CERA Age-related macular degeneration- (AMD) information forum

Hosted by Professor Robyn Guymer Head of the Macular Research Unit, Centre for Eye Research Australia (CERA) Topics to be covered: “Hope in sight: new treatments for dry AMD” Dr Katarina Creese, Research Fellow, CERA “Update on the nanosecond laser” Pyrawy Sivarajah, Clinical Trials Orthoptist, CERA “Looking forward: the future of AMD treatment” Professor Robyn Guymer, Head of Macular Research Unit, CERA Q&A panel discussion With the speakers about their presentations or broader AMD research

Age related macular degeneration (AMD) Drusen extracellular of lipid rich aggregates Normal macula Early stages of AMD-

Age related macular degeneration (AMD) In the disease AMD you end up with a moth eaten hole in the retina or a big scar due to bleeding This causes this to happen with your vision. Late stage disease results in legal blindness < 6/60

Lucentis clinics and injecting rooms Because we weredoing trial injecitons for ytears we were well able t omake the transition to the clinic with getting injectiong rooms set up and protocols in place such that the eand e was unitl recently the only public hospital offering free lucentis in Aust

Hope in sight: new treatments for Geographic Atrophy Dr Katarina Creese, Research Fellow, CERA

Geographic atrophy Geographic Atrophy (GA) is a disease characterized by thinning and loss of the retinal pigment epithelium and concurrent atrophy of photoreceptors and choriocapillaris. Clinically, GA is characterized by islands of dead retinal cells in the back of the eye that gradually expand. GA - endstage, advanced form of AMD RPE - important for metabolism of the photoreceptors, hence if RPE dies, photoreceptors die as well - loss of vision GA very slowly progressing condition, VA can be affected after a very long time when the atrophy involves the centre of vision.

Wet AMD - fluid under the retina

Color Fundus Photograph Fundus Auto Fluorescence SD OCT Infrared Fundus Imaging Fluorescein Angiogram Multimodal imaging State of the art imaging is required to be part of new studies looking at dry AMD and early AMD. New endpoints are being identified and evaluated which would allow to detect the progression of GA much earlier. Unlike wet AMD where change in vision is the main endpoint. It is thanks to the new methods of medical imaging we are able to measure the size of the atrophic lesions. This is important as the current GA treatment studies measure the change in size of the lesions and thus effectiveness of the tested drug.

Multi-modal imaging Fundus Auto Fluorescence new endpoint: rate of growth of GA Need state of the art imaging to be part of new studies as looking at dry AMD and early AMD, need new endpoints. Not just VA as in wet AMD,

IR, early FFA

Two examples of acceptable areas of GA Note: The boundaries of the circles are: inner 1000 μm; middle 3000 μm, outer 6000 μm

Trials in Geographic atrophy Four trials at CERA natural history (Proxima A,B) investigational drugs inhibiting complement system (Spectri/Chroma and Filly) known medication - testing its neuroprotective effect and reduction of progression of GA (Beacon) Natural History - proxima A,B - patients who have GA. No treatment, bloods for genetic testing, tested every 6 months for a progression of GA Spectri and Filly - trials testing medication influencing the complement. C is a part of our immune system, but if overactive, inflammation can damage surrounding healthy tissues. Aim of these new medication is to slow down or stop the undesired inflammation and reduce the growth of GA Brimonidine - well established drug for treatment of glaucoma. protects nerve cells including photoreceptors, from damaging influence of inflammation. It is believed that it has influence on the pathway slowing down the apoptosis, pre-programmed dying of retinal nerve cells. Special applicator, slow release)

Stem cell treatment Types of stem cells human embryonic stem cells adult stem cells induced pluripotent stem cells hESC - removed from an embryo in-vitro, can be cultured to any type of cell Adult stem cells - from bone marrow or umbilical cord blood, less able to differentiate than hESC iPSC - from skin or retina, limited ability to differentiate

Stem Cells retinal pigment epithelium - helps with metabolism of photoreceptors. Stem cells - production of new RPE cells or RPE and photoreceptor cells. Advanced Cell Technology (Ocata) - transplant of RPE derived from hESC in patients with advanced AMD and Stargardt’s disease. Injection of stem cell derived RPE cells in the sub retinal space during a surgery. Patients reported stable vision. the eye is “immunoprivileged” - able to tolerate foreign antigens without an immune response. The subretinal space is protected by the blood-ocular barrier, and is characterised by antigen-specific inhibition of both the cellular and humoral immune responses. Also,for locally delivered, intraocular treatments, low doses are needed compared with systemic therapies.

X Aim: Preventing vision loss Early stages of AMD Late stage AMD Drusen and pigmentary abnormalities Late stage AMD Neovascular “Wet” AMD Atrophic or “dry” X a major aim in AMD research is to slow or prevent the progression of AMD from early changes ot vision threatening late AMD

Laser Intervention in Early Age Related Macular Degeneration Pyrawy Sivarajah, Clinical Trial Orthoptist, Macular Research Unit

AMD Age-related macular degeneration (AMD) is the leading cause of vision loss in Australia. Affects people aged 50 years and older

AMD Late AMD Wet AMD Dry AMD Early AMD

AMD treatment for Late AMD Wet AMD Intravitreal anti-VEGF injections Dry AMD No effective treatment available

LEAD Trial The world first Pilot study of the Ellex nanosecond laser in the treatment of Early AMD showed promising results Reduction of drusen Improvement in Macular function

LEAD Trial – Study aim To determine whether the 2RT Nanosecond laser can slow or partially reverse the progression of the disease, before any late changes develop.

LEAD trial - 2RT nanosecond laser by Ellex Nanosecond pulsed laser Uses very low energy levels Targets the pigmented cells within the retina that have been affected by AMD Causes change in pigmented cells Healthy cells will divide and bridge over the gap the laser has left New cells will function to clear away the debris Doesn’t leave burns (current retinal lasers do) Painless

LEAD Trial – Study protocol World’s first multi-centred, randomised control trial of nanosecond laser in the treatment of early AMD double-masked clinical trial Duration of 3 years 6 month follow-up Full comprehensive eye exam Vision testing Multimodal imaging Macular function testing Retinal exam performed by ophthalmologist

LEAD Update CERA (Melbourne) = 162 Lions Eye Institute (Nedlands, WA) = 50 Marsden Eye Research (Sydney) = 33 Heriot Eye Care (Melbourne) = 20 Adelaide Eye and Retinal Centre (Adelaide, SA) = 17 Belfast Heath and Social Care Trust (Belfast, Northern Ireland) = 10

LEAD Update Recruitment finished March 2015 Approximately 350 people screened at CERA site alone Total number of participants enrolled = 292 Some participants have already completed the study Expected year of completion – April, 2018

Subhead 1 Italic Sub • Bullet points 18 pt text Once identified as potential trial patient they are taken out of the busy clinic by one of my research co-odinators and everything therefafter occurs with certified, trained interantionally accredited trial staff

Teaching optometry, getting ready for new trials TRRRiC = treatment ready research ready eye clinic

Monitoring progression of disease Years What about monitoring progression from early to late this process takes years , wait a long time in trials for endpoints

New findings on OCT scans Nascent GA Reticular pseudo drusen

Home monitoring and remote surveillance

Thank you for coming ANY QUESTIONS