Adaptive Optics Flood Illumination Research Articles

Multilayer Retinal Correspondence of the Structural and Vascular Anomalies in Eyes With Early Macular Telangiectasia Type 2.

To assess the correspondence between interdigitation zone (IZ) reflectivity, ellipsoid zone (EZ) loss, inner retinal layer reflectivity, patterns of capillary dilation, and telangiectasia in eyes with early macular telangiectasia type 2 (MacTel). Twenty-eight eyes of 22 patients with grade 0-2 MacTel (according to the MacTel project classification) and 28 healthy control eyes were included in this study. Multimodal imaging, including optical coherence tomography (OCT) angiography, adaptive optics flood illumination ophthalmoscopy (AO-FIO) and blue light reflectance (BLR), was performed. The EZ, IZ, and outer plexiform layer (OPL) were analyzed on the structural OCT C-scans. The vascular density (VD) was measured on the binarized and skeletonized angiograms of the superficial vascular plexus and deep capillary complex. The vascular diameter index (VDI) was calculated by dividing the binarized VD by the skeletonized VD. On AO-FIO, cone density in the MacTel zone was significantly lower in MacTel eyes than in controls, even in areas located outside the EZ loss (P < 0.001). A distinctive pattern of IZ reflectivity attenuation extended beyond the area of EZ attenuation. The shape and size of a strong OPL hyper-reflectivity corresponded to the MacTel white area (MacTel zone) seen on BLR. Capillary dilation and rarefaction were colocalized with this area, extending beyond visible telangiectasia. The VDI was higher in MacTel eyes than in controls (P < 0.001). These findings suggest that in early MacTel eyes, photoreceptor signal alteration, OPL hyper-reflectivity, and capillary dilation, potentially associated with Müller cell dysfunction, precede the EZ loss.

Are the Hypo-Reflective Clumps Associated With Age-Related Macular Degeneration in Adaptive Optics Ophthalmoscopy Autofluorescent?

Hypo-reflective clumps (HRCs) are structures associated with age-related macular degeneration (AMD) that were identified using flood-illumination adaptive optics ophthalmoscopy (FIAO) and hypothesized to be either macrophages that have accumulated melanin through the phagocytosis of retinal pigmented epithelial (RPE) cell organelles or transdifferentiated RPE cells. HRCs may be autofluorescent (AF) in the near infrared (NIR) but clinical NIR autofluorescence imaging lacks the resolution to answer this question definitively. Here, we used near infrared autofluorescence (NIRAF) imaging in fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to determine whether HRCs are AF. Patients with AMD and HRCs underwent imaging with FIAO, optical coherence tomography (OCT), and multi-modal AOSLO (confocal, NIRAF, and non-confocal multi-offset detection using a fiber bundle). HRCs were segmented on FIAO and images, co-registered across modalities, and HRC morphometry and AF were quantified. Eight patients participated (mean age = 79 years, standard deviation [SD] = 5.7, range = 69-89 years, and 5 female patients). Most HRCs (86%, n = 153/178) were autofluorescent on AOSLO. HRC AF signal varied but most uniformly dark HRCs on FIAO showed corresponding AF on AOSLO, whereas heterogeneous HRCs showed a smaller AF area or no AF. These findings are consistent with the hypothesis that HRCs contain AF RPE organelles. A small proportion of HRCs were not AF; these may represent macrophages that have not yet accumulated enough organelles to become AF. HRCs may have clinical significance but further study is needed to understand the interplay among HRCs, RPE cells, and macrophages, and their relationship to geographic atrophy (GA) progression in AMD.

Foveolar Drusen Decrease Fixation Stability in Pre-Symptomatic AMD.

This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD). We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. FEM were measured with high precision (RMS-S2S = 0.0015degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

Mapping the human parafoveal vascular network to understand flow variability in capillaries.

Capillary flow is known to be non-homogenous between vessels and variable over time, for reasons that are poorly understood. The local properties of individual vessels have been shown to have limited explanatory power in this regard. This exploratory study investigates the association of network-level properties such as vessel depth, branch order, and distance from the feeding arteriole with capillary flow. Detailed network connectivity analysis was undertaken in 3 healthy young subjects using flood-illuminated adaptive optics retinal imaging, with axial depth of vessels determined via optical coherence tomography angiography. Forty-one out of 70 vessels studied were of terminal capillary type, i.e. fed from an arterial junction and drained by a venous junction. Approximately half of vessel junctions were amenable to fitting with a model of relative branch diameters, with only a few adhering to Murray's Law. A key parameter of the model (the junction exponent) was found to be inversely related to the average velocity (r = -0.59, p = 0.015) and trough velocity (r = -0.67, p = 0.004) in downstream vessels. Aspects of cellular flow, such as the minimum velocity, were also moderately correlated (r = 0.46, p = 0.009) with distance to the upstream feeding arteriole. Overall, this study shows that capillary network topology contributes significantly to the flow variability in retinal capillaries in human eyes. Understanding the heterogeneity in capillary flow is an important first step before pathological flow states can be properly understood. These results show that flow within capillary vessels is not affected by vessel depths but significantly influenced by the upstream feeder distance as well as the downstream vessel junction exponents, but there remains much to be uncovered regarding healthy capillary flow.

Adaptive Optics Flood Illumination Ophthalmoscopy in Nonhuman Primates: Findings in Normal and Short-term Induced Detached Retinae

To describe adaptive optics flood illumination ophthalmoscopy (AO-FIO) of the photoreceptor layer in normal nonhuman primates (NHPs) and in the case of a short-term induced retinal detachment (RD). Longitudinal fundamental research study. Four NHPs were used to image normal retinae with AO-FIO (in comparison with 4 healthy humans); 2 NHPs were used to assess the effects of RD. The photoreceptor layer (cone mosaic metrics, including cone density, cone spacing, and cone regularity) was followed with AO-FIO imaging (rtx1, Imagine Eyes) during a surgically induced RD in 2 NHPs using a vehicle solution containing dimethyl sulfoxide, classically used as a chemical solvent. We also performed functional testing of the retina (full-field and multifocal electroretinogram [ERG]). Correlation of cone mosaic metrics (cone density, spacing, and regularity) between normal retinae of NHPs and humans, and cone metrics, power spectrum, and ERG wave amplitudes after RD. Imaging features were very similar in terms of cone reflectivity, cell density, regularity, and spacing values, showing strong positive correlations between NHPs and humans. After RD, AO-FIO revealed several alterations of the cone mosaic slowly recovering during the 3 months after the reattachment, which were not detected functionally by ERG. These results demonstrate by invivo AO-FIO imaging the transient structural changes of photoreceptors after an RD in the primate retina. They also provide an interesting illustration of the AO-FIO potential for investigating photoreceptor toxicity during preclinical studies in NHPs with a high translatability to human studies. Proprietary or commercial disclosure may be found after the references.

Volume-accumulated reflectivity of the outer retina (integral) on spectral domain optical coherence tomography as a predictor of cone cell density: a pilot study

BackgroundThe study aims to investigate the relationship between the volume-accumulated reflectivity (termed “integral”) on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging.MethodsIn this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1.ResultsIntegrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p < 0.001) and those with IRD (r = 0.823, p < 0.001) than direct measurements of reflectivity on OCT images. A strong correlation was found between best corrected visual acuity (BCVA) and cone density at 2° eccentricity (r = -0.857, p = 0.002). BCVA was also correlated with the integral of the IZ at the foveola (r = -0.746, p = 0.013) and fovea (r = -0.822, p = 0.004).ConclusionsThe new parameter “integral” of the photoreceptor outer segment measured from SD-OCT was noted to correlate with cone density and visual function in this pilot study.

Comprehensive automatic processing and analysis of adaptive optics flood illumination retinal images on healthy subjects.

This work presents a novel fully automated method for retinal analysis in images acquired with a flood illuminated adaptive optics retinal camera (AO-FIO). The proposed processing pipeline consists of several steps: First, we register single AO-FIO images in a montage image capturing a larger retinal area. The registration is performed by combination of phase correlation and the scale-invariant feature transform method. A set of 200 AO-FIO images from 10 healthy subjects (10 images from left eye and 10 images from right eye) is processed into 20 montage images and mutually aligned according to the automatically detected fovea center. As a second step, the photoreceptors in the montage images are detected using a method based on regional maxima localization, where the detector parameters were determined with Bayesian optimization according to manually labeled photoreceptors by three evaluators. The detection assessment, based on Dice coefficient, ranges from 0.72 to 0.8. In the next step, the corresponding density maps are generated for each of the montage images. As a final step, representative averaged photoreceptor density maps are created for the left and right eye and thus enabling comprehensive analysis across the montage images and a straightforward comparison with available histological data and other published studies. Our proposed method and software thus enable us to generate AO-based photoreceptor density maps for all measured locations fully automatically, and thus it is suitable for large studies, as those are in pressing need for automated approaches. In addition, the application MATADOR (MATlab ADaptive Optics Retinal Image Analysis) that implements the described pipeline and the dataset with photoreceptor labels are made publicly available.

