In Vivo Detection of Laminar and Peripapillary Scleral Hypercompliance in Early Monkey Experimental Glaucoma

PubMed Central

Ivers, Kevin M.; Yang, Hongli; Gardiner, Stuart K.; Qin, Lirong; Reyes, Luke; Fortune, Brad; Burgoyne, Claude F.

2016-01-01

Purpose To compare optical coherence tomography (OCT) detected, optic nerve head (ONH) compliance within control and experimental glaucoma (EG) eyes of 15 monkeys at EG onset. Methods Intraocular pressure (IOP) was chronically elevated in one eye of each animal using a laser. Experimental glaucoma onset was identified using confocal scanning laser tomography (CSLT). Optical coherence tomography ONH imaging (40 radial B-scans) was performed at 10 mm Hg before and after laser. At EG onset, OCT scans were obtained at IOP 10 and 30 mm Hg. Optical coherence tomography landmarks within the IOP 10/30 images were delineated to quantify IOP 10/30 differences (compliance) for anterior lamina cribrosa surface depth (ALCSD) relative to Bruch's membrane opening (BMO) (ALCSD-BMO), ALCSD relative to peripheral BM (ALCSD-BM), and BMO depth relative to peripheral BM (BMOD-BM). A linear mixed effects model assessed for acute IOP elevation effects, control versus EG eye effects, and their interaction Results Effects of IOP elevation were greater in EG versus control eyes for ALCSD-BMO (−46 ± 45 vs. −8 ± 13 μm, P = 0.0042) and ALCSD-BM (−92 ± 64 vs. −42 ± 22 μm, P = 0.0075). Experimental glaucoma eye-specific ALCSD-BMO and ALCSD-BM compliance exceeded the range of control eye compliance in 9 and 8 of the 15 EG eyes, respectively. Post-laser peak IOP (R2 = 0.798, P < 0.0001) and post-laser mean IOP (R2 = 0.634, P < 0.0004) most strongly correlated to EG versus control eye differences in ALCSD-BMO compliance. Conclusions Laminar (ALCSD-BMO) and peripapillary scleral (ALCSD-BM) hypercompliance are present in most monkey eyes at the onset of EG. PMID:27409498

Comparative anatomy and evolution of the cardiac innervation in New World monkeys (Platyrrhini, e. Geoffroy, 1812).

PubMed

Kawashima, Tomokazu; Thorington, Richard W; Whatton, James F

2009-05-01

The morphology of the autonomic cardiac nervous system (ACNS) was examined in 24 sides of 12 New World monkeys (Platyrrhini) of all four families to document the morphology systematically and to study the evolutionary changes of the ACNS in this primate lineage. We report the following: (1) Although several trivial intra- and inter-specific variations are present, a family-dependent morphology of the ACNS does not exist in New World monkeys. (2) The sympathetic ganglia in New World monkeys consist of the superior cervical, the middle cervical, and the cervicothoracic which is composed of the inferior cervical and first and second thoracic, and the thoracic ganglia starting with the third thoracic. The general cardiac nervous system is the sympathetic middle and inferior cardiac nerves and all parasympathetic vagal cardiac branches. (3) The morphology of the ACNS in the New World monkeys is almost consistent regardless of the number of vertebrae, the cardiac position and deviation (axis), and the great arterial branching pattern of the aortic arch, and it is very similar to that in the Old World monkeys, with only one difference: the superior cervical ganglion in the New World monkeys tends to be relatively smaller, higher, and provides a narrower contribution to the spinal nerves than in the Old World monkeys. The ACNS morphology exhibits significant evolutionary changes within the primate lineage from New and Old World monkeys to humans. The comparative morphology within the lineage is concordant with the phylogeny, suggesting that the primate ACNS preserves its evolutionary history in close alignment with phylogeny.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque.

PubMed

Irwin, Z T; Schroeder, K E; Vu, P P; Tat, D M; Bullard, A J; Woo, S L; Sando, I C; Urbanchek, M G; Cederna, P S; Chestek, C A

2016-08-01

Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey's finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Translamina Cribrosa Pressure Difference as Potential Element in the Pathogenesis of Glaucomatous Optic Neuropathy.

PubMed

Jonas, Jost B; Wang, Ningli; Yang, Diya

2016-01-01

The main proven risk factor for glaucomatous optic neuropathy (GON) is an intraocular pressure (IOP) higher than the pressure sensibility of the optic nerve head allows. Fulfilling Koch postulates, numerous studies have shown that the presence of high IOP leads to GON, that lowering IOP stops the progression of GON, and that a re-increase in IOP again causes the progression of GON. There are, however, many patients with glaucoma who have statistically normal or low IOP, and despite low IOP values, they develop progressing GON. These observations led to findings that IOP is only 1 of 2 determinants of the translamina cribrosa pressure difference (TLCPD), which is the main pressure-related parameter for the physiology and pathophysiology of the optic nerve head. The second parameter influencing TLCPD is orbital cerebrospinal fluid pressure (CSFP) as the counter pressure against IOP across the lamina cribrosa. Recent experimental and clinical studies have suggested that a low CSFP could be associated with GON in normal-pressure glaucoma. These investigations included studies with an experimental long-term reduction in CSFP in monkeys, population-based studies, and clinical retrospective and prospective investigations on patients with normal-pressure glaucoma. Besides TLCPD, other ocular parameters influenced by CSFP may be choroidal thickness, retinal vein pressure and diameter, occurrence of retinal vein occlusions, and occurrence and severity of diabetic retinopathy.

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications.

PubMed

Yang, Hongli; Reynaud, Juan; Lockwood, Howard; Williams, Galen; Hardin, Christy; Reyes, Luke; Stowell, Cheri; Gardiner, Stuart K; Burgoyne, Claude F

2017-07-01

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Scleral Biomechanics in the Aging Monkey Eye

PubMed Central

Girard, Michaël J. A.; Suh, J-K. Francis; Bottlang, Michael; Burgoyne, Claude F.; Downs, J. Crawford

2010-01-01

Purpose To investigate the age-related differences in the inhomogeneous, anisotropic, nonlinear biomechanical properties of posterior sclera from old (22.9 ± 5.3 years) and young (1.5 ± 0.7 years) rhesus monkeys. Methods The posterior scleral shell of each eye was mounted on a custom-built pressurization apparatus, then intraocular pressure (IOP) was elevated from 5 to 45 mmHg while the 3D displacements of the scleral surface were measured using speckle interferometry. Each scleral shell geometry was digitally reconstructed from data generated by a 3D digitizer (topography) and 20 MHz ultrasounds (thickness). An inverse finite element (FE) method incorporating a fiber-reinforced constitutive model was used to extract a unique set of biomechanical properties for each eye. Displacements, thickness, stress, strain, tangent modulus, structural stiffness, and preferred collagen fiber orientation were mapped for each posterior sclera. Results The model yielded 3-D deformations of posterior sclera that matched well with those observed experimentally. The posterior sclera exhibited inhomogeneous, anisotropic, nonlinear mechanical behavior. The sclera was significantly thinner (p = 0.038), and tangent modulus and structural stiffness were significantly higher in old monkeys (p < 0.0001). On average, scleral collagen fibers were circumferentially oriented around the optic nerve head (ONH). We found no difference in the preferred collagen fiber orientation and fiber concentration factor between age groups. Conclusions Posterior sclera from old monkeys is significantly stiffer than that from young monkeys and is therefore subject to higher stresses but lower strains at all levels of IOP. Age-related stiffening of the sclera may significantly influence ONH biomechanics, and potentially contribute to age-related susceptibility to glaucomatous vision loss. PMID:19494203

Deformation of the Early Glaucomatous Monkey Optic Nerve Head Connective Tissue after Acute IOP Elevation in 3-D Histomorphometric Reconstructions

PubMed Central

Yang, Hongli; Thompson, Hilary; Roberts, Michael D.; Sigal, Ian A.; Downs, J. Crawford

2011-01-01

Purpose. To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes. Methods. Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n = 3), 30 (n = 3), or 45 (n = 3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP. Results. Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation. Conclusions. The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants. PMID:20702834

Palisade endings are present in canine extraocular muscles and have a cholinergic phenotype.

PubMed

Rungaldier, Stefanie; Pomikal, Christine; Streicher, Johannes; Blumer, Roland

2009-11-20

Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was detected in the EOMs of each species including sheep, cat, rabbit, rat, monkey, and human examined so far: the palisade ending. Until now no clear evidence appeared that palisade endings are also present in canine EOMs. Here, we analyzed dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and transmission electron microscopy. In EOM wholemount preparations stained with antibodies against neurofilament and synaptophysin we could demonstrate typical palisade endings. Nerve fibers coming from the muscle extend into the tendon. There, the nerve fibers turn 180 degrees and return to branch into preterminal axons which establish nerve terminals around a single muscle fiber tip. Fine structural analysis revealed that each palisade ending in dog EOMs establish nerve terminals on the tendon. In some palisade endings we found nerve terminals contacting the muscle fiber as well. Such neuromuscular contacts have a basal lamina in the synaptic cleft. By using an antibody against choline acetyltransferase (ChAT) we proved that canine palisade endings are ChAT-immunoreactive. This study shows that palisade endings are present in canine EOMs. In line with prior findings in cat and monkey, palisade endings in dog have a cholinergic phenotype.

Optic Nerve Lymphoma. Report of Two Cases and Review of the Literature

PubMed Central

Kim, Jennifer L.; Mendoza, Pia; Rashid, Alia; Hayek, Brent; Grossniklaus, Hans E.

2014-01-01

Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation. PMID:25595061

Movement of retinal vessels toward the optic nerve head after increasing intraocular pressure in monkey eyes with experimental glaucoma.

PubMed

Kuroda, Atsumi; Enomoto, Nobuko; Ishida, Kyoko; Shimazawa, Masamitsu; Noguchi, Tetsuro; Horai, Naoto; Onoe, Hirotaka; Hara, Hideaki; Tomita, Goji

2017-09-01

A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim thinning indicates the progression of glaucomatous optic neuropathy. In chronic open angle glaucoma, individuals with RBV positional shifts exhibit more rapid visual field loss than those without RBV shifts. The retinal vessels reportedly move onto the optic nerve head (ONH) in response to glaucoma damage, suggesting that RBVs are pulled toward the ONH in response to increased cupping. Whether this phenomenon only applies to RVBs located in the vicinity or inside the ONH or, more generally, to RBVs also located far from the ONH, however, is unclear. The aim of this study was to evaluate the movement of RBVs located relatively far from the ONH edge after increasing intraocular pressure (IOP) in an experimental monkey model of glaucoma. Fundus photographs were obtained in 17 monkeys. High IOP was induced in the monkeys by laser photocoagulation burns applied uniformly with 360° irradiation around the trabecular meshwork of the left eye. The right eye was left intact and used as a non-treated control. Considering the circadian rhythm of IOP, it was measured in both eyes of each animal at around the same time-points. Then, fundus photographs were obtained. Using Image J image analysis software, an examiner (N.E.) measured the fundus photographs at two time-points, i.e. before laser treatment (time 1) and the last fundus photography after IOP elevation (time 2). The following parameters were measured (in pixels): 1) vertical diameter of the ONH (DD), 2) distance from the ONH edge to the first bifurcation point of the superior branch of the central retinal vein (UV), 3) distance from the ONH edge to the first bifurcation point of the inferior branch of the central retinal vein (LV), 4) ONH area, and 5) surface area of the cup of the ONH. We calculated the ratios of UV to DD (UV/DD), LV to DD (LV/DD), and the cup area to disc area ratio (C/D). The mean UV/DD at time 1 (0.656 ± 0.233) was decreased at time 2 (0.542 ± 0.192) (p < 0.01), and the mean LV/DD at time 1 (0.642 ± 0.151) was decreased at time 2 (0.534 ± 0.171) (p < 0.01). The mean C/D at time 1 (0.303 ± 0.035) was increased at time 2 (0.556 ± 0.110) (p < 0.01). The mean IOP at time 1 was 19.8 ± 2.5 and that at time 2 was 54.2 ± 15.8. The amount and rate of the change in LV/DD and C/D between time 1 and time 2 were significantly correlated (r = -0.654 and -0.536, p = 0.004 and 0.026, respectively). Therefore, in an experimental monkey model of glaucoma, RBVs located relatively far from the ONH were pulled toward the ONH as cupping increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

PubMed Central

Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen.

PubMed

Larson, Shawnessy D; Schelegle, Edward S; Walby, William F; Gershwin, Laural J; Fanuccihi, Michelle V; Evans, Michael J; Joad, Jesse P; Tarkington, Brian K; Hyde, Dallas M; Plopper, Charles G

2004-02-01

Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O(3)) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O(3), or HDMA + O(3) for 11 episodes (5 days each, 0.5 ppm O(3), 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P < 0.05) decrements in the density of epithelial nerves in monkeys exposed to HDMA or O(3), while in monkeys exposed to HDMA + O(3) there was a greater significant (P < 0.05) reduction in epithelial innervation. In animals exposed to O(3) or HDMA + O(3) there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium.

Palisade endings are present in canine extraocular muscles and have a cholinergic phenotype

PubMed Central

RUNGALDIER, Stefanie; POMIKAL, Christine; STREICHER, Johannes; BLUMER, Roland

2016-01-01

Classical proprioceptors, like Golgi tendon organs and muscle spindles are absent in the extraocular muscles (EOMs) of most mammals. Instead, a nerve end organ was detected in the EOMs of each species including sheep, cats, rabbits, rats, monkeys, and man examined so far: the palisade ending. Until now no evidence appeared that palisade endings are present in canine EOMs. We analyzed dog EOMs by confocal laser scanning microscopy, 3D reconstruction, and transmission electron microscopy. In EOM wholemount preparations stained with antibodies against neurofilament and synaptophysin we found typical palisade endings. Nerve fibers coming from the muscle extended into the tendon. There, the nerve fibers turned 180° and returned to branch into preterminal axons which established nerve terminals around a single muscle fiber tip. Fine structural analyses revealed that each palisade ending in dog EOMs established nerve terminals on the tendon. In some palisade endings we found nerve terminals contacting the muscle fiber as well. Such neuromuscular contacts had a basal lamina in the synaptic cleft thereby resembling motor terminals. By using antibodies against choline acetyltransferase (ChAT) we proved that canine palisade endings are ChAT-immunoreactive. This study shows that palisade endings are present in canine EOMs. In line with prior findings in cat and monkey, palisade endings in dog have a cholinergic phenotype. PMID:19766165

In-vivo effects of intraocular and intracranial pressures on the lamina cribrosa microstructure

PubMed Central

Smith, Matthew A.; Kostanyan, Tigran; Schmitt, Samantha E.; Bilonick, Richard A.; Jan, Ning-Jiun; Kagemann, Larry; Tyler-Kabara, Elizabeth C.; Ishikawa, Hiroshi; Schuman, Joel S.; Wollstein, Gadi

2017-01-01

There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the rest of their body lying prone on a surgical table. The LC was imaged at a variety of IOP/ICP combinations, and microstructural parameters, such as the thickness of the LC collagenous beams and diameter of the pores were analyzed. LC microstructure was confirmed by histology. We determined that LC microstructure deformed in response to both IOP and ICP changes, with significant interaction between the two. These findings emphasize the importance of considering both IOP and ICP when assessing optic nerve health. PMID:29161320

Effect of the Age Cross-Link Breaker Alagebrium on Anterior Segment Physiology, Morphology, and Ocular Age and Rage

PubMed Central

Kiland, Julie A.; Gabelt, B’Ann T.; Tezel, Gülgün; Lütjen-Drecoll, Elke; Kaufman, Paul L.

