2004-2005 Research Grants

Understanding Glaucoma in Menopausal Women

In the last few years, research has found a relationship among hormones, menopause and glaucoma. Recent studies suggest that menopause might be one of the causes of glaucoma. In 2001, reports indicated that women who go through menopause before the age of 45 have a higher risk of developing primary open-angle glaucoma and that estrogens or hormone replacement therapy might protect against it.

These findings led Dr. Mark R. Lesk, a glaucoma specialist, and his PhD student, Ms Micheline C. Deschênes at the University of Montreal to investigate the effect of menopause on the retina and optic nerve in relation to glaucoma. They found that a group of menopausal women who do not suffer from glaucoma and never used estrogen replacement therapy have reduced retinal blood flow and a thinner retinal nerve fiber layer (two clinical signs in the development of glaucoma) compared to a group of women who were on estrogen replacement therapy.

Since estrogens are known to improve blood flow in arteries and protect brain cells, the two scientists believe that a decline in estrogen level throughout menopause may have a negative effect on the retinal and optic nerve circulation and the retinal ganglion cells and nerve fiber layer of the eye in menopausal women, and that estrogen replacement therapy may be protective.

This year’s research grant allows Dr. Lesk and Ms Deschênes to study the retinal and optic nerve structure and blood flow in menopausal monkeys on estrogen and in a group not on estrogen.

Proposal Title:
Estradiol and Soy Phytoestrogen: Investigation of their Vasodilator and Neuroprotector Properties on the Retina and the Optic Nerve in Monkeys by Histological Studies

Authors:
Dr. Mark Lesk, Micheline Deschenes, PhD Student

Using Digital Images to Screen for Glaucoma

Canadians with glaucoma in rural areas may be under diagnosed because of a shortage of eye care professionals. Tele-medicine and recent technological advances in optic nerve imaging have made it possible to assess people for glaucoma even if they don’t have access to an ophthalmologist.

In this study, patients will have their optic nerves photographed stereoscopically with an ophthalmic digital camera. These stereoscopic images will be downloaded over the Internet onto a secure server, and then uploaded to an image-reading centre in another location. An ophthalmologist will examine the stereoscopic optic nerve images on a computer using special software to look for changes seen in glaucoma. These results will be compared to the current gold standard of 35mm stereoscopic slides and a hand-held stereoviewer to diagnose glaucoma.

If the results are comparable, screening people in under-serviced rural areas by sending their digital optic nerve images to a reading centre may help combat glaucoma.

Proposal Title:
Comparison of Stereoscopic Digital Photography to Stereoscopic 35mm Slide Photography in Assessment of the Optic Nerve in Tele-Glaucoma

Authors:
Dr. Iqbal K. Ahmed M.D., FRCS(C), Dr. Paul Sanghera M.D

Assessing the Two Most Common Glaucoma Drainage Implants

The only treatment to prevent visual loss in glaucoma is by lowering eye pressure – typically with medications and lasers. If these therapies don’t work, surgery is needed.

Drainage implants have been used for over 30 years for eyes in which glaucoma surgery has failed, or in certain types of high risk glaucoma. Often, a patient getting drainage implants has a very advanced and complex disease, requiring major surgery to preserve what little eyesight remains. In a glaucoma drainage implant, a small silicone tube is inserted into the eye and fluid passes through it into a reservoir placed on the eyeball.

Two implant devices are predominantly used in North America:

the Ahmed implant which consists of a valve to help control pressure, and
the Baerveldt implant which does not have a valve and has a different timing mechanism for releasing fluid from within the eye.
This is the first well-designed, prospective, and randomized study to clarify which implant is more effective in reducing intra-ocular pressure and which has fewer side effects.

Proposal Title:
Prospective Randomized Study Comparing the Ahmed Glaucoma Valve and the Baerveldt Glaucoma Device

Authors:
Dr. Iqbal I Ahmed, Dr. Christoph Kranemann, Dr. Baseer Khan, Dr. Khalid Hasanee

Studying New Anti-Glaucoma Medications on People of Different Ethnicities

Over the past few years, several new anti-glaucoma medications have been approved for use in Ontario. Three of them – Xalatan, Travatan, and Lumigan – comprise the prostaglandin/prostamide class and are effective and safe medications for lowering elevated eye pressure, or intra-ocular pressure.

Several large multi-centred trials have shown that lowering intra-ocular pressure reduces the rate of glaucoma damage. Most of these studies have been performed with patients mainly from European or Caucasian ethnic backgrounds. Because these drugs may act differently in people with different ethnic backgrounds, this research will study and compare the effectiveness and safety of these drugs in people from five major ethnic groups – Caucasian, African, East Indian, Asian and Hispanic.

Proposal Title:
Prostaglandin Efficacy and Safety Study Undertaken by Race (PRESSURE)

Authors:
Dr. Catherine Birt, Dr. Iqbal I. Ahmed

Studying the Effect of Inhaling Large Amounts of Carbon Dioxide on Blood Flow in the Eye

Some people with glaucoma may have unstable or inadequate blood supply to the retina suggesting impaired vascular function. Inhaling enriched oxygen or safe amounts of carbon dioxide can induce blood vessel narrowing or widening and allow assessment of the reactivity of the blood vessels at the back of the eye or retina.

Using non-invasive techniques, this study will determine the effect of breathing excess amounts of carbon dioxide on the reactivity of the retinal blood vessels of patients with glaucoma and of age-matched subjects without glaucoma.

Proposal Title:
Retinal Vascular Reactivity in Response to Isoxic Hypercapnia in POAG

Authors:
Dr. Chris Hudson, Dr. John Flanagan, Dr. Subha Venkataraman

Understanding the Environment in which Optic Nerve Cells Survive and Die

In glaucoma, the nerve that connects the eyeball to the visual processing centre of the brain becomes damaged. This optic nerve is made up of almost a million nerve cells that form a portion of the retina – the seeing part of the eye. Adjacent cells in the retina protect these delicate nerve cells. Some cells keep the retina free from a harmful imbalance of light and chemicals. If these cells cannot perform these protective functions, the delicate nerve cells become damaged.

This research project will provide a better understanding of the environment in which optic nerve cells survive and die. Identifying specific stressors such as those induced by harmful types of oxygen and their effect on the environment of the nerve cells may provide clues to what causes nerve damage.

Currently, there are no available treatments to rescue an injured optic nerve. Discovering the cause of the nerve damage could lead to therapies that would prevent injury to a healthy nerve, rescue an injured nerve, and perhaps resuscitate portions of a dead nerve.

Proposal Title:
The Role of p38 Mitogen-Activated Protein Kinase in Human Retinal Pigment Epithelial Cells Under Oxidative Stress

Authors:
Dr. Cindy M.L. Hutnik, Tianqing Peng and Qingping Feng

Exploring Protein Abnormalities in Glaucoma

Glaucoma is associated with elevated pressure within the eye. High intra-ocular pressure can block the transport of essential proteins in the optic nerve, the major connection between the eye and the brain. This blockage is implicated in nerve cell death in glaucoma.

In untreated glaucoma, nerve cell death extends from the eye to major vision centres of the brain. The spread of disease from nerve cells to connected nerve cells in the brain, and abnormal proteins such as Aß-amyloid, and tau, are hallmarks of some neuro-degenerative diseases.

This project will explore the possibility that these underlying protein abnormalities exist in glaucoma. Knowledge of Aß-amyloid and tau protein pathologies in glaucoma will have a major impact on understanding the disease processes, and may lead to new therapeutic strategies that target abnormal proteins and prevent blindness from glaucoma.

Proposal Title:
Amyloid and Tau Proteins in Human and Experimental Glaucoma

Authors:
Dr. Yeni Yucel, Dr. Neeru Gupta

Developing a “Flicker” Visual Field to Detect Early Glaucoma and Monitor Vision Changes as the Disease Progresses

Evaluating a patient’s peripheral visual function (visual field) is essential for both detecting and managing patients with glaucoma. Standard clinical techniques often only show repeatable defects after up to 40% of the eye’s nerve fibres have been lost.

The major problem with detecting early functional loss is the noisy results received when testing the visual field. New techniques such as short wavelength automated perimetry and frequency doubling perimetry have selectively tested specific aspects of vision and detected some glaucoma defects early.

In another technique, a visual illusion called the phantom contour is generated using a very fast, flickering border. It appears as a dull edge or contour and can be used to create simple shapes and patterns. These patterns are called flicker defined form (FDF). FDF has been successfully used to screen for glaucoma using a letter-based test.

This project will develop a FDF-based visual field test with the potential to detect early functional loss in glaucoma and monitor change in visual function as the disease progresses.

Proposal Title:
Clinical Application of Flicker Defined Form

Authors:
Dr. John Flanagan and Dr. Patrick Quaid