Safety and efficacy of topical diquafosol for the treatment of dry eye disease: An updated meta-analysis of randomized controlled trials

Dry eye disease (DED) is a common multi-factorial disease that is characterized by tear film instability. Diquafosol tetrasodium (DQS), an ophthalmic solution, has been shown to be beneficial in the treatment of DED. The goal of this study was to provide an update on the safety and efficacy of topical 3% DQS in treating DED patients. A thorough search for all the published randomized controlled trials (RCTs) up to March 31, 2022 in CENTRAL, PubMed, Scopus, and Google Scholar databases was performed. Data were reported as standardized mean difference (SMD) with 95% confidence interval (CI). Modified Jadad scale was used for sensitivity analysis. Funnel plot and Egger’s regression test assessed the publication bias. Fourteen RCTs evaluating the safety and efficacy of topical 3% DQS treatment in DED patients were included. Eight included RCTs reported data on the DED after cataract surgery. Overall findings suggest that 3% DQS treatment in DED patients was associated with significantly better improvement at 4 weeks in tear breakup time, Schirmer test, fluorescein staining scores, and Rose Bengal staining score as compared to patients treated with others eye drops including artificial tears or 01% sodium hyaluronate. However, no significant difference in ocular surface disease index was observed. Our findings suggest that 3% DQS treatment is safer and had a superior efficacy compared to artificial tears or sodium hyaluronate for treating DED in general and DED after cataract surgery.

Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction dry eye after corneal refractive surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the therapeutic effect of the diquafosol sodium combined with intense pulsed light(IPL)on meibomian gland dysfunction(MGD)dry eye after refractive surgery.METHODS:A total of 64 patients(128 eyes)with MGD dry eye diagnosed within 6mo after laser corneal refractive surgery in our hospital from March 2021 to December 2021 were selected. They were randomly divided into control group and experimental group. A total of 33 patients(66 eyes)in the control group were treated with sodium hyaluronate combined with IPL, and 31 patients(62 eyes)in the experimental group were treated with diquafosol sodium combined with IPL. Ocular symptom scores were performed before each IPL treatment in both groups to examine non-invasive tear breakup time(NIBUT), tear meniscus height, lipid layer grade of tear film, meibomian gland deletion rate and uncorrected visual acuity.RESULTS:After IPL treatment, ocular symptom scores and meibomian gland deletion rate score of two groups were decreased continuously. NIBUT, tear meniscus height and lipid layer grade of tear film were increased continuously, and there was no significant change in uncorrected visual acuity. NIBUT of patients in the experimental group was better than that in the control group before the third IPL treatment(6.24±0.27s vs. 5.51±0.24s, P=0.046).CONCLUSIONS:Both diquafosol sodium and sodium hyaluronate combined with IPL showed good therapeutic effect on MGD dry eye, but there was no significant difference in the short-term efficacy between the two groups.

Diquafosol sodium combined with intense pulsed light in the treatment of meibomian gland dysfunction / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effect of 3% diquafosol sodium eye drops combined with intense pulsed light on the treatment of meibomian gland dysfunction and the change of meibomian glands.METHODS: Prospective study. A total of 141 patients(282 eyes)who were diagnosed with meibomian gland dysfunction from January 2021 to May 2022 in our hospital were selected and they were randomly divided into the control group(73 cases, 146 eyes)and the observation group(68 cases, 136 eyes)according to random number table. The control group was given 0.3% sodium hyaluronate eye drops combined with intense pulsed light, and the observation group was treated with 3% diquafosol sodium eye drops combined with intense pulsed light. The subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density before and after the treatment were compared between the two groups at 2wk after the end of treatment.RESULTS: There were no differences in the subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density between the two groups of patients before treatment(P>0.05). After 2wk of treatment, the symptom scores and physical sign scores of patients in the two groups continued to decrease, non-invasive tear break-up time and lipid layer thickness continued to increase, and the meibomian gland density also increased. The tear meniscus height in the observation group increased, while the control group showed no significant changes. The observation group had better clinical indicators than the control group(P<0.05). No obvious complications were observed in all patients.CONCLUSION: The combination of diquafosol sodium eye drops and intense pulsed light is synergistic in the treatment of meibomian gland dysfunction, with significant therapeutic effects and improvement of meibomian gland repair, which is significantly superior to simple intense pulsed light therapy.

Clinical analysis of P2Y2 receptor agonist in the treatment of diabetic dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of P2Y2 agonist diquafosol sodium(DQS)eye drops in the treatment of diabetic dry eye.METHODS: A total of 80 patients(160 eyes)with diabetic dry eye who admitted to our hospital from January 2022 to March 2022 were selected. They were randomly divided into study group and control group. A total of 40 patients(80 eyes)in the study group were treated with 3% DQS eye drops and 40 patients(80 eyes)in the control group were treated with 0.3% sodium hyaluronate eye drops. The ocular surface disease index(OSDI)score, non-invasive tear meniscus height(NITMH), first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tarsal gland loss score, lipid layer thickness grade and bulbar redness analysis(including conjunctival grade and ciliary grade), were examined before treatment and at 1wk, 1 and 3mo after treatment, respectively. Furthermore, corneal fluorescence staining and conjunctival lissamine green staining were analyzed based on the ocular surface staining score(OSS), and the conjunctival impression cytology and confocal microscopy were evaluated before and 3mo after treatment, respectively.RESULTS: There were no differences in OSDI score, tarsal gland loss score, conjunctival grade score and ciliary grade score between the two groups before and after treatment(P>0.05). OSS scores in the study group were lower than those in the control group, while NITMH, NIBUTf and NIBUTav were higher than those in the control group at 1 and 3mo after treatment(P<0.05). After 3mo of treatment, the density of conjunctival goblet cells increased and corneal dendritic cells decreased in the study group compared with the baseline(all P<0.05), while there were no significant changes in the control group compared with the baseline(all P>0.05).CONCLUSION: 3% DQS eye drops were effective in treating diabetic dry eye without serious complications.

Intense pulsed light combined with meibomian gland massage and diquafosol sodium eye drops in the treatment of lipid deficiency / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the efficacy of intense pulsed light combined with meibomian gland massage and diquafosol eye drops in lipid deficiency dry eye disease and related cytokines.METHODS: A total of 511 patients(1 022 eyes)with lipid deficiency dry eye diagnosed in the ophthalmology clinic of our hospital from January to December 2021 were selected as the research objects. They were divided into two groups according to the patient's wishes: 294 cases(588 eyes)in the study group were treated with diquafosol sodium eye drops combined with intense pulsed light and meibomian gland massage, while 217 cases(434 eyes)in the control group were treated with artificial tears combined with intense pulsed light and meibomian gland massage. The levels of tear tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and lactoferrin(LF)before and after treatment were detected, the corneal fluorescein staining(CFS)score, tear film break-up time(BUT), and Schirmer Ⅰ(SⅠt)under no surface anesthesia, ocular surface disease index(OSDI)were compared, the correlation between TNF-α, IL-1β, LF levels and CFS, BUT, SⅠt, OSDI before treatment was analyzed, and the occurrence of adverse reactions was observed.RESULTS: There was no significant difference in preoperative OSDI, SⅠt, BUT, CFS and levels of TNF-α, IL-1β and LF between the two groups(P>0.05). The SⅠt, BUT, CFS and levels of TNF-α, IL-1β and LF in the study group at 3, 6 and 9wk after treatment were better than those of control group(P<0.05). There were no differences in OSDI score of both groups at 9wk after treatment(P>0.05). The TNF-α and IL-1β were negatively correlated with SⅠt and BUT, while they were positively correlated with CFS and OSDI; LF and SⅠt were positively correlated with SⅠt and BUT, while they were negatively correlated with CFS and OSDI(all P<0.01); The adverse reaction rate of the study group(5.78%)was significantly lower than that of the control group(11.52%; P<0.05).CONCLUSION: Intense pulsed light combined with meibomian gland massage and diquafosol sodium eye drops is effective and well tolerated in the treatment of lipid deficiency dry eye.

