Diquafosol Research Articles

Practical and Efficient Approach to the Preparation of Diquafosol Tetrasodium

A scalable and practical route to synthesize the P2Y2 receptor agonist diquafosol tetrasodium has been described. Diquafosol tetrasodium was obtained via a four-step process starting from commercia...

RETRACTED ARTICLE: Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial

BackgroundThis 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).MethodsThis 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.ResultsAt 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.ConclusionsThe 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.Trial registrationKCT0002180, retrospectively registered on 23 December 2016.

The Protective Effect of a Topical Mucin Secretagogue on Ocular Surface Damage Induced by Airborne Carbon Black Exposure.

Exposure to airborne particulate matter can induce ocular surface damage and inflammation. We evaluated the effects of a topical mucin secretagogue on the mitigation of ocular surface damage induced by exposure to airborne carbon black (CB). Sprague-Dawley rats were exposed to ambient CB for 2 hours twice daily for 5 days. Corneal staining score and tear lactic dehydrogenase (LDH) activity were measured to evaluate ocular surface damage. Serum immunoglobulin (Ig) G and IgE levels and the sizes of cervical lymph nodes were also measured. The expressions of interleukin (IL)-4, IL-17, and interferon (IFN)-γ were measured by Western blot analysis. Diquafosol tetrasodium was instilled six times a day for 5 days, and the extent of ocular surface damage was evaluated. After exposure to airborne CB, the median corneal staining score and LDH activity were significantly increased. Serum IgG and IgE levels and the sizes of cervical lymph nodes were also significantly increased. Additionally, the expression of IL-4 and IFN-γ was elevated in the anterior segment of the eyeball. Furthermore, the expression of IL-4, IL-17, and IFN-γ was elevated in the cervical lymph nodes. When exposed to airborne black carbon, topical diquafosol tetrasodium significantly increased tear MUC5AC concentration and decreased tear LDH activity. Exposure to airborne CB induced ocular surface damage and increased proinflammatory cytokines in the eyes and cervical lymph nodes. Topical mucin secretagogues seem to have a protective effect on the ocular surface against exposure to airborne particulate matters.

Therapeutic effects of 3% diquafosol ophthalmic solution in patients with short tear film break-up time-type dry eye disease

BackgroundTo investigate therapeutic effects of topical diquafosol tetrasodium 3% ophthalmic solution in patients with short tear film break-up time (TFBUT)-type dry eye (DE).MethodsThe prospective study was performed in 70 eyes of 70 patients with short TFBUT-type DE. Diagnosis of short TFBUT-type DE was made based on the presence of DE symptoms, TFBUT value ≤5 s, corneoconjunctival staining score ≤ 2 (on a scale of 0 to 4), and Schirmer I value > 5 mm. Patients with systemic immunologic disorders or ocular graft-versus-host disease were excluded. Before and after instillation of 3% diquafosol ophthalmic solution six times per day for 4 weeks, subjective DE symptoms, TFBUT, corneoconjunctival staining score, and Schirmer I value were examined and compared. Also, demographic factors were compared between patients who showed improvement in each DE parameter by treatment and those who did not.ResultsFour-week treatment with 3% diquafosol ophthalmic solution significantly improved DE symptoms (p < 0.0001), increased TFBUT (p < 0.0001), and reduced corneoconjunctival staining scores (p < 0.0001). Schirmer I values were not changed by treatment. The age of patients who showed improvement in subjective DE symptoms after treatment was significantly lower than that of patients who did not (53.4 ± 27.5 vs. 63.3 ± 13.9 years, p = 0.012). Ocular side effects developed in 3 patients (4.3%), including conjunctival chemosis (n = 1) and persistent stinging sensation (n = 2).ConclusionsDiquafosol tetrasodium 3% ophthalmic solution is effective in improving subjective symptoms and tear film stability in short TFBUT-type DE patients.Trial registrationThe study was retrospectively registered on Clinical Research Information Service (CRiS), Republic of Korea.Trial registration number: KCT0003134.Date of registration: 2018-08-15.

RGN-259 (thymosin \u03b24) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model

This study evaluated the clinical activity of RGN-259 (thymosin β4) in comparison with cyclosporine A (CsA), diquafosol (DQS), and lifitegrast (LFA) in a murine model of dry eye. The model was NOD.B10-H2b mice in a 30–40% humidified environment together with daily scopolamine hydrobromide injections for 10 days. After desiccation stress, all drugs were evaluated after 10 treatment days. RGN-259 increased tear production similar to that in the DQS- and LFA-treated mice while CsA was inactive. RGN-259 improved corneal smoothness and decreased fluorescein staining similar to that of LFA group while CsA and DQS were inactive. Corneal epithelial detachment was reduced by RGN-259, and DQS and LFA showed similar activity but the CsA was inactive. RGN-259 increased conjunctival goblet cells and mucin production comparable to that seen with CsA, while DQS and LFA were inactive. RGN-259 reduced the over-expression of inflammatory factors comparable to that with CsA and LFA, while DQS was inactive. RGN-259 increased mucin production comparable to that observed with CsA, while DQS and LFA were inactive. In conclusion, RGN-259 promoted recovery of mucins and goblet cells, improved corneal integrity, and reduced inflammation in a dry eye mouse model and was equal to or more effective than prescription treatments.

Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye.

Complex mechanisms underlie dry eye (DE) symptom provocation. In particular, corneal hypersensitivity may provoke symptoms in short tear break-up time (BUT) DE characterized by tear film instability. We hypothesized that improved tear film stability may alleviate corneal sensitivity in patients with short tear BUT DE. Therefore, we investigated the effect of topical diquafosol tetrasodium (DQS) on corneal sensitivity in unstable tear film DE. This prospective, randomized study included 27 subjects (age: 39.1 ± 8.4years; range: 25-59years) with short tear BUT DE, defined based on the presence of DE symptoms and tear film instability. Subjects were randomly divided into DQS (3% DQS, 12 subjects) and artificial tear (AT; preservative-free AT, 15 subjects) groups. Subjects applied the medication 6 times a day for 5weeks. The perception of touch (S-touch) and pain (S-pain) sensitivity was measured using a Cochet-Bonnet esthesiometer. Tear evaluation, corneal sensitivity, and DE symptoms were compared before and after DQS or AT administration. The correlation between the improvement degrees of corneal sensitivity and DE symptoms following medication was analyzed. DQS significantly improved tear BUT and tear meniscus height (TMH) scores (p < 0.05), while AT significantly improved tear BUT (p < 0.05) but not TMH score. Mean S-pain and DE symptom scores were lower after medication use in the DQS (S-pain and DE symptoms: p < 0.05) and AT groups (S-pain: p = 0.05; DE symptoms: p < 0.05). However, S-touch did not change significantly in either group. A positive correlation was observed between the improvement degrees of S-pain and DE symptoms in the overall subjects studied. Both DQS and AT alleviate corneal hypersensitivity and DE symptoms in eyes with short tear BUT DE. However, DQS seems to be more effective to adjust tear environment, leading to the normalization of corneal sensitivity and DE symptoms. UMIN Clinical Trials Registry Identifier, UMIN000014536.

A Prospective, Randomized Trial of Two Mucin Secretogogues for the Treatment of Dry Eye Syndrome in Office Workers

The purpose of the study was to compare the two mucin secretogogues, diquafosol (DQS) and rebamipide (RBM), for the treatment of dry eye syndrome (DES) in office workers. Dry eye patients using computers for >4 h/day were randomly assigned treatment with either DQS or RBM. Main outcomes measures included changes in tear film break-up time (TBUT) and subjective symptoms assessed by the Dry Eye-Related Quality of Life Score (DEQS). The subjects had scheduled examinations at 0 and 4 weeks, and the examinations at 2 and 8 weeks were optional. Changes in keratoconjunctival fluorescein score and a patient satisfaction questionnaire were also recorded. Both groups showed significant improvements in the DEQS scores at 2, 4, and 8 weeks following the initiation of the study. Both groups showed significant increases in the TBUT at 2 and 4 weeks. No significant difference was found between the DQS and RBM groups at any time periods. Patients reported more comfort with the use of DQS compared with the use of RBM. No local or systemic side effects were noted. The results of the present study indicated that both DQS and RBM were effective for the treatment of DES in office workers.

