On Tuesday, December 18, 2017, the United States Food and Drug Administration approved the first ever gene therapy for an inherited disease. Patients with a type of Leber congenital amaurosis (LCA), a blinding childhood eye disease, due to mutations in the RPE65 gene will now be able to receive treatment to improve their sight. This is a landmark day, and one which countless scientists, physicians, and patients have worked toward for decades.

LCA is a genetic condition which causes severe vision loss and blindness in childhood. Affected children are often born with very poor vision, and parents may notice their child never seems to make eye contact, has roving eye movements, or nystagmus, where the eyes shake back and forth. Almost all LCA is autosomal recessive, meaning each parent is a carrier for the disease, that each child of these two parents will have a 25% risk of developing the disease, and that affected individuals have a <1% chance of passing it on to their future children. Until the late-2017 FDA approval of voretigene, there were precisely zero commercially-available treatments for LCA.

Fortunately, and miraculously, this is changing.

Scientists have developed a treatment, called voretigene neparvovec (Luxturna is the trade name), which can be given to patients with this specific type of LCA. This treatment is a type of gene therapy, which means that the correct version of the defective gene is given to the patient, allowing the RPE65 protein product to perform its normal function in the eyes (RPE65 is an enzyme involved in recycling Vitamin A in the visual cycle).

Voretigene makes use of a benign virus to carry the correct version of the RPE65 gene into the patient's eyes. The patient undergoes a surgery, under general anesthesia, during which voretigene is injected very carefully, by highly trained vitreoretinal surgeons, underneath the retina.

I have seen several patients who underwent this treatment during voretigene's clinical trial. I was very impressed with the results -- children with no functional vision were suddenly able to see well enough to navigate the room. Results from the phase 3 clinical trial were published recently in the prestigious journal Lancet, with my friend and training mentor Dr. Stephen Russell of the University of Iowa as the lead author.

Voretigene represents a historic breakthrough on multiple levels. Not only is it the first medical treatment for a previously untreatable disease, allowing blind people to see for the first time, but it is also the first gene therapy for an inherited disease of any kind. It will also pave the way for future research and development of similar treatments for similar diseases. As a pediatric ophthalmologist and inherited eye disease specialist, it is difficult to overstate how excited I am about this!

Curious as to what kind of a difference this treatment can really make? Check out these next two videos. The first shows a boy with RPE65-LCA trying to navigate an obstacle course prior to his treatment. Notice how much he struggles.

Now, watch this same boy, a few months after treatment with voretigene, navigating a similar obstacle course. It's a night-and-day difference!

The future is bright for people with LCA and other inherited eye disease, and I enjoy dedicating part of my practice to holding a special clinic just for patients with these conditions.

At the 2017 meeting of the American Association for Pediatric Ophthalmology and Strabismus, Dr. Alex Levin, pediatric ophthalmologist at Wills Eye Hospital, pointed out that there are only 70-80 ocular geneticists in the world. Dr. Levin himself is one, and so am I. Having completed a year of inherited eye disease fellowship at the University of Iowa with experts like Dr. Edwin Stone, in addition to working as a comprehensive pediatric ophthalmologist and taking care of every type of childhood eye problem, I now dedicate part of my practice to patients with rare, blinding diseases of childhood. I'm happy to be able to offer this service to the region, as area patients formerly had to go to Seattle or Portland to receive this specialty care.

At the Spokane Eye Clinic, my pediatric inherited eye disease clinic takes place once each month, and they are some of my favorite days of work. I schedule just a few patients that day, so that each patient can receive the same high-quality, comprehensive care that I learned to provide in fellowship.

The evaluation begins even before the patients arrive, with a review of the medical record from the patient's referring eye doctor. I read and assess the available information and develop an individualized plan for each patient's visit. Upon arrival, a member of our team initiates the eye exam, and then I visit with each family and take a thorough history, focusing on when the first symptoms began, what they were, how they have changed over time, any prior diagnoses that have been made or genetic testing that has been done, the family history, and several other points.

“The Spokane Eye Clinic has built a diagnostic testing suite with specialized equipment that rivals that typically found in an academic medical center.”

In fact, the machines we use here are the exact same that I used at the University of Iowa! Some of the advanced technology that I routinely use in the inherited eye disease clinic includes the following:

Kinetic visual fields: Whereas standard visual field machines like the Humphrey are designed to check for glaucoma and typically test the patient's central-most vision, the Octopus perimeter allows for the patient's far peripheral vision to be evaluated as well. This is crucial for patients with inherited eye diseases, because these conditions often affect peripheral vision first.
Heidelberg Spectralis optical coherence tomography (OCT): The advent of OCT was a revelation within ophthalmology. Equivalent to an ultrasound that uses light instead of sound, OCT allows for detailed imaging of different areas of the eye. This quick, painless test gives a cross-sectional image of the patient's retina, allowing me to see the photoreceptor cells (rods and cones) which are damaged in many inherited eye diseases -- sometimes before the patient has developed any symptoms.
Topcon and Optos fundus cameras: These state-of-the-art cameras let our specialized photographers take pictures of the patient's retina, capturing nuances and providing a baseline against which future eye exams may be compared. With the Topcon, our photographers can take several shots and electronically "stitch" them together into a montage image, like you see below. The Optos, an even newer technology, can be a great option to get a quick montage-like image, especially from a wiggly child!

*Montage fundus image taken with a Topcon camera*

Electrophysiology equipment, including electroretinography (ERG), multifocal electroretinography (mfERG), and visual evoked potential (VEP). This highly specialized equipment measures the function of the patient's retina and optic nerve. Our ERG and VEP technology is top-of-the-line, and the only setup of its kind in the inland northwest region.

After a detailed history, eye exam, and any diagnostic testing that may be helpful, I review the likely diagnosis with the patient's family and we formulate a plan. This plan could include additional specialized testing, examining family members, or performing genetic testing to identify the change in the patient's DNA that has led to their eye problem. Individualized treatment of patients with inherited eye diseases, with the goal of restoring vision or preventing additional loss, is an exceedingly promising area of research, and dramatic advances have already been made. As additional trials and treatments become available, I will work with the academic medical centers -- like the University of Iowa -- where these are offered, to get my patients "plugged in."

Giving Sight to the Blind: First Treatment for Leber Congenital Amaurosis Gains FDA Approval

Ocular Genetics at the Spokane Eye Clinic