MULTIMODAL IMAGING OF MULTIFOCAL CHOROIDITIS WITH ADAPTIVE OPTICS OPHTHALMOSCOPY.

To describe longitudinal, anatomical, and functional alterations caused by inflammatory and neovascular lesions of idiopathic multifocal choroiditis/punctate inner choroidopathy using adaptive optics imaging and microperimetry. Longitudinal case study using multiple imaging modalities, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, flood illumination adaptive optics, and microperimetry. A 21-year-old myopic Asian man presented with blurred vision in the right eye. Clinical examination was notable for an isolated hypopigmented, perifoveal lesion in each eye. Multimodal imaging showed inflammatory lesions in the outer retina, retina pigment epithelium, and inner choroid lesions of both eyes. The right eye additionally exhibited active Type-2 macular neovascularization with loss of cone mosaic regularity that was associated with reduced sensitivity on microperimetry. The clinical picture was consistent with multifocal choroiditis/punctate inner choroidopathy. The patient was treated with oral steroids and three injections of intravitreal bevacizumab in the right eye. After therapy, imaging showed reestablishment of the cone mosaic on flood illumination adaptive optics and improvement in sensitivity on microperimetry. Adaptive optics imaging and microperimetry may detect biomarkers that help to characterize the nature and activity of multifocal choroiditis lesions and to help monitor response to therapy. With timely intervention, structural abnormalities in the outer retina and choroid can be treated, and anatomical improvements precede improvements in visual function.

Autofluorescent hyperreflective foci on infrared autofluorescence adaptive optics ophthalmoscopy in central serous chorioretinopathy

PurposeTo test the hypothesis that hyperreflective foci in central serous chorioretinopathy (CSCR) are autofluorescent and may represent macrophages that have engulfed outer retinal fluorophores from the retinal pigment epithelium (RPE) and photoreceptors. MethodsEnrolled subjects underwent spectral domain and swept-source optical coherence tomography, adaptive optics flood-illumination, and adaptive optics scanning laser ophthalmoscopy (AOSLO), including near-infrared autofluorescence (AO-IRAF). For the AO-IRAF imaging, retinal fluorophores were excited using 795 nm light and collected in an emission band from 814 to 850 nm. ResultsIn 2 of 3 eyes, a hyperautofluorescent signal was detected with an elliptical shape and punctate, granular aspects surrounded by a hypoautofluorescent halo. The size of these structures in the active case was measured to be 17 ± 4 μm in diameter, with at least 45 individual hyperautofluorescent foci identified from the AO-IRAF montage in the active stage of patient 2. In the asymptomatic case there were fewer structures visible (∼10) and their size was smaller (11 ± 4 μm). These hyper-AF foci were colocalized with hyperreflective foci on OCT and visible in simultaneously acquired confocal AOSLO images in active stage. The hyperautofluorescent foci in the patient with active CSCR disappeared coincident with clinical resolution. Conclusion and importanceWe show here the first AO-IRAF images from patients with CSCR, demonstrating hyper-autofluorescent punctate foci, colocalized with hyper-reflective foci on confocal AOSLO images and in OCT. The autofluorescence of these foci may be driven by the accumulation of photoreceptor and RPE fluorophores within macrophages during the active stage of the disease.

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort.

