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

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.