Clinical trial NCT05682547: Diquafosol vs Hyaluronic Acid for Diabetic Dry Eye
Official title: A Single Center, Randomized, Controlled Trial Comparing the Clinical Efficacy of 3% Diquafosol Tetrasodium and 0.1 % Hyaluronic Acid 0.1% in Diabetic Patients With Dry Eye Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Eye Problems
Keywords: Dry eye
Diquafosol
Hyaluronate
Diabetic dry eye
Lead sponsor: He Eye Hospital
Sponsor class: OTHER
First posted: 2023-01-12
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomised control trial.
Primary purpose: SUPPORTIVE_CARE

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.

Detailed description: 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 Current \[19\] 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.

Eligibility criteria: 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

Primary outcomes:
measure: Non-invasive tear break-up time
timeFrame: Day-0 (baseline), day-14 and day-28
Secondary outcomes:
measure: Conjunctival hyperemia (RS score)
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Quality of meibum grade
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Expressibility of meibum grade
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Conjunctivocorneal epithelial staining grade
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Tear Film Lipid Layer
timeFrame: Day-0 (baseline), day-14 and day-28
measure: OSDI Score
timeFrame: Day-0 (baseline), day-14 and day-28
measure: MMP-9 detection
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Tear meniscus height (TMH)
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Corneal Sensitivity Score
timeFrame: Day-0 (baseline), day-14 and day-28
measure: Corneal nerves and immune/inflammatory cells change
timeFrame: Day-0 (baseline), week-4, and week-8
Other outcomes:
Locations:
city: Shenyang
country: China
facility: He Eye Hospital
state: Liaoning
Study officials:
affiliation: He Eye Hospital, Shenyang, China
name: Emmanuel Eric Pazo
role: STUDY_CHAIR
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