Diquafosol Ophthalmic Solution Research Articles

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.

Evaluation of Tear Meniscus Dynamics Using Anterior Segment Swept-Source Optical Coherence Tomography After Topical Solution Instillation for Dry Eye.

To investigate tear meniscus dynamics using anterior segment swept-source optical coherence tomography (SS-OCT) after the instillation of topical solutions for dry eye. Prospective, observational, cross-sectional study. Thirty-six healthy subjects (28 men and 8 women; mean age, 34.4 ± 6.7 years) were enrolled in this study. The lower tear meniscus height, tear meniscus area, and tear meniscus volume were assessed using anterior SS-OCT. After baseline measurements, 40 μL of 0.1% sodium hyaluronate, 0.3% sodium hyaluronate, 3% diquafosol ophthalmic solution, or 2% rebamipide ophthalmic solution was instilled in one eye of 10 subjects each, whereas 40 μL saline was instilled in the other eye. Tear meniscus measurements were obtained using SS-OCT at 30 seconds and 1, 3, 5, 10, 15, 20, and 30 minutes after instillation. The tear meniscus measurements showed a significant increase until 1, 3, 10, 10, and 3 minutes after the instillation of saline, 0.1% sodium hyaluronate, 0.3% sodium hyaluronate, 3% diquafosol, and 2% rebamipide, respectively, compared with the baseline levels (P < 0.05). Compared with those after saline instillation, the tear meniscus measurements were significantly higher until 30 seconds and 3, 30, and 15 minutes after the instillation of 0.1% sodium hyaluronate, 0.3% sodium hyaluronate, 3% diquafosol, and 2% rebamipide, respectively (P < 0.05). The instillation of ophthalmic solutions for the treatment of dry eye greatly increased tear meniscus measurements in healthy subjects. Thus, SS-OCT can be a practical tool for the quantitative evaluation of early-phase tear fluid dynamics.

Tear volume estimation using a modified Schirmer test: a randomized, multicenter, double-blind trial comparing 3% diquafosol ophthalmic solution and artificial tears in dry eye patients.

PurposeWe aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients.Patients and methodsA randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests.ResultsAccording to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears.ConclusionThe modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear-secreting compounds for dry eye.

Clinical evaluation of the effect of diquafosol ophthalmic solution in glaucoma patients with dry eye syndrome

To investigate the effects of diquafosol on intraocular pressure (IOP) and dry eye symptoms in glaucoma patients with dry eye syndrome (DES). This study evaluated a total of 138 glaucoma patients with DES who were treated with diquafosol ophthalmic solution (DIQUAS(®)). Before treatment and 1, 4, 12, 36, and 52weeks after treatment, IOP, ocular surface disease index (OSDI), tear film break-up time (BUT), Schirmer I test scores, fluorescein staining, conjunctival impression cytology, and adverse drug reactions were evaluated. Throughout the treatment period, the mean IOP for all the patients remained stable after treatment with diquafosol (15.4±2.8mmHg at baseline and 16.0±2.8mmHg at 52weeks). The mean OSDI score improved significantly at 4, 12, and 52weeks after diquafosol treatment. The BUT and Schirmer I test scores were significantly increased after diquafosol treatment. The Oxford scheme score was significantly decreased at 1, 4, 12, 36, and 52weeks after diquafosol treatment. A significant improvement in goblet cell density was observed after 4weeks of treatment with diquafosol. Adverse drug reactions were reported in 22 (15.9%) patients. There were no serious adverse drug reactions. Diquafosol was effective in improving objective and subjective symptoms and maintained a stable IOP in glaucoma patients with DES. Therefore, the addition of diquafosol treatment in glaucoma patients with DES or ocular surface side effects using anti-glaucoma medication may be beneficial.

Effectiveness and Optical Quality of Topical 3.0% Diquafosol versus 0.05% Cyclosporine A in Dry Eye Patients following Cataract Surgery.

Purpose. To evaluate the effectiveness and optical quality of 3.0% topical diquafosol versus 0.05% cyclosporine A in dry eye patients following cataract surgery. Methods. In total, 40 eyes of 40 patients newly diagnosed with dry eye syndrome 1 week after cataract surgery were randomized to receive either 3.0% diquafosol ophthalmic solution six times daily or 0.05% cyclosporine A twice daily for 3 months. Outcome measures were tear film break-up time (TBUT), results on Schirmer 1 test, ocular surface staining score, the ocular surface disease index (OSDI) score, and higher-order aberrations (HOAs). Measurements were taken at baseline and at 1, 2, and 3 months. Results. In the diquafosol group, TBUT showed higher outcomes than the cyclosporine A group at 1 and 3 months. Both groups showed increased scores on Schirmer 1 test. The ocular surface staining score decreased in all periods in both groups. Vertical coma and total HOAs decreased more in the cyclosporine A group than in the diquafosol group at 3 months. Conclusion. Both 3.0% diquafosol and 0.05% cyclosporine A were effective in treating dry eye after cataract surgery. Diquafosol was more effective in increasing the tear secretion, but cyclosporine A was more effective in improving optical aberrations.

The Effect of 3% Diquafosol Tetrasodium on Corneal Wetting Property and Mucin-5AC Concentration in Rabbits

Purpose: To evaluate the immediate effects of 3% diquafosol ophthalmic solution on tear MUC5AC concentration and corneal wetting property in rabbit eyes. Methods: Six New Zealand white rabbits were used in the present study. Fifteen minutes after instilling 50 μL of 3% diquafosol into the right eye of each rabbit and 50 μL of saline into the left eye, corneal wetting property, tear MUC5AC concentrations and the area of periodic acid-Schiff (PAS)-stained conjunctival goblet cells were evaluated under general anesthesia using conjunctival impression cytology. Corneal wetting property was evaluated by measuring the duration from when the image of the microscopic light beam was clear on the corneal surface immediately after blinking to when the image began to blur. Results: The mean time of corneal wetting property was 86.40 (± 17.90) seconds in the diquafosol group and 49.00 (± 6.35) seconds in the control group. There was a significant difference between the two groups (p = 0.043). The mean concentration of tear MUC5AC was significantly higher in the diquafosol group (18.21 ± 1.52 ng/mL) than the control group (12.75 ± 1.82 ng/mL; p = 0.028). Conjunctival impression cytology showed the area of PAS-stained conjunctival goblet cells was significantly lower in the diquafosol group (23.17 ± 0.05%) than the control group (32.49 ± 0.08%; p = 0.028). Conclusions: Immediately after instilling 3% diquafosol, corneal wetting property improved significantly. Also tear MUC5AC concentration, which was released from conjunctival goblet cells increased compared to saline. J Korean Ophthalmol Soc 2016;57(2):208-213

Clinical Effects and Safety of 3% Diquafosol Ophthalmic Solution for Patients With Dry Eye After Cataract Surgery: A Randomized Controlled Trial

To compare the efficacies and safety profiles of 3% diquafosol and 0.1% sodium hyaluronate in patients with dry eye after cataract surgery. Randomized controlled trial. setting: Soonchunhyang University Hospital, Seoul, South Korea. In all, 130 eyes of 86 dry eye patients who had undergone cataract surgery between January 2014 and January 2015 were enrolled and randomly divided into a diquafosol group and a sodium hyaluronate group. The diquafosol group used diquafosol 6 times a day and the hyaluronate group used sodium hyaluronate 6 times a day after cataract surgery. Evaluations of efficacy were conducted based on an Ocular Surface Disease Index questionnaire, tear breakup time (TBUT), Schirmer I test, corneal fluorescein and conjunctival lissamine green staining scores, serial measurement of ocular higher-order aberrations (HOAs), corneal HOAs, and uncorrected distance visual acuity test. Safety evaluations were based on anterior chamber inflammation and discontinuation of the eye drops. Objective signs and subjective symptoms were aggravated at 1 week postoperatively and began to recover significantly 4 weeks after surgery. The diquafosol group showed significantly superior TBUT (P < .001), corneal fluorescein (P = .045), and conjunctival staining (P = .001) compared to the sodium hyaluronate group throughout the study period. TBUT (P < .001) and the change in HOAs (P = .018) recovered significantly more quickly in the diquafosol group. The safety evaluations showed no intergroup differences. Eye drops of 3% diquafosol may be an effective and safe treatment for the management of cataract surgery-induced dry eye aggravation in patients with preexisting dry eye.

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.

Diquafosol promotes corneal epithelial healing via intracellular calcium-mediated ERK activation

