Safety and Efficacy of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops Treatment for Dry Eye Diseases Post Refractive Surgery and Associated With Blepharospasm

A Clinical Study of the Safety and Efficacy of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops Treatment for Dry Eye Diseases Post Refractive Surgery and Associated With Blepharospasm

The purpose of this study is to evaluate the preliminary safety and effectiveness of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops in the treatment of dry eye diseases post refractive surgery and associated with blepharospasm

Study Overview

• Status: Not yet recruiting
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops

Detailed Description

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by instability of the tear film and the prevalence has been estimated to reach 20%-40%. Especially, dry eye symptoms are common complaints of patients with blepharospasm or refractive surgery history, seriously affecting their quality of life. There are many conventional therapies for DED which include ocular lubricants, oral essential fatty acid supplementation, lid hygiene and warm compresses, punctal occlusion, various treatments to obstructed meibomian glands, topical antibiotics, topical corticosteroids, topical secretagogues, topical non-glucocorticoid immunomodulatory drugs and scleral contact lenses. However, the overall efficacy is still unsatisfactory with apparent side effects, long periods of treatment, and high-costs. Mesenchymal stem cell-derived exosomes (MSC-Exo) are 30-150nm microvesicles secreted by mesenchymal stem cells (MSCs), which can mediate the therapeutic efficacy of mesenchymal stem cells by the encapsulated proteins, miRNAs and other bioactive substances, and showed potential in the treatment of various diseases. This study aims to evaluate the preliminary safety and effectiveness of PSC-MSC-Exo in the treatment of dry eye diseases post refractive surgery and associated with blepharospasm.

This is an open-label, single-arm, before-after study with 12 subjects with dry eye diseases and the history of refractive surgery or blepharospasm. There are 5 visits over the course of 12 weeks. Visit 1: Week-1 Visit 2: Week-2 Visit 3: Week-4 Visit 4: Week-8 Visit 5: Week-12

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qi Gao, Doc.; Phone Number: 86-15088774002; Email: gaoqi8977@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310000
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Qi Gao, Doc; Phone Number: 86-15088774002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis of apparent dry eye symptoms by ophthalmologists.
• patients experience dry eye symptoms with a definitive history of FS-LASIK or SMILE surgery, or blepharospasm, and previous application of artificial tears for more than 3 months could not relieve the dry eye symptoms.
• have the following symptoms in at least one eye: dryness, burning sensation, foreign body sensation, discomfort in the ocular surface or visual fatigue;
• tear secretion test (Schirmer's Test) of either eye ≤ 10 mm / 5 min;
• the corneal fluorescein staining score (FLCs) was more than 3 and less than 6.
• Tear break up time (TBUT) is less than 10 seconds.

Exclusion Criteria:

• Those who are allergic to any component of the drug in this study;
• Pregnant or nursing women;
• Patients with active fungal, bacterial or viral keratitis or conjunctivitis;
• have serious heart, lung, liver or kidney diseases;
• Other incurable ocular diseases before the study; such as glaucoma, uveitis, retinitis pigmentosa.
• Wearing contact lenses and unwilling to take off in the study;
• Performed ocular surgery (including cataract surgery) in recent three months;
• Enrolled in other interventional clinical studies at the same time;
• Application of eye drops that might affect the clinical study in the past 24 hours;
• Unable to complete the study according to the investigators' requirements;
• Application of eye drops other than artificial tears.
• Application of systemic medication known to reduce tear production, such as anti-anxiety drugs, antipsychotics and steroids.
• Eyelids or eyelashes anomaly.
• Serious systemic diseases.
• Refused to sign the informed consent form to participate in the experiment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PSC-MSC-Exo Eye Drops Treatment; Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by PSC-MSC-Exo eye drop intervention for 12 weeks.	Drug: Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops; Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by PSC-MSC-Exo eye drops 0.125 ml/single eye/one time, four times a day for 12 weeks. The follow-up visit will be 12 weeks since the administration of PSC-MSC-Exo eye drops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ocular Surface Disease Index (OSDI)	The OSDI questionnaire contains 12 questions to measure dry eye symptoms. OSDI scores range from 0 to 100. The lower the score, the more alleviation of dry eye symptoms. Compared with the baseline, a reduction of more than 10 points indicates improvement.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tear Secretion Test (Schirmer test)	A paper strip is placed on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. A positive change from baseline indicates an improvement in each eye.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Tear Film Break-up Time	Time required for dry spots to appear on the surface of the eye after blinking was measured in seconds. A positive change from baseline indicates improvement in each eye.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Ocular Surface Staining Score	Damage of the ocular surface was measured by slit-lamp examination after staining with non-toxic fluorescein sodium. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The lower the score, the less signs of dry eye disease a patient exhibits. A negative change from baseline indicates an improvement in each eye.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Best Corrected Visual Acuity (BCVA)	Whether exosomes affect visual acuity.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Conjunctiva Redness Score	Conjunctival hyperemia was graded in each eye under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo. A negative change from baseline indicates an improvement in each eye.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Tear Meniscus Height	The distance between the line of reflection along the top of the tear prism to the edge of the eyelid was measured in millimeters. A positive number change from baseline indicates improvement.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Corneal confocal microscopy	The morphology, distribution and quantity of corneal nerve fibers were recorded by confocal image after LASIK and SMILE.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Meibomian gland expressibility scores	Squeeze the central meibomian glands of the lower eyelid and assess the expressibility of the five central glands, where 0= All glands have meibum extruded, 1= 3-4 glands have meibum extruded, 2=1-2 glands have meibum extruded, 3=no glands have meibum extruded.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Meibomian Glands Photography	The morphology, quantity and blockage of meibomian gland can be assigned a score of 0 to 3 points according to meibomian gland dropout, where 0=normal without dropout; 1=meibomian gland dropout<1/3; 2=meibomian gland dropout 1/3-2/3; 3=meibomian gland dropout >2/3. The total score of upper and lower meibomian glands is 6 points, of which Grade 0=0-1 point; Grade 1=2-3 points; Grade 2=4-5 points; Grade 3=6 points.	1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Zhejiang University; Hangzhou yuansheng biotechnology Co., Ltd
• Investigators: Study Chair: Juan Ye, Doc., 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Estimate): February 22, 2023

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: dry eye disease; post refractive surgery; blepharospasm; exosomes; mesenchymal stem cell; pluripotent stem cell
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eyelid Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Blepharospasm; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: 2022-0290

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No