Clinical study on 3% Diquafosol Sodium eye drops in treatment of meibomian gland dysfunction-related dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical effect of 3% diquafosol sodium eye drops in treatment of meibomian gland dysfunction-related dry eye.METHODS: The study involved 280 patients totally with meibomian gland dysfunction-related dry eye in the ophthalmology department, Hangzhou Hospital of Traditional Chinese Medicine from May 2020 to May 2021. Patients were divided into the treatment group(160 cases with 320 eyes)and the control group(120 cases with 240 eyes)according to the randomized number table method. The control group was treated with YangXueRunMu formula combined with 0.3% sodium hyaluronate eye drops, the treatment group was treated with YangXueRunMu formula combined with 3% diquafosol sodium eye drops. Both groups were administered for 4wk. The following indicators were measured before and after treatment at 2 and 4wk, respectively: the ocular surface disease index(OSDI)score, Schirmer I test( SⅠt), comprehensive analysis of tear meniscus height(TMH), non-invasive tear film break-up time(NITBUT), meibomian gland lipid secretion of smooth degree scoring and meibomian gland loss rate score, the determination of interleukin-6(IL-6)in tears and the level of tumor necrosis factor-alpha(TNF-α). The efficacy of these tests results was evaluated among these indicators.RESULTS: The overall effective rates of the treatment group and the control group were 95.6% and 81.7% respectively(P<0.05). After 2, 4wk of treatment, the ocular surface disease index(OSDI), NITBUT, meibomian gland lipid secretion scoring, meibomian gland loss rate score and the levels of IL-6 and TNF-α in tears of two groups were significantly different than before treatment(P<0.05). and the treatment group was better than the control group; there was no difference between the SⅠt and TMH groups before and after treatment in the two groups(P>0.05).CONCLUSION: The 3% diquafosol sodium eye drops can promote the normal secretion of meibomian gland by prolonging the homeostasis of the tear membrane, and it can also inhibit the release of inflammatory factors in tears in the treatment of blebomian gland dysfunction-related dry eye.

Effect of Diquafosol on Hyperosmotic Stress-induced Tumor Necrosis Factor-α and Interleukin-6 Expression in Human Corneal Epithelial Cells

The glycocalyx barrier function in ocular surface and its alteration in dry eye disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Some studies have shown that the glycocalyx barrier formed by highly glycosylated mucin and galectin-3 in the epithelial cells of the eyeball is important for the maintenance of moisturization and lubrication of the surface of the eye. The decrease in the wettability of the eye surface and the shortening of the tear film breakup time in dry eye patients are closely related to the damage of the glycocalyx barrier. This article outlines the composition of the glycocalyx barrier on ocular surface and its changes in the dry eye patients. It will also introduce a new method for assessing the damage of the glycocalyx barrier in dry eye patients. Finally, two ophthalmological drugs, which target regulating the abnoemality of transmembrane mucins in dry eye disease will be mentioned.

Effect of 3% Diquafosol Tetrasodium on Tear Film Stability after Laser-assisted in situ Keratomileusis

PURPOSE: To evaluate the efficacy of 3% diquafosol tetrasodium (DQ) after laser-assisted in-situ keratomileusis (LASIK). METHODS: This prospective randomized study included 150 eyes in 75 patients who were scheduled for LASIK. The patients in the 3% diquafosol tetrasodium (DQ) group (37 patients, 74 eyes) were instructed to apply one drop of DQ, six times daily post-op, while the patients in the 0.3% sodium hyaluronate (HA) group (38 patients, 76 eyes) were instructed to apply one drop of HA, six times daily post-op. A Schirmer test, tear film break-up time (BUT), corneal and conjunctival fluorescein staining score (FLSS), and ocular surface disease index (OSDI) were evaluated pre-op and at 1, 4, and 12 weeks post-op while the tear osmolarity was evaluated pre-op and at 4 and 12 weeks post-op. RESULTS: There was no significant difference between the two groups regarding Schirmer test results or tear osmolarity and conjunctival FLSS. The BUT was significantly higher in the DQ group at 1 week and 12 weeks post-op. The corneal FLSS was significantly lower in the DQ group at 1 week, 4 weeks and 12 weeks post-op. The OSDI was significantly lower in the DQ group at 1 week post-op. CONCLUSIONS: Use of 3% diquafosol tetrasodium after surgery improved ocular dryness and increased the tear film stability.

Efficacy of Topical Cyclosporine Nanoemulsion 0.05% Compared with Topical Cyclosporine Emulsion 0.05% and Diquafosol 3% in Dry Eye

