High resolution imaging analysis of female carriers and patients of choroideremia with CHM gene mutation

Purpose To report the high resolution imaging features of Japanese patient and female carriers of choroideremia using adaptive optics(AO) and other imaging modalities. Methods Three carriers and one patient underwent comprehensive examinations including AO fundus camera (rtx1™ Imagine eyes, France), spectral domain optical coherence topography (SD-OCT)and fundus autofluoresence (FAF). Cone density was measured by peak density method and compared with the data of 34 normal controls. The mutation analysis of the CHM gene was performed by Sanger sequencing. The protocol conformed to the tenets of the Declaration of Helsinki and was approved by the IRB of The Jikei University and Nippon Medical School. Results Three female carriers 1, 2, 3 (sister 9 y.o, mother 37 y.o and grandmother 65 y.o) and one patient (6 y.o, male). They had same CHM mutation, c.646delA, p.T216LfsX16. All carriers did not complain any symptoms, the BCVA of all were over 20/20. Fundus examination of carrier 2 showed mild generation in only periphery, the other carriers showed diffuse degeneration. AF showed mottled hypo-autofluoresence in degeneration area. SD-OCT of the carriers showed nearly normal,although peripheral SD-OCT and patient showed diffuse disruptions of interdigitation and ellipsoid zones.Cone density was measured at 2 to 8 degree temporal from the fovea in every 1 degree, using 50 x 50 micron images. Cone counting was performed by AO detect (Imagine eyes) with manual correction. Patient showed lower cone density more than 2 SD of normal control. The carriers showed lower cone density only at 7 and 8 degrees. Conclusions AO cone counting showed reduction of photoreceptors in carriers mainly at peripheral region. To elucidate the mechanism of peripheral degeneration and foveal sparing of female carriers may help preventing the disease progression of choroideremia patients.