research

Clinical Research is an integral part of the Galen Eye Centre’s mandate. Some of this research has to do with diagnostic equipment, some with medical management and others with surgical treatments. We are striving to advance the understanding, diagnosis, identification of progression and management of glaucoma.

• Bimatoprost Sustained Release
• Rho Kinase Elevated Pressure Treatment Trial (Rocket-3)
• Aqueous Suppression and Bleb Encapsulation Rates of Ahmed Valves
• Application of Triggerfish Device Prior to Ophthalmic Outflow Modifying Therapeutics
• Primary SLT for Steroid Induced Ocular Hypertension
• Comparison of Trabeculectomy versus Ex-PRESS™ Miniature Glaucoma Device
• Refractive Error, Eye Depth, & Narrow Angle Incidence Study
• Toronto Glaucoma Prevalence Pilot Study
• Population Based Trials on Glaucoma Risk Factors Meta-analysis
• Evaluation of Investigator Bias in Industry Funded Clinical Trials of Latanoprost
• Risk Factors for Glaucoma Study

Bimatoprost Sustained Release

Status: Currently enrolling
Description:
Bimatoprost is a prostaglandin analog used to control the progression of glaucoma. Applied topically (as eye drops), it reduces intraocular pressure (IOP) by increasing the outflow of aqueous fluid from the eyes. The drug is effective, but only when used regularly.  Unfortunately, many patients (30-40%) do not take the drops regularly or properly and are thus not able to control their glaucoma’s progression. Glaucoma reduces field of vision too slowly for some patients to take seriously enough to commit to a medication regime.  For other patients, applying eye drops consistently can be physically difficult or hard to remember.

Allergan, the maker of the drug, has developed a sustained release form of Bimatoprost that can be injected into the eye and will slowly dissolve over a 6 month period. The new delivery system is in phase 2 trials globally.

The goal of this project is to determine the efficacy of this Bimatoprost Sustained Release (SR) (Phase 2 trial).The study attempts to improve the understanding and methodology in the field of Ophthalmology. If proven effective, this delivery method should improve outcomes for many less diligent patients who would otherwise not take currently available medications properly and it may circumvent the side effects encountered on the surface of the eye when using a drop. Making treatments more consistent like this might also enable better study of how the disease responds to treatment across the patent population.

If you would like more information regarding this clinical trial please contact the Galen Eye Centre at 613-507-4800.

Rho Kinase Elevated Intraocular Pressure Treatment Trial (Rocket-3)

Status: Currently enrolling
Description:
This research study involves the investigational drug AR13324 Ophthalmic Solution 0.02%, in subjects with elevated intraocular pressure or glaucoma. An investigational drug is one that has not been approved by Health Canada.

The purpose of this research study is to test the safety of AR13324 Ophthalmic Solution 0.02%, compared to Timolol Maleate Ophthalmic Solution 0.5% which is commercially available for lowering of intraocular pressure in patients with glaucoma or ocular hypertension (raised intraocular pressure)

If you would like more information regarding this clinical trial please contact the Galen Eye Centre at 613-507-4800.

Aqueous Suppression and Bleb Encapsulation Rates of Ahmed Valves

Status: Currently enrolling
Description:
An Ahmed Valve is a medical shunt used in the treatment of glaucoma to reduce the eye's intraocular pressure (IOP). A flow tube is inserted into the anterior chamber of the eye and a plate is implanted underneath the conjunctiva to allow flow of aqueous fluid out of the eye into an outlet chamber called a bleb. By bypassing the trabecular meshwork and redirecting the outflow of aqueous humor out of the eye, IOP is reduced.

However, the body often forms a capsule around the bleb. When the bleb is fully encapsulated the drainage stops and pressure returns. The cause of this encapsulation is not well understood. The eye produces a great deal of inflammatory material and chemicals in response to the surgery's insult to the eye, and this material drains through the valve to the bleb. It is thought by many that the encapsulation of the bleb is an immune response of the tissue around the bleb to this material that thickens and remodels the tissue to form that capsule. It is generally thought that quickly draining this material is the best way to improve response to the surgery. However, we conceived that possibly the opposite is true and reducing flow might slow and reduce overall encapsulation.
The purpose of this study is to determine if reducing aqueous flow rate through the valve at first sign of bleb encapsulation will reduce the rate of encapsulation. If successful, this would improve the success rates with the Ahmed valve procedure.

If you would like more information regarding this clinical trial please contact the Galen Eye Centre at 613-507-4800.

Application of Triggerfish Device Prior to Outflow modifying therapeutics

Status: Enrollment closed
Description:
Measuring intraocular pressure (IOP) is used for diagnosing and monitoring glaucoma patients. However, these measurements are normally only snapshots in time. A recent sleep lab study has found large spikes in IOP during sleep cycles. Also, it is unknown to what extent IOP readings, like blood pressure, can be affected by other daily activities.
The new SENSIMED Triggerfish sensor is a soft hydrophilic single use contact lens containing strain gauges embedded in the silicone to monitor fluctuations in diameter of the corneoscleral junction. This is directly correlated to fluctuations in IOP. Also embedded are a telemetric chip and micro-loop antenna for wireless reception of power and data output. A signal is sent wirelessly from the micro-antenna to an adhesive antenna, worn around the eye, which is connected to a portable recorder through a thin flexible data cable.

The patient wears the Triggerfish for 24 hours and assumes normal activities including sleep periods. When the patient returns to his doctor, the data is transferred from the recorder to the practitioner's computer via Bluetooth technology for immediate analysis.
Therefore the goal of this study is to use the Triggerfish to study daily IOP cycles in the glaucoma population both pre and post glaucoma laser treatment. We subsequently expanded the scope of the study to use the Triggerfish to study IOP cycles of patents treated using medications.

If you would like more information regarding this clinical trial please contact the Galen Eye Centre at 613-507-4800.

Primary SLT for Steroid Induced Ocular Hypertension

Status: Enrollment closed
Description:
Selective Laser Trabeculoplasty (SLT) is a glaucoma treatment that uses a laser to target melanocytes in the pigmented trabecular meshwork.  It disrupts the meshwork without causing thermal or coagulative damage to surrounding structures.  It can be used as a primary treatment when a patient is first diagnosed with glaucoma, as adjunctive treatment with medications, or as an end-stage treatment to avoid surgery after a patient is already on multiple medications.

Steroids are sometimes injected into the eye to try to control inflammation after surgery.  They are also used to reduce blood vessel leakage in the eyes of diabetes patients, which can cause fluid to collect in the retina and some vision loss.  However, a side effect of the steroid treatment is increased ocular fluid pressure.  It is thought that steroids cause a proliferation of intercellular matrix by-products like proteoglycans and aminoglycans that then causes the cells that handle waste for the eye to swell and clog drainage.  Standard treatment for this condition is drop therapies, and surgery if this is not effective.

The purpose of the study is to determine if the use of SLT as a primary treatment can reduce steroid induced ocular hypertension and to compare its effectiveness to standard drop therapies.

Comparison of Trabeculectomy versus Ex-PRESS™ Miniature Glaucoma Device

Status: Enrollment closed
Description:
Glaucoma filtration surgery has been associated with short, medium and long-term complications, including hypotony, endophthalmitis, choroidal detachment, bleb dysesthesia and cataract.  Therefore, under the current treatment paradigm, surgery is pursued after medical management has been deemed to be insufficiently managing the patient’s glaucoma.

The Ex PRESS^TM Miniature Glaucoma Device is a glaucoma drainage device that has been demonstrated to be easy to install and may be an alternative to standard trabeculectomy. The un-valved stainless-steel device is miniature (3mm x 0.5mm) compared to other devices that have been devised to create a shunt through the trabecular meshwork. Various pre-clinical and clinical studies have demonstrated that the implantation is relatively easy compared to standard glaucoma drainage device implantation, and its efficacy is comparable to trabeculectomy.  Furthermore, there is no need for a critical step in trabeculectomy surgery known as an iridectomy where a portion of the peripheral iris is removed.  Therefore, theoretically there is less inflammation incited and the risk of bleeding is lower than traditional trabeculectomy.  A comparison to standard trabeculectomy has demonstrated a superior safety profile for the ExPRESS^TM and as good or possibly superior efficacy profile.  However, there have been no prospective randomized clinical trials comparing it directly to trabeculectomy.

