While RP has no cure, many patients can significantly benefit from optimizing their remaining vision. All patients should undergo a sight test to have their refractive ability checked. Many patients will benefit from assistance from a low-vision specialist (either an ophthalmologist or optometrist), who can help them obtain various visual aids such as glasses, magnifiers, or telescopes.
Vitamin A and docosahexaenoic acid (fish oils)
High doses of oral vitamin A slow the rate of decline of retinal function, as measured by electroretinogram responses.[30]Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993 Jun;111(6):761-72.
http://www.ncbi.nlm.nih.gov/pubmed/8512476?tool=bestpractice.com
Vitamin A supplementation is routinely recommended by some centers but opposed by others. Patients with cone-rod dystrophy should avoid vitamin A, due to the potential hazards that have been observed in mice with ABCA4 mutations, which had more accumulation of phototoxic A2-E (N-retinylidene-N-retinylethanol-amine) compounds.[31]Radu RA, Hu J, Peng J, et al. Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells. J Biol Chem. 008 Jul 11;283(28):19730-8.
https://www.jbc.org/content/283/28/19730.full
http://www.ncbi.nlm.nih.gov/pubmed/18474598?tool=bestpractice.com
A2-E is detrimental to retinal pigment epithelial (RPE) cell function by a variety of mechanisms, including inhibition of lysosomal degradative capacity, loss of membrane integrity, and phototoxicity.[32]Schütt F, Davies S, Kopitz J, et al. Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2303-8.
https://iovs.arvojournals.org/article.aspx?articleid=2123494
http://www.ncbi.nlm.nih.gov/pubmed/10892877?tool=bestpractice.com
Long-term high-dose vitamin A supplementation seems safe for other variants of RP, but it can elevate liver enzymes and triglycerides and increase the risk of osteoporosis.[33]Sibulesky L, Hayes KC, Pronczuk A, et al. Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa. Am J Clin Nutr. 1999 Apr;69(4):656-63.
https://ajcn.nutrition.org/content/69/4/656.full
http://www.ncbi.nlm.nih.gov/pubmed/10197566?tool=bestpractice.com
Patients receiving vitamin A should be monitored by their physician for these potential adverse effects. The decision to use or not use vitamin A will depend on the center and patient preference. The use of vitamin A has not been studied in children with RP and therefore is usually avoided. Beta-carotene (a precursor of vitamin A) has been suggested to be beneficial in the treatment of retinitis pigmentosa, but these results are still preliminary and require further study before a formal recommendation can be made.[34]Rotenstreich Y, Belkin M, Sadetzki S, et al. Treatment with 9-cis β-carotene-rich powder in patients with retinitis pigmentosa: a randomized crossover trial. JAMA Ophthalmol. 2013 Aug;131(8):985-92.
http://www.ncbi.nlm.nih.gov/pubmed/23700011?tool=bestpractice.com
[35]Pennesi ME. A little algae a day keeps the retinal degeneration specialist away? JAMA Ophthalmol. 2013 Aug;131(8):983-4.
http://www.ncbi.nlm.nih.gov/pubmed/23700100?tool=bestpractice.com
Docosahexaenoic acid (DHA) is a fatty acid present in high concentrations in the photoreceptors and may be a precursor for neuroprotective factors. Two randomized studies in patients with RP did not show a significant benefit of DHA supplementation.[36]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
[37]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
One 4-year single-site phase II clinical trial evaluating the efficacy of DHA in patients with X-linked RP also showed no therapeutic benefit in slowing the rate of cone electroretinography (ERG) functional loss.[38]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.
http://www.ncbi.nlm.nih.gov/pubmed/24805262?tool=bestpractice.com
Many centers still recommend DHA supplementation due to the theoretical benefit, low risk, and minimal side effect profile.[39]Hughbanks-Wheaton DK, Birch DG, Fish GE, et al. Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: the 4-year DHAX trial. Invest Ophthalmol Vis Sci. 2014 Jul 11;55(8):4958-66.
