Artificial intelligence (AI) offers immense potential in healthcare, from improving diagnostics to streamlining drug development... but is it reliable?
The silent threat of radiation retinopathy, explored at EURETINA.
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by Matt Herman
Sustainability in retinal surgery—and ophthalmology in general—was on the docket for an early morning Day 2 session at the 24th Congress of the European Society of Retina Specialists (EURETINA 2024). Luminaries from across the subspecialty spoke on challenges and controversies facing greener retinal care—and gave glimpses of the way forward.
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Ruchi
How do the needs of patients intersect with the health of our planet? The question of sustainability in ophthalmology is a thorny one, where surgical safety and patient needs are often pitted against one another on opposite ends of a sliding scale.
But it doesn’t have to be that way, according to panelists at a symposium on the topic. A global panel from EURETINA Board Member Prof. Martin Zinkernagel (Switzerland) to Dr. Vivek Dave (India) presented the latest on not only how ophthalmologists can make ophthalmic surgery greener—but also whether it is safe to do so.
Session moderator Prof. Jens Kiilgaard (Denmark) began by framing the debate with an unorthodox perspective. Arguing over whether humans are causing climate change is ultimately fruitless, he stated, as it does not change our responsibility to slow the warming of the planet.
Prof. Kiilgaard then gave some personal examples from his time practicing in Greenland, where the effects of climate change and its impacts on human society are front and center.
“Animals like polar bears are coming closer and closer to buildings and people,” he recounted.
“When I was there as a consultant, they actually had to shoot two polar bears who had come into the city and attacked the sledge dogs.”
The purpose of the session has its roots in episodes like this, according to Prof. Kiilgaard. “The Greenlandic people directly feel this warming and the consequences it has in their daily lives. This is the purpose of the session we’re having here—it’s not to find the correct solution today, but to change the mindset of the whole community,” he said.
Changing this mindset, however, is a tall task—and each session in the panel broke this down into its component parts. And with a potential looming ban in the European Union this year on per- and polyfluoroalkyl substances (PFAS), a reduction or cessation of reliance on these gases took center stage.
Dr. George Moussa (UK) tackled this issue in his talk on sulfur hexafluoride (SF6), a potent greenhouse gas used widely in retinal surgeries.
The first part of Dr. Moussa’s talk dealt with the differences in SF6 gas delivery methods. The issue, Dr. Moussa said, is that although the use of larger cylinders of SF6 might seem environmentally friendly, this turns out not to be the case.
The pivotal issue with larger cylinders is waste. Multiple cylinders of SF6 must be used concurrently for workflow purposes, and even the busiest clinics in the world are unable to use entire cylinders before their expiry date.
The resulting counterintuitive effect of using such large vessels is unmistakable. “In Manchester, we had 8 kg of SF6 ordered over 4 years, which is enough for 50,000 procedures—but we only did 1,200,” he said. And this doesn’t even account for more waste caused by improper handling and disposal of excess SF6.
Switching to single-use cylinders is one solution he offered. The per-procedure carbon emission equivalent of changing from 1,500 km driven by a car with cylinders to 45 with single-use canisters. But this would come at a significant financial cost.
Another option would be to offer more sensibly-sized canisters, such as in the United States, where cylinders come in sizes from 20-450 g.
Yet another would be to switch to other gasses, like air tamponades. Though he admitted safety data on this is scarce, his stance was clear.
“You don’t need to use SF6 to get good outcomes. In Coventry, for example, they use air tamponades for all retinal detachments that meet the pivot criteria,” he said. “My argument would be that most of the cases we use SF6 in would actually be just fine with an air tamponade.”
Reducing waste without compromising safety?
Intravitreal injections were another key focus, with noted green eye care advocate Dr. Redmer van Leeuwen (Netherlands) speaking on this topic.
He broke intravitreal injection waste into four main areas, following a seminal article in Eye: energy and water use, patient and staff travel, manufacturing of medication and materials, and waste disposal.1
For energy and water use, he proposed a simple solution. “Some hospitals use the OR to perform injections, which is much more energy consuming than a clinic or office. So this is an easy change,” he said, adding that using alcohol instead of water to sterilize also has a role to play.
