Clinical trial NCT05738629: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Dry Eye Disease
Keywords: dry eye disease; post refractive surgery; blepharospasm; exosomes; mesenchymal stem cell; pluripotent stem cell
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Zhejiang University
name: Hangzhou yuansheng biotechnology Co., Ltd
First posted: 2023-02-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Ocular Surface Disease Index (OSDI)
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Secondary outcomes:
measure: Tear Secretion Test (Schirmer test)
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Tear Film Break-up Time
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Ocular Surface Staining Score
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Conjunctiva Redness Score
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Tear Meniscus Height
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Corneal confocal microscopy
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Meibomian gland expressibility scores
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
measure: Meibomian Glands Photography
timeFrame: 1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
name: Juan Ye, Doc.
role: STUDY_CHAIR
References: