Microbiome-Focused Food Supplement for Evaporative Dry Eye Due to Meibomian Gland Dysfunction

Participants with moderate evaporative DED associated with MGD will be randomized 1:1 to receive either a microbiome-focused oral food supplement or matching placebo for 8 weeks. The primary endpoint is change in Ocular Surface Disease Index (OSDI) from baseline to Week 8 and at 16 week follow-up. Key secondary endpoints include changes in tear film breakup time (TBUT), Schirmer I test, and ocular surface staining. Safety and tolerability will be assessed throughout the study. Standard supportive care (e.g., preservative-free artificial tears) will be permitted if kept stable and documented.

Oral food-grade supplement designed to modulate gut microbiome-linked metabolic pathways relevant to ocular surface homeostasis (gut-eye axis). Administered once daily for 8 weeks (e.g., sachet/capsule taken with water). Packaging and appearance are matched to placebo.

Dietary Supplement: Dietary Supplement: Microbiome-targeted oral supplement

Participants receive a matched placebo once daily for 8 weeks, plus permitted background dry eye care.

Other: Placebo

Oral food-grade supplement designed to modulate gut microbiome-linked metabolic pathways relevant to ocular surface homeostasis (gut-eye axis). Administered once daily for 8 weeks (e.g., sachet/capsule taken with water).

Matched placebo (appearance, taste/odor, packaging) administered once daily for 8 weeks (oral).

Plazo: Baseline to Week 8 (end of treatment)

The Ocular Surface Disease Index-6 (OSDI-6) is a shortened 6-item patient-reported outcome measure recommended by TFOS DEWS III as the standardized screening questionnaire for dry eye disease. Each item is scored from 0 to 4, and the total score is calculated as the sum of the 6 item scores, yielding a total score range of 0 to 24. Higher scores indicate worse dry eye symptom burden. According to TFOS DEWS III, OSDI-6 scores may be interpreted as follows: 0-3, normal range; 4-8, mild-to-moderate symptom severity; and \>8, severe symptom severity. A score of 4 or higher is considered consistent with a positive symptom screen for dry eye disease. The primary endpoint is the mean change from baseline in OSDI-6 total score at Week 8, corresponding to the end of the intervention period.

Plazo: Baseline to Week 16

The Ocular Surface Disease Index-6 (OSDI-6) is a 6-item, patient-reported symptom questionnaire for dry eye disease. Each item is scored from 0 to 4, and the total score is calculated as the sum of the 6 item responses, yielding a total score range of 0 to 24, with higher scores indicating worse symptoms. The outcome is the mean change from baseline in OSDI-6 total score at the Week 16 follow-up visit to assess durability of symptom response after stopping intervention. TFOS DEWS III classifies OSDI-6 scores as 0-3 normal, 4-8 mild-to-moderate, and \>8 severe.

Plazo: Baseline to Week 8 and Baseline to Week 16

NIBUT (seconds) is a device-based measure of tear film stability obtained without fluorescein dye. The endpoint is mean change from baseline in NIBUT, defined as the average of repeated measurements per protocol (e.g., 2-3 recordings; specify in protocol SOP). Higher values indicate more stable tear film.

Plazo: Baseline to Week 8 and Baseline to Week 16

Conjunctival fluorescein staining will be graded using the Oxford grading scheme. Scores range from 0 to 5, with higher scores indicating more severe ocular surface staining (worse ocular surface integrity). The outcome is the mean change from baseline in conjunctival staining score.

Plazo: Baseline to Week 8 and Baseline to Week 16

Meibomian gland function will be evaluated by standardized digital expression of the lower eyelid meibomian glands. Meibum quality will be graded in eight lower eyelid glands using a 4-point ordinal scale (0-3 per gland), where 0 = clear meibum, 1 = cloudy meibum, 2 = cloudy meibum with particulate debris, and 3 = inspissated/toothpaste-like meibum. A composite meibum quality score will be calculated by summing grades across 8 glands (total score range: 0 to 24). Higher scores indicate worse meibum quality (greater gland secretion abnormality). The outcome is the mean change from baseline in composite meibum quality score at the specified assessment time point(s).

Plazo: Baseline to Week 8 (end of treatment) and Baseline to Week 16 (8 weeks post-treatment)

Non-contact infrared meibography of the upper and lower eyelids will be performed using the SIRIUS device. Meibomian gland dropout will be graded using a pre-specified meiboscore (0 to 3) for each eyelid, where 0 indicates no gland loss and 3 indicates severe gland loss. A total meibography dropout score will be calculated for each eye by summing upper and lower eyelid scores (range 0 to 6), with higher scores indicating worse meibomian gland loss. For each visit, the participant-level value will be the mean of both eyes. The outcome is the mean change from baseline in total meibography dropout score.

Plazo: Baseline to Week 8 and Baseline to Week 16

Meibomian gland expressibility will be assessed by standardized digital expression of five central glands of the lower eyelid. Expressibility will be graded using a 4-point ordinal scale (0-3) based on the number of glands yielding liquid secretion: 0 = all five glands expressible; 1 = three to four glands expressible; 2 = one to two glands expressible; and 3 = no glands expressible. The total expressibility score ranges from 0 to 3. Higher scores indicate worse meibomian gland expressibility (greater gland obstruction/dysfunction). The outcome is the mean change from baseline in meibomian gland expressibility score

Plazo: Baseline (Week 0), Week 8 (End of Treatment), and Week 16 (Follow-up)

Change from baseline in conjunctival redness severity graded using the Efron Grading Scale for bulbar conjunctival hyperemia. The Efron scale ranges from 0 to 4 (including half grades, if used per protocol), with higher scores indicating greater conjunctival redness (worse hyperemia). The outcome is the mean change from baseline in conjunctival redness score.

Plazo: Baseline (Week 0), Week 8 (End of Treatment), and Week 16 (Follow-up)

Schirmer I test without topical anesthesia measures aqueous tear production using standardized paper strips placed in the lower fornix for 5 minutes. Results are recorded in millimeters of wetting (mm/5 min). The outcome is the mean change from baseline in Schirmer I test value. Higher values indicate greater tear production (improved tear secretion).

Plazo: Baseline to Week 8 (end of treatment) and Baseline to Week 16 (8 weeks post-treatment)

Average number of rescue artificial tear instillations per day recorded by diary or structured recall over a defined window prior to each visit. Lower values indicate reduced need for rescue therapy.

Plazo: Baseline through Week 16 (8 weeks post-treatment)

Number of participants experiencing any AE/SAE; severity and relatedness assessed by investigator.

Plazo: Baseline to Week 8

Alpha diversity computed from 16S rRNA sequencing data; change from baseline.

Plazo: Baseline to Week 8

Community structure shift tested via PERMANOVA; within-subject distances summarized.

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial Evaluating the Efficacy and Safety of a Microbiome-Focused Oral Food Supplement in Adults With Moderate Evaporative Dry Eye Disease Associated With Meibomian Gland Dysfunction