It’s been almost 4 years since voretigene neparvovec (Luxturna, Spark) hit the market, and we are still talking about it as if we had found the Holy Grail. For many patients with Leber congenital amaurosis (LCA) caused by biallelic RPE65 mutations, it’s been a dream come true. The success stories simply melt your heart, especially those of pediatric patients who can do things they might never have been able to do without this gene therapy.

Now that we have had a small taste of victory, we want more, because treatment for inherited retinal diseases (IRDs) isn’t possible with just one Holy Grail (as far as we know). The AAV vector worked for the RPE65 gene; what else can it do? Perhaps it will prove successful in treatments for other forms of LCA, retinitis pigmentosa (RP), X-linked retinoschisis, choroideremia, and achromatopsia. Each of these diseases affects a small patient population, but if voretigene neparvovec taught us anything, it was that a successful gene therapy can be life-altering and well worth the winding journey through clinical investigation.

More than 30 trials are under way for various gene therapy candidates and delivery methods, including AAV vectors, lentivirus vectors, antisense oligonucleotides, CRISPR therapy, and optogenetics. We seem to get updates and new interim data constantly. Some are positive (a patient with RP regained some visual perception after treatment with gene therapy and training with specialized goggles), whereas others are less so (Biogen’s investigation of timrepigene emparvovec for the treatment of choroideremia did not meet its primary efficacy endpoint at 12 months).1,2

But these findings are all positive, in the long run, because every trial is an opportunity to learn more about the genetic underpinnings of the disease in question, the transduction, the surgical technique, etc. What we see as a failed trial today will teach us something that will help to make the next trial a success tomorrow.

It’s a lot to follow, and many of us are too busy caring for patients in the here and now to wade through the onslaught of phase 1/2 trials, 6-month interim data, and case reports. In this issue of Retina Today, we have boiled it down to what you really need to know. IRD experts share their thoughts on how the research is going, what to expect in the near future, and which trials are worth watching. Other leaders in the field provide pointers on evaluating patients for IRDs and how to order genetic testing.

We are learning volumes about IRDs and the mutations that cause them. With the help of genetic testing and gene registries we are better able to identify patients and help move research forward. But it takes a concerted effort by all of us to screen patients, order genetic testing, and recommend participation in appropriate clinical trials. Caring for patients with IRDs now involves far more than simply counseling them on what to expect as the disease progresses. It takes time to discuss the gene therapy candidates in the pipeline and why any given trial may—or may not—be right for each patient. But our IRD patients are hungry for information, and we should be just as eager to share it as they are to receive it. After all, we have the same goal: preserving vision.

1. Sahel JA, Boulanger-Scemama E, Pagot C, et al. Partial recovery of visual function in a blind patient after optogenetic therapy. Preprint. Posted online May 24, 2021. Nat Med.

2. Biogen announces topline results from phase 3 gene therapy study in choroideremia [press release]. Biogen. June 14, 2021. Accessed June 22, 2021. investors.biogen.com/news-releases/news-release-details/biogen-announces-topline-results-phase-3-gene-therapy-study