Effects of Carboxymethylcellulose Artificial Tears on the Eye Microbiome

Study Overview
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Brief Summary
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Carboxymethylcellulose (CMC), a common component in artificial tears, has been shown to modify the gut microbiome. The study is examining its effects on the eye microbiome, which may have implications on ocular disease and artificial tear choice. The study will administer artificial tears containing CMC to the treatment group and artificial tears without CMC to the control group. Surveys and conjunctival swabs will be collected before and after treatment for bacterial genome sequencing and analyzed by R statistical packages.

Official Title
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Effects of Carboxymethylcellulose Artificial Tears on the Eye Microbiome: a Randomized, Controlled, Double-Blind Study

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: Carboxymethylcellulose (CMC) Artificial Tears
* Drug: Preservative-free, CMC-free Artificial Tears (control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults above age 18 of either sex who can self-administer artificial tears and return for follow-up at the UF Oaks Eye Clinic. Exclusion Criteria: Individuals with active eye infections or have prosthetic eyes. Are immunocompromised, or are diagnosed with autoimmune diseases or malignant neoplasms about the eye. Individuals who take immunomodulatory therapy, steroids, antibiotics, medicated eyedrops, or are already using CMC eyedrops within 1 week of the study will also be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Carboxymethylcellulose (CMC) Artificial Tears<br>Refresh brand artificial tears containing 0.5% carboxymethylcellulose will be self-administered three times a day in each eye by the participants for 1 week in the experimental arm. | Drug: Carboxymethylcellulose (CMC) Artificial Tears<br>* A pack of 21 vials of artificial tears containing carboxymethylcellulose 0.5% will be given to subjects in the treatment group.<br>* Other names: Refresh Plus;|
| Placebo Comparator: Preservative-free, CMC-free Artificial Tears<br>Systane brand artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be self-administered three times a day in each eye by the participants for 1 week in the control arm. | Drug: Preservative-free, CMC-free Artificial Tears (control)<br>* A pack of 21 vials of artificial tears containing 0.4% polyethylene glycol 400 and 0.3% propylene glycol will be given to subjects in the control group.<br>* Other names: Systane Ultra PF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Species Richness | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Faith's phylogenetic diversity was used as a measure of species richness, calculated as the sum of all phylogenetic tree branch lengths using the QIIME2 faith_pd plugin. The units for this measure are the number of nucleotide substitutions (phylogenetic distance, i.e. length) per branch, which is a scale measure from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species richness. | Assessed at day 1 and day 7, day 7 reported. | 
| Species Diversity | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold. Shannon's diversity index was used as a measure of species diversity, calculated as the sum of -p/ln(p), where p is the proportion of the sample made up of each OTU using the QIIME2 shannon_pd plugin. This measure is a unitless scale proportion ranging from zero to infinity. Zero indicates a completely homogenous sample, and higher scores indicate greater species diversity. | Assessed at day 1 and day 7, day 7 reported. | 
| Beta Diversity (Unweighted UniFrac) | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Unweighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin. The unweighted UniFrac is a unitless scale proportion ranging from zero to one. Greater UniFrac distances indicate greater beta diversity. | Assessed at day 1 and day 7, difference between day 1 and day 7 reported. | 
| Beta Diversity (Weighted UniFrac) | Sampled 16S rRNA sequences were organized into 'operational taxonomic units' (OTUs) at a 97% sequence similarity threshold, and a phylogenetic tree was constructed from sampled OTUs using the QIIME2 bioinformatics platform. Weighted UniFrac distances were calculated as the number of shared nucleotide substitutions between two samples divided by the number of shared nucleotide substitutions among all samples using the QIIME2 unifrac plugin, with samples weighted by abundance of species. The weighted UniFrac (weighted by number of duplicate OTUs) is a unitless scale proportion ranging from zero to infinity. Greater UniFrac distances indicate greater beta diversity. | Assessed at day 1 and day 7, difference between day 1 and day 7 reported. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index Score | The Ocular Surface Disease Index (OSDI) is a 12-item scale for the assessment of symptoms related to dry eye disease and their effect on vision. Participants conducted a survey before and after intervention, and the difference will be used as the outcome measure. The OSDI ranges from 0 to 48, and a higher score indicates greater ocular surface dryness. If reporting the difference, a more negative change in OSDI indicates greater improvement in dry eye symptoms. Pairwise Wilcoxon signed rank tests were used to compare changes in OSDI between intervention groups at a two-tailed 95% confidence interval. | Assessed at day 1 and day 7, difference between day 1 and day 7 reported. | 
| Artificial Tear Use | Patients will be asked 1 week after intervention how many times they administered eye drops each day. This measures compliance with intervention, ranging from zero drops per day to infinite drops per day. If a patient is perfectly compliant, the number of drops should be 3. Mann-U-Whitney tests were used to compare compliance between intervention groups at a two-tailed 95% confidence interval. | Assessed at day 7 |