2009-01-01

Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys. Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry. Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 ± 6.0%; P ≤ .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm’s canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining. Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies. PMID:20126491

[Pharmacological profiles of latanoprost (Xalatan), a novel anti-glaucoma drug].

PubMed

Nomura, S; Hashimoto, M

2000-05-01

Latanoprost is a novel prostaglandin F2 alpha (PGF2 alpha) derivative. Topically applied latanoprost into the glaucomatous monkey eyes lowered intraocular pressure (IOP). Latanoprost, however, failed to produce the hypotensive effect in either rabbit or cat eyes. This species difference may be attributed to its high selectivity for the FP receptor and differences in prostaglandin receptor subtypes existed in the eye amongst these species. In ligand binding studies with bovine corpus luteum cell membranes, the Kd value for the FP receptor of latanoprost was the same as that for PGF2 alpha, 2.8 nM. Latanoprost augmented uveoscleral outflow (Uv) in monkeys without affecting trabecular outflow or outflow facility like PGF2 alpha. Although the precise mechanism of the increase in Uv is not fully understood, it is suggested that a decrease in extracellular matrix components in ciliary muscle may contribute to the increase in Uv. On the other hand, an increase in blood flow at the optic nerve head and neuroprotective action in addition to the IOP lowering effect may contribute to the efficacy of latanoprost in glaucoma therapy. Only tolerable conjunctival hyperemia was seen in rabbits. A phase III clinical trial revealed latanoprost (0.005%) once daily produced sustained reduction of IOP in ocular hypertension or primary open-angle glaucoma patients to a greater extent than timolol did. Furthermore, the effects of latanoprost on aqueous humor dynamics in normal human volunteers were similar to those in monkeys, indicating that latanoprost lowers IOP by the increase in Uv in humans.

Effects of Monoclonal Antibodies against Nerve Growth Factor on Healthy Bone and Joint Tissues in Mice, Rats, and Monkeys: Histopathologic, Biomarker, and Microcomputed Tomographic Assessments.

PubMed

Gropp, Kathryn E; Carlson, Cathy S; Evans, Mark G; Bagi, Cedo M; Reagan, William J; Hurst, Susan I; Shelton, David L; Zorbas, Mark A

2018-01-01

Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all NGF inhibitors. Three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor muMab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, Sprague-Dawley rats, and C57BL/6 mice. Joint and bone endpoints included histology, immunohistochemistry, microcomputed tomography (mCT) imaging, and serum biomarkers of bone physiology. Responses of bone endpoints to tanezumab were evaluated in monkeys at 4 to 30 mg/kg/week for 26 weeks and in rats at 0.2 to 10 mg/kg twice weekly for 28 days. The effects of muMab911 at 10 mg/kg/week for 12 weeks on selected bone endpoints were determined in mice. Tanezumab and muMab911 had no adverse effects on any bone or joint parameter. There were no test article-related effects on bone or joint histology, immunohistochemistry, or structure. Reversible, higher osteocalcin concentrations occurred only in the rat study. No deleterious effects were observed in joints or bones in monkeys, rats, or mice administered high doses of tanezumab or muMab911.

Age-Related Differences in Longitudinal Structural Change by Spectral-Domain Optical Coherence Tomography in Early Experimental Glaucoma

PubMed Central

Yang, Hongli; He, Lin; Gardiner, Stuart K.; Reynaud, Juan; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Downs, J. Crawford; Fortune, Brad; Burgoyne, Claude F.

2014-01-01

Purpose. To characterize age-related differences in the magnitude of spectral-domain optical coherence tomography (SD-OCT) structural change in early experimental glaucoma (EG). Methods. Both eyes from four young (1.4–2.6 years) and four old (18.6–21.9 years) rhesus monkeys were imaged at least three times at baseline, and then every 2 weeks after laser-induced, chronic, unilateral IOP elevation until the onset of EG (confocal scanning laser tomographic surface change confirmed twice). Two to 20 weeks after EG onset, animals were euthanized and optic nerve axon counts for all eyes were performed. Masked operators delineated retinal and ONH landmarks in 40 radial B-scans from each eye and imaging session to quantify change from baseline in five SD-OCT neural and connective tissue parameters. The effects of EG, age, and EG × age interactions on the magnitude, rate (magnitude per postlaser time), and IOP responsiveness (magnitude per cumulative IOP insult) of postlaser parameter change were individually assessed using general estimating equation models. Results. Presac SD-OCT RNFLT and minimum rim width change and postmortem axon loss was not significantly different in old compared with young EG eyes. The rate of change and IOP responsiveness of the parameters anterior lamina cribrosa surface depth relative to Bruch's membrane opening (BMO) and BMO depth relative to peripheral Bruch's membrane were significantly lower (P < 0.05) in the old compared with the young EG eyes. Conclusions. At similar postlaser times, levels of cumulative IOP insult and axonal damage, SD-OCT–detected ONH connective tissue structural change is greater in young compared with old monkey EG eyes. PMID:25190652

Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.

PubMed

Taurone, S; Ripandelli, G; Minni, A; Lattanzi, R; Miglietta, S; Pepe, N; Fumagalli, L; Micera, A; Pastore, F S; Artico, M

2016-01-01

The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.

Mapping in-vivo optic nerve head strains caused by intraocular and intracranial pressures

NASA Astrophysics Data System (ADS)

Tran, H.; Grimm, J.; Wang, B.; Smith, M. A.; Gogola, A.; Nelson, S.; Tyler-Kabara, E.; Schuman, J.; Wollstein, G.; Sigal, I. A.

2017-02-01

Although it is well documented that abnormal levels of either intraocular (IOP) or intracranial pressure (ICP) can lead to potentially blinding conditions, such as glaucoma and papilledema, little is known about how the pressures actually affect the eye. Even less is known about potential interplay between their effects, namely how the level of one pressure might alter the effects of the other. Our goal was to measure in-vivo the pressure-induced stretch and compression of the lamina cribrosa due to acute changes of IOP and ICP. The lamina cribrosa is a structure within the optic nerve head, in the back of the eye. It is important because it is in the lamina cribrosa that the pressure-induced deformations are believed to initiate damage to neural tissues leading to blindness. An eye of a rhesus macaque monkey was imaged in-vivo with optical coherence tomography while IOP and ICP were controlled through cannulas in the anterior chamber and lateral ventricle, respectively. The image volumes were analyzed with a newly developed digital image correlation technique. The effects of both pressures were highly localized, nonlinear and non-monotonic, with strong interactions. Pressure variations from the baseline normal levels caused substantial stretch and compression of the neural tissues in the posterior pole, sometimes exceeding 20%. Chronic exposure to such high levels of biomechanical insult would likely lead to neural tissue damage and loss of vision. Our results demonstrate the power of digital image correlation technique based on non-invasive imaging technologies to help understand how pressures induce biomechanical insults and lead to vision problems.

Seeing the Hidden Lamina: Effects of Exsanguination on the Optic Nerve Head

PubMed Central

Tran, Huong; Wallace, Jacob; Zhu, Ziyi; Lucy, Katie A.; Voorhees, Andrew P.; Schmitt, Samantha E.; Bilonick, Richard A.; Schuman, Joel S.; Smith, Matthew A.; Wollstein, Gadi; Sigal, Ian A.