The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5–56 years, underwent a detailed ophthalmic examination including visual acuity and color vision testing, electroretinography (ERG), visually evoked potential recording (VEP), fundus examination, and spectral domain optical coherence tomography (SD-OCT). Adaptive optics flood illumination ophthalmoscopy was performed in five patients. All patients had received diagnostic genetic testing and were selected upon the presence of apparent biallelic variants in known BBS-associated genes. All patients had retinal dystrophy with morphologic changes of the retina. Visual acuity decreased from ~0.2 (decimal) at age 5 to blindness 0 at 50 years. Visual field examination could be performed in only half of the patients and showed a concentric constriction with remaining islands of function in the periphery. ERG recordings were mostly extinguished whereas VEP recordings were reduced in about half of the patients. The cohort of patients showed 51 different likely biallelic mutations—of which 11 are novel—in 12 different BBS-associated genes. The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5 (21 alleles) and BBS1 c.1169T>G;p.M390R (18 alleles). The phenotype associated with the different BBS-associated genes and genotypes in our cohort is heterogeneous, with diverse features without genotype–phenotype correlation. The results confirm and expand our knowledge of this rare disease.

Impact of Reference Center Choice on Adaptive Optics Imaging Cone Mosaic Analysis.

PurposeFoveal center marking is a key step in retinal image analysis. We investigated the discordance between the adaptive optics (AO) montage center (AMC) and the foveal pit center (FPC) and its implications for cone mosaic analysis using a commercial flood-illumination AO camera.MethodsThirty eyes of 30 individuals (including 15 healthy and 15 patients with rod–cone dystrophy) were included. Spectral-domain optical coherence tomography was used to determine the FPC, and flood-illumination AO imaging was performed with overlapping image frames to create an AO montage. The AMC was determined by averaging the (0,0) coordinates in the four paracentral overlapping AO image frames. Cone mosaic measurements at various retinal eccentricities were compared between corresponding retinal loci relative to the AMC or FPC.ResultsAMCs were located temporally to the FPCs in 14 of 15 eyes in both groups. The average AMC–FPC discordance was 0.85° among healthy controls and 0.33° among patients with rod-cone dystrophy (P < 0.05). The distance of the AMC from the FPC was a significant determinant of the cone density (β estimate = 218 cells/deg2/deg; 95% confidence interval [CI], 107–330; P < 0.001) and inter-cone distance (β estimate = 0.28 arcmin/deg; 95% CI, 0.15–0.40; P < 0.001), after adjustment for age, sex, axial length, spherical equivalent, eccentricity, and disease status.ConclusionsThere is a marked mismatch between the AMC and FPC in healthy eyes that may be modified by disease process such as rod–cone dystrophy. We recommend users of AO imaging systems carefully align the AO montage with a foveal anatomical landmark, such as the FPC, to ensure precise and reproducible localization of the eccentricities and regions of interest for cone mosaic analysis.

A New Method for Visualizing Drusen and Their Progression in Flood-Illumination Adaptive Optics Ophthalmoscopy.

PurposeDrusen are dynamic sub-RPE deposits that are risk factors for late-stage age-related macular degeneration (AMD). Here we show a new imaging method using flood-illumination adaptive optics (FIAO) that reveal drusen with high contrast and resolution.MethodsA fovea-centered 4° × 4° FIAO image and eight surrounding images with gaze displaced by ±2° vertically and horizontally were acquired. Clinical color fundus and spectral-domain optical coherence tomography were acquired for clinical grading and comparison. Custom software registered overlapping FIAO images and fused the data statistically to generate a fovea-centered 4° × 4° gaze-dependent image. Our dataset included 15 controls (aged 31–72) and 182 eyes from 104 AMD patients (aged 56–92), graded as either normal aging (n = 7), and early (n = 12), intermediate (n = 108) and late AMD (n = 42); 27 had subretinal drusenoid deposits (SDDs), and 83 were imaged longitudinally.ResultsNo gaze varying structures were detected in young eyes. In aging eyes with no evidence of age-related changes, putative drusen <20 µm in diameter were visible. Gaze-dependent images revealed more drusen and many smaller drusen than visible in color fundus images. Longitudinal images showed expansion and fusion of drusen. SDDs were lower contrast, and RPE atrophy did not yield a consistent signal.ConclusionsGaze-dependent imaging in a commercially available FIAO fundus camera combined with image registration and postprocessing permits visualization of drusen and their progression with high contrast and resolution.Translational RelevanceThis new technique offers promise as a robust and sensitive method to detect, map, quantify, and monitor the dynamics of drusen in aging and AMD.

Short-Term Parafoveal Cone Loss Despite Preserved Ellipsoid Zone in Rod Cone Dystrophy.

