With aging populations, age-related macular degeneration (AMD) is set to increase. AMD, which causes progressive blindness, may already be present in the early stages in 20% of 60 year-olds and those who are older in some countries. Whilst 10 years ago there were hardly any treatments for AMD, the age of targeted drugs like vascular endothelial growth factor (VEGF) suppressants has changed the way in which AMD is controlled.
In The Lancet Series on Ophthalmology, professor Tien Yin Wong from the Singapore Eye Research Institute at the National University of Singapore, and his team discuss the issues that surround AMD.
AMD is a leading cause for loss of vision worldwide. The progressive chronic disease affects the central retina and whilst the condition is usually asymptomatic in the early stages, as the condition progresses, patients start accumulating white or yellow spots of a material called drusen, which becomes visible on examining the retina.
Most of the visual loss occurs in the late stages of the condition and is commonly brought on due to the ‘wet’ or ‘late dry’ process. In the former process, a sudden leakage of blood and fluids occurs in the central retina, which could lead to a rapid deterioration in vision and subsequent permanent visual loss due to scarring, whilst the ‘late dry’ form involves experiencing a progressive loss of vision due to a slow degeneration and decline in retinal function.
The care for wet AMD has been transformed with the development of two drugs, i.e. Lucentis (ranibizumab) and Avastin (bevacizumab). Both drugs are targeted to suppress VEGF and data indicates they are able to prevent a severe loss of vision in 95% of patients and considerably improve 40% of vision.
At $1,593 USD, Lucentis is much more expensive per injection than Avastin at $42 USD. However, Lucentis has been approved for treating AMD, whilst Avastin has so far not yet been approved, even though it is widely used on an off-label basis.
In the UK, Novartis, the manufacturer of Lucentis has started taking legal action in order to prevent the UKs National Health Service Trusts from using Avastin for this purpose. Given that both therapies require monthly injections and long-term safety data are not yet available, the paper has also raised safety issues as continuous suppression of VEGF may raise the risk of vascular events, for which, according to the researchers, more data is needed.
Environmental and lifestyle factors have a major impact on AMD. Smoking has consistently proven to raise the risk of developing AMD. The same goes for obesity and having insufficient antioxidant levels in one’s diet, like vitamin A, C, E and zinc. Older age is a risk factor that is non-modifiable, i.e. nothing can be changed about it, having a darker iris, previous cataract surgery, or being long-sighted are also known to increase the risk.
Another key discovery is that AMD has a strong genetic link, including genes associated with the immune system, HDL or good cholesterol, as well as those genes that are associated with mechanisms that affect collagen, the eye’s extra-cellular matrix, and angiogenesis, or the growth of new blood vessels.
Aside from Lucentis and Avastin, there are currently other new VEGF suppressant drugs in development. Research is investigating into potential roles for anti-inflammatory drugs, genetic approaches, stem-cell therapy, and retinal prostheses.
The authors conclude:
“Age-related macular degeneration is a major cause of visual impairment in older adults. No effective preventive drug therapies exist although nutritional and behavioral modifications can reduce progression to advanced age-related macular degeneration…anti-VEGF therapies have proven to be effective in reducing and, in some cases, reversing visual loss in those with AMD, although the monthly or bi-monthly treatment burden is high and the systemic long-term safety of these drugs remains unclear. A host of novel treatment modalities, including inhibition of other angiogenic factors, new preventive approaches, regenerative therapy, and visual prostheses, are on the horizon. These hold the promise of even better outcomes in the near future.”
Written By Petra Rattue