After two years in limbo due to the disruptions of COVID-19, the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) made the difficult decision to move ahead with RANZCO Scientific Congress as a virtual event.
mivision asked ophthalmologists Dr Amy Cohn from Victoria and Dr Rushmia Karim from New South Wales to share their experiences attending RANZCO from the couch.
Diary of an Avid Learner
Dr Rushmia Karim
Rather than enjoying the sunshine while sipping iced lattes on the Southbank of Brisbane, for me RANZCO was about juggling family life and conferencing.
Although I know we are all missing the face-to-face, for those of us with young children, virtual conferences certainly are convenient. And, having become used to logging in to engage with the global ophthalmology community over the last two years, nothing felt foreign about attending this virtual event… a silver lining as a result of the pandemic.
Indeed, there was something comforting about browsing through the amazing posters at my own pace, over a coffee and sheltered from the chaotic weather outside my home.
I even tried the chat function and, while I was there, checked out a game which turned out to be an attendance brownie point score.
Points for asking a question and joining a chat seemed easy enough… but by the end of the day the winner had racked up more than 19,830 points compared to my piddly 250. Nevertheless, I felt my ranking in 40th place was acceptable.
CLOSING THE GAP AND GLOBAL CONTRIBUTIONS
Our Plenary lecture highlighted the inequality of access for ophthalmology services, especially in rural and regional areas. This has been exacerbated by the COVID pandemic, particularly among Indigenous communities. Acknowledging these access problems in both Australia and New Zealand is the first step towards closing the gap. Training in regional Australia, as well as exposure to paediatric ophthalmology which has experienced a chronic workforce shortage, may help us retain trainees in subspecialties in these areas.
The Dame Ida Mann Memorial Lecture, given by Professor Alex Hewitt, emphasised the high quality of research output by RANZCO fellows, which is contributing to eye care globally. The best papers by our next generation of ophthalmologists reiterated the high calibre of trainees, researchers and fellows in our midst – the future of research is in safe eyes.
The Congress lunch break – usually a highlight of the day – gave little opportunity to mingle with interstate colleagues, friends and current work mates. However, I took time to enjoy a quiet avocado and tomato salad with corn and broccoli followed by white coffee – my third for the day – and was thrilled when someone messaged me through the RANZCO chat function. It was a blast from the past and nice to re-connect.
I also took time to browse through the paediatric abstracts. Myopia is a pandemic in itself and it’s good to know newer interventions, such as 0.01% atropine eye drops, are a safe and effective (equivocal) treatment modality for reducing myopia progression, in terms of both spherical equivalent as well as axial length.
OCULOPLASTICS, PAEDIATRICS AND MORE
During my afternoon post-prandial slump, I enjoyed videos of oculoplastics with considerations of ectropion and entropion surgery using lateral tarsal strips and wedge excisions. The ptosis surgery summary stressed the importance of patient communication, setting expectations and the need for a detailed history. During a very visual lecture series, we were reminded not to overlook differentials like myasthenia gravis.
Professor Keith Martin, who has flown the nest of the Queen like myself, chaired the glaucoma Australian and New Zealand Glaucoma Society symposium. Who knew discussions regarding drop compliance with Professor Goldberg would be so entertaining? Pliers for drop therapy? Wow, these might need to come in a glaucoma starter pack given that one sixth of patients are unable to put drops in the eye. This alarming statistic makes it imperative to offer alternative strategies, like selective laser trabeculectomy for long-term glaucoma care. Patient communication is also key, as Dr Frank Howes emphasised.
The pitfalls of optical coherence tomography (OCT), part one, by Professor Helen Danesh- Meyer, was a whirlwind education session. OCT is one of the most important tests for glaucoma nerve assessment, however the machine has ‘no brain’, so we need to use our own. It’s good to be reminded that while we have many tools and aids in our clinical practice, looking at the whole picture and pattern of progression is key.
A rapid fire summary on OCT angiography (OCTA) highlighted how far we’ve come from the days when the only imaging we had was our slit lamp. I was amazed by the precision and clarity of the foveal avascular zone (FAZ) and vessels for the diagnosis and management of diabetic retinopathy. This modality can image capillaries and capillary non-perfusion and can track new changes in vessels. OCTA doesn’t detect diabetic macular oedema directly, but the cross sectional OCT provides this information and thus, both image modalities are complementary. It’s clear that OCTA could replace fundus fluorescein angiograms (FFA) in the majority of diabetic patients. Quantitative measurements, including FAZ, circularity, vessel density and intracapillary area, can be used in research output.
