Atrius Health

Angela Turalba

More than three million Americans are estimated to be living with glaucoma – but only half are aware they have the disease. Glaucoma is a progressive deterioration of the optic nerve that results in blindness if uncontrolled. Since there are typically no symptoms to warn patients of the disease, glaucoma can go undetected for the early part of many patients’ lives. Glaucoma is one of the leading causes of irreversible, age-related blindness worldwide and while there is no cure for it, medication and/or surgery can help prevent further vision loss.

Glaucoma is an expensive condition for our healthcare system, annually costing the U.S. economy $2.86 billion in direct costs and productivity losses. Due to the age-related nature of the disease, we expect increasing expenses of diagnostics, medication and treatment for glaucoma as the U.S. population ages.

Worldwide, glaucoma affects millions of patients and is a complex disease to translate across different populations. There are several sub-types of glaucoma, each with different clinical characteristics. On a global level, the distribution of these glaucoma sub-types vary and therefore, the screening protocols must address specific populations’ needs.

The heterogeneity of this disease creates numerous challenges in screening, diagnostics and treatment. For example, African-Americans with glaucoma can present with high eye pressures, and using eye pressures for screening in this population is reasonable. However, 90 percent of patients with glaucoma in Japan present with average eye pressures and screening with eye pressures may not be as effective there. Similarly, because the U.S. population is so diverse, universal screening guidelines or protocols are difficult to adopt.

Additionally, there is no single diagnostic test for glaucoma. The detection of disease often relies on a clinical diagnosis rather than a single lab test that unequivocally determines whether a patient has the disease. This affects costs as clinicians often monitor patients for life, making it difficult for clinicians to remove high-risk patients from monitoring protocols. Like with many cancers, there is no cure for glaucoma and many treatments can only delay its progression. So treatments are also life-long for many patients.

The field is gaining a better understanding of the genetics of the disease and making revolutionary advances in screening and diagnostics. There have been several genes now linked with smaller subsets of inherited glaucoma conditions that can be used to screen high-risk patients. On a broader scale, epidemiologic studies have helped clinicians to better target screenings. In the United States, there is a higher incidence of glaucoma in African-Americans compared to Whites. A 2017 study in Baltimore, Maryland focusing on African-American patients saw success using a sequential referral approach to assess specific factors in a group of individuals over 50 years in age. After an initial screening, individuals were referred for a complete eye examination - after which 51 percent ultimately received diagnoses of glaucoma.

Telemedicine is being used for better access and imaging tools to screen patients at risk of glaucoma. Researchers are exploring ways patients can take a photo of their optic nerve using an app and camera on their smartphones to send to an ophthalmologist. Clinicians are also looking at better imaging tools that incorporate Artificial Intelligence (AI) into screenings as well. For example, clinicians are able to take photographs of nerves and use AI to interpret whether a nerve is normal or abnormal.

AI can be used in visual field testing to check patients’ peripheral vision and determine whether a field test is normal, abnormal, or getting worse over time. Since clinicians still rely on their experience and expertise to interpret these diagnostic tests, developing AI tools will hopefully assist clinicians to make those decisions more accurately, with fewer tests, and earlier in the disease course.

These advances in diagnostics are complemented by recent advances in treatment, with new medications that address the disease using different mechanisms. Since the 1980s, five new classes of medications and various combination medications have been developed for glaucoma. Two recent FDA-approved medications – Vyzulta® and Rhopressa® - each work differently from other existing glaucoma medications. Vyzulta® is the first nitric oxide-containing medication for glaucoma and helps lower eye pressure by relaxing the trabecular meshwork. Rhopressa® lowers eye pressure by decreasing resistance to drainage or outflow in the conventional outflow pathway.

However, patient non-adherence is a significant problem in the medical treatment of glaucoma. Many patients have difficulty using eye drops, remembering medications, and tolerating side effects from the drops. To combat this, researchers are developing devices which slowly release medications on the surface of patients’ eyes and even in their eyes. Drug-delivery devices include surgical implants – such as the topical bimatoprost ocular insert, drug-eluting punctal plugs, drug-eluting contact lenses, and bimatoprost and travoprost intraocular implants. These may prove to have the advantage of being more effective because they help remove patient adherence from the equation. Additionally, there are established laser treatments that have been shown to be effective in treating some forms of glaucoma that serve as an alternative to self-administered drops.

There are also surgical techniques to lower eye pressure and prevent disease progression. Though effective, older more invasive procedures have been associated with vision-threatening risks. More recent innovations in minimally-invasive glaucoma surgery have transformed the surgical management of glaucoma because of their improved safety profile. The iStent® and Hydrus® are approved implants used at the time of cataract surgery that enhance the eye’s pathways that regulate eye pressure. The XEN gel stent® is another approved implant that facilitates the flow of fluid out of the eye in a controlled and less-invasive technique.

While several challenges still exist in managing glaucoma, clinicians in the United States remain optimistic about technological innovations in the field and the potential for improved patient care. By advancing screening, diagnostic and treatment modalities for this disease both in the United States and abroad, ophthalmologists can establish a clear vision for improving the lives of millions around the world.