Gene therapy
Adeno-associated viral (AAV) vectors can be used to transfer genes to photoreceptors and retinal pigment epithelium (RPE) cells. In a phase 3 trial of the AAV vector voretigene neparvovec, navigational abilities, light sensitivity, and visual fields improved and persisted to 1 year follow-up in patients with confirmed biallelic RPE65 mutations.[37]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 Aug 26;390(10097):849-60.
https://www.sciencedirect.com/science/article/pii/S0140673617318688?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/28712537?tool=bestpractice.com
Previous studies have shown variable effect durability depending on the gene constructs, vector formulations, and surgical approaches used.[38]Bainbridge JW, Mehat MS, Sundaram V, et al. Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med. 2015 May 14;372(20):1887-97.
https://www.nejm.org/doi/10.1056/NEJMoa1414221
http://www.ncbi.nlm.nih.gov/pubmed/25938638?tool=bestpractice.com
[39]Jacobson SG, Cideciyan AV, Roman AJ, et al. Improvement and decline in vision with gene therapy in childhood blindness. N Engl J Med. 2015 May 14;372(20):1920-6.
https://www.nejm.org/doi/10.1056/NEJMoa1412965
http://www.ncbi.nlm.nih.gov/pubmed/25936984?tool=bestpractice.com
[40]Bennett J, Wellman J, Marshall KA, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet. 2016 Aug 13;388(10045):661-72.
https://www.sciencedirect.com/science/article/pii/S0140673616303713?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/27375040?tool=bestpractice.com
Clinical trials of AAV vectors have also started in patients with X-linked choroideraemia.[41]MacLaren RE, Groppe M, Barnard AR, et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014 Mar 29;383(9923):1129-37.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171740
http://www.ncbi.nlm.nih.gov/pubmed/24439297?tool=bestpractice.com
[42]Dimopoulos IS, Hoang SC, Radziwon A, et al. Two-year results after AAV2-mediated gene therapy for choroideremia: the Alberta experience. Am J Ophthalmol. 2018 Jun 27;193:130-42.
http://www.ncbi.nlm.nih.gov/pubmed/29940166?tool=bestpractice.com
Voretigene neparvovec is approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of biallelic RPE65 mutation-associated retinal dystrophy. It remains the only gene therapy approved for retinitis pigmentosa, where it is only authorised for a very small subset of patients who are positive for the RPE65 gene mutation (approximately 0.3%-1% of all cases).[7]Ferrari S, Di Iorio E, Barbaro V, et al. Retinitis pigmentosa: genes and disease mechanisms. Curr Genomics. 2011 Jun;12(4):238-49.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131731
http://www.ncbi.nlm.nih.gov/pubmed/22131869?tool=bestpractice.com
[43]Cross N, van Steen C, Zegaoui Y, et al. Current and future treatment of retinitis pigmentosa. Clin Ophthalmol. 2022 Aug 31;16:2909-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441588
http://www.ncbi.nlm.nih.gov/pubmed/36071725?tool=bestpractice.com
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that has been used with limited success in patients with retinitis pigmentosa. One study used docosahexaenoic acid in conjunction with vitamin A (retinol) therapy and showed a small effect on disease progression in the first 2 years of treatment.[44]Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol. 2004 Sep;122(9):1297-305.
http://www.ncbi.nlm.nih.gov/pubmed/15364708?tool=bestpractice.com
[45]Hoffman DR, Locke KG, Wheaton DH, et al. A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol. 2004 Apr;137(4):704-18.
http://www.ncbi.nlm.nih.gov/pubmed/15059710?tool=bestpractice.com
[46]Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004 Sep;122(9):1306-14.
http://www.ncbi.nlm.nih.gov/pubmed/15364709?tool=bestpractice.com
However, long-term supplementation (up to 4 years) did not effectively slow disease progression in male patients with X-linked retinitis pigmentosa.[47]Hoffman DR, Hughbanks-Wheaton DK, Pearson NS, et al. Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial. JAMA Ophthalmol. 2014 Jul;132(7):866-73.
https://jamanetwork.com/journals/jamaophthalmology/fullarticle/1867506
http://www.ncbi.nlm.nih.gov/pubmed/24805262?tool=bestpractice.com
Overall, one Cochrane review concluded that it is uncertain if treatment with docosahexaenoic acid offers benefits to people with retinitis pigmentosa.[35]Schwartz SG, Wang X, Chavis P, et al. Vitamin A and fish oils for preventing the progression of retinitis pigmentosa. Cochrane Database Syst Rev. 2020 Jun 18;6(6):CD008428.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388842
http://www.ncbi.nlm.nih.gov/pubmed/32573764?tool=bestpractice.com