2018-01-01

Purpose To introduce an experimental approach for direct comparison of the primate optic nerve head (ONH) before and after death by exsanguination. Method The ONHs of four eyes from three monkeys were imaged with spectral-domain optical coherence tomography (OCT) before and after exsanguination under controlled IOP. ONH structures, including the Bruch membrane (BM), BM opening, inner limiting membrane (ILM), and anterior lamina cribrosa (ALC) were delineated on 18 virtual radial sections per OCT scan. Thirteen parameters were analyzed: scleral canal at BM opening (area, planarity, and aspect ratio), ILM depth, BM depth; ALC (depth, shape index, and curvedness), and ALC visibility (globally, superior, inferior, nasal, and temporal quadrants). Results All four ALC quadrants had a statistically significant improvement in visibility after exsanguination (overall P < 0.001). ALC visibility increased by 35% globally and by 36%, 37%, 14%, and 4% in the superior, inferior, nasal, and temporal quadrants, respectively. ALC increased 4.1%, 1.9%, and 0.1% in curvedness, shape index, and depth, respectively. Scleral canals increased 7.2%, 25.2%, and 1.1% in area, planarity, and aspect ratio, respectively. ILM and BM depths averaged −7.5% and −55.2% decreases in depth, respectively. Most, but not all, changes were beyond the repeatability range. Conclusions Exsanguination allows for improved lamina characterization, especially in regions typically blocked by shadowing in OCT. The results also demonstrate changes in ONH morphology due to the loss of blood pressure. Future research will be needed to determine whether there are differences in ONH biomechanics before and after exsanguination and what those differences would imply. PMID:29847664

Microvasculature of the Olfactory Organ in the Japanese Monkey (Macaca fuscata fuscata)

NASA Astrophysics Data System (ADS)

Okada, Shigenori; Schraufnagel, Dean E.

2002-06-01

Olfaction is an important and primitive sense. As its importance has changed with evolution, anatomic adjustments have occurred in its structure and vasculature. Primates are a family of vertebrates that have had to develop their visual system to adapt to the arboreal environment and have evolved from a macrosmatic to a microsmatic species as the optic system has enlarged. This has resulted in anatomic changes of a small but critical area at the base of the brain. This paper describes the three-dimensional vascular anatomy of the olfactory organ of the Japanese monkey (Macaca fuscata fuscata). This is best understood by dividing the organ into three parts: the olfactory tract, olfactory bulb, and olfactory nerves in the nasal mucosa. The bulb can be partitioned into an outer or cortical part and inner or medullary part. The vasculature and tissue were examined grossly and with light microscopy and scanning electron microscopy of vascular corrosion casts. The olfactory tract and bulb were supplied by an arteriole from the anterior cerebral artery on each side. The tract was supplied by capillaries running spirally with a coarse network. At the olfactory bulb, the arteriole ramified into the intracortical and medullary branches that formed capillary networks. The bulbar intracortical capillaries were divided into two layers with different densities and vascular patterns. The capillaries of the superficial layer had a ladder-like pattern. The branches that ran into the medulla of the olfactory bulb were more widely spaced. Twigs from the posterior ethmoidal artery ran along the nerve fiber and formed intra- and extrafascicular networks. Each region of the olfactory organ had characteristic three-dimensional vascular patterns that were related to their cellular architecture.

Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

NASA Astrophysics Data System (ADS)

Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

2016-08-01

Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

Limited Susceptibility of Cynomolgus Monkeys (Macaca fascicularis) to Leprosy after Experimental Administration of Mycobacterium leprae

PubMed Central

Walsh, Gerald P.; Dela Cruz, Eduardo C.; Abalos, Rodolfo M.; Tan, Esterlina V.; Fajardo, Tranquilino T.; Villahermosa, Laarni G.; Cellona, Roland V.; Balagon, Maria V.; White, Valerie A.; Saunderson, Paul R.; Walsh, Douglas S.

2012-01-01

Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis—importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1–19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration. PMID:22855766

Optic Nerve Decompression

MedlinePlus

... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

Sporadic Premature Aging in a Japanese Monkey: A Primate Model for Progeria

PubMed Central

Oishi, Takao; Imai, Hiroo; Go, Yasuhiro; Imamura, Masanori; Hirai, Hirohisa; Takada, Masahiko

2014-01-01

In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes. PMID:25365557

RGC Neuroprotection Following Optic Nerve Trauma Mediated By Intranasal Delivery of Amnion Cell Secretome

PubMed Central

Grinblat, Gabriela A.; Khan, Reas S.; Dine, Kimberly; Wessel, Howard; Brown, Larry; Shindler, Kenneth S.

2018-01-01

Purpose Intranasally delivered ST266, the biological, proteinaceous secretome of amnion-derived multipotent progenitor cells, reduces retinal ganglion cell (RGC) loss, optic nerve inflammation, and demyelination in experimental optic neuritis. This unique therapy and novel administration route delivers numerous cytokines and growth factors to the eye and optic nerve, suggesting a potential to also treat other optic neuropathies. Thus, ST266-mediated neuroprotection was examined following traumatic optic nerve injury. Methods Optic nerve crush injury was surgically induced in C57BL/6J mice. Mice were treated daily with intranasal PBS or ST266. RGC function was assessed by optokinetic responses (OKRs), RGCs were counted, and optic nerve sections were stained with luxol fast blue and anti-neurofilament antibodies to assess myelin and RGC axon damage. Results Intranasal ST266 administered daily for 5 days, beginning at the time that a 1-second optic nerve crush was performed, significantly attenuated OKR decreases. Furthermore, ST266 treatment reduced damage to RGC axons and myelin within optic nerves, and blocked RGC loss. Following a 4-second optic nerve crush, intranasal ST266 increased RGC survival and showed a trend toward reduced RGC axon and myelin damage. Ten days following optic nerve crush, ST266 prevented myelin damage, while also inducing a trend toward increased RGC survival and visual function. Conclusions ST266 significantly attenuates traumatic optic neuropathy. Neuroprotective effects of this unique combination of biologic molecules observed here and previously in optic neuritis suggest potential broad application for preventing neuronal damage in multiple optic nerve disorders. Furthermore, results support intranasal delivery as a novel, noninvasive therapeutic modality for eyes and optic nerves. PMID:29847652

[Gradient-index (GRIN) endoscopic examinations from the inner structures of the optic nerve meninges].

PubMed

Sens, Frank Michael; Killer, Hanspeter Esriel; Meyer, Peter

2003-03-01

Due to the excellent image quality and the small outer diameter of the GRIN-(gradient index) endoscope tips we were able to examine the subdural and the subarachnoidal space of the optic nerve meninges by endoscopy. This examination was performed to obtain more information about the inner structure of the optic nerve meninges. In this post-mortem study 7 optic nerves were examined from the chiasm to the globe by GRIN endoscopy (Volpi, Schlieren, Switzerland), with an outer diameter of 0.89 mm, integrated optic of 0.5 mm diameter and an integrated fluid channel of 0.2 mm diameter. In all cases the endoscopic examination of the optic nerve meninges was technically easy to perform. It was possible to study the inner surface of the nerve sheaths and the nerve sheath spaces in close-up. We found horizontal and vertical cords on the inner surface of the dura mater, which could tighten by movements of the optic nerve. With a gradient-index (GRIN) endoscope we obtained new information about the inner structure of the optic nerve meninges. New theories about the changes of the optic nerve meninges during movements of the optic nerve may evolve from this study. Further studies with this new method should be encouraged.

Magnetic resonance imaging of optic nerve

PubMed Central

Gala, Foram

2015-01-01

Optic nerves are the second pair of cranial nerves and are unique as they represent an extension of the central nervous system. Apart from clinical and ophthalmoscopic evaluation, imaging, especially magnetic resonance imaging (MRI), plays an important role in the complete evaluation of optic nerve and the entire visual pathway. In this pictorial essay, the authors describe segmental anatomy of the optic nerve and review the imaging findings of various conditions affecting the optic nerves. MRI allows excellent depiction of the intricate anatomy of optic nerves due to its excellent soft tissue contrast without exposure to ionizing radiation, better delineation of the entire visual pathway, and accurate evaluation of associated intracranial pathologies. PMID:26752822

Optic nerve head axonal transport in rabbits with hereditary glaucoma.

