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

N/AEnrolling By InvitationNCT07453212

Varol TUNALI130 enrolled

Overview

Dry eye disease (DED) is a common chronic condition characterized by ocular surface discomfort and tear film instability. Evaporative DED associated with meibomian gland dysfunction (MGD) is a frequent phenotype and is often driven by inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial evaluates whether an oral microbiome-focused food supplement improves dry eye symptoms and objective clinical signs compared with placebo over 8 weeks in adults with moderate evaporative DED due to MGD.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Enrollment

130

Conditions

Dry Eye Evaporative Dry Eye Disease

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Incluison criteria: 1. Adults aged 18-65 years. 2. Participants were required to meet all of the following criteria: * Presence of dry eye symptoms, defined as an OSDI-6 summed score ≥4 at baseline. * Objective evidence of tear film homeostasis loss in at least one eye, defined by at least one of the following: A: Non-invasive tear break-up time (NIBUT) \<10 seconds, and/or B: Ocular surface fluorescein staining consistent with DED, defined as: * Corneal and/or conjunctival fluorescein staining graded ≥1 using the Oxford scale, and/or * Lid wiper epitheliopathy graded ≥1 using the Korb grading system 3. Ability to provide written informed consent and comply with study procedures. 4. Willingness to maintain stable use of permitted background measures (e.g., preservative-free artificial tears) and to avoid initiating new probiotics/prebiotics during the trial. Exclusion criteria: 1. Sjögren syndrome or other active systemic autoimmune disease with significant ocular involvement (investigator judgment). 2. Active ocular infection, acute blepharitis flare, or active allergic conjunctivitis requiring escalation of therapy. 3. Ocular surgery (including cataract) or significant ocular trauma within 6 months prior to the Screening Visit. 4. Previous LASIK or any prior corneal surgery at any time. 5. Use of topical cyclosporine, lifitegrast, or topical ocular corticosteroids within 6-8 weeks prior to baseline, or planned initiation during the treatment period. 6. Punctal plugs within 3 months prior to baseline or planned during the study. 7. Use of glaucoma medications or history of glaucoma filtering surgery. 8. Contact lens use within 30 days prior to baseline or planned use during the study. 9. Systemic isotretinoin within 6 months prior to baseline. 10. Systemic antibiotic use within 8 weeks prior to baseline. 11. Eyelid abnormalities affecting lid function (e.g., lagophthalmos, blepharospasm, ectropion, entropion, severe trichiasis). 12. Active thyroid eye disease (thyroid orbitopathy) or clinically significant ocular surface exposure secondary to thyroid dysfunction. 13. Extensive ocular surface scarring or conditions compromising ocular surface integrity, including Stevens-Johnson syndrome, prior chemical burn, recurrent corneal erosions, persistent epithelial defects, or prior severe ocular trauma. 14. Known hypersensitivity to study product ingredients. 15. Any medical or ocular condition that, in the investigator's opinion, would compromise patient safety or study integrity. 16. Pregnancy or breastfeeding (if applicable) or planning pregnancy during the intervention period. 17. Gastrointestinal diseases known to significantly affect digestion, absorption, or intestinal physiology, including but not limited to inflammatory bowel disease, celiac disease, or a history of major gastrointestinal surgery 18. Individuals following restrictive or specialized dietary patterns, including ketogenic, vegan, or similar diets

Outcomes

Primary Outcomes

Change from baseline in Ocular Surface Disease Index-6 (OSDI-6) total score

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.

Time frame: Baseline to Week 8 (end of treatment)

Secondary Outcomes

Change from baseline in Ocular Surface Disease Index-6 (OSDI-6) total score (durability)

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.

Time frame: Baseline to Week 16

Change from baseline in Non-Invasive Break-Up Time (NIBUT)

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.

Time frame: Baseline to Week 8 and Baseline to Week 16

Change from baseline in conjunctival staining score (Oxford grading scheme)

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.

Time frame: Baseline to Week 8 and Baseline to Week 16

Change from baseline in meibum quality score

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).

Time frame: Baseline to Week 8 and Baseline to Week 16

Change from baseline in meibomian gland dropout score (meibography; SIRIUS)

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.

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

Change from baseline in meibomian gland expressibility score

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

Time frame: Baseline to Week 8 and Baseline to Week 16

Conjunctival redness severity (Efron grading scale)

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.

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

Change from baseline in Schirmer I test without anesthesia (mm/5 min)

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).

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

Change from baseline in rescue artificial tear use (drops/day)

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.

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

Incidence of adverse events (AEs) and serious adverse events (SAEs)

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

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

Change in gut microbiome alpha diversity (e.g., Shannon index)

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

Time frame: Baseline to Week 8

Change in gut microbiome beta diversity (Bray-Curtis distance)

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

Time frame: Baseline to Week 8

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

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes