Multimodal Imaging of Photoreceptor Structure in Choroideremia

Abstract

PurposeChoroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions.MethodsTwelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques.ResultsEleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina.ConclusionsEarly IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors.

Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2

“…27 Split detector AOSLO has been used previously to image remnant cone structure at the borders of atrophic lesions, where cone structure abruptly terminates, in choroideremia. 33 In our study, clusters of cones became visible at follow-up examinations on confocal AOSLO in areas previously identified as intralesional on SDOCT. These changes on confocal AOSLO have been reported previously, 9 but the mechanism for this change remains unclear.…”

The Effect of Retinal Melanin on Optical Coherence Tomography Images

“…1 Its superior axial resolution makes it valuable in studying individual retinal layers, and implementation of summed volume projections can provide detailed, layer-specific en face images. 2–5 Despite its use, controversy remains regarding the anatomic origin of the hyperreflective signals corresponding to the photoreceptors and other outer retinal structures on OCT.…”

Cellular imaging of inherited retinal diseases using adaptive optics

“…There is, therefore, strong rationale for the complementary use of both confocal and non-confocal AOSLO in the assessment of retinal structure, especially in IRDs ( Fig. 3) [23,[55][56][57]. Disadvantages of AOSLO include its propensity for image distortion, as well as the inefficiency of its serial image creation [58].…”