PurposeRod–cone dystrophy (RCD) is characterized by centripetal loss of rod followed by cone photoreceptors. In this prospective, observational cohort, we used flood-illumination adaptive optics (AO) imaging to investigate parafoveal cone loss in regions with preserved ellipsoid zone (EZ) in patients with RCD.MethodsEight patients with RCD and 10 age-matched healthy controls underwent spectral-domain optical coherence tomography and AO imaging. The RCD cohort underwent a follow-up examination after 6 months. Cone density (CD) and intercone distance (ICD) measurements were performed at 2° temporal from the fovea. Baseline CD and ICD values were compared between the control and patient groups, and longitudinal changes were calculated in the patient group. Residual EZ span in patients was measured in horizontal foveal B-scans.ResultsBetween the control and patient groups, there was no significant difference in the baseline CD (2094 vs. 1750 cells/deg2, respectively; P = 0.09) and ICD (1.46 vs. 1.62 arcmin, respectively; P = 0.08). Mean CD declined by 198 cells/deg2 (−11.3%; P < 0.01), and mean ICD increased by 0.09 arcmin (+5.6%; P = 0.01) at the 6-month follow-up in the patient group. Mean baseline and follow-up residual EZ spans in the six patients with EZ defect were 3189 µm and 3065 µm, respectively (−3.9%; P = 0.08).ConclusionsAO imaging detected significant parafoveal cone loss over 6-month follow-up even in regions with preserved EZ. Further studies to refine AO imaging protocol and validate cone metrics as a structural endpoint in early RCD are warranted.Translational RelevanceCD and ICD may change prior to EZ span shortening in RCD.

Evaluation of focus and deep learning methods for automated image grading and factors influencing image quality in adaptive optics ophthalmoscopy

Adaptive optics flood illumination ophthalmoscopy (AO-FIO) is an established imaging tool in the investigation of retinal diseases. However, the clinical interpretation of AO-FIO images can be challenging due to varied image quality. Therefore, image quality assessment is essential before interpretation. An image assessment tool will also assist further work on improving the image quality, either during acquisition or post processing. In this paper, we describe, validate and compare two automated image quality assessment methods; the energy of Laplacian focus operator (LAPE; not commonly used but easily implemented) and convolutional neural network (CNN; effective but more complex approach). We also evaluate the effects of subject age, axial length, refractive error, fixation stability, disease status and retinal location on AO-FIO image quality. Based on analysis of 10,250 images of 50 × 50 μm size, at 41 retinal locations, from 50 subjects we demonstrate that CNN slightly outperforms LAPE in image quality assessment. CNN achieves accuracy of 89%, whereas LAPE metric achieves 73% and 80% (for a linear regression and random forest multiclass classifier methods, respectively) compared to ground truth. Furthermore, the retinal location, age and disease are factors that can influence the likelihood of poor image quality.

Assessing Photoreceptor Status in Retinal Dystrophies: From High-Resolution Imaging to Functional Vision

PurposeTo describe the value of integrating phenotype/genotype data, disease staging, and evaluation of functional vision in patient-centered management of retinal dystrophies.Methods(1) Cross-sectional structure-function and retrospective longitudinal studies to assess the correlations between standard fundus autofluorescence (FAF), optical coherence tomography, visual acuity (VA), and perimetry (visual field [VF]) examinations to evaluate photoreceptor functional loss in a cohort of patients with rod-cone dystrophy (RCD); (2) flood-illumination adaptive optics (FIAO) imaging focusing on photoreceptor misalignment and orientation of outer segments; and (3) evaluation of the impact of visual impairment in daily life activities, based on functional (visual and mobility) vision assessment in a naturalistic environment in visually impaired subjects with RCD and subjects treated with LuxturnaⓇ for RPE65-related Leber congenital amaurosis before and after therapy.ResultsThe results of the cross-sectional transversal study showed that (1) VA and macular sensitivity were weakly correlated with the structural variables; and (2) functional impairment (VF) was correlated with reduction of anatomical markers of photoreceptor structure and increased width of autofluorescent ring. The dimensions of the ring of increased FAF evolved faster. Other criteria that differed among groups were the lengths of the ellipsoid zone, the external limiting membrane, and the foveal thickness. FIAO revealed a variety of phenotypes: paradoxical visibility of foveal cones; heterogeneous brightness of cones; dim, inner segment–like, and RPE-like mosaic. Directional illumination by varying orientation of incident light (Stiles-Crawford effect) and the amount of side illumination (gaze-dependent imaging) affected photoreceptor visibility. Mobility assessment under different lighting conditions showed correlation with VF, VA, contrast sensitivity (CS), and dark adaptation, with different predictive values depending on mobility study paradigms and illumination level. At high illumination level (235 lux), VF was a predictor for all mobility performance models. Under low illumination (1 and 2 lux), VF was the most significant predictor of mobility performance variables, while CS best explained the number of collisions and segments. In subjects treated with LuxturnaⓇ, a very favorable impact on travel speed and reduction in the number of collisions, especially at low luminance, was observable 6 months following injection, in both children and adults.ConclusionsOur results suggest the benefit of development and implementation of quantitative and reproducible tools to evaluate the status of photoreceptors and the impact of both visual impairment and novel therapies in real-life conditions. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Adaptive Optics Imaging in Patients Affected by Pseudoxanthoma Elasticum