Effectiveness of Combined Tear Film Therapy in Patients with Evaporative Dry Eye with Short Tear Film Breakup Time

The aim of this study was to evaluate the effectiveness of combined tear film therapy targeted to aqueous, mucin, and lipid layers in patients with refractory evaporative dry eye (EDE) with short tear film breakup time (TBUT). The patients who had EDE with short TBUT and severe symptoms refractory to artificial tears were treated with hyaluronic acid (HA) 0.15% and diquafosol tetrasodium (DQS) 3% (Group 1), HA and carbomer-based lipid-containing eyedrops (Liposic EDO Gel, LPO) (Group 2), or HA, DQS, and LPO (Group 3). Ocular Surface Disease Index (OSDI) score, visual analog scale (VAS) symptom score, TBUT, Schirmer score, and corneal and conjunctival staining scores were evaluated, and noninvasive tear film breakup time (NIBUT) and tear meniscus height were measured using Keratograph® 5 M before and 1 and 3 months after treatment. OSDI scores, VAS scores, TBUT, and NIBUT were improved at 1 and 3 months after treatment in all groups (all P < 0.05). At each follow-up visit, the total OSDI, OSDI symptom, and all VAS scores were significantly lower in group 3 compared with groups 1 and 2 (all P < 0.05). In addition, TBUT and NIBUT were significantly higher in group 3 compared with groups 1 and 2 (all P < 0.05). No significant adverse effects were noted in the groups during treatment. Mucin or lipid-targeting agents combined with aqueous supplements in patients with refractory EDE with short TBUT might improve subjective symptoms and TBUT. Of this, targeting whole tear film layers was most effective in improving ocular symptoms and tear film quality.

Effect of diquafosol tetrasodium 3% on the conjunctival surface and clinical findings after cataract surgery in patients with dry eye.

To investigate the effects of diquafosol tetrasodium (DT) 3% on conjunctival impression cytologic findings in addition to clinical symptoms and signs after cataract surgery in patients with preexisting dry eye disease (DED). Ninety-four eyes of 94 patients with DED who underwent uneventful cataract surgery were included. In total, 50 patients were treated with DT 3% (group A), while 44 patients were treated with sodium hyaluronate 0.1% (group B) postoperatively, along with topical antibiotics and steroids. Conjunctival impression cytology was performed at baseline and at 4 and 12weeks after surgery. Visual acuity, ocular surface disease index (OSDI), tear film breakup time (TBUT), keratoepitheliopathy score, Schirmer's test, and tear clearance rate were measured at baseline and at 1, 4, and 12weeks, and corneal aberration was analyzed at baseline and at 4 and 12weeks. The grade of conjunctival squamous metaplasia was lower at 12weeks, and goblet cell density was higher at 4 and 12weeks in group A than in group B (P<0.05). Compared with group B, group A showed significantly lower OSDI scores at 4 and 12weeks, longer TBUT at 1, 4, and 12weeks, lower keratoepitheliopathy scores at 1 and 12weeks, and lower total root-mean-square score and spherical aberrations at 4weeks after surgery (P<0.05). DT 3% eye drops application after cataract surgery was effective in improving conjunctival epithelial morphology and goblet cell density as well as clinical findings in patients with DED.

Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells

This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.

Diquafosol for Soft Contact Lens Dryness: Clinical Evaluation and Tear Analysis.

To evaluate the efficacy of topical application of 3% diquafosol tetrasodium solution for the treatment of soft contact lens (SCL) wearers with dryness. In addition to clinical tests and subjective symptoms, we assessed the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) used as a marker of membrane-associated mucins and sialic acid concentration in tear fluids as a marker of secreted mucins. Twelve SCL wearers with dryness symptoms were treated with diquafosol for 4 weeks. Clinical tests included the tear film break-up time (BUT), corneal and conjunctival fluorescein staining scores, and Schirmer values. Subjective symptoms were evaluated by the Dry Eye-Related Quality-of-Life Score (DEQS). Fluorescence intensities in the central cornea were measured by fluorophotometry at 5 minutes after a 5% F-WGA solution was applied to the eye. The tears collected by the Schirmer test strips were analyzed by high-performance liquid chromatography (HPLC), and the concentrations of sialic acid; total protein; and the four major tear proteins secretory IgA, lactoferrin, lipocalin-1, and lysozyme proteins were measured. Comparing the results before and after diquafosol treatment, BUT (p < 0.01), kerato-conjunctival staining score (p < 0.05), corneal staining score (p < 0.05), and DEQS score (p < 0.01) showed statistically significant improvements. The F-WGA fluorescence intensities (p < 0.0001) significantly increased after treatment, whereas the concentrations of sialic acid and tear proteins remained unchanged. Topical application of diquafosol solution to the SCL wearers with dryness improved biomarker of membrane-associated mucins, BUT, staining of cornea and conjunctiva, and subjective symptoms.

