Preliminary Clinical Study of the Effectiveness and Safety of Ocular Surface Microbiota Transplantation in the Treatment of Dry Eye Disease

Preliminary Clinical Study of the Effectiveness and Safety of Ocular Surface Microbiota Transplantation in the Treatment of Dry Eye Disease: a Randomized, Single-blind,-Controlled Trial.

Evaluate the efficacy and safety of ocular surface microbiota transplantation as an adjunctive therapy for dry eye, and explore its impact on the structure of the ocular surface microbiota.

Study Overview

• Status: Recruiting
• Conditions: Dry Eye
• Intervention / Treatment: Biological: Ocular surface microbiota transplantation; Biological: Placebo Group

Detailed Description

Evaluate the efficacy and safety of ocular surface microbiota transplantation as an adjunctive therapy for dry eye, and explore its impact on the structure of the ocular surface microbiota.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: yifeng Yu, Ph.D; Phone Number: +8613979180258; Email: 171018170@qq.com

Study Locations

• China
  • Jiangxi
    • Nanchang, Jiangxi, China, 330008
      • Recruiting
      • Yifeng Yu
      • Contact: yifeng Yu, Ph.D; Phone Number: +8613979180258; Email: 171018170@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Dry Eye Patient Group:

  • Aged 18 to 70 years, male or female.
  • Meets the diagnostic criteria for moderate to severe mixed dry eye according to the Expert Consensus on Dry Eye (2020), including:
  • At least one subjective symptom (e.g., dryness, foreign body sensation, burning, fatigue, discomfort, redness, or vision fluctuation).
  • Fluorescein tear film break-up time (FBUT) ≤ 5 seconds.
  • Willing and able to actively cooperate with the prescribed course of standard dry eye medications and ocular surface microbiota transplantation therapy for the study duration.
  • Voluntarily agrees to participate and signs the informed consent form.

• Healthy Donor Group:

  • A family member of a participating subject.
  • Aged 18 to 50 years.
  • Normal ocular surface structure and function, with no ocular diseases or related symptoms, and good visual function.

Exclusion Criteria:

• Dry Eye Patient Group:

  • History of systemic chronic diseases (e.g., uncontrolled diabetes, autoimmune disorders).
  • Current or past history of eyelid abnormalities, conjunctival disease, or lacrimal duct obstruction.
  • History of any ocular surgery or regular wear of corneal contact lenses.
  • Active infection in the eye(s) or any other part of the body.
  • History of multiple episodes of viral keratitis or presence of significant neurotrophic keratitis.
  • Any other condition deemed by the investigator to be unsuitable for participation.

• Healthy Donor Group:

  • Known infectious diseases (e.g., HIV, Hepatitis B).
  • Signs or symptoms suggestive of active ocular surface infection or other viral infections.
  • Current or past history of eyelid, conjunctival, or lacrimal duct diseases.
  • Use of systemic medications (including antibiotics), traditional Chinese herbal medicine, or probiotic supplements within 1 month prior to screening.
  • Pregnancy, lactation, or any other condition that may potentially affect the study outcomes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Transplant group; Transplant operation to dry eye patients	Biological: Ocular surface microbiota transplantation; Ocular surface microbiota transplantation
Placebo Comparator: Placebo group; Fake transplantation to dry eye patients	Biological: Placebo Group; Fake transplant operation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Score on the Visual Analog Scale (VAS) for Ocular Discomfort	The severity of ocular discomfort (e.g., dryness, pain) is assessed using a 100-mm Visual Analog Scale (VAS). Participants mark their level of discomfort on a line from 0 mm ("no discomfort") to 100 mm ("worst imaginable discomfort"). The score is the distance measured in millimeters (mm). A higher score indicates more severe symptoms (worse outcome).	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corneal Fluorescein Staining Score (using the NEI scale)	Corneal epithelial damage is assessed by fluorescein staining and graded according to the National Eye Institute (NEI) scale. Each of the five corneal areas is scored from 0 (no staining) to 3 (severe confluent staining). The total score is the sum of all areas, ranging from 0 to 15. A higher score indicates more severe corneal damage (worse outcome).	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.
Change in conjunctival sac microbiota composition assessed by 16S rRNA gene sequencing	Microbiota from conjunctival sac swab samples is analyzed using 16S rRNA gene sequencing. Key outcomes include: 1) Alpha diversity change (Shannon Index, unitless), where a higher index indicates greater microbial richness and evenness; 2) Beta diversity change (Weighted UniFrac distance, unitless), measuring compositional shifts between samples; and 3) Change in relative abundance (%) of specific bacterial taxa (e.g., *Corynebacterium*, *Pseudomonas*).	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.
Result of Schirmer I Test (without anesthesia)	Tear production is measured by the Schirmer I test (without topical anesthesia). A standardized paper strip is placed in the lateral canthus for 5 minutes. The length of wetting is measured in millimeters (mm). A lower value indicates reduced tear secretion.	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.
Tear Film Break-Up Time (TBUT)	Tear film stability is assessed by measuring the tear film break-up time (TBUT). After instillation of fluorescein, the time interval between the last complete blink and the first appearance of a dry spot on the cornea is recorded in seconds (s). A shorter time indicates greater tear film instability.	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.
Score on the Ocular Surface Disease Index (OSDI) Questionnaire	Symptoms related to dry eye disease and their impact on vision-related function are assessed using the Ocular Surface Disease Index (OSDI) questionnaire. The total score ranges from 0 to 100, calculated based on responses to 12 items. A higher score indicates more severe disability (worse outcome).	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.
Change in tear fluid inflammatory cytokine levels	Levels of inflammatory cytokines in tear fluid samples are measured using a multiplex immunoassay (e.g., Luminex assay or ELISA). The concentration of specific cytokines (e.g., IL-1β, IL-6, IL-8, TNF-α) is reported in picograms per milliliter (pg/mL). An increase in concentration indicates a higher level of inflammation (worse outcome).	At baseline (pre-intervention), and at 1 week, 2 weeks, and 4 weeks post-intervention.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Nanchang University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 23, 2025
• First Submitted That Met QC Criteria: December 20, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: dry eye; ocular surface diseases; Microbiota transplantation
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Dry Eye Syndromes
• Other Study ID Numbers: IIT-I-2025-081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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