PubMed

Bunt-Milam, A H; Dennis, M B; Bensinger, R E

1987-04-01

Rabbits with hereditary glaucoma develop ocular changes that resemble human congenital glaucoma and buphthalmia. The inheritance is autosomal recessive (bu). Previous research was performed primarily on albino bu/bu rabbits that were unhealthy and bred poorly. We have bred pigmented bu/bu rabbits to determine if this would improve hardiness and provide a better model for the disease in humans. First-generation offspring from matings of bu/bu albino with bu/bu pigmented rabbits were all affected, indicating that the bu gene is found at the same locus in both strains. The pigmented bu/bu offspring had a high degree of mortality, as reported previously for albino bu/bu rabbits. Newborn bu/bu rabbits initially had normal intraocular pressure (IOP; 15-23 mmHg); after 1- to 3 months, the IOP increased to 26-48 mmHg. The eyes became buphthalmic and the IOP returned to normal or sub-normal levels after 6-10 months. Since the lamina cribrosa is absent or poorly formed in the rabbit optic nerve head (ONH), this model was used to test the role of mechanical factors in the etiology of ONH pathology caused by increased IOP. Orthograde axonal transport was evaluated in both eyes from eight normal and 24 bu/bu rabbits of different ages, using intravitreal injections of [3H]leucine to mark orthograde axonal transport, followed by light- and electron-microscopic radioautography of the ONHs and superior colliculi. Normal rabbits of all ages showed no blockage of axonal transport in the ONH. All optic axons from young bu/bu rabbits with normal IOP and most axons from older buphthalmic rabbits that previously had elevated IOP were normal morphologically. Small zones of transport blockage occurred in bu/bu eyes while IOP was elevated; most affected axons lay immediately adjacent to ONH connective tissue beams that radiate outward from the central retinal vessels to the optic-nerve sheath. Thus, the rabbit, which lacks a true lamina cribrosa, does not show marked blockage of axonal transport as occurs in the LS of the monkey and cat ONH when IOP is elevated acutely. This anatomic difference appears to be protective against axonal damage, since bu/bu rabbits with chronic IOP elevation did not show significant loss of optic axons. These results are consistent with the proposed 'mechanical' theory of ONH damage resulting from increased IOP. Electron-microscopic radioautography revealed that chronically elevated IOP in bu/bu rabbits, which caused small foci of blocked ONH axonal transport against ONH beams, also caused degeneration of a few optic nerve terminals in the superior colliculi as the disease progressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Histone deacetylase expression patterns in developing murine optic nerve

PubMed Central

2014-01-01

Background Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. However, little is known about HDAC expression or function within the optic nerve. As a first step in understanding the role of HDACs in optic nerve, this study examines the spatio-temporal expression patterns of methylated histone 3 (K9), acetylated histone 3 (K18), and HDACs 1–6 and 8–11 in the developing murine optic nerve head. Results Using RT-qPCR, western blot and immunofluorescence, three stages were analyzed: embryonic day 16 (E16), when astrocyte precursors are found in the optic stalk, postnatal day 5 (P5), when immature astrocytes and oligodendrocytes are found throughout the optic nerve, and P30, when optic nerve astrocytes and oligodendrocytes are mature. Acetylated and methylated histone H3 immunoreactivity was co-localized in the nuclei of most SOX2 positive glia within the optic nerve head and adjacent optic nerve at all developmental stages. HDACs 1–11 were expressed in the optic nerve glial cells at all three stages of optic nerve development in the mouse, but showed temporal differences in overall levels and subcellular localization. HDACs 1 and 2 were predominantly nuclear throughout optic nerve development and glial cell maturation. HDACs 3, 5, 6, 8, and 11 were predominantly cytoplasmic, but showed nuclear localization in at least one stage of optic nerve development. HDACs 4, 9 and10 were predominantly cytoplasmic, with little to no nuclear expression at any time during the developmental stages examined. Conclusions Our results showing that HDACs 1, 2, 3, 5, 6, 8, and 11 were each localized to the nuclei of SOX2 positive glia at some stages of optic nerve development and maturation and extend previous reports of HDAC expression in the aging optic nerve. These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation and methylation contributes to glial development as well as their injury response. PMID:25011550

Estimating 3D topographic map of optic nerve head from a single fundus image

NASA Astrophysics Data System (ADS)

Wang, Peipei; Sun, Jiuai

2018-04-01

Optic nerve head also called optic disc is the distal portion of optic nerve locating and clinically visible on the retinal surface. It is a 3 dimensional elliptical shaped structure with a central depression called the optic cup. This shape of the ONH and the size of the depression can be varied due to different retinopathy or angiopathy, therefore the estimation of topography of optic nerve head is significant for assisting diagnosis of those retinal related complications. This work describes a computer vision based method, i.e. shape from shading (SFS) to recover and visualize 3D topographic map of optic nerve head from a normal fundus image. The work is expected helpful for assessing those complications associated the deformation of optic nerve head such as glaucoma and diabetes. The illumination is modelled as uniform over the area around optic nerve head and its direction estimated from the available image. The Tsai discrete method has been employed to recover the 3D topographic map of the optic nerve head. The initial experimental result demonstrates our approach works on most of fundus images and provides a cheap, but good alternation for rendering and visualizing the topographic information of the optic nerve head for potential clinical use.

Application of phosphorescence quenching by O2 to the investigation of O2 delivery to ocular tissues

NASA Astrophysics Data System (ADS)

Chamot, Stephane R.; Petrig, Benno L.; Pournaras, Constantin J.; Percicot, Christine L.; Lambrou, George N.; Riva, Charles E.

2001-10-01

The technique of phosphorescence quenching by O2 (PQ) allows the non-invasive measurement of the partial pressure of oxygen in blood (pO2blood). This technique and its application to the investigation of the pO2blood in the microvasculature of the retina and optic nerve head (ONH) of two animal species is described. Using the imaging mode of PQ, 2-dimensional pO2blood maps were obtained to investigate the response of the pO2blood to various physiological stimuli in miniature pigs and the effect of experimental glaucoma in monkeys. Applied in its focal mode, PQ allows measurements of the pO2blood with a time resolution of 1 second and is adequate to investigate the pO2blood time course during light stimulation.

Farris-Tang retractor in optic nerve sheath decompression surgery.

PubMed

Spiegel, Jennifer A; Sokol, Jason A; Whittaker, Thomas J; Bernard, Benjamin; Farris, Bradley K

2016-01-01

Our purpose is to introduce the use of the Farris-Tang retractor in optic nerve sheath decompression surgery. The procedure of optic nerve sheath fenestration was reviewed at our tertiary care teaching hospital, including the use of the Farris-Tang retractor. Pseudotumor cerebri is a syndrome of increased intracranial pressure without a clear cause. Surgical treatment can be effective in cases in which medical therapy has failed and disc swelling with visual field loss progresses. Optic nerve sheath decompression surgery (ONDS) involves cutting slits or windows in the optic nerve sheath to allow cerebrospinal fluid to escape, reducing the pressure around the optic nerve. We introduce the Farris-Tang retractor, a retractor that allows for excellent visualization of the optic nerve sheath during this surgery, facilitating the fenestration of the sheath and visualization of the subsequent cerebrospinal fluid egress. Utilizing a medial conjunctival approach, the Farris-Tang retractor allows for easy retraction of the medial orbital tissue and reduces the incidence of orbital fat protrusion through Tenon's capsule. The Farris-Tang retractor allows safe, easy, and effective access to the optic nerve with good visualization in optic nerve sheath decompression surgery. This, in turn, allows for greater surgical efficiency and positive patient outcomes.

Optic Nerve Disorders

MedlinePlus

The optic nerve is a bundle of more than 1 million nerve fibers that carry visual messages. You have one connecting ... retina) to your brain. Damage to an optic nerve can cause vision loss. The type of vision ...

Synthesis of elastic microfibrillar components fibrillin-1 and fibrillin-2 by human optic nerve head astrocytes in situ and in vitro.

