Related Experiment Video
Updated: Jun 23, 2025
Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina
Published on: May 6, 2015
Twelve-month Natural History Study of Centrosomal Protein 290 (CEP290)-associated Inherited Retinal Degeneration
Eric A Pierce1, Bright S Ashimatey2, Thiran Jayasundera3
1Ocular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
Purpose:
To define the clinical characteristics of centrosomal protein 290 (CEP290)-associated inherited retinal degeneration (IRD) and determine which assessments may provide reliable endpoints in future interventional trials.
Design:
Participants in this natural history study were enrolled into 2 best-corrected visual acuity (BCVA) cohorts: light perception to > 1.0 logarithm of the minimum angle of resolution (logMAR) and 1.0 logMAR to 0.4 logMAR. Each comprised 4 age cohorts (3-5, 6-11, 12-17, and ≥ 18 years).
Participants:
Patients with CEP290-associated IRD caused by the intron 26 c.2991+1655A>G mutation and BCVA ranging from light perception to 0.4 logMAR.
Methods:
Best-corrected visual acuity, full-field stimulus threshold (FST) sensitivity, Ora-Visual Navigation Challenge (Ora-VNC) composite score, and OCT-outer nuclear layer (OCT-ONL) average thickness were assessed at screening, baseline, 3 months, 6 months, and 12 months.
Main Outcome Measures:
Best-corrected visual acuity, FST sensitivity, Ora-VNC composite score, and OCT-ONL average thickness.
Results:
Twenty-six participants were included in this analysis. Nineteen were female. All participants were White and 4 reported Hispanic ethnicity. At screening, 13 of 16 adult and 9 of 10 pediatric participants had BCVA > 1.0 logMAR. Baseline BCVA was variable (median [range] = 2.0 [0.5, 3.9] logMAR) and was uncorrelated with age, as were VNC composite score, FST sensitivity, and OCT-ONL average thickness. Mean (95% confidence interval [CI]) test-retest variability was -0.04 (-0.09, 0.01) logMAR for BCVA (n = 25); 0.6 (-0.1, 1.3) for VNC composite score (n = 18); and 0.10 (-0.07, 0.27) log cd.s/m2 for red FST (n = 14). A greater than expected test-retest variability (5 [0, 10] μm, n = 14) was observed for OCT-ONL average thickness as nystagmus impacted ability to repeat measures at the same retinal location. Functional assessments were stable over 12 months. Mean (95% CI) change from baseline was 0.06 (-0.17, 0.29) logMAR for BCVA (n = 23); -0.1 (-1.2, 1.0) for VNC composite score (n = 21); and -0.15 (-0.43, 0.14) log cd.s/m2 for red FST (n = 16).
Conclusions:
Vision was stable over 12 months. Best-corrected visual acuity, FST, and VNC composite score are potentially viable endpoints for future studies in CEP290-associated IRD. Repeatability of OCT measures poses challenges for quantifying anatomical changes in this population.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