With a Bootylicious start to Congress’ Sunday morning, we heard from amazing speakers on the other side of the world who’d stayed up to take our questions on refractive and cataract training, as well as esteemed local colleagues who provided insights on astigmatic correction in the Norman McAlister Gregg Lecture. I have to hand it to Dr David Lockington: who knew I was performing the ‘Beyonce method’ when guiding registrars in cataract surgery? Having trained in London, Dr Lockington’s presentation brought back memories of injecting egg white into eyes and troubleshooting the simulator for left handed trainees like myself.
A presentation by Dr Damien Gatinel on Artificial Intelligence: Applications for Pathologies of the Anterior Segment of the Eye, reminded us that ophthalmology is at the forefront of big data and its potential clinical applications are mind-blowing. We must never close our eyes to emerging trends.
The Oria Plenary included presentations from a variety of subspecialties, from glaucoma progression predictive models, and graft free treatment for Fuchs’ corneal dystrophy, to the repair of mitochondrial mutations, all chaired by Professor Stephanie Watson.
Further boot camp presentations highlighted different cases of, and practical tips for, both mild to advanced glaucoma. Discussions regarding drop therapy, SLT and surgical interventions have continued to push the boundaries for prevention of sight impairment, but beware the odd visual field defect (on the rare occasion it may be neurological); if the pieces don’t fit, it’s important to think laterally.
While I, of course, remained alert for paediatric/strabismus and uveitis rapid fire sessions, I had my own paediatric kid sitting on my lap yelling at the screen. Thankfully, this was no problem as I could catch-up with on demand talks that were most relevant to my practice including optic disc swelling assessment in children, retinopathy of prematurity, and the hyperoxygenation drive, as well as the ever-increasing issue of myopia and the use of low dose atropine. The ability to do so highlighted the flexibility of this virtual format.
Day three arrived and Monday blues were wiped away with a full day of sessions on neuro-ophthalmology. I often say that neuro-ophthalmologists are the “cleverest of the bunch” and Lynn Gordon’s masterful talk on the complications of immune checkpoint inhibitor therapy for cancer really humbled me. It is so important to understand the adverse events associated with many new innovative treatment modalities. The afternoon neuro-ophthalmology course, chaired by Associate Professor Samantha Bell-Fraser, was a must for general clinicians, training registrars and orthoptists. Bread and butter topics of optic neuritis, multiple sclerosis, neuromyelitis optica, and giant cell arteritis were discussed, with presenters delving into the clinical presentation, investigations, diagnostic criteria and management modalities of each.
I always love a controversy and RANZCO didn’t disappoint with myopia control again at the forefront of the paediatric dilemma. Managing the expectations of anxious, motivated parents with limited data will continue to challenge our sub-specialty.
At lunch, I browsed through some of the refractive intraocular lens (IOL) talks I missed. It was good to see promising results with multifocal IOLs, and to be reminded of the need to always consider the patient in front of us. When I first started, toric IOLs were a rare entity and they are still hard to access in developing areas. Professor Lawless presented on the Vivity IOL in compromised corneas (Post LASIK, dry eye). The results show it behaves the same as a monofocal in terms of visual quality, provides a modest near improvement, and can be used at the surgeon’s discretion in these cases.
Alas, leave was cancelled for Tuesday and work awaited, so final sessions were moved to my ‘to do’ list for the ensuing weeks.
As the deadline for this paper loomed, I reflected on my time at RANZCO Congress; I’d been put through a whirlwind of innovation, creativity and education in the space of three days.
As someone who hasn’t been to a RANZCO Congress since I was a very junior doctor 12 years ago, I thoroughly enjoyed the talks, discussions and sense of community we feel in Australia. Of course, nothing can replace the face-to- face collegiality of the RANZCO conference, especially the chance to escape work and family life to become immersed in the collective education. However, the virtual platform canvased by RANZCO was easy to use and provided utmost convenience. I would applaud a hybrid model, where choice is available, for future conferences.
I was also impressed to see so many exceptional female leaders in our field of ophthalmology. While we can always do better (50:50) it was a step in the right direction in regards to equal representation and I look forward to more of our younger generation of women considering an active role in our RANZCO executive.
While sad that it’s over and we’re back to the reality of life, I can’t wait for Congress 2.0 in Brisbane in November 2022… and don’t forget, the presentations are available online until the end of May 2022 – I encourage you to visit some of the sessions missed and revisit others.
