Early signs of longitudinal progressive cone photoreceptor degeneration in achromatopsia.
OBJECTIVE
To characterise longitudinal progressive retinal changes in achromatopsia.


METHODS
Ultrahigh-resolution spectral optical coherence tomography (Copernicus, 3 μm axial resolution) was used to obtain tomograms of the fovea from five children and three adults with achromatopsia. Each patient was scanned twice with a mean follow-up time of 16 months. Progressive changes in reflectivity at the inner segment/outer segment (IS/OS) junction, the central macular and outer nuclear layer thickness were analysed.


RESULTS
Younger patients (<10 years; patient 1-5) showed progressive morphological changes at the IS/OS junction between visits 1 and 2. However, older patients (>40 years; patients 6-8) did not have any changes in the retinal morphology between visits 1 and 2. In patients 1 and 2, IS/OS discontinuities (visit 1) developed into a hyper-reflective zone confined to the fovea (visit 2). In patient 3, the hyper-reflective zone (visit 1) progressed to form an IS/OS disruption and early formation of a small hypo-reflective zone (visit 2). Patients 4 and 5 had a hypo-reflective zone (visit 1) which subsequently increased in size (visit 2). There was a decrease in central macular and outer nuclear layer thickness between visits 1 and 2 in children.


CONCLUSIONS
For the first time, we show progressive longitudinal changes in retinal morphology in achromatopsia. Early changes include subtle IS/OS reflectivity alterations. The dynamic retinal changes in younger patients provide evidence that it represents a progressive disorder, and implementation of gene therapy during the early stages of the disease may provide best prognosis.
Ophthalmology Group, School of Medicine, University of Leicester, Leicester, UK.
Mervyn George
MG
Thomas
Rebecca Jane
RJ
McLean
Susanne
S
Kohl
Viral
V
Sheth
Irene
I
Gottlob
D000328:Adult; D002648:Child; D002675:Child, Preschool; D003117:Color Vision Defects / Q000235:genetics / Q000473:pathology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D005584:Fovea Centralis / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology*; D041623:Tomography, Optical Coherence
C518238:CNGA3 protein, human; C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels