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Mariya Moosajee, Simon C Ramsden, Graeme C Black, Anthony T Moore, Andrew Webster; Spectrum of CHM mutations, structural retinal features and their progression in choroideremia patients within the UK. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6431.
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Choroideremia (CHM) is an X-linked recessive chorioretinal dystrophy, which exhibits high inter- and intra-familial variability, and is caused by mutations involving the CHM gene located at chromosome Xq21.2. The advent of clinical gene therapy trials calls for suitable imaging techniques to discern any response to treatment. The purpose of this study is to describe CHM mutations in the UK cohort, and investigate the structural retinal features of CHM using high resolution longitudinal in vivo imaging to monitor disease progression.
Thirty-two male patients from 30 CHM families (average age 39.9 years, range 10-76 years), with a mean follow-up of 51.6 months (range 6-127 months) underwent genetic analysis, serial spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging. Macular thickness and structural retinal abnormalities were recorded. The Vista 2 Retinal Area Analysis Tool was used to measure the area (square-degrees) and rate of FAF loss at the macula (square-degrees/months).
Molecular analysis of the CHM gene identified the majority of mutations were nonsense (10/30), frameshift and larger deletions, however there was one missense mutation (H507R). SD-OCT showed central macular thinning in CHM patients (255.2 ± 33.2 μm) compared to healthy individuals (270.2 ± 22.5 μm), P<0.05. All patients showed the presence of outer retinal tubulations and 44% revealed cystoid macular oedema (CMO). The rate of FAF loss over time was 0.42 ± 0.62 square-degrees/months, with variation between age groups but no decade showing a statistically significant difference.
The first gene therapy trial for choroideremia has begun, the use of FAF will be a useful long-term indicator of outcome. As younger patients are recruited, SD-OCT imaging may provide a more accurate image of retinal thickness and remodeling, evidence of CMO and progressive thinning.
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