diquafosol tetrasodium formulations for ophthalmic inserts: A design of experiments approach.

This study aimed to develop, optimize, and evaluate hot-melt-extruded ophthalmic inserts capable of sustained release of diquafosol tetrasodium (DQS) via a design of experiments approach. DQS, a tear stimulant for dry eye management, faces challenges of frequent administration and low bioavailability. The developed insert uses biodegradable polymers in varied proportions to achieve sustained release. Optimized through mixture design, the insert completely dissolved within 24 h and maintained a stable drug content, thickness, and surface pH over three months at room temperature. In vitro corneal permeation studies on excised rabbit corneas demonstrated increased bioavailability, suggesting a reduced dosing frequency compared with conventional eye drops. Therefore, this insert has potential to enhance treatment outcomes by improving patient compliance and providing sustained drug effects.

Effect of Long-Acting Diquafosol Sodium on Astigmatism Measurement Repeatability in Preoperative Cataract Cases with Dry Eyes: A Multicenter Prospective Study.

INTRODUCTION: Dry eye can compromise corneal astigmatism measurement repeatability during preoperative cataract surgery examination. No previous studies have analyzed the effectiveness of long-acting 3% diquafosol sodium (LA-DQS) on astigmatism measurement repeatability. This research assessed the effect of LA-DQS on astigmatism measurement repeatability in preoperative patients with cataract and short tear break-up time (TBUT) type dry eyes in both eyes of the same patient. Correlations between repeatability and TBUT, corneal high-order aberrations (HOAs), and corneal astigmatism magnitude were also analyzed. METHODS: In total, 122 eyes (61 patients) with short TBUT-type dry eye were enrolled. Preoperatively, only one eye of all patients was treated with LA-DQS for 4 weeks. TBUT and corneal HOAs were checked using CASIA 2 before and 4 weeks post-treatment. The cylindrical power and meridian of astigmatism were measured at 3- and 4-week post-treatment using IOLMaster 700. Power vectors J0 and J45 were used for astigmatism calculations. Repeatability of astigmatism measurements was assessed as the within-subject standard deviation (Sw). The relative effects of TBUT and HOAs on J0 Sw and J45 Sw were also analyzed. Comparative changes in these variables were evaluated between treated and non-treated eyes, with additional analysis of their correlations. RESULTS: Treated eyes exhibited significant improvements in TBUT, HOAs, and post-treatment measurements of J0 Sw and J45 Sw at 3 and 4 weeks. In non-treated eyes, J0 Sw and J45 Sw showed significant correlation with TBUT and corneal HOAs. HOAs showed stronger relative associations with J0 Sw and J45 Sw than TBUT. In non-treated eyes, no significant correlation was found between cylindrical power and astigmatism measurement repeatability. CONCLUSIONS: In short TBUT-type dry eye, preoperative treatment with LA-DQS significantly improved astigmatism measurement repeatability. This may improve the precision of intraocular lens (IOL) power calculations regardless of the magnitude of corneal astigmatism, especially when toric IOLs are used.

Effect of diquafosol sodium combined with sodium hyaluronate on improving tear film stability after wearing orthokeratology lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effect of diquafosol sodium(SD)eye drops combined with sodium hyaluronate eye drops on improving tear film stability after wearing orthokeratology lenses.METHODS:Prospective study. A total of 82 patients(82 right eyes)who were recruited from the outpatient department of Anhui Aier Eye Hospital from March to August 2022. Participants were assigned to three groups: sodium hyaluronate(SH)group(30 eyes), SD group(24 eyes), and sodium diquafosol combined with sodium hyaluronate(CG)group(28 eyes)according to random number table method. All groups wore the same brand of orthokeratology lens. Non-invasive tear breakup time(NIBUT), non-invasive tear meniscus height(NITMH)and lipid layer thickness were examined before treatment, and after wearing orthokeratology lens for 1 d, 1 wk, and 1 mo. Corneal spot staining was also recorded.RESULTS:The NITMH and NIBUT of CG group and the SD group at 1 mo after treatment were higher than those before wearing lenses(both P<0.05), and the NIBUT and NITMH of the CG group were 19.74±3.29 s and 0.30±0.05 mm, respectively, which were better than those of the SD group(NIBUT: 16.09±2.98 s, NITMH: 0.22±0.08 mm)and the SH group(NIBUT: 15.67±3.90 s, NITMH: 0.22±0.04 mm; all P<0.01). There were no significant differences in lipid layer thickness between the groups(all P>0.05). The incidence of corneal staining did not differ significantly among the groups(P>0.05).CONCLUSION:The combination of diquafosol sodium and sodium hyaluronate eye drops demonstrates a superior effect in improving NIBUT and NITMH after wearing orthokeratology lenses for 1 mo, effectively enhancing tear film stability in patients wearing orthokeratology lenses.

