Diquafosol vs Hyaluronic Acid for Diabetic Dry Eye

NCT05682547 | Completed DMC

• 1 other identifier: DMDEDQS-2022-12
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

Diquafosol ophthalmic solution (DQS) stimulates P2Y2 receptors on the ocular surface, which enhances mucin secretion from goblet cells. Therefore, tear film stability and hydration of the ocular surface can be achieved independent from lacrimal glands function. While it has been observed that 0.1 percent hyaluronate (HA) in artificial tears promotes corneal re-epithelium and improves corneal healing.This prospective, open label pilot study will include 60 eyes of 30 diabetic patients diagnosed with DED and will be randomly assigned to either DQS (n=30 eyes) or ATD group (n=30 eyes). Participants in the DQS group will receive 3% Diquafosol ophthalmic solution, while HA group will receive 0.1% Sodium hyaluronate artificial tears. The dosage for both drugs will be one drop, six times per day for 4 weeks. Tear film lipid layer (TFLL), non-invasive breakup time (NITBUT), corneoconjunctival staining score (CS), meibum gland (MG), conjunctival hyperemia (RS score), ocular surface disease index (OSDI) will be assessed and compared at baseline, day-14, and day-28.

Conditions

Diabetic Eye Problems

Keywords

Dry eye; Diquafosol; Hyaluronate; Diabetic dry eye

Outcome Measures

Primary Outcomes (1)

• Non-invasive tear break-up time

  Non-invasive initial tear film breaking time will be assessed using the Keratograph 5M (Oculus, Germany) topographer. Three sequentially readings will be captured, and the median value will be included in the final analysis. The median value will be recorded. * Changes at week-4, and week-8 will be compare with baseline measurements. * Comparison between groups at baseline, week-4, and week-8 will also be examined.

  Day-0 (baseline), week-4, and week-8

Secondary Outcomes (9)

• Conjunctival hyperemia (RS score)

  Day-0 (baseline), week-4, and week-8

• Quality of meibum grade

  Day-0 (baseline), week-4, and week-8

• Expressibility of meibum grade

  Day-0 (baseline), week-4, and week-8

• Conjunctivocorneal epithelial staining grade

  Day-0 (baseline), week-4, and week-8

• Tear Film Lipid Layer

  Day-0 (baseline), week-4, and week-8

Study Arms (2)

DQS group

EXPERIMENTAL

Participants in DQS group will be administered one drop of 3% DQS (Diquas, Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times per day for 8 weeks.

Drug: 3% Diquafosol tetrasodium

HA group

ACTIVE COMPARATOR

Participants in HA group will be administered one drop of 0.1% Sodium hyaluronate artificial tears (preservative free) six times per day for 8 weeks

Drug: 0.1% hyaluronate

Interventions

3% Diquafosol tetrasodium DRUG

3% Diquafosol tetrasodium eye drops will be used to assess its usefulness in diabetic dry eye symptoms

Also known as: Diquas

DQS group

0.1% hyaluronate DRUG

0.1% hyaluronate eye drops will be used to assess its usefulness in diabetic dry eye symptoms and compared to 3% Diquafosol tetrasodium eye drops.

Also known as: Artificial tears

HA group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Clinical diagnosed and confirmed with type 2 diabetes for one year or more
• Able and willing to comply with the treatment/follow-up schedule
• Bilateral signs and symptoms of dry eye disease

You may not qualify if:

• Participants with systemic immune-mediated illnesses, such as secondary Sjögren's syndrome or graft-versus-host disease
• Patients using topical medication(s) for the treatment of ocular disorders such as glaucoma or allergic conjunctivitis were excluded from the study.
• Previous ocular surgery or trauma
• month history of blepharal and periorbital skin disease or allergies
• Severe dry eyes with corneal epithelial defect
• Limbic keratitis
• Pterygium
• Corneal neovascularization
• Glaucoma
• Breastfeeding
• Rheumatic immune systemic diseases
• Herpes zoster infection
• Pregnant women
• Allergic to fluorescein
• Contact lens wearers

Sponsors & Collaborators

• He Eye Hospital: lead

Study Sites (1)

He Eye Hospital

Shenyang, Liaoning, 110001, China

Location

Related Publications (28)

• Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017 Jun 3;389(10085):2239-2251. doi: 10.1016/S0140-6736(17)30058-2. Epub 2017 Feb 10.

  PMID: 28190580 RESULT

• Weisman A, Fazli GS, Johns A, Booth GL. Evolving Trends in the Epidemiology, Risk Factors, and Prevention of Type 2 Diabetes: A Review. Can J Cardiol. 2018 May;34(5):552-564. doi: 10.1016/j.cjca.2018.03.002. Epub 2018 Mar 13.

