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Although there are many ophthalmic conditions with a genetic cause, there are also numerous ongoing studies of gene therapies for IRDs. The first of these agents to receive regulatory approval was voretigene neparvovec, and learnings from the clinical trial program of voretigene neparvovec are expected to inform future development of ocular gene therapies in broader patient groups.

In the clinical management of individuals with IRDs, improvements in the identification and diagnosis of patients are needed. Options are available to IRD patients beyond gene therapy, such as prenatal or preimplantation genetic diagnosis, but in each case the identification of the causative gene is required. Referral of all IRD patients to an IRD super-specialist is therefore advisable, so that the molecular diagnosis can be confirmed and treatment provided, if available. Indeed, early clinical experience with voretigene neparvovec has demonstrated the importance of expert treatment specialist centers to provide an optimum standard of care for patients with IRDs. These experiences are applicable to the development of future ocular gene therapies.

“To conclude, voretigene neparvovec is a truly life-changing treatment which improves visual function and retinal sensitivity, which in turn improves the patient’s ability to perform activities of daily living,” said Dr. Leroy. “The first patients have been treated successfully in several countries. Moving forward, positive collaborations between the referring clinician and the IRD super-specialist will be required for this ground-breaking treatment to be implemented most effectively.”


In collaboration with I. Audo, S. Mohand-Said, P.O. Barale, G. Bouters, C. Devisme, C. Pagot, and the teams from the National Reference Center REFERET and STREETLAB.

1. Lorenz B, Poliakov E, Schambeck M, et al. A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation. Invest Ophthalmol Vis Sci. 2008;49:5235-5242.

2. Weleber RG, Michaelides M, Trzupek KM, et al. The phenotype of Severe Early Childhood Onset Retinal Dystrophy (SECORD) from mutation of RPE65 and differentiation from Leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2011;52:292-302.

3. Chung DC, Bertelsen M, Lorenz B, et al. The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 gene. Am J Ophthalmol. 2019;199:58-70.

4. FDA. FDA News Release. December 2017. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. Available at: https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm589467.htm. Accessed October 2018.

5. EMA. 21 September 2018. New gene therapy for rare inherited disorder causing vision loss recommended for approval. Available at: https://www.ema.europa.eu/en/news/new-gene-therapy-rare-inherited-disorder-causing-vision-loss-recommended-approval. Accessed November 8, 2018.

6. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390:849-60.

7. Chung DC, McCague S, Yu ZF, et al. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies. Clin Exp Ophthalmol. 2018;46:247-59.

8. Drack AV. Abstract presented at American Association for Pediatric Ophthalmology and Strabismus meeting 2019. San Diego, CA, USA.

9. Russell S. Abstract presented at Retina Society 48th Annual Scientific Meeting 2015, Paris, France.

10. Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010;29:335-375.

11. RetNet. The Retinal Information Network. 2019. Available at: https://sph.uth.edu/retnet/. Accessed July 17, 2019.

12. Nash BM, Wright DC, Grigg JR, et al. Retinal dystrophies, genomic applications in diagnosis and prospects for therapy. Transl Pediatr. 2015;4:139-163.

13. Sheck L, Davies WIL, Moradi P, et al. Leber congenital amaurosis associated with mutations in CEP290, clinical phenotype, and natural history in preparation for trials of novel therapies. Ophthalmology. 2018;125:894-903.

14. Collin RW, den Hollander AI, van der Velde-Visser SD, et al. Antisense Oligonucleotide (AON)-based therapy for Leber congenital amaurosis caused by a frequent mutation in CEP290. Mol Ther Nucleic Acids. 2012;1:e14.

15. den Hollander AI, Black A, Bennett J, et al. Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies. J Clin Invest. 2010;120:3042-3053.

16. Daly A. ERN-EYE: the journey so far. Presentation at 3rd ERN conference, Vilnius, Lithuania. March 9, 2017. Available at: https://ec.europa.eu/health/sites/health/files/ern/docs/20170309_rt4_05_daly_pres_en.pdf. Accessed September 2019.

17. White SJ, Cantsilieris S. (eds). Genotyping: methods and protocols. Springer, New York. 2017.

18. Huang H, Chen Y, Chen H, et al. Systematic evaluation of a targeted gene capture sequencing panel for molecular diagnosis of retinitis pigmentosa. PLoS One. 2018;13:e0185237.

19. Pinkel D, Segraves R, Sudar D, et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet. 1998;20:207-211.

20. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-424.

21. Novartis. Voretigene neparvovec Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/luxturna-epar-product-information_en.pdf. Accessed October 15, 2019.

Bart P. Leroy, MD, PHD
  • Ghent University and Ghent University Hospital, Ghent, Belgium
  • Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Mark E. Pennesi, MD, PHD
  • Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA
José-Alain Sahel, MD
  • Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris
  • University of Pittsburgh Medical School, Pittsburgh, PA, USA