PubMed

Pena, J D; Mello, P A; Hernandez, M R

2000-05-01

The purpose of this study was to identify elastic microfibrillar components fibrillin-1 and fibrillin-2 in optic nerve heads of adult normal and glaucomatous subjects, in cultured optic nerve head astrocytes (type 1B astrocytes), as well as fibrillin-1 in fetal optic nerve heads. To characterize synthesis and gene expression of microfibrillar proteins in human optic nerve heads and cultured type 1B astrocytes, light microscopy immunohistochemistry, in situ hybridization, and RT-PCR or Northern blots were performed. Our results demonstrated that fibrillin-1 was associated with blood vessels, astrocytes in the glial columns and cribriform plates, and with astrocyte processes in the nerve bundles in all samples. In glaucomatous optic nerves there was enhanced fibrillin-1 immunoreactivity, especially surrounding blood vessels. Fibrillin-2 was localized primarily to blood vessels in all samples, without qualitative differences between normal and glaucomatous samples. In fetal optic nerve heads fibrillin-1 mRNA was localized to glial cells and to the blood vessel walls. In adult optic nerve heads, there was little fibrillin-1 mRNA as detectable by in situ hybridization and RT-PCR. There was no detectable upregulation of fibrillin-1 mRNA in glaucoma. In cultured type 1B astrocytes, fibrillin-1 staining was mostly pericellular. There was little fibrillin-2 immunoreactivity. In conclusion, astrocytes from the optic nerve head deposit elastic microfibrillar components in situ and in vitro, with a predominance of fibrillin-1. Upregulation of fibrillin-1 mRNA was not observed in glaucoma, suggesting that increased transcription may occur early in the disease process. Cultures of type 1B astrocytes from the optic nerve head provides a useful model to study mechanisms regulating the interactions of elastin and the microfibrils in optic nerve head astrocytes.

Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis

PubMed Central

Goodkin, Olivia; Altmann, Daniel R.; Jenkins, Thomas M.; Miszkiel, Katherine; Mirigliani, Alessia; Fini, Camilla; Gandini Wheeler-Kingshott, Claudia A. M.; Thompson, Alan J.; Ciccarelli, Olga; Toosy, Ahmed T.

2016-01-01

Abstract In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T 1 -weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients’ optic radiations decreased ( P = 0.018) and radial diffusivity increased ( P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year ( P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year ( P = 0.034 for both). Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration. PMID:26912640

[Pay attention on optical coherence tomography evaluation for optic nerve diseases].

PubMed

Wang, M

2016-12-11

Optical coherence tomography(OCT) had become the most important imaging technique in ophthalmology. OCT is able to segment the retinal nerve fiber layer and retinal ganglion cell layer accurately. Quantitative analysis can be performed for both layers. OCT is very important to evaluate the neuron and axon loss in optic nerve diseases diagnosis. Meanwhile, OCT has great value for differentiating glaucoma and macular diseases from optic nerve diseases. This review presented OCT application in optic nerve diseases diagnosis, differentiation diagnosis, the key points in use and the features of en face OCT and OCT angiography. It gave us suggestions that it should be pay more attention to OCT examination in diagnosis and treatment of optic nerve diseases. (Chin J Ophthalmol, 2016, 52: 885 - 888) .

[Glaucoma and optic nerve drusen: Limitations of optic nerve head OCT].

PubMed

Poli, M; Colange, J; Goutagny, B; Sellem, E

2017-09-01

Optic nerve head drusen are congenital calcium deposits located in the prelaminar section of the optic nerve head. Their association with visual field defects has been classically described, but the diagnosis of glaucoma is not easy in these cases of altered optic nerve head anatomy. We describe the case of a 67-year-old man with optic nerve head drusen complicated by glaucoma, which was confirmed by visual field and OCT examination of the peripapillary retinal nerve fiber layer (RNFL), but the measurement of the minimum distance between the Bruch membrane opening and the internal limiting membrane (minimum rim width, BMO-MRW) by OCT was normal. OCT of the BMO-MRW is a new diagnostic tool for glaucoma. Superficial optic nerve head drusen, which are found between the internal limiting membrane and the Bruch's membrane opening, overestimate the value of this parameter. BMO-MRW measurement is not adapted to cases of optic nerve head drusen and can cause false-negative results for this parameter, and the diagnosis of glaucoma in this case should be based on other parameters such as the presence of a fascicular defect in the retinal nerve fibers, RNFL or macular ganglion cell complex thinning, as well as visual field data. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

NASA Astrophysics Data System (ADS)

Anderson, David M. G.; Spraggins, Jeffrey M.; Rose, Kristie L.; Schey, Kevin L.

2015-06-01

The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

Continuous-wave infrared optical nerve stimulation for potential diagnostic applications

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Cilip, Christopher M.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2010-09-01

Optical nerve stimulation using infrared laser radiation has recently been developed as a potential alternative to electrical nerve stimulation. However, recent studies have focused primarily on pulsed delivery of the laser radiation and at relatively low pulse rates. The objective of this study is to demonstrate faster optical stimulation of the prostate cavernous nerves using continuous-wave (cw) infrared laser radiation for potential diagnostic applications. A thulium fiber laser (λ=1870 nm) is used for noncontact optical stimulation of the rat prostate cavernous nerves in vivo. Optical nerve stimulation, as measured by an intracavernous pressure (ICP) response in the penis, is achieved with the laser operating in either cw mode, or with a 5-ms pulse duration at 10, 20, 30, 40, 50, and 100 Hz. Successful optical stimulation is observed to be primarily dependent on a threshold nerve temperature (42 to 45 °C), rather than an incident fluence, as previously reported. cw optical nerve stimulation provides a significantly faster ICP response time using a lower power (and also less expensive) laser than pulsed stimulation. cw optical nerve stimulation may therefore represent an alternative mode of stimulation for intraoperative diagnostic applications where a rapid response is critical, such as identification of the cavernous nerves during prostate cancer surgery.

Ganglion Cell and Displaced Amacrine Cell Density Distribution in the Retina of the Howler Monkey (Alouatta caraya)

PubMed Central

Muniz, José Augusto Pereira Carneiro; de Athaide, Luana Modesto; Gomes, Bruno Duarte; Finlay, Barbara L.; Silveira, Luiz Carlos de Lima

2014-01-01

Unlike all other New World (platyrrine) monkeys, both male and female howler monkeys (Alouatta sp.) are obligatory trichromats. In all other platyrrines, only females can be trichromats, while males are always dichromats, as determined by multiple behavioral, electrophysiological, and genetic studies. In addition to obligatory trichromacy, Alouatta has an unusual fovea, with substantially higher peak cone density in the foveal pit than every other diurnal anthropoid monkey (both platyrrhines and catarrhines) and great ape yet examined, including humans. In addition to documenting the general organization of the retinal ganglion cell layer in Alouatta, the distribution of cones is compared to retinal ganglion cells, to explore possible relationships between their atypical trichromacy and foveal specialization. The number and distribution of retinal ganglion cells and displaced amacrine cells were determined in six flat-mounted retinas from five Alouatta caraya. Ganglion cell density peaked at 0.5 mm between the fovea and optic nerve head, reaching 40,700–45,200 cells/mm2. Displaced amacrine cell density distribution peaked between 0.5–1.75 mm from the fovea, reaching mean values between 2,050–3,100 cells/mm2. The mean number of ganglion cells was 1,133,000±79,000 cells and the mean number of displaced amacrine cells was 537,000±61,800 cells, in retinas of mean area 641±62 mm2. Ganglion cell and displaced amacrine cell density distribution in the Alouatta retina was consistent with that observed among several species of diurnal Anthropoidea, both platyrrhines and catarrhines. The principal alteration in the Alouatta retina appears not to be in the number of any retinal cell class, but rather a marked gradient in cone density within the fovea, which could potentially support high chromatic acuity in a restricted central region. PMID:25546077

Lamina Cribrosa Microarchitecture in Monkey Early Experimental Glaucoma: Global Change

PubMed Central

Reynaud, Juan; Lockwood, Howard; Gardiner, Stuart K.; Williams, Galen; Yang, Hongli; Burgoyne, Claude F.