Patient and staff travel is perhaps the point with the largest consumption. Solutions he suggested included injecting when the patient is already in the hospital and simultaneous bilateral injections is one quick fix.
Advancements in drugs will also yield improvements on this front. More advanced treat-and-extend protocols and decentralized injection hubs will lessen frequent travel to the clinic, as will longer-acting and sustained-release drugs.
Material waste, the third area for improvement, is a much larger topic. Transparency in the manufacture of medication is not known, and Dr. van Leeuwen called for more.
As far as equipment is concerned, Dr. van Leeuwen advocated for the formation of responsible intravitreal injection equipment packages and the omission of materials he believes may be obsolete in the procedure, including gowns, face drapes and plastic instrument trays, among others.
He referenced a German study that investigated the safety impact of reducing these materials, which generally found little negative effects when cutting out materials like face drapes and specula.3
For Dr. van Leeuwen, it ultimately comes down to surgeons adopting a new mindset. “Ask questions,” he urged. “Is this intravitreal injection really meaningful, or can we skip it? Can I prevent the patient from traveling to the hospital? And do I really need all these disposables?” he suggested.
Dr. Vivek Dave then took a deeper look at the impact of these issues in his native India, where sustainability goes hand-inhand with critical reductions in procedure costs.
His talk revolved around the promise—and challenges to safety—involved in reusing ophthalmic instruments.
“This topic is a little controversial, because over the years one of the sacrosanct ways of going about surgery is to discard and dispose of everything opened up for a particular patient,” he said.
Despite the myriad environmental benefits this would yield, the main obstacle remains the burden of resterilization and minimizing risk of infection. But he introduced intriguing data to indicate that reusing instruments may not be as risky as previously thought.
In one study in India, materials like cassettes, trocar cannulas and cutters were reused. Surprisingly, the study found resulting endophthalmitis rates of 0.06% with resterilization, well within the 0.020.84% average.4
Similarly encouraging results were found in another large study outside of India. But despite these large-scale studies, Dr. Dave believes the data is still inconclusive, calling for more research.5
“This topic is a little controversial, because over the years, one of the sacrosanct ways of going about surgery is to discard and dispose of everything opened up for a particular patient.”
- Dr. Vivek Dave
Endophthalmitis is not the only problem, and Dr. Dave also pointed out other drawbacks. Prion diseases, and the man hours and carbon footprint of resterilization are other valid arguments against the practice. A series of particularly gruesome
videos involving intraoperative instrument breaks also highlighted the dangers of a lack of protocol and pushing instruments beyond their intended usage limits.
In the end, though, Dr. Dave advocated for a nuanced and responsible approach involving reusable interests, for the health of both the planet and the people on it who need more financially reasonable procedures.
“Reusability should be a serious consideration in practice,” he said, providing the following guidelines:
• Reusing solid instruments over hollow ones
• Indicating a recycling policy in a consent form
• Giving the patient the informed right to choose
• Creating a reprocessing and reuse committee
• Strict oversight of central reprocessing, infection control, biomedical engineering and cost accounting
The organizations making it happen
And just as Dr. Dave suggested committees overseeing the reuse and sterilization of instruments, the final topic of the day was the organizations and infrastructure being created before our very eyes to put sustainability into practice.
EyeSustain is one of them. The organization comprises a global coalition of ophthalmologists, societies and industry committed to greener practices in eye care, with a star-studded advisory board packed with some of the most recognizable names in global eye care to boot.
Dr. Diana Silveira e Silva (Portugal), a member of the European Society of Cataract and Refractive Surgeons (ESCRS) and a co-chair of the EyeSustain Global Council, introduced the organization and its framework for reducing ophthalmology’s global footprint, so head over to their website to check out their impressive array of resources.
EURETINA is, of course, another leader on this front. As a EURETINA Board Member, Prof. Martin Zinkernagel went over many of the measures and guidelines EURETINA is putting into place as a leader in ophthalmic sustainability.
Chief among these was reducing conference travel by choosing centralized, easily accessible Congress sites, like next year’s meeting in Paris.
