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.

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.

IMPORTANCE Clinical trial registries are intended to increase clinical research transparency by nonselectively identifying and documenting clinical trial designs and outcomes. Inconsistencies in reported data undermine the utility of such registries and have previously been noted in general medical literature. OBJECTIVE To assess whether inconsistencies in reported data exist between ophthalmic literature and clinical trial registries.

PurposeTo present ophthalmic imaging findings in the case of a 40-year-old male with sustained visual loss after a single episode of acute central serous retinopathy (CSR).ObservationsA male subject presented with visual acuity decline to 20/50 OS and was diagnosed with acute CSR. The initial pigment epithelial detachment and subretinal fluid resolved within 6 weeks, but visual acuity remained impaired. Using directional optical coherence tomography (D-OCT) and confocal and split-detector adaptive optics scanning light ophthalmoscopy (AOSLO), we imaged pathologic alterations in the photoreceptor mosaic of the affected eye. A foveal region of intermittent missing cones, a temporal parafoveal region of confluent missing cones, and a nasal parafoveal region of misdirected cones were observed.Conclusions and ImportancePathologic alterations in photoreceptor microanatomy underlie residual visual acuity deficits in this case of acute CSR. Observations of missing cones correlated well across all imaging modalities in the fovea and the temporal parafoveal region of missing cones. However, in the nasal parafovea where cones were present but misdirected, D-OCT and AOSLO may be able to identify and image photoreceptors with greater fidelity as compared to non-directional SDOCT (spectral domain OCT). D-OCT may thus have a clinical role in rapidly assessing photoreceptor mosaic integrity in pathology.