Abstract
Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.
Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development.
Results: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age.
Conclusions: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.
Original language | English |
---|---|
Pages (from-to) | 4384-4391 |
Number of pages | 8 |
Journal | Investigative ophthalmology & visual science |
Volume | 59 |
Issue number | 11 |
DOIs | |
Publication status | Published - 4 Sept 2018 |
Keywords
- Adolescent
- Adult
- Antigens, Neoplasm/genetics
- Child
- Child, Preschool
- Electroretinography
- Female
- Follow-Up Studies
- Gene Amplification
- High-Throughput Nucleotide Sequencing
- Humans
- Infant
- Introns/genetics
- Leber Congenital Amaurosis/diagnosis
- Male
- Middle Aged
- Mutation
- Neoplasm Proteins/genetics
- Polymerase Chain Reaction
- Retina/diagnostic imaging
- Retrospective Studies
- Tomography, Optical Coherence
- Visual Acuity/physiology
- Young Adult