Optic Nerve Head Region Research Articles

Glaucoma in Pathological Myopia, Diagnosis and Treatment Approaches

The rising global prevalence of myopia is contributing to an increase in pathological myopia (PM). Myopia has been extensively documented as a risk factor for primary open-angle glaucoma. However, glaucomatous changes in eyes with PM typically occur at normal intraocular pressures. Moreover, the unique anatomical alterations observed in PM result in distinctive differences in the clinical appearance of the optic nerve head and peripapillary region. Consequently, the evaluation of optic nerve cupping is more challenging in these cases than in those of normal eyes. Therefore, the diagnosis and treatment of glaucoma in this patient group is challenging. Furthermore, these patients may present with established visual field defects that can mimic glaucoma. On the other hand, optical coherence tomography is less useful for the detection and monitoring of disease due to the lack of normative data for these anatomically unique eyes. The most crucial factor in detecting early glaucomatous changes is the monitoring of the progression of retinal nerve fiber layer thinning over time. Consequently, the most effective method of monitoring glaucoma patients with PM is through longitudinal follow-up. Finally, the medical and surgical management of glaucoma in patients with pathologic myopic glaucoma presents its own unique challenges.

Longitudinal Assessment of Retinal Microvasculature in Preclinical Alzheimer's Disease.

To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time. Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2years. Positron emission tomography (PET) was used to determine the amyloid beta (Aβ) status of participants. The VD and FAZ of 148 participants (54% female) were analyzed at baseline and follow-up (mean time between measurements, 2.24 ± 0.35years). The mean age of the participants was 68.3 ± 6.0years at baseline and 70.3 ± 5.9years at follow-up. Participants were divided into three groups: control group, participants who had negative Aβ status at both measurements (Aβ-, n = 116); converter group, participants who transitioned from negative to positive between baseline and follow-up (Aβ-+, n = 18); and participants who were consistently positive at both visits (Aβ++, n = 14). The VD of both Aβ+ groups demonstrated non-significant increases over time in both macula and optic nerve head (ONH) regions. The Aβ- group was found to be significantly higher in both ONH and macular regions. The VD of the Aβ++ group was significantly higher in the macula inner and outer rings compared to the Aβ-+ and Aβ- groups. No significant change was found in FAZ values over time. Alterations in VD seem to manifest already in pAD, exhibiting distinct variations between the ONH and macula. Further longitudinal studies with a longer follow-up design and known amyloid pathology should be undertaken to validate these observations.

OCTA-based research on changes of retinal microcirculation in digestive tract malignancy

PurposeThis cross-sectional study measured retinal vessel density (VD) in patients with digestive tract malignancy by optical coherence tomography angiography (OCTA), and compared them with healthy controls to explore the retinal microcirculation changes in patients with digestive tract malignancy. Methods106 eligible participants were divided into three groups: gastric cancer (GC) group (36 individuals), colorectal cancer (CRC) group (34 individuals), and healthy control group (36 individuals). Angio 6 × 6 512 × 512 R4 and ONH Angio 6 × 6 512 × 512 R4 modes were performed to collect retinal vessel density data centered on fovea and papillary, respectively. The retina was automatically segmented into different layers (superficial vascular plexus (SVP), the inner retinal layer, radial peripapillary capillary plexus (RPCP), deep vascular plexus (DVP)) and areas to analyze. ResultsAt the optic nerve head (ONH) region, the VD of the inner retinal layer increased in both GC and CRC groups in all quadrants and areas. In the papillary area, VD in the inner retinal layer, SVP, and RPCP increased in the GC and CRC groups. In the parapapillary area, VD in the inner retinal layer increased in the GC and the CRC groups. Significant increase in the global VD were found in the GC group of the RPCP and SVP. Regarding the macular region, no statistical differences were observed in each layer. ConclusionsThe study suggested that retinal vessel density changed in patients with digestive tract malignancy, especially in the inner retinal layer of the ONH region, revealing the potential relevance of the relation between gastrointestinal cancer and retinal microcirculation.

Retinal microglial cells increase expression and release of IL-1β when exposed to ATP.

