Effect of a Dietary Supplement on Gut Microbiota and Ocular Surface Outcomes in Dry Eye Disease

Not Applicable

Recruiting

• Conditions: Dry Eye; Age-Related Macular Degeneration (AMD); Age-related Macular Degeneration (ARMD)

• Registration Number: NCT07148271
• Lead Sponsor: Varol TUNALI

Brief Summary

This prospective clinical study investigates whether a dietary supplement product can modulate the gut microbiota and improve ocular surface outcomes in patients with dry eye disease. Participants will be recruited from Istanbul Medipol University Hospital (Department of Ophthalmology) and Liv Hospitals (Vadi Istanbul and Ulus). Each participant will receive the dietary supplement product for 8 weeks. Gut microbiota analyses will be conducted at baseline and week 8. Ocular surface assessments including Schirmer test and invasive tear breakup time (TBUT) will be performed at baseline and week 8.

Detailed Description

Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by chronic tear film instability, hyperosmolarity, and ocular surface inflammation. It represents one of the most common reasons for ophthalmology consultations worldwide and has a profound impact on patient quality of life. Conventional treatment approaches primarily target symptoms and tear film supplementation, but disease-modifying interventions remain limited.

Emerging evidence suggests that the gut microbiota exerts systemic immunomodulatory effects, influencing diseases beyond the gastrointestinal tract, including ocular conditions. Dysbiosis has been implicated in autoimmune, metabolic, and inflammatory disorders, and a growing body of literature indicates that the gut-eye axis may play a role in the pathogenesis of DED. Specific microbiota-derived metabolites, microbial antigens, and immune pathways are believed to modulate ocular surface inflammation and tear film stability. This provides a strong rationale for exploring microbiome-targeted interventions in DED.

This single-arm, prospective interventional trial investigates the impact of an 8-week course of a defined dietary supplement product on gut microbiota composition and diversity, alongside established ocular surface clinical endpoints. Participants will be recruited from Istanbul Medipol University Hospital (Department of Ophthalmology) and Liv Hospitals (Vadi Istanbul and Ulus). All enrolled patients will receive the dietary supplement once daily for the study duration.

Microbiome assessment: Stool samples will be collected at baseline and at week 8, with DNA extraction followed by metagenomic sequencing. Microbiota analysis will focus on alpha diversity (e.g., Shannon index) and taxonomic/functional profiling to detect shifts in microbial composition associated with the intervention.

Ophthalmological assessment: Clinical evaluations will be performed at baseline and at week 8, including the Schirmer test, invasive tear breakup time (TBUT), Ocular Surface Disease Index (OSDI), and Dry Eye Scoring System (DESS). These standardized measures provide quantitative and qualitative assessment of tear production, stability, and patient-reported symptoms.

Safety and adherence: Safety monitoring will include the recording of adverse events throughout the trial, with particular attention to potential gastrointestinal or ocular side effects. Adherence will be assessed through participant reporting and calculation of percentage of doses taken.

Statistical considerations: Data will be analyzed using SPSS v22.0. Non-parametric tests (Mann-Whitney U for between-group and Wilcoxon signed-rank for within-group comparisons, where applicable) will be employed, as clinical data are expected to be non-normally distributed. Descriptive statistics will summarize adherence and adverse events.

This study aims to provide mechanistic insights into the gut-eye axis by linking microbiome modulation with ocular surface outcomes. Although exploratory in design, the findings may lay the groundwork for future randomized controlled trials evaluating microbiome-targeted interventions as adjunctive therapy for DED.

Study Timeline

• Study First Submitted: 2025-08-22
• Study First Submitted QC: 2025-08-22
• Study First Posted: 2025-08-29
• Status Verified: 2025-09
• Study Start: 2025-09-01
• Last Update Submitted: 2025-09-03
• Last Update Posted: 2025-09-10
• Primary Completion: 2025-11-15
• Study Completion: 2026-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Clinical diagnosis of dry eye disease.
• Age 18-65 years.
• Willing and able to provide informed consent.

Exclusion Criteria

• Current restrictive diet (ketogenic, elimination, prolonged fasting, etc.).
• Colonoscopy or systemic antibiotic use within the past 4 weeks.
• Use of probiotic, prebiotic, or fecal microbiota-related products within the past 4 weeks.
• Other systemic or ocular conditions that could interfere with study outcomes.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Change in Schirmer Test Score	From enrollment to the end of treatment at 8 weeks	Tear production will be assessed using the Schirmer Test without anesthesia at baseline and at week 8. Standardized Schirmer paper strips will be placed in the lower eyelid, and the length of strip wetting (measured in millimeters) will be recorded after 5 minutes.; The Schirmer Test yields values ranging from 0 mm (no tear production) to approximately 35 mm (normal/high tear production) over 5 minutes. Higher values represent better tear production, while values \<10 mm/5 min are commonly associated with clinically significant dry eye disease.; The primary endpoint is the mean change in Schirmer Test score from baseline to week 8.

Secondary Outcome Measures

Name	Time	Method
Change in Dry Eye Scoring System (DESS)	From enrollment to the end of treatment at 8 weeks	The Dry Eye Scoring System (DESS) will be administered at baseline and week 8 to evaluate the severity and frequency of dry eye symptoms. Scores range from 0 (no symptoms) to 44 (maximum severity and frequency of symptoms). Higher scores represent worse outcomes.
Change in Tear Breakup Time (TBUT, invasive)	From enrollment to the end of treatment at 8 weeks	Tear film stability will be assessed at baseline and week 8 using the Fluorescein Tear Breakup Time Test. After instillation of fluorescein dye into the tear film, the time (in seconds) between a complete blink and the appearance of the first dry spot on the cornea will be recorded. TBUT values typically range from 0 seconds (immediate breakup, very unstable tear film) to \>10 seconds (normal tear film stability). Shorter TBUT values indicate worse tear film stability and more severe dry eye disease.
Change in Ocular Surface Disease Index (OSDI)	From enrollment to the end of treatment at 8 weeks	The Ocular Surface Disease Index (OSDI) questionnaire will be administered at baseline and week 8. The OSDI consists of 12 items evaluating ocular discomfort, vision-related function, and environmental triggers. Scores range from 0 to 100, where 0 indicates no symptoms and 100 indicates the most severe dry eye symptoms. Higher scores represent worse outcomes.
Change in gut microbiota diversity (Shannon index)	From enrollment to the end of treatment at 8 weeks	Stool samples will be collected at baseline and week 8 for metagenomic sequencing. Alpha diversity will be measured using the Shannon Diversity Index, which accounts for both richness and evenness of microbial communities. Shannon index values are non-negative and typically range from 0 (no diversity) to approximately 5-6 (very high diversity in complex communities). Higher Shannon index values represent greater microbial diversity, which is generally considered a favorable outcome.

Trial Locations

Locations (1)

Medipol University; Istanbul, Turkey (Türkiye)