While Retinitis pigmentosa (RP) has no cure, many patients can significantly benefit from optimising 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 consultant (either an ophthalmologist or optometrist), who can help them obtain various visual aids such as glasses, magnifiers, or telescopes.
Vitamin A (retinol)
Although high doses of oral vitamin A (retinol) were previously recommended to slow the decline of retinal function, based on a historical randomised clinical trial data, this recommendation no longer applies. One study published in 2023 re-evaluated the historical data, and sequence banked DNA samples from the original trial to determine whether certain genotypes responded preferentially to vitamin A (retinol) supplementation.[38]Comander J, Weigel DiFranco C, Sanderson K, et al. Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. JCI Insight. 2023 Aug 8;8(15):e167546.
https://insight.jci.org/articles/view/167546
http://www.ncbi.nlm.nih.gov/pubmed/37261916?tool=bestpractice.com
The authors found that baseline electroretinogram (ERG) 30 Hz cone flicker implicit time (the time it takes for the retina to fully respond to dim light) was an independent and strong predictor of RP progression for subjects enroled in the clinical trial. In contrast, there was no evidence for a generalised neuroprotective effect of vitamin A (retinol) supplementation in this patient population.[38]Comander J, Weigel DiFranco C, Sanderson K, et al. Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker. JCI Insight. 2023 Aug 8;8(15):e167546.
https://insight.jci.org/articles/view/167546
http://www.ncbi.nlm.nih.gov/pubmed/37261916?tool=bestpractice.com
This study has fundamentally changed understanding of the role vitamin A (retinol) supplementation in the management of patients with RP.[8]Jain N, Maguire MG, Flaxel CJ, et al. Dietary supplementation for retinitis pigmentosa: a report by the American Academy of Ophthalmology. Ophthalmology. 2025 Mar;132(3):354-67.
https://www.aaojournal.org/article/S0161-6420(24)00553-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39453328?tool=bestpractice.com
Furthermore, patients with cone-rod dystrophy should avoid vitamin A (retinol), 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.[39]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.[40]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 (retinol) supplementation can also elevate liver enzymes and triglycerides, and increase the risk of osteoporosis.[41]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 (retinol), notably children, older adults, or patients with liver disease, hyperlipidaemia, high alcohol intake, or a combination thereof, should be monitored by their physician for these potential adverse effects.[8]Jain N, Maguire MG, Flaxel CJ, et al. Dietary supplementation for retinitis pigmentosa: a report by the American Academy of Ophthalmology. Ophthalmology. 2025 Mar;132(3):354-67.
https://www.aaojournal.org/article/S0161-6420(24)00553-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39453328?tool=bestpractice.com
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.[8]Jain N, Maguire MG, Flaxel CJ, et al. Dietary supplementation for retinitis pigmentosa: a report by the American Academy of Ophthalmology. Ophthalmology. 2025 Mar;132(3):354-67.
https://www.aaojournal.org/article/S0161-6420(24)00553-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39453328?tool=bestpractice.com
[42]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
[43]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)
DHA is an omega-3 fatty acid and key component of fish oils. It is present in high concentrations in the photoreceptors and may be a precursor for neuroprotective factors.[8]Jain N, Maguire MG, Flaxel CJ, et al. Dietary supplementation for retinitis pigmentosa: a report by the American Academy of Ophthalmology. Ophthalmology. 2025 Mar;132(3):354-67.
https://www.aaojournal.org/article/S0161-6420(24)00553-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39453328?tool=bestpractice.com
Two randomised studies in patients with RP did not show a significant benefit of DHA supplementation.[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
One 4-year single-site phase 2 clinical trial evaluating the efficacy of DHA in patients with X-linked RP also showed no therapeutic benefit in slowing the rate of cone ERG functional loss.[46]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 centres still recommend DHA supplementation due to the theoretical benefit, low risk, and minimal side effect profile.[47]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 dietary carotenoid, found in the human retina and dark green leafy vegetables. A randomised controlled trial examined the efficacy of lutein to slow visual field loss in patients with RP who were taking vitamin A.[48]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.[48]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.[49]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 oedema (CMO)
Carbonic anhydrase inhibitors such as topical dorzolamide or oral acetazolamide are effective for treatment of CMO in some patients.[50]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
[51]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 drugs 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 drugs such as paraesthesias 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 oedema before cataract extraction because this can worsen after surgery. Occult weak zonules require appropriate surgical precautions to minimise 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 biallelic RPE65 mutations when injected into the subretinal space.[52]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
[53]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
[54]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
[55]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
[56]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
[57]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 voretigene neparvovec.[58]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 longer-term efficacy.[59]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
[60]Maguire AM, Russell S, Chung DC, et al. Durability of voretigene neparvovec for biallelic RPE65-mediated inherited retinal disease: phase 3 results at 3 and 4 years. Ophthalmology. 2021 Oct;128(10):1460-8.
https://www.aaojournal.org/article/S0161-6420(21)00236-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33798654?tool=bestpractice.com
Many other clinical trials for novel therapeutics to treat other forms of RP and Leber congenital amaurosis have been completed or are currently underway.[61]Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, et al. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020 Mar;26(3):354-9.
http://www.ncbi.nlm.nih.gov/pubmed/32094925?tool=bestpractice.com
[62]Michaelides M, Besirli CG, Yang Y, et al. Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) gene therapy: safety and efficacy in RPGR-associated X-linked retinitis pigmentosa. Am J Ophthalmol. 2024 Nov;267:122-34.
https://www.ajo.com/article/S0002-9394(24)00244-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38871269?tool=bestpractice.com
[63]Lam BL, Pennesi ME, Kay CN, et al. Assessment of visual function with cotoretigene toliparvovec in X-linked retinitis pigmentosa in the randomized XIRIUS phase 2/3 study. Ophthalmology. 2024 Sep;131(9):1083-93.
http://www.ncbi.nlm.nih.gov/pubmed/38423215?tool=bestpractice.com
[64]Yang P, Pardon LP, Ho AC, et al. Safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D: a phase 1/2, multicentre, open-label, unilateral dose escalation study. Lancet. 2024 Sep 7;404(10456):962-70.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01447-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/39244273?tool=bestpractice.com