Cytokine IL-1β is an early component of inflammatory cascades, with both priming and activation steps required before IL-1β release. Here, the P2X7 receptor (P2X7R) for ATP was shown to both prime and release IL-1β from retinal microglial cells. Isolated retinal microglial cells increased expression of Il1b when stimulated with endogenous receptor agonist extracellular ATP; ATP also rapidly downregulated expression of microglial markers Tmem119 and Cd206. Changes to all three genes were reduced by specific P2X7R antagonist A839977, implicating the P2X7R. Microglial cells expressed the P2X7R on ramifications and responded to receptor agonist BzATP with robust and rapid rises in intracellular Ca 2+ . BzATP increased expression of IL-1β protein colocalizing with CX3CR1-GFP in retinal wholemounts consistent with microglial cells. ATP also triggered release of IL-1β from isolated retinal microglia into the bath; release was inhibited by A839977 and induced by BzATP, supporting a role for the P2X7R in release as well as priming. The IL-1β release triggered by ATP was substantially greater from microglial cells compared to astrocytes from the optic nerve head region. Il1b expression was increased by a transient rise in intraocular pressure and Il1b levels remained elevated 10 days after a single IOP elevation. In summary, this study suggests the P2X7 receptor can both prime IL-1β levels in microglial cells and trigger its release. The P2Y12R was previously identified as a chemoattractant for retinal microglia, suggesting the recruitment of the cells towards the source of released extracellular ATP could position microglia for P2X7R receptor, enabling both priming and release of IL-1β.

Assessing the efficacy of 2D and 3D CNN algorithms in OCT-based glaucoma detection

Glaucoma is a progressive neurodegenerative disease characterized by the gradual degeneration of retinal ganglion cells, leading to irreversible blindness worldwide. Therefore, timely and accurate diagnosis of glaucoma is crucial, enabling early intervention and facilitating effective disease management to mitigate further vision deterioration. The advent of optical coherence tomography (OCT) has marked a transformative era in ophthalmology, offering detailed visualization of the macula and optic nerve head (ONH) regions. In recent years, both 2D and 3D convolutional neural network (CNN) algorithms have been applied to OCT image analysis. While 2D CNNs rely on post-prediction aggregation of all B-scans within OCT volumes, 3D CNNs allow for direct glaucoma prediction from the OCT data. However, in the absence of extensively pre-trained 3D models, the comparative efficacy of 2D and 3D-CNN algorithms in detecting glaucoma from volumetric OCT images remains unclear. Therefore, this study explores the efficacy of glaucoma detection through volumetric OCT images using select state-of-the-art (SOTA) 2D-CNN models, 3D adaptations of these 2D-CNN models with specific weight transfer techniques, and a custom 5-layer 3D-CNN-Encoder algorithm. The performance across two distinct datasets is evaluated, each focusing on the macula and the ONH, to provide a comprehensive understanding of the models’ capabilities in identifying glaucoma. Our findings demonstrate that the 2D-CNN algorithm consistently provided robust results compared to their 3D counterparts tested in this study for glaucoma detection, achieving AUC values of 0.960 and 0.943 for the macular and ONH OCT test images, respectively. Given the scarcity of pre-trained 3D models trained on extensive datasets, this comparative analysis underscores the overall utility of 2D and 3D-CNN algorithms in advancing glaucoma diagnostic systems in ophthalmology and highlights the potential of 2D algorithms for volumetric OCT image-based glaucoma detection.

Effect of anti-VEGF on retinal blood flow in diabetic mice using laser speckle flowgraphy.

To assess intra- (repeatability) and inter-observer (reproducibility) variability of laser speckle flowgraphy (LSFG) for retinal blood flow (RBF) measurement in 20 eyes of wild type (C57BL/6J) mice and effect of intravitreal Aflibercept on RBF in optic nerve head (ONH) region of 10 eyes of Ins2 (Akita) diabetic mice. 'Mean blur rate (MBR)' was measured for all quadrants of tissue area (MT), vessel (MV) and total area (MA) of ONH region. Changes in MT were analysed at each timepoint. Repeatability was evaluated by measuring MBR variability without changing mouse head position, and reproducibility after resetting mouse head position by another operator. Coefficient of repeatability (CR) through Bland-Altman plot method coefficient of variation (COV) and Intraclass correlation coefficient (ICC) was calculated. Intravitreal Aflibercept (1 μg) was administered to Akita eyes and intraocular pressure (IOP) was measured using a tonometer at baseline, day 7, 14, 21 and 28 post-injection. Hurvich and Tsai's criterion was used. Coefficient of repeatability values of repeatability and reproducibility for all quadrants were within limits of agreement. Reliability was excellent (ICC 0.98-0.99) and reproducibility was moderate to excellent (ICC 0.64-0.96). There was a non-significant IOP increase in all Akita eyes at Day 28 (p > 0.05), and significant increase in MT in all quadrants at Day 21 and superior, inferior and temporal quadrants at Day 28 (p < 0.05). Laser speckle flowgraphy demonstrates excellent repeatability and moderate to excellent reproducibility in measuring RBF. Intravitreal Aflibercept injection results in a significant increase in MT up to 28 days post-injection without significant increase in IOP.

