The Effects of BAK on the Blood Aqueous Barrier of Pseudophakic Patients

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.

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndromes
• Intervention / Treatment: Drug: Hydroxypropylmethylcellulose; Drug: Carboxymethylcellulose

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Campinas, SP, Brazil
      • Department of Ophthalmology, University of Campinas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Preserved (BAK 0.006%) lubricating drop; One group will receive preserved lubricating drops 4 times a day for 1 month.	Drug: Hydroxypropylmethylcellulose; 22 patients will receive this lubricating drop 4 times a day for 1 month; Other Names: Retin Active
Active Comparator: Preservative-free lubricating drops; The second group will receive preservative-free lubricating drops 4 times a day for 1 month.	Drug: Carboxymethylcellulose; 22 patients will receive this lubricating drop 4 times a day for 1 month.; Other Names: Optive UD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 15 days and 30 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 15 days and 30 days.

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Vital P Costa, MD, Department of Ophthalmology, University of Campinas

Publications and helpful links

General Publications

• Baudouin C, Labbe A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010 Jul;29(4):312-34. doi: 10.1016/j.preteyeres.2010.03.001. Epub 2010 Mar 17.
• Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004 Jul;23(5):490-6. doi: 10.1097/01.ico.0000116526.57227.82.
• Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells. Adv Ther. 2010 Nov;27(11):837-45. doi: 10.1007/s12325-010-0070-1. Epub 2010 Oct 7.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (Estimate): January 20, 2011

Study Record Updates

• Last Update Posted (Estimate): July 18, 2012
• Last Update Submitted That Met QC Criteria: July 12, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: cornea; dry eye; pseudophakia; lubricating drop; BAK; blood aqueous barrier; blood-retina barrier
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Dry Eye Syndromes; Gastrointestinal Agents; Laxatives; Carboxymethylcellulose Sodium
• Other Study ID Numbers: VPC1