AAO 2020 at a glance

Originally due to take place in Las Vegas, USA, the 124^th annual meeting of the American Academy of Ophthalmology (AAO) was held virtually - for the first time in its history - due to the COVID-19 pandemic. AAO 2020 Virtual consisted of 215 interactive live sessions spanning a total of 100 hours, together with a further 700 hours of additional on-demand content in the form of 1216 individual videos. Overall, the congress was attended by 8706 delegates hailing from 101 different countries. The agenda for the world’s largest ophthalmology meeting consisted of a mixture of subspeciality day events, scientific symposia, ask the expert sessions, skills transfer courses, instructional courses, original paper sessions and poster discussions.

RETINAL DISEASES IN THE COVID-19 ERA: GLOBAL PERSPECTIVES

Opening Session

The opening session of AAO 2020 Virtual saw the passing of the gavel from current President Anne Coleman, Los Angeles, USA, to President Elect, Tamara Fountain, Chicago, USA.

David Parke, Academy CEO, Oklahoma, USA, and Saul Levin, CEO of the American Psychiatric Association (APA), Washington, USA, discussed the impact of COVID-19 on physicians and their practices from a psychiatrist’s perspective. The COVID-19 crisis has caused rising levels of stress, anxiety and depression among both patients and physicians. Dr Levin stressed that, although trained to be stoic and resilient, it is vital that physicians take care of their own mental health. Prolonged stress can lead to burnout which exerts a heavy toll on health and well-being, and can also result in compromised patient care. For ophthalmologists, as in other medical disciplines, maintaining social contacts with colleagues is critical, said Dr Levin. The APA offers a dedicated resource via its website www.psychiatry.org/wellbeing designed to help physicians manage everyday stress during the ongoing pandemic.

AAOE Opening Session: From Recovery to Resilience (Creating a Thriving Practice Post-COVID)

Essential elements of a resilient practice in the COVID-19 era

Ruth Williams, Wheaton, USA, explored the roles of strategy, culture and leadership in practice management and noted that key decisions made during the COVID-19 pandemic were underpinned by the core principle of keeping both employees and patients safe. Dr Williams explained that culture can be created in an organisation by defining and communicating values and by modelling these values at all levels, including in the hiring process and during social interactions. Resiliency of leadership is also important in practice management. A resilient leader is: an “excellentist”, not a perfectionist; recovers from failure and acknowledges it as normal; is a sober optimist; keeps energy high and invests in others. Dr Williams suggested that challenging times are also times of opportunity and, for ophthalmologists, constantly learning new skills and acquiring knowledge for the future remains vital.

Retina Around the World

Jose Roca, Lima, Peru, explored evidence supporting the internal limiting membrane (ILM) flap technique as a safe and effective surgical approach for idiopathic large macular holes (>400 mm), which improves both functional and anatomical outcomes. Potential histopathological mechanisms underpinning the inverted ILM include induction of glial cell proliferation and provision of a scaffold to support cell proliferation, thereby creating a favourable microenvironment for correct photoreceptor positioning.

The question of when to operate in myopic traction maculopathy was considered by Kazuaki Kadonosono, Yokohama, Japan. The tendency for myopic retinoschisis to worsen over time is well-known, with less than 4% of cases showing a natural decrease or resolution in a natural history study of 207 eyes. Vitrectomy including ILM peeling provides both anatomical and functional improvement in myopic retinoschisis. Dr Kadonoso explained that myopic retinoschisis with subfoveal detachment is well-tolerated for surgery; however, surgery for other types of myopic retinoschisis remains more controversial.

Paul Bernstein, Utah, USA, gave an update on macular telangiectasia (MacTel) type 2, an orphan retinal disease with a global prevalence of 1 in 5000. In the past year, SPTLC1 and SPLTC2 have been discovered as highly penetrant causative genes for MacTel. Analysis of these genes provides an important insight into the molecular mechanisms of MacTel as a disorder of serine and sphingolipid metabolism - and also raises the possibility of personalised and universal treatment approaches. Serine supplementation is already established as a treatment for hereditary sensory autonomic neuropathy type 1 (HSAN1), which is often linked to MacTel in familial clusters, and a clinical trial in MacTel is due to begin soon.

Serine and sphingolipids in MacTel

Treatment-naïve non-exudative macular neovascularisations (MNVs) in age-related macular degeneration (AMD) enlarge over time indicating biological activity, explained Giuseppe Querques, Milan, Italy.

Non-indocyanine green angiography (ICGA) diagnostic criteria for polypoidal choroidal vasculopathy (PCV)

Some cases have a higher propensity for activation and present with different OCT angiography (OCT-A) features suggestive of differing underlying pathologic pathways. Dr Querques therefore proposed the possibility of diagnosing MNVs without exudation. High rates of growth could then be used to predict early activation of non-exudative MNVs and guide treatment in the absence of exudation.

Gemmy Chui Ming Cheung, Singapore, outlined non-indocyanine green angiography (ICGA) diagnostic criteria for polypoidal choroidal vasculopathy (PCV) developed by the Asia-Pacific Ocular Imaging Society (APOIS). Of nine signs evaluated, three were found to be diagnostic for PCV with a positive predictive value of 93%. Dr Cheung also highlighted recent findings from dynamic ICGA which suggest disturbances in choroidal perfusion pressure may be important in the pathogenesis of pachyvessels.

CUTTING-EDGE INSIGHTS INTO RETINAL DISEASES

Scientific Findings from Big Data from the RPB/AAO Award for IRIS Registry Research Symposium

Michael Chiang, Vancouver, Canada, introduced the Intelligent Research in Sight (IRIS) Registry, the nation’s first comprehensive eye disease clinical database initiated in March 2014. Its key aim is to improve care delivery and patient outcomes by providing individual feedback on performance and comparison to national benchmarks.

2020 RPB/AAO awardees for IRIS Registry Research included Thomas Lietman, San Francisco, USA, who was recognised for his ongoing research into infectious and inflammatory eye disease epidemic detection and seasonality. His project aims to improve the tracking, identification and prediction of ocular disease epidemics in the US and provide unique data on the epidemiology of conjunctivitis, including frequency of epidemics, estimation of latency period and transmission between regions.

Rishi Singh, Cleveland, USA, received the Research to Prevent Blindness (RPB)/AAO award for characterising the use of anti-VEGF treatment of diabetic macular edema (DME) among ethnic minorities in a retrospective cohort study of 203,673 patients from the IRIS Registry. Hispanic ethnicity and Medicaid insurance status were found to be the strongest associated factors for worse-presenting VA, while the converse (non-Hispanic ethnicity and private insurance) was linked with better long-term VA outcomes. Non-Hispanic ethnicity, private insurance and white race all correlated with mean anti-VEGF injection number. Dr Singh concluded that the natural history of DME depends on multiple interrelated factors, including ethnicity and socioeconomic status.

The natural history of DME depends on multiple interrelated factors

Artificial Intelligence (AI) and the Future of Eye Care

Thomas Hwang, Portland, USA, outlined the key problems AI is trying to solve in ophthalmology:

• Faster adoption of best clinical knowledge
• Better patient care at lower cost
• Increased physician satisfaction
• Improved doctor–patient relationships
• Fewer medical errors
• Greater equity in healthcare

With a current time lag of 17 years from clinical research discoveries to standard-of-care, Dr Hwang stressed that change is urgently needed. As a result, we are now entering the fourth industrial revolution in human history, driven by AI, big data and robotics - with the promise of more advances still to come.

Sally Baxter, San Diego, USA, delivered an AI primer for 2020. AI describes a branch of applied computer science where algorithms are trained to perform tasks typically associated with human intelligence. In medicine, this involves the use of algorithms to extract relevant information from data to assist clinical decision-making. Deep learning is a subset or advancement of machine learning which is fueling the current boom in AI. It uses neural network models to understand large volumes of data with multiple features requiring a high level of accuracy. Big data and big science are other key elements in the overall AI equation. When it comes to translating AI to the clinic setting, Dr Baxter explained that biomedical informatics will prove critical, with interpretability particularly important for building clinician trust and revealing potential biases.

