The 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024) kicked off with a series of engaging discussions on the latest in wet age-related macular degeneration (AMD) treatment on Day 1.
Get ready to dive into the evolving landscape of therapies for this complex condition, where speakers explored everything from anti-VEGF breakthroughs to novel approaches like gene therapies. But it wasn’t all just about the science—real-world challenges like fibrosis, cataract surgery in AMD patients and the need for more effective treatment regimens took center stage.
The current state of anti-VEGFs
When it comes to wet AMD, anti-VEGF therapies are the tried-and-true hero, though they aren’t without their quirks. Prof. Timothy Lai (Hong Kong) pointed out that “50% of [nAMD] patients still have unresolved fluid,” which complicates treatment and leads to frequent visits, patient non-adherence and gaps in care.
Faricimab (Vabysmo™; Roche, Basel, Switzerland), with its dual pathway inhibition approach of targeting both VEGF-A and angiopoietin-2, is the latest star on the block. Dr. Adrian Koh (Singapore) noted that faricimab works particularly well at stabilizing polypoidal lesions and reducing inflammation.
Studies like the TENAYA and LUCERNE trials suggest that with faricimab, intervals can stretch up to 16 weeks, offering patients not only longer relief but also significant visual gains.1
But that’s not all. Aflibercept 8 mg (Eylea HD®; Bayer & Regeneron) is also stepping up with longer dosing intervals, in some cases extending to 24 weeks, which promises a more sustainable, patient-friendly treatment approach.2
There’s no one-size-fits-all, however. Patient selection remains critical. Prof. Sobha Sivaprasad (United Kingdom) noted that patients with better baseline visual acuity (more than 54 ETDRS letters) and a central subfield thickness (CST) of less than 500 microns tend to fare better with aflibercept treatment. Those who still have significant fluid after the loading phase may require further monthly treatment before extending treatment intervals.3
The future, however, holds exciting possibilities. Emerging treatments like gene therapies, including RGX-314 (Regenxbio, Rockville, MD, USA), and tyrosine kinase inhibitors are showing promise in early trials, with the potential to reduce the frequency of injections while preserving vision.4
Meanwhile, innovations in drug delivery, like the Port Delivery System (Susvimo®; Roche), are also making waves. Prof. Lai suggested that the PDS, which allows for continuous ranibizumab (Lucentis®; Roche) delivery with refills every six months, could be a game-changer for patients who long for fewer interventions.5
All about fibrosis
Fibrosis, however, remains a stubborn issue in wet AMD. Prof. Usha Chakravarthy (United Kingdom) delved into this persistent problem, explaining how fibrosis can significantly affect patient outcomes, despite advances in anti-VEGF therapy. “There is huge variability in the way scars develop,” she remarked, pointing out that patients with seemingly similar disease severity can show vastly different scarring patterns.
Detecting fibrosis remains an ongoing challenge, as imaging techniques like color photography, fluorescein angiography (FA) and spectral domain OCT (SD-OCT) can show significant differences. One key discovery, however, is that the presence of hyperreflective material (HRM) on SD-OCT is a strong indicator of fibrosis, correlating with poorer visual outcomes and more severe macular atrophy–as reported in results of the IVAN trial.6
The link between PCV and PNV
Prof. Kenji Yamashiro (Japan) took the audience on a journey into the evolving understanding of PCV and its relationship to pachychoroid-driven neovascularization (PNV). He challenged the classic notion that AMD is always drusen-driven, suggesting that for East Asians, conditions like pachychoroid—characterized by choroidal vascular hyperpermeability—might play a more prominent role in AMD.7
Prof. Yamashiro also offered new insights into PCV subtypes, suggesting that smaller PCV lesions, which are genetically closer to normal control, could have a better prognosis than larger, more severe lesions. With this, he made a compelling case for redefining disease classification and treatment strategies, urging for more research into these variations.
A biomarker for AMD
Dr. David Wong (Canada) turned the spotlight on pigment epithelial detachments (PEDs) as crucial biomarkers in managing neovascular AMD. He emphasized that PED thickness correlates with the presence of intraretinal and subretinal fluid, making it a key factor in determining the course of treatment. In short: the greater the thickness of the PED, the higher the probability of intraretinal and subretinal fluid.8
“Drusenoid PEDs are lipid materials that slowly deposit, breaking the RPE membrane… and then the pump gets affected,” Dr. Wong explained. In contrast, fibrovascular PEDs, often associated with type 1 and type 3 choroidal neovascularization, and serous PEDs require heightened attention.
