Dry Eye
Conditions
Keywords
dry eye, artificial tears, tear osmolarity, residence time
Brief summary
Background: Osmolarity is defined as the concentration of particles dissolved in a solution. Normal tears contain various dissolved particles including proteins, salts and other electrolytes. The investigators plan to investigate how osmolarity of the tear film changes over time after instillation of artificial tears containing hyaluronate. This is one kind of artificial tear that is used to treat dry eye. Dry eye and tear osmolarity: Dry eye is a significant health problem, but diagnosis and treatment are often ambiguous and ineffective. There has been a resurgence of interest and research in dry eye in the past 5 years, and tear osmolarity has emerged as perhaps, one of the most effective ways to evaluate tear quality and dry eye status. Dry eye is usually treated with artificial tears, and many formulations are available. The investigators will test an isotonic solution that contains hyaluronate. Hyaluronate binds water and should help to maintain water on the eye. Objective: We plan to study the time course of possible changes in tear film osmolarity following instillation of an isotonic artificial tear containing hyaluronate. The investigators will use the TearLab, a new clinical instrument that has been developed to quickly and easily measure tear film osmolarity. Understanding how artificial tears affect tear film osmolarity over time can help doctors determine efficacy and dosing schedules. The investigators will test the isotonic hyaluronate (Blink Contacts) artificial tears relative to normal saline solution. Hypothesis: The investigators should be able to measure a decrease in tear osmolarity over time following instillation due to the water-binding effect of hyaluronate artificial tears relative to a control (normal saline solution).
Detailed description
ABSTRACT: Introduction: Tear hyper-osmolarity may be a fundamental cause of dry eye in many cases. Hyaluronate is an agent used in some artificial tears, which binds water and can protect against evaporation. It may therefore be an effective treatment for tear hyper-osmolarity. Purpose: Our purpose was to measure changes in tear osmolarity over time following instillation of Blink Contacts, an isotonic ocular lubricant containing hyaluronate. We hypothesized that even in isotonic solution, the water-binding properties of hyaluronate would reduce tear osmolarity. This will help us better understand efficacy of this treatment and develop a rational basis for dosing schedules. Methods: After baseline osmolarity measurements, eight subjects received either Blink Contacts or normal saline drops in both eyes. We re-measured osmolarity five minutes later, and then at 15-minute intervals up to 95 minutes. Subjects also rated comfort at each time. The next day, the experiment was repeated with the alternate drops for each subject.
Interventions
DRUGArtificial tears
At random, subjects will receive isotonic artificial tear or a control (normal saline).
Sponsors
Thomas O Salmon, OD, PhD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* At least 18 years of age Normal vision in both eyes (20/30 best corrected) Preference for patient with dry eye symptoms
Exclusion criteria
* No ocular disease other than dry eye Currently taking no ocular or systemic medications that might affect results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Baseline, followed by 7 measurements made after instillation (5, 20, 35, 50, 65, 80, 95 minutes post-instillation). | Raw data: Baseline (pre-instillation) tear osmolarity was measured for right and left eyes for each subject. Then measurements were repeated at 7 times (5, 20, 35, 50, 65 890 and 95 minutes) after instillation. Data processing: 1) Baseline osmolarity was subtracted from each post-baseline measurement to give a change-from-baseline values. 2) Right and left eye change values averaged to give a mean osmolarity change for each subject at each of the seven times. 3) Mean osmolarity changes values were averaged across 8 subjects for each of the 7 times and entered in the table below. Row 1 is for Drop A (hyaluronate); Row 2 for Drop B (saline). Column are for the 7 times. |
Countries
United States
Participant flow
Recruitment details
A convenience sample of 8 subjects was recuitted from among the student population at the NSU Oklahoma College of Optometry during May-June 2012.
