Probiotic in Dry Eye Syndromes

Study Overview
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Brief Summary
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This study will evaluate efficacy and safety of systemic and ophthalmic probiotic from bacterial lysate of Lactobacillus sakei on microbiota, immunological and clinical outcomes of patients with Dry Eye Syndrome.

Detailed Description
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The ocular surface is comprised of the cornea and its overlying tissue, the conjunctiva. The ocular surface is continuously exposed to the external environment and, therefore, to different microbial species. A resident ocular surface microbiota has been found in various studies. Although little is known so far, some elements of this microbiota and/or its metabolites could represent protective cofactosr in the pathogenesis of common ocular diseases. On the other hand, the gut microbiota is known to influence host homeostasis in distal tissues, such as brain (gut-barin axis), lungs (gut-lungs axis) and skin (gut-skin axis). However, little is known about distal effects of the gut microbiota on the ocular surface. In this study we sought to evaluate the efficacy and safety aspects of L.sakei as both ophtalmic probiotic lysate and oral live probiotic on Dry Eye Syndrome, using a factorial design, against placebo.

Official Title
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Efficacy and Safety of Systemic and Ophthalmic Probiotic on Microbiota, Immunological and Clinical Outcomes of Patients With Dry Eye Syndrome

Conditions
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Dry Eye Syndrome

Intervention / Treatment
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* Drug: Ophthalmic Probiotic
* Drug: Opthalmic Placebo
* Dietary Supplement: Oral Probiotic Capsule
* Dietary Supplement: Oral Placebo Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female 18<age<60 BCVA (Best Corrected Visual Acuity) >=9/10 At least 2 subjective complaints compatible with dry eye TBUT (Tear Break-Up Time) <= 10 sec, Schirmer's test <= 10mm Signed informed consent, voluntary adherence to treatment Exclusion Criteria: Pregnancy/breastfeeding Conjunctivitis Thyroid disease Diabetes Rheumatologic diseases including Sjogren's syndrome Neurologic conditions, including stroke, Bell's palsy, Parkinson's, trigeminal nerve problem Refractive surgery (LASIK or PRK) Other Eye Surgeries HSV Keratitis Medication/supplement use, including psychiatric medicines, OTC cold medicines, anti-histamines, beta-blockers, pain relievers, sleeping pills, diuretics, Hormones replacement, and oral contraceptives Chemical splashes / injuries to the eyes Contact lens use Environmental (dusty, windy, hot/dry) Any treatment for dry eye in previous 4 weeks (including lubricants, steroids, cyclosporine)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ophthalmic probiotic<br>1 active drop in each eye/ 5 hours plus oral placebo capsule, for 4 weeks | Drug: Ophthalmic Probiotic<br>* Bacterial lysate of Lactobacillus sakei, hydroxypropylmethylcellulose (HPMC), boric acid, sodium chloride, purified water.<br>Dietary Supplement: Oral Placebo Capsule<br>* Hydroxypropylmethylcellulose hard capsule, filled with maltodextrin excipient<br>|
| Placebo Comparator: Placebo<br>1 placebo drop in each eye/ 5 hours plus oral placebo capsule, for 4 weeks | Drug: Opthalmic Placebo<br>* Placebo contains complete formulation of the active drug except for bacterial lysate of Lactobacillus sakei (i.e. HPMC, boric acid, sodium chloride, purified water)<br>Dietary Supplement: Oral Placebo Capsule<br>* Hydroxypropylmethylcellulose hard capsule, filled with maltodextrin excipient<br>|
| Experimental: Opthalmic Probiotic + Oral Probiotic<br>1 active drop in each eye/ 5 hours plus oral probiotic capsule, for 4 weeks | Drug: Ophthalmic Probiotic<br>* Bacterial lysate of Lactobacillus sakei, hydroxypropylmethylcellulose (HPMC), boric acid, sodium chloride, purified water.<br>Dietary Supplement: Oral Probiotic Capsule<br>* Live Lactobacillus sakei (5 billion cfus) in hydroxypropylmethylcellulose hard capsule, with maltodextrin excipient<br>|
| Experimental: Oral Probiotic<br>1 placebo drop in each eye/ 5 hours plus oral probiotic capsule, for 4 weeks | Drug: Opthalmic Placebo<br>* Placebo contains complete formulation of the active drug except for bacterial lysate of Lactobacillus sakei (i.e. HPMC, boric acid, sodium chloride, purified water)<br>Dietary Supplement: Oral Probiotic Capsule<br>* Live Lactobacillus sakei (5 billion cfus) in hydroxypropylmethylcellulose hard capsule, with maltodextrin excipient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index | Subjective score | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tear break up time (TBUT) | Slit exam | 4 weeks | 
| Schirmer test | physical exam using Schirmer strip | 4 weeks | 
| Ocular surface microbiota composition | measured by 16s rRNA method | 4 weeks | 
| Tear Interleukin level | measured by ELISA | 4 weeks |