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Ophthalmology. 2014 Jan;121(1):234-45. doi: 10.1016/j.ophtha.2013.08.017. Epub 2013 Oct 20.

Retinal structure and function in achromatopsia: implications for gene therapy.

Author information

1
UCL Institute of Ophthalmology, University College London, London, UK; Moorfields Eye Hospital, London, UK.
2
UCL Institute of Ophthalmology, University College London, London, UK.
3
Summer Program for Undergraduate Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
4
Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin.
5
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin.
6
Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin.
7
UCL Institute of Ophthalmology, University College London, London, UK; Moorfields Eye Hospital, London, UK. Electronic address: michel.michaelides@ucl.ac.uk.

Abstract

PURPOSE:

To characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy.

DESIGN:

Cross-sectional study.

PARTICIPANTS:

Forty subjects with ACHM.

METHODS:

All subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (1) continuous inner segment ellipsoid (ISe), (2) ISe disruption, (3) ISe absence, (4) presence of a hyporeflective zone (HRZ), and (5) outer retinal atrophy including retinal pigment epithelial loss. Foveal and outer nuclear layer (ONL) thickness was measured and presence of hypoplasia determined.

MAIN OUTCOME MEASURES:

Photoreceptor appearance on SD-OCT imaging, foveal and ONL thickness, presence of foveal hypoplasia, retinal sensitivity and fixation stability, and association of these parameters with age and genotype.

RESULTS:

Forty subjects with a mean age of 24.9 years (range, 6-52 years) were included. Disease-causing variants were found in CNGA3 (n = 18), CNGB3 (n = 15), GNAT2 (n = 4), and PDE6C (n = 1). No variants were found in 2 individuals. In all, 22.5% of subjects had a continuous ISe layer at the fovea, 27.5% had ISe disruption, 20% had an absent ISe layer, 22.5% had an HRZ, and 7.5% had outer retinal atrophy. No significant differences in age (P = 0.77), mean retinal sensitivity (P = 0.21), or fixation stability (P = 0.34) across the 5 SD-OCT categories were evident. No correlation was found between age and foveal thickness (P = 0.84) or between age and foveal ONL thickness (P = 0.12).

CONCLUSIONS:

The lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore, the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor preservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selecting subjects for future trials and measuring the trials' impact.

PMID:
24148654
PMCID:
PMC3895408
DOI:
10.1016/j.ophtha.2013.08.017
[Indexed for MEDLINE]
Free PMC Article
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