Azithromycin for Meibomian Gland Disease

Study Overview
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Brief Summary
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This study aims to elucidate the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction.

Detailed Description
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This is a randomized, placebo-controlled, double masked trial of the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction. Dry eye syndrome (DES) is a persistent feeling of ocular discomfort that encompasses dryness, irritation, foreign body sensation and burning. In the United States, it is the most common non-refractive cause of visits to eye care providers, and has been shown to have a significant impact on quality of life of patients who suffer from this condition. most common cause of DES is Meibomian gland disease (MGD). In the vast majority of cases, MGD is not binding, but rather causes persistant ocular discomfort. Oral antibiotics, particularly the tetracyclines and macrolides, are frequently prescribed for the treatment of MGD. There is little good-quality evidence to support this practice. This study is designed to evaluate the effectiveness of oral azithromycin on patient-reported dry eye symptoms. Concomitantly, we will also study the composition of the ocular surface microbiome in MGD, and its response for oral antibiotics.

Official Title
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A Randomized, Controlled Trial to Evaluate the Role of Oral Azithromycin in the Treatment of Symptomatic Meibomian Gland Disease and Its Effect on the Ocular Surface Microbiome

Conditions
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Dry Eye, Neuropathic Eye Pain, Ocular Microbiome, Depression, Anxiety

Intervention / Treatment
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* Drug: Azithromycin Oral Product
* Drug: Placebo Oral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic Meibomian gland disease, defined as patient-reported ocular surface symptoms such as dryness, grittiness, foreign body sensation, or eye fatigue in combination with clinically identifiable Meibomian gland disease with Grade 2 or greater involvement on the Meibomian Gland Grading Scale (Section XV, item 2). OSDI Score greater than or equal to 20 Ability to give informed consent Exclusion Criteria: Age less than 18 years Allergy or intolerance to oral azithromycin or topical dexamethasone Allergy or intolerance to the preservatives used in topical ophthalmic 0.1% dexamethasone: sodium bisulfite, phenylethyl alcohol, benzalkonium chloride History of prolonged QT interval, history of torsades des pointes, congenital long QT syndrome, bradyarrhythmias, heart failure Patients currently taking medications that prolong the QT interval (Table 1) Aqueous deficiency dry eye defined as Schirmer's strip testing without anesthesia with £ 5mm of tears on two separate tests. Ocular surface inflammatory disease, including cicatrizing conjunctivitis, graft versus host disease, Stevens Johnson syndrome Atopic disease with ocular involvement Limbal stem cell deficiency Oral or topical ophthalmic antibiotic use within the last 90 days Oral prednisone use >5mg per day Topical ophthalmic steroid use within the past 30 days Topical ophthalmic anti-inflammatory (including non-steroidal anti-inflammatory medications, lifitegrast, or cyclosporine) use within the past 30 days Patients who are currently pregnant, planning on becoming pregnant during the study period, or currently breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo Oral<br>* Oral placebo tablet<br>|
| Active Comparator: Azithromycin<br> | Drug: Azithromycin Oral Product<br>* Oral azithromycin dosed at 1 gram per week for 3 weeks<br>* Other names: Zithromax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index (OSDI) Questionnaire | Ocular surface disease index - used to evaluate the degree of dry eye symptoms. Scores will range from 0 to 48, where 48 indicates severe dry eye. | Baseline to 1 month. | 
| Ocular Surface Disease Index (OSDI) Questionnaire | Ocular surface disease index - used to evaluate the degree of dry eye symptoms. Scores will range from 0 to 48, where 48 indicates severe dry eye. | Baseline to 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular surface microbiome testing | To evaluate the composition of the ocular surface microbiome using Shannon's diversity index. The alpha diversity (local species pool) of the population will be analyzed and compared pre-and post-treatment within and between the azithromycin and control groups. The difference between the bacterial microbiome in the azithromycin and placebo arm will be assessed using a PERMANOVA with an L2 norm distance measure. Secondary analyses will include L1 and L0 norms, as well as a phylogenetic distance. In addition, we will assess whether bacterial alpha diversity is decreased in the antibiotic treated arm with the primary outcome being the Simpson's index (L2), with secondary analyses assessing Shannon's (L1) and Richness (L0). | Baseline to 1 month. | 
| Ocular surface microbiome testing | To evaluate the composition of the ocular surface microbiome using Shannon's diversity index. The alpha diversity (local species pool) of the population will be analyzed and compared pre-and post-treatment within and between the azithromycin and control groups. The difference between the bacterial microbiome in the azithromycin and placebo arm will be assessed using a PERMANOVA with an L2 norm distance measure. Secondary analyses will include L1 and L0 norms, as well as a phylogenetic distance. In addition, we will assess whether bacterial alpha diversity is decreased in the antibiotic treated arm with the primary outcome being the Simpson's index (L2), with secondary analyses assessing Shannon's (L1) and Richness (L0). | Baseline to 3 months. | 
| Dry Eye Questionnaire 5 (DE-5) | Dry eye questionnaire 5 - used to evaluate the degree of dry eye symptoms. Scores range from 0-22. A score of 0 represents the minimum dry eye symptoms someone may have and a score of 22 represents the maximum dry eye symptoms someone may have. | Baseline to 1 month. | 
| Dry Eye Questionnaire 5 (DE-5) | Dry eye questionnaire 5 - used to evaluate the degree of dry eye symptoms. Scores range from 0-22. A score of 0 represents the minimum dry eye symptoms someone may have and a score of 22 represents the maximum dry eye symptoms someone may have. | Baseline to 3 months. | 
| Neuropathic Pain Inventory for the Eye (NPSI-E) | Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain. | Baseline to 1 month. | 
| Neuropathic Pain Inventory for the Eye (NPSI-E) | Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain. | Baseline to 3 months. | 
| Personal Health Questionnaire (PHQ-9) | Personal Health Questionnaire - a brief anxiety and depression questionnaire. Will be used in this study to evaluate the interaction between depression/anxiety and response to treatment. | Baseline to 1 month. | 
| Personal Health Questionnaire (PHQ-9) | Personal Health Questionnaire - a brief anxiety and depression questionnaire. Will be used in this study to evaluate the interaction between depression/anxiety and response to treatment. | Baseline to 3 months. |