PURPOSE: To evaluate the efficacy and safety of cyclosporine nanoemulsion 0.05% compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. METHODS: This was a multicenter, randomized, evaluator-masked, active control, parallel, phase IV study. A total of 227 patients were randomly allocated to instill cyclosporine nanoemulsion 0.05% (CN) twice daily, cyclosporine emulsion 0.05% (CE) twice daily, or diquafosol sodium 3% (DQ) six times daily. Non-inferiority of CN was analyzed by primary endpoint (cornea and conjunctival staining scores at week 12). The secondary endpoints were scores of corneal staining, conjunctival staining, tear break-up time, Schirmer test, and Ocular Surface Disease Index at weeks 4 and 12. RESULTS: Primary endpoints showed statistically significant improvements in all groups. Primary endpoints were −6.60 for the CN group, −5.28 for the CE group, and −6.63 for the DQ group (National Eye Institute scale from 0 to 33), verifying the non-inferiority of CN compared to CE (95% confidence interval, −0.15 to 2.80, Δ>−2.88). In intergroup comparison between CN and CE groups, the CN group had significantly more decreased conjunctival staining score at week 12. Intergroup comparison between CN and DQ groups showed consistent statistically significant improvements in TBUT and Schirmer test in the CN group. In the DQ group, TBUT showed late statistically significant improvement at week 12 and Schirmer test showed relatively short-term statistically significant improvement at week 4. CONCLUSIONS: Cyclosporine nanoemulsion 0.05% was equivalently efficient compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. In addition, CN showed significant improvements in several parameters for treatment of dry eyes.

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.

Changes in Tear Volume after 3% Diquafosol Treatment in Patients with Dry Eye Syndrome: An Anterior Segment Spectral-domain Optical Coherence Tomography Study

PURPOSE: To evaluate changes in the tear meniscus area and tear meniscus height over time in patients with dry eye syndrome, using anterior segment spectral-domain optical coherence tomography after the instillation of 3% diquafosol ophthalmic solution. METHODS: Sixty eyes from 30 patients with mild to moderate dry eye syndrome were included. Tear meniscus images acquired by anterior segment spectral-domain optical coherence tomography were analyzed using National Institutes of Health's image-analysis software (ImageJ 1.44p). Tear meniscus area and tear meniscus height were measured at baseline, 5 minutes, 10 minutes, and 30 minutes after instillation of a drop of diquafosol in one eye and normal saline in the other eye. Changes in ocular surface disease index score, tear film break-up time, corneal staining score by Oxford schema, and meibomian expressibility were also evaluated at baseline, and after 1 week and 1 month of a diquafosol daily regimen. RESULTS: Sixty eyes from 30 subjects (mean age, 29.3 years; 8 men and 22 women) were included. In eyes receiving diquafosol, tear volume was increased at 5 and 10 minutes compared with baseline. It was also higher than saline instilled eyes at 5, 10, and 30 minutes. Changes in tear volume with respect to baseline were not statistically different after the use of diquafosol for 1 month. Ocular surface disease index score, tear film break-up time, and Oxford cornea stain score were significantly improved after 1 week and 1 month of daily diquafosol instillation, but meibomian expressibility did not change. CONCLUSIONS: Topical diquafosol ophthalmic solution effectively increased tear volume for up to 30 minutes, compared to normal saline in patients with dry eye syndrome.

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 microL of 3% diquafosol into the right eye of each rabbit and 50 microL 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.

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.

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.

Clinical Efficacy of Topical 3% Diquafosol Tetrasodium in Short Tear Film Break-Up Time Dry Eye

PURPOSE: To evaluate the clinical efficacy of topical diquafosol tetrasodium 3% ophthalmic solution in patients with short tear film break-up time (BUT) dry eye. METHODS: This prospective study involved 30 eyes in 30 patients with dry eye who had tear film BUT values or =5 mm, and showed no improvement with non-preservative sodium hyaluronate (SH) 0.1% artificial tears. All patients were treated with topical diquafosol tetrasodium 3% 6 times a day, in addition to SH 0.1% artificial tears. Schirmer's 1 test, tear film BUT, keratoepitheliopathy score with fluorescein, conjunctival staining score with lissamine green, and Ocular surface disease index (OSDI) score were evaluated at before treatments, and 1 month and 3 months after treatments. RESULTS: Significant improvements of tear film BUT and OSDI were observed at 1 month and 3 months after diquafosol tetrasodium 3% administration. At before treatment, and followed up at 1 and 3 months, tear film BUTs were 3.3 +/- 1.2, 4.4 +/- 1.0 (p < 0.01) and 4.9 +/- 1.1 seconds (p < 0.01), respectively, and OSDI scores were 43.5 +/- 24.4, 34.6 +/- 25.0 (p = 0.01) and 26.7 +/- 21.5 (p < 0.01), respectively. There were no significant changes of Schirmer's score, keratoepitheliopathy, and conjunctival staining score. After diquafosol tetrasodium 3% administration, severe adverse effects were not found in any of the patients. CONCLUSIONS: Topical diquafosol tetrasodium 3% administration was shown to be an effective treatment for improvements of tear film stability and dry eye symptoms.

Recent advance in P2Y2 receptor agonist for the treatment of dry eye / 中华实验眼科杂志

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.