Effect of diquafosol sodium combined with sodium hyaluronate on dry eye after pterygium surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the clinical efficacy of 3% diquafosol sodium eye drops combined with sodium hyaluronate eye drops in the treatment of dry eyes after pterygium surgery with lacrimal insufficiency.METHODS: A total of 64 cases(64 eyes)of pterygium patients with lacrimal insufficiency were treated with pterygium resection combined with limbal stem cell transplantation, and they were given routine anti-inflammatory and infection prevention treatment postoperatively. In terms of postoperative dry eye treatment, all patients were randomly divided into two groups. The observation group was treated with 3% diquafosol sodium eye drops combined with sodium hyaluronate eye drops, and the control group was treated with sodium hyaluronate eye drops. The break-up time of tear film(BUT), fluorescein(FL), Schirmer's Ⅰ test(SⅠt), ocular surface disease index(OSDI)score, central corneal thickness(CCT)changes, adverse reactions and complications were observed and compared between the two groups at different times postoperatively.RESULTS: Both groups of pterygium patients were accompanied with mild to moderate dry eyes with insufficient tear secretion preoperatively. At 2 wk after operation, both groups showed shorter BUT and higher FL score compared with those preoperatively(P<0.05). There was no significant difference between the two groups(P>0.05). At 4 wk after operation, BUT in the observation group was prolonged, OSDI score was decreased(both P<0.05), and FL score in both groups was decreased compared with those at with 2 wk after operation(P<0.05). The observation group was better than the control group(P<0.05). At the first day after operation, the CCT of the two groups was thicker than that preoperatively(P<0.05), and there was no significant difference in SⅠt between the two groups before and after operation(P>0.05).CONCLUSION: In the treatment of dry eye after pterygium surgery with lacrimal insufficiency, 3% diquafosol sodium eye drops combined with sodium hyaluronate eye drops can effectively reduce the postoperative dry eye symptoms, and its clinical effect is better than that of sodium hyaluronate eye drops alone.

Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

A protocol for a single center, randomized, controlled trial comparing the clinical efficacy of 3% diquafosol and 0.1% hyaluronic acid in diabetic patients with dry eye disease.

BACKGROUND: The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients. METHODS: This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS (n = 101) and HA (n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8. DISCUSSION: This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment. TRIAL REGISTRATION: ClinicalTrials.govNCT05682547. Registered on December 05, 2022.

Effects of diquafosol sodium in povidone iodine-induced dry eye model.