None of the studies to date investigating the ExPRESS^TM device have investigated its impact on the corneal endothelial cells.  Corneal endothelial cells are sensitive cells that have a pump function and act to keep the cornea dry; when they are damaged the cornea swells and becomes opaque and since these cells do not replicate this is a permanent complication that requires a corneal transplant to fix.  The proximity of the ExPRESS^TM device to these cells and the possibility of device-cornea touch may lead to their damage.

Therefore the goal of this study is to compare the mid-term efficacy, the complications and the endothelial cell count in patients with primary open angle glaucoma who undergo trabeculectomy versus Ex-PRESS^TM miniature glaucoma device implantation. The study attempted to improve the understanding and methodology in the field of Ophthalmology.

Publication:
Wagschal L.D., Trope G.E., Jinapriya D., Jin Y., Buys Y.M. Prospective Randomized Study Comparing ExPRESS to Trabulectomy: 1-Year Results. J Glaucoma. 2013

Beltran L., Trope G.E., Jin Y., Wagschal L.D., Jinapriya D., Buys Y.M.  Comparison of visual recovery following ExPRESS versus trabeculectomy: Results of a prospective randomized controlled trial. J                                                 Glaucoma. 2013, June 25.

Refractive Error, Eye Depth, & Narrow Angle Incidence Study

Status: Enrollment closed
Description:
There are 2 main types of glaucoma, open-angle and closed-angle.  Open angle glaucoma is where drainage through the trabecular meshwork in the eye is open but insufficient.  With closed angle glaucoma drainage is closed.

The first step in treatment is to determine the type, since type will dictate treatment algorithms.  Open-angle glaucoma accounts for about 90% of glaucoma cases in the North America.  Patients are profiled as being much more likely to have closed angle glaucoma if they are of East Asian or Inuit decent, or if they are farsighted.  A commonly held theory for this is that shorter eyeballs may cause the lens to crowd the angle.

Anecdotally, this ophthalmologist noted many more closed angle cases in practice than recognized statistics would suggest for Southern Ontario.  This was across ethnicities and eyeglass prescriptions.

This study aimed to determine the relationship between both refractive error and eye length on the incidence of narrow angle glaucoma.

Toronto Glaucoma Prevalence Pilot Study

Status: Enrollment closed
Description:
Based on Canada-wide Census health surveys, in 2007 Perruccio reported that the prevalence of self-reported glaucoma among Canadians over 40 years of age was 2.7% (3.9% for ages ≥50 years), which is higher than the results derived from population studies in the USA (1.9%) and England and Wales (1.4%). This statistically higher prevalence rate seemed too high.  Worse, this was a survey that did not verify the validity of the responses.  We know (from the Risk Factors for Glaucoma Study) that most newly diagnosed cases are moderate or severe, so the actual prevalence of the disease is likely much higher than the prevalence of diagnosed cases.

We know that race, gender, and age are significant factors.  We know environment also plays a role, but this is not understood.  The goal is to determine the prevalence rate of glaucoma in Toronto.  Accurate statistics would be highly useful for policymakers, particularly if the actual numbers were departures from Western norms.

The findings suggest that the prevalence of undiagnosed glaucoma appears to be higher in Toronto when compared with prior estimates of overall glaucoma prevalence from other Western countries: Definite glaucoma (4.4%); Probably glaucoma (3.9%); Glaucoma Suspects (16%).   Further studies with larger numbers of participants are required to confirm this finding.  A larger study aiming to identify the prevalence of glaucoma in Canada has been designed and has been submitted to the Canadian Institute of Health Research for research funding.

Publication:
Anraku A, Jin Y, Butty Z, Jinapriya D., Alasbali T, Mammo Z, Flannagan J, Trope GE.  The Toronto epidemiology glaucoma survey – a pilot study.  Can J Ophthalmol. Aug; 46(4):352-7.

Population Based Trials on Glaucoma Risk Factors Meta-analysis

Status: Enrollment closed
Description:
There have been many population based studies around the world of glaucoma and its risk factors.  The studies have therefore been done with different populations (race, environments, lifestyles, etc.) and have not all come to the same conclusions.  With so much variation, it is hard for practitioners to know or text books to agree as to what the risk factors really are.  Though there is some consensus about some risk factors (high ocular pressures), there has been no consensus on any of the attempts to quantify or order the risk factors.

The goal of this project is to develop odds ratios and relative risk statistics for risk factors and ocular findings as they pertain to glaucoma.

The study attempts to improve the understanding and methodology in the field of Ophthalmology.  This was the first published meta-study of its type in the field.

Evaluation of Investigator Bias in Industry Funded Clinical Trials of Latanoprost

Status: Enrollment closed
Description:
The study attempted to improve the understanding and methodology in the field of Ophthalmology.

Prostaglandin analogues (PGA) are synthetic molecules which are manufactured to bind to a prostaglandin receptor.  They are used in the management of open-angle glaucoma, where they reduce intra-ocular pressure (IOP) by enhancing uveoscleral outflow and may also have some effect on the trabecular meshwork.  Within this class, the 3 most commonly used are Latanoprost 0.005% (Pfizer), Travoprost 0.004% (Alcon) and Bimatoprost 0.03% (Allergan).

A number of studies have been published with dissimilar conclusions.  There was a suspicion in the ophthalmology community that drug company sponsorship may be influencing and impacting the integrity of the studies.  If present, this type of bias would result in exaggerated intraocular pressure (IOP) lowering reported by the sponsoring company for their own PGA and perhaps smaller IOP lowering effects for a competing PGA.

A study (Alasbali et al.) found that in 62% of published PGA trials sponsored by the pharmaceutical industry, the abstract conclusions were not in keeping with the results of the main outcome measure.

The goal of this project is to determine if sponsorship of PGA clinical trials results in investigator bias for IOP measurements.

We found that when comparing Randomized Control Trials of similar quality, regardless of who the study sponsor was, IOP lowering effect of Latanoprost was the same, suggesting no bias at the procedural level.  This is useful in that the intraocular pressure measurement data presented in Randomized Clinical Trials can be regarded as being free of bias.  Furthermore, it is important for the reader to look at the results and form their own conclusions and not trust the conclusions listed in the article, because the conclusions have been shown to be prone to bias depending on who the sponsor of the study is.

Publication:
Jinapriya D., Anraku A., Alasbali T., Trope G.E., Buys Y.M.  Evaluation of investigator bias in industry funded clinical trials of latanoprost.  Can J Ophthalmol. Dec; 46(6):531-6.

Risk Factors for Glaucoma Study

Status: Enrollment closed
Description:
The study attempted to improve the understanding and methodology in the field of Ophthalmology.

Glaucoma is a disease in which the optic nerve is damaged, leading to progressive and irreversible loss of vision.  It is often associated with increased pressure in the eye, but large population based studies on Western populations has demonstrated that only 50% of patients with primary open angle glaucoma actually have elevated ocular pressure.

The goal of this project is to determine what the risk factors for glaucoma in Canada are.  Understanding these risk factors might help treatment development programs and would certainly improve diagnostics (particularly if the risk related parameter is easy to measure or assess).

We found that cup-to-disk ratio, corneal thickness, intraocular pressure, visual field, and retinal fiber layer thickness are all significant risk factors for glaucoma.

We also found that glaucoma is not caught early enough in Canada, with the majority of patients being referred from Optometrists to Ophthalmologists and many having moderate to severe glaucoma at their initial presentation to the Ophthalmologist.  A better understanding of risk factors for glaucoma and a better ability to diagnose glaucoma is required amongst primary eye care practitioners.