http://www.ncbi.nlm.nih.gov/pubmed/25015354?tool=bestpractice.com
Lutein
Lutein is a carotenoid, found in the human retina and dark green leafy vegetables. A randomized controlled trial examined the efficacy of lutein to slow visual field loss in patients with RP who were taking vitamin A.[40]Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010 Apr;128(4):403-11.
http://www.ncbi.nlm.nih.gov/pubmed/20385935?tool=bestpractice.com
The study showed a reduction in the loss of mid-peripheral visual fields.[40]Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010 Apr;128(4):403-11.
http://www.ncbi.nlm.nih.gov/pubmed/20385935?tool=bestpractice.com
However, others have challenged the conclusions of this study.[41]Massof RW, Fishman GA. How strong is the evidence that nutritional supplements slow the progression of retinitis pigmentosa? Arch Ophthalmol. 2010 Apr;128(4):493-5.
http://www.ncbi.nlm.nih.gov/pubmed/20385948?tool=bestpractice.com
Cystoid macular edema (CME)
Carbonic anhydrase inhibitors such as topical dorzolamide or oral acetazolamide are effective for treatment of CME in some patients.[42]Grover S, Apushkin MA, Fishman GA. Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa. Am J Ophthalmol. 2006 May;141(5):850-8.
http://www.ncbi.nlm.nih.gov/pubmed/16546110?tool=bestpractice.com
[43]Fishman GA, Gilbert LD, Fiscella RG, et al. Acetazolamide for treatment of chronic macular edema in retinitis pigmentosa. Arch Ophthalmol. 1989 Oct;107(10):1445-52.
http://www.ncbi.nlm.nih.gov/pubmed/2803090?tool=bestpractice.com
Patients must often remain on these medicines for several months before an effect is seen. The effect can wear off with time, and some patients do not benefit. Furthermore, some patients cannot tolerate the adverse effects of these medicines such as paresthesias and frequent urination.
Cataracts
Posterior subcapsular cataracts are especially common and often affect central vision. Cataract extraction can benefit many patients, especially if the degeneration has not involved the central macula. It is important to rule out the presence of cystoid macular edema before cataract extraction because this can worsen after surgery. Occult weak zonules require appropriate surgical precautions to minimize the risks of complications during cataract surgery.
Gene replacement therapy
Voretigene neparvovec, a recombinant adeno-associated virus vector carrying a normal copy of the RPE65 gene, has demonstrated improved vision in patients with Leber congenital amaurosis secondary to mutations in the RPE65 gene when injected into the subretinal space.[44]Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2240-8.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802315#t=article
http://www.ncbi.nlm.nih.gov/pubmed/18441370?tool=bestpractice.com
[45]Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2231-9.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802268#t=article
http://www.ncbi.nlm.nih.gov/pubmed/18441371?tool=bestpractice.com
[46]Hauswirth WW, Aleman TS, Kaushal S, et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008 Oct;19(10):979-90.
http://www.ncbi.nlm.nih.gov/pubmed/18774912?tool=bestpractice.com
[47]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/full/10.1056/NEJMoa1414221#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25938638?tool=bestpractice.com
[48]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/full/10.1056/NEJMoa1412965#t=article
http://www.ncbi.nlm.nih.gov/pubmed/25936984?tool=bestpractice.com
[49]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.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30371-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27375040?tool=bestpractice.com
A subsequent phase 3 trial showed improved functional vision in patients with RPE65-mediated inherited retinal dystrophy who were treated with the AAV vector-based gene therapy, voretigene neparvovec.[50]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.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31868-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/28712537?tool=bestpractice.com
Follow-up studies of the phase 3 trial and an earlier phase 1 trial demonstrated a consistent safety profile and developing longer-term efficacy.[51]Maguire AM, Russell S, Wellman JA, et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology. 2019 Sep;126(9):1273-85.
http://www.ncbi.nlm.nih.gov/pubmed/31443789?tool=bestpractice.com
Voretigene neparvovec is approved for the treatment of biallelic RPE65 mutation-associated retinal dystrophy. Voretigene neparvovec is not only the first approved treatment for retinal dystrophy, but is the first approved gene therapy for the eye. Other clinical trials for Usher syndrome type 1 due to mutations in MYO7A, and X-linked RP due to mutations in RPGR are underway.