The Impact of Topical Prostaglandins on the Biomechanical Properties of the Cornea in Patients With Open Angle Glaucoma

February 24, 2021 updated by: Dr. Paul Harasymowycz, Maisonneuve-Rosemont Hospital

The Impact of Topical Prostaglandin Analogs on the Biomechanical Properties of the Cornea in Patients With Open Angle Glaucoma

The purpose of this study is to determine the influence of topical prostaglandin analog (PGA) medication on corneal biomechanical properties in patients undergoing PGA treatment for open-angle glaucoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients: Thirty five patients (seventy eyes) with bilateral open angle glaucoma on monotherapy with topical PGA medication in both eyes were recruited from the Montreal Glaucoma Institute, Montreal, QC, Canada. Informed consent was acquired from all participants. The research protocol of this study adhered to the tenets of the Declaration of Helsinki. It was approved by the Maisonneuve-Rosemont Hospital Ethics committee (Montreal, QC, Canada) and all patients signed a research consent form.

Study Procedures: Consenting patients undergoing topical PGA treatment in both eyes were asked to discontinue the PGA in their best eye and to continue the administration of PGA in the contralateral eye. All measurements were taken before PGA cessation (Visit 1) and repeated 6 weeks after cessation (Visit 2). Patients then restarted the application of PGA to the experimental eye and all measurements were repeated once more after an additional 6 weeks (Visit 3).

The best eye was selected based on less glaucoma damages. It was defined by the results of the Humphrey Visual Field (HFA, Carl Zeiss Meditec, Inc., Dublin, CA), Heidelberg Retinal Tomograph (HRT II, Heidelberg Engineering GmbH, Heidelberg, Germany) and Optical Coherence Tomography (CIRRUS HD-OCT, Carl Zeiss Meditec, Inc., Dublin, CA). The Humphrey Visual Field defines early glaucoma as a mean defect (MD) of -2.00 to -6.00 db, moderate glaucoma as a MD of -6.10 to -12.0 db and advanced as a MD less than -12.0 db. The Optical Coherence Tomography enables the identification of the better linear Cup/Disk ratio, Rim area, RNFL thickness and ganglion cells analysis between both of the patient's eyes. The lesser of the maximum IOP values recorded in each of the patient's eyes also contributed to the selection of the best eye.

Instruments: The Ocular Response Analyzer (ORA) (Reichert, INC, Depew, NY) was used to assess the biomechanical properties of the cornea. This instrument utilizes a dynamic bi-directional applanation process to measure the biomechanical properties of cornea and estimate IOP. A rapid air pulse applies force to the cornea and an advanced electro-optical system monitors corneal deformation. A precisely-metered collimated-air-pulse pushes the cornea inwards, past a flat state and into a slight concavity. Milliseconds after applanation, the air pump shuts off and the pressure gradually declines. As the pressure decreases, the cornea first passes through an applanated state before resuming its original curved structure. The applanation detection system monitors the corneal movement throughout the entire process. Two separate pressure values are derived from the INWARD and OUTWARD applanation events. The difference between these two pressure values is termed CH. This biomechanical property reflects corneal absorption and dissipation of the energy from an applied force. Derived from the measurement of CH is the Corneal resistance factor (CRF). CRF represents the cornea's ability to resist deformation in the presence of an external force.

Goldmann applanation tonometry (Haag-Streit AG, Koeniz, Switzerland) is still recognized as the gold standard for measuring IOP in glaucoma patients and it was performed in all patients at all visits. The ORA takes the CH and CRF measurements into account to generate the corneal-compensated intraocular pressure (IOPcc) value, which is mean to be less affected by corneal biomechanical properties than the Goldmann-IOP. The IOP bias is estimated as the difference between IOPcc and Goldmann-IOP (IOPcc - Goldmann IOP). A positive bias value indicates that the IOPcc is larger than the Goldmann-IOP, meaning that Goldman tonometry underestimated IOP in comparison to the IOPcc.

Four ORA measurements were taken per eye and the mean value was recorded for each parameter (CH, CRF and IOPcc). Central corneal thickness (CCT) was measured by ultrasound pachymetry (DGH Technology, INC, Exton, PA) and the average of three measurements was recorded. All study measurements were performed by the same trained observer (RM), with the same equipment and at the same time of day. All of the equipment needed for this research was calibrated prior to each use.

Statistical Analysis: The hypothesis of no effect regarding the discontinuation of PGA on the biomechanical properties was examined by a linear mixed-effect model using the nlme package in R. Random-effects were defined on two levels: the patient (level-1) and the eye within each patient (level-2). Those random-effects were added to the model to account for the intra-individual variance due to the repeated-measure design. Age was also included in the model as a covariate. Contrasts between the eyes and times were estimated using adjusted p-values to control for familywise error rate using multcomp package in R.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1V 1G5
        • Montreal Glaucoma Institut

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients with bilateral open angle glaucoma on monotherapy with topical PGA medication in both eyes

Exclusion Criteria:

  • corneal disease (such as Fuchs' endothelial dystrophy or keratoconus)
  • past history of corneal trauma or surgery (including refractive surgery) that may affect hysteresis measurements
  • contact lens wearers
  • uncontrolled glaucoma or advanced visual field (VF) damage (mean defect < -12.0 db)
  • patients taking systemic prostaglandin medication, non-steroidal anti-inflammatory drugs, or undergoing hormone replacement therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: topical prostaglandin analogs
Drug: topical prostaglandin analogs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The Corneal Hysteresis (in mmHg) difference in patient with PGAs and without PGAs based on the integrated analysis of the data collected from the Reichert Ocular Response Analyzer (ORA)
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
The intraocular pressure (in mmHg) difference in patient with PGAs and without PGAs based on the integrated analysis of the data collected from Goldmann tonometry
Time Frame: 12 weeks
12 weeks
The corneal thickness (in µm) difference in patient with PGAs and without PGAs based on the integrated analysis of the data collected from pachymetry
Time Frame: 12 weeks
12 weeks
The Corneal Resistance Factor (in mmHg) difference in patient with PGAs and without PGAs based on the integrated analysis of the data collected from the Reichert Ocular Response Analyzer (ORA)
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maisonneuve-Rosemont Hospital

Investigators

  • Principal Investigator: Paul Harasymowycz, Dr, Maisonneuve-Rosemont Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 6, 2013

Primary Completion (Actual)

June 30, 2016

Study Completion (Actual)

November 16, 2016

Study Registration Dates

First Submitted

December 20, 2014

First Submitted That Met QC Criteria

March 9, 2015

First Posted (Estimate)

March 17, 2015

Study Record Updates

Last Update Posted (Actual)

February 26, 2021

Last Update Submitted That Met QC Criteria

February 24, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MaisonneuveRH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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