AIM: To investigate the effects of diquafosol sodium (DQS) for dry eye model induced with povidone-iodine (PI) solution. METHODS: Ten Sprague Dawley rats as the control group. Thirty Sprague Dawley rats were used to establish the dry eye model with stimulation of 10 g/L PI for 14d, then divided rats into three groups: dry eye group with no treatment (DED group, n=10); phosphate buffer saline treated group (PBS group, n=10); diquafosol treated group (DQS group, n=10). Clinical changes were observed by tear production test, fluorescein staining, tear break-up time (TBUT) test, corneal confocal microscope and ocular surface comprehensive analyzer. Eyeballs were collected on day 10 of treatment for hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and alcian blue staining. TUNEL assay, polymorphonuclear (PMN) and mucin 1 (MUC1) immunofluorescence were performed and corneal ultrastructural changes were detected by electron microscopy. RESULTS: Compared with DED and PBS groups, tear production (7.26±0.440 vs 4.07±0.474 mm; 7.26±0.440 vs 3.74±0.280 mm; all P<0.01) and TBUT (7.37±0.383s vs 1.49±0.260s; 7.37±0.383s vs 1.42±0.437s; all P<0.01) were significantly increased in DQS group. HE, PAS, and alcian blue staining and MUC1 immunofluorescence showed mucins and conjunctival goblet cells density (8.45±0.718 vs 5.21±0.813 cells/0.1 mm2; 8.45±0.718 vs 5.36±0.615 cells/0.1 mm2; all P<0.01) increased in DQS group. Confocal microscopy, PMN immunofluorescence and TUNEL staining showed inflammatory infiltration and corneal epithelial cells apoptosis decreased in DQS group. The increased number of microvilli in corneal epithelial and the recovered cell junction were observed in DQS group. CONCLUSION: PI instillation can induce goblet cells and mucin loss, epithelial cell apoptosis and inflammation, which are consistent with the pathological manifestations of dry eye. Diquafosol can repair the ocular surface damage caused by PI, reduce corneal inflammation, inhibit corneal epithelial cell apoptosis, promote mucin secretion and maintain tear film stability.

Treatment of Dry Eye Disease (DED) in Asia: Strategies for Short Tear Film Breakup Time-Type DED.

Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time-type DED, which has become a global problem in recent years, is common. While the mainstay of DED treatment in the West is the suppression of inflammation, the first goal of treatment is the stabilization of the tear film in Asia. To date, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side-effects (cataracts, increased intraocular pressure). This review evaluates the new generation therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on considerations, it is proposed that the optimal treatment for the short tear film breakup time-type DED is the initial application of mucin-secretion-enhancing eye drops (long-acting diquafosol) and oral supplements; and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

Combination Therapy With Diquafosol Sodium and Sodium Hyaluronate in Eyes With Dry Eye Disease After Small Incision Lenticule Extraction.

BACKGROUND/AIM: To evaluate the clinical efficacy of combination therapy with diquafosol sodium and sodium hyaluronate in dry eye patients after small incision lenticule extraction (SMILE). PATIENTS AND METHODS: A prospective randomized controlled study was conducted on consecutive patients who were diagnosed with dry eye disease (DED) and ready to accept SMILE from January 2021 to December 2021. The participants were randomly allocated to either a combination with diquafosol sodium 3% and sodium hyaluronate 0.3% group (DQS group, n=40) or a sodium hyaluronate 0.3% group (HA group, n=41). Dry eye disease parameters included tear film break-up time (TBUT), Shirmer I test (SIT), corneal and conjunctival fluorescein staining score (FS score), and Ocular Surface Disease Index (OSDI); tests were conducted before surgery and at 1 week, 1 month, and 3 months after surgery. RESULTS: At 1 week after surgery, there were no statistically significant overall differences in DED parameters between the 2 groups. At postoperative month 1, the FS score was significantly lower in the DQS group than in the HA group (1.20±1.06 vs. 1.83±1.41 respectively, p=0.026). At 3 months after the surgery, the DQS group was significantly superior to the HA group in OSDI (12.98±7.29 vs. 16.82±8.25, p=0.029), TBUT (5.83±2.02 vs. 4.24±0.94, p=0.0002), and SIT (7.75±3.92 vs. 5.24±3.42, p=0.003). CONCLUSION: Our study showed that combination therapy with diquafosol and hyaluronate was beneficial for improving both signs and symptoms of dry eye patients after small incision lenticule extraction.

The Combined Impact of Intense Pulsed Light Combined and 3% Diquafosol Ophthalmic Solution on Evaporative Dry Eye: A Randomized Control Study.

