Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults above 50 years of age. And we just had a new report published that answers a question that we have long asked: would the approved supplements help in late stage disease? Before we get there, a quick summary.
The burden
The disease represents a huge financial and social burden. In the early and intermediate stages, there are deposits of fatty proteins in the retina which we cal drusen. In the later stage though, AMD can be classified into two subgroups, dry or wet, according to presence of new vessels that grow beneath the retina. There is no cure for the condition, but the biggest issue resides in that the only treatment approved to halt the dry form of AMD is based on repeated injections into the eyes which carry a significant cost. And this is approved to use in the very late stage of dry AMD where there is “scar tissue” known as geographic atrophy. The efficacy of this treatment also seems to be modest; it was just approved in the beginning of the year though, so hopefully we will have longer-term data coming soon. Otherwise, the treatment options rely on lifestyle modifications and oral supplements.
The AREDS supplements
The age-related eye disease study (AREDS) and its follow-up study (AREDS2) were arguably the most important studies in the dry form of AMD. It thoroughly modified the field, with a huge amount of information being put forward from the data provided in these studies. The oral supplement proposed in these studies is known as the AREDS formulation, which is based on a specific combination of micronutrients with antioxidant properties. The AREDS formula then swapped beta-carotene for lutein/zeanxanthin in the AREDS2 study given concerns about a higher incidence of lung cancer in smokers in the beta-carotene group. I talked all about this in a podcast episode (embedded below), so feel free to give it a listen if you are interested. But the point here is that the AREDS supplements were shown to slow progression from intermediate stage AMD to late stage AMD, which we know for many years now. However, a question about its efficacy in the late disease stage/geographic atrophy remains.
Is the supplement still effective in late stage disease (geographic atrophy)?
Well, if you’ve asked before this new report, the transparent answer would be “we don’t truly know.” However, data analysed retrospectively (also called post hoc) from the AREDS and AREDS2 studies suggested that patients with late stage disease may also benefit from the supplements.
The imaging tests from the patients in the two AREDS studies was re-analysed by calculating the rate of expansion and the location of the scarred tissue. When the very center of the retina is affected (a region named fovea), supplementation had no benefit. However, in patients who developed the geographic atrophy away from the fovea, there was considerable benefit: the AREDS supplements slowed the rate of disease progression towards the centre of the retina/fovea. For full clarity, the fovea is responsible for our central vision; the same vision we use for driving, reading, using our computers, etc. So, this is a huge finding indeed.
Stats for nerds (like me – don’t be ashamed!)
In the group of patients who received the antioxidants (Vit C, E and beta-carotene) and had sparing of the central retina (n=208), progression towards the central region of the retina was slower than the ones that did not receive these (p=0.012). Specifically, there was an increase in the scarred region of 50.7 µm per year in patients taking the supplements vs 72.9 µm per year in patients taking placebo, which implies a slower rate of progression. This was also the case for patients who received the formulation without beta-carotene (n=325) – the scarred area was 80.1 µm per year vs 114.4 µm per year for placebo, which was also significant (p=0.011). This difference was not significant though in patients where the fovea/central retina was not spared.
One consideration to make is that this data was looked retrospectively, or after the event took place (in this case, after the clinical trial has ended and the data fully acquired). Essentially, this means that the hypothesis was generated after the data had already been observed. While it is not ideal, this new analysis does provide evidence of a potential benefit. Hopefully, these findings can be confirmed in a future clinical trial.
Have a nice week. I will see you in the next article!
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Thales A. C. de Guimaraes, MD, PhD
Host and Founder | Eyes On Research