Pre-assignment details
Subjects were assigned random ID numbers in preparation for assignment into the two groups. Half (4 subjects) chosen at random, would be assigned to Group 1, and receive Drop A on Day 1, then return 24 hours (Day 2) later to received Drop B. The other 4 subjects would be assigned to Group 1, and receive Drop B on Day 1 and Drop A on Day 2.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1. Isotonic Hyaluronate Artificial Tear FIRST Per sequence. Four subject, chosen at random, will receive isotonic hyaluronate artificial tear in Session 1. After a 24-hour washout period, they will return for Session 2, when they will receive saline eye drops. | 4 |
| Arm 2. Normal Saline FIRST Per sequence. The four remaining subject (see comments to left), will receive saline eye drops in Session 1. After a 24-hour washout period, they will return for Session 2, when they will receive isotonic hyaluronate artificial tears. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Arm 2. Normal Saline FIRST | Arm 1. Isotonic Hyaluronate Artificial Tear FIRST | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Continuous | 28.0 years STANDARD_DEVIATION 4.8 | 25.8 years STANDARD_DEVIATION 1.5 | 26.9 years STANDARD_DEVIATION 3.5 |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes)
Raw data: Baseline (pre-instillation) tear osmolarity was measured for right and left eyes for each subject. Then measurements were repeated at 7 times (5, 20, 35, 50, 65 890 and 95 minutes) after instillation. Data processing: 1) Baseline osmolarity was subtracted from each post-baseline measurement to give a change-from-baseline values. 2) Right and left eye change values averaged to give a mean osmolarity change for each subject at each of the seven times. 3) Mean osmolarity changes values were averaged across 8 subjects for each of the 7 times and entered in the table below. Row 1 is for Drop A (hyaluronate); Row 2 for Drop B (saline). Column are for the 7 times.
Time frame: Baseline, followed by 7 measurements made after instillation (5, 20, 35, 50, 65, 80, 95 minutes post-instillation).
Population: Eight subjects recruited from among students at the NSU Oklahoma College of Optometry, including 6 males and 2 females who were at least 18 years of age and who had no known ocular or systemic disease other than dry eye. Six subjects did not have dry eye and 2 were diagnosed with dry eye based on Ocular Surface Disease Index (OSDI) survey scores.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | -0.8 mOsmols/L | Standard Error 0.97 |
| 5 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | -0.94 mOsmols/L | Standard Error 0.62 |
| 20 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | 7.25 mOsmols/L | Standard Error 1.49 |
| 20 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | -2.1 mOsmols/L | Standard Error 1.43 |
| 35 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | 2.5 mOsmols/L | Standard Error 2.09 |
| 35 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | 5.31 mOsmols/L | Standard Error 2.19 |
| 50 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | -4.25 mOsmols/L | Standard Error 1.26 |
| 50 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | 4.4 mOsmols/L | Standard Error 1.35 |
| 65 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | 4.9 mOsmols/L | Standard Error 1.31 |
| 65 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | 7.5 mOsmols/L | Standard Error 1.61 |
| 80 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | 1.9 mOsmols/L | Standard Error 1.32 |
| 80 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | 2.31 mOsmols/L | Standard Error 1.54 |
| 95 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop B | 8.6 mOsmols/L | Standard Error 1.9 |
| 95 Minutes | Osmolarity Change From Baseline (mOsms/L) as a Function of Time (Minutes) | Drop A | 9.25 mOsmols/L | Standard Error 1.39 |
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.4Wilcoxon (Mann-Whitney)
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.109Wilcoxon (Mann-Whitney)
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.779Wilcoxon (Mann-Whitney)
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.262Wilcoxon (Mann-Whitney)
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.15Wilcoxon (Mann-Whitney)
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.726Wilcoxon (Mann-Whitney)
Comparison: Drop A: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.055Wilcoxon (Mann-Whitney)
Comparison: Drop B: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.945Wilcoxon (Mann-Whitney)
Comparison: Drop B: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.844Wilcoxon (Mann-Whitney)
Comparison: Drop B: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.945Wilcoxon (Mann-Whitney)
Comparison: Drop B: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.383Wilcoxon (Mann-Whitney)
Comparison: Mean change in osmolarity from baseline. H0: No change (e.g. mean change = 0) H1: Significant change (mean change ≠ 0)p-value: 0.383Wilcoxon (Mann-Whitney)
Comparison: Drop B: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.672Wilcoxon (Mann-Whitney)
Comparison: Drop B: Mean change in osmolarity from baseline H0: No osmolarity change from baseline (e.g. mean change = 0) H1: Significant osmolarity change from baseline (mean change ≠ 0)p-value: 0.107Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.64Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.04Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.2Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.15Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.73Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.89Wilcoxon (Mann-Whitney)
Comparison: Comparison of Drop A versus Drop B change in osmolarity at this point in time. H0: No difference in osmolarity change between Drop A and B (Drop A = Drop B) H1: Significant difference in osmolarity change between Drop A and Drop Bp-value: 0.89Wilcoxon (Mann-Whitney)