Adaptive Optics Optical Coherence Tomography Research Articles

Improvements on speed, stability and field of view in adaptive optics OCT for anterior retinal imaging using a pyramid wavefront sensor.

We present improvements on the adaptive optics (AO) correction method using a pyramid wavefront sensor (P-WFS) and introduce a novel approach for closed-loop focus shifting in retinal imaging. The method's efficacy is validated through in vivo adaptive optics optical coherence tomography (AO-OCT) imaging in both, healthy individuals and patients with diabetic retinopathy. In both study groups, a stable focusing on the anterior retinal layers is achieved. We further report on an improvement in AO loop speed that can be used to expand the imaging area of AO-OCT in the slow scanning direction, largely independent of the eye's isoplanatic patch. Our representative AO-OCT data reveal microstructural details of the neurosensory retina such as vessel walls and microglia cells that are visualized in single volume data and over an extended field of view. The excellent performance of the P-WFS based AO-OCT imaging in patients suggests good clinical applicability of this technology.

Multimodal High-Resolution Imaging in Retinitis Pigmentosa: A Comparison Between Optoretinography, Cone Density, and Visual Sensitivity.

Retinitis pigmentosa (RP), the most common inherited retinal disease, is characterized by progressive photoreceptor degeneration. It remains unknown to what extent surviving photoreceptors transduce light and support vision in RP. To address this, we correlated structure and functional measures using adaptive optics scanning laser ophthalmoscopy (AOSLO), adaptive optics microperimetry, and adaptive optics optical coherence tomography (AO-OCT)-based optoretinograms (ORGs). Four patients with RP were imaged with AOSLO across the visual field covering the transition zone (TZ) of normal to diseased retina. Cone density was estimated in discrete regions spanning the TZ. Visual sensitivity was assessed by measuring increment thresholds for a 3-arcmin stimulus targeted via active eye tracking in AOSLO. ORGs were measured at the same locations using AO-OCT to assess the cones' functional response to a 528 ± 20-nm stimulus. Individual cone outer segment (COS) lengths were measured from AO-OCT in each subject. Cone density was significantly reduced in patients with RP. Density reduction correlated with TZ location in 3 patients with RP, while a fourth had patches of reduced density throughout the retina. ORG amplitude was reduced in regions of normal and reduced cone density in all patients with RP. ORG response and COS length were positively correlated in controls but not in patients with RP. Despite deficits in cone density and ORG, visual sensitivity remained comparable to controls in three of four patients with RP. ORG-based measures of retinal dysfunction may precede deficits in cone structure and visual sensitivity. ORG is a sensitive measure of RP disease status and has significant potential to provide insight into disease progression and treatment efficacy.

Quantification of Human Photoreceptor-Retinal Pigment Epithelium Macular Topography with Adaptive Optics-Optical Coherence Tomography.

Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques. We used the cellular resolution and depth-sectioning capabilities of a custom, high-speed Fourier domain mode-locked laser-based adaptive optics-optical coherence tomography (FDML-AO-OCT) platform to characterize human PR-RPE complex topography across the temporal macula from eleven healthy volunteers. With the aid of a deep learning algorithm, key metrics were extracted from the PR-RPE complex of averaged AO-OCT volumes including PR and RPE cell density, PR outer segment length (OSL), and PR/RPE ratio. We found a tight grouping among our cohort for PR density, with a mean (±SD) value of 53,329 (±8106) cells/mm2 at 1° decreasing to 8669 (±737) cells/mm2 at 12°. We observed a power function relationship between eccentricity and both PR density and PR/RPE ratio. We found similar variability in our RPE density measures, with a mean value of 7335 (±681) cells/mm2 at 1° decreasing to 5547 (±356) cells/mm2 at 12°, exhibiting a linear relationship with a negative slope of -123 cells/mm2 per degree. OSL monotonically decreased from 33.3 (±2.4) µm at 1° to 18.0 (±1.8) µm at 12°, following a second-order polynomial relationship. PR/RPE ratio decreased from 7.3 (±0.9) µm at 1° to 1.5 (±0.1) µm at 12°. The normative data from this investigation will help lay a foundation for future studies of retinal pathology.

Reducing manual labeling requirements and improved retinal ganglion cell identification in 3D AO-OCT volumes using semi-supervised learning.

