The purpose of this project is to record information about how AMD is managed using both existing and these new treatments, and about which combinations of treatments have the best results. We will develop guidelines for ophthalmologists to use to provide the best management for their patients with AMD. We will also use the results to determine whether the new treatments are safe and effective.

Another component of the project involves linkage of databases for drug use, deaths and hospital separations with the aim of tracking possible systemic complications of the new treatments.

The Project is a collaborative initiative between the Save Sight Institute, Sydney; Centre for Eye Research Australia, Melbourne; and Lions Eye Institute, Perth and will also involve up to 12 private ophthalmology practices. Funded by the Royal Australian and New Zealand College of Ophthalmologists’ Eye Foundation. Additional funding is also sought.

Link: FRB! website

This study is investigating the effects of an anti-Vascular Endothelial Growth Factor substance which possibly inhibits new vessel growth and leakage associated with age-related macular degeneration. Seven patients are enrolled at the Save Sight Institute. Recruitment has closed.

A 2 year clinical trial comparing a slow release pellet of brimonidine tartrate to sham (pretend) injection into the vitreous (jelly) of the eye to study its safety and effectiveness in the treatment of dry macular degeneration. Due to commence early 2009.

A 24 week clinical trial of an investigational drug injected into the vitreous (jelly) of the eye in combination with standard ranibizumab therapy to study the safety and tolerability of this combination of treatments in the treatment of wet age related macular degeneration.

This study aims to identify how treatment with a particular steroid (intravitreal triamcinolone) is best combined with conventional laser photocoagulation for the treatment of diabetic macular oedema. Fifty four patients are enrolled in the study. Recruitment has closed and data are being analysed.

A 3 year clinical trial comparing an oral tablet to placebo tablet to study the effectiveness in reducing macular edema associated with diabetes mellitus. Due for completion February 2009.

A 3 year clinical trial comparing a slow release pellet of dexamethasone to a sham (pretend) injection which is injected into the vitreous (jelly) of the eye to study its safety and effectiveness in treating macular edema associated with diabetes. Currently enrolling.

This open label study proposes to determine the effectiveness of ranibizumab in patients who have diabetic macular oedema, which is resistant not only to standard laser therapy but also the alternate steroid treatment (triamcinolone).

This study aims to determine whether ranibizumab alone or in conjunction with laser therapy is effective in preventing or recovering vision loss due to diabetic macular oedema.

This study is investigating a proposed new treatment for macula oedema secondary to branch retinal vein thrombosis. ranibizumab will be used in conjunction with laser treatment - the current therapy for this condition. This study is still open to recruitment.

This study is an international survey across 25 sites worldwide, aiming to develop new treatments for MacTel through better understanding of its clinical features. In particular we will identify how loss of vision occurs and investigate whether there is a genetic factor that contributes to the disease. First degree relatives of the participants (primarily siblings; secondarily parents) are included in a family genetics sub-study. The Save Sight Institute is a major centre in the study.

Link: http://www.mactelresearch.org

Dr Alice Len
Diabetes, a condition that affects close to 1 million Australians, was named the 6th leading contributing cause of death in Australia in 2002. It is a disease which can lead to a myriad of complications, one of which is diabetic retinopathy. Diabetic retinopathy is the primary cause of blindness in people of working age.

One of the earliest features of DR is a breakdown of the blood-retinal barrier. This leads to abnormal blood vessel growth and leakage of molecules from inner retinal blood vessels into the surrounding retinal tissues, resulting in swelling and loss of vision. We are using proteomic techniques to study the protein changes as a way to identify disease mechanisms in vitreous and retina from eyes with early diabetic retinopathy. We hope that this will result in new ways to prevent and treat loss of vision in people with diabetes.

Dr Alice Len
Macular telangiectasia is an eye condition affecting the retinal blood vessels by an as yet unknown mechanism and currently there is no recognized therapy. The disease is characterized by retinal capillary dilation and tortuosities, which subsequently leads to leakiness then eventually blindness from central retinal atrophy or neovascularisation.

Identification of disease biomarkers may lead to development of treatments to prevent and possibly reverse loss of vision from macular telangiectasia. This can be achieved by analyzing the vitreous humor and macula from patients with the condition.

Dr Weiyong Shen
The blood-retinal barrier (BRB) is formed by tight junctions between vascular endothelial cells and lack of fenestrations. The BRB breakdown is a key feature for a number of retinal diseases including diabetic retinopathy and age-related macular degeneration, in which vascular endothelial cells respond to abnormal expression of growth factors produced in pathological conditions.

This project aims to establish a reliable laboratory assay to model the BRB using cultured cells, and to test the effects of a number of factors that may contribute to or inhibit BRB breakdown.

Dr Weiyong Shen
Diabetic retinopathy is a sight threatening, chronic ocular disorder that develops with time in nearly all people with diabetes. Vascular endothelial dysfunction is an early feature of diabetic retinopathy. Bone marrow derived progenitor cells (BM-EPCs) are capable of differentiating into a variety of cell types including vascular endothelium and have physiological roles in the maintenance and rescue of the existing retinal vasculature. However, in diabetes the number of BM-EPCs is reduced and their functions are impaired.

This project aims to investigate the cellular and molecular mechanisms of BM-EPC dysfunction in diabetic retinopathy and to combat it from a novel angle via regulation of diabetic BM-EPCs for functional recovery.

Dr Weiyong Shen
Macular telangiectasis (MacTel) type 2 is a potentially blinding condition of the central retina. The predominant and most consistent clinical features in this retinal disease include loss of retinal transparency, vascular leak, small vessel telangiectasis, disturbance of photoreceptors and the retinal cavitation. Currently, the causes of MT are entirely unknown. Recent studies conducted by our group indicate that the primary defect in MT may reside in dysfunction of glial-neuronal-vascular interactions in the retina.

This project aims to investigate the relationship between glial dysfunction and retinal vascular abnormalities as well as neuronal damage. This is being tested in a number of ways including a glia-specific toxin, siRNA targeting glutamine synthatase (a key enzyme for retinal glutamine homeostasis) and viral vector-mediated gene transfer in several species including rodents and non-human primates.

Robert Rapkins
We have identified significantly elevated levels of β-catenin in the cytosolic fraction of diabetic rat retina. To date there have been no studies reported that have examined ?-catenin or Wnt signalling in the pathogenesis of diabetic retinopathy or any of the other complications of diabetes.

To further investigate the role of β-catenin and Wnt signalling in diabetic retinopathy we have employed the use of a Wnt focused PCR array in diabetic mice. Preliminary data has revealed that a range of Wnt signalling genes are up- or down-regulated in diabetic retinopathy. Moreover, we have been able to isolate the precise cell-type in which a number of these genes have displayed varied express patterns by immunohistochemistry.

Future investigations will focus on determining the precise Wnt pathway(s) affected by diabetic retinopathy in the hope of better understanding the mechanisms that underlie the aetiology of this debilitating disease, with the prospect of providing more focused drug targets.

Zhang, Gillies
Diabetic retinopathy is a severe sight-threatening complication of diabetes. Increased vascular permeability due to a breakdown in the blood retinal barrier (BRB) is one of the earliest detectable signs of diabetic retinopathy. Furthermore, there is evidence that the pathogenesis of diabetic retinopathy also has a primary neuropathic element.

Triamcinolone acetonide is a long acting steroid. In our 2 year, double-masked, placebo-controlled, randomized clinical trial, eyes with diabetic macular oedema that were treated with intravitreal injection of triamcinolone acetonide had twice the chance of improving vision and half the risk of further loss. However, the mechanism of the action of TA still remains uncertain.

Vascular endothelial growth factor-A (VEGF-A)/vascular permeability factor is believed to contribute to vascular leak in major retinal diseases such as diabetic retinopathy and age-related macular degeneration. The action of VEGF-A is mediated through its two cell surface receptors, FLT-1 and FLK-1. Inhibition of VEGF over-expression is thus a potential treatment for diabetic retinopathy.

Steroids treatment has been proved to protect retinal neurons, but little is known about the potential protective signaling cascade involved.

To find out how intravitreal steroid therapy effects diabetic retinopathy, we investigated the effects of intravitreal injection of TA on the expression of VEGF-A and its receptors at both transcriptional and translational levels, we then correlated the expression of these proteins with breakdown of the blood-retinal barrier. The neuro-protective effects of TA were further evaluated, in a rodent model of early diabetic retinopathy.