Dr Rushmia Karim BSc MBBS MMed (Ophthsc) MMed (Clinical Epidemiology) Hons Genomics (PG Cert) FRCOphth is a UK-trained ophthalmologist with over 10 years of experience. She specialises in children’s eye health and is a skilled surgeon, performing cataract, lens and strabismus surgery in both adults and children. She also has a special interest in neuro-ophthalmology. Dr Karim has an extensive research portfolio. She has performed and published systematic reviews including Cochrane reviews, randomised controlled studies and observational studies. Dr Karim consults at Vision Eye Institute in Chatswood, Drummoyne and Tuggerah Lakes (Central Coast) in New South Wales.
Notes from a Retinal Perspective
Dr Amy Cohn
The last two years have been full of firsts – the first pandemic in one hundred years, the first state-wide lockdowns, and the first virtual RANZCO congress. If you had asked me in 2019 if I thought a fully streamed, virtual conference would not only be possible but incredibly well run and a major educational highlight in the ophthalmology calendar, I would have had my doubts. How wrong I would have been! The congress was an absolute success. The lead time to move from an in-person congress to a virtual event was just on eight weeks. The congress organisers and RANZCO scientific committee pivoted quickly, and over 2,000 people registered for 10 courses and symposium, seven rapid fire sessions and nine keynote addresses in an action packed 4.5 days!
As a retinal specialist, it was fantastic to hear so many talks – both from our extraordinary local talent and our invited overseas speakers. Here is a snapshot of what I enjoyed over the four-day event.
OCT-ANGIOGRAPHY IN RETINAL DISEASE MANAGEMENT
There was a full symposium dedicated to use of optical coherence tomographyangiography (OCT-A) in retinal disease management in 2022. Four speakers gave an excellent summary of not only the principles of OCT-A but its current applications. The main advantages of OCT-A are real time, in-vivo visualisation of the retinal and peri-papillary vessels, including down to the capillary level. Unlike tradition fluorescein angiography, OCT-A can image both the deep and superficial capillary plexi, allowing greater understanding of retinal perfusion. It is incredibly quick to acquire the images and critically, no dye is needed, instead using motion contrast to detect blood flow. Successive A scans of the same retinal location are captured and computed as volume scans. The difference in signals is detected and is due to movement of red blood cells within the vessels and is known as a decorrelation signal. These signals are then used to generate a decorrelation map, allowing representation of the different vascular networks within the retina. In addition, successive B scans are taken at fixed time intervals to generate decorrelation maps in the deeper retinal layers. Software then generates retinal ‘slabs’ for analysis. The segmentation of the slabs is based on reflectivity and texture of the retinal substance in healthy eyes. Segmentation can be affected by oedema, haemorrhage, drusen and any anatomical variation, such as staphyloma. As such, there is a certain learning curve associated with corrected segmentation analysis.
One of the perceived downsides of OCT-A is the large amount of artefact evident in the images. Projection artefacts, also known as decorrelation tails, are particularly important. These occur when blood flow and vascular elements on the superficial layer cast shadows onto the deeper layers, resulting in the appearance of false vascular networks on the en face images.
Despite some limitations, OCT-A remains an excellent addition to our imaging armamentarium. Superficial and deep vascular slabs, and foveal avascular zone imaging are excellent for vascular diseases such as diabetes. The ORCC slab (outer retina to choriocapillaris) is a great screening tool for the presence of choroidal neovascular membranes (CNVM) in age-related macular degeneration (AMD). Newer uses include looking for ‘white dots’ in posterior uveitis and imaging the peripapillary vessels in glaucoma, which can be affected before retinal nerve fibre layer (RNFL) thinning occurs on standard OCT.
Treatment for geographic atrophy (GA) due to AMD remains an urgent unmet need. There are several trials looking at potential therapeutics for GA, some of which were presented in this symposium
The application of OCT-A in the diagnosis and management of neo-vascular AMD (nAMD) was looked at in this session. It was discussed that all types of choroidal neovascular membrane (CNVM) can be identified using the technology – type 1 (‘occult’ or sub- RPE lesions), type 2 (‘classic’ or sub-retinal lesions) and type 3 (‘RAP’ representing an anastomosis between the retinal and choroidal circulations). Professor Paul Mitchell from Sydney presented his data for using OCT-A to image all newly diagnosed CNVM presenting to his practice in 2021. The group found that OCT-A detected the presence of a CNVM in 83.3% of cases. Difficulty in detection of CNVM occurred if there was significant geographic atrophy, a large retinal pigment epithelium (RPE) rip or media opacities. Additionally, there was excellent correlation between OCT-A findings for CNVM, with more traditional fluorescein and indocyanine green angiography.
