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Concept: Optic nerve


Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye by using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, panuveitis, and infection of the cornea, iris, optic nerve, and ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, given that Axl(-/-), Mertk(-/-), and Axl(-/-)Mertk(-/-) double knockout mice sustained levels of infection similar to those of control animals. We also detected abundant viral RNA in tears, suggesting that virus might be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

Concepts: Immune system, Gene, Virus, Infection, Eye, Ophthalmology, Tears, Optic nerve


To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone.

Concepts: Optics, Glaucoma, Ophthalmology, Myopia, Lens, Presbyopia, Optic nerve, ARIA Charts


It is generally acknowledged that structural loss can precede functional loss in some patients with early glaucoma. However, conventional standard automated perimetry (SAP) has limitations in the detection of functional loss, especially in the macular area. This study explores visual field loss in the macular areas of patients with preperimetric glaucoma exhibiting structural thinning in the area by examining the correlations between the ganglion cell-inner plexiform layer (GCIPL) and the results of matrix frequency-doubling technology (FDT) 10-2 tests. The structure-function relationships between the GCIPL thicknesses and the mean sensitivities (MSs) of the corresponding areas based on conventional SAP 24-2, FDT 10-2, and FDT 24-2 were examined in 62 patients. The highest correlation was found for FDT 10-2 (r = 0.544, P < 0.001) followed by FDT 24-2 (r = 0.433, P = 0.002) and SAP (r = 0.346, P = 0.007). The correlation coefficients between each GCIPL sector and the corresponding central MS according to FDT 24-2 and 10-2 were all statistically significant, and the correlations were significantly stronger for FDT 10-2 than 24-2 in the inferior and inferonasal sectors. In conclusion, preperimetric glaucoma patients with structural loss in the macula as indicated by GCIPL thinning also exhibited functional loss as revealed by FDT 10-2, and the functional loss was less evident with conventional SAP.

Concepts: Statistics, Spearman's rank correlation coefficient, Arithmetic mean, Ophthalmology, Correlation and dependence, Pearson product-moment correlation coefficient, Optic nerve, Visual field


To investigate the site specificity of visual field changes in eyes with normotensive preperimetric glaucoma (PPG), and to determine factors influencing visual field progression.

Concepts: Retina, Eye, Photoreceptor cell, Visual system, Ophthalmology, Optic nerve, Visual field, Blind spot


Retinal cell apoptosis occurs in many ocular neurodegenerative conditions including glaucoma-the major cause of irreversible blindness worldwide. Using a new imaging technique that we have called DARC (detection of apoptosing retinal cells), which until now has only been demonstrated in animal models, we assessed if annexin 5 labelled with fluorescent dye DY-776 (ANX776) could be used safely in humans to identify retinal cell apoptosis. Eight patients with glaucomatous neurodegeneration and evidence of progressive disease, and eight healthy subjects were randomly assigned to intravenous ANX776 doses of 0.1, 0.2, 0.4 and 0.5 mg in an open-label, phase 1 clinical trial. In addition to assessing the safety, tolerability and pharmacokinetics of ANX776, the study aimed to explore whether DARC could successfully visualize individual retinal cell apoptosis in vivo in humans, with the DARC count defined as the total number of unique ANX776-labelled spots. DARC enabled retinal cell apoptosis to be identified in the human retina using ANX776. Single ANX776-labelled cells were visualized in a dose-dependent pattern (P < 0.001) up to 6 h after injection. The DARC count was significantly higher (2.37-fold, 95% confidence interval: 1.4-4.03, P = 0.003) in glaucoma patients compared to healthy controls, and was significantly (P = 0.045) greater in patients who later showed increasing rates of disease progression, based on either optic disc, retinal nerve fibre layer or visual field parameters. Additionally, the DARC count significantly correlated with decreased central corneal thickness (Spearman's R = -0.68, P = 0.006) and increased cup-disc ratios (Spearman's R = 0.47, P = 0.038) in glaucoma patients and with increased age (Spearman's R = 0.77, P = 0.001) in healthy controls. Finally, ANX776 was found to be safe and well-tolerated with no serious adverse events, and a short half-life (10-36 min). This proof-of-concept study demonstrates that retinal cell apoptosis can be identified in the human retina with increased levels of activity in glaucomatous neurodegenerative disease. To our knowledge, this is the first time individual neuronal apoptosis has been visualized in vivo in humans and is the first demonstration of detection of individual apoptotic cells in a neurodegenerative disease. Furthermore, our results suggest the level of apoptosis ('DARC count') is predictive of disease activity, indicating the potential of DARC as a surrogate marker. Although further trials are clearly needed, this study validates experimental findings supporting the use of DARC as a method of detection and monitoring of patients with glaucomatous neurodegeneration, where retinal ganglion cell apoptosis is an established process and where there is a real need for tools to non-invasively assess treatment efficacy.

Concepts: Nervous system, Neuron, Apoptosis, Action potential, Retina, Optic nerve, Ganglion cell, Nerve fiber layer


Retinal prosthesis technologies require that the visual system downstream of the retinal circuitry be capable of transmitting and elaborating visual signals. We studied the capability of plastic remodeling in late blind subjects implanted with the Argus II Retinal Prosthesis with psychophysics and functional MRI (fMRI). After surgery, six out of seven retinitis pigmentosa (RP) blind subjects were able to detect high-contrast stimuli using the prosthetic implant. However, direction discrimination to contrast modulated stimuli remained at chance level in all of them. No subject showed any improvement of contrast sensitivity in either eye when not using the Argus II. Before the implant, the Blood Oxygenation Level Dependent (BOLD) activity in V1 and the lateral geniculate nucleus (LGN) was very weak or absent. Surprisingly, after prolonged use of Argus II, BOLD responses to visual input were enhanced. This is, to our knowledge, the first study tracking the neural changes of visual areas in patients after retinal implant, revealing a capacity to respond to restored visual input even after years of deprivation.

Concepts: Retina, Visual perception, Visual system, Prosthetics, Retinitis pigmentosa, Thalamus, Lateral geniculate nucleus, Optic nerve


Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision.

Concepts: Clinical trial, Electricity, Electromagnetic radiation, Electric current, Glaucoma, Ophthalmology, Alternating current, Optic nerve


Information about self-motion and obstacles in the environment is encoded by optic flow, the movement of images on the eye. Decades of research have revealed that flying insects control speed, altitude, and trajectory by a simple strategy of maintaining or balancing the translational velocity of images on the eyes, known as pattern velocity. It has been proposed that birds may use a similar algorithm but this hypothesis has not been tested directly. We examined the influence of pattern velocity on avian flight by manipulating the motion of patterns on the walls of a tunnel traversed by Anna’s hummingbirds. Contrary to prediction, we found that lateral course control is not based on regulating nasal-to-temporal pattern velocity. Instead, birds closely monitored feature height in the vertical axis, and steered away from taller features even in the absence of nasal-to-temporal pattern velocity cues. For vertical course control, we observed that birds adjusted their flight altitude in response to upward motion of the horizontal plane, which simulates vertical descent. Collectively, our results suggest that birds avoid collisions using visual cues in the vertical axis. Specifically, we propose that birds monitor the vertical extent of features in the lateral visual field to assess distances to the side, and vertical pattern velocity to avoid collisions with the ground. These distinct strategies may derive from greater need to avoid collisions in birds, compared with small insects.

Concepts: Scientific method, Insect, Optic nerve, Horizontal plane, Flight, Flying and gliding animals, Insect flight, Bird flight


Purpose To assess intracranial visual system changes of newly diagnosed Parkinson disease in drug-naïve patients. Materials and Methods Twenty patients with newly diagnosed Parkinson disease and 20 age-matched control subjects were recruited. Magnetic resonance (MR) imaging (T1-weighted and diffusion-weighted imaging) was performed with a 3-T MR imager. White matter changes were assessed by exploring a white matter diffusion profile by means of diffusion-tensor imaging-based parameters and constrained spherical deconvolution-based connectivity analysis and by means of white matter voxel-based morphometry (VBM). Alterations in occipital gray matter were investigated by means of gray matter VBM. Morphologic analysis of the optic chiasm was based on manual measurement of regions of interest. Statistical testing included analysis of variance, t tests, and permutation tests. Results In the patients with Parkinson disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density (F, -8.28; P < .05), a significant increase in optic radiation mean diffusivity (F, 7.5; P = .014), and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes (P < .05). Moreover, the chiasmatic area and volume were significantly reduced (P < .05). Conclusion The findings show that visual system alterations can be detected in early stages of Parkinson disease and that the entire intracranial visual system can be involved. (©) RSNA, 2017 Online supplemental material is available for this article.

Concepts: Statistics, Cerebrum, Visual perception, Visual system, Analysis of variance, Thalamus, Lateral geniculate nucleus, Optic nerve


OBJECTIVE: To determine the effect of clinical and radiologic disease activity on the rate of thinning of the ganglion cell/inner plexiform (GCIP) layer and the retinal nerve fiber layer in patients with multiple sclerosis (MS) using optical coherence tomography (OCT). METHODS: One hundred sixty-four patients with MS and 59 healthy controls underwent spectral-domain OCT scans every 6 months for a mean follow-up period of 21.1 months. Baseline and annual contrast-enhanced brain MRIs were performed. Patients who developed optic neuritis during follow-up were excluded from analysis. RESULTS: Patients with the following features of disease activity during follow-up had faster rates of annualized GCIP thinning: relapses (42% faster, p = 0.007), new gadolinium-enhancing lesions (54% faster, p < 0.001), and new T2 lesions (36% faster, p = 0.02). Annual GCIP thinning was 37% faster in those with disability progression during follow-up, and 43% faster in those with disease duration <5 years vs >5 years (p = 0.003). Annual rates of GCIP thinning were highest in patients exhibiting combinations of new gadolinium-enhancing lesions, new T2 lesions, and disease duration <5 years (70% faster in patients with vs without all 3 characteristics, p < 0.001). CONCLUSIONS: MS patients with clinical and/or radiologic nonocular disease activity, particularly early in the disease course, exhibit accelerated GCIP thinning. Our findings suggest that retinal changes in MS reflect global CNS processes, and that OCT-derived GCIP thickness measures may have utility as an outcome measure for assessing neuroprotective agents, particularly in early, active MS.

Concepts: Nervous system, Optics, Magnetic resonance imaging, Multiple sclerosis, Retina, Optical coherence tomography, Optic nerve, Nerve fiber layer