RESUMEN
CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit-risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.
Asunto(s)
Amaurosis Congénita de Leber , Adulto , Antígenos de Neoplasias/genética , Ceguera/genética , Proteínas de Ciclo Celular/genética , Niño , Proteínas del Citoesqueleto/metabolismo , Humanos , Amaurosis Congénita de Leber/tratamiento farmacológico , Amaurosis Congénita de Leber/genética , Oligonucleótidos Antisentido/efectos adversos , Visión OcularRESUMEN
A rare case of idiopathic exercise-induced diplopia was reported. A 28-year-old male experienced diplopia during and after intensive exercise. These symptoms had been present for over a year. Upon first examination, orthophoria was found. Upon examination after intensive exercise, an esophoria of 10∆ at near and an esotropia of 4∆ at distance was found. Neuroimaging and neurological, cardiological, and hematological evaluations were normal. A prism correction, to be used during exercise, partially resolved the diplopia. This case report aims to highlight and create general awareness about exercise-induced diplopia.
