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Kreissig Lecture A Legacy of Retinal Detachment Research
by Tan Sher Lynn
The 2024 Kreissig Award Lecture, delivered by recipient Prof. Taiji Sakamoto from Japan on Day 3 of the 24th Congress of the European Society of Retina Specialists (EURETINA 2024) was a moving tribute to both innovation in retinal surgery and the profound mentorship of Professor Ingrid Kreissig, one of the pioneering figures in retinal detachment treatment.
This year’s Kreissig Award Lecture not only highlighted Prof. Sakamoto’s extensive contributions to the field of ophthalmology but also underscored the enduring legacy of Prof. Kreissig, a pioneering figure in retinal detachment treatment who became the first woman to serve as a surgical chair in ophthalmology at the University of Tübingen (Germany) in 1979.
A role model for many, especially women in medicine, Prof. Kreissig’s influence has been profound, both in Europe and worldwide.
In his speech, Prof. Sakamoto honored her leadership, recalling how she mentored
him while he prepared for the lecture. “Sometimes her guidance was strict, but there was always warmth and kindness in her comments. It was a privilege to receive her direct feedback,” he recalled.
Then, Prof. Sakamoto, who is currently the Vice President of Kagoshima University in Japan and the President of the Japan Retinal Virtual Society, took the audience on a journey through his 30-year career in ophthalmology, which he divided into three key phases: his work in basic science, his clinical practice, and his current role as a leader in academic society.
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He shared groundbreaking research, particularly his work on developing better treatments for retinal detachment by controlling cell death with drugs.
“I came to think, I could develop better treatment for retinal detachment without using surgery. I took three different approaches. The first one was to inhibit triggers of cell death. The second was to inhibit cell degeneration processes. The third was to enhance the neural degeneration of retinal detachment,” he said.
He explained that in normal eyes, histones remain in cell nuclei. But in retinal detachment or proliferative diabetic retinopathy, they are abundantly released.
Histones are toxic, killing cells and inducing pro-inflammatory cytokines
like IL-8. In retinal detachment, they worsen degeneration by thickening the outer nuclear layer, with most cells dying within 24 hours of exposure.
Prof. Sakamoto recalled that one of his students accidentally applied PGL-40, leading to the discovery that most of the cells are still alive after 24 hours, with dead cells limited to the histoneaffected areas. “This revealed that PGL-40 can neutralize the toxic effect of histone,” he said.
However, since PGL-40 cannot be used in surgery, they tried hyaluronic acid, achieving similar results. This discovery improved retinal surgery techniques. “If the retina is too fragile or inflammatory, you should put an ocular viscous device (OVD) on top,” Prof. Sakamoto explained.
He also added that when opening a closed retina, perfluorosilicone liquid (PSL) should be used. This method,
Espansione Announces Six-Month Results from the Lightwave I Clinical Trial for Dry AMD Patients
by Diana Truong
Espansione Group (Argelato, Italy), a provider of photobiomodulation (PBM) medtech solutions for ophthalmology, has announced the six-month safety, tolerability and short-term efficacy results from their LightWave I clinical trial, which explored the impact of Light Modulation® low-level light therapy (LM® LLLT) on patients with dry age-related macular degeneration (dAMD).
The results, published in the September issue of Springer’s Ophthalmology and Therapy, underline the safety, tolerability, and efficacy of Espansione’s LM LLLT on the Eye-light® PBM device. The study included 152 eyes from 76 patients and revealed improvements in both best-corrected visual acuity (BCVA) and drusen volume reduction, making it a potential game-changer for dAMD management.
All patients in the study showed high compliance with treatment protocols, and only mild ocular adverse events were reported by one-fifth of the patients in the PBM-treated group. This reinforces the therapy’s
non-invasive nature and patientfriendliness.*
Best corrected visual acuity (BCVA) improvements were statistically significant, with 20.3% of PBMtreated patients achieving a gain of five or more letters post-treatment, compared to 8.9% in the sham group (p=0.043). In addition, drusen volume reductions were significantly greater in the PBM-treated group compared to the sham group (p=0.013). These results highlight PBM’s potential to not only stabilize but also enhance visual function in patients with dAMD.*
Given the growing global challenge of managing AMD, these results could
known as the “soft-shell technique,” reduces retinal damage during surgery.
Prof. Sakamoto also discussed two key findings regarding silicone oil tamponade in retinal detachment surgery. While silicone oil is necessary in some cases, it has been associated with numerous adverse events.
Due to its low frequency of use and the complexity of retinal detachment cases, randomized clinical trials (RCT) are impractical. Instead, a nationwide retrospective study using propensity score analysis compared 2,042 gas tamponade cases with 55 silicone oil cases.
The results showed that, even after matching for case difficulty, visual acuity was consistently better in patients treated with gas than those treated with silicone oil, which should be used sparingly, he noted.
herald a new era in the treatment of early and intermediate stages of the disease. The ability to reduce drusen, a key marker of dAMD progression, and improve visual outcomes without invasive procedures may provide an invaluable option for clinicians.
“The LightWave I trial represents a major milestone deepening our understanding of light therapy’s impact in the management of degenerative retinal conditions such as dry AMD,” noted lead investigator Prof. Enrico Borrelli (Italy) in a news release.
As Espansione continues with the LightWave I multicenter research effort, the ophthalmic community eagerly anticipates more long-term results with photobiomodulation, hoping that it can offer a durable, non-invasive solution to slow dAMD disease progression and improve patients’ quality of life.
Reference
* Borrelli E, Coco G, Pellegrini M, et al. Safety, tolerability and short-term efficacy of low-level light therapy for dry age-related macular degeneration. Ophthal Ther. 13 September 2024. Epub ahead of print. Available at: https://link.springer.com/article/10.1007/s40123-02401030-w. Accessed on 21 September 2024.
APVRS Delivers Consensus on
Polypoidal Choroidal Vasculopathy at EURETINA 2024
by Diana Truong
The Asia-Pacific Vitreo-retina Society (APVRS) took over the podium on Day 3 of the 24th Congress of the European Society of Retina Specialists (EURETINA 2024) to deliver their consensus statements on polypoidal choroidal vasculopathy (PCV). With new links to neovascular age-related macular degeneration (nAMD) and future breakthroughs on the horizon, the session delivered the latest on this complex retinal disease.
Polypoidal choroidal vasculopathy (PCV) has long been recognized as a distinct, recurrent exudative maculopathy, but as Dr. Yasuo Yanagi (Japan) emphasized during the APVRS session, recent findings have redefined PCV as a subtype of neovascular AMD (nAMD).
PCV is marked by aneurysmal dilations at the ends of branching neovascular networks, and while its roots were once thought to lie purely in choroidal vascular disease, today it is considered a variant of type 1 macular neovascularization (MNV).
Dr. Yanagi detailed the genetic overlap between PCV and typical nAMD, with both conditions sharing susceptibility loci such as ARMS2 and HTRA1.
“There is a genetic overlap between PCV and cardiovascular AMD,” he noted, emphasizing that, despite these similarities, certain features—like its predilection for Asian and other pigmented populations—set PCV apart. Additionally, PCV tends to arise from localized ischemic or inflammatory responses,
sometimes linked to pachychoroid conditions.
This reclassification underscores the importance of viewing PCV through the broader lens of nAMD, while recognizing its unique characteristics and risk factors.
Non-ICGA imaging
While indocyanine green angiography (ICGA) remains the gold standard for diagnosing PCV, Prof. Timothy Lai (Hong Kong) highlighted the growing role of noninvasive imaging, like spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) in identifying key PCV features. “PCV can be differentiated from non-PCV neovascular AMD using OCT in the majority of cases,” he explained.
Prof. Lai highlighted that multimodal imaging—incorporating fundus photography, fluorescence angiography, OCT and OCT angiography (OCTA)—is recommended for a comprehensive initial assessment. “We should use multiple imaging modalities…to diagnose them and manage them properly,” he said.
SD-OCT’s ability to visualize polyps as anterior dome-shaped elevations of the retinal pigment epithelium (RPE) is pivotal. In particular, OCTA’s potential to detect blood flow irregularities in polypoidal lesions provides additional diagnostic insight. While not
a complete replacement for ICGA, these tools allow clinicians to monitor disease progression and treatment response with greater precision.
For cases with suboptimal anti-VEGF response, Prof. Lai stressed that nonICGA features—such as the sharp peak PED—guide photodynamic therapy (PDT), reinforcing the vital role of OCT-based diagnostics in modern PCV management.
Medical treatment
Medical treatment options for PCV need to balance efficacy and long-term vision maintenance. Prof. Seung-Young Yu (South Korea) noted that “the closure of active polypoidal lesions is crucial for achieving both optimal visual improvement and long-term visual maintenance in PCV treatment.”
Prof. Yu detailed two primary approaches: anti-VEGF monotherapy and combination therapy, each with strong clinical backing. The PLANET trial supports anti-VEGF monotherapy, while combination therapy—anti-VEGF and verteporfin photodynamic therapy (PDT)—has shown great results in trials like EVEREST and EVEREST II.1,2,3
“Anti-VEGF monotherapy can be used as the first-line treatment based on outcomes from the PLANET trial, while combination therapy is also supported by the EVEREST trials,” she noted.
Prof. Yu also discussed the potential of a treat-and-extend approach, offering patients fewer injections with sustained outcomes. Additionally, longer-lasting anti-VEGF agents present new possibilities, further enhancing treatment flexibility and durability.
Surgical management
PCV patients may suffer hemorrhaging, which will require surgical treatment. “Submacular hemorrhages have poor visual prognosis due to fibrosis or atrophic scars,” explained Prof. Dr. Paisan Ruamviboonsuk (Thailand), highlighting the urgency of treatment.
For medium to large hemorrhages, Prof. Ruamviboonsuk presented various options, including pneumatic gas displacement, vitrectomy, and submacular injections
of anti-VEGF and tissue plasminogen activator (TPA). He emphasized that “surgery achieved better visual improvement and higher displacement of blood” compared to other methods, especially in large hemorrhages.
For instance, he shared a case where a patient with extensive submacular hemorrhage was treated with vitrectomy and gas. “After a month, the blood in the macular area dispersed, and the acuity improved,” Prof. Ruamviboonsuk noted.
Upcoming developments
Prof. Gemmy Cheung (Singapore) illuminated several novel treatments on the horizon for PCV. Among the most anticipated developments is faricimab, which targets both VEGF and Ang2, offering “dual action” and “longer durability,” which could lead to fewer injections and sustained efficacy for PCV patients.
The 16-week analysis of this study will be presented during the upcoming APVRS 2024 congress in November.
Another innovation is the port delivery system, designed to maintain a consistent drug level in the eye. “The port delivery
References
system may offer an advantage in keeping the drug level at a very narrow therapeutic window,” Prof. Cheung explained, noting that it could alleviate the need for frequent treatments.
Prof. Cheung also spotlighted therapies targeting VEGF-C and VEGF-D, which are elevated in PCV. A promising Phase 2b study combines an anti-VEGF-C/D agent with ranibizumab, showing superior visual acuity gains in PCV patients compared to standard treatments. This novel approach is now advancing to Phase 3 trials, with a specific focus on PCV outcomes.
These emerging treatments reflect a deeper understanding of PCV’s unique biology, as Prof. Cheung stressed the importance of developing therapies tailored specifically to the condition, rather than repurposing those designed for AMD.
From breakthroughs in imaging techniques to the introduction of innovative treatments like faricimab and the port delivery system, it’s clear that the future holds promising advancements. As novel therapies continue to emerge, the consensus remains clear: understanding the intricacies of PCV will be key to unlocking more effective, long-lasting solutions.
1. Lee WK, Iida T, Ogura Y, et al. Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy in the PLANET Study: A randomized clinical trial. JAMA Ophthalmol. 2018;136(7):786-793.
2. Koh A, Lee WK, Chen LJ, et al. EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina. 2012;32(8):1453-1464.
3. Lim TH, Lai TYY, Takahashi K, et al. Comparison of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy: The EVEREST II randomized clinical trial. JAMA Ophthalmol. 2020;138(9):935-942.
Bayer’s Aflibercept 8 mg Prefilled Syringe
First Impressions at EURETINA 2024
Bayer’s prefilled aflibercept 8 mg syringe, OcuClick, made its debut at the 24th Congress of the European Society of Retinal Specialists (EURETINA 2024). We dropped by their booth in Barcelona to chat with Bayer Vice President, Global Ophthalmology Lead Anna Braeken about the device—and get first impressions from new user Dr. Darren McAteer (Ireland).
Bayer continues to roll out innovations in retinal medicine.
The firm’s most recent addition, a prefilled syringe for their new higherdose aflibercept 8 mg called OcuClick, was recently approved by the European Medicines Agency (EMA)— and they hosted demos of the device at their booth at EURETINA 2024.
We stopped by after the firm’s Day 3 lunch symposium to find out what OcuClick is all about.
The device is a successor, in many ways, to the German firm’s prefilled
syringe for aflibercept 2 mg. Bayer has stated that the design philosophy behind OcuClick comprises three pillars—safety, precision and ease of use, and Ms. Braeken echoed this during our conversation.
“The prefilled syringe for us is an absolute must-have these days in terms of the treatment and convenience for healthcare practitioners, ” explained Ms. Braeken. “But with this pre-filled syringe, we also wanted to ensure safety for the patient with exact dosing—and doing all this in a format that made it easy to use.”
by Matt Herman
Dr. McAteer’s first impressions reflected this design emphasis on safety. “I got a look at it for the first time two days ago, and what I like about it, first, is that the dose is fixed,” he said.
“With normal syringes, there can be issues with overdosing—sometimes we can’t be sure where the bevel is or where the line actually is. So the fact that this will only give you 0.07 ml is what I really like about it.”
This is the specific feedback that Bayer had in mind during the design process, according to Ms. Braeken. And it all started with listening to doctors around the world on the first iteration of the device.
“We took a lot of feedback from healthcare professionals on that first pre-filled syringe,” she said. “They
told us what worked well and what they really needed for their specific practice. So we did listen carefully and then we designed something that we could launch with aflibercept 8 mg that responded to the needs expressed to us.”
“Some of those needs revolved around the dosing and ease of use,” she said in a nod to Dr. McAteer’s comments.
Sustainability from the ground up
Another key consideration for OcuClick was to align it with Bayer’s mission in green ophthalmology—a focal point at EURETINA 2024, and in modern ophthalmology in general.
The sustainability of intravitreal injections in particular has been a hot topic at the Congress, and Ms. Braeken explained that this was a ground-level consideration in designing what is, by necessity, a disposable instrument.
“The environmental footprint was absolutely an important aspect,” she said. “Sustainability comes, first of all, with the less frequent dosing intervals we’re seeing with aflibercept 8 mg— less travel for the patient, but also less injections and less waste.”
But Bayer decided to take things a step further with OcuClick in a bid to further minimize the drug’s environmental footprint. “We then looked at the packaging and asked,
how can we reduce the size? This package is actually 40% smaller than the previous syringe. So we’re actively looking [at sustainability] from a lot of different angles.”
Ease of use and capacity constraints
Back with Dr. McAteer, the conversation on the device’s ease of use took a turn to a topic close to every European ophthalmologist: the looming shortage of ophthalmologists and resulting capacity constraints.
“We don’t yet have nurse injectors where I practice, and I think there’ll be some trepidation among some of our nurses to start doing intravitreal injections, especially with the responsibility of making sure they have the right dose,” he said.
“Some parts of Ireland do have nurse injectors, and if we’re looking for nurses to start to step forward, which we need with capacity constraints, we need to ease them into it,” Dr. McAteer continued. “Removing that extra little bit of responsibility about getting the dose exactly right, I think, would convince a lot of them to do it.”
This ties into one of the device’s more unexpectedly alluring aspects—it’s undeniable tactile appeal. Bayer representatives have encouraged doctors to be hands-on with the OcuClick demos at their EURETINA 2024 booth, and it’s no surprise why.
The haptic feedback in the clicks and cracks that come with proper use of the device add an ‘it’ factor to OcuClick. The satisfaction on the faces of eye care practitioners as they twisted, popped and pulled the demo syringes was undeniable—but this playing around at the demo table translates to real utility in the injection chair.
“We don’t yet have nurse injectors where I practice, and I think there’ll be some trepidation among some of our nurses to start doing intravitreal injections, especially with the responsibility of making sure they have the right dose.”
- Dr. Darren McAteer
“There’s that mechanism on the device where you can push it to the right point and you feel that. You turn it 90 degrees, it clicks, and when you push it again, it doesn’t go any further. It’s very straightforward,” Dr. McAteer said.
“It’s definitely not a toy,” Ms. Braeken laughed when asked about booth visitors’ obvious delight in handling the instrument.
“But we made sure that healthcare professionals are able to touch it and play with it a little bit, to feel it. The feedback is that it’s simple and they don’t have to worry about the dose line, and that gives them confidence. And there’s definitely satisfaction with that click—they really like the click.”
Click or no, Bayer’s hope is that the sum of these intentional design choices equates to real impacts in the lives of patients and the surgeons that serve them—for safer intravitreal injections, a greener ophthalmic office—and the preservation of sight well into the future.