INTRODUCTION: The primary objective of this study is to assess whether the combination of intense pulsed light (IPL) with 3% diquafosol (DQS) ophthalmic solution is more effective than intense pulsed light in alleviating signs and symptoms of dry eye disease (DED). METHODS: This randomized study included 66 participants with evaporative dry eye (EDE) who received IPL + DQS therapy (n = 44 eyes), IPL therapy (n = 44 eyes), or sham therapy (n = 44 eyes). All participants were examined at baseline (D0), day 14 (D14), and day 28 (D28) for non-invasive break-up time (NITBUT), tear-film lipid layer (TFLL), corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expression (MGEx), and ocular surface disease index (OSDI). RESULTS: At day 28, comparison among the IPL + DQS therapy, IPL therapy, and sham therapy found significant differences in the mean NITBUT (12.03 ± 1.27 versus 10.47 ± 3.48 versus 4.57 ± 0.46; p < 0.001), TFLL (2.09 ± 0.29 versus 2.27 ± 0.45 versus 2.89 ± 0.65; p < 0.001), CS (1.43 ± 0.82 versus 1.93 ± 1.32 versus 3.52 ± 1.00; p < 0.001), MGQ (1.55 ± 0.66 versus 1.91 ± 0.77 versus 2.66 ± 0.53; p < 0.001), MGEx (1.27 ± 0.45 versus 1.75 ± 0.44 versus 2.41 ± 0.50; p < 0.001), and OSDI score (19.36 ± 7.01 versus 24.77 ± 4.68 versus 42.61 ± 7.49; p < 0.001); significant improvements in NITBUT, TFLL, CS, MGQ, MGEx, and OSDI were found in the IPL + DQS therapy and IPL therapy, while the sham therapy had no significant improvements. CONCLUSION: Combining 3% diquafosol ophthalmic solution with intense pulsed light was superior to IPL therapy alone in relieving the signs and symptoms of patients with severe evaporative DED. TRIAL REGISTRATION: Clinical Trials Identifier: NCT05694026.

Effectiveness and Adherence of Dry Eye Patients Who Switched from Short- to Long-Acting Diquafosol Ophthalmic Solution.

Long-acting (lasting extend) diquafosol ophthalmic solution 3% (DQSLX) is administered three times daily versus six times daily for the currently approved diquafosol ophthalmic solution (DQS). We investigated the efficacy and adherence of switching from DQS to DQSLX in patients with dry eye disease. We retrospectively enrolled 54 patients (17 men and 37 women) with eye drop prescription changes from DQS to DQSLX between December 2022 and March 2023. The number of eye drops, subjective symptoms, tear breakup time (TBUT), and fluorescein staining scores from baseline to 4 weeks after starting DQSLX were evaluated. Participants then chose between DQSLX and DQS. Patients administered DQSLX three times per day, as listed on the package insert, 88.9% of the time; significantly higher than the 5.6% of patients who used DQS six times per day, as instructed. The DQSLX group showed significant improvements in symptoms and fluorescein staining scores (23.3 ± 20.1 and 0.8 ± 1.7, respectively) compared with the baseline (37.8 ± 24.1 and 1.1 ± 1.5, p = 0.01 and <0.001, respectively). The TBUT in the DQSLX group (5.0 ± 2.5 s) did not significantly improve compared to the DQS group (4.5 ± 1.7 s) (p = 0.75). Fifty-one (94.4%) patients opted to continue DQSLX because of the pleasant feeling of the eye drops, long-lasting moisture, and less frequent administration. The efficacy and adherence of DQSLX was comparable to DQS.

Short-term application of diquafosol ophthalmic solution benefits children with dry eye wearing orthokeratology lens.

