Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome

Abstract

PurposeThe purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO).MethodsNineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO.ResultsDespite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse.ConclusionsFoveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

Multimodal Imaging of Photoreceptor Structure in Choroideremia

“…[32, 45] These registered and averaged AOSLO images were manually montaged using Adobe Photoshop (Adobe Systems, Inc., CA) as previously described. [32] Line scanning ophthalmoscope (LSO) images from the Cirrus HD-OCT and volume intensity projection images from the Bioptigen SD-OCT were exported and, together with AOSLO montages, aligned to the clinical fundus images. The relative sizes of multimodal images were derived by scaling the visual angle for an ideal eye with an axial length of 24 mm, 291 μm/degree, in proportion to the subject’s measured axial length.…”

Central Retina Functional Damage in Usher Syndrome Type 2: 22 Years of Focal Macular ERG Analysis in a Patient Population From Central and Southern Italy

“…Furthermore, it indicates that the number of cones is significantly reduced in the central retina of patients with USH, compared with control values. 22 Taken together, these studies suggest that alongside severe peripheral deficits, loss of both structure and function of the central cone system in USH may characterize the early stages of the disease, preceding losses in visual acuity and perimetric sensitivity. Thus, identifying other sensitive functional measures of central retina cone function may certainly be helpful.…”

“…Despite the presence of normal ellipsoid and interdigitation zones detectable with OCT, foveal and parafoveal cone densities were significantly reduced with respect to control data when analyzed with AOSLO. 22 These changes were mainly due to the prevalence of cones with nonwave-guiding characteristics. The abnormal cones had intact inner segments, leading to the conclusion that foveal and parafoveal cone FIGURE 3. fERG, BCVA, and Goldmann V4e visual field versus age.…”

“…Indeed, cone density can be reduced by nearly 40% before visual acuity goes below 8/10 (logMAR 0.097), 22 and histopathologic studies show that RP patients may have relatively high acuity ante mortem ( ‡8/10), and yet retain a single rim of cones in the fovea. 34,35 The early and rapid fERG decline we found could represent an electrophysiologic correlate of the early abnormalities in structure and density found for central cones in USH.…”

“…In USH2 however, abnormal sensitivity has also been reported within the central region encompassed by the intact ellipsoid zone in the early disease stages. 22 Confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO) shows that central and paracentral cones in USH may be altered in their structure and probably in their waveguide function long before visual acuity loss. Furthermore, it indicates that the number of cones is significantly reduced in the central retina of patients with USH, compared with control values.…”