Diquafosol is known as a purinergic P2Y2 receptor (P2Y2R) agonist that stimulates water and mucin secretion from conjunctival epithelial cells and goblet cells, leading to tear film stability in dry eye. However, its effect on corneal epithelial healing has not yet been elucidated. The aim of the present study was to evaluate the effect of diquafosol on corneal epithelial healing in vivo and on P2Y2R-related downstream signaling pathways in vitro. We administered 3% diquafosol ophthalmic solution on 3 mm-diameter epithelial defects made in rat corneas and assessed the wound closure over time. Corneal epithelial healing was significantly accelerated in diquafosol-treated eyes compared to control eyes at 12 and 24 h. During wound healing, P2Y2R staining appeared stronger in the re-epithelized margin near the wound defect. To evaluate whether diquafosol stimulates epidermal growth factor receptor/extracellular-signal-regulated kinase (EGFR/ERK)-related cell proliferation and migration, simian virus 40-transfected human corneal epithelial (THCE) cells were used for in vitro experiments. Cell proliferation was accelerated by diquafosol at concentrations from 20 to 200 μM during 48 h, but inhibited at concentrations over 2000 μM. The intracellular calcium ([Ca2+]i) elevation was measured in diquafosol (100 μM)-stimulated cells using Fluo-4/AM ([Ca2+]i indicator). [Ca2+]i elevation was observed in diquafosol-stimulated cells regardless of the presence of calcium in media, and suramin pretreatment inhibited the calcium response. The effect of diquafosol on phosphorylation of EGFR, ERK and Akt, and cell migration was determined by western blotting and in vitro cell migration assay. Diquafosol induced phosphorylation of EGFR at 2 min post-stimulation, and phosphorylation of ERK at 5 min post-stimulation. Phosphorylation of ERK was attenuated in cells pretreated with suramin or BAPTA/AM ([Ca2+]i chelator), and partially with AG1478 (EGFR inhibitor). Likewise, diquafosol-treated cells showed acceleration of gap closure in cell migration assay, which was inhibited by suramin, BAPTA/AM, AG1478, and U0126 (MEK inhibitor). These studies demonstrate that diquafosol is effective in promoting corneal epithelial wound healing and that this effect may result from ERK-stimulated cell proliferation and migration via P2Y2R-mediated [Ca2+]i elevation.

Intraocular Scattering after Instillation of Diquafosol Ophthalmic Solution.

To assess the changes in intraocular scattering before and after instillation of diquafosol ophthalmic solution in patients with short tear breakup time (TBUT) dry eye. We prospectively examined 20 eyes of 20 short TBUT dry eye patients (study group) and age-matched 20 eyes of 20 healthy subjects (control group). Intraocular scattering was measured as the objective scattering index (OSI) at 0.5-second intervals over 10 seconds without blinking. Patients were instructed to start topical administration of 3% diquafosol ophthalmic solution six times daily for 4 weeks. The OSI significantly deteriorated after 7.0 seconds compared with the initial value of OSI after the blinking in the study group. The OSI was also significantly higher in the study group than in the control group at 4.5 to 10.0 seconds after the blinking (p < 0.05). We found significant improvements 2 weeks after treatment not only in TBUT (p < 0.001) but also in the mean OSI, the OSI change rate, and the slope of the linear regression line of the OSI within 10 seconds (p < 0.001, p = 0.003, and p = 0.002, respectively). We also found significant improvements 4 weeks after treatment in these variables. Intraocular scattering deteriorates significantly with time in patients with short TBUT dry eye. Diquafosol ophthalmic solution exhibits an improvement not only in TBUT but also in intraocular scattering, indicating that diquafosol is also effective for improving the optical quality of the eye.

Prominent Decrease of Tear Meniscus Height With Contact Lens Wear and Efficacy of Eye Drop Instillation.

To investigate the change in tear meniscus height (TMH) before and after wearing soft contact lenses (CLs) of different water contents (WCs) and the influence of eye drop instillation on TMH during CL wear. Tear meniscus heights were measured using anterior segment optical coherence tomography in 20 normal subjects wearing a high-WC CL (WC, 69%) in 1 eye and a low-WC CL (WC, 24%) in the other. Tear meniscus height change after eye drop instillation with 3% diquafosol ophthalmic solution or saline with CL wear was evaluated at 5, 15, 30, and 60 min after instillation. A significant decrease in TMH was observed after lens insertions of both CLs. Tear meniscus height was significantly decreased with high-WC CL wear compared with that with low-WC CL wear. With high-WC CL wear, TMH increased significantly (P<0.001) at 5 min after the instillation of 3% diquafosol ophthalmic solution compared with the baseline values and then returned to the pre-instillation level. No significant TMH changes were found with the instillation of either eye drop (diquafosol or saline) with low-WC CL wear. Tear meniscus height decreased with CL wear, especially with high-WC CL wear. Significant increases in TMH were observed at 5 min after the instillation of diquafosol ophthalmic solution with high-WC CL wear. The increases in TMH after diquafosol instillation tended to be greater than those after saline instillation at least for 30 min with both high-WC and low-WC CLs.

Prolonged increase in tear meniscus height by 3% diquafosol ophthalmic solution in eyes with contact lenses.