Barriers to and gaps in the implementation of AI solutions in the eye clinic were discussed by Michael Boland, Boston, USA. Studies thus far have been limited by their focus on easily-defined conditions (e.g. glaucoma) or those with clear grading criteria (e.g. AMD and retinopathy) rather than diseases requiring multimodal clinical diagnostic data. To realise AI as a clinical reality, Dr Boland suggested a shift to more challenging clinical problems, development of explainable systems and increased awareness of coverage bias. It will also be important not to ‘teach’ systems existing health disparities, to work collaboratively with regulators and payors, and to develop robust ethical and legal frameworks.

What are the barriers to AI implementation?

Aaron Lee, Mercer Island, USA, presented a dystopian view of AI and eye care in 2030. Currently, ophthalmology is ascending the Gartner Hype Cycle and moving towards the peak of inflated expectations; by 2030, the slope of enlightenment will have been reached. In a truly dystopian future, the scope of practice for AI models will have expanded, leading to reduced enrollment into medical schools and a shrinking number of human experts in the eye care profession. In the alternative dystopian future, things will remain broadly the same due to the fragility of AI. Dr Lee conceded that AI sometimes fails and when it does, it makes complete, inhuman errors. Limitations also exist in what AI is able to do and the underlying decision-making process remains inscrutable.

The opposing utopian view for AI in 2030 was provided by Dr Chiang. One of today’s major diagnostic challenges is that real-world patients present on a continuous spectrum of ophthalmic disease and different clinicians draw cut-off lines in different places. AI offers the potential for objective disease classification and quantitative scales for clinical diagnosis. These quantitative AI tools could be used for screening and triaging of care in resource poor setting, as well as to improve risk prediction and help pinpoint disease prognosis and progression. In this utopian future, ophthalmologists would then be free to focus on improved ‘doctoring’ and optimised disease management.

Diabetic Retinopathy Treatments: Clinically Relevant Results from the Diabetic Retinopathy Clinical Research (DRCR) Network

Chirag Jhaveri, Austin, USA, showcased results from a randomised, 55-site clinical trial comparing the efficacy and safety of panretinal photocoagulion (PRP) to intravitreous ranibizumab for proliferative diabetic retinopathy (PDR). VA in the eyes of most patients that completed follow-up was very good and severe vision loss or serious PDR complications were uncommon in both groups. However, ranibizumab-treated patients had lower rates of developing vision-impairing diabetic macular edema (DME) and less visual field loss. No meaningful differences in patient-centred outcomes were observed between groups. Overall, Dr Jhaveri concluded that these findings support the use of either ranibizumab or PRP as viable therapeutic options for PDR. Patient-specific factors including anticipated visit compliance, number of visits, cost and systemic health should also be considered when choosing treatment.

5-year outcomes from the Protocol T Extension Study were presented by John Wells, West Columbia, USA. Protocol T was a randomised, multicentre clinical trial of 660 patients with centre-involved DME on OCT who were treated with aflibercept, bevacizumab or ranibizumab for 2 years. After Protocol T ended, 95% of patients received retinal care and 68% had at least one anti-VEGF injection. On average, patients demonstrated visual gains from baseline but mean VA worsened between 2 and 5 years, although no significant changes in central subfield thickness were observed during this period. Dr Wells acknowledged that these results differ from previous clinical trials in DME, such as Protocol I, which have shown better maintenance of VA gains. Moving forward, strategies to improve long-term visual outcomes in clinical care among eyes with DME are needed.