Deep-Learning-Based Group Pointwise Spatial Mapping of Structure to Function in Glaucoma

PurposeTo establish generalizable point-wise spatial relationship between structure and function through occlusion analysis of a deep-learning (DL) model for predicting the visual field (VF) sensitivities from three-dimensional (3D) optical coherence tomography (OCT) scan. DesignRetrospective cross-sectional study. Participants2151 eyes from 1129 patients. MethodsA DL model was trained to predict 52 VF sensitivities of 24-2 standard automated perimetry from 3D spectral-domain OCT images of the optic nerve head (ONH) with 12915 OCT-VF pairs. Using occlusion analysis, the contribution of each individual cube covering a 240 x 240 x 31.25 μm region of the ONH to the model's prediction was systematically evaluated for each OCT-VF pair in a separate test set that consisted of 996 OCT-VF pairs. After simple translation (shifting in x and y-axes to match the ONH center), group t-statistic maps were derived to visualize statistically significant ONH regions for each VF test point within a group. This analysis allowed for understanding the importance of each super voxel (240 x 240 x 31.25 μm covering the entire 4.32 x 4.32 x 1.125 mm ONH cube) in predicting VF test points for specific patient groups. Main Outcome MeasuresThe region at the ONH corresponding to each VF test point and the effect of the former on the latter. ResultsThe test set was divided to two groups, the healthy-to-early-glaucoma group (792 OCT-VF pairs, VF mean deviation (MD): -1.32 ± 1.90 dB) and the moderate-to-advanced-glaucoma group (204 OCT-VF pairs, VF MD: -17.93 ± 7.68 dB). Two-dimensional group t-statistic maps (x, y projection) were generated for both groups, assigning related ONH regions to visual field test points. The identified influential structural locations for VF sensitivity prediction at each test point aligned well with existing knowledge and understanding of structure-function spatial relationships. ConclusionsThis study successfully visualized the global trend of point-by-point spatial relationships between OCT-based structure and VF-based function without the need for prior knowledge or segmentation of OCTs. The revealed spatial correlations were consistent with previously published mappings. This presents possibilities of learning from trained machine learning models without applying any prior knowledge, potentially robust and free from bias.

EPIRETINAL MACROPHAGE-LIKE CELLS ON OPTICAL COHERENCE TOMOGRAPHY: Potential Inflammatory Imaging Biomarker of Severity in Diabetic Retinopathy.

To investigate the clinical value of epiretinal macrophage-like cells (eMLCs) in different stages of diabetic retinopathy (DR), including diabetic macular edema (DME). One hundred and seventy-six eyes of 176 patients, including 31 diabetes eyes without retinopathy, 24 with mild nonproliferative DR (NPDR), 37 with moderate NPDR, 32 with severe NPDR, and 52 with proliferative DR, were compared with 30 healthy controls. The optic nerve head and macular region were examined using en face optical coherence tomography and optical coherence tomography angiography. A previously described technique was employed to measure the eMLCs on the inner limiting membrane. The optic nerve head and macular eMLC densities increased with worsening DR stage and were higher in moderate, severe NPDR, and proliferative DR, especially in eyes with DME (all adjusted P < 0.01). The optic nerve head and macular eMLC densities in the DME groups were higher than those in their corresponding non-DME groups at the same DR stage (all P < 0.05). The average macular thickness was correlated with macular eMLC density (standardized β = 0.661, P < 0.001) in patients with diabetes. The proportion of eyes with larger and plumper eMLCs increased with worsening DR and was higher in moderate, severe NPDR, proliferative DR, and eyes with DME ( P = 0.018, P < 0.001, P < 0.001, and P < 0.001, respectively). Increased density along with morphological changes of eMLCs is observed beginning with moderate NPDR and correlates with the progression of DR, including DME.

Glaucoma detection model by exploiting multi-region and multi-scan-pattern OCT images with dynamical region score.

