Dry Eye Syndromes
Conditions
Keywords
dry eye, pseudophakia, cornea, lubricating drop, BAK, blood aqueous barrier, blood-retina barrier
Brief summary
BAK is one of the most frequent preservatives in eye drops. BAK is a quaternary ammonium salt with surfactant qualities. It can be bacteriostatic or bactericidal depending on the concentrations used. It has been shown to be effective against most bacteria with a few exceptions, such as Pseudomonas aeruginosa, or picornaviruses. It as been widely used in eyedrops, nose sprays, hand and face washes, mouthwashes, spermicidal creams, and in various other cleaners, sanitizers, and disinfectants. BAK gained popularity when it was first introduced because it also enhances corneal penetration of some drugs by causing epithelial separation. It is present in several ophthalmic formulations, including most of the antiglaucoma medications. If used chronically, BAK has been found to cause ocular surface changes, such as dry eye and punctuate keratitis. BAK has also been suggested to promote a break in the blood aqueous barrier, which may lead to undesirable consequences, such as uveitis and cystoid macular edema. However, this information is controversial. The purpose of this study is to evaluate the consequences of BAK on the blood-retinal and blood-aqueous barriers of pseudophakic patients receiving BAK-preserved lubricating drops.
Detailed description
The primary hypothesis behind the study is that BAK may lead to a break in the blood-retina barrier in pseudophakic eyes, leading to an increase in macular thickness, compared to a non-BAK containing solution. The secondary hypothesis is that solutions containing BAK will increase the permeability of the blood aqueous barrier compared to non-BAK solutions. If the hypotheses are confirmed, they may serve as a contraindication to the use of BAK-preserved drops in pseudophakic eyes requiring chronic use of medications. This is a prospective, randomized, examiner-masked, controlled study involving 44 pseudophakic eyes of 44 patients. Patients receiving any other eyedrop, with a previous history of uveitis, posterior capsule rupture or any other ophthalmic surgery will be excluded. Patients will be randomized to the use of a BAK-preserved lubricating drop or to the use of a non-preserved lubricating drop q.i.d for one month. Effects on the blood aqueous barrier will be objectively measured with a laser flare meter (Kowa, Japan) at baseline, 15 days and one month after inclusion. Patients will also have OCT images (Cirrus, Zeiss, USA) of the macula at the same time intervals to evaluate the possible effects on the blood-retina barrier. Macular thickness and the presence of cystoid macular edema will be evaluated at each time interval.
Interventions
22 patients will receive this lubricating drop 4 times a day for 1 month
22 patients will receive this lubricating drop 4 times a day for 1 month.
Sponsors
Merck Sharp & Dohme LLC
University of Campinas, Brazil
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Pseudophakic eyes that underwent cataract surgery at least 6 months before.
Exclusion criteria
* Use of any eyedrop. * Other conditions associated with a break in the blood-aqueous or blood retina barrier (ie diabetes, ARMD, vasculitis, uveitis) * Previous history of cystoid macular edema. * Previous ocular surgery other than cataract surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aqueous Humor Flare | Baseline, 15 days and 30 days. | Aqueous humor flare indicates the degree of a break in the blood-aqueous barrier. It is objectively measured with a Laser flare meter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Macular Thickness | Baseline, 15 days and 30 days. | Macular thickness will be measured with an Optical coherence tomography (OCT). Measures 5% under the normal population according to the OCT software will be considered break in the blood-retina barrier. |
Countries
Brazil
Participant flow
Recruitment details
Recruitment period started on March 2011 through December 2011 in the Department of Ophthalmology at the Hospital das Clínicas - State University of Campinas.
Participants by arm
| Arm | Count |
|---|---|
| Preserved (BAK 0.006%) Lubricating Drop One group will receive preserved lubricating drops 4 times a day for 1 month. | 22 |
| Preservative-free Lubricating Drops The second group will receive preservative-free lubricating drops 4 times a day for 1 month. | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Preservative-free Lubricating Drops | Preserved (BAK 0.006%) Lubricating Drop | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 15 Participants | 16 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 13 Participants |
| Age Continuous | 65.2 years STANDARD_DEVIATION 12.2 | 69 years STANDARD_DEVIATION 10.7 | 67.1 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment Brazil | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 13 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Aqueous Humor Flare
Aqueous humor flare indicates the degree of a break in the blood-aqueous barrier. It is objectively measured with a Laser flare meter.
Time frame: Baseline, 15 days and 30 days.
Population: Statiscal power of 80%.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Preserved (BAK 0.006%) Lubricating Drop | Aqueous Humor Flare | Baseline | 8.4 photons/msec | Standard Deviation 2.7 |
| Preserved (BAK 0.006%) Lubricating Drop | Aqueous Humor Flare | 15 days | 11.4 photons/msec | Standard Deviation 5.1 |
| Preserved (BAK 0.006%) Lubricating Drop | Aqueous Humor Flare | 30 days | 11.9 photons/msec | Standard Deviation 5.9 |
| Preservative-free Lubricating Drops | Aqueous Humor Flare | Baseline | 9.3 photons/msec | Standard Deviation 2.6 |
| Preservative-free Lubricating Drops | Aqueous Humor Flare | 15 days | 8.4 photons/msec | Standard Deviation 2.8 |
| Preservative-free Lubricating Drops | Aqueous Humor Flare | 30 days | 8.4 photons/msec | Standard Deviation 2.5 |
Secondary
Macular Thickness
Macular thickness will be measured with an Optical coherence tomography (OCT). Measures 5% under the normal population according to the OCT software will be considered break in the blood-retina barrier.
Time frame: Baseline, 15 days and 30 days.
Population: Statiscal power of 80%
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Preserved (BAK 0.006%) Lubricating Drop | Macular Thickness | 15 days | 254.9 μm | Standard Deviation 24.2 |
| Preserved (BAK 0.006%) Lubricating Drop | Macular Thickness | Baseline | 258.5 μm | Standard Deviation 26.7 |
| Preserved (BAK 0.006%) Lubricating Drop | Macular Thickness | 30 days | 255.9 μm | Standard Deviation 25.1 |
| Preservative-free Lubricating Drops | Macular Thickness | Baseline | 259.2 μm | Standard Deviation 26.8 |
| Preservative-free Lubricating Drops | Macular Thickness | 15 days | 256.4 μm | Standard Deviation 27.6 |
| Preservative-free Lubricating Drops | Macular Thickness | 30 days | 258.3 μm | Standard Deviation 29.1 |