The Efficacy of Diquafosol Ophthalmic Solution in Non-Sjögren and Sjögren Syndrome Dry Eye Patients Unresponsive to Artificial Tear.

This study evaluates the efficacy of 3% diquafosol tetrasodium ophthalmic solution in Sjögren's syndrome (SS) and non-SS dry eye patients unresponsive to conventional artificial tear. This retrospective study included 38 dry eye patients (11 with SS and 27 with non-SS) who were treated with 3% diquafosol due to lack of response to artificial tear treatment for more than 3 months. Signs such as tear film break-up time (TBUT), Schirmer-I test, and total ocular staining score (OSS), which consisted of corneal OSS and conjunctival OSS, were evaluated at baseline and the first visit after treatment. Symptoms were quantified using visual analog scale (VAS) and ocular surface disease index (OSDI) scores. Changes of parameters after treatment in all the patients and differences of changes in SS and non-SS were evaluated. In total population, total OSS and corneal OSS improved average 6 weeks after diquafosol treatment (all P < 0.05, paired t-test), although conjunctival OSS had no improvement. TBUT increased after treatment (P = 0.036), while Schirmer-I test, OSDI, and VAS showed no improvement. With respect to comparisons, total and corneal OSS improved in non-SS patients and TBUT improved in SS patients (all P < 0.05). Three percent diquafosol tetrasodium treatment could be considered as an additive or substitute treatment when artificial tear treatment is insufficient, as it improved OSS and TBUT. This study also demonstrated that diquafosol treatment is beneficial for TBUT improvement in SS, while it is beneficial for OSS improvement in non-SS dry eye patients.

The Effect of Topical Diquafosol Tetrasodium 3% on Dry Eye After Cataract Surgery

ABSTRACTPurpose: To evaluate the effectiveness of 3% diquafosol tetrasodium for treating dry eye after cataract surgery.Methods: Among patients who underwent bilateral cataract surgery, 34, who met the diagnostic criteria for dry eye syndrome 1 week postoperatively, were enrolled. Patients were randomly assigned to receive 3.0% diquafosol tetrasodium ophthalmic solution in one eye and 0.9% saline in the other eye four times daily for 8 weeks. Dry eye severity was measured at 1, 5, and 9 postoperative weeks using the Schirmer 1 test (SIT), tear film breakup time (TBUT), and fluorescein corneal staining. tear meniscus height (TMH), tear meniscus depth (TMD), and tear meniscus area (TMA) measured using Fourier-domain optical coherence tomography and symptom questionnaire scores.Results: TBUT and corneal staining significantly improved 8 weeks postoperatively in eyes treated with 3.0% diquafosol tetrasodium (p < 0.01, p < 0.01) and were better than normal saline-treated eyes (p < 0.01, p < 0.01). SIT did not improve (p = 0.26). TMH, TMD, and TMA did not improve at 4 and 8 weeks. All symptom questionnaire scores improved in eyes treated with 3.0% diquafosol tetrasodium (all p < 0.01).Conclusion: The 3.0% diquafosol tetrasodium treatment improved tear film stability and subjective symptoms of dry eye after cataract surgery. Increased mucin production as a result of diquafosol treatment may have caused these results.

Comparison of Therapeutic Effects of 3% Diquafosol Tetrasodium with Aging in Dry Eye

Purpose: The aim of this study was to evaluate the clinical effect of 3% diquafosol in dry eye patients aged around 60 years. Methods: In total, 68 patients with dry eye syndrome were divided by age into 2 groups, Group I (29 patients, 29 eyes) under the age of 60 years and Group II (39 patients, 39 eyes) over the age of 60 years. To evaluate the effectiveness of 3% diquafosol, we measured the tear film break-up time (tBUT), performed the Schirmer I test, and used the corneal staining score as an objective indicator and the ocular surface disease index (OSDI) score as a subjective indicator at initial visit, 1 month, 2 months, and 4 months. Results: Significant improvements in the tear film break-up time, Schirmer I test, and OSDI were observed at 1,2, and 4 months after treatment with 3% diquafosol tetrasodium in both dry eye groups, but significant difference in the corenal staining score were not observed (p > 0.05). There were statistically significant improvement between the 2 age groups in the tBUT at 1 month (p = 0.012), 2 months (p = 0.005), and 4 months (p = 0.005), and improvements in the Schirmer I test between the 2 age groups at 1 month (p = 0.015), 2 months (p = 0.005), and 4 months (p = 0.005) were also observed. But, there was no significant difference in the corneal staining score and OSDI score between the 2 groups at 1, 2, and 4 months (p > 0.05). Conclusions: Topical 3% diquafosol tetrasodium administration was shown to be an effective treatment to improve clinical symptoms and objective indicators in dry eye patients regardless of age, showing significant improvements in tBUT and the Schirmer I test under the age of 60. J Korean Ophthalmol Soc 2016;57(5):734-741

Real-world assessment of diquafosol in dry eye patients with risk factors such as contact lens, meibomian gland dysfunction, and conjunctivochalasis: subgroup analysis from a prospective observational study.

