The Impact of Topical Prostaglandins on the Biomechanical Properties of the Cornea in Patients With Open Angle Glaucoma
Condition: Glaucoma, Open-Angle
MeSH terms: Glaucoma; Glaucoma, Open-Angle
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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.
    

Intervention name(s): topical prostaglandin analogs
Intervention type(s): Drug
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prostaglandin analogs; Corneal biomechanics; Corneal Hysteresis; Glaucoma, Open-Angle