An interesting clinical question is how we should manage sub-clinical (non-exudative) CNVM lesions. Professor Mitchell showed how OCT-A can be used to evaluate the important ‘double layer’ sign on OCT, which was first described by Sato et al in 2007. This is the appearance of two highly reflective layers on OCT representing a separation of RPE from Bruch’s membrane due to the presence of a CNVM. Importantly, there is no associated ‘fluid’, which often is the trigger for starting anti- VEGF therapy. The groups imaged 214 fellow eyes of patients with active CNVM requiring treatment and found subclinical CNVM in one in eight people. Long-term follow-up of these patients shows they are anywhere from four to 13 times more likely to convert to nAMD than eyes without subclinical disease. This begs the question – should we be treating these patients with asymptomatic disease pre-emptively with anti-VEGF? Conventional wisdom suggests not – but it remains important to be vigilant as these eyes are likely to convert to nAMD.
RAPID FIRE: RETINAL DISEASE MANAGEMENT
There were nine presentations in the rapid-fire sessions highlighting the latest research into retinal diseases.
Dr Lawrence Lee presented the Phase 3 NORSE TWO study results of ONS- 5010 bevacizumab monthly intravitreal injections compared to Ranibizumab for nAMD. ONS-5010 (bevacizumabvikg) has the potential to be the first ophthalmic bevacizumab solution approved by the United States Food and Drug Administration (FDA). While we are all familiar with the use of intravitreal Bevacizumab, it remains off label in Australia. The study met its primary endpoint, suggesting the proportion of patients gaining 15 or more letters was similar between the ONS-5010 and ranibizumab groups. This supports filing ONS-5010 for approval for use in management of nAMD.
Associate Professor Andrew Chang spoke about the Archway phase 3 trial of the Port Delivery System with ranibizumab (PDS) for neovascular AMD. The PDS has been approved by the FDA for management of nAMD in the USA but approval is pending in Australia and New Zealand. The PDS allows for continuous delivery of a modified form of ranibizumab via a permanent, indwelling, refillable ocular implant. The implant is surgically placed at the pars plana, and can be refilled in the clinic at pre-defined time intervals. The phase 3 Archway trial evaluated the safety and efficacy of the PDS with refill at 24 weeks compared to monthly intravitreal ranibizumab injections. The primary end point was best corrected visual acuity (BCVA) change. The PDS with modified ranibizumab met this end point after it was found to be non-inferior to monthly ranibizumab. The PDS procedure was well tolerated. There were five cases of endophthalmitis, 15 cases of vitreous haemorrhage and 11 cases of conjunctival erosions and retraction. The latter were addressed with flap revisions or partial thickness corneal grafts. Much has been learnt about optimal surgical technique for device placement, which has led to less post-operative complications. While not as straight forward as intravitreal injections, standardised surgical training and post procedural evaluations are an important part of optimising patient outcomes and minimising complications.
Treatment for geographic atrophy (GA) due to AMD remains an urgent unmet need. There are several trials looking at potential therapeutics for GA, some of which were presented in this symposium. Firstly, Professor Robyn Guymer reported on the systemic administration of IONISFB for the treatment of GA. AMD has long been associated with overactivity of the complement system. Genetic analysis has shown that specific activating Factor B (FB) polymorphisms increase AMD risk and inactivation of FB variants can protect against AMD. It is thought that FB is a key regulatory protein produced in the liver, and that a reduction in plasma concentrations of FB dampens the alternative pathway overactivity observed in patients with AMD. This makes it a potential target for AMD treatment. IONIS-FB is a novel RNA treatment that specifically targets the alternate complement pathway by reducing production of FB. It is delivered as an infrequent subcutaneous injection to treat bilateral GA. Professor Guymer presented results of a phase 1 study looking at the safety and efficacy of single and repetitive doses of IONIS-FB in healthy participants. There was shown to be a significant decrease in plasma concentration of FB levels in a dose dependant fashion and reduced alternate pathway activity in participants. This has led to the phase two GOLDEN study, which is a double-masked, randomised, placebo-controlled study enrolling 330 patients with GA to either sham injections or treatment with IONISFB. The end point measures will be change in GA size on fundus autofluorescence (FAF) and BCVA. The study is now enrolling and remains an exciting option for a devastating eye condition for which there is no current treatment.
