Project RPD: A pathway to translation: uncovering novel causes, genetic associations, and potential intervention strategies for AMD

This project aims to uncover the underlying aetiology of reticular pseudodrusen, (RPD) which we hypothesize are genetically determined and once identified, will provide critical information for developing new interventions and biomarkers to improve outcomes for those with high risk AMD.

This project is in collaboration with the research groups of Professors Erica Fletcher, Melanie Bahlo and Alice Pebay.

Laser intervention in Early stages of Age-related macular Degeneration (LEAD) study

The LEAD study is a 36-month, multicenter, randomized, sham-controlled trial of nanosecond laser used to slow progression of intermediate stage AMD. It reported the primary outcome in 2018. In participants with iAMD without signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving laser and sham treatment were observed.

However, subthreshold nanosecond laser treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. We continue to follow the majority of cases for 5 years and will see the last participants in mid 2020. (ACTRN12612000704897) and (NCT01790802).

Microperimetry in Atrophy Progression Study (MAPS)

This project examines whether a new method to measure the ability of to perceive different light levels within the area where tissue loss is occurring could help us better evaluate promising new treatments in atrophic AMD.

Predictive Imaging in the Early Stages of AMD (PRIME) Study

This prospective project aims to combine modern imaging methods including optical coherence tomography angiography (OCTA) and artificial intelligence to improve risk stratification and identification of high-risk AMD individuals to monitor more frequently to enable the early detection of neovascular AMD.

Multi-spectral functional imaging study

Subjects with early stages of AMD are often associated with poor night vision due to rod photoreceptor dysfunction. Currently, assessing rod photoreceptor function using a subjective psychophysical test is arduous, variable and lack of spatial resolution.

This project aims to develop a multi-spectral functional imaging technique for assessing rod photoreceptor function objectively with a high spatial resolution. The technique will allow better studying the disease pathophysiology and monitoring progression clinically.

This research is conducted in collaboration with A/Prof Peter van Wijngaarden and Dr Xavier Hadoux.

ASPREE: ASPirin in Reducing Events in the Elderly (ASPREE) trial: AMD substudy

A primary prevention, randomized clinical trial (in conjunction with Monash University, Professor John McNeil) investigating the effect of low dose aspirin on the incidence and progression of AMD.

AI collaborations

Using Artificial intelligence (AI) to analyse OCT images in AMD

With several different international academic groups and industry we work with leaders in AI research in AMD we are collaborating on finding ways to predict progression of AMD, to identify high risk characteristics and to develop automatic algorithm to allow high speed detection of these markers.

In addition we are working to understand the best protocols to use when considering treating neovascular AMD to achieve the best long term visual results with the minimum number of treatments.

International intervention trials

First in disease studies

MacTel Phase 3 Renexus (NT-501) Trial

This study investigates  the safety and efficacy of ciliary neurotrophic factor (CNTF) in participants with macular telangectasia type 2 (MacTel) in a Phase 3 clinical trial. NCT03316300

LASER LIGHT-01

Evaluation of the R:GEN Laser System as an Intervention in Subjects with Early Stages of Age-related Macular Degeneration (AMD) for Safety and Exploratory Efficacy Outcomes (Lutronics)

OcuDyne

The Primary study objective is to evaluate the safety and feasibility of the OcuDyne Ophthalmic Micro Balloon Angioplasty System in subjects with nonexudative age-related macular degeneration. ACTRN12619001315101 (OcuDyne)

International natural history trials

NEI-ARIS study

The ARIS aims to further characterise Reticular Pseudodrusen (RPD) and to further understand the progression of early AMD to late stage disease. NCT03092492

MacTel natural history study

This study enrols affected Mactel Type 2 people and their affected family members into a registry to learn more about the disease. The register is used to identify persons eligible for treatment trials.

IMPACT/SWAGGER

This trial aims to better understand the role of the choriocapillaris (CC) in the formation and progression of non-exudative AMD by imaging the retinal pigment epithelium (rpe) and the choroidal microvasculature and by studying their inter-dependence.

This study will determine if the loss of the CC could prove useful as an anatomic clinical trial endpoint in future drug trials. NCT03688243

Scope

An observational  study to evaluate the natural progression  of anatomical and functional visual parameters in genetically defined subjects with Geographic Atrophy (GA) secondary to.to AMD.NCT03894020 (Gyroscope)

Telescope

The objective of this study is to broaden the participation of community eye care professionals in identifying people with GA secondary to AMD so that they can be invited to participate in SCOPE.

Classification of Atrophy international consensus group (CAM)

As a part of the International classification of Atrophy group we work towards consensus documents to define AMD based upon new imaging criteria to enable researchers and industry to use agreed upon staging criteria for their own research objectives.

Community eye care

Online education course – “Age-Related Macular Degeneration for Primary Eyecare Practitioners”

We have recently completed an online course on the newest advances in AMD clinical management, designed for optometrists and primary health providers in the community.

The course was designed in collaboration with colleagues at the University of Melbourne, and is available here.

Community Eyecare professional trial network (CiTN)

We are working to develop a network of community based eye care professional to be part of a new way of recruiting for trials, and to provide ongoing, sustainable training and education in chronic eye diseases.

Preclinical research

We have a preclinical laboratory which works on models of AMD and retinal degenerations. The team works with biotech companies to perform early pre-clinical studies to advance them towards clinical trials.