Research has always been a fundamental pillar of ICR Ophthalmology Center. Currently we are working in clinical trials and studies in several subjects. We interviewed Dr. Ignasi Jürgens, medical director and Head of the Retina and Vitreous Department, so that he could explain the current research in new treatments for retina diseases, such as macular degeneration or diabetic retinopathy.
What are the treaments currently available for retina diseases?
It depends on the disease. For atrophic age-related macular degeneration (85% of AMD) there is no treatment for now. It is a chronic disease consisting in the aging of the retina with a very slow progress.
On the other hand, diabetic retinopathy and exudative AMD have shorter term effects. They are usually treated with intravitreal injections, which are administered in different periods of time depending on the case of the patient. The introduced medicine is usually a component that fights the VEGF (vascular endothelial growth factor, a portein that affects veins). In some cases cortisone is also used in extended release, which can las between 1 month and 3 years depending on the type used.
Are these the most advanced options?
Yes, they are currently the newest treatments available for these diseases. At Institut Català de Retina we work with the latest scientific discoveries that have been proven to be effective for patients.
However, new treatments are being researched. Which ones?
There are currently several clinical trials in progress. For atrophic macular degeneration, the most frequent, new treatments to soothe swelling through the complement are being introduced.
What is the complement?
In order to explain it, a little background on atrophic AMD is needed. It is a kind of degeneration that makes very slow progress, but that in the long haul can provoke an important loss of sight. In this disease, waste that is usually removed by accountable cells is given off into the retina. In the case of atrophic macular degeneration, this waste accumulates, causing the death of surrounding cells. When this happens, the neurons in the retina stop working. In this process of programmed cellular death intervenes the complement system, which activates whenever there is swelling.
Therefore new treatments would act before retina neurons stop working and cause loss of vision?
Exactly. Two years ago we started taking part in a clinical trial exploring this way. It is a study with injections with the function of blocking this complement and the goal to prevent wear from growing. The pharmaceutical in question is called Zimura and in the results of the previous phase we can see that the disease does not advance as fast in patients treated with these injections. In these trials we can’t evaluate the improvement of the vision, because it is usually already lost, but we can control the disease and prevent it from advancing fast.
Are there more studies in progress?
Yes, at ICR we are close to entering in two more clinical trials to treat atrophic macular degeneration through the complement. Each one of them takes a different research path.
The first one is a treatment with pills, avoiding a needle in the eye.
The second one is similar to the system that we are already studying, but in this case it is treated with the intravitreal administration of a gene that codes the natural substance which inhibits this complement, the C-59. Cells are infected with a virus —RNA which codes the C-59— and they start making an analogous of the natural inhibitor.
Is it the same mechanism of the messenger RNA from COVID vaccines?
It is the same premise, but it works a little different. The system in the vaccine against covid-19 stimulates the making of antibodies. RNA synthesizes the antigen and the organism makes antibodies to provide a defense against this antigen. In the case of the medicine for the eye, we work with the missing protein or the necessary medication to fight the disease.
Is there a previous case of gene therapy within Ophthalmology?
There already is a pharmaceutical with gene therapy that is used to treat Leber congenital amaurosis. It is a virus that carries a “correct” gene, which replaces the faulty one with this disease. This gene synthesizes the defective protein. It is the first gene therapy approved for human use, in 2018. It is already in use, but it is a very specific medication for this disease that affects newborns, which could be around 20 in all Spain.
However, the treatments that we are researching from ICR along with other centers could benefit more than a million people.
What are the advantages of gene therapy?
With the treatment that we are researching, the cells keep working and the frequency of the injections is vastly reduced. In fact, this clinical trial is with a single injection. After one or two years, we observe the results.
The gene therapy is growing and it is a good tool because we are introducing something in the eye that starts to make on its own the needed element to treat the disease.
Are all these treatments for atrophic AMD?
Gene strategy is also being tested for exudative AMD. A gene producing the natural inhibitor is introduced in the eye, so it can synthesize it itself. With this option, the patient should undergo an intravitreal injection in a very inferior frequency.
What about the diabetes afections in the retina?
Exudative macular degeneration and diabetes share the same mediator, the mentioned VEGF, a protein that affects the veins in the same way in both diseases. That is why the medication that is being tested for one of them, will work for the other as well.
Could we “cure” these diseases with these new treatments?
In these studies we are not trying to recover the vision when it is lost; the goal of these treatments is avoiding the loss of vision when there is still some.
Could these treatments be useful for other vision disorders?
There are studies being made for neuroprotection, to avoid neuron deterioration or death. This research would also be useful to treat other pathologies, such as diabetic edema or glaucoma.
Regarding uveitis, when it happens due to swelling, the pharmaceuticals being used until now were immunosuppressive, very agressive —the same kind that are used in chemotherapy, for cancer. That is why this medication has been removed and another kind has been introduced: the immunomodulators, also known as biologic pharmaceuticals. This kind of medicine allows the reduction of corticoids dosage and therefore its side effects as well. There is a line of research in this medicine, in which ICR is also currently working on a clinical trial with Dr. Menezo, head of the Uveitis Deparment.
Do you think that the new treatments could replace the current ones?
For exudative AMD or diabetes, it is not a matter of a treatment complementing or replacing the previous ones: the goal of the current investigation is to reduce the frequency of (intravitreal) injections, whether it is with pharmaceuticals with a longerlasting effect inside the eye, with capsules releasing the medicine for 6 months to a year, or introducing the gene inside the eye for it to synthesize it on its own.
For atrophic AMD, the goal is finding a treatment, since for now there is none.
When are the new treatments expected to be available?
In general, it takes 10 years from the start of a clinical trial in phase 1 until the treatment is included. From phase 2, like in the case of the first study that we have mentioned, it takes about 5 years. But this numbers may vary. Indeed, we are talking about long periods of time, it will take a few years, but we must remain on the lookout.
Will these treatments be implementet at ICR?
Definetely. At ICR we try to implement any product, treatment or intervention that has been scientifically proven that can benefit our patients. In the case of atrophic AMD, it is perfectly clear, since for now there is no treatment whatsoever. Nevertheless, we must be very careful and deeply analyze all novelties, regarding both the benefits and the risks.
What should a patient with atrophic AMD know?
What we can do as of today is act upon the risk factors, such as reducing smoking, controling hypertension and cholesterol, having a balanced diet… Besides, from ICR we can try to recruit patients to enter some of these clinical trials. However, these trias have very strict admission requirements. If it is a patient with very bad sight, they will not be able to enter. However, in the case of a patient recently diagnosed or starting to develop symptoms, it is important for them to ask for an appointment with our doctors, so we can ease their admission to a study. At ICR we have recruited patients for the studies we have mentioned.
What can a patient do if they have not received this diagnosis?
It is important to pay attention to the main alert signs of macular degeneration:
- Loss of sight. The macula is the area in the eye with the maximum visual acuity.
- Visual distorsion, seeing as deformed lines that are actually straight.
If a person experiences any of this symptoms, it is important to undergo an ophthalmological checkup. At ICR we can adivse them and recruit them for a clinical trial for their benefit. It has been done multiple times before.