Following on from her first talk on novel treatments for GA, Professor Guymer presented findings from the phase 3 DERBY and OAKS studies. These studies looked at the safety and efficacy of intravitreal pegacetacoplan for GA, which is a complement factor C3 inhibitor delivered intravitreally. The DERBY and OAKS studies were global phase 3 trials which randomised patients to pegacetacoplan monthly or every other month, compared to sham monthly or sham every other month. The primary end point was the change from baseline of size and GA at 12 months, as measured on FAF. The pegacetacoplan-treated patients receiving either regime reached their primary end point in the OAKS study but not DERBY. In the OAKS study, the monthly pegacetacoplan injection group showed a 22% reduction in growth of GA lesions at month 12 compared to sham, while the every other month pegacetacoplan regime had a 16% reduction. This was statistically significant. While DERBY did report a reduction in growth of GA lesions of 16% for monthly and 25% for every other month in the actively treated arms, this failed to reach statistical significance. In the pooled analysis for both studies, pegacetacoplan slowed GA growth compared to SHAM, supporting the phase 2 FILLY study of the same drug. Interestingly, pegacetacoplan demonstrated greater efficacy in patients with extrafoveal lesions at baseline. A small proportion of patients in all three groups developed exudative AMD during the study and were treated with standard anti-VEGF therapy. Both IONIS-BF and pegacetacoplan are promising therapeutics for GA, which remains a devastating, untreatable cause of vision loss in our community.
The rapid-fire session was an amazing snapshot of current research and the exciting options that hopefully will benefit all our patients in the not-too-distant future
The final three talks dealt with faricimab – a novel molecule that targets both angiopoietin 2 and VEGF-A. Under normal circumstances, the angiopoietin-1/ Tie signalling pathway regulates vascular homeostasis and controls vessel permeability, inflammation and angiogenic responses. However, under pathological conditions, increased levels of Ang-2 levels prevent activation of Tie 2 by Ang-1, which weakens endothelial cells and leads to vascular instability. Faricimab is a bispecific antibody that binds to both Ang-2 and VEGF-A, resulting in reduction in vascular leakage. The YOSEMITE and RHINE Phase 3 trials looked at faricimab for management of DME and the one-year results were presented by Associate Professor Samantha Bell. Faricimab has recently been approved by the FDA for both DME and nAMD but is yet to be approved in Australia or New Zealand. The YOSEMITE and RHINE studies were identical randomised, double-masked, phase 3 studies investigating faricimab in treatment na.ve DME patients. Patients were randomised to one of three arms – either faricimab 6mg eight weekly after six monthly injections, faricimab 6.0mg personalised treatment interval (PTI) after four monthly injections, or finally, eight weekly aflibercept. The primary endpoint was change from BCVA from baseline at one year. Both YOSEMITE and RHINE met their primary end point – that is they were non-inferior to aflibercept in terms of BCVA. In the PTI arm, more than 50% of patients could be extended to 16 weekly treatment and more than 70% could be at least 12 weekly treatment. Improved anatomic outcomes also favoured faricimab – it was superior at drying the retina and patients were more likely to have complete resolution of their DME. Importantly, no cases of vasculitis or occlusive retinitis were observed.
The TENAYA and LUCERNE Phase 3 studies dealt with the use of faricimab in the management of neovascular AMD. The week 48 results from these studies were presented by Professor Guymer. Patients were randomised to receive either faricimab 6.0mg up to 16 weekly after four monthly injections compared with aflibercept eight weekly after three initial monthly injections. Based on disease activity at weeks 20 and 24, faricimabtreated patients were then allocated to either eight weekly, 12 weekly or 16 weekly treatments until week 60. The primary endpoint was BCVA change from baseline. In year two, patients were treated via a personalised treatment interval (PTI). Both TENAYA and LUCERNE studies met their endpoints of non-inferiority compared with aflibercept. Nearly 80% of patients receiving faricimab could be treated at least at 12 weekly intervals. There were also low rates of ocular inflammation and no cases of occlusive vasculitis.
The rapid-fire session was an amazing snapshot of current research and the exciting options that hopefully will benefit all our patients in the not-too-distant future.
While all Fellows had hopes of an in-person meeting, the virtual RANZCO Congress was an absolute success – incredible educational opportunities delivered in a professional, interesting format. We look forward to Brisbane 2022!
Dr Amy Cohn FRANZCO, MBBS (Hons), MMed is a Melbourne based ophthalmologist with special interest in medical retina and cataract surgery. She is on the RANZCO Scientific Committee Executive as well as being a Visiting Medical Officer at RVEEH and a Senior Research Fellow at the Centre for Eye Research Australia. Dr Cohn sees patients privately in East Melbourne, Footscray, Glen Waverley and Armadale.