PurposeTo evaluate the efficacy and safety of diquafosol (DQS) ophthalmic solution in dry eye (DE) patients wearing contact lenses (CLs) or with concomitant meibomian gland dysfunction (MGD) or conjunctivochalasis in a real-world setting.Patients and methodsFrom a cohort of patients enrolled in a prospective observational study, DE patients who met the Japanese diagnostic criteria and who received DQS as a monotherapy were extracted and stratified according to the presence or absence of CL use, MGD, and conjunctivochalasis. Corneal and conjunctival fluorescein staining score, tear film break-up time, total symptom score (12 DE-related subjective symptoms), patient-reported outcomes, and adverse reactions were investigated.ResultsDQS treatment resulted in significant improvement in total symptom score, corneal and conjunctival fluorescein staining score, and tear film break-up time without significant differences between patient subgroups with versus without CL use, MGD, or conjunctivochalasis. Comparable proportions of patients perceived symptomatic improvements in all subgroups. There were no adverse reactions specifically associated with the CL use or any comorbidity of MGD or conjunctivochalasis.ConclusionDQS can be used effectively and safely as a monotherapy for the treatment of DE patients wearing CLs or with concomitant MGD or conjunctivochalasis.

Clinical Efficacy of Topical Diquafosol Tetrasodium after Laser Epithelial Keratomileusis

Purpose: To evaluate the clinical effectiveness of topical diquafosol tetrasodium (DQS) after laser epithelial keratomileusis (LASEK). Methods: This randomized prospective study included 97 eyes of 49 patients who were scheduled for LASEK. Patients in the DQS group used both 0.3% sodium hyaluronate and 3% DQS for 3 months after surgery while patients in the control group used only 0.3% sodium hyaluronate. Corneal staining score, tear film break-up time (TF-BUT), Schirmer test and ocular surface disease index (OSDI) were evaluated before surgery and 2, 4, 8, 12 and 16 weeks after surgery. Results: There was no significant difference in visual acuity, spherical equivalent and corneal haziness between the 2 groups after surgery. Corneal staining score was significantly lower in the DQS group than in the control group 2 weeks after LASEK (p < 0.01) and increased in the control group after LASEK compared with the preoperative value (2 weeks after LASEK, p < 0.01), but decreased in the DQS group (12 and 16 weeks after LASEK, p < 0.05). TF-BUT was significantly higher in the DQS group than in the control group 2 to 16 weeks after LASEK (p < 0.01) and increased values were observed in the DQS group after LASEK compared with the preoperative value (4 to 16 weeks after LASEK, p < 0.05). The mean OSDI was significantly higher 4 to 16 weeks after LASEK in the control group than in the DQS group (p < 0.01). Conclusions: Subjective dry eye symptoms and objective markers were worse for 4 weeks after LASEK. The use of 3% DQS for 12 weeks after surgery improved these symptoms and markers with the effect lasting 16 weeks after LASEK. J Korean Ophthalmol Soc 2015;56(9):1324-1330

Diquafosol Tetrasodium Increases the Concentration of Mucin-like Substances in Tears of Healthy Human Subjects

Purpose: This study was undertaken to determine the effect of topical application of diquafosol tetrasodium on proteins and mucin-like substances from tears of clinically healthy subjects. Methods: Tears were collected from both the eyes of 10 healthy volunteers. Diquafosol tetrasodium solution (3%) was applied once to the right eye and 0.9% sodium chloride solution (saline) once to the left eye. Tear samples were collected by Schirmer test strips before application and 5, 15, 30 and 60 min after application. Sialic acid, a marker of mucin-like substances, and major tear proteins including secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured by high performance liquid chromatography. Results: Levels of total protein, sIgA and lysozyme were transiently decreased in both groups but returned to baseline levels within 15 min after application. The concentration of lactoferrin and lipocalin-1 did not change significantly in both groups. Sialic acid in tears was significantly decreased 5 min after saline application, but significantly increased 5 min after diquafosol application. No significant difference in sialic acid was seen after 15 min in both groups. Conclusions: Topical application of saline and diquafosol resulted in transient decrease of tear proteins possibly due to wash out or dilution effects. In contrast, diquafosol application significantly increased sialic acid, although the effect was transient. This suggests diquafosol stimulates the secretion of mucins from ocular tissues of healthy human subjects.

