Using Spectral-Domain Optical Coherence Tomography to Follow Outer Retinal Structure Changes in a Patient with Recurrent Punctate Inner Choroidopathy

Punctate inner choroidopathy (PIC) is a rare idiopathic inflammatory disorder of the retina and choroid usually affecting healthy, young, myopic females and presenting with photopsia, paracentral scotomata, and blurred vision. It is characterized by yellow-white chorioretinal lesions concentrated in the posterior pole, no vitritis, relapsing inflammatory activity of the retina and choroid, and frequent development of choroidal neovascular membranes. Here we describe a case in which spectral-domain optical coherence tomography (SD-OCT) imaging was used to monitor outer retinal structure changes associated with recurrent PIC over time. SD-OCT, which is both quantative and objective, provides an efficient, non-invasive way to follow recurrent inflammatory chorioretinal lesion activity, choroidal neovascular membrane development, and treatment response in patients with recurrent PIC

Subclinical Photoreceptor Disruption in Response to Severe Head Trauma

Commotio retinae is a transient opacification of the retina due to outer retinal disruption occurring in a contrecoup fashion after blunt trauma.Histological studies in animals and humans after ocular blunt trauma have revealed that disruption occurs at the level of the photoreceptor outer segments and retinal pigment epithelium.Recent reports using optical coherence tomography (OCT) have shown detectable disruption at the level of the photoreceptor inner segment/outer segment junction and retinal pigment epithelium and that these changes may be reversible over time with restoration of normal outer retinal architecture.However, the resolution of existing OCT technology may not be sensitive enough to detect photoreceptor disruption. Adaptive optics (AO) imaging systems enable cellular-resolution imaging of the human retina, and there is a growing number of cases where deficits have been visible on AO images but not on OCT. Herein, we report a case of subclinical photoreceptor disruption after head trauma as seen by an AO scanning ophthalmoscope (AOSO) but not apparent clinically or on spectral-domain OCT (SD-OCT)

Outer Retinal Structure in Best Vitelliform Macular Dystrophy

Importance Demonstrating the utility of adaptive optics scanning light ophthalmoscopy (AOSLO) to assess outer retinal structure in Best vitelliform macular dystrophy (BVMD). Objective To characterize outer retinal structure in BVMD using spectral-domain optical coherence tomography (SD-OCT) and AOSLO. Design, Setting, and Participants Prospective, observational case series. Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee. Intervention Thickness of 2 outer retinal layers corresponding to photoreceptor inner and outer segments was measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in 2 subjects. Main Outcome and Measure Photoreceptor structure. Results Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size were consistent with Henle fibers. Conclusions and Relevance The AOSLO findings indicate that substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation

Photoreceptor Inner Segment Morphology in Best Vitelliform Macular Dystrophy

PURPOSE To characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors. METHODS Five individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period. RESULTS The AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed. CONCLUSION Combined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD

Assessing Errors Inherent in OCT-Derived Macular Thickness Maps

SD-OCT has become an essential tool for evaluating macular pathology; however several aspects of data collection and analysis affect the accuracy of retinal thickness measurements. Here we evaluated sampling density, scan centering, and axial length compensation as factors affecting the accuracy of macular thickness maps. Forty-three patients with various retinal pathologies and 113 normal subjects were imaged using Cirrus HD-OCT. Reduced B-scan density was associated with increased interpolation error in ETDRS macular thickness plots. Correcting for individual differences in axial length revealed modest errors in retinal thickness maps, while more pronounced errors were observed when the ETDRS plot was not positioned at the center of the fovea (which can occur as a result of errant fixation). Cumulative error can exceed hundreds of microns, even under “ideal observer” conditions. This preventable error is particularly relevant when attempting to compare macular thickness maps to normative databases or measuring the area or volume of retinal features

Microscopic Inner Retinal Hyper-reflective Phenotypes in Retinal and Neurologic Disease

Purpose. We surveyed inner retinal microscopic features in retinal and neurologic disease using a reflectance confocal adaptive optics scanning light ophthalmoscope (AOSLO). Methods. Inner retinal images from 101 subjects affected by one of 38 retinal or neurologic conditions and 11 subjects with no known eye disease were examined for the presence of hyper-reflective features other than vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper-reflective features in the AOSLO images were grouped based on size, location, and subjective texture. Clinical imaging, including optical coherence tomography (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for comparison. Results. Seven categories of hyper-reflective inner retinal structures were identified, namely punctate reflectivity, nummular (disc-shaped) reflectivity, granular membrane, waxy membrane, vessel-associated membrane, microcysts, and striate reflectivity. Punctate and nummular reflectivity also was found commonly in normal volunteers, but the features in the remaining five categories were found only in subjects with retinal or neurologic disease. Some of the features were found to change substantially between follow up imaging months apart. Conclusions. Confocal reflectance AOSLO imaging revealed a diverse spectrum of normal and pathologic hyper-reflective inner and epiretinal features, some of which were previously unreported. Notably, these features were not disease-specific, suggesting that they might correspond to common mechanisms of degeneration or repair in pathologic states. Although prospective studies with larger and better characterized populations, along with imaging of more extensive retinal areas are needed, the hyper-reflective structures reported here could be used as disease biomarkers, provided their specificity is studied further

Multimodal Imaging of Photoreceptor Structure in Choroideremia

Purpose Choroideremia 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. Methods Twelve 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. Results Eleven 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. Conclusions Early 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

The Effect of Cone Opsin Mutations on Retinal Structure and the Integrity of the Photoreceptor Mosaic

Purpose. To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations. Methods. Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array. Results. While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic. Conclusions. The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy