by Mark Steedman, PhD
This week’s blog is the second in a series focusing on eye health, which we are writing in advance of the launch of a global report on eye health at the November 2018 World Innovation Summit for Health (WISH). Our first blog in the series focused on glaucoma. This blog examines in more detail another leading cause of eye morbidity that affects millions of people around the world – age-related macular degeneration (AMD).
AMD is a chronic disease that causes blurring or loss of central vision as a result of changes to the macula – the small area in the centre of the retina that allows us to see small details clearly. The macula also controls most of our colour vision, as it is densely packed with light-sensitive photoreceptor ‘cone’ cells. As AMD progresses, many of these cells die, which results in the loss of the ability to discern fine details in our central vision. Overall, an estimated two million people worldwide are blind from AMD, and a further 8.4 million have moderate to severe visual impairment.1 The pathology of the disease is also complicated, as AMD comes in two forms – dry and wet.
Dry AMD, also known as early AMD, develops due to a build-up of waste material under the macula, which becomes thinner as a result. Dry AMD is the precursor and less severe of the two forms, as most people with dry AMD have near normal vision or mild sight loss, often characterised by visual distortions and increased blurriness that gradually get worse over several years. Currently, there is no treatment for dry AMD. However, a number of risk factors have been identified through research, including age, family history and genetics, race, smoking, obesity, and cardiovascular disease.2 In some people – about ten per cent of all people with AMD – the dry form of AMD progresses to the wet form.3
Wet AMD, often called ‘exudative’ or ‘neovascular’ AMD, is different. Small, abnormal blood vessels grow underneath the retina, which are susceptible to leaking or rupturing. Bleeding and the subsequent scarring that can occur from one or more of these blood vessels rupturing can lead to severe, permanent loss of central vision. However, unlike dry AMD, there are treatments available for wet AMD. The most successful of these treatments are intravitreal injections (injections directly into the eye) of anti-vascular endothelial growth factor (anti-VEGF), which are generally given every one to two months. Anti-VEGF inhibits the growth of new blood vessels in the eye, and repeated injections of the drug can lead to slower progression of the disease and, in some cases, moderate gains in vision.4
My own interest in AMD – and inhibiting the growth of blood vessels in the eye – goes back to my time as a PhD student at the University of California San Francisco. Part of my PhD dissertation focused on developing a biodegradable implant that could deliver anti-VEGF to the eye over an extended period of time. The long-term goal of my research was to develop a device small enough that it could be injected into the eye in the same manner as current injections, but it would deliver anti-VEGF in a sustained release profile. Consequently, the concentration of anti-VEGF in the eye would remain at a constant level over time, making the drug more effective. Figure 1 shows theoretical anti-VEGF concentration profiles for an anti-VEGF implant versus three injections of anti-VEGF over time.
Figure 1. Anti-VEGF concentration profiles over time
Source: Deloitte LLP, 2018
The studies I performed as part of my PhD were very preliminary, and by the time I completed my dissertation in 2010 it seemed that it would take many more years of research and development for a functional device that fit all the required parameters to become available on the market. Now, eight years later, the results of a Phase II study using a device similar to what my research group and I envisioned have been published, showing the device to be safe and effective. The current version of the device is slightly longer than a grain of rice and is refillable but not biodegradable, and it delivers anti-VEGF for six months or longer before it needs refilling. With the success of the Phase II trial, a Phase III clinical trial is expected to begin later this year.5
This exciting advance in AMD treatment follows on from another breakthrough in AMD treatment that was announced in March of this year, in which stem cell-derived retina tissue was implanted in two patients who were able to regain reading vision. I explored this breakthrough in more detail in a previous blog on tissue regeneration.
These and other advances in eye health demonstrate that innovation is alive and well, and that there is hope on the horizon for treating some of the most intractable eye diseases. However, epidemiologists are predicting that the growth of non-communicable diseases – particularly diabetes, and consequently other eye diseases like diabetic retinopathy – will lead to a staggering increase in global visual impairment in the years to come. We will explore diabetic retinopathy in more detail in our next blog in this series, as well as some of the strategies that could potentially limit the burden these diseases place on health systems and the global community.