To describe the retinal findings of patients affected by pseudoxanthoma elasticum (PXE) using a multimodal imaging approach including flood-illumination adaptive optics ophthalmoscopy (AO). Retrospective case series. Patients affected by PXE were retrospectively studied. Clinical data, color, infrared and autofluorescence fundus imaging, optical coherence tomographic scans, and AO examinations were collected. Furthermore, the photoreceptor count was assessed. PXE diagnosis was confirmed by a positive skin biopsy and/or genetic testing. Twenty-one eyes of 18 patients (11 females and 7 males) were included in the study. In 3 patients, both eyes were studied. The mean age at examination was 37 ± 16.4 years (range 11-66) and the mean best-corrected visual acuity (BCVA) was 0.1 ± 0.2 logMAR (range 0-1). We identified 3 types of angioid streaks (AS) using AO: "crack," "band," and "hypopigmented." The first 2 were very similar and they differed in size; the third type showed specific clinical features. Comet lesions appeared as hyper-reflective round lesions on AO imaging. In all eyes, the cone mosaic appeared reduced inside the streaks compared to the neighboring areas (13,532.8 ± 1,366.5 cones/mm2 vs 16,817.1 ± 1,263.0 cones/mm2 respectively). Using AO imaging in PXE-related retinopathy, we were able to observe the presence of the photoreceptors within the angioid streaks, differentiate 3 types of angioid streaks, based on size and reflective features, and identify the very small crystalline bodies not identifiable using other retinal imaging techniques.

Solar retinopathy-correlation between adaptive optics and spectral domain optical coherence tomography with visual acuity.

To study the characteristics of photoreceptors on adaptive optics (AO) in patients of solar retinopathy and its correlation to changes in spectral domain optical coherence tomography (SDOCT) and visual acuity. This is a cross-sectional observational study of six eyes of five patients with clinically diagnosed solar retinopathy. Five age-matched controls were included for comparison. A flood-illuminated adaptive optics retinal camera (AO; rtx1, Imagine Eyes, Orsay, France) was used to image the photoreceptors and a spectral domain optical coherence tomography (SDOCT; Spectralis™ Heidelberg Engineering, Germany) was used to study the retinal layers in these patients. The corrected distance visual acuity (CDVA) was assessed using Snellen's chart. Defects on the SDOCT were smaller (0.25 to 0.75°) at the fovea compared with AO (more than 1°). The cone mosaic was preserved beyond 1°. The cone count from the foveal center at 0.75, 1, 2, and 3° was decreased in all patients of solar retinopathy (mean value 5352) compared with age-matched controls (mean value 15693). A corresponding increase in spacing (mean value 19.13) compared with controls (mean value 9.34) was also observed. The CDVA ranged from 20/30 to 20/80. There was no statistically significant relationship between cone density, at any of the eccentricities measured, with CDVA or OCT defect (p > 0.05, for all). Adaptive optics is a sensitive and accurate tool to analyze photoreceptor damage in solar maculopathy. It can be used as an adjunct for better understanding of the pathology and to observe or predict changes in these patients.

Kilohertz retinal FF-SS-OCT and flood imaging with hardware-based adaptive optics.

