Durable vision improvement after a single intravitreal treatment with antisense oligonucleotide in CEP290-LCA: Replication in two eyes

PURPOSE: An intravitreally injected antisense oligonucleotide, sepofarsen, was designed to modulate splicing within retinas of patients with severe vision loss due to deep intronic c.2991 + 1655A > G variant in the CEP290 gene. A previous report showed vision improvements following a single injection in one eye with unexpected durability lasting at least 15 months. The current study evaluated durability of efficacy beyond 15 months in the previously treated left eye. In addition, peak efficacy and durability were evaluated in the treatment-naive right eye, and re-injection of the left eye 4 years after the first injection. OBSERVATIONS: Visual function was evaluated with best corrected standard and low-luminance visual acuities, microperimetry, dark-adapted chromatic perimetry, and full-field sensitivity testing. Retinal structure was evaluated with OCT imaging. At the fovea, all visual function measures and IS/OS intensity of the OCT showed transient improvements peaking at 3–6 months, remaining better than baseline at ∼2 years, and returning to baseline by 3–4 years after each single injection. CONCLUSIONS AND IMPORTANCE: These results suggest that sepofarsen reinjection intervals may need to be longer than 2 years.