By Christopher Brittain, MB, MRCOphth, Vice President, Global Head of Ophthalmology Product Development at Genentech
Until about 15 years ago, vision loss due to retinal conditions related to age and diabetes was fairly common, and no treatments were available to return vision that was lost. However, with the introduction of revolutionary treatments in the mid-2000s, people with conditions like wet age-related macular degeneration (AMD) and diabetic macular edema (DME) have been able to both prevent disease progression, and in some cases even restore some of their sight.
The development of these treatments was a triumph of biomedical research that began with the discovery of the potent blood vessel growth-promoting agent, vascular endothelial growth factor (VEGF), during the second half of the 20th century. Excess VEGF production causes blood vessels to grow out of control, leak fluid and destroy function in the retina, the light-detecting surface at the back of the eye. By the first decade of the 21st century, scientists developed a pioneering medicine to block VEGF activity in the macula, the area of the retina that provides sharp, central vision for activities such as reading and recognizing faces.
VEGF inhibitors represented a seminal breakthrough for treatment of retinal conditions such as wet AMD and DME. At the same time, they were only the first step in a journey toward the elimination of vision loss due to these conditions. Over the next decade, we envision an ambitious opportunity to further improve patient outcomes through innovative new treatments and drug delivery methods. We’re also developing new artificial intelligence (AI) technology to improve early diagnosis rates and assessment of treatment options. Taken together, these advances have the potential to help us eventually prevent vision loss due to these retinal conditions altogether.
Better delivery systems for existing treatments
One of the biggest real-world limitations in effectively treating people with retinal conditions is the significant burden of treatment: anti-VEGF medicine must be injected into the eye as often as once a month. We know that patients don’t always get treated as often as needed, which can cause vision loss that might otherwise be avoided. To address this issue, we are developing and testing devices that can release medicine into the eye over many months. The hope is that patients will benefit from more consistent treatment without having to visit their doctor as often. We are researching ways to optimize these devices to better track drug delivery, optimize dosing and monitor the need for additional treatment.
New ways to limit vessel growth
VEGF’s central role in the branch-like growth of blood vessels makes it a natural first target for treatments that seek to stop the progression of retinal conditions. But it is far from the only one. Vessel growth is the result of interactions across a complex network of many growth factors, proteins and molecular regulators. We have a long history of fundamental research dedicated to fully understanding all of the mechanisms that drive blood vessel growth that can help us identify additional therapeutic targets. In recent years, our researchers have focused on several new pathways that play a central role in blood vessel growth and stability, such as Angiopoietin-2. By blocking multiple pathways, newer treatments may be able to utilize a different approach than blocking VEGF alone. A second target could also offer multiple treatment options depending on which aspects of the vessel growth process predominate in a given patient or type of retinal condition.
Artificial intelligence tools for improved diagnostics and treatment
Underdiagnosis of retinal conditions continues to be a huge missed opportunity for timely treatment. Up to 50% of people with diabetic eye disease and up to 25% of people with wet AMD are not diagnosed in time to prevent severe vision loss, partly because the conditions progress too far before a person notices vision impairment and seeks medical care. Our scientists are currently developing AI technology that can be used to identify the earliest stages of disease among people who still see well but are at high risk of vision loss due to age or diabetes. In the future, low-cost screenings can be executed through telemedicine appointments that leverage AI tools for accurate, economical and user-friendly remote monitoring and diagnosis. These and other tools would therefore have the potential to result in early disease detection, prevention of underdiagnosis and signiﬁcant reduction in the risk of vision loss.
Once these conditions are detected, current treatment for wet AMD and related conditions is fairly straightforward because VEGF inhibitors represent the gold-standard of care. But we believe that as more medicines become available, it will be important to refine our ability to assess the most important drivers of disease for each patient and to personalize dosing and therapy type before treatment begins. There is potential for the use of AI in this task as well, perhaps by developing algorithms that subdivide patients into treatment groups based on images of their retina. Eventually, these techniques could be used to personalize the right treatment for the right patient at the right time.
A hopeful future
The development of VEGF-inhibitors has been a pivotal breakthrough in the history of ophthalmology.
That essential development has reduced the rate of blindness in some conditions by 50%, but that was only the first step on a larger journey that we are taking toward eradicating vision loss due to retinal conditions. As we learn more about the underlying biology of these conditions, develop better ways to deliver treatments and harness emerging technologies to diagnose patients and personalize care, our hope is to have the ability to entirely prevent vision loss from the list of infirmities that come with age or as a result of diabetes.
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