A retinal imaging system was designed for full-field (FF) swept-source (SS) optical coherence tomography (OCT) with cellular resolution. The system incorporates a real-time adaptive optics (AO) subsystem and a very high-speed CMOS sensor, and is capable of acquiring volumetric images of the retina at rates up to 1 kHz. While digital aberration correction (DAC) is an attractive potential alternative to AO, it has not yet been shown to provide resolution allowing visualization of cones in the fovea, where early detection of functional deficits is most critical. Here we demonstrate that FF-SS-OCT with hardware AO permits resolution of foveal cones, imaged at eccentricities of 1° and 2°, with volume rates adequate to measure light-evoked changes in photoreceptors. With the reference arm blocked, the system can operate as a kilohertz AO flood illumination fundus camera with adjustable temporal coherence and is expected to allow measurement of light-evoked changes caused by common path interference in photoreceptor outer segments (OS). In this paper, we describe the system's optical design, characterize its performance, and demonstrate its ability to produce images of the human photoreceptor mosaic.

IN VIVO OBSERVATION OF RETINAL VASCULAR DEPOSITS USING ADAPTIVE OPTICS IMAGING IN FABRY DISEASE.

To report a novel finding in patients with Fabry disease, that is, the observation by adaptive optics ophthalmoscopy of intracellular lipidic deposits in retinal vessels. Observational two-center case series. Eighteen patients with genetically proven Fabry disease underwent flood-illumination adaptive optics ophthalmoscopy imaging (rtx1; Imagine Eyes, Orsay, France) of retinal vessels. Fourteen patients (78% of all patients; 7 of the 10 women and 7 of the 8 men) showed paravascular punctuate or linear opacities in both eyes. In the least-affected patients, these were seen only in the wall of precapillary arterioles as discrete spots of 5 µm to 10 µm large, whereas in those more severely affected, capillaries and first-order vessels were also involved with diffuse opacification of the wall. These deposits sometime showed a striated pattern, suggesting colocalization with vascular smooth muscle cells. Adaptive optics ophthalmoscopy of retinal vessels may be of interest for patients with Fabry disease, providing noninvasive, gradable evaluation of microvascular involvement.

EVALUATION OF PHOTORECEPTORS, RETINAL CAPILLARY PLEXUSES, AND CHORIOCAPILLARIS IN PATIENTS WITH BIRDSHOT CHORIORETINOPATHY.

To assess the status of the cone photoreceptors using adaptive optics flood illumination ophthalmoscopy in patients with birdshot chorioretinopathy and to study their relationship with optical coherence tomography (OCT) angiography. Seventeen patients with birdshot chorioretinopathy were studied using standard automated perimetry, color vision testing, fluorescein angiography, indocyanine green angiography, spectral domain OCT, enhanced depth imaging OCT, and adaptive optics flood illumination ophthalmoscopy (rtx1, Imagine Eyes, Orsay, France) in a 90 × 90-μm area at 1.5° temporal of the fovea and OCT angiography (Spectralis OCT2, Heidelberg Engineering, Heidelberg, Germany). For adaptive optics flood illumination ophthalmoscopy, spectral domain OCT, and OCT angiography, a control group of 12 healthy patients (12 eyes) matched for age, sex, and refractive error was included. After excluding low-quality adaptive optics flood illumination ophthalmoscopy images, 12 eyes (12 patients, 7 women, mean age 53.5 ± 10.8 years) were analyzed. Best-corrected visual acuity was 0.01 ± 0.03 LogMAR (20/25 Snellen equivalent), and foveal threshold at standard automated perimetry was 35.2 ± 3.0. Cone density at 1.5° of the fovea in the birdshot chorioretinopathy group (11,435.25 ± 4,342.9 cells/mm) was significantly smaller than in the control group (24,594.04 ± 4,764.3 cells/mm, P < 0.001). In the same area, birdshot chorioretinopathy eyes showed disruption of the ellipsoid/interdigitation zone and vascular abnormalities, such as capillary loops (58.3%), increased superficial intercapillary spaces (75%), increased deep intercapillary spaces (58.3%), capillary dilations (58.3%), telangiectatic vessels (66.6%), and absence of choriocapillary flow (58%). Cone density at 1.5° was associated with duration of the disease (Spearman's rho -0.8, P = 0.01), although it was not associated with OCT angiography abnormalities in the same area. Birdshot chorioretinopathy can result in a reduction in cone density and development of macular vascular abnormalities even in the presence of preserved visual function.