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

Varol TUNALI20 enrolled

Overview

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.

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. As this is a single-arm, within-subject study, changes over time will be evaluated using one-way repeated-measures analysis of variance (ANOVA) when distributional assumptions are met. Effect sizes will be reported as partial eta squared (η²p). When a significant main effect of time is detected, post-hoc pairwise comparisons will be performed with Bonferroni correction. Descriptive statistics will be used to 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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: Adults aged 18-65 years. Clinical diagnosis of dry eye disease with clinically significant symptoms, defined as Ocular Surface Disease Index (OSDI) score ≥23 at screening and/or baseline. Evidence of tear film instability consistent with dry eye disease, defined as fluorescein tear break-up time (TBUT) ≤10 seconds in at least one eye at screening and/or baseline. Willing and able to provide written informed consent. Willing to maintain habitual diet and lifestyle during the study period and to avoid initiating new microbiome-active products (e.g., probiotic/prebiotic/synbiotic supplements) during the intervention. Exclusion Criteria: Current restrictive dietary pattern likely to materially alter gut microbiota (e.g., ketogenic diet, elimination diets, prolonged fasting) or planned major dietary change during the study period. Colonoscopy within the past 4 weeks. Systemic antibiotic use within the past 4 weeks. Use of probiotic, prebiotic, synbiotic, postbiotic, or fecal microbiota-related products within the past 4 weeks. Active ocular infection or acute ocular inflammation requiring treatment escalation (e.g., acute blepharitis flare, active allergic conjunctivitis requiring escalation), at screening/baseline. Sjögren syndrome or other active systemic autoimmune disease with clinically significant ocular involvement, in the investigator's judgment. Ocular surgery (including refractive surgery) or significant ocular trauma within the past 6 months. Contact lens wear within 30 days prior to baseline or planned contact lens use during the study. Topical cyclosporine, lifitegrast, or topical ocular corticosteroid use within 8-12 weeks prior to baseline, or planned initiation during the study. Punctal plug placement within the past 3 months or planned during the study. Known hypersensitivity to any component of the study product. Any other systemic or ocular condition that, in the investigator's judgment, could compromise participant safety or interfere with study outcomes.

Outcomes

Primary Outcomes

Change in Schirmer Test Score

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 and from baseline to Week 16 (Follow-up).

Time frame: Baseline to Week 8 (Treatment End) and Baseline to Week 16 (Follow-up)

Secondary Outcomes

Change in Tear Breakup Time (TBUT, invasive)

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.

Time frame: Baseline to Week 8 (Treatment End) and Baseline to Week 16 (Follow-up)

Change in Ocular Surface Disease Index (OSDI)

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.

Time frame: Baseline to Week 8 (Treatment End) and Baseline to Week 16 (Follow-up)

Change in Dry Eye Questionnaire-5 (DEQ-5)

The Dry Eye Questionnaire-5 (DEQ-5) will be administered at baseline, Week 8, and Week 16 to assess the severity and frequency of dry eye symptoms. The DEQ-5 consists of five items evaluating ocular discomfort and dryness. Total scores range from 0 (no symptoms) to 22 (maximum severity and frequency of symptoms). Higher scores indicate more severe dry eye symptoms and worse outcomes.

Time frame: Baseline to Week 8 (Treatment End) and Baseline to Week 16 (Follow-up)

Change in gut microbiota diversity (Shannon index)

Stool samples will be collected at baseline and week 8 for 16S rRNA amplicon 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.

Time frame: From enrollment to the end of treatment at 8 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes