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Use of 3% Diquafosol Topical Ophthalmic Solution for Diabetic Dry Eye

Primary Purpose

Diabetic Eye Problems

Status

Not yet recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

3% Diquafosol tetrasodium

About this trial

This is an interventional supportive care trial for Diabetic Eye Problems focused on measuring Dry eye, Diquafosol, Hyaluronate, Diabetic dry eye

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

He Eye Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DQS group

Arm Description

Participants in DQS group will be administered one drop of 3% DQS (Diquas, Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times per day for 4 weeks (28 days).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Fluorescein and lissamine conjunctival and cornea staining

Fluorescein and lissamine staining of the ocular surface will be divided into three zones comprising nasal conjunctival, corneal, and temporal conjunctival areas. The staining score ranged from 0 to 3 for each zone, yielding a total score of 0-9 for the ocular surface (Uchino et al., 2012).

Tear Film Lipid Layer Score

Tear Film Lipid Layer interferometry will be assessed using DR-1 (Kowa, Nagoya, Japan). - Tear Film Lipid Layer will be scored as follows: grade 1, somewhat gray color, uniform distribution; grade 2, somewhat gray color, nonuniform distribution; grade 3, a few colors, nonuniform distribution; grade 4, many colors, nonuniform distribution; grade 5, corneal surface partially exposed.

Corneal Sensitivity Score

Corneal Sensitivity Score measured with Cochet-Bonnet esthesiometer (in mm filament length) two times (the measurements will be done immediately before starting the medication, including 3 measurements each time.

MMP-9 detection

InflammaDry, (Rapid Pathogen Screening Inc., Sarasota, FL, USA) is a patented and proprietary modification of a traditional lateral flow device and uses direct sampling microfiltration technology. Two antigen-specific antibodies capture MMP-9 antigens in the sample, and this complex is captured in a proprietary mode at the test result line, giving rise to a visually observable signal.

Tear meniscus height

Non-invasive first tear film breakup time using the Keratograph 5M (Oculus, Germany) topographer will be measured three times consecutively and the median value was recorded. of the three values was calculated.

Conjunctival hyperemia (RS score)

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.

Meibomian gland function and secretion quality

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).

Corneal nerves and immune/inflammatory cells change

HRT III RCM, (Heidelberg Engineering GmbH, Dossenheim, Germany) will be used to record corneal nerves and immune/inflammatory cells change. A total of 5-8 sequence/volume scans were taken from the center of each cornea, focusing on all corneal layers: superficial, intermediate, and basal epithelial layers, sub-basal nerve plexus, anterior, central and posterior stroma, and endothelium. Special attention was given to the basal epithelial layer and sub-basal nerve plexus area to evaluate the nerve plexi and epithelial DC density. Three representative images of the sub-basal nerve plexus and epithelial DCs were selected for analysis for each eye, considering criteria such as whole image in the same layer, best focus and good contrast.

Dry eye Questionnaire Score

Chinese translated version of the questionnaire will be used to assess the subjective dry eye symptoms.

Full Information

NCT ID

NCT05193331

First Posted

January 2, 2022

Last Updated

December 8, 2022

Sponsor

He Eye Hospital

Collaborators

Santen Pharmaceutical(China) Co.,LTD

1. Study Identification

Unique Protocol Identification Number

NCT05193331

Brief Title

Use of 3% Diquafosol Topical Ophthalmic Solution for Diabetic Dry Eye

Official Title

3% Diquafosol Topical Ophthalmic Solution in Diabetic Patients With Dry Eye

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 1, 2023 (Anticipated)

Primary Completion Date

August 30, 2023 (Anticipated)

Study Completion Date

November 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

He Eye Hospital

Collaborators

Santen Pharmaceutical(China) Co.,LTD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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. This prospective, open label pilot study will include 140 eyes of 70 diabetic patients diagnosed with DED and will be consecutively assigned to DQS (n=140 eyes). Participants in the DQS group will receive 3% Diquafosol ophthalmic solution. The dosage of 3% Diquafosol 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.

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 [ethics approval number: IRB(2022)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. Shift to sedentary lifestyle, ageing population and obesity has significantly contributed to the global rise in the prevalence of T2DM. 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. Negative alterations to the tear film, corneal epithelium, corneal endothelium, and corneal nerves have been observed in 47-64% of patients with diabetes. 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, leads of superficial punctate keratitis[8], delay and impede wound repair[9], and decrease in corneal sensitivity due to neuropathy. Additionally, DM patients have also been noted to have compromised tear quantity and quality due to conjunctival goblet cell loss as documented on cytologic analysis. 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 and increased expression of inflammatory cytokines in the conjunctiva. 0.1% hyaluronate (HA) used in artificial tears have been reported to promote corneal re-epithelium and improve corneal healing. 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. The corneal epithelium, conjunctival epithelium, lacrimal gland ductal epithelium, meibomian gland sebaceous cells, and meibomian gland ductal cells all express the P2Y2 receptor. 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 and the year 2020's 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 topical eye drops.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Eye Problems

Keywords

Dry eye, Diquafosol, Hyaluronate, Diabetic dry eye

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Prospective study

Masking

None (Open Label)

Allocation

N/A

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

DQS group

Arm Type

Experimental

Arm Description

Participants in DQS group will be administered one drop of 3% DQS (Diquas, Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times per day for 4 weeks (28 days).

Intervention Type

Drug

Intervention Name(s)

3% Diquafosol tetrasodium

Other Intervention Name(s)

Diquas

Intervention Description

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

Primary Outcome Measure Information:

Title

Non-invasive tear break-up time

Description

Time Frame