  PMID: 29731019 RESULT

• Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019 Nov;157:107843. doi: 10.1016/j.diabres.2019.107843. Epub 2019 Sep 10.

  PMID: 31518657 RESULT

• Abdelkader H, Patel DV, McGhee CNj, Alany RG. New therapeutic approaches in the treatment of diabetic keratopathy: a review. Clin Exp Ophthalmol. 2011 Apr;39(3):259-70. doi: 10.1111/j.1442-9071.2010.02435.x. Epub 2011 Apr 4.

  PMID: 20973888 RESULT

• Vieira-Potter VJ, Karamichos D, Lee DJ. Ocular Complications of Diabetes and Therapeutic Approaches. Biomed Res Int. 2016;2016:3801570. doi: 10.1155/2016/3801570. Epub 2016 Mar 28.

  PMID: 27119078 RESULT

• El-Agamy A, Alsubaie S. Corneal endothelium and central corneal thickness changes in type 2 diabetes mellitus. Clin Ophthalmol. 2017 Mar 2;11:481-486. doi: 10.2147/OPTH.S126217. eCollection 2017.

  PMID: 28280298 RESULT

• Lee JS, Oum BS, Choi HY, Lee JE, Cho BM. Differences in corneal thickness and corneal endothelium related to duration in diabetes. Eye (Lond). 2006 Mar;20(3):315-8. doi: 10.1038/sj.eye.6701868.

  PMID: 15832184 RESULT

• Inoue K, Okugawa K, Amano S, Oshika T, Takamura E, Egami F, Umizu G, Aikawa K, Kato S. Blinking and superficial punctate keratopathy in patients with diabetes mellitus. Eye (Lond). 2005 Apr;19(4):418-21. doi: 10.1038/sj.eye.6701497.

  PMID: 15286669 RESULT

• Shih KC, Lam KS, Tong L. A systematic review on the impact of diabetes mellitus on the ocular surface. Nutr Diabetes. 2017 Mar 20;7(3):e251. doi: 10.1038/nutd.2017.4.

  PMID: 28319106 RESULT

• Murphy PJ, Patel S, Kong N, Ryder RE, Marshall J. Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects. Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1737-42. doi: 10.1167/iovs.03-0689.

  PMID: 15161834 RESULT

• Dogru M, Katakami C, Inoue M. Tear function and ocular surface changes in noninsulin-dependent diabetes mellitus. Ophthalmology. 2001 Mar;108(3):586-92. doi: 10.1016/s0161-6420(00)00599-6.

  PMID: 11237914 RESULT

• Sagdik HM, Ugurbas SH, Can M, Tetikoglu M, Ugurbas E, Ugurbas SC, Alpay A, Ucar F. Tear film osmolarity in patients with diabetes mellitus. Ophthalmic Res. 2013;50(1):1-5. doi: 10.1159/000345770. Epub 2013 Feb 22.

  PMID: 23445780 RESULT

• Barbosa FL, Xiao Y, Bian F, Coursey TG, Ko BY, Clevers H, de Paiva CS, Pflugfelder SC. Goblet Cells Contribute to Ocular Surface Immune Tolerance-Implications for Dry Eye Disease. Int J Mol Sci. 2017 May 5;18(5):978. doi: 10.3390/ijms18050978.

  PMID: 28475124 RESULT

• Marko CK, Menon BB, Chen G, Whitsett JA, Clevers H, Gipson IK. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye. Am J Pathol. 2013 Jul;183(1):35-48. doi: 10.1016/j.ajpath.2013.03.017. Epub 2013 May 10.

  PMID: 23665202 RESULT

• Park Y, Song JS, Choi CY, Yoon KC, Lee HK, Kim HS. A Randomized Multicenter Study Comparing 0.1%, 0.15%, and 0.3% Sodium Hyaluronate with 0.05% Cyclosporine in the Treatment of Dry Eye. J Ocul Pharmacol Ther. 2017 Mar;33(2):66-72. doi: 10.1089/jop.2016.0086. Epub 2016 Dec 8.

  PMID: 27929721 RESULT

• Jeon HS, Hyon JY. The Efficacy of Diquafosol Ophthalmic Solution in Non-Sjogren and Sjogren Syndrome Dry Eye Patients Unresponsive to Artificial Tear. J Ocul Pharmacol Ther. 2016 Sep;32(7):463-8. doi: 10.1089/jop.2015.0081. Epub 2016 Jun 13.

  PMID: 27294831 RESULT

• Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998 Sep;67(3):341-6. doi: 10.1006/exer.1998.0520.

  PMID: 9778415 RESULT

• Dota A, Sakamoto A, Nagano T, Murakami T, Matsugi T. Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats. Clin Ophthalmol. 2020 Apr 1;14:1019-1024. doi: 10.2147/OPTH.S242764. eCollection 2020.

  PMID: 32280196 RESULT

• Kulkarni AA, Trousdale MD, Stevenson D, Gukasyan HJ, Shiue MH, Kim KJ, Read RW, Lee VH. Nucleotide-induced restoration of conjunctival chloride and fluid secretion in adenovirus type 5-infected pigmented rabbit eyes. J Pharmacol Exp Ther. 2003 Jun;305(3):1206-11. doi: 10.1124/jpet.103.049221. Epub 2003 Mar 20.

  PMID: 12649304 RESULT

• Cowlen MS, Zhang VZ, Warnock L, Moyer CF, Peterson WM, Yerxa BR. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003 Jul;77(1):77-84. doi: 10.1016/s0014-4835(03)00068-x.

  PMID: 12823990 RESULT

• Tanioka H, Kuriki Y, Sakamoto A, Katsuta O, Kawazu K, Nakamura M. Expression of the P2Y(2) receptor on the rat ocular surface during a 1-year rearing period. Jpn J Ophthalmol. 2014 Nov;58(6):515-21. doi: 10.1007/s10384-014-0342-4. Epub 2014 Sep 2.

  PMID: 25179431 RESULT

• Yuko, T.S.; NAKAMURA, M. Stimulatory Effect of Diquafosol Tetrasodium on the Expression of Membrane-Binding Mucin Genes in Cultured Human Corneal Epithelial Cells. Journal of the eye 2011, 28, 425-429.

  RESULT

• Kaido M, Kawashima M, Shigeno Y, Yamada Y, Tsubota K. Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye. Adv Ther. 2018 May;35(5):697-706. doi: 10.1007/s12325-018-0685-1. Epub 2018 Apr 18.

  PMID: 29671255 RESULT

• Ji YW, Kim HM, Ryu SY, Oh JW, Yeo A, Choi CY, Kim MJ, Song JS, Kim HS, Seo KY, Kim KP, Lee HK. Changes in Human Tear Proteome Following Topical Treatment of Dry Eye Disease: Cyclosporine A Versus Diquafosol Tetrasodium. Invest Ophthalmol Vis Sci. 2019 Dec 2;60(15):5035-5044. doi: 10.1167/iovs.19-27872.

  PMID: 31800960 RESULT

• Amano S, Inoue K. Effect of topical 3% diquafosol sodium on eyes with dry eye disease and meibomian gland dysfunction. Clin Ophthalmol. 2017 Sep 14;11:1677-1682. doi: 10.2147/OPTH.S148167. eCollection 2017.

  PMID: 29075094 RESULT

• Ohashi Y, Munesue M, Shimazaki J, Takamura E, Yokoi N, Watanabe H, Nomura A, Shimada F. Long-Term Safety and Effectiveness of Diquafosol for the Treatment of Dry Eye in a Real-World Setting: A Prospective Observational Study. Adv Ther. 2020 Feb;37(2):707-717. doi: 10.1007/s12325-019-01188-x. Epub 2019 Dec 13.

  PMID: 31834617 RESULT

• Chen J, Zhang Y, Yu S, Zhang Q, He W, Qin G, He X. The Impact of 3% Diquafosol Ophthalmic Solution on Tear Film and Corneal Nerve Density in Patients with Diabetes and Dry Eye Disease: A Randomized Controlled Study. Ophthalmol Ther. 2025 Oct;14(10):2527-2541. doi: 10.1007/s40123-025-01223-x. Epub 2025 Aug 21.

  PMID: 40839332 DERIVED

• Chen J, Chen Y, Qin G, Li L, Li M, Cheng Y, Zhuang S, Li Z, Zhang Q, Wu Y, Yang L, Moutari S, Moore JE, Xu L, He W, Yu S, Pazo EE, He X. 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. Trials. 2023 Dec 12;24(1):803. doi: 10.1186/s13063-023-07818-8.

  PMID: 38087329 DERIVED

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

Lubricant Eye Drops

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Ophthalmic Solutions; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Lubricants; Specialty Uses of Chemicals

Study Officials

• Emmanuel Eric Pazo

  He Eye Hospital, Shenyang, China

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Masked examiner for all clinical assessments will not involved in the data collection or group allocation procedure for this research. The investigator will not be aware of the two groups.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomised control trial.

Study Record Dates

• First Submitted: December 5, 2022
• First Posted: January 12, 2023
• Study Start: December 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: July 25, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CN (1)