05/27/2020

There are some 6,000 known genetic disorders, caused by one or more mutations in DNA. Many affect the eyes, and some, such as retinitis pigmentosa, are specific to the eyes. Because genetic disorders are complex, the needs of patients with these disorders are often complex too.

To address the needs of patients with genetic eye disease, doctors Jefferson Doyle and Mandeep Singh have established the Wilmer Genetic Eye Disease Center (GEDi) at Johns Hopkins Medicine. The center offers coordination of care for patients with genetic eye diseases, along with dedicated genetic counseling and access to subspecialists in all fields of ophthalmology.

At GEDi, patients are triaged to match them with the right subspecialist for their condition. The center’s patient care coordinator can schedule appointments with multiple providers, sometimes in multiple departments at Johns Hopkins, to minimize the need for repeated visits. Because testing for conditions such as inherited retinal dystrophies can be difficult to conduct for very young children, GEDi offers special testing modalities for children as young as 1, as well as for older children and adults with developmental or physical issues that may prevent them from having standard testing. This can allow diagnoses for people who might otherwise go undiagnosed for years.

Highly Specialized Care

For some patients with a suspected systemic genetic condition, subtle eye findings may help confirm a diagnosis. Other patients may present with an isolated eye finding that is genetic but may not be readily recognized as genetic. “If we identify a particular feature in the eyes that may suggest a systemic genetic problem, having the knowledge to send that person for work-up with other groups around the hospital is really important,” says Doyle.

In fact, it can be critical. Marfan syndrome, one of Doyle’s specialties, is a systemic condition that can cause lens dislocation. It can also cause potentially deadly aortic dissection. “I had a patient come in with a lens dislocation whose father had died from a ruptured aorta, yet no one had ever done a work-up for Marfan syndrome,” says Doyle. “She'd never had an echocardiogram to make sure she wasn’t at risk of aortic rupture.”

Often, one of the biggest challenges for patients with a genetic condition is identifying a diagnosis, and many spend years trying to find one. Having a diagnosis is important because it can tell the patient what is the likely course of a disease, whether family members are at risk, the chance that future offspring will be affected and what treatment options may be available. With a diagnosis in hand, patients can also find out if there are any clinical trials they could participate in (or benefit from, if trials produce new treatments). Christy Smith, GEDi’s board certified genetic counselor, can advise patients and families on all of these issues and help them navigate the maze.

Having a dedicated genetic counselor on-site can also speed up the process for patients who might otherwise have to wait for an appointment with a genetic counselor. This can be particularly important for patients who require genetic testing in order to participate in a clinical trial. Long wait times can also affect the ability to treat a disease before it damages the eyes.

Game-Changing Therapies

In recent years, significant advancements in the field of genetics have been made, and there are new opportunities for therapeutic intervention. Nowhere is this more apparent than in the field of ophthalmology, which pioneered some of the first gene therapies approved by the Food and Drug Administration (FDA). In 2017, the FDA approved a gene therapy for Leber congenital amaurosis, a rare form of inherited vision loss. Doyle and Singh foresee many more gene therapies coming on line — therapies that may greatly improve the quality of life for those affected by genetic eye diseases.

For example, genetic forms of glaucoma have traditionally been treated much the same as nongenetic forms, with the goal of lowering eye pressure with eyedrops or surgery. But, says Doyle, “If you have a gene therapy that can negate the need for lifelong eyedrop use in children, or negate the need for really challenging, repeated surgeries that have significant complications, that would be a game changer.”

GEDi is already well-positioned to become a major center for genetic clinical trials. Current, completed and upcoming genetic clinical trials at GEDi include those for Stargardt disease, X-linked retinitis pigmentosa and juvenile glaucoma.

For patients whose disease has already progressed — perhaps due to late diagnosis — the hope is that regenerative therapy, such as stem cell therapy, will be useful to replace what has been lost. “I think the field is in a position where there is such opportunity to help many people,” says Doyle, “and Hopkins is really the ideal place to do it. You have this incredible wealth of knowledge and experience that is the Wilmer Eye Institute, and you also have one of the top departments of genetic medicine.”

Strength in Numbers

With its potential to draw a large number of patients, GEDi may produce important insights on the research front. For example, the center may see two or more patients whose condition strongly points to a genetic syndrome, but whose genetic testing comes back negative. Being able to identify a group of patients with similar presentations may indicate a novel gene mutation as the cause of their condition. “If you start to see enough of those patients and do gene discovery on them, you’re potentially pushing the field forward,” says Doyle.

Jefferson Doyle, a pediatric ophthalmologist who trained at Johns Hopkins and Harvard University, has a Ph.D. in genetics. Mandeep Singh is an adult vitreoretinal surgeon and retinal dystrophy specialist who trained at the University of Oxford, where he also obtained a Ph.D. in stem cell therapy. Among only a handful of ocular genetics specialists in the U.S., both are practicing clinician-scientists at Wilmer Eye Institute with dedicated clinics for patients with genetic eye diseases.