Cumulative probability of retinal detachment in the anti-VEGF and control groups

Andrew Antoszyk, Charlotte, USA, reviewed results from a secondary analysis of five DRCR Retinal Network clinical trials which evaluated the risk of progression to retinal detachment with anti-VEGF therapy - a phenomenon known as the ‘retinopathy of prematurity (ROP) crunch’. Results showed that anti-VEGF therapy in eyes with PRD was not associated with an increased risk of traction retinal detachment (TRD) compared with the control arm. In fact, rates of TRD were numerically lower in the anti-VEGF group. A potential caveat of this analysis was that eyes with TRD involving the macular or TRD for which vitrectomy was planned or imminent were not included.

Findings from DRCR Retina Network Protocol V looking at the management of eyes with centre-involved DME and good VA with initial observation were reviewed by Carl Baker, Hilton Head Island, USA. Most eyes initially managed with observation did not require subsequent aflibercept for VA loss. In total, 66% of observation eyes did not receive aflibercept and median VA in these eyes was 20/20. In this group, 31% had spontaneous DME resolution at 2 years. Eyes in the observation group that required aflibercept still achieved good visual outcomes at 2 years on average.

The second presentation by Dr Jhaveri focused on results from Protocol S, evaluating visual field loss over 5 years in patients treated with panretinal photocoagulation (PRP) or ranibizumab for PDR. Eyes in this protocol had VF loss at baseline. Application of scatter laser treatment was associated with large losses in VF, with endolaser causing the greatest amount. VF loss in the ranibizumab group, which occurred predominantly after two years of follow-up, was only explained in part by laser treatments. Dr Jhaveri concluded that more precise conclusions are currently precluded by the limitations of the available data but further clinical research is warranted to clarify this situation.

Vitrectomy for Complications of Proliferative Diabetic Retinopathy: Clips and Tips

A step-by-step illustrative review of the key principles of tractional retinal detachment (TRD) and TRD/rhegmatogenous retinal detachment (RRD) repair was provided by Petros Carvounis, Houston, USA. The posterior hyaloid face (PHF) should be transected 360 degrees as peripherally as possible, turning the cutter port in the direction of travel and not above or below the level of the PHF. The next step is to trim the unformed vitreous. During membrane separation/delamination, it is important to try and eliminate nerve to retina traction. When segmenting with the cutter and advancing though the membrane, the membrane must be engaged within the port and the port ideally directed up. The flapback technique is useful for removing small islands or flaps of membrane while, for peeling membranes, end-grasping, platform or ILM forceps work well.

A step-by-step illustrative review of the key principles of tractional retinal detachment repair

Andrew Barkmeier, Rochester, USA, walked through the stepwise process of diabetic vitrectomy in a case of large tractional retinal detachment involving the macular. Dr Barkmeier advised using the normal micro-incision vitrectomy surgery (MIVS) cutter for all but the most extreme cases, looking to identify “low-hanging fruit”, trim the vitreous short and pinpoint any lose adhesions. When engaging the tissue with traction, elevation is important to reduce the risk of mobile retina jumping up into the cutter. Dr Barkmeier advocated a switch to vertical scissors if the macular is elevated and visibility is poor. Curved delaminating scissors are also an excellent instrument for use in areas that cannot be safely accessed with the vitreous cutter. It is important to use both hands to access the different planes from different directions.

What are the criteria for safe removal of thick subretinal fluid?

Nora Khatib, San Diego, USA, showed an instructional video highlighting the versatility of the cutter when peeling membranes in TRD. She explained that several approaches exist to manage diabetic tractional retinal detachments and that the cutter itself can be used in many different ways. It is also important to be flexible when carrying out this procedure, looking for different plains or locations to proceed, and using different techniques with available instrumentation.

Annal Meleth, Smyrna, USA, outlined his typical approach for dealing with TRD in diabetic retinopathy which is to carry out the core vitrectomy and get down to the membranes before applying endolaser PRP. This provides an ‘insurance policy’ if the view becomes compromised later due to extensive bleeding or further retinal detachment. In cases with extensive nonperfusion and severe tractional detachments, PRP can be taken down all the way into the arcades. Dr Meleth explained that he prefers to treat patients with an initial course of anti-VEGF injections prior to TRD repair as this makes the membranes more avascular, facilitating a smoother procedure.

