What do our eyes tell us?

This story is part of a series on current advancements in regenerative medicine. This piece begins a series dedicated to the eye and vision restoration improvements.

In 1999, I defined regenerative medicine as the set of interventions that restore normal function to tissues and organs damaged by disease, injured by trauma, or worn down by time. I encompasses a full spectrum of chemical, gene and protein based drugs, cell based therapies and biomechanical interventions that achieve that goal.

The field of regenerative medicine is developing rapidly and offers new hope to individuals suffering from visual disorders. In particular, there is growing potential to restore vision and transform lives with breakthrough treatments.

The human eye, an intricate sensory organ responsible for our ability to perceive the world, has numerous complex structures, such as the cornea, iris, lens, retina, and optic nerve. With these complex structures comes the potential for diseases and conditions that can lead to blindness and visual impairment.

Cataracts, glaucoma, diabetic retinopathy and age-related macular degeneration are the most common optical conditions affecting millions of people worldwide. While cataracts lead to clouding of the lens, leading to blurred vision, glaucoma is caused by damage to the optic nerve, leading to loss of peripheral vision. People with diabetes can also develop diabetic retinopathy, a condition that affects the blood vessels in the retina and leads to visual impairment if left untreated.

A recent review delved deeper into age-related macular degeneration and the role of regenerative medicine in its treatment. Age-related macular degeneration, a leading cause of vision loss in people over 50, affects the center of the retina, leading to blurry or distorted vision.

Age-related macular degeneration and disease burden

Age-related macular degeneration (AMD), a chronic eye disease, will affect 196 million people worldwide as of 2020, and with an expected increase to 288 million by 2040, the prevalence is increasing. AMD has a major impact, reducing people’s quality of life, mobility and independence. This in turn leads to more falls and depression.

This disease has become a major global cause of disease burden and a major cause of inequality in health outcomes, disproportionately affecting low-income countries with low human development index values.

The disease burden in Africa is more than twice as high as in America. In addition, Asia, which accounts for about 60% of the world’s population, is expected to carry more than a third of all AMD cases. Despite significant advances in treatment, age-related macular degeneration remains a major public health problem.

Classify macular degeneration

Age-related macular degeneration is a medical condition that causes a loss of central vision in the affected eye. This can make daily activities such as reading or driving difficult. It occurs when the cells of the macula, the small area in the center of the retina, begin to deteriorate over time.

The Beckman Initiative for Macular Research proposed a clinical classification system for AMD in 2013, which is now commonly used in research and clinical settings. This classification system only requires clinical examination or color fundus images, making it universally accessible and applicable.

Color fundus images capture intricate details of the fundus. The pictures can provide insight into the retina, blood vessels, macula, and optic disc. It allows doctors to identify vascular abnormalities, monitor disease progression, and evaluate the effectiveness of treatment. These images are essential in diagnosing and treating AMD.

Neovascular AMD, also known as wet macular degeneration, is defined as the presence of neovascularization beneath the retinal pigment epithelium.

Geographic atrophy, also known as dry macular degeneration, involves the loss of photoreceptors and retinal pigment epithelium and presents as a sharply defined pale area with exposed underlying choroidal blood vessels.

Both types of age-related macular degeneration (AMD) can be asymptomatic in their early stages, but can cause night blindness and difficulty adjusting to low light. Early detection and monitoring are crucial for identifying neovascular complications and ensuring timely medical intervention.

What Causes Macular Degeneration?

Age-related macular degeneration is a chronic retinopathy that develops from oxidative damage to the retina over time. This damage affects several eye structures, including photoreceptors, Bruch’s membrane, choriocapillaris, and the retinal pigment epithelium.

Retinal pigment epithelial cells (RPE) accumulate intracellular waste as we age, primarily lipofuscin or drusen. This buildup leads to oxidative damage and the aggregation of debris in sub-RPE deposits, manifesting as drusen – the hallmark of AMD. This buildup over time is why age is the main risk factor for the condition.

While age is an important risk factor for macular degeneration, other factors such as diet and heredity may also play a role. While lifestyle factors such as diet fall under modifiable risk factors, less controllable factors such as genetics cannot be easily changed.

Smoking poses the highest risk of all preventable factors, tripling the chance of developing the condition. Still, quitting smoking can help reduce this risk. Regular exercise may provide some protection, but research has shown it to be an important mitigating factor in developing macular degeneration.

Research leads us to future treatment insights

While progress has been made in the treatment of age-related macular degeneration, there are still gaps in our understanding of the disease and its treatment. Currently, research is focused on studies of early intervention to slow or prevent disease progression.

To improve the accessibility and efficiency of studies, regulatory-approved primary endpoints play a critical role. However, to date, such measures of disease progression have not been approved, with late-stage age-related macular degeneration being a notable exception. Contrast sensitivity, best corrected visual acuity, and geographic atrophy lesion growth rate remain the only measures recognized by these agencies.

Researchers are actively exploring methods to streamline the progression of early intervention trials. They focus on developing clinical endpoints by collecting patient feedback and using anatomical and functional markers. To achieve this goal, experts have teamed up to form a consensus group to establish a more comprehensive classification of age-related macular severity accounting for early biomarkers and surrogate endpoints.

Innovation in technology and strategies such as integrating AI into screening tools, developing advanced home-based monitoring tools and prioritizing marginalized and vulnerable groups hold promise in the fight against age-related macular degeneration and other retinal diseases.

Effective therapies for macular degeneration have the potential to open a new era of transformative outcomes, significantly reducing the burden of disease for aging populations. Investing in the development of treatments for age-related macular degeneration can have far-reaching consequences that benefit millions of people worldwide.

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