Currently, deep learning-based methods have achieved success in glaucoma detection. However, most models focus on OCT images captured by a single scan pattern within a given region, holding the high risk of the omission of valuable features in the remaining regions or scan patterns. Therefore, we proposed a multi-region and multi-scan-pattern fusion model to address this issue. Our proposed model exploits comprehensive OCT images from three fundus anatomical regions (macular, middle, and optic nerve head regions) being captured by four scan patterns (radial, volume, single-line, and circular scan patterns). Moreover, to enhance the efficacy of integrating features across various scan patterns within a region and multiple regional features, we employed an attention multi-scan fusion module and an attention multi-region fusion module that auto-assign contribution to distinct scan-pattern features and region features adapting to characters of different samples, respectively. To alleviate the absence of available datasets, we have collected a specific dataset (MRMSG-OCT) comprising OCT images captured by four scan patterns from three regions. The experimental results and visualized feature maps both demonstrate that our proposed model achieves superior performance against the single scan-pattern models and single region-based models. Moreover, compared with the average fusion strategy, our proposed fusion modules yield superior performance, particularly reversing the performance degradation observed in some models relying on fixed weights, validating the efficacy of the proposed dynamic region scores adapted to different samples. Moreover, the derived region contribution scores enhance the interpretability of the model and offer an overview of the model's decision-making process, assisting ophthalmologists in prioritizing regions with heightened scores and increasing efficiency in clinical practice.

Fibrous finite element modeling of the optic nerve head region

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other fiber-specific effects in a fibrous structure. We present a fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics. Statement of SignificanceThe microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.

End-to-end algorithm for the automatic detection of the neural canal opening in OCT images based on a multi-task deep learning model

Neural canal opening (NCO) are important landmarks of the retinal pigment epithelium layer in the optic nerve head region. Conventional NCO detection employs multimodal measurements and feature engineering, which is usually suitable for one specific task. In this study, we proposed an end-to-end deep learning scenario for NCO detection based on single-modality features (OCT). The proposed method contains two visual tasks: one is to verify the existence of NCO points as a binary classification, and the other is to locate the NCO points as a coordinate regression. The feature representation of OCT images, extracted by a MobileNetV2 architecture, was evaluated under new testing data, with an average Euclidean distance error of 5.68 ± 4.45 pixels and an average intersection over union of 0.90 ± 0.03. This suggests that data-driven scenarios have the opportunity to provide a universal and efficient solution to various visual tasks from OCT images.

Computed tomographic finding of bilateral optic nerve head drusen in a dog – a case report

Optic nerve head drusen are acellular calcified deposits in the optic nerve head reported in humans. A six year old, male, Rottweiler dog with a history of respiratory distress and epistaxis for the previous two months was anaesthetised and a computed tomographic scan of the head was performed. The axial view of the computed tomography scan with a slice thickness of 1mm was viewed in a soft tissue window (380x40 HU). There was an incidental discovery of a characteristic discrete round hyper dense area in the optic nerve head region in both eyes during the routine computed tomographic scan. The Hounsfield Unit of the optic nerve head drusen in the right eye measured 91 HU, of 2 mm2 and in the left eye 131 HU of 1 mm2 confirming the diagnosis of optic nerve head drusen. To the authors’ knowledge, this is the first report of optic nerve head drusen in a dog.

Optical Coherence Tomography and Optical Coherence Tomography Angiography: Essential Tools for Detecting Glaucoma and Disease Progression.

Early diagnosis and detection of disease progression are critical to successful therapeutic intervention in glaucoma, the leading cause of irreversible blindness worldwide. Optical coherence tomography (OCT) is a non-invasive imaging technique that allows objective quantification in vivo of key glaucomatous structural changes in the retina and the optic nerve head (ONH). Advances in OCT technology have increased the scan speed and enhanced image quality, contributing to early glaucoma diagnosis and monitoring, as well as the visualization of critically important structures deep within the ONH, such as the lamina cribrosa. OCT angiography (OCTA) is a dye-free technique for noninvasively assessing ocular microvasculature, including capillaries within each plexus serving the macula, peripapillary retina and ONH regions, as well as the deeper vessels of the choroid. This layer-specific assessment of the microvasculature has provided evidence that retinal and choroidal vascular impairments can occur during early stages of glaucoma, suggesting that OCTA-derived measurements could be used as biomarkers for enhancing detection of glaucoma and its progression, as well as to reveal novel insights about pathophysiology. Moreover, these innovations have demonstrated that damage to the macula, a critical region for the vision-related quality of life, can be observed in the early stages of glaucomatous eyes, leading to a paradigm shift in glaucoma monitoring. Other advances in software and hardware, such as artificial intelligence-based algorithms, adaptive optics, and visible-light OCT, may further benefit clinical management of glaucoma in the future. This article reviews the utility of OCT and OCTA for glaucoma diagnosis and disease progression detection, emphasizes the importance of detecting macula damage in glaucoma, and highlights the future perspective of OCT and OCTA. We conclude that the OCT and OCTA are essential glaucoma detection and monitoring tools, leading to clinical and economic benefits for patients and society.

