Diquafosol Ophthalmic Solution for Dry Eye Symptoms

January 10, 2023 updated by: He Eye Hospital

Impact of Diquafosol Ophthalmic Solution on Tear Film and Dry Eye Symptom in Type 2 Diabetic Dry Eye: A Four-week Randomized Control, Single Masked Pilot Study.

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will be conducted in compliance with the tenets of the Declaration of Helsinki and the Institutional Review Board of He Eye Specialist Hospital, Shenyang, China (approval number: IRB2019.K002.01).

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic illness that causes relative insulin insufficiency in target organs owing to pancreatic β-cell dysfunction and insulin resistance [1]. Shift to sedentary lifestyle, ageing population and obesity has significantly contributed to the global rise in the prevalence of T2DM [2]. In 2019 the prevalence of diabetes was documented to be 9.3% (463 million people) and in 2030 it is estimated to rise to 10.2% (578 million) and T2DM accounts for approximately 90% of all diabetic occurrence[3]. Negative alterations to the tear film, corneal epithelium, corneal endothelium, and corneal nerves have been observed in 47-64% of patients with diabetes[4] [5]. Ocular surface manifestation of signs and symptoms secondary to DM has been termed as diabetic keratopathy (DK). DK has been documented to increase central corneal thickness[6], decrease in endothelial cell density[7], leads of superficial punctate keratitis[8], delay and impede wound repair[9], and decrease in corneal sensitivity due to neuropathy[10]. Additionally, DM patients have also been noted to have compromised tear quantity and quality[11][12] due to conjunctival goblet cell loss as documented on cytologic analysis [13]. Goblet cells secrete mucin, which stabilizes the tear film, minimizes tear evaporation, and reduces mechanical friction. Goblet cell loss in animal models suggests that it disrupts the ocular surface's immune tolerance [14] and increased expression of inflammatory cytokines in the conjunctiva[15]. 0.1% hyaluronate (HA) used in artificial tears have been reported to promote corneal re-epithelium and improve corneal healing[16].

Additionally, HA has been reported to decrease the rate of tear evaporation and enhance the stability of tear film [17]. Diquafosol tetrasodium is a dinucleotide polyphosphate which a purinoceptor agonist, when administered to the ocular surface, it binds to P2Y2 receptors and stimulates mucin and tear secretion[18-20]. The corneal epithelium, conjunctival epithelium, lacrimal gland ductal epithelium, meibomian gland sebaceous cells, and meibomian gland ductal cells all express the P2Y2 receptor. [21,22]. Subsequently, enhanced secretion of mucin and tear secretion due to Diquafosol tetrasodium ophthalmic solution (DQS) stabilize the tear film, minimizes tear evaporation, and reduces mechanical friction thereby protecting the corneal epithelium [23]. Various reports have concluded that that 3% DQS is effective in the treatment of dry eye disease [24-26] and Dota et al.'s [19] findings suggest that DQS improves corneal epithelial damage in T2DM rat model.

However, the effect of DQS on the tear film of T2DM humans has not been previously assessed. Therefore, the purpose s to assess subjective and objective diabetic dry eye findings after using 3% DQS or 0.1% HA topical eye drops.

Study Type

Interventional

Enrollment (Anticipated)

101

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Liaoning
      • Shenyang, Liaoning, China, 110001
        • He Eye Hospital
        • Sub-Investigator:
          • Qing Zhang, M.D.
        • Sub-Investigator:
          • Hongda Zhang, M.D.
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 1-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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DQS group
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
3% Diquafosol tetrasodium eye drops will be used to assess its usefulness in diabetic dry eye symptoms
Other Names:
  • Diquas
Active Comparator: HA group
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
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.
Other Names:
  • Artificial tears

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-invasive tear break-up time
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Changes in 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 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks
Tear Film Lipid Layer
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Tear Film Lipid Layer interferometry will be assessed using DR-1 (Kowa, Nagoya, Japan).

  • Changes at 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks
OSDI Score
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Chinese translated, and validated OSDI (Allergan Inc, Irvine, USA) version will beused to assess and quantify DE symptom. The 12 items of the questionnaire can be tabulated into a score that ranges from 0 (no symptoms) to 100 (severe symptoms) points

  • Changes at 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Conjunctival hyperemia (RS score)
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Conjunctival hyperemia (RS score) will be assessed by keratograph image (Oculus, Germany) of 1156*873 pixels, redness score (RS) (accurate to 0.1 U) was displayed on the computer screen that ranged from 0.0 to 4.0.

  • Changes at 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks
Quality of meibum grade
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Meibum quality will be assessed under a slit-lamp:

Five meibomian gland in the middle parts of the eyelid will be assessed using a scale of 0 to 3 for each gland (0 represented clear meibum; 1 represented cloudy meibum; 2 represented cloudy and granular meibum; and 3 represented thick, toothpaste like consistency meibum).

  • Changes at 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks
Expressibility of meibum grade
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Meibum expressibility will be assessed under a slit-lamp:

Eight meibomian glands in the middle part will be evaluated on a scale of 0 to 3 (0 denoted that all glands expressible; 1 denoted that 3 to 4 glands expressible; 2 denoted those 1 to 2 glands expressible; and 3 denoted that no glands were expressible). The overall score was computed using the mean scores of these eight glands.

  • Changes at 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks
Conjunctivocorneal epithelial staining grade
Time Frame: Day-0 (baseline), 4-weeks, 8-weeks

Conjunctivocorneal epithelial staining will be assessed under a slit-lamp:

Conjunctivocorneal epithelial staining will be assess corneal and conjunctival epithelium damage. Double vital staining approach with two microliters of a preservative-free solution containing 1% lissamine green and 1% sodium fluorescein will be instilled in the conjunctival sac.

The eye will be sectioned into three equal pieces (temporal conjunctiva, cornea, and nasal conjunctiva). Each region receives a maximum staining score of three points and a minimum of zero points. The combined scores from all three parts were then recorded on a scale ranging from 0 (normal) to 9 (severe).

  • Changes at 4-weeks and 8-weeks will be compare with baseline measurements.
  • Comparison between groups at baseline, 4-weeks and 8-weeks will also be examined
Day-0 (baseline), 4-weeks, 8-weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

He Eye Hospital

Investigators

  • Study Chair: Emmanuel Eric Pazo, He Eye Hospital, Shenyang, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 3, 2023

Primary Completion (Anticipated)

August 31, 2023

Study Completion (Anticipated)

November 1, 2023

Study Registration Dates

First Submitted

July 19, 2021

First Submitted That Met QC Criteria

July 19, 2021

First Posted (Actual)

July 28, 2021

Study Record Updates

Last Update Posted (Actual)

January 12, 2023

Last Update Submitted That Met QC Criteria

January 10, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DMDEDQS-2021-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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