The Ophthalmology Department of Hospital de Sant Pau, together with the Ophthalmology Research Group of the Sant Pau Research Institute (IR Sant Pau), has recently participated in an international clinical trial of gene therapy for age-related macular degeneration (AMD) in its wet form, one of the leading causes of vision loss in older adults.
The procedure was carried out a few weeks ago and marked a milestone for the hospital, becoming the first surgery of its kind performed in Catalonia as part of the trial. The operation was completed without complications and marks the beginning of Sant Pau’s participation in this international phase 3 study, which is evaluating the efficacy and safety of the drug ABBV-RGX-314. “This is an innovative surgery in which we deliver the drug beneath the retina. The procedure went well, and we are now in the patient follow-up phase,” explains Dr. Ignacio Vela, principal investigator of the study at Sant Pau.
AMD is a degenerative retinal disease that affects central vision, making everyday tasks such as reading, recognizing faces, or handling money difficult. Although it does not cause total blindness, it significantly limits the independence of those impacted. It is estimated that between 4% and 8% of people over 70 years old suffer from this disease, whose incidence continues to rise as life expectancy increases.
There are two main forms of AMD: dry and wet. The dry form, which accounts for most cases, progresses slowly and currently has no effective treatment in clinical practice, though several trials are underway. The wet form, on the other hand, progresses much faster and can cause significant vision loss within a few months if left untreated.
Since 2006, the standard treatment for wet AMD has consisted of intravitreal injections of antiangiogenic drugs, which block the proliferation of abnormal blood vessels beneath the retina and prevent fluid or blood from leaking into the macula. Thanks to these drugs, thousands of patients have managed to slow the progression of the disease and preserve part of their vision for years. At the time, they represented a major breakthrough in the management of this condition, which until then almost inevitably led to severe visual loss in a very short period.
Despite their effectiveness, this approach has important limitations. The treatment requires a very intensive schedule: during the first year, patients usually receive six to eight injections, followed by ongoing treatments every two or three months for the rest of their lives. Each of these visits involves injecting the medication directly into the eye, which causes anxiety and discomfort—especially among older adults who often have other chronic conditions. Moreover, each procedure carries a small risk of complications, such as infection or ocular inflammation, which requires careful monitoring.
“We manage to stop vision loss, but at the cost of highly demanding treatments for both patients and the healthcare system. The idea behind gene therapy is precisely to avoid this dependence on continuous injections into the eye,” notes Dr. Vela.
The new approach seeks to overcome these limitations with a different strategy: enabling the eye itself to continuously produce the substance that controls the disease. Instead of relying on periodic injections to deliver the drug externally, gene therapy aims for retinal cells to produce the antiangiogenic protein on their own, creating a treatment “from within” that acts consistently and stably over time.
“What’s new here is that with a single surgery, the eye could continuously produce the medication we currently administer through injections. It’s an entirely different concept with great potential,” says the Sant Pau researcher.
This approach has not only medical implications but also social and economic ones. If the therapy works as expected, it could significantly reduce the burden of care by decreasing hospital visits and the need for repeated procedures. At the same time, it could improve patients’ quality of life by freeing them from the anxiety and impact associated with frequent injections. Although still an experimental strategy and pending confirmation of results, the potential of this approach makes it one of the most promising research avenues in the fight against wet AMD.
The procedure involves a microincision eye surgery in which the investigational drug ABBV-RGX-314 is delivered beneath the retina. This gene therapy drug uses a viral vector to carry a therapeutic gene. Once inside retinal cells, this gene enables them to produce a protein with an antiangiogenic effect, similar to the one found in already-approved medications.
The procedure requires extreme precision, as the medication must be placed exactly in the subretinal space and in a specific dose. To ensure safety and proper administration, international specialists oversee the entire process in the initial cases—from the storage of the product in the pharmacy to the moment of injection in the operating room.
The study is currently in phase 3 and includes about 500 patients worldwide. In Spain, around ten centers are participating, although each has been able to recruit only a very limited number of patients due to strict inclusion criteria. In Catalonia, Sant Pau has been the only hospital to perform the gene therapy surgery, while other centers have been assigned to the control arm with conventional injections.
The trial compares three groups of patients: two treated with gene therapy at different doses and a third continuing with standard treatment. Recruitment has now closed, and the one-year follow-up phase is underway to determine whether patients require fewer injections than before and, above all, to assess the safety and efficacy of this new strategy.
“We now have to wait for the results. It’s important to emphasize that this is not an available treatment, but an ongoing clinical trial. The expectation is that it may reduce the need for injections and improve patients’ quality of life, but we don’t yet know if it will work, and we must remain cautious,” stresses Dr. Vela.
The procedure performed at Sant Pau took place a few weeks ago, and the initial follow-up is positive, though it is still too early to assess results. “We need to wait at least one year of follow-up and then review the overall study findings. Until then, what we can highlight is the importance of Sant Pau’s participation in this pioneering international research,” notes the specialist.
Macular degeneration is an increasing problem in aging societies such as ours, and having innovative alternatives like gene therapy represents an opportunity that must always be pursued with scientific rigor. Participation in this trial reinforces the institution’s commitment to innovation in ophthalmology and contributes to advancing the development of future solutions for a disease whose prevalence continues to grow as the population ages.