Late-breaking Developments Part II

Findings from analysis of the AAO IRIS Registry evaluating geographic atrophy (GA) secondary to AMD in real-world clinical practice were presented by Ehsan Rahimy, Palo Alto, USA. This was the largest retrospective database study of GA natural history progression to date and showed that a large proportion of patients with GA fail to return for follow-up after 2 years. While VA at the initial encounter was relatively well preserved, especially in eyes with extrafoveal GA lesions, eyes with good vision tended to lose more letters in the first 2 years compared to eyes with poor vision at baseline. Progression to neovascular AMD (nAMD) was considerably higher if nAMD was present in the fellow eye.

Challenging Cases in Neovascular AMD

This rapid-fire instructional course focused on a number of real-world challenging cases in nAMD.

Luiz Lima, Sao Paulo, Brazil, presented three cases of nAMD illustrating how acquired vitelliform lesions (AVL) can occur in association with large drusen (>125 μm). He explained that abnormalities leading to drusen formation or processes that function in parallel to these may be causative in AVL formation.

Eduardo Rodrigues, Saint Louis, USA, presented the case of a 59-year old Caucasian patient with non-exudative macular neovascularisation (MNV). Dr Rodrigues explained that optimal management of such patients is close observation (with follow-up every 3–4 months). In the PRO-CON study, quarterly aflibercept prophylaxis did not affect conversion though Month 24.

Retinal pigment epithelial (RPE) rips in nAMD are a frustrating and complex diagnosis which threatens the visual outcome of patients, said Amani Fawzi, Chicago, USA. Recognising high-risk eyes is important. Patients should also be counselled about the risk of rips which occur spontaneously at a rate of 10% and 15–20% with anti-VEGF injections. If rips develop, there is a good chance of safeguarding vision by persisting with injections, especially if the fovea is preserved.

Risk factors for RPE rips in nAMD

Jay Chhablani, Hyderabad, India, discussed the role of anti-VEGF therapy in combination with steroids for subretinal exudation in wet AMD. His patient, a 69-year-old male, failed to improve after anti-VEGF therapy alone but achieved a good response and complete resolution of subretinal hyper-reflective material (SHRUM) after treatment with intravitreal triamcinolone acetate (IVTA) and aflibercept. Anti-VEGF therapy plus steroids may therefore exert potential synergistic effects, improving anatomical outcomes with a favourable effect on subretinal hyper-reflective exudation.

Submacular haemorrhage (SMH) is a potentially devasting complication of AMD that can cause photoreceptor damage within 24 hours. Baruch Kuppermann, Irvine, USA, summarised potential treatment options which include: anti-VEGF therapy, pneumatic displacement with expansive gas ± tissue plasminogen activator (tPA), PPV ± subretinal tPA and even retinal translocation. Each approach has benefits and limitations, although combination therapy appears more effective in larger SMH.

Michel Farah, Sao Paulo, Brazil, recounted the recalcitrant case of a 65-year old woman with a multimodal diagnosis of retinal angiomatous proliferation (RAP). Retinal fluid resolved with just one injection of aflibercept and treatment was stopped after four injections. However, after 2 years, the patient developed new visual symptoms and
3-monthly aflibercept injections were reinitiated with a great anatomical response.

Rishi Singh, Cleveland, USA, explained that PCV is far more prevalent than previously thought and has varied presentations depending on the race of the patient. It can also masquerade as neovascular AMD which can confound diagnosis, hence specific OCT and IGA findings should be used to aid identification. Significant polyp regression, decreased injection frequency and better vision outcomes have been shown for PDT with anti-VEGF versus monotherapy alone.

What are the ethnic differences in clinical presentation of PCV?

Closing remarks

Looking ahead to next year, the 125^th congress of the AAO is scheduled to take place at the Ernest N Morial Convention Centre in New Orleans, USA between 13–15^th November 2021.

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