“To sum it up, EURETINA is truly committed to being a leader in sustainability, along with other societies like ESCRS and AAO,” he said. He concluded the session with a call to action.
“But we need all members to play their part, and for this we need to educate and raise awareness. We want to bring in the young retina specialist viewers, the young ophthalmologists to bring about the kind of sustainability we just heard about, so it’s really important to get these players on board.”
Sustainability by Reducing Clinical Waste. Klin Monbl Augenheilkd. 2024 Apr 4. English, German. [Epub ahead of print.] Erratum in: Klin Monbl
2024 Apr 16.
3. Buchan JC, Thiel CL, Steyn A, et al. Addressing the environmental sustainability of eye health-care delivery: a scoping review. Lancet Planet Health. 2022;6(6):e524-e534. Erratum in: Lancet Planet Health. 2022;6(8):e644.
4. Shah PN, Mishra DK, Shanmugam MP, et al; VRSI Study Group. Incidence of post vitrectomy endophthalmitis in India - A multicentric study by VRSI study Group. Eye (Lond). 2023;37(14):2915-2920. [Epub 2023 Feb 8.]
5. Silpa-Archa S, Kumsiang K, Preble JM. Endophthalmitis after pars plana vitrectomy with reused single-use devices: a 13year retrospective study. Int J Retina Vitreous. 2021;7(1):2.
by Tan Sher Lynn
Artificial intelligence (AI) offers immense potential in healthcare, from improving diagnostics to streamlining drug development. However, concerns over its unpredictability, bias and responsibility loom large. On Day 2 of the 24th Congress of the European Society of Retina Specialists (EURETINA 2024), experts discussed the need for robust validation and collaboration between human expertise and machine learning to ensure AI’s reliability.
First speaker Prof. David Wong (UK) highlighted the significant challenge of uncertainty in AI, raising questions about its safety and predictability.
He shared a concerning example of a pedestrian being hit by a self-driving car, asking, “Who takes the responsibility?”
Errors in AI, Prof. Wong explained, arise either from a lack of knowledge, known as epistemic uncertainty or the randomness of data.
Unlike Newtonian systems where cause and effect are deterministic, AI’s outcomes can be chaotic and unpredictable.
Prof. Wong offered two perspectives: one, that errors can be eliminated through more data and better models, and another, that errors may be unavoidable, referencing mathematician Henri Poincaré’s work on the three-body problem.
based on comparison—like in Adaptive Comparative Judgment (ACJ) —can offer a pragmatic solution.
“Comparison may be a pragmatic and flexible semi-automated approach to that measurement of the screening. AI based on comparison can be trusted, because the safety levels can be set by you,” he concluded.
“Comparison may be a pragmatic and flexible semi-automated approach to that measurement of the screening. AI based on comparison can be trusted, because the safety levels can be set by you.”
- Prof. David Wong
by the biases in their training data. “Humans are inconsistent and susceptible to various biases,” he said.
Next, Prof. Adnan Tufail (UK)’s talk on validating AI in medical imaging emphasized the complexity of designing effective AI systems for healthcare, particularly for diabetic retinopathy (DR).
“Validating AI is really trying to design the instrument right at the start,” he explained, with key steps involving “the right data sets, collecting it, annotating it correctly and validating with the right comparators.”
Prof. Tufail highlighted new regulations such as the AI Act in Europe, which classified most medical AIs as “high risk” and mandated stricter validation processes.
He noted that AI systems, while good at recognizing patterns, are influenced
Discussing AI’s use in healthcare, he pointed out that false positives and false negatives are common challenges. Yet, he emphasized that AI
He concluded by advocating for independent testing and largescale studies to ensure AI is “as
safe or better than human graders”, referencing key papers on AI validation and urging further study of these methodologies.
Meanwhile, Dr. Jayashree Nair-Sahni (UK) discussed AI’s expanding role in drug development, particularly for DR. She highlighted that the pharmaceutical industry has invested over $70 billion in AI for drug discovery, manufacturing and image analysis.
“Pharma has been using AI not just for image evaluation but for drug development and discovery,” she noted.