Donut: Augmentation Technique for Enhancing The Efficacy of Glaucoma Suspect Screening.

Glaucoma is the second most common cause of blindness. A glaucoma suspect has risk factors that increase the possibility of developing glaucoma. Evaluating a patient with suspected glaucoma is challenging. The "donut method" was developed in this study as an augmentation technique for obtaining high-quality fundus images for training ConvNeXt-Small model. Fundus images from GlauCUTU-DATA, labelled by randomizing at least 3 well-trained ophthalmologists (4 well-trained ophthalmologists in case of no majority agreement) with a unanimous agreement (3/3) and majority agreement (2/3), were used in the experiment. The experimental results from the proposed method showed the training model with the "donut method" increased the sensitivity of glaucoma suspects from 52.94% to 70.59% for the 3/3 data and increased the sensitivity of glaucoma suspects from 37.78% to 42.22% for the 2/3 data. This method enhanced the efficacy of classifying glaucoma suspects in both equalizing sensitivity and specificity sufficiently. Furthermore, three well-trained ophthalmologists agreed that the GradCAM++ heatmaps obtained from the training model using the proposed method highlighted the clinical criteria.Clinical relevance- The donut method for augmentation fundus images focuses on the optic nerve head region for enhancing efficacy of glaucoma suspect screening, and uses Grad-CAM++ to highlight the clinical criteria.

Evaluation of optic nerve head vessels density changes after phacoemulsification cataract surgery using optical coherence tomography angiography.

To evaluate optic nerve head (ONH) vessel density (VD) changes after cataract surgery using optical coherence tomography angiography (OCTA). This was a prospective observational study. Thirty-four eyes with mild/moderate cataracts were included. ONH scans were obtained before and 3mo after cataract surgery using OCTA. Radial peripapillary capillary (RPC) density, all VD, large VD and retinal nerve fiber layer thickness (RNFLT) in total disc, inside disc, and different peripapillary sectors were assessed and analyzed. Image quality score (QS), fundus photography grading and best-corrected visual acuity (BCVA) were also collected, and correlation analyses were performed between VD change and these parameters. Compared with baseline, both RPC and all VD increased in inside disc area 3mo postoperatively (from 47.5%±5.3% to 50.2%±3.7%, and from 57.87%±4.30% to 60.47%±3.10%, all P<0.001), but no differences were observed in peripapillary area. However, large VD increased from 5.63%±0.77% to 6.47%±0.72% in peripapillary ONH region (P<0.001). RPC decreased in inferior and superior peripapillary ONH parts (P=0.019, <0.001 respectively). There were obvious negative correlations between RPC change and large VD change in inside disc, superior-hemi, and inferior-hemi (r=-0.419, -0.370, and -0.439, P=0.017, 0.044, and 0.015, respectively). No correlations were found between VD change and other parameters including QS change, fundus photography grading, postoperative BCVA, and postoperative peripapillary RNFLT. RPC density and all VD in the inside disc ONH region increase 3mo after surgery in patients with mild to moderate cataract. No obvious VD changes are found in peripapillary area postoperatively.

Dense optic nerve head deformation estimated using CNN as a structural biomarker of glaucoma progression.