2016-01-01

Purpose The purpose of this study was to characterize experimental glaucoma (EG) versus control eye differences in lamina cribrosa (LC), beam diameter (BD), pore diameter (PD), connective tissue volume fraction (CTVF), connective tissue volume (CTV), and LC volume (LV) in monkey early EG. Methods Optic nerve heads (ONHs) of 14 unilateral EG and 6 bilateral normal (BN) monkeys underwent three-dimensional reconstruction and LC beam segmentation. Each beam and pore voxel was assigned a diameter based on the largest sphere that contained it before transformation to a common cylinder with inner, middle, and outer layers. Full-thickness and layer averages for BD, PD, CTVF, CTV, and LV were calculated for each ONH. Beam diameter and PD distributions for each ONH were fit to a gamma distribution and summarized by scale and shape parameters. Experimental glaucoma and depth effects were assessed for each parameter by linear mixed-effects (LME) modeling. Animal-specific EG versus control eye differences that exceeded the maximum intereye difference among the six BN animals were considered significant. Results Overall EG eye mean PD was 12.8% larger (28.2 ± 5.6 vs. 25.0 ± 3.3 μm), CTV was 26.5% larger (100.06 ± 47.98 vs. 79.12 ± 28.35 × 106 μm3), and LV was 40% larger (229.29 ± 98.19 vs. 163.63 ± 39.87 × 106 μm3) than control eyes (P ≤ 0.05, LME). Experimental glaucoma effects were significantly different by layer for PD (P = 0.0097) and CTVF (P < 0.0001). Pore diameter expanded consistently across all PDs. Experimental glaucoma eye-specific parameter change was variable in magnitude and direction. Conclusions Pore diameter, CTV, and LV increase in monkey early EG; however, EG eye-specific change is variable and includes both increases and decreases in BD and CTVF. PMID:27362781

Continuous-wave vs. pulsed infrared laser stimulation of the rat prostate cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Cilip, Christopher M.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2011-03-01

Optical nerve stimulation has recently been developed as an alternative to electrical nerve stimulation. However, recent studies have focused primarily on pulsed delivery of the laser radiation and at relatively low pulse rates. The objective of this study is to demonstrate faster optical stimulation of the prostate cavernous nerves using continuouswave (CW) infrared laser radiation, for potential diagnostic applications. A Thulium fiber laser (λ = 1870 nm) was used for non-contact optical stimulation of the rat prostate cavernous nerves, in vivo. Optical nerve stimulation, as measured by an intracavernous pressure (ICP) response in the penis, was achieved with the laser operating in either CW mode, or with a 5-ms pulse duration at 10, 20, 30, 40, 50, and 100 Hz. Successful optical stimulation was observed to be primarily dependent on a threshold nerve temperature (42-45 °C), not an incident fluence, as previously reported. CW optical nerve stimulation provides a significantly faster ICP response time using a laser with lower power output than pulsed stimulation. CW optical nerve stimulation may therefore represent an alternative mode of stimulation for intra-operative diagnostic applications where a rapid response is critical, such as identification of the cavernous nerves during prostate cancer surgery.

An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

PubMed Central

Tang, Zhongshu; Zhang, Shuihua; Lee, Chunsik; Kumar, Anil; Arjunan, Pachiappan; Li, Yang; Zhang, Fan; Li, Xuri

2011-01-01

Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness. The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy. Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result. PMID:21540827

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

PubMed

Lim, Michele C; Tanimoto, Suzana A; Furlani, Bruno A; Lum, Brent; Pinto, Luciano M; Eliason, David; Prata, Tiago S; Brandt, James D; Morse, Lawrence S; Park, Susanna S; Melo, Luiz A S

2009-07-01

To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

OPTIC NERVE INFILTRATION BY RETINOBLASTOMA: Predictive Clinical Features and Outcome.

PubMed

Kaliki, Swathi; Tahiliani, Prerana; Mishra, Dilip K; Srinivasan, Visweswaran; Ali, Mohammed Hasnat; Reddy, Vijay Anand P

2016-06-01

To identify the clinical features predictive of any optic nerve infiltration and postlaminar optic nerve infiltration by retinoblastoma on histopathology and to report the outcome (metastasis and death) in these patients. Retrospective study. Of the 403 patients who underwent primary enucleation for retinoblastoma, 196 patients had optic nerve tumor infiltration (Group 1) and 207 patients had no evidence of optic nerve tumor infiltration (Group 2). Group 1 included patients with prelaminar (n = 47; 24%), laminar (n = 74; 38%), and postlaminar tumor infiltration with or without involving optic nerve transection (n = 74; 38%). Comparing Group 1 and Group 2, the patients in Group 1 had prolonged duration of symptoms (>6 months) (16% vs. 8%; P = 0.02) and were associated with no vision at presentation (23% vs. 10%; P = 0.01), higher rates of secondary glaucoma (42% vs. 12%; P < 0.0001), iris neovascularization (39% vs. 23%; P < 0.001), and larger tumors (mean tumor thickness, 12.8 mm vs. 12 mm; P = 0.0001). There was a higher prevalence of metastasis in Group 1 than in Group 2 (4% vs. 0%; P = 0.006). On multivariate analysis, clinical features predictive of any optic nerve tumor infiltration secondary glaucoma (hazard ratio = 5.38; P < 0.001) and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization (hazard ratio = 2.66; P = 0.001) and secondary glaucoma (hazard ratio = 3.13; P < 0.001). In this study, clinical features predictive of any optic nerve tumor infiltration included secondary glaucoma and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization and secondary glaucoma. Despite adjuvant treatment in those with postlaminar optic nerve tumor infiltration, metastasis occurred in 8% of patients.

Relationship Between Optic Nerve Appearance and Retinal Nerve Fiber Layer Thickness as Explored with Spectral Domain Optical Coherence Tomography

PubMed Central

Aleman, Tomas S.; Huang, Jiayan; Garrity, Sean T.; Carter, Stuart B.; Aleman, Wendy D.; Ying, Gui-shuang; Tamhankar, Madhura A.

2014-01-01

Purpose To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT). Methods Records from patients with spectral domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with refractive errors > 6D were excluded. Optic nerve appearance by slit lamp biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to visual field results. Results Ninety-one patients (176 eyes; mean age: 49 ± 15 years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average peripapillary RNFL thickness in eyes with pallor (mean ± SD = 76 ± 17 μm) was thinner compared to eyes without pallor (91 ± 14 μm, P < 0.001). Optic nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and specificity of 81%) when RNFL had thinned by ∼ 40%. Most patients with pallor had RNFL thinning with (66%) or without (25%) visual field loss; the remainder had normal RNFL and fields (5%) or with visual field abnormalities (4%). Conclusions Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and specificity, although it is optimally sensitive/specific only when substantial RNFL loss has occurred. Translational Relevance Finding an acceptable relationship between the optic nerve appearance by ophthalmoscopy and spectral domain-OCT RNFL measures will help the clinician's interpretation of the information provided by this technology, which is gaining momentum in neuro-ophthalmic research. PMID:25374773

[Basic and clinical studies of pressure-independent damaging factors of open angle glaucoma].

