100 Vision-Saving Procedures and Counting: Q&A With Retinal Gene Therapy Expert Dr. Aaron Nagiel 

His newly treated patients might show significant improvements on their eye chart tests, but Aaron Nagiel, MD, PhD, will tell you that the truest signs of visual progress come through the texts he receives from parents days, weeks, and months after their child’s treatment.

There’s no shortage of stories: A toddler truly seeing animals at the zoo for the first time. A young girl noticing her shadow on the sidewalk. A 7-year-old who can now read the blackboard at school and ride her bike through the neighborhood at dusk.

For kids with a rare genetic eye disorder called Leber congenital amaurosis (LCA), these moments are monumental. Children with LCA experience a rapid decline in their vision as they grow, starting with poor vision in dim light and night blindness. Ultimately, patients lose all of their sight by middle age. 

But since 2018, Dr. Nagiel and his team at the Vision Center of Children’s Hospital Los Angeles have been treating these patients with a pioneering gene therapy called Luxturna. A national leader in pediatric gene therapy, CHLA was the first center on the West Coast to administer this treatment after it was approved by the Food and Drug Administration in 2017. 

Recently, CHLA celebrated its 100th retinal gene therapy procedure, which includes more Luxturna procedures than anywhere else in the country. Dr. Nagiel shares how this therapy works, why early treatment is critical, and how he uses both his hands—and feet—to deliver it. 

What led you to a career treating pediatric retinal eye diseases? 

It started during my early research career at Rockefeller University. I was investigating a fundamental question: How do 100 billion connections form in our brain to empower humans to do everything we do?  

That led me to an interest in ophthalmology, especially retina research, because it’s this piece of the brain we can see with the naked eye. So many different cell types have to connect properly to inform all the beautiful imagery we see daily. I also knew that I loved working with the pediatric population. Ultimately, my research led me to CHLA where Dr. Thomas Lee was an established leader in pediatric retina.

How does this treatment improve vision for kids with retinal diseases? 

For this form of retinal disease, the patient’s vision will start declining from a very early age, and by their mid-40s, they will be almost completely blind.

With Luxturna gene therapy, not only do patients experience visual improvements, but the therapy may actually stave off retinal degeneration and retinal cell loss.

I often tell patients and their families that the retina is kind of like a factory. The patient’s ‘factory’ is at a total standstill because one tiny tool is missing—it just can't produce what it needs to keep the retina healthy.  

What we're doing with Luxturna is restoring that tool so that the factory can start functioning again. If we wait too long to treat someone, though, the factory might shut down completely. 

That’s why our emphasis here has always been on treating kids as early as possible so we can give that tool back to these ‘factories’ and help children maintain their vision over the course of their lifetime.  

… The retina is kind of like a factory. The patient’s ‘factory’ is at a total standstill because one tiny tool is missing—it just can't produce what it's supposed to in order to keep the retina healthy… Luxturna is restoring that tool so the factory can start functioning again.

How does Luxturna gene therapy work?  

Gene therapies represent a method of permanently altering the course of disease—and the person’s life—through a single procedure.

Luxturna packages a healthy copy of a specific gene—the gene that is mutated and not functional in these patients—inside a specially designed carrier called a viral vector. This vector is a harmless virus that has one job only: to deliver the normal copy of the gene into the patient’s cells, so that those cells can now form healthy proteins and thus function properly.

One important note is that treatment is a one-time occurrence. Once that gene is functional within the cells and healthy proteins can be made, the patient’s retinal cells start functioning correctly, and hopefully this lasts for the life of the patient.  

Gene therapies represent a method of permanently altering the course of disease—and the person’s life—through a single procedure.

Who is eligible for Luxturna?  

Patients must be older than 12 months and show mutations in both copies of a gene called RPE65. If a patient has one healthy copy of this gene, they don’t have the disease. 

We lean on CHLA’s Center for Personalized Medicine for this part of the screening. CHLA is one of the only pediatric medical centers with in-house genomic and molecular pathology support. This is critical because more than 300 genes can cause these retinal degenerations. We need to be sure beyond a doubt that patients have this particular form of LCA before we treat them. 

What is the procedure like? 

It’s complex and highly specialized, with many logistical considerations. The medicine itself needs to be kept in a special freezer at -112 degrees Fahrenheit. Once the dose is thawed and prepared, it must be used within four hours. Our pharmacy staff have been amazing partners in that critical aspect of preparation and delivery. We also have great anesthesiology support to ensure smooth surgical delivery of the medication. 

The first part of the surgery involves a standard retinal technique called a vitrectomy. Both parts of the procedure require both my hands and feet, and my eyes, but the second part is much more delicate. 

I insert the gene therapy medication directly under the retina, which is extremely thin—about 1/4 of a millimeter. I hold the medication dose in one hand and a light in the other. With my left foot, I control an advanced microscope. And with my right foot, I control the rate of the medication delivery via a special pedal.  

When do patients start to see results?  

Some patients start observing significant improvements within the first week. They’re essentially seeing things that they could never have seen before.

I've had patients who, during their first follow-up visit, can make out the fish in the fish tank for the first time. Parents have also told me the stories of their kids noticing a bird flying, or a cloud in the sky, for the first time in their lives. One mom sent me a picture of her daughter, Ashlyn, seeing her shadow for the first time.  

No longer night-blind, kids also gain the confidence and independence to finally do classic kid things, like reading a book by the light of a window, going trick-or-treating, or riding their bikes at dusk.

There aren’t many advanced ways to capture this visual progression clinically. So having parents tell us that their child is finally excited at the zoo because he can see the tigers, see the light on the smoke alarm or the clock on the microwave, or see other cars while being driven around at night, is critical feedback.  

Many patients start to see significant improvements within the first week. They’re essentially seeing things that they could never have seen before.

What’s next for the retinal gene therapy program? 

We continue to recruit people for several clinical trials advancing the leading edge of gene therapy treatment. There are a number of adults, for whom gene therapies weren’t available when they were young, who come to CHLA for treatment and also participate in these trials.  

Today, these diseases are often diagnosed in childhood, so there's no reason we should even be treating adults in the future. In 10 years, we hope that all patients with these diseases can be identified when they’re young, treated when they’re young—and experience life-changing vision improvements for their lifetimes.  

In 10 years, we hope that all patients with these diseases can be identified when they’re young, treated when they’re young—and experience life-changing vision improvements for their lifetimes.