Journal article
Restoration of Cone Sensitivity to Individuals with Congenital Photoreceptor Blindness within the Phase 1/2 Sepofarsen Trial
Ophthalmology science, Vol.2(2), 100133
2022
DOI: 10.1016/j.xops.2022.100133
PMCID: PMC9562351
PMID: 36249682
Abstract
Purpose
To understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the centrosomal protein 290 (CEP290) gene.
Design
Phase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial.
Participants
A homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15–41 years) selected for detailed analyses. Medical histories of 4 participants were consistent with congenital binocular blindness, whereas 1 participant showed evidence of spatial vision in early life that was later lost.
Intervention
Participants received a single intravitreal injection of sepofarsen (160 or 320 μg) into the study eye.
Main Outcome Measures
Full-field stimulus testing (FST), visual acuity (VA), and transient pupillary light reflex (TPLR) were measured at baseline and for 3 months after the injection.
Results
All 5 participants with LP vision demonstrated severely abnormal FST and TPLR findings. At baseline, FST threshold estimates were 0.81 and 1.0 log cd/m2 for control and study eyes, respectively. At 3 months, study eyes showed a large mean improvement of –1.75 log versus baseline (P < 0.001), whereas untreated control eyes were comparable with baseline. Blue minus red FST values were not different than 0 (P = 0.59), compatible with cone mediation of remnant vision. At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline. Specialized tests performed in 1 participant confirmed and extended the standardized results from all 5 participants.
Conclusions
By subjective and objective evidence, intravitreal sepofarsen provides improvement of light sensitivity for individuals with LP vision. However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity.
Details
- Title: Subtitle
- Restoration of Cone Sensitivity to Individuals with Congenital Photoreceptor Blindness within the Phase 1/2 Sepofarsen Trial
- Creators
- Artur V Cideciyan - Penn Presbyterian Medical CenterSamuel G Jacobson - Penn Presbyterian Medical CenterAllen C Ho - Wills Eye HospitalArun K KrishnanAlejandro J Roman - Penn Presbyterian Medical CenterAlexandra V Garafalo - Penn Presbyterian Medical CenterVivian WuMalgorzata Swider - Penn Presbyterian Medical CenterAlexander Sumaroka - Penn Presbyterian Medical CenterCaroline Van Cauwenbergh - Ghent University HospitalStephen R RussellArlene V Drack - University of IowaBart Leroy - Ghent University HospitalMichael R SchwartzAniz Girach - ProQR Therapeutics
- Resource Type
- Journal article
- Publication Details
- Ophthalmology science, Vol.2(2), 100133
- Publisher
- Elsevier BV
- DOI
- 10.1016/j.xops.2022.100133
- PMID
- 36249682
- PMCID
- PMC9562351
- ISSN
- 2666-9145
- Language
- English
- Date published
- 2022
- Academic Unit
- Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984363658102771
Metrics
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