Dry Eye, Neuropathic Eye Pain, Ocular Microbiome, Depression, Anxiety
Conditions
Brief summary
This study aims to elucidate the effectiveness of oral azithromycin in treating symptomatic dry eye syndrome secondary to Meibomian gland dysfunction.
Detailed description
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.
Interventions
Oral azithromycin dosed at 1 gram per week for 3 weeks
DRUGPlacebo Oral
Oral placebo tablet
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Surface Disease Index (OSDI) Questionnaire | Baseline to 1 month | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Surface Microbiome Testing | Baseline to 1 month | 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). |
| Dry Eye Questionnaire 5 (DE-5) | Baseline to 1 month | 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. |
| Neuropathic Pain Inventory for the Eye (NPSI-E) | Baseline to 1 month. | Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain. |
| Personal Health Questionnaire (PHQ-9) | Baseline to 1 month | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo Oral: Oral placebo tablet | 1 |
| Azithromycin Azithromycin Oral Product: Oral azithromycin dosed at 1 gram per week for 3 weeks | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated due to lack of funding prior to data collection for for outcomes and adverse events | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Azithromycin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Baseline to 1 month
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Primary
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.
Time frame: Baseline to 3 months
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
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.
Time frame: Baseline to 1 month
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
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.
Time frame: Baseline to 3 months
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
Neuropathic Pain Inventory for the Eye (NPSI-E)
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Time frame: Baseline to 3 months
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
Neuropathic Pain Inventory for the Eye (NPSI-E)
Neuropathic pain inventory for the eye - used to study neuropathic vs stimulatory eye pain.
Time frame: Baseline to 1 month.
Population: study terminated prior to any data analysis
Secondary
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).
Time frame: Baseline to 1 month
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
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).
Time frame: Baseline to 3 months
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
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.
Time frame: Baseline to 3 months
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.
Secondary
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.
Time frame: Baseline to 1 month
Population: Study terminated prior to data collection for outcomes. No data were collected for this outcome measure.