Cutting-edge solutions and revolutionary advancements poised to reshape retinal medicine in 2024
From novel drugs and gene therapies to the integration of artificial intelligence and advanced surgical tools, 2024 promises groundbreaking advancements in retinal care. Experts shared the latest trends that ophthalmologists are buzzing about, providing a glimpse into the transformative landscape of retinal medicine for the year ahead
One of the most dynamic and fast-paced fields in medicine, retina is constantly evolving and improving, with new cutting-edge solutions emerging seemingly every minute. These solutions often prove to be game- changers for surgeons and patients, leading to better diagnoses, shorter surgery times, smaller incisions, improved surgical safety and better outcomes.
Exploring the latest advancements, such as drugs, artificial intelligence (AI), 3D visualization and gene therapy, we take a look at the innovations and trends that ophthalmologists are discussing and eagerly anticipating in the retina field for the coming year.
A focus on anti-VEGF agents
The competition is ramping up in the battle against retinal diseases, thanks to the emergence of a couple of promising anti-vascular endothelial growth factor (anti-VEGF) agents. These additions bolster retina’s armamentarium in the fight against conditions such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).
“We have probably seen a ‘ceiling effect’ with regard to the efficacy of the anti-VEGF treatments available now,” shared Dr. Lee Mun Wai, vitreoretinal surgeon and medical director of Lee Eye Centre. “Newer molecules coming out are focused on reducing the burden of treatment by extending the intervals between treatments.”
Faricimab is one such treatment, gaining in popularity for its unique mechanism of action, which involves blocking both angiopoietin-2 and VEGF-A. It has the potential for extended durability with 16-week dosing.
Dr. Mae-Lynn Catherine Bastion, a vitreoretinal surgeon at the National University of Malaysia (UKM), shared that the YOSEMITE and RHINE phase 3 randomized clinical trials concluded that robust vision gains and anatomical improvements with faricimab were achieved through adjustable, with dosing up to every 16 weeks. This demonstrates the potential for faricimab to offer extended durability in the treatment of patients with DME.
“This is the newest agent on the Malaysian market,” she said. “It provides an option for patients looking to increase the interval between treatments, and it’s also suitable for those in whom other agents have proven ineffective.”
Dr. Manish Nagpal, a vitreoretinal consultant at Retina Foundation, India, said: “New anti-VEGFs are emerging, and I would be pleased to see one with a long-acting or sustained release profile. Faricimab has just been launched in India, and we have started using it.” Though it is still early, he said he expects it to exhibit superior efficacy compared to other currently utilized anti-VEGF agents.
Dr. Alay Banker, a vitreoretinal surgeon at Banker’s Retina Clinic and Laser Centre, India, couldn’t agree more. “Faricimab [in my opinion] is a superior molecule with a better outcome,” he said. “This is a definitive positive for our patients,” added Dr. Lee. He said he looks forward to hearing about experiences from retinal specialists in the Asia-Pacific region, continuously delivering medication over an extended period, the PDS aims to maintain the clinical benefits of monthly intravitreal anti-VEGF therapy while decreasing the injection burden. “PDS is another exciting development that we hope will reduce the number of injections patients get without compromising efficacy. This includes depot anti- VEGF repositories with slow release,” shared Dr. Bastion. The PDS was originally designed for ranibizumab in the treatment of nAMD, with the potential for future use with other molecules.
Gene therapy: Bringing hope to IRDs
Developments in gene therapy are being closely monitored for potential new treatments targeting inherited retinal diseases (IRDs), such as retinitis pigmentosa (RP) and Stargardt disease, which are caused by broken or mutated genes. While still in its infancy, many are optimistic that gene therapy has the potential to significantly benefit patients suffering from IRDs and provide positive outcomes. Gene therapy technology is directed to the appropriate part of the eye through a delivery vehicle, typically a safe and modified virus called a viral vector.