With advancements in imaging, Dr. Wong noted that clinicians now have more precise tools to track PED behavior, allowing for more accurate predictions of disease progression and treatment outcomes.
When it comes to treatment, “Faricimab dries PEDs better than aflibercept 2 mg, especially PEDs greater than 125 microns,” Dr. Wong reported, highlighting the bispecific antibody’s potential in improving long-term outcomes (as reported in the post hoc analysis of the pooled TENAYA/LUCERNE trials).9
Cataract and AMD
Cataract surgery in AMD patients was another hot topic, with Dr. Hemal Mehta (Australia) sharing critical insights. “With an aging population, we’re going to see more of these conditions occurring concurrently,” he observed. “The question arises, as a clinician, how do you approach the management of these conditions when they occur at the same time?”
Dr. Mehta stressed the importance of waiting at least six months after starting anti-VEGF therapy before considering surgery, to allow for better control of neovascular AMD and prevent vision loss. “Patients who had cataract surgery within six months of initiating anti-VEGF therapy were more likely to lose vision,” he noted.10
Dr. Mehta also warned against the use of trifocal intraocular lenses, which can impair contrast sensitivity, as well as small aperture IOLs. “If you imagine a patient who’s got advancing age-related macular degeneration becoming increasingly reliant on extrafoveal fixation, then having a small aperture intraocular lens is not going to be beneficial to their quality of life,” he explained.
As Dr. Mehta pointed out, postoperative care is just as crucial. “In patients who’ve had more than 10 previous intravitreal injections, there was a 2.59 times greater likelihood of posterior capsule rupture,” he reported, underscoring the complexity of managing these patients.10
Editor’s Note: Reporting for this story took place during the 17th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2024) from 22-24 November in Singapore.
References
- Khanani AM, Kotecha A, Chang A, et al. TENAYA and LUCERNE: Two-year results from the Phase 3 neovascular age-related macular degeneration trials of faricimab with treat-and-extend dosing in year 2. Ophthalmology. 2024;131(8):914-926.
- Lanzetta P, Korobelnik JF, Heier JS, et al. Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial. Lancet. 2024;403(10432):1141-1152.
- Chandra S, Gurudas S, Sivaprasad S, et al. Baseline characteristics of eyes with early residual fluid post loading phase of aflibercept therapy in neovascular AMD: PRECISE study report 3. Eye (Lond). 2024;38(7):1301-1307.
- Campochiaro PA, Avery R, Brown DM, et al. Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study. Lancet. 2024;403(10436):1563-1573.
- Holekamp NM, Campochiaro PA, Chang MA, et al. Archway randomized Phase 3 trial of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration. Ophthalmology. 2022;129(3):295-307.
- Chakravarthy U. Characterization of associations between macular atrophy and subretinal fibrosis in treated neovascular AMD: 7 year findings from the IVAN trial. IOVS. 2022;63:1322.
- Yagi M, Miyake M, Yamashiro K, et al. Natural course of pachychoroid pigment epitheliopathy. Ophthalmol Sci. 2022;2(4):100201.
- Sarraf D, Khanani AM, Wong DT, et al. Pigment epithelial detachment thickness and variability affects visual outcomes in patients with neovascular age-related macular degeneration. Retina. 2024;44(1):10-19.
- Khanani A, Ambresin A, Avery R, et al. Reduction in pigment epithelial detachment with faricimab vs aflibercept: A subgroup analysis of patients with large and serous PEDs from the pooled Phase 3 TENAYA and LUCERNE trials. 19 September 2024. Available at: https://medically.roche.com/global/en/ophthalmology/euretina-2024/medical-material/EURETINA-2024-presentation-khanani-reduction-in-pigment-epithelial-detachment-pdf.html. Accessed on 22 November 2024.
- Mehta H. Management of cataract in patients with age-related macular degeneration. J Clin Med. 2021;10(12):2538.
