To compare the quality of four OCT-angiography(OCT-A) modules. The retina of nineteen healthy volunteers were scanned with four OCT-devices (Topcon DRI-OCT Triton Swept-source OCT, Optovue RTVue-XR, a prototype Spectralis OCT2, Heidelberg-Engineering and Zeiss Cirrus 5000-HD-OCT). The device-software generated en-face OCT-A images of the superficial (SCP) and deep capillary plexuses (DCP) were evaluated and scored by 3 independent retinal imaging experts. The SCP vessel density was assessed using Angiotool-software. After the inter-grader reliability assessment, a consensus grading was performed and the modules were ranked based on their scoring. There was no significant difference in the vessel density among the modules (Zeiss 48.7±4%, Optovue 47.9±3%, Topcon 48.3±2%, Heidelberg 46.5±4%, p = 0.2). The numbers of discernible vessel-bifurcations differed significantly on each module (Zeiss 2±0.9 bifurcations, Optovue 2.5±1.2, Topcon 1.3±0.7 and Heidelberg 0.5±0.6, p≤0.001). The ranking of each module differed depending on the evaluated parameter. In the overall ranking, the Zeiss module was superior and in 90% better than the median (Bonferroni corrected p-value = 0.04). Optovue was better than the median in 60%, Topcon in 40% and Heidelberg module in 10%, however these differences were not statistically significant. Each of the four evaluated OCT-A modules had particular strengths, which differentiated it from their competitors.

Purpose. Glia are the main cellular CNS elements initiating defense mechanisms against destructive influences and promoting regenerative processes. The aim of the current work was to characterize the microglial response within the visual pathway in a rat model of experimental glaucoma and to correlate the microglial response with the severity of axonal degeneration. Methods. Experimental glaucoma was induced in each right eye of adult Sprague-Dawley rats by translimbal laser photocoagulation of the trabecular meshwork. Rats were subsequently killed at various times from 3 days to 6 weeks. Tissue sections were obtained from globes, optic nerves, chiasmata, and optic tracts for immunohistochemistry and toluidine blue staining. Results. This model of experimental glaucoma led to a marked activation of microglia in the retina, optic nerve, and tract. Indeed, microglial activity remained elevated, even after intraocular pressure returned to basal levels. It is postulated that this process accompanies ongoing axonal degeneration. The degree of activation in the optic nerve correlated with axonal damage. Activation was characterized by increased density and morphologic changes. Both major histocompatibility complex (MHC) class I and MHC class II surface proteins were persistently upregulated in optic nerves and localized to microglial cells; however, this did not correlate with any significant T-cell infiltration. Interestingly, MHC class II expression was not detected in the retina. Conclusions. The present data may have implications for the study of the pathology associated with the visual pathway in diseases such as glaucoma.

The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas.

Research from JAMA Ophthalmology — Effect of Upper Eyelid Surgery on Corneal Topography

Microglia-associated inflammation is closely related to the pathogenesis of various retinal diseases such as uveitis and diabetic retinopathy, which are associated with increased vascular permeability. In this study, we investigated the effect of systemic lipopolysaccharide (LPS) exposure to activation and proliferation of retinal microglia /macrophages. Balb/c and Cx3cr1gfp/+ mice were challenged with LPS (1 mg/kg) daily for four consecutive days. For microglia depletion, mice were treated with colony-stimulating factor 1 receptor (CSF-1R) inhibitor PLX5622 1 week before the first LPS challenge and until the end of the experiment. In vivo imaging of the retina was performed on days 4 and 7 after the first LPS challenge, using optical coherence tomography and fluorescein angiography. Flow cytometry analysis, retinal whole mount, and retinal sections were used to investigate microglia and macrophage infiltration and proliferation after LPS challenge. Cytokines were analyzed in the blood as well as in the retina. Data analysis was performed using unpaired t tests, repeated measures one-way ANOVA, or ordinary one-way ANOVA followed by Tukey’s post hoc analysis. Kruskal-Wallis test followed by Dunn’s multiple comparison tests was used for the analysis of non-normally distributed data. Repeated LPS challenge led to activation and proliferation of retinal microglia, infiltration of monocyte-derived macrophages into the retina, and breakdown of the blood-retina barrier (BRB) accompanied by accumulation of sub-retinal fluid. Using in vivo imaging, we show that the breakdown of the BRB is highly reproducible but transitory. Acute but not chronic systemic exposure to LPS triggered a robust release of inflammatory mediators in the retina with minimal effects in the blood plasma. Inhibition of the CSF-1R by PLX5622 resulted in depletion of retinal microglia, suppression of cytokine production in the retina, and prevention of BRB breakdown. These findings suggest that microglia/macrophages play an important role in the pathology of retinal disorders characterized by breakdown of the BRB, and suppression of their activation may be a potential therapeutic target for such retinopathies.