“Gene therapy is evolving, and I would be happy to see some concrete developments, especially in dystrophies such as Stargardt disease and retinitis pigmentosa,” said Dr. Nagpal.
Below are several ongoing developments in research on Stargardt disease and RP. Ascidian Therapeutics (Boston, USA) is set to launch a Phase 1/2 clinical trial for ACDN-01, its RNA exon editing therapy designed for people with Stargardt disease, an inherited form of macular degeneration caused by mutations in the ABCA4 gene. The trial, known as STELLAR, is scheduled for enrollment in the first half of 2024. Unlike genetic therapies that deliver an entire healthy gene to replace the mutated one or edit DNA, ACDN-01 rewrites RNA, the genetic message derived from DNA that cells read to make proteins
Belite Bio, a San Diego, US-based biopharmaceutical company, is also enrolling patients with Stargardt disease in DRAGON, its Phase 3 clinical trial for tinlarebant—an emerging oral medication designed to slow disease progression and vision loss. The medication aims to inhibit a protein known as retinol- binding protein 4 to reduce the uptake of vitamin A to the retina, thereby decreasing the production and accumulation of toxic vitamin Z byproducts, a telltale sign of Stargardt disease.
Nanoscope Therapeutics (Dallas, USA), a biotech company, has dosed at least six participants in its Phase 2 STARLIGHT clinical trial of its optogenetic therapy for individuals with advanced Stargardt disease. Some patients have reported vision improvements following this emerging treatment, administered via intravitreal injection. The therapy uses a human-engineered virus to deliver copies of the multi- characteristic opsin (MCO) gene to bipolar cells—cells that do not normally sense light but often survive after photoreceptors are lost to advanced retinal disease.
Alkeus (Cambridge, USA), another biotech company, is conducting a multi-center Phase 2 clinical trial for ALK-001, a drug designed to target the toxic build-up in the retina believed to cause degeneration and vision loss. This emerging therapy involves a modified form of vitamin A, which, when metabolized in the retina, results in less waste production.
Spark Therapeutics’ (Philadelphia, USA) vision-restoring RPE65 gene therapy, LUXTURNA (voretigene, neparvovec), has received marketing approval from the US FDA, making it the first gene therapy to gain regulatory approval in the US for the eye or any inherited condition. LUXTURNA demonstrated its efficacy in restoring vision during a clinical trial for patients with Leber congenital amaurosis caused by mutations in the RPE65 gene. The treatment is also designed to work for patients with RP caused by RPE65 mutations.
GenSight, Bionic Sight, and Nanoscope have launched separate clinical trials for their optogenetic therapies for RP and potentially other retinal diseases.
“Gene therapy and stem cells are always in the conversation when it comes to retinal diseases, and I look forward to seeing continued progress in this field,” said Dr. Lee. “I believe it will be the ultimate solution if a safe and effective method for delivering gene or stem cell therapy to the retina [can be established].”
Dr. Bastion noted, “I think the anticipated developments would be in therapies for inherited retinal diseases such as retinitis pigmentosa, in which programmed cell death occurs, and for which no other therapy is available.
“Hence, we have heard of gene therapy in which a viral vector reprograms the defective cells, thus halting the progression of the disease. These interventions need to be introduced prior to irreversible damage.”
However, Dr. Bastion acknowledged that challenges persist in safely introducing the viral vector to the subretinal space. “Hence, there is growing interest in suprachoroidal and subretinal access for these therapies,” she added.
Embracing the era of AI
While some may fear the onslaught of AI in this day and age, with concerns mounting about the potential for this disruptive technology to take away jobs, ophthalmologists not only expect further advancement of artificial intelligence (AI) this year but also anticipate its positive impact in the ophthalmic industry.
AI has the potential to further penetrate several aspects of healthcare, including imaging diagnostics, surgical platforms, telemedicine and administrative tasks. Deep learning algorithms can be used to screen for conditions such as diabetic retinopathy, retinopathy of prematurity and other diseases. They can also predict future disease progression from optical coherence tomography (OCT) scans.
According to Dr. Banker, future innovations could look into AI- based systems that facilitate improved screening of common retinal diseases in remote areas. These systems may also predict outcomes and determine the need for treatment in patients.
“In the coming years, I think operating and imaging systems will become more affordable, with a lot of AI incorporated into their platforms. This advancement will aid surgeons and diagnostics, facilitating better decision-making and improving patient outcomes,” Dr. Banker predicted.
“Artificial intelligence is already being used to screen and diagnose retinal diseases, and I look forward to the development of more mature algorithms and seamless integration into our clinical practices, which will ultimately benefit our patients,” chimed in Dr. Lee.
Advanced cutters and imaging: Sharper than a serpent’s tooth
While medical retina has enjoyed groundbreaking advancements, the field of surgical retina has also seen its fair share of innovations—from faster cutters to improved viewing systems.
“Vitrectomy systems have progressed to improve surgical efficiency and safety,” shared Dr. Lee. “Newer designs of vitrectomy cutters with a beveled tip allow for better tissue manipulation, while smaller gauge cutters of 27G and high-speed cutting of up to 20,000 cuts per minute contribute to improved safety for our patients,” he added. Higher cutting rates reduce pulsatile fluid flow, an important source of vitreoretinal traction.
The HYPERVIT Dual Blade Vitrectomy Probe by Alcon (Geneva, Switzerland) features a continuous duty cycle with a speed of 20,000 cuts per minute. The beveled-tip design is available in 23, 25+ and 27+ gauge sizes, boosting cutting efficiency while minimizing fluidic turbulence.
Recent advances in endoillumination technology focus not only on improving safety and brightness but also on enhancing the durability and versatility of tools.
“In retinal surgery, visualization is everything, and the improved illumination systems integrated with our machines have improved visualization significantly,” said Dr. Lee.
Digital imaging in vitreoretinal surgery is also becoming more accessible to the masses, and this has the potential to revolutionize the way surgeons operate. Instead of depending solely on microscopic viewing, this technology offers a promising alternative, he added.
Dr. Nagpal concurred. “Surgically, new high-speed 20,000 cutters have been recently introduced in India. They are excellent in increasing efficacy and safety for the patient,” he said.
New generation vitrectomy machines are in development, and Dr. Nagpal expects to see some emerging in the next few years that would improve the technology used as well as enhance safety. “Imaging systems, of course, keep evolving, and we might see new ones or more advanced versions of the same in the coming years,” he noted. Dr. Bastion is also anticipating new developments in state-of-the-art imaging and viewing systems. A ‘heads-up’ approach in surgery has many advantages, including an increased depth of field, ergonomic benefits, reduced fatigue and teaching benefits.
One heads-up system, the Alcon NGENUITY, can be used with any microscope. It features a 55-inch viewing LED screen with four colors per pixel, providing customized images, hues, colors and resolution. The system is continuously upgraded. “Viewing methods have advanced further, with 3D viewing preferred for surgery, especially macula surgery. Three-dimensional viewing systems make the surgery more comfortable for surgeons and a delight for the trainees, as they can all see the surgery in 3D, not just the assistant,” shared Dr. Bastion.
She added that in this area of macular surgery, intraoperative OCT also remains helpful. “However, the cost remains a challenge for both these technologies in Malaysia. Therefore, 3D viewers need to be truly affordable before they can be widely utilized,” she noted. When it comes to retinal imaging, Dr. Bastion looks forward to wide-field imaging non-mydriatic cameras, wide-field OCTs and wider- field OCTA— all with more easily interpretable and motion-adjusted capacities.
There you have it. As technology continues to progress, we can anticipate further advances in retinal treatment that will enhance outcomes for patients. Indeed, 2024 is shaping up to be a very exciting year.
Editor’s Note: A version of this article was first published in PIE Magazine Issue 29.
