Therapeutic Effect of Stem Cell Eye Drops on Dry Eye Disease

Study Overview
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Brief Summary
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The goal of this non-randomized, prospective, open, one-arm clinical study is to learn about the clinical efficacy of stem cell eye drops in patients with dry eye disease (DED) who failed to respond to artificial tear sodium hyaluronate eye drops three times a day for two weeks. The main question aims to answer are: How effective are stem cell eye drops in patients with DED? How safe are stem cell eye drops for patients with DED? Participants will be treated with mesenchymal stem cells (MSCs) eye drops, 5×10^5 /50μl in each eye, twice a day for two weeks and they will be followed up for three months after treatment.

Detailed Description
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This study was mainly divided into three parts: screening period, treatment period and late treatment period. (1) Screening period: For the DED patients with artificial tear sodium hyaluronate drops three times a day and no effect for two consecutive weeks, OSDI score, fluorescein sodium stain score, tear secretion test and tear film rupture time examination were performed. 10 eligible subjects were screened out according to the inclusion/exclusion criteria, and the subjects were asked to sign informed consent. Relevant clinical examination data were collected and subjects were enrolled. 1) OSDI questionnaire: it was divided into 3 dimensions, including ocular symptoms, visual function, and environmental factors.2) Fluorescein staining score of ocular surface: After staining with 0.25% fluorescein sodium, defect staining was observed under slit lamp microscope. Cornea was scored in 3 areas: top, center and bottom. Each area was scored by 0 points (without any staining), 1 points (partial staining), 2 points (staining of more than half of the area), and 3 points (staining of the whole area). The total was divided into the sum of 3 areas. A higher score indicates more severe ocular surface damage. 3) Schirmer test: Standard tear test paper was taken and held in the conjunctival sac at 1/3 of the lower outer eyelid, and the patient was instructed to close the eyes gently. The results were observed 5 minutes later. The tear secretion test < 10mm/5min was abnormal. 4) Tear break-up time: After staining with 0.25% fluorescein sodium, patients were instructed to close their eyes under the slit lamp microscope. The tear film rupture time was calculated from the time of eye opening to the appearance of the first burst spot, and the average value was taken for three consecutive tests. The rupture time of tear film was less than 10s. (2) Treatment period: Formal clinical treatment: 10 enrolled patients received MSC eye drops twice a day for two weeks. OSDI score, ocular fluorescein sodium stain score, tear secretion test and tear film rupture time examination were performed every weekend during drug administration. Adverse events, serious adverse events and drug-related adverse events ≥Ⅲ during treatment were recorded to evaluate drug safety. (3) Late treatment: 3 months of follow-up after the end of treatment. OSDI score was performed during weekly telephone follow-up, and clinical indicators (OSDI score, fluorescein sodium staining score of ocular surface, tear secretion test and tear film rupture time test) were examined every four weeks to evaluate the treatment effect of DED.

Official Title
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Clinical Study of Mesenchymal Stem Cell Eye Drops for Treating Dry Eye Disease

Conditions
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Mesenchymal Stem Cell, Dry Eye Syndromes

Intervention / Treatment
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* Drug: MSCs eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: As determined by the investigator, the subject is able to understand and comply with the protocol requirements; Subject or subject's legal representative (if applicable) sign and date the written informed consent or any privacy authorization document required prior to the commencement of the study process; Age 40-60; Female patients; The subject has received artificial tear sodium hyaluronate treatment with eye drops three times a day, but the treatment has no effect for two weeks, and the clinical examination results are consistent with: OSDI score ≥13; Schirmer test < 10mm/5min; Tear break-up time < 10s; Fluorescein sodium staining on the ocular surface was positive. Exclusion Criteria: Eye exclusion criteria: Subjects with other eye diseases such as glaucoma, cataract, uveitis, optic neuritis, etc.； The subjects had undergone eye surgery (e.g., cataract surgery) within the last three months; Subjects who wear contact lenses for a long time and are unwilling to remove them in the study; The subject has received eye drops in the past 24 hours that may affect the clinical study. Exclusion criteria related to infectious diseases: The subject has fungal, bacterial or viral keratitis or conjunctivitis with evidence of infection; The subject has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection; The subject has any identified congenital or acquired immunodeficiency (e.g., common immunodeficiency, human immunodeficiency HIV infection, organ transplantation); The subject has active tuberculosis (TB positive); Subjects receive any live vaccine within 30 days prior to screening. Exclusion criteria for general circumstances: The subject is allergic to the stem cell eye drops; The subject has any unstable or uncontrolled cardiovascular, pulmonary, liver, kidney, gastrointestinal, urogenital, hematological, clotting, immunological, endocrine/metabolic, or other medical condition that the investigator deems to interfere with the study or endanger the safety of the subject; Subjects had had any surgery requiring general anesthesia within 30 days prior to enrollment, or planned to have a larger procedure during the study period surgery; Subjects have a history of severe neurological diseases, including stroke, multiple sclerosis, brain tumors, or neurodegenerative diseases； The subjects had active psychosis, which the researchers thought might interfere with their compliance with the study process; Lactating female subjects, or female subjects with positive serum pregnancy test results during the screening period, or positive urine pregnancy test results prior to study drug administration.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>The MSCs eye drops was administered to enrolled patients with 5×10^5 /50μl in each eye, twice a day for 2 weeks. | Drug: MSCs eye drops<br>* MSCs were used to prepare single-cell suspension, and 0.9% sodium chloride was added to balance PH value to prepare the effective, safe and stable eye drops. Giving the patient with 5×10^5 /50μl in each eye, twice a day for 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of OSDI score | OSDI questionnaire: It was divided into 3 dimensions, including ocular symptoms, visual function, and environmental factors. The total score is less than 13. | 1 week | 
| The change of Schirmer test | Standard tear test paper was taken and held in the conjunctival sac at 1/3 of the lower eyelid, and the patient was instructed to close the eyes gently. The results were observed 5 minutes later. Schirmer test < 10mm/5min was abnormal. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tear break-up time | After staining with 0.25% fluorescein sodium, patients were instructed to close their eyes under the slit lamp microscope. The tear film rupture time was calculated from the time of eye opening to the appearance of the first burst spot, and the mean value was taken for three consecutive tests. The tear film rupture time < 10s is abnormal | 1 week | 
| Fluorescein sodium staining of the ocular surface. | After staining with 0.25% fluorescein sodium, defect staining was observed under slit lamp microscope. Cornea was scored in 3 areas (FIG. 1) : top, center and bottom. Each area was scored according to 0 points (without any staining), 1 points (partial staining), 2 points (staining of more than half of the area) and 3 points (staining of the whole area), and the total was divided into the sum of 3 areas. A higher score indicates more severe ocular surface damage. | 1 week |