Age-related macular degeneration (AMD) is the leading cause of visual disability in people over 50 years of age. © Adobe Stock
Age-related macular degeneration (AMD) is the leading cause of visual disability in people over 50 years of age. Improving the treatment offering for patients is a major challenge for research. In a new study, a team of researchers from Inserm, CNRS and Sorbonne Université at the Vision Institute[1] in Paris describes the efficacy of dopaminergic drugs in slowing the progression of one of the forms of the disease, namely the neovascular or ‘wet’ form which is characterised by the proliferation of dysfunctional blood vessels under the retina. These specific drugs are already used in the treatment of Parkinson’s disease. These findings have been published in The Journal of Clinical Investigation.
AMD is a multifactorial disease of the retina that affects people over 50 years of age. It is when part of the retina – the macula – degenerates, with the potential loss of central vision. Although highly incapacitating, it never causes complete blindness since the peripheral part of the retina remains intact.
There are two forms of the disease whose prevalence is roughly equivalent: the neovascular form – known as the ‘exudative’ or ‘wet’ form and the atrophic – ‘advanced dry’ form (see box).
While there is currently no curative treatment for the dry form of the disease, the neovascular form can be slowed down by regular injections administered directly into the eye (intravitreal injections). Although necessary, these injections can represent a major therapeutic burden due to their frequency, which is monthly or bimonthly depending on the course of the disease. It is therefore useful to continue to identify new alternatives for patients.
Medicines for Parkinson’s
Previous epidemiological studies have already shown a possible association between Parkinson’s disease and a reduced risk of neovascular AMD[2]. In this new study, researchers from Inserm, CNRS and Sorbonne Université at the Vision Institute explored the underlying mechanisms that would explain this potential protection.
In cell and animal models, the scientists have shown that L-Dopa, a drug in the dopaminergic family[3] used to treat Parkinson’s disease, activates a specific receptor in the brain known as DRD2. This activation blocks the formation of new blood vessels in the eye, which is a key process in the development of neovascular AMD.
To go further, the team then analysed the health data of over 200 000 patients with neovascular AMD in France[4]. They showed that those patients who took L-Dopa or other drugs that inhibit the DRD2 receptor (DRD2 agonists) to treat their Parkinson’s disease developed neovascular AMD later in life and required fewer intravitreal injections. Indeed, such patients developed the disease at 83 years of age instead of 79 years of age for the other patients.
‘These findings open up new perspectives for patients with wet AMD. We now have a serious avenue for delaying the progression of this disease and reducing the burden of current treatments’, explains Florian Sennlaub, Inserm Research Director at the Vision Institute (CNRS/Sorbonne Université/Inserm).
Thibaud Mathis, university professor and hospital practitioner in the ophthalmology department of Croix-Rousse Hospital-Hospices civils de Lyon, and researcher at Université Lyon 1, as well as at the Vision Institute, agrees: ‘These findings suggest that dopaminergic drugs, beyond their role in Parkinson’s disease, could have a beneficial effect in the prevention and treatment of neovascular AMD.’
While more in-depth clinical studies will be needed to confirm these findings and evaluate the efficacy and safety of these drugs in the treatment of AMD, this discovery opens up encouraging new perspectives for the fight against the neovascular form, offering hope of a more effective and less burdensome treatment for patients.
Two forms of AMD
Wet AMD is characterised by the proliferation of new dysfunctional vessels under the retina. Blood can leak through their walls and lead to the formation of macular oedema from which blood sometimes escapes, leading to retinal haemorrhages.
The wet form of AMD progresses rapidly if not managed. Previously, loss of central vision could occur within weeks or even days. This process can now be stopped thanks to drugs (anti-VEGF) injected into the eye, which inhibit the growth of new vessels. However, after several years of treatment, the disease can progress to an atrophic form.
In atrophic or ‘advanced dry’ AMD, the photoreceptors in the macula gradually disappear, followed by the retinal pigment epithelial cells. This process generates holes of increasing size in the macula, visible by simply observing the retina (dilated eye exam). This process is slow and usually takes between five and ten years before the patient loses their central vision. Currently, no treatment for this form of AMD is approved in Europe.
Mixed forms of the disease may be observed, and each of these two forms may precede the appearance of the second.
[1]This research is the result of collaboration with teams from Université de Lyon, Lyon University Hospital, Université de Bourgogne and the Brain Institute in Paris.
[2]Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration, Max J Hyman et al. Ophthalmology retina 2023
[3]Dopaminergic drugs provide the dopamine needed for the brain to function. In Parkinson’s disease, dopamine reduces the intensity of tremor, rigidity and akinesia.
[4] Data from the French national health information database (Système National des Données de Santé [SNDS]).