PurposeThis study aimed to evaluate the increase in tear meniscus height (TMH) induced by 3% diquafosol ophthalmic solution in eyes with contact lens (CL).MethodsTen healthy subjects wearing high-water-content CLs received topical instillation of two ophthalmic solutions – 3% diquafosol ophthalmic solution in one eye and artificial tears in the other eye. Lower TMH was measured at 5 minutes, 10 minutes, 15 minutes, 30 minutes, and 60 minutes after instillation by anterior segment optical coherence tomography.ResultsTMH increased significantly (P<0.001) at 5 minutes and 15 minutes after instillation of saline compared with the baseline values. After instillation of 3% diquafosol ophthalmic solution, TMH significantly increased (P<0.05) at 5 minutes, 15 minutes, 30 minutes, and 60 minutes compared with the baseline values. Increases in TMH after diquafosol instillation were significantly greater (P<0.05) at 15 minutes, 30 minutes, and 60 minutes than increases in TMH after saline instillation.ConclusionTopical instillation of 3% diquafosol ophthalmic solution increases TMH for up to 60 minutes in eyes with high-water-content CLs.

Efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye: a systematic review of randomized clinical trials.

To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events. A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization. Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

Clinical utility of 3% diquafosol ophthalmic solution in the treatment of dry eyes.

Diquafosol is a drug used for dry eye treatment with a novel mechanism of action. It stimulates the secretion of tear fluid and mucin on the ocular surface, thus enabling us to selectively treat the tear film layer, playing an important role in the establishment of the concept of “Tear Film Oriented Therapy (TFOT)”, an effective therapeutic approach to dry eye in Japan. The 3% diquafosol ophthalmic solution has been widely used for the treatment of dry eye in clinical practice, and it is currently available in Japan and South Korea. This review provides an overview of the clinical utility of 3% diquafosol ophthalmic solution, focusing on the results of clinical studies on various types of dry eye, including aqueous-deficient dry eye, short tear film breakup time-type dry eye, and post dry eye after laser in situ keratomileusis. It also introduces the additive effect of diquafosol on sodium hyaluronate monotherapy for dry eye, and the effect of 3% diquafosol ophthalmic solution for dry eye-related conditions. Additionally, it summarizes the ocular effects of diquafosol in healthy human eyes. Lastly, the importance of improving tear film stability in dry eye treatment, as well as general advances in dry eye treatments, are described.

A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore

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...

Clinical usefulness of diquafosol for real-world dry eye patients: a prospective, open-label, non-interventional, observational study.

This study was designed to evaluate the efficacy and safety of 3% diquafosol ophthalmic solution in dry eye patients in clinical practice. Subjects were dry eye patients who had never used diquafosol, and observation was conducted prospectively over 2 months. The corneal and conjunctival fluorescein staining score, tear film break-up time, 12 dry eye-related subjective symptoms, patient-reported outcomes, and adverse events were investigated. Data were collected from 465 medical institutions for 3,196 patients. Diquafosol led to significant improvement in all subjective symptoms and objective findings (P < 0.001, paired t test). Diquafosol was effective regardless of the degree of severity according to the corneal and conjunctival fluorescein staining score or therapeutic pattern. Overall, 76.0% patients responded that their condition had improved. Adverse reactions were observed in 6.3% of patients. The major adverse reactions were eye discharge, eye irritation, and eye pain. Diquafosol was effective for various dry eye patients in clinical practice, and no significant safety-related problems occurred.

Expression of the P2Y₂ receptor on the rat ocular surface during a 1-year rearing period.

P2Y2 receptors are expressed on ocular surface tissues. Diquafosol ophthalmic solution (DIQUAS(®) ophthalmic solution 3 %; Santen Pharmaceutical Co., Ltd.) acts on these receptors and promotes the secretion of water and mucin. It has been shown to be an efficient dry eye treatment. If P2Y2 receptor expression on the ocular surface decreases with age, the effect of diquafosol may be reduced in elderly persons. In this study, we investigated the changes in P2Y2 receptor expression on the rat ocular surface over an extended period of time. P2Y2 receptor expression in the conjunctiva, cornea, meibomian gland and lacrimal glands of male and female Sprague-Dawley rats was examined from 5 weeks until 53 weeks of age using immunostaining and quantitative-PCR. In the immunohistological examinations, P2Y2 receptor expression was observed in the conjunctival epithelium containing goblet cells, corneal epithelium, meibomian gland ductal epithelium and lacrimal gland ductal epithelium. However, its expression was not significantly different between each age group or between sexes. Regarding P2Y2 receptor mRNA expression, there was an age-related increase in the bulbar conjunctiva. In particular, a significant increase was observed in the 53-week-old age group as compared to the 5-week-old female age group. However, age-related changes in expression were not observed in the cornea or meibomian gland in males or females. We observed no significant age-related decrease was observed for P2Y2 receptor protein and mRNA expression on rat ocular surface tissues.

Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye.

To investigate the short- and long-term effects of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Sixteen eyes in 16 patients with mild or moderate aqueous-deficient dry eye were treated with 3% diquafosol ophthalmic solution. Ocular higher-order aberrations (HOAs) were measured with a wavefront sensor before and at 15 min after diquafosol instillation at the baseline visit and at 4 weeks after treatment initiation. Dry eye symptoms, tear break-up time (BUT), corneal/conjunctival fluorescein staining and Schirmer's test were also evaluated before and after treatment with diquafosol. Treatment with diquafosol ophthalmic solution significantly improved dry eye symptoms, corneal staining and BUT. Compared with mean total HOAs at baseline (0.180 ± 0.06 μm), those at 4 weeks after treatment significantly decreased (0.148 ± 0.039 μm; p = 0.035), whereas those 15 min after diquafosol instillation at the baseline visit did not change significantly (0.170 ± 0.049 μm; p = 0.279). Although no significant change in HOAs was observed as a short-term effect of a single-drop instillation of diquafosol, long-term use of diquafosol to treat aqueous-deficient dry eye reduced HOAs as well as improved corneal epithelial damage and tear film stability.

Conjunctival expression of the P2Y2 receptor and the effects of 3% diquafosol ophthalmic solution in dogs

Conjunctival epithelial and goblet cell P2Y2 nucleotide receptors regulate ion transport and secretory function. Diquafosol is a P2Y2 purinergic receptor agonist that stimulates secretion of aqueous tear components from conjunctival epithelial cells and secretion of mucin from conjunctival goblet cells. In humans suffering from keratoconjunctivitis sicca (dry eye), topical administration of diquafosol improves corneal epithelial integrity and stabilises the tear film. The aim of the present study was to investigate P2Y2 receptor expression and to determine the effect of topical administration of diquafosol on mucin and aqueous tear production in dogs.Canine conjunctival P2Y2 receptor expression was evaluated by Western blotting and immunohistochemical analysis. The effect of diquafosol on mucin secretion was evaluated by examining mucin-5 subtype AC (MUC5AC) concentration in tears. The effect of diquafosol on aqueous secretions was evaluated by performing the Schirmer tear test (STT) and phenol red thread test. Expression of the P2Y2 receptor was confirmed in canine bulbar and palpebral conjunctivae and receptors were identified at the conjunctival epithelial and goblet cell surface. Tear MUC5AC concentration significantly increased after administration of 3% diquafosol ophthalmic solution, although neither STT nor phenol red thread test values showed any significant change after diquafosol instillation. Topical ocular administration of 3% diquafosol might improve corneal epithelial disorders in dogs through stabilisation of the tear film, by virtue of an increase in MUC5AC secretion.

Facilitation of Tear Fluid Secretion by 3% Diquafosol Ophthalmic Solution in Normal Human Eyes

To evaluate the increase in tear fluid volume induced by 3% diquafosol ophthalmic solution in normal human eyes. Prospective, randomized, double-masked, comparative study. Twenty healthy adults (17 males and 3 females; mean age, 38.8 years) underwent topical instillation of 2 ophthalmic solutions, artificial tears in 1 eye and 3% diquafosol ophthalmic solution in the fellow eye, in a masked manner. The radius of curvature of the central lower tear meniscus was measured at 5, 10, 15, 30, and 60 minutes after instillation by use of reflective meniscometry, and subjects' self-evaluated symptoms of wetness and stinging using a visual analog scale. Changes after instillation in the radius of curvature from baseline (artificial tear group vs diquafosol group; mean ± standard error of the mean) were as follows: at 5 minutes, -0.008 ± 0.012 vs 0.045 ± 0.013; at 10 minutes, 0.001 ± 0.014 vs 0.057 ± 0.016; at 15 minutes, -0.012 ± 0.014 vs 0.037 ± 0.019; at 30 minutes, -0.010 ± 0.016 vs 0.030 ± 0.025; and at 60 minutes, -0.029 ± 0.012 vs -0.020 ± 0.012. The diquafosol group showed significantly greater values from 5 to 30 minutes after instillation. Of the 40 eyes, 13 showed abnormal tear film breakup time (≤5 seconds). The diquafosol group had significantly more wetness at 15 minutes after instillation than did the artificial tear group. Topical instillation of 3% diquafosol ophthalmic solution increases tear fluid on the ocular surface for up to 30 minutes in normal human eyes.