Non-Proliferative Diabetic Retinopathy Is Characterized by Nonuniform Alterations of Peripapillary Capillary Networks.

Purpose: The purpose of this study was to use three-dimensional confocal microscopy to quantify the spatial patterns of capillary network alterations in nonproliferative diabetic retinopathy (NPDR). Methods: The retinal microvasculature was perfusion-labelled in seven normal human donor eyes and six age-matched donor eyes with NPDR. The peripapillary microcirculation was studied using confocal scanning laser microscopy. Capillary density and diameters of the radial peripapillary capillary plexus (RPCP), superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were quantified and compared. Three-dimensional visualization strategies were also used to compare the communications between capillary beds and precapillary arterioles and postcapillary venules. Results: Mean capillary diameter was significantly increased in the NPDR group (P < 0.001). Intercapillary distance was significantly increased in the DCP (P = 0.004) and RPCP (P = 0.022) of the NPDR group (P = 0.010) but not the SCP (P = 0.155) or ICP (P = 0.103). The NPDR group was associated with an increased frequency of inflow communication between the SCP and ICP/DCP and a decreased frequency of communication between the SCP and RPCP (P = 0.023). There was no difference in the patterns of outflow communications between the two groups (P = 0.771). Conclusions: This study demonstrates that capillary plexuses are nonuniformly perturbed in NPDR. These structural changes may be indicative of perturbations to blood flow patterns between different retinal layers. Our findings may aid the interpretation of previous clinical observations made using optical coherence tomography angiography as well as improve our understanding of the pathogenesis of NPDR.

Three-Dimensional Microscopy Demonstrates Series and Parallel Organization of Human Peripapillary Capillary Plexuses.

Purpose: To define the three-dimensional topologic organization of the human peripapillary capillary plexuses in order to better understand the hemodynamic characteristics of this retinal circulation. Methods: The retinal microvasculature was perfusion labeled in five normal human donor eyes, and optical stacks were collected from regions immediately superior, temporal, inferior, and nasal to the optic disk by using confocal scanning laser microscopy. The spatial location and morphometric characteristics of capillary plexuses were compared. Three-dimensional visualization strategies were used to document the organization of vascular conduits that interconnect capillary beds and to study the communications between capillary beds and precapillary arterioles and postcapillary venules. Results: The peripapillary microcirculation is composed of four capillary plexuses, including the radial peripapillary capillary plexus at the level of the nerve fiber layer, the superficial capillary plexus (SCP) at the level of the ganglion cell layer, the intermediate capillary plexus located at the inner boundary of the inner nuclear layer, and the deep capillary plexus located at the outer boundary of the inner nuclear layer. Capillary diameter and density were significantly different between the four plexuses (both P ≤ 0.011). The SCP is the only capillary bed that receives feeding and draining branches directly from precapillary arterioles and postcapillary venules, respectively. Four different inflow and outflow patterns characterized the communication between the SCP and surrounding capillary beds. Conclusions: The capillary plexuses of the human peripapillary microcirculation are arranged in series and parallel and manifest specializations that likely reflect the unique metabolic demands and biochemical environment of the retinal layers.

Posterior Choroidal Stroma Reduces Accuracy of Automated Segmentation of Outer Choroidal Boundary in Swept Source Optical Coherence Tomography.

Purpose: To determine the influence of choroidal boundary morphology on the accuracy of automated measurements of subfoveal choroidal thickness (SFCT) in swept source optical coherence tomography (SSOCT). Methods: A retrospective image analysis of foveal-centered horizontal line scans from normal and diseased eyes using the Topcon DRI OCT-1 Atlantis SSOCT was conducted. Subfoveal choroid-scleral junction (CSJ) and retina-choroidal junction (RCJ) morphologies were graded by two observers. Automated SFCT (A-SFCT) was compared with manual SFCT (M-SFCT) measurements from Bruch's membrane to the posterior limits of choroidal vessel, hyperreflective stroma, and hyporeflective lamina fusca. Agreement in boundary grading was assessed by Cohen's kappa. A-SFCT and M-SFCT were compared using Bland-Altman analysis and paired t-tests. Results: A total of 200 eyes of 100 patients with a mean (SD) age of 62 (18) years were included. The choroidal vessel, stromal, and lamina fusca boundaries were visible in 100%, 58%, and 38% of the eyes, respectively. Interobserver agreement in RCJ and CSJ grading was high (kappa = 0.974 and 0.851). Mean A-SFCT differed from M-SFCT by only 2 µm at posterior choroidal vessel boundary (P = 0.801). A-SFCT overestimated SFCT at the posterior vessel wall boundary by 17 µm (P = 0.026) and 23 µm (P = 0.001) in the presence of a visible posterior choroidal stroma and lamina fusca, respectively. Conclusions: Automated outer choroidal boundary segmentation tends to identify the posterior limit of the choroidal vessel. Agreement between A-SFCT and M-SFCT is reduced by the presence of posterior stromal layer and lamina fusca. A-SFCT should be interpreted with RCJ and CSJ boundary grading.

Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy.

PURPOSE: Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate. METHODS: ERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy. RESULTS: Serial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient's serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots. CONCLUSIONS: A spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.

Past, Present, and Future Concepts of the Choroidal Scleral Interface Morphology on Optical Coherence Tomography.

The choroid is the most vascular tissue in the eye and it has been implicated in the pathophysiology of a variety of ocular diseases. A new era of research in the choroid began with the improved ability to visualize this layer and its inner and outer boundaries using spectral domain optical coherence tomography (OCT) with enhanced depth imaging and swept source OCT. The accuracy and precision of qualitative and quan-titative assessments of the choroidal layer support the potential use of OCT-derived choroidal parameters for diagnosis, monitoring of disease progression, planning surgical access, and evaluating treatment response. Although there is increasing interest in measuring choroidal thickness, there is currently no consensus nomenclature to classify choroidal layers and boundaries. Furthermore, the definition and description of the choroidal scleral interface is inconsistent in the literature, contributing to interstudy variation in choroidal thickness measurements. The purpose of this review is to provide an overview of the literature on the definition of choroidal layers and choroidal scleral boundary, review the discrepan-cies, and harmonize the terminology so that a consensus nomenclature can be proposed.