An Open-label Extension Of A Randomised Clinical Trail Of Intravitreal Triamcinolone For Diabetic Macular Oedema
Funder
National Health and Medical Research Council
Funding Amount
$167,733.00
Summary
A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, ....A 25 fold increase in the risk of going blind on diagnosis of diabetes is one of the most daunting threats that patients face. Most cases of vision impairment in diabetes are due to macular oedema that persists or recurs after laser treatment. There are now a number of uncontrolled, anecdotal reports that intravitreal triamcinolone (IVTA) is highly effective for the treatment of diabetic macular edema which is refractory to conventional laser treatment. We commenced the first placebo-controlled, double masked clinical trial of intravitreal triamcinolone for refractory macular oedema in 2002. The 3 month results from this study provide the first scientific proof of principle that intravitreal triamcinolone reduces macular thickness and improves vision. The two year results will be available in March 2005, but confidential interim analysis of efficacy data in September 2004 suggested that the beneficial effect of triamcinolone treatment persisted. Thus it appears that treatment with intravitreal triamcinolone may be the most significant development for the prevention of blindness in people with diabetes since the introduction of laser treatment. It would also be a highly cost-effective intervention that could be administered by general ophthalmologists. The treatment cannot be recommended for routine use, however, until its long term efficacy and safety have been established. Since we already have a well studied group of patients who have received treatment for 2 years, we are in a unique position to extend the study in order to provide the long-term (5-year) safety and efficacy data that does not appear to be forthcoming from any other source. The results of this study will significantly improve knowledge of long-term outcomes of local high dose steroids for diabetic macular oedema, allowing the treatment to be used more rationally. Thus the study is very likely to directly reduce the risk of blindness in people with diabetes.Read moreRead less
Modulation Of Endothelial Junctions As Selective Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$911,387.00
Summary
We have developed a new drug (CD5-2) that targets the junctions of endothelial cells, the cell that lines all vessels. CD5-2 reduces oedema in diseases such as diabetic retinopathy and tumours. Thus it has potential as a new therapeutic in chronic inflammatory diseases where leaky blood vessels are central to the pathology. This grant will provide fundamental understanding of how CD5-2 induces such profound effects to alter the levels of oedema and alter inflammatory cell infiltrates in tissues.
Improving Clinical Translation In Stroke: Targeting Cerebral Oedema In A Large Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$637,530.00
Summary
A common and life-threatening complication of stroke is brain swelling which is the leading cause of death within one week of stroke and a predictor of poor outcome. Current treatments for brain swelling are inadequate. We have developed a drug that blocks the action of the neuropeptide substance P, which is involved in the development of swelling. We will assess the efficacy of this treatment to reduce brain swelling and improve long-term outcome in a relevant pre-clinical model of stroke.
Blood-Spinal Cord Barrier Structure And Function In Syringomyelia
Funder
National Health and Medical Research Council
Funding Amount
$82,630.00
Summary
Syringomyelia is a disorder in which a fluid-filled cyst forms within the spinal cord. These cysts expand over time resulting in paralysis or even death. Syringomyelia occurs in association with spinal cord injury and a number of congenital conditions. In this project we aim to investigate the underlying cause of cyst formation, which is currently unknown. It is hoped that these studies will improve our understanding of cyst formation and facilitate development of better treatment strategies.
The aim of this project is to better understand the events that cause the onset of uveitis, a common cause of visual impairment and blindness in adults. Toll like receptors (TLR) are a new group of cell surface receptors tinflammatory mediators.hat are important in immune function and the immune system's ability to recognise and respond to to microbes by recognising signature molecules contained in microbes. The TLR system is the early warning system of immune defence and activation of the TLR s ....The aim of this project is to better understand the events that cause the onset of uveitis, a common cause of visual impairment and blindness in adults. Toll like receptors (TLR) are a new group of cell surface receptors tinflammatory mediators.hat are important in immune function and the immune system's ability to recognise and respond to to microbes by recognising signature molecules contained in microbes. The TLR system is the early warning system of immune defence and activation of the TLR system induces the generation of multiple mediators that initiate and perpetuate inflammation. There has been intense interest and research into this novel family of receptors and they have been shown to play an important role in human diseases such as inflammatory bowel disease and psoriasis. The role of TLRs in uveitis has not been studied. We hypothesise that TLRs play a central role linking certain bacteria and the induction of uveitis. TLR4, a member of the TLR family has been clearly identified as the key receptor for cell wall components of gram negative bacteria (a chemical called LPS). In vitro data shows that TLR4 stimulation by LPS causes the release of inflammatory mediators. This project is designed to study the expression of TLRs in the eye, factors that control their expression and the results of stimultaing TLRs with their target chemicals. Better understanding ofd the causes and mechanisms of uveitis will allow the development of more specific and effective treatments.Read moreRead less
Gene Profiling To Develop A Neuroprotective Strategy In A Large Animals Model Of Following Ischaemic Stroke.
Funder
National Health and Medical Research Council
Funding Amount
$359,897.00
Summary
Stroke affects 15 million people worldwide each year. At present, the diagnosis and treatment of stroke is not optimal. The use of gene profiling may provide us with information that could allow us to more accurately identify individuals at risk of stroke, predict stroke outcome and effectively treat stroke patients. In addition, by using a targeted approach to therapy we have the potential to reduce brain swelling and improve outcome following stroke with neuroprotective agents.
A Multicentre Randomised Clinical Trial Of Laser Treatment Plus Intravitreal Traimcilone For Diabetic Macular Oedema
Funder
National Health and Medical Research Council
Funding Amount
$529,500.00
Summary
A diagnosis of diabetes immediately confers a 25 fold increase in a person's risk of blindness. The macula is the vision centre of the retina, which is like the film in a camera. In people with diabetes, swelling of the macula (macular oedema) due to leakage of retinal blood vessels is the commonest cause of loss of vision. Laser treatment is proven to be helpful in reducing the risk of vision loss in eyes with diabetic macular oedema (DMO), but it does not work in 40% of cases. Injection of slo ....A diagnosis of diabetes immediately confers a 25 fold increase in a person's risk of blindness. The macula is the vision centre of the retina, which is like the film in a camera. In people with diabetes, swelling of the macula (macular oedema) due to leakage of retinal blood vessels is the commonest cause of loss of vision. Laser treatment is proven to be helpful in reducing the risk of vision loss in eyes with diabetic macular oedema (DMO), but it does not work in 40% of cases. Injection of slow release steroids is an emerging revolutionary treatment for DMO. We are the first in the world to perform a randomised clinical trial of triamcinolone injection into the eye with DMO that has failed laser treatment. A randomised clinical trial is when an equal number of eyes are randomly allocated to the treatment and placebo (no treatment) groups, so that none of the patients or the doctors knows whether each particular eye is receiving treatment or placebo. The preliminary results of our study in progress have proved that, at least in the short term, intravitreal triamcinolone (IVTA) leads to reduction of macular oedema and improved vision. We now propose a two year randomised clinical trial to test whether the combination of IVTA with laser treatment will result in a further improvement in vision in eyes with DMO. We are in a unique position to conduct such a study, having recently concluded the world's first randomised clinical trial of IVTA for wet age-related macular degeneration in 151 eyes. We have extensive experience of IVTA's significant but manageable adverse event profile. The Australian Retinal Collaboration is a group of academic retinal specialists who are committed to attaining the highest possible standards in clinical research in Australia for common blinding conditions of the retina. The results of the proposed study are likely to lead directly to a reduction of the risk of vision impairment and blindness in people with diabetes.Read moreRead less
Pharmacological Strategy For Blocking Lung Cell Damage By Toxic Smoke Constituents.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, ....People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, where the lung is flooded with fluids and is unable to perform its respiratory function. At present, the clinical approaches used to treat smoke inhalation victims are mostly directed against offsetting the symptoms of lung injury and do not take into account the role of lung cell injury by toxic substances in smoke such as acrolein. This project will provide a better understanding of the chemical events underlying the injury caused by smoke to lung cells, and also into possible drug strategies for treating victims of smoke inhalation. The work will explore the ability of a range of compounds that are chemically related to a blood pressure-lowering medicine (hydralazine) to protect lung cells against such smoke-induced damage. The work will employ a range of modern research techniques to understand the events occurring in lung cells exposed to smoke. Once this is understood, these approaches will be used to test the various drug compounds for their abilities to prevent the death of cells exposed to smoke or its toxic constutuent acrolein. This work will yield new information on a series of compounds concerning their ability to block the toxicity of smoke to lung cells. The goal is to identify one or two molecules that can be carried forward to testing in smoke-exposed animals.Read moreRead less