Adaptive optics-optical coherence tomography (AO-OCT) allows for the three-dimensional visualization of retinal ganglion cells (RGCs) in the living human eye. Quantitative analyses of RGCs have significant potential for improving the diagnosis and monitoring of diseases such as glaucoma. Recent advances in machine learning (ML) have made possible the automatic identification and analysis of RGCs within the complex three-dimensional retinal volumes obtained with such imaging. However, the current state-of-the-art ML approach relies on fully supervised training, which demands large amounts of training labels. Each volume requires many hours of expert manual annotation. Here, two semi-supervised training schemes are introduced, (i) cross-consistency training and (ii) cross pseudo supervision that utilize unlabeled AO-OCT volumes together with a minimal set of labels, vastly reducing the labeling demands. Moreover, these methods outperformed their fully supervised counterpart and achieved accuracy comparable to that of human experts.

Adaptive Optics Optical Coherence Tomography Analysis of Induced Pluripotent Stem Cell-Derived Retinal Organoid Transplantation in Retinitis Pigmentosa.

This study evaluates the transplantation of induced pluripotent stem cell (iPSC)-derived retinal organoids into patients with advanced retinitis pigmentosa using adaptive optics optical coherence tomography (AO-OCT) to monitor retinal changes over two years post transplantation. Our results confirmed successful engraftment and increased retinal thickness, with AO-OCT providing detailed visualization of cellular structures such as an outer plexiform layer-like line and highly reflective particles within rosette-like formations, indicative of photoreceptor development. Immunohistological analysis in a parallel monkey model confirmed these structures as mature, functional photoreceptor rosettes. The integration of high-resolution AO-OCT with immunohistology provides critical insights into the structural and functional outcomes of transplantation and represents a promising advancement in the treatment of retinal degenerative diseases.

Detection of capillary abnormalities in early diabetic retinopathy using scanning laser ophthalmoscopy and optical coherence tomography combined with adaptive optics

This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices.

Cellular Determinants of Visual Outcomes in Eyes with Epiretinal Membrane: Insights from Adaptive Optics OCT

Objective or PurposeIn this study, we aimed to evaluate cellular alterations in the foveal neuroglia of eyes with idiopathic epiretinal membrane (ERM) and examine their correlation with visual function. We also aimed to identify prognostic markers for visual outcomes post-vitrectomy. DesignA prospective longitudinal study. Subjects, Participants, and/or ControlsThe study comprised 84 subjects, including 50 eyes diagnosed with idiopathic ERM and 34 healthy eyes serving as controls. MethodsThe foveal neuroglial changes in eyes with idiopathic ERM were determined using adaptive optics optical coherence tomography (AO-OCT) by comparing them with healthy eyes. For patients with ERM, the ERM and inner limiting membrane were removed during vitrectomy in all eyes. Main Outcome MeasuresFoveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) and M-CHARTS scores, evaluated preoperatively and at 1, 3, and 6 months postoperatively, and associations between foveal neuroglial changes and these parameters. ResultsAO-OCT revealed discernible differences in the foveal cones of the eyes with ERM and their healthy counterparts. The thickness of the ellipsoid zone (EZ) band was augmented in eyes with ERM. The alignment of the Müller cells was more vertical, and the density of the foveal cone cell nuclei was higher in eyes with ERM than in healthy eyes. Within the AO-OCT parameters, the higher cone nuclei count correlated with worse M-CHARTS scores, both preoperatively and 6 months postoperatively (P = 0.004, 0.010, respectively). Greater EZ thickness was significantly associated with poorer 6-month postoperative BCVA (P = 0.005). ConclusionsAO-OCT can be used to precisely identify cellular alterations in eyes with ERM that are closely related to visual function impairments. These cellular insights enhance our understanding of ERM pathology and offer promising prognostic indicators of visual outcome after vitrectomy.

Revealing speckle obscured living human retinal cells with artificial intelligence assisted adaptive optics optical coherence tomography

BackgroundIn vivo imaging of the human retina using adaptive optics optical coherence tomography (AO-OCT) has transformed medical imaging by enabling visualization of 3D retinal structures at cellular-scale resolution, including the retinal pigment epithelial (RPE) cells, which are essential for maintaining visual function. However, because noise inherent to the imaging process (e.g., speckle) makes it difficult to visualize RPE cells from a single volume acquisition, a large number of 3D volumes are typically averaged to improve contrast, substantially increasing the acquisition duration and reducing the overall imaging throughput.MethodsHere, we introduce parallel discriminator generative adversarial network (P-GAN), an artificial intelligence (AI) method designed to recover speckle-obscured cellular features from a single AO-OCT volume, circumventing the need for acquiring a large number of volumes for averaging. The combination of two parallel discriminators in P-GAN provides additional feedback to the generator to more faithfully recover both local and global cellular structures. Imaging data from 8 eyes of 7 participants were used in this study.ResultsWe show that P-GAN not only improves RPE cell contrast by 3.5-fold, but also improves the end-to-end time required to visualize RPE cells by 99-fold, thereby enabling large-scale imaging of cells in the living human eye. RPE cell spacing measured across a large set of AI recovered images from 3 participants were in agreement with expected normative ranges.ConclusionsThe results demonstrate the potential of AI assisted imaging in overcoming a key limitation of RPE imaging and making it more accessible in a routine clinical setting.

Cellular-Level Visualization of Retinal Pathology in Multiple Sclerosis With Adaptive Optics.

To apply adaptive optics-optical coherence tomography (AO-OCT) to quantify multiple sclerosis (MS)-induced changes in axonal bundles in the macular nerve fiber layer, ganglion cell somas, and macrophage-like cells at the vitreomacular interface. We used AO-OCT imaging in a pilot study of MS participants (n = 10), including those without and with a history of optic neuritis (ON, n = 4), and healthy volunteers (HV, n = 9) to reveal pathologic changes to inner retinal cells and structures affected by MS. We found that nerve fiber layer axonal bundles had 38% lower volume in MS participants (1.5 × 10-3 mm3) compared to HVs (2.4 × 10-3 mm3; P < 0.001). Retinal ganglion cell (RGC) density was 51% lower in MS participants (12.3 cells/mm2 × 1000) compared to HVs (25.0 cells/mm2 × 1000; P < 0.001). Spatial differences across the macula were observed in RGC density. RGC diameter was 15% higher in MS participants (11.7µm) compared to HVs (10.1µm; P < 0.001). A nonsignificant trend of higher density of macrophage-like cells in MS eyes was also observed. For all AO-OCT measures, outcomes were worse for MS participants with a history of ON compared to MS participants without a history of ON. AO-OCT measures were associated with key visual and physical disabilities in the MS cohort. Our findings demonstrate the utility of AO-OCT for highly sensitive and specific detection of neurodegenerative changes in MS. Moreover, the results shed light on the mechanisms that underpin specific neuronal pathology that occurs when MS attacks the retina. The new findings support the further development of AO-based biomarkers for MS.

Deep learning-enabled volumetric cone photoreceptor segmentation in adaptive optics optical coherence tomography images of normal and diseased eyes.

Objective quantification of photoreceptor cell morphology, such as cell diameter and outer segment length, is crucial for early, accurate, and sensitive diagnosis and prognosis of retinal neurodegenerative diseases. Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional (3-D) visualization of photoreceptor cells in the living human eye. The current gold standard for extracting cell morphology from AO-OCT images involves the tedious process of 2-D manual marking. To automate this process and extend to 3-D analysis of the volumetric data, we propose a comprehensive deep learning framework to segment individual cone cells in AO-OCT scans. Our automated method achieved human-level performance in assessing cone photoreceptors of healthy and diseased participants captured with three different AO-OCT systems representing two different types of point scanning OCT: spectral domain and swept source.

Retinal imaging using adaptive optics optical coherence tomography with fast and accurate real-time tracking.

One of the main obstacles in high-resolution 3-D retinal imaging is eye motion, which causes blur and distortion artifacts that require extensive post-processing to be corrected. Here, an adaptive optics optical coherence tomography (AOOCT) system with real-time active eye motion correction is presented. Correction of ocular aberrations and of retinal motion is provided by an adaptive optics scanning laser ophthalmoscope (AOSLO) that is optically and electronically combined with the AOOCT system. We describe the system design and quantify its performance. The AOOCT system features an independent focus adjustment that allows focusing on different retinal layers while maintaining the AOSLO focus on the photoreceptor mosaic for high fidelity active motion correction. The use of a high-quality reference frame for eye tracking increases revisitation accuracy between successive imaging sessions, allowing to collect several volumes from the same area. This system enables spatially targeted retinal imaging as well as volume averaging over multiple imaging sessions with minimal correction of motion in post processing.

Advances in Optical Coherence Tomography Imaging Technology and Techniques for Choroidal and Retinal Disorders.

Optical coherence tomography (OCT) imaging has played a pivotal role in the field of retina. This light-based, non-invasive imaging modality provides high-quality, cross-sectional analysis of the retina and has revolutionized the diagnosis and management of retinal and choroidal diseases. Since its introduction in the early 1990s, OCT technology has continued to advance to provide quicker acquisition times and higher resolution. In this manuscript, we discuss some of the most recent advances in OCT technology and techniques for choroidal and retinal diseases. The emerging innovations discussed include wide-field OCT, adaptive optics OCT, polarization sensitive OCT, full-field OCT, hand-held OCT, intraoperative OCT, at-home OCT, and more. The applications of these rising OCT systems and techniques will allow for a closer monitoring of chorioretinal diseases and treatment response, more robust analysis in basic science research, and further insights into surgical management. In addition, these innovations to optimize visualization of the choroid and retina offer a promising future for advancing our understanding of the pathophysiology of chorioretinal diseases.

