Age-related macular degeneration (AMD) is a complex disease with many characteristics – which CERA Deputy Director Professor Robyn Guymer AM has dedicated her career to unravelling. 

One factor is the development of reticular pseudodrusen – small deposits that build up in the retina of some people diagnosed with the disease. 

“We thought these deposits were very rare, but with the latest imaging devices we now find them quite often in people, particularly during the late stages of age-related macular degeneration,” says Professor Guymer. 

“There is evidence to suggest that reticular pseudodrusen increases the risk of progressing to the late stage of the disease and with that, severe vision loss. 

“Additionally, in a study that aimed to slow down disease progression, people with reticular pseudodrusen did worse compared to those without.” 

Professor Guymer says that up to eight in 10 people with late-stage macular degeneration have reticular pseuduodrusen. 

“We really need to concentrate on this group as they appear to have a more sinister disease.” 

The Synergy High Risk AMD Study was established to understand exactly what these deposits are and why they are so bad for the eye. 

The five-year project with colleagues from the University of Melbourne and WEHI is now ending, and resulting in important discoveries. 

Genetic difference 

To learn as much as possible about people who have reticular pseudodrusen, CERA researchers coordinated the collection of images and samples from 14 different sites across the globe. 

“This was an enormous effort led by Dr Carla Abbott to harmonise how images of the eye were captured and graded, and collect genetic results,” says Professor Guymer. 

“This work has taken us five years which involved at times accessing other group’s images so that we could check that we’re all in harmony when looking for and defining that these deposits were present or not – which is not easy to do and agree on.” 

While CERA researchers have been coordinating this massive undertaking, colleagues at the University of Melbourne and WEHI have been developing and studying models of AMD and performing genetic analysis of samples. 

Collectively their work will hopefully lead to discoveries that will explain the cause of these deposits, leading to new avenues in treatment. 

Changing research

A cornerstone of their collective work is the discovery of one region of DNA that is strongly linked to the development of reticular pseudodrusen. 

This is a different region of DNA to that previously associated with AMD, representing a new pathway for the disease. 

Beyond genetic analysis, the scope of the project has resulted in many other achievements that can improve how AMD is understood. 

Dr Himeesh Kumar who completed his PhD during the project – supervised by Associate Professor Zhichao Wu – developed an AI algorithm that can detect and measure the amount of reticular pseudodrusen in people. 

Professor Guymer says that this work is an important step towards understanding AMD. 

“We know one gene that is associated with reticular pseudodrusen so now we need to determine what the gene regulates to better understand their cause. 

“We are now working to keep the impetus and experience of these research groups going so that together we can work towards more answers.” 

This story was originally published in Share our vision: Annual Review 2024.