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Durham University



Publication details for Professor Marko Nardini

Sundaram, V., Wilde, C., Aboshiha, J., Cowing, J., Han, C., Langlo, C.S., Chana, R., Davidson, A.E., Sergouniotis, P.I., Bainbridge, J.W., Ali, R.R., Dubra, A., Rubin, G., Webster, A.R., Moore, A.T., Nardini, M., Carroll, J. & Michaelides, M. (2014). Retinal Structure and Function in Achromatopsia Implications for Gene Therapy. Ophthalmology 121(1): 234-245.

Author(s) from Durham


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, 6e52 years) were included. Disease-causing
variants were found in CNGA3 (n [ 18), CNGB3 (n ¼ 15), GNAT2 (n ¼ 4), and PDE6C (n ¼ 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 ¼ 0.77), mean retinal sensitivity (P ¼ 0.21), or fixation stability (P ¼ 0.34) across the 5 SD-OCT categories were
evident. No correlation was found between age and foveal thickness (P ¼ 0.84) or between age and foveal ONL
thickness (P ¼ 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.

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