Dr. Nair-Sahni emphasized that despite two decades of anti-VEGF therapies, 50% of patients are not responsive, signaling an unmet need even in developed countries. She suggested that AI could help identify patients who would benefit from alternative treatments, such as steroids or new therapies. AI could also address complex retinal issues like ischemia and non-perfusion.
“We need technology solutions to address these challenges.”
- Dr. Jayashree Nair-Sahni
She also stressed the importance of technology in managing the global diabetes pandemic, especially in regions with limited healthcare infrastructure. “We need technology
solutions to address these challenges,” she said, particularly in screening and early identification of DR.
Next, Prof. Simon Harding (UK) highlighted the transformative potential of AI in DR screening, particularly for global health. He noted that the World Health Organization (WHO) advocates for organized screening to mitigate vision loss in diabetic patients, yet systematic programs exist in only eight countries, primarily hindered by limited personnel and treatment capacity.
“AI must adapt quickly to our changing screening protocols.”
- Prof. Simon Harding
Prof. Harding acknowledged the initial enthusiasm for AI as a solution but pointed out its slow adoption. Despite advancements in image quality systems and population screening initiatives, significant barriers remain.
“AI must adapt quickly to our changing screening protocols,” he emphasized, referring to recent updates in England’s DR screening guidelines that complicate algorithm training.
He identified several areas where AI could improve the screening process, including image quality assessment and prioritizing at-risk patients. However, he cautioned against over-
reliance on technology, stressing that “AI will not replace humans.” Instead, it should complement human expertise, especially in complex cases.
Ultimately, Prof. Harding’s insights underscored the need for careful integration of AI into healthcare systems, addressing the obstacles while enhancing screening efficiency and patient outcomes. “We need to focus on building a trustworthy AI framework,” he concluded, highlighting the path forward in DR management.
Last but not least, Dr. Sarah McGhee (Hong Kong) discussed the potential of health-economic arguments to support AI implementation in DR screening, emphasizing resource efficiency in healthcare.
She shared that in Xiamen, China, nearly half of the 400,000 diabetics are unaware of their condition, leading to high rates of sight-threatening DR.
Current opportunistic screening results in only 15% receiving treatment. Dr. McGhee’s modeling suggested that organized screening could increase treatment rates to 55%, significantly reducing blindness cases.
Her economic model evaluated the status quo against an organized screening approach, which could avoid blindness for 100,000 individuals. While the organized system incurs higher costs, its cost-effectiveness ratio remains favorable compared to China’s GDP per capita. “Economic models can be trustworthy and highly informative,” she highlighted, advocating for organized screening to enhance health outcomes while managing costs.
Dr. McGhee concluded that variations in models could yield consistent outcomes, emphasizing the need for “economic analysis to support the case to policymakers.” With new guidelines for reporting health economic evaluations using AI, the future of DR screening looks promising.
by Diana Truong
A Day 2 session at the 24th Congress of the European Society of Retina Specialists (EURETINA 2024), handled the complexities of radiation retinopathy—a slow, silent condition that can wreak havoc on vision post-tumor treatment.
Radiation retinopathy (RR) is a slow, progressive vasculopathy primarily affecting endothelial cells, as Prof. Jens Kiilgaard (Denmark) outlined during the symposium.
“We often see after treatment of tumors in the posterior pole… development of small budding capillaries, which later become cotton wool spots,” he explained. This damage, confined to the area receiving radiation, can occur with any form of radiation—even external treatments for orbital or brain tumors.
The condition often mirrors diabetic retinopathy, yet Prof. Kiilgaard emphasized a key distinction. While
diabetic retinopathy involves the loss of pericytes, RR leads to the loss of endothelial cells. As the disease progresses, maculopathy becomes severe, causing significant visual impairment.
He highlighted the challenges of treating this condition, particularly as vision deteriorates despite interventions like anti-VEGF or steroids, often leading to poor outcomes. “I hope for a good discussion with this session,” he concluded, acknowledging the ongoing debate surrounding the best approaches to manage this devastating condition.
RR is a slowly progressive condition that typically emerges around 18 months post-treatment, but can develop as early as six months. Affecting between 20% to 53% of patients, RR remains a significant challenge, with macular edema often serving as the earliest clinical manifestation.
However, despite its frequency, there is no uniform classification system to guide treatment planning. “The term radiation retinopathy includes all of the vascular changes—proliferative, non-proliferative and macular forms,” noted Dr. Rana’a Al-Jamal (Finland). “It would be more precise to separate these entities to address the treatment of each.”
Instead, he suggested classifying cases as non-ischemic and ischemic because, “Macular edema precedes ischemic radiation maculopathy which is treatable, before ischemia is established, where no treatment is available.”
Multiple classification proposals exist, yet none have achieved universal acceptance. Dr. Al-Jamal emphasized the importance of developing a standardized system. “We need a universal classification system for early pre-planning,” he urged.
Such a system would better equip clinicians to detect and treat the condition before significant vision loss occurs, allowing for more personalized and effective management of this challenging disease.
Biomarkers play a pivotal role in RR early detection and treatment planning. As Prof. Raffaele Parrozzani (Italy) explained, the earliest stage of radiation maculopathy can be detected before any clinical symptoms emerge, thanks to advanced imaging techniques.
“A few weeks after radiotherapy, you see a reduction in vascularization in the macula, without any symptoms for the patient,” he noted, pointing to OCT hyperreflective retinal foci (HRF) as a key preclinical imaging biomarker.
Prof. Parrozzani also emphasized the importance of recognizing these small, punctiform lesions that measure under 30 micrometers, as their presence can predict the development of macular edema—a treatable aspect of radiation retinopathy. “We can consider this as predictors of macular edema,” he said, underscoring the potential of these biomarkers in guiding therapeutic decisions.
Prof. Dr. Antonia Joussen (Germany) tackled one of the most pressing challenges in radiation retinopathy: how to maintain function in irradiated eyes, especially after treatment for choroidal melanoma. “We need to stabilize the musculature. We need to stabilize the capillaries,” she emphasized, setting the stage for discussing both preventative measures and treatment strategies.
While scatter-laser coagulation has long been a go-to treatment for preventing the ischemia driving radiation retinopathy, Prof. Dr. Joussen highlighted advancements in therapy.
Anti-VEGF injections, for example, have proven effective at reducing macular edema in irradiated eyes, though she pointed out, “As soon
as you stop after half a year of consequent treatment, then you have recurrence.”
“There is data that shows that patients receiving early and consistent treatment show a lesser proportion of plaque radiotherapy.”
- Prof. Dr. Antonia Joussen
The possibility of prevention excites researchers. “There is data that shows that patients receiving early and consistent treatment show a lesser proportion of plaque radiotherapy,” she said. Proton beam irradiation, along with advanced imaging techniques like 3T MRI, offer more precise targeting, reducing collateral damage.
Prof. Dr. Joussen also touched on emerging therapies, including targeted cytotoxicity using light-activated drugs that attack tumor cells without harming surrounding tissue.
There are a multitude of questions when it comes to RR treatment, particularly what happens without intervention. Dr. Arun Singh (USA) underscored the many unanswered questions, such as “which patient to
treat, when to start treatment, how often to inject, which agent to use first, and when to stop.”
Dr. Singh then introduced Protocol AL, a pivotal clinical trial under the DRCR Retina Network designed to address the unanswered questions surrounding RR.
This multi-center study will compare long-term visual acuity outcomes in patients treated with faricimab or fluocinolone acetonide implants versus those initially observed. With 600 patients to be enrolled, the trial aims to gather crucial data on the natural progression of RR using frequent multimodal imaging.
“We have 15 patients so far,” Dr. Singh shared. “And hopefully in the next two or three years, we’ll have them all.”
The retina community is eagerly anticipating the results, as this study holds the potential to shape future treatment protocols and provide clarity on the most effective approaches for managing radiation retinopathy.
With a growing understanding of RR, the need for standardized guidelines and more effective treatments has become more urgent. Many clinicians hope these advances will improve patient outcomes in this oftenoverlooked condition. EURETINA 2024 provided a platform for sharing cuttingedge knowledge, setting the stage for future innovations in RR care.