To present a new structural biomarker for detecting glaucoma progression based on structural transformation of the optic nerve head (ONH) region over time. Dense ONH deformation was estimated using deep learning methods namely DDCNet-Multires, FlowNet2, and FlowNetCorrelation, and legacy computational methods namely the topographic change analysis (TCA) and proper orthogonal decomposition (POD) methods. A candidate biomarker was estimated as the average magnitude of deformation of the ONH and evaluated using longitudinal confocal scans of 12 laser treated and 12 contralateral normal eyes of 12 primates from the LSU Experimental Glaucoma Study (LEGS); and 36 progressing eyes and 21 longitudinal normal eyes from the UCSD Diagnostic Innovations in Glaucoma Study (DIGS). Area under the ROC curve (AUC) was used to assess the diagnostic accuracy of the biomarker. AUROC (95% CI) for LEGS were: 0.83 (0.79, 0.88) for DDCNet-Multires; 0.83 (0.78, 0.88) for FlowNet2; 0.83 (0.78, 0.88) for FlowNet-Correlation; 0.94 (0.91, 0.97) for POD; and 0.86 (0.82, 0.91) for TCA methods. For DIGS: 0.89 (0.80, 0.97) for DDCNet-Multires; 0.82 (0.71, 0.93) for FlowNet2; 0.93 (0.86, 0.99) for FlowNet-Correlation; 0.86 (0.76, 0.96) for POD; and 0.86 (0.77, 0.95) for TCA methods. Lower diagnostic accuracy of the learning-based methods for LEG study eyes were due to image alignment errors in confocal sequences. Deep learning methods trained to estimate generic deformation were able to estimate ONH deformation from image sequences and provided a higher diagnostic accuracy. Our validation of the biomarker using ONH sequences from controlled experimental conditions confirms the diagnostic accuracy of the biomarkers observed in the clinical population. Performance can be further improved by fine-tuning these networks using ONH sequences.

The endothelin receptor antagonist macitentan ameliorates endothelin-mediated vasoconstriction and promotes the survival of retinal ganglion cells in rats.

Glaucoma is a chronic and progressive eye disease, commonly associated with elevated intraocular pressure (IOP) and characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells (RGCs). The pathological changes in glaucoma are triggered by multiple mechanisms and both mechanical effects and vascular factors are thought to contribute to the etiology of glaucoma. Various studies have shown that endothelin-1 (ET-1), a vasoactive peptide, acting through its G protein coupled receptors, ETA and ETB, plays a pathophysiologic role in glaucoma. However, the mechanisms by which ET-1 contribute to neurodegeneration remain to be completely understood. Our laboratory and others demonstrated that macitentan (MAC), a pan endothelin receptor antagonist, has neuroprotective effects in rodent models of IOP elevation. The current study aimed to determine if oral administration of a dual endothelin antagonist, macitentan, could promote neuroprotection in an acute model of intravitreal administration of ET-1. We demonstrate that vasoconstriction following the intravitreal administration of ET-1 was attenuated by dietary administration of the ETA/ETB dual receptor antagonist, macitentan (5 mg/kg body weight) in retired breeder Brown Norway rats. ET-1 intravitreal injection produced a 40% loss of RGCs, which was significantly lower in macitentan-treated rats. We also evaluated the expression levels of glial fibrillary acidic protein (GFAP) at 24 h and 7 days post intravitreal administration of ET-1 in Brown Norway rats as well as following ET-1 treatment in cultured human optic nerve head astrocytes. We observed that at the 24 h time point the expression levels of GFAP was upregulated (indicative of glial activation) following intravitreal ET-1 administration in both retina and optic nerve head regions. However, following macitentan administration for 7 days after intravitreal ET-1 administration, we observed an upregulation of GFAP expression, compared to untreated rats injected intravitreally with ET-1 alone. Macitentan treatment in ET-1 administered rats showed protection of RGC somas but was not able to preserve axonal integrity and functionality. The endothelin receptor antagonist, macitentan, has neuroprotective effects in the retinas of Brown Norway rats acting through different mechanisms, including enhancement of RGC survival and reduction of ET-1 mediated vasoconstriction.

Light conditions influence optic nerve OCT angiography parameter in healthy subjects with neutral pupils

Optical coherence tomography angiography measurements are influenced by a range of environmental factors as blood pressure and physical fitness. The present study aimed to evaluate the effects of light and dark exposure in eyes with neutral and mydriatic pupils on vessel density in the macular and optic nerve head regions, as measured using optical coherence tomography angiography (OCTA). 55 eyes of 55 healthy volunteers (28 patients with neutral pupils; 27.18 ± 4.33 years) were examined using a high-speed and high-resolution spectral-domain OCT XR Avanti system with a split-spectrum amplitude de-correlation angiography algorithm. OCTA imaging was performed after dark adaptation and after exposure to light. The vessel density data of the superficial and deep retinal macular and optic nerve head region OCT-angiogram were analyzed for these two light conditions. Through Bonferroni correction for multiple testing, the p- value was adapted from 0.05 to 0.017. In eyes with neutral pupils, a significant increase was found in the capillary region of the optic nerve head region (p = 0.002), comparing dark- and light-adaptation. In the macular region of eyes with neutral (p = 0.718) and mydriatic pupils (p = 0.043), no significant differences were observed, as were any in the optic nerve head region of the mydriatic eyes (p = 0.797). This observation suggests that light conditions could be a possible factor influencing OCTA measurements. After dark exposure, vessel density data were significantly different between eyes with neutral and mydriatic pupils (nerve head region: p < 0.0001, superficial macula: p < 0.0001, deep macula: p = 0.0025). These data warn for the effect of mydriatic drops on vessel density measurements.

Abstract Number ‐ 255: Laser Speckle Flowgraphy As A Surrogate Marker For Symptomatic Carotid Stenosis

Introduction The severity of internal carotid artery (ICA) atherosclerosis is assessed through measurements of degree of stenosis. This approach does not factor in mechanisms compensating for reduced distal perfusion, such as collateral circulation. An alternative approach is evaluating severity of carotid stenosis based on downstream changes in ocular perfusion. Laser speckle flowgraphy (LSFG) is a non‐invasive tool that quantifies intraocular blood flow. This pilot study investigated whether LSFG metrics could be surrogates for degree of stenosis. Additionally, we quantified changes in flow through the stenosed vessel before and after stenting usingsyngoiFlow (iFlow). Methods Fourteen patients had stents placed to treat symptomatic carotid stenosis. LSFG metrics were obtained before and after stenting. Mean blur rate (MBR), an index of ocular blood velocity, and associated waveform parameters were extracted from the optic nerve head (ONH) region of the eye. iFlow quantified time to peak (TTP), an index of peak cerebral contrast flow, by transforming digital subtraction angiography (DSA) images into perfusion heat maps.TTPswere extracted for seven regions of interest (ROIs) by two raters. Results Two LSFG waveform parameters were significantly negatively correlated with degree of stenosis. These parameters, flow acceleration index (FAI) and rising rate (RR), also increased significantly after stenting. Intraclass correlation coefficients calculated for TTPs showed substantial agreement across all ROIs. Significant decreases in TTP after stenting were observed in ROIs placed in the high cervical ICA, cavernous segment of the ICA, and brain parenchyma. Conclusions LSFG provides biometrics that can accurately measure the impact of ICA stenosis by quantifying distal perfusion. Indices of ocular blood flow acceleration may serve as surrogate metrics for degree of stenosis. iFlow is a sensitive tool to quantify changes in flow after stenting. Non‐invasive flow‐dependent methods are promising in the assessment of patients with ICA stenosis.

Combining retinal neuronal and microvascular measurements improves discriminative power for multiple sclerosis patients without previous optic neuritis

AbstractPurpose: Quantitative thinning of optic nerves and changes in retinal microvasculature have been detected in multiple sclerosis patients without optic neuritis (MSNON). However, data on how both retinal neuronal and microvascular parameters jointly influence the diagnostic performance is lacking. To investigate the diagnostic performance of neuronal and microvascular changes to detect the presence of MSNON from normal controls.Methods: This is a cross‐sectional study of 51 MS participants (n = 76 eyes) and 71 age‐ and sex‐matched healthy controls (n = 117 eyes). Retinal macular ganglion cell complex (GCC) and retinal nerve fibre layer (RNFL) thicknesses and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the optical coherence tomography (Cirrus AngioPlex model HD‐OCT 5000). We also compensated RNFL thickness for ocular anatomical factors. Thickness and vascular measurements and their corresponding areas under the receiver operating characteristic curves (AUCs) were compared between groups.Results: All retinal structural and vascular parameters were significantly altered in MS (p ≤ 0.012). The best neuronal parameter for detecting MS was compensated RNFL from the optic nerve head region (AUC = 0.85), followed by GCC from the macular region (AUC = 0.79) while the best microvasculature parameter was the SCP (AUC = 0.66). Combining retinal neuronal and microvascular parameters improved its diagnostic performance for MS detection (AUC = 0.90; P &lt; 0.001). The joint model including both neuronal and microvasculature significantly improved the discrimination between MS and normal compared with each parameter separately (p = 0.027).Conclusions: Combining retinal neuronal and microvasculature parameters improved the discrimination of MSNON. Further studies may be warranted to evaluate the clinical utility of retinal parameters in risk prediction for disease progression.