Purpose: This aim of this study was to evaluate the effect of 3% Diquafosol Ophthalmic Solution (DQS) on children with dry eye from wearing overnight orthokeratology (OrthoK) lenses. Methods: Myopic children aged 8-18 years with dry eye syndrome were enrolled in this prospective observational study, and they were grouped according to their OrthoK treatment history for at least 1 year. All participants received DQS 4 times per day for 1 month. The following indicators were measured at baseline 1 month after treatment: the Dry Eye Questionnaire-5 (DEQ-5), non-invasive tear meniscus height (TMH), non-invasive tear film break-up time (first and average, NIBUT-F and NIBUT-A), meibomian gland score (MG score), conjunctival hyperemia redness score (R-scan), and blink pattern analysis. Results: A total of 104 participants (189 eyes) including 40 OrthoK wearers (72 eyes) and 64 Orthok candidates (117 eyes) completed the study. Of all, after DQS treatment for 1 month, DEQ-5 scores reduced from 5.54 ± 3.25 to 3.85 ± 2.98 (t = -3.36, p = 0.00). TMH increased from 0.20 ± 0.05 mm to 0.21 ± 0.05 mm (t = 2.59, p = 0.01), NIBUT-F and NIBUT-A were prolonged from 6.67 ± 4.71 s to 10.32 ± 6.19 s and from 8.86 ± 5.25 s to 13.30 ± 6.03 s (all p = 0.00), respectively. R-scan decreased from 0.69 ± 0.28 to 0.50 ± 0.25 (t = -9.01, p = 0.00). Upper MG scores decreased from 1.04 ± 0.32 to 0.97 ± 0.36 (t = -2.14, p = 0.03). Lower MG scores, partial blink rate, partial blinks, and total blinks did not change significantly. Both break-up time (BUT) and R-scan improved significantly after DQS treatment for 1 month (all p = 0.00) in OrthoK candidates and OrthoK wearers. Among the OrthoK wearers, TMH and dry eye symptoms increased significantly (all p = 0.00) but did not increase in OrthoK candidates (p > 0.05). There were no adverse events related to DQS. Conclusion: Diquafosol Ophthalmic Solution was effective for children wearing overnight orthokeratology in relieving dry eye symptoms and improving ocular surface parameters, which may help improve children's OrthoK wearing tolerance and compliance.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Comparison of matrix metallopeptidase-9 expression following cyclosporine and diquafosol treatment in dry eye.

PURPOSE: We sought to evaluate the expression of matrix metalloproteinase-9 (MMP-9) in dry eyes treated with 0.05% cyclosporin A and 3.0% diquafosol tetrasodium. METHODS: One-hundred ninety-five eyes of 195 patients with dry eye were divided into three groups as follows: group 1, cyclosporin group (n = 69); group 2, diquafosol group (n = 59); and group 3, artificial tears eyes (n = 67). All eyes were treated and followed up for three months. Schirmer I Test, corneal staining, tear-film break-up time (TBUT), and tear-film MMP-9 content were measured at three months and compared between groups. The expression of MMP-9 was confirmed using a point-of-care test device (InflammaDry®; RPS Diagnostics, Sarasota, FL, USA) and graded as zero to four points. RESULTS: At the third month, MMP-9 expression was lower in group 1 as compared with in groups 2 and 3 (p = 0.020 and 0.006, respectively). The mean MMP-9 grade according to point-of-care testing was also lower in group 1 than in groups 2 or 3 (p = 0.002 and 0.038, respectively). MMP-9 showed a correlation with corneal staining in both groups 1 and 2 (all p < 0.001) and with Schirmer I Test and TBUT in group 1 (p = 0.018 and 0.015, respectively). CONCLUSIONS: MMP-9 expression and grade were lower after treatment with cyclosporin than after treatment with diquafosol in the dry eye disease. Anti-inflammatory treatment can decrease ocular MMP-9 levels in dry eye disease.

MMP-9 expression and grade were lower after treatment with cyclosporin than after treatment with diquafosol in the dry eye disease. Anti-inflammatory treatment can decrease ocular MMP-9 levels in dry eye disease.

Topical diquafosol versus hyaluronic acid for the treatment of dry eye disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Diquafosol enhances fluid transfer and mucin secretion on ocular surface, which has been suggested as an effective treatment for dry eye disease (DED). The aim of the systematic review and meta-analysis was to compare the efficacy and safety of topical diquafosol versus hyaluronic acid (HA) for DED. METHODS: Relevant randomized controlled trials were obtained via search of electronic including PubMed, Embase, Cochrane Library, and Web of Science. A random-effects model was used to pool the results after incorporating the influence of potential heterogeneity. RESULTS: A total of nine RCTs involving 1295 patients with DED were included in the meta-analysis. Compared to treatment with 0.1% HA, topical treatment with 3% diquafosol significantly improved the Ocular Surface Disease Index (mean difference (MD): - 3.59, 95% confidence interval (CI): - 4.68 to - 2.50, p < 0.001; I2 = 6%), results of Schirmer's test (MD: 1.08 mm, 95% CI: 0.41 to 1.76, p = 0.002; I2 = 0%), tear breakup time (MD: 0.60 s, 95% CI: 0.20 to 0.99, p = 0.003; I2 = 63%), corneal fluorescein staining score (MD: - 0.20, 95% CI: - 0.37 to - 0.03, p = 0.02; I2 = 58%), and ocular rose bengal staining score (MD: - 0.62, 95% CI: - 0.88 to - 0.35, p < 0.001; I2 = 15%). No severe adverse events were reported. Topical use of diquafosol was associated with a higher risk of overall adverse events as compared to HA (odds ratio: 1.71, 95% CI: 1.08 to 2.71, p = 0.02; I2 = 18%). CONCLUSIONS: Topical treatment with 3% diquafosol may be more effective than 0.1% HA for patients with DED. However, the long-term efficacy and tolerability of diquafosol still need to be determined.

Combination therapy with 3% diquafosol tetrasodium ophthalmic solution and sodium hyaluronate: an effective therapy for patients with dry eye after femtosecond laser-assisted in situ keratomileusis.

Purpose: To assess the effect of combination therapy with 3% diquafosol tetrasodium (DQS) and sodium hyaluronate (HA) for dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Design: Prospective nonrandomized comparative trial. Methods: The prospective study included 80 eyes of 40 patients who underwent FS-LASIK with or without preoperative dry eye. Patients were divided into a combination group and a HA group according to their willingness and the doctor's advice. The combination group was treated with DQS six times a day and HA four times a day, and the HA group was treated with HA four times a day after FS-LASIK. Ocular surface disease index (OSDI), ocular symptom score, vision-related score, environmental score, tear meniscus height (TMH), first non-invasive tear breakup time (NIBUT-First), average non-invasive tear breakup time (NIBUT-Ave), tear breakup time (TBUT), Schirmer I test (SIT), corneal fluorescein staining score (CFS), bulbar redness score, limbal redness score, lipid layer grade (LLG), meiboscore, lid margin abnormality, corneal sensitivity, and corneal nerve parameters were examined before surgery and at 1 week and 1 month after surgery. Surface regularity index (SRI) was also examined before surgery and at 1 month postoperatively. Results: OSDI score (p = 0.024) and vision-related score (p = 0.026) were significantly lower in the combination group than in the HA group at 1 month after FS-LASIK, especially in patients with preoperative dry eye symptoms. The increasements of CFS (p = 0.018), bulbar redness score (p = 0.021), and limbal redness score (p = 0.009) were significantly lower in the combination group than in the HA group at 1 week after FS-LASIK. But other ocular surface parameters showed no difference between both groups at 1 week and 1 month after FS-LASIK. LLG was significantly higher in the combination group than in the HA group at 1 week (p = 0.004) and 1 month (p < 0.001) after surgery, especially in patients with high meiboscore. Additional DQS significantly improved corneal sensitivity in patients without preoperative dry eye symptoms at 1 month after FS-LASIK (p = 0.041). Conclusion: The combination therapy with DQS and HA significantly relieved subjective symptoms, improved ocular surface status, and had the potential to promote corneal nerve growth in patients after FS-LASIK.