Application of Adaptive Optics in Ophthalmology

The eye, the photoreceptive organ used to perceive the external environment, is of great importance to humans. It has been proven that some diseases in humans are accompanied by fundus changes; therefore, the health status of people may be interpreted from retinal images. However, the human eye is not a perfect refractive system for the existence of ocular aberrations. These aberrations not only affect the ability of human visual discrimination and recognition, but restrict the observation of the fine structures of human eye and reduce the possibility of exploring the mechanisms of eye disease. Adaptive optics (AO) is a technique that corrects optical wavefront aberrations. Once integrated into ophthalmoscopes, AO enables retinal imaging at the cellular level. This paper illustrates the principle of AO in correcting wavefront aberrations in human eyes, and then reviews the applications and advances of AO in ophthalmology, including the adaptive optics fundus camera (AO-FC), the adaptive optics scanning laser ophthalmoscope (AO-SLO), the adaptive optics optical coherence tomography (AO-OCT), and their combined multimodal imaging technologies. The future development trend of AO in ophthalmology is also prospected.

Long-term assessment of internal limiting membrane peeling for full-thickness macular hole using en face adaptive optics and conventional optical coherence tomography

ObjectiveTo evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). DesignInterventional case series. ParticipantsPatients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. MethodsEleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. ResultsAO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. ConclusionIRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Müller cell reactive gliosis were identified with AO-OCT.

Cell - Vessel Mismatch in Glaucoma: Correlation of Ganglion Cell Layer Soma and Capillary Densities.

PurposeThe purpose of this study was to characterize the relationship between retinal ganglion cell layer (GCL) soma density and capillary density in glaucomatous eyes.MethodsSix glaucoma subjects with known hemifield defects and 6 age-matched controls were imaged with adaptive optics – optical coherence tomography (AO-OCT) at 6 locations: 3 degrees, 6 degrees, and 12 degrees temporal to the fovea above and below the midline. GCL soma density and capillary density were measured at each location. Coefficients of determination (pseudo R2) and slopes between GCL soma and capillary density were determined from mixed-effects regressions and were compared between glaucoma and control subjects, between more and less affected hemifield in subjects with glaucoma, and between subjects with early and moderate glaucoma, both in a local, bivariate model and then a global, multivariable model controlling for eccentricity and soma size.ResultsThe global correlation between GCL soma and capillary density was stronger in control versus subjects with glaucoma (R2 = 0.59 vs. 0.22), less versus more affected hemifields (R2 = 0.55 vs. 0.01), and subjects with early versus moderate glaucoma subjects (R2 = 0.44 vs. 0.18). When controlling for eccentricity and soma size, we noted an inverse soma-capillary density local relationship in subjects with glaucoma (−388 ± 190 cells/mm2 per 1% change in capillary density, P = 0.046) and more affected hemifields (−602 ± 257 cells/mm2 per 1% change in capillary density, P = 0.03).ConclusionsAn inverted soma-capillary density local relationship in areas affected by glaucoma potentially explains weaker global correlations observed between GCL soma and capillary density, suggesting cell–vessel mismatch is associated with the disease.

Human Foveal Cone and Müller Cells Examined by Adaptive Optics Optical Coherence Tomography.

PurposeThe purpose of this study was to image and investigate the foveal microstructure of human cone and Müller cells using adaptive optics-optical coherence tomography.MethodsSix healthy subjects underwent the prototype adaptive optics-optical coherence tomography imaging, which allowed an axial resolution of 3.4 µm and a transverse resolution of approximately 3 µm. The morphological features of the individual retinal cells observed in the foveola were qualitatively and quantitatively evaluated.ResultsIn the six healthy subjects, the image B-scans showed hyper-reflective dots that were densely packed in the outer nuclear layer. The mean number, diameter, and density of hyper-reflective dots in the foveola were 250.8 ± 59.6, 12.7 ± 59.6 µm, and 6966 ± 1833/mm2, respectively. These qualitative and quantitative findings regarding the hyper-reflective dots were markedly consistent with the morphological features of the foveal cone cell nuclei. Additionally, the images showed the funnel-shaped hyporeflective bodies running vertically and obliquely between the inner and external limiting membranes, illustrating the cell morphology of the foveal Müller cells.ConclusionsUsing adaptive optics, we succeeded in visualizing cross-sectional images of the individual cone and Müller cells of the human retina in vivo.Translational RelevanceAdaptive optics-optical coherence tomography would help to improve our understanding of the pathogenesis of macular diseases.

Interpretation of anatomic correlates of outer retinal bands in optical coherence tomography.

By providing the sectioning capability to differentiate individual retinal layers, optical coherence tomography (OCT) is revolutionizing eye disease diagnosis and treatment evaluation. A better understanding of the hyper- and hypo-reflective bands in retinal OCT is essential for accurate interpretation of clinical outcomes. In this article, we summarize the interpretations of clinical OCT and adaptive optics (AO) OCT (AO-OCT) of the outer retina in the human eye, and briefly review OCT investigation of the outer retina in animal models. Quantitative analysis of outer retinal OCT bands is compared to established parameters of retinal histology. The literature review and comparative analysis support that both inner/outer segment (IS/OS) junction and IS ellipsoid zone nonexclusively contribute to the second band; and OS, OS tips, and retinal pigment epithelium apical processes contribute to the third band in conventional OCT. In contrast, AO-OCT might predominantly detect the IS/OS junction and OS tip signals at the second and third bands due to its improved sectioning capability and possible AO effect on the sensitivities for recording ballistic and diffusive photons from different regions of the outer retina.

Weakly supervised individual ganglion cell segmentation from adaptive optics OCT images for glaucomatous damage assessment.

Cell-level quantitative features of retinal ganglion cells (GCs) are potentially important biomarkers for improved diagnosis and treatment monitoring of neurodegenerative diseases such as glaucoma, Parkinson's disease, and Alzheimer's disease. Yet, due to limited resolution, individual GCs cannot be visualized by commonly used ophthalmic imaging systems, including optical coherence tomography (OCT), and assessment is limited to gross layer thickness analysis. Adaptive optics OCT (AO-OCT) enables in vivo imaging of individual retinal GCs. We present an automated segmentation of GC layer (GCL) somas from AO-OCT volumes based on weakly supervised deep learning (named WeakGCSeg), which effectively utilizes weak annotations in the training process. Experimental results show that WeakGCSeg is on par with or superior to human experts and is superior to other state-of-the-art networks. The automated quantitative features of individual GCLs show an increase in structure-function correlation in glaucoma subjects compared to using thickness measures from OCT images. Our results suggest that by automatic quantification of GC morphology, WeakGCSeg can potentially alleviate a major bottleneck in using AO-OCT for vision research.

Quantification of Retinal Ganglion Cell Morphology in Human Glaucomatous Eyes.

PurposeTo characterize retinal ganglion cell morphological changes in patients with primary open-angle glaucoma associated with hemifield defect (HD) using adaptive optics–optical coherence tomography (AO-OCT).MethodsSix patients with early to moderate primary open-angle glaucoma with an average age of 58 years associated with HD and six age-matched healthy controls with an average age of 61 years were included. All participants underwent in vivo retinal ganglion cell (RGC) imaging at six primary locations across the macula with AO-OCT. Ganglion cell layer (GCL) somas were manually counted, and morphological parameters of GCL soma density, size, and symmetry were calculated. RGC cellular characteristics were correlated with functional visual field measurements.ResultsGCL soma density was 12,799 ± 7747 cells/mm2, 9370 ± 5572 cells/mm2, and 2134 ± 1494 cells/mm2 at 3°, 6°, and 12°, respectively, in glaucoma patients compared with 25,058 ± 4649 cells/mm2, 15,551 ± 2301 cells/mm2, and 3891 ± 1105 cells/mm2 (P < 0.05 for all locations) at the corresponding retinal locations in healthy participants. Mean soma diameter was significantly larger in glaucoma patients (14.20 ± 2.30 µm) compared with the health controls (12.32 ± 1.94 µm, P < 0.05 for all locations); symmetry was 0.36 ± 0.32 and 0.86 ± 0.13 in glaucoma and control cohorts, respectively.ConclusionsGlaucoma patients had lower GCL soma density and symmetry, greater soma size, and increased variation of GCL soma reflectance compared with age-matched control subjects. The morphological changes corresponded with HD, and the cellular level structural loss correlated with visual function loss in glaucoma. AO-based morphological parameters could be potential sensitive biomarkers for glaucoma.

Three-dimensional composition of the photoreceptor cone layers in healthy eyes using adaptive-optics optical coherence tomography (AO-OCT).

To assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT). Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different planes: the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST) and full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements. Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC > .99). In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology.