@article {1661816,
	title = {Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy},
	journal = {Am J Ophthalmol},
	volume = {249},
	year = {2023},
	month = {2023 May},
	pages = {108-125},
	abstract = {PURPOSE: To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy. DESIGN: Pooled analysis of safety data from 5 clinical studies. METHODS: A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2. RESULTS: Almost all patients (95.2\%) received 9\&nbsp;{\texttimes}\&nbsp;1010 viral genomes and 87.8\% had at least 2 years of follow-up. Most patients (75.1\%) experienced at least one systemic AE, but systemic treatment-related AEs occurred in 3 patients; none were serious. Intraocular inflammation was reported in 75.6\% of lenadogene nolparvovec-treated eyes. Almost all intraocular inflammations occurred in the anterior chamber (58.8\%) or in the vitreous (40.3\%), and were of mild (90.3\%) or moderate (8.8\%) intensity; most resolved with topical corticosteroids alone. All IOP increases were mild to moderate in intensity. No AE led to study discontinuation. Bio-dissemination of lenadogene nolparvovec and systemic immune response were limited. The safety profile was comparable for patients treated bilaterally and unilaterally. CONCLUSIONS: Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, consistent with limited bio-dissemination. The product was well tolerated, with mostly mild ocular side effects responsive to conventional ophthalmologic treatments.},
	keywords = {Genetic Therapy, Genetic Vectors, Humans, Inflammation, Optic Atrophy, Hereditary, Leber, Parvovirinae},
	issn = {1879-1891},
	doi = {10.1016/j.ajo.2022.11.026},
	author = {Vignal-Clermont, Catherine and Yu-Wai-Man, Patrick and Newman, Nancy J and Carelli, Valerio and Moster, Mark L and Biousse, Valerie and Subramanian, Prem S and Wang, An-Guor and Donahue, Sean P and Leroy, Bart P and Sadun, Alfredo A and Klopstock, Thomas and Sergott, Robert C and Rebolleda Fernandez, Gema and Chwalisz, Bart K and Banik, Rudrani and Taiel, Magali and Roux, Michel and Sahel, Jos{\'e}-Alain and LHON Study Group}
}