Recent advance in P2Y2 receptor agonist for the treatment of dry eye

Dry eye is a group of multifactor-induced ocular surface symptoms.The conventional therapy for dry eye is to increase the tear passively,such as topical administration of artificial tears eye drops and blockage of lacrimal punctum.However,with a better understanding of pathogenesis of dry eye,it is thought that an ideal method for dry eye is to promote the secretion of tear.Studies showed that P2Y2 receptor agonists can promote the lacrimal gland to secrete tear actively.Up to now,multiple synthetic P2Y2 receptor agonist mimics have been studied,and these studies confirmed that these drugs can improve the secretion of not only water-like tear but also mucoprotein,which can alleviate symptoms in patients with dry eye.In addition,good safety also is clarified by clinical trial of phase Ⅰ.This review briefly summarize the researches on active mechanism,clinical efficacy and applying prospect of P2Y2 receptor agonist for the treatment of dry eye. Key words: P2Y2 receptor agonist; Diquafosol tetrasodium; Dry eye/ therapy

Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in situ keratomileusis.

To evaluate the effect of diquafosol tetrasodium (DQS) for the treatment of persistent dry eye after laser in situ keratomileusis (LASIK). Miyata Eye Hospital, Miyazaki, Japan. Noncomparative case series. This prospective study included 30 eyes of 15 patients in whom dry eye had persisted for over 12 months after LASIK, and the symptoms had not improved with artificial tears and sodium hyaluronate treatment. In addition, treatment with DQS 3% eye drops, 6 times a day, was performed for 12 weeks. Best-corrected visual acuity, tear secretion with the Schirmer test, tear break-up time, and fluorescein and lissamine green staining scores on the cornea and conjunctiva were examined before and at 1, 4, and 12 weeks after the addition. A subjective questionnaire of 14 symptoms was also assessed before and 12 weeks after treatment. The fluorescein and lissamine green staining scores significantly improved over 12 weeks; however, the best-corrected visual acuity and tear secretion did not change. The symptoms of fatigue, dryness, grittiness, discomfort, difficulty in reading, and discomfort within the area of dryness improved after the additional DQS treatment. The DQS treatment improved the subjective and objective symptoms of persistent dry eye after LASIK. Increased mucin production because of the addition of DQS probably improved the tear film stability and reduced the symptoms of dry eye in patients who had persistent dry eye after LASIK.

Combination Therapy With Diquafosol Tetrasodium and Sodium Hyaluronate in Patients With Dry Eye After Laser In Situ Keratomileusis

To evaluate the possible advantages of combination therapy with diquafosol tetrasodium and sodium hyaluronate for dry eye after laser in situ keratomileusis (LASIK). Prospective randomized comparative trial. A total of 206 eyes of 105 patients who underwent LASIK were enrolled in this study. Patients were randomly assigned to 1 of 4 treatment groups according to the postoperative treatment: artificial tears, sodium hyaluronate, diquafosol tetrasodium, and a combination of hyaluronate and diquafosol. Questionnaire responses reflecting subjective dry eye symptoms, uncorrected and corrected visual acuity, functional visual acuity, manifest refraction, tear break-up time, fluorescein corneal staining, Schirmer test, and corneal sensitivity were examined before and 1 week and 1 month after LASIK. Distance uncorrected visual acuity was significantly better in the combination group than in the hyaluronate group 1 week and 1 month after LASIK. Near uncorrected visual acuity was significantly better in the combination group than in the artificial tear and diquafosol groups 1 week and 1 month after LASIK. Distance functional visual acuity improved significantly only in the combination group 1 month after LASIK. The Schirmer value in the combination group was significantly higher than that in the hyaluronate group at 1 month after LASIK. Subjective dry eye symptoms in the combination group improved significantly compared with those in the other groups 1 week after surgery. Our results suggest that hyaluronate and diquafosol combination therapy is beneficial for early stabilization of visual performance and improvement of subjective dry eye symptoms in patients after LASIK.