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

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.

Podcast: Retinitis Pigmentosa

I recently had the privilege of joining the Four-Timers Club as a guest on the excellent Straight From the Cutter's Mouth podcast. During this episode, host Dr. Jay Sridhar and I reviewed retinitis pigmentosa and some systemic syndromes, such as Usher syndrome and Bardet-Biedl syndrome, that include retinitis pigmentosa as part of the condition.

Here's a link to subscribe to this top-notch podcast on iTunes.

Retina podcast

Ocular Genetics at the Spokane Eye Clinic

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

Montage fundus image taken with a Topcon camera

The Diagnosys ERG unit

The Diagnosys ERG unit

  • 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."

ReSpectacle: Helping People See

I recently saw a patient in clinic who has been through a tough stretch in life. He has exotropia, which means his eyes drift apart, and this causes him constant double vision, which is why he came to see me. I have also seen his children as patients, and I know his is a family that tries hard, but has many challenges.

During my clinic visit with him, he decided he wanted to have surgery to fix his exotropia, and so we picked a date. I explained that I would need to see him again in clinic once more prior to surgery to remeasure his strabismus to help me with surgical planning, and that for best accuracy, he needed to be wearing glasses; he is significantly nearsighted, and didn't have glasses, so I prescribed him a new pair.

The day of the pre-operative visit arrived, and I entered the room, eager to see him again. Timidly, he let me know that he hadn't been able to get the eyeglasses I had prescribed, because he couldn't afford them. He went on to say that because he couldn't see well without glasses, he wasn't able to drive a car.

Fortunately, most people in the United States are not in the situation where they must choose between being able to see and being able to eat, but many are. This man needed more than just surgery to realign his eyes, and I realized that getting him glasses would likely have an even larger impact than fixing his double vision.

Thinking quickly, I remembered my friend and colleague Dr. Jeffrey Lynch, whom I met while we were both training in ophthalmology at the University of Iowa. Dr. Lynch, recognizing this same issue that faced my patient, started a 501(c)3 nonprofit organization known as ReSpectacle, which, via volunteers, collects high-quality used eyeglasses, cleans them, photographs them, and categorizes them into an online database which patients and providers domestically and internationally can access.

On ReSpectacle's website, the patient or eye doctor enters the patient's glasses prescription, and instantly, the screen displays a number of different possible "matches," complete with a photograph, a description of the glasses, including the prescription, and a color-coded numerical score that describes how well each option matches the patient's own prescription. The user selects the desired glasses, enters a small amount of basic demographic information, and the glasses are shipped for free to the address desired. Amazing!


I recently posed a few questions to Dr. Lynch, who kindly agreed to be interviewed for this story.

MW: What prompted you to start ReSpectacle?

JL: A decade ago on an ophthalmic mission trip...I was disappointed with the haphazard organization and poor quality of the used glasses we had available to us using a traditional eyeglass recycling model. There are many people eager to donate their used glasses and there are many people eager to accept them, the challenge lies in effectively transferring the resource.

As I saw it, the problem was two-fold: 1) A glasses prescription is highly specific to an individual (there are over 10 million possible eyeglass prescriptions) 2) An acceptable style frame is often as critical as (or in some cultures more critical than) the accuracy of the prescription.  

A website seemed like an ideal location to store large volumes of donations yet keep them highly searchable and accessible. The inclusion of photographs & other descriptors gives our users the dignity of choosing a preferred style among available options.  

MW: What has been the biggest challenge in starting or running ReSpectacle?

JL: Finding the time to give the organization the attention it deserves, among competing responsibilities and interests as a young physician and parent. 

MW: How do you envision ReSpectacle growing in the future?

JL We expect it to continue growing small chapters organically at academic medical centers, taking advantage of the natural migration patterns of our medical student volunteers as they 'match' to different residency programs across the country. Simultaneously, we will be collaborating and developing our own chapters that can accommodate larger volumes of glasses and offer quicker turnaround times on orders. At some point we expect to grow our network to include international locations as good opportunities arise.

MW: How many pairs of eyeglasses has ReSpectacle recycled?

JL: We recently processed our 10,000th order here in the United States, and have recycled a similar number internationally.

A woman in Nepal with her glasses prescription, which ReSpectacle was able to match and provide. Used with permission.

A woman in Nepal with her glasses prescription, which ReSpectacle was able to match and provide. Used with permission.

MW: Is the process for obtaining glasses internationally any different from doing so within the United States?

JL: Yes, currently we do not support shipping of individual orders internationally, as the cost is prohibitive. Instead, we partner with mission groups or established eye care providers in underserved areas abroad and supply glasses to them in batches. They will typically send us 'mugshots' of patients holding their prescriptions, which are then matched to the best pair of glasses in our database taking into account the prescription power and gender/style. We have worked with over 30 mission groups and offer significant flexibility depending on their needs.

MW: My patient was in disbelief that something like this was even possible, and he was the happiest I have seen him, thanking me with a big smile over and over again. Thanks, Dr. Lynch, for helping him, and thousands of others, enjoy life more fully with better vision.

To learn more about ReSpectacle, including how you can support the cause, click here.

My efforts as an artist: learning to draw the retina

While in training at the University of Iowa's ophthalmology department, I was fortunate enough to have Dr. Stephen R. Russell as one of my mentors. Dr. Russell, a vitreoretinal surgeon and researcher, had himself trained at Iowa, and developed a love for retinal drawings.

In the past, ophthalmologists would often spend 30 minutes or more drawing a picture of what they saw during the patient's eye exam. The retina, the thin layer that lines the inside of the back of your eye, is the most expressive part of the eye, and even the exact same disease can look different from one patient to the next.

Since the advent of improved ophthalmic photographic techniques -- and the increase in the number of patients needing to be seen each day -- ophthalmologists don't take nearly as much time to draw their findings anymore. Lamenting this, Dr. Russell put together a beautiful book containing many exquisite drawings done by dozens of different ophthalmologists at Iowa.

Looking through this book for the first time was an emotional experience. Taking care of people's eyes means so much to me, and I could literally feel the love that these doctors -- all of whom had walked the same halls I was then walking, and many of whom had gone on to become giants in our profession -- had for their patients and their craft as they made these meticulous, beautiful drawings. I decided to put a little more effort into my drawings as time allowed.

Take a look at my own comparatively very unimpressive retinal art in this slideshow, and then scroll down to see a showstopping example from Dr. Russell's book.