PubMed

Araie, Makoto

2011-03-01

Pathogenesis of open-angle glaucoma involves both pressure-dependent damaging factors and pressure-independent damaging factors. The high prevalence of open-angle glaucoma with normal pressure (normal-tension glaucoma) in Japan implies that treatment of pressure-independent damaging factors in Japanese open-angle glaucoma patients is of importance. In an attempt to investigate the roles of pressure-independent damaging factors in open-angle glaucoma, we carried out basic and clinical studies and obtained the following results. 1. The rate of deterioration of visual field after trabeculectomy in normal tension glaucoma patients with post-operative intraocular pressure (IOP) of 10 mmHg was found to be -0.25 dB/year of mean deviation (MD), suggesting that contribution of pressure-independent damaging factors to the deterioration of MD in open-angle glaucoma is around -0.25 dB/year of mean deviation (MD). 2. Experiments using isolated purified cultured retinal ganglion cells (RGCs) indicated that calcium-channel blockers and some of antiglaucoma drugs showed neuroprotective effects on RGCs at concentrations of 0.01 microM or higher. 3. In mice, damage to RGCs resulted in secondary degeneration of neurons and activation of glial cells in the lateral geniculate nucleous (LGN) and superior colliculus, and these secondary changes in the central nervous system (CNS) due to RGC damage was partly ameliorated by systemic administration of memantine. 4. Mice experimental high IOP glaucoma models could be established using laser irradiation of the limbal area, and the usefulness of Tonolab in IOP measurements of mice eye was confirmed. 5. Monkey experimental high IOP glaucoma models revealed that in the glaucomatous optic nerve head vaso-constrictive reactions to an alpha-1 agonist was abolished, while vasodilative reaction to a prostaglandin FP receptor agonist was retained. 6. In monkeys with experimental high IOP glaucoma, secondary damage to neurons in the LGN and the glial reaction to it were also found, similar to the mice experiments. In living monkeys the glial reaction in the LGN could be observed by means of positron emission tomography. 7. In the LGN of monkeys with experimental high IOP glaucoma, the M-cell system was preferentially damaged in the early stage, while in the later stages both the M- and P-cell systems were damaged. 8. In a single-instituted prospective double-blinded clinical trial, oral administration of nilvadipine at 4 mg/day, a DHP calcium-channel blocker, was found to significantly retard the visual field progression in normal tension glaucoma patients over 3 years, while significantly increasing the choroidal and optic nerve blood flow by about 35%. 9. A multi-instituted prospective double-blinded clinical trial in normal tension glaucoma patients revealed that the rate of MD deterioration under monotherapy with either topical nipradilol or timolol was around -0.05 dB/year, thought to be considerably slower than -0.25 dB/year, the commonly estimated rate of MD deterioration by pressure-independent damaging factors. The current results indicate the possibility of treatment of pressure-independent damaging factors of open-angle glaucoma in Japanese open-angle glaucoma patients with oral nilvadipine and topical anti-glaucoma agents.

A history of the optic nerve and its diseases.

PubMed

Reeves, C; Taylor, D

2004-11-01

We will trace the history of ideas about optic nerve anatomy and function in the Western world from the ancient Greeks to the early 20th century and show how these influenced causal theories of optic nerve diseases. Greek and Roman humoral physiology needed a hollow optic nerve, the obstruction of which prevented the flow of visual spirit to and from the brain and resulted in blindness. Medieval physicians understood that the presence of a fixed dilated pupil indicated optic nerve obstruction, preventing the passage of visual spirit, and that cataract surgery in such cases would not restore sight. During the Renaissance, the organ of vision was transferred from the lens to the optic nerve, which was generally believed to be on the axis of the eye. The acuity of central vision (at the optic disc) was explained by the concentration of visual spirit where the optic nerve met the retina. The growth of anatomy and influence of mechanical philosophy from the 17th century led to visual spirit being replaced with the concept of nerve force, which later became associated with electricity travelling along nerve fibres. This coincided with discourse about the nature of the nervous system and a shift in orientation from understanding illness holistically in terms of an individual's humoral imbalance to the concept of organ-based diseases. Both the microscope and the ophthalmoscope allowed visualisation of the optic nerve, but problems of interpretation persisted until conceptual transformations in medical science were made.

Quantitative characterization of optic nerve atrophy in patients with multiple sclerosis

PubMed Central

Smith, Alex K; Lyttle, Bailey; Box, Bailey; Landman, Bennett A; Bagnato, Francesca; Pawate, Siddharama; Smith, Seth A

2017-01-01

Background Optic neuritis (ON) is one of the most common presentations of multiple sclerosis (MS). Magnetic resonance imaging (MRI) of the optic nerves is challenging because of retrobulbar motion, orbital fat and susceptibility artifacts from maxillary sinuses; therefore, axonal loss is investigated with the surrogate measure of a single heuristically defined point along the nerve as opposed to volumetric investigation. Objective The objective of this paper is to derive optic nerve volumetrics along the entire nerve length in patients with MS and healthy controls in vivo using high-resolution, clinically viable MRI. Methods An advanced, isotropic T2-weighted turbo spin echo MRI was applied to 29 MS patients with (14 patients ON+) or without (15 patients ON–) history of ON and 42 healthy volunteers. An automated tool was used to estimate and compare whole optic nerve and surrounding cerebrospinal fluid radii along the length of the nerve. Results and conclusion Only ON+ MS patients had a significantly reduced optic nerve radius compared to healthy controls in the central segment of the optic nerve. Using clinically available MRI methods, we show and quantify ON volume loss for the first time in MS patients. PMID:28932410

Noncontact optical measurement of lens capsule thickness ex vivo

NASA Astrophysics Data System (ADS)

Ziebarth, Noel M.; Manns, Fabrice; Uhlhorn, Stephen; Parel, Jean-Marie

2004-07-01

Purpose: To design a non-contact optical system to measure lens capsule thickness in cadaver eyes. Methods: The optical system uses a 670nm laser beam delivered to a single-mode fiber coupler. The output of the fiber coupler is focused onto the tissue using an aspheric lens (NA=0.68) mounted on a motorized translation stage. Light reflected from the sample is collected by the fiber coupler and sent to a silicon photodiode connected to a power meter. Peaks in the power signal are detected when the focal point of the aspheric lens coincides with the capsule boundaries. The capsule thickness is proportional to the distance between successive peaks. Anterior and posterior lens capsule thickness measurements were performed on 13 human, 10 monkey, and 34 New Zealand white rabbit lenses. The cadaver eyes were prepared for optical measurements by bonding a PMMA ring on the sclera. The posterior pole was sectioned, excess vitreous was removed, and the eye was placed on a Teflon slide. The cornea and iris were then sectioned. After the experiments, the lenses were excised, placed in 10% buffered formalin, and prepared for histology. Results: Central anterior lens capsule thickness was 9.4+/-2.9μm (human), 11.2+/-6.6μm (monkey), and 10.3+/-3.6μm (rabbit) optically and 14.9+/-1.6μm (human), 17.7+/-4.9μm (monkey), and 12.6+/-2.3μm (rabbit) histologically. The values for the central posterior capsule were 9.4+/-2.9μm (human), 6.6+/-2.5μm (monkey), and 7.9+/-2.3μm (rabbit) optically and 4.6+/-1.4μm (human), 4.5+/-1.2μm (monkey), and 5.7+/-1.7μm (rabbit) histologically. Conclusions: This study demonstrates that a non-contact optical system can successfully measure lens capsule thickness in cadaver eyes.

An experimental vestibular neural prosthesis: design and preliminary results with rhesus monkeys stimulated with modulated pulses.

PubMed

Nie, Kaibao; Ling, Leo; Bierer, Steven M; Kaneko, Chris R S; Fuchs, Albert F; Oxford, Trey; Rubinstein, Jay T; Phillips, James O

2013-06-01

A vestibular neural prosthesis was designed on the basis of a cochlear implant for treatment of Meniere's disease and other vestibular disorders. Computer control software was developed to generate patterned pulse stimuli for exploring optimal parameters to activate the vestibular nerve. Two rhesus monkeys were implanted with the prototype vestibular prosthesis and they were behaviorally evaluated post implantation surgery. Horizontal and vertical eye movement responses to patterned electrical pulse stimulations were collected on both monkeys. Pulse amplitude modulated (PAM) and pulse rate modulated (PRM) trains were applied to the lateral canal of each implanted animal. Robust slow-phase nystagmus responses following the PAM or PRM modulation pattern were observed in both implanted monkeys in the direction consistent with the activation of the implanted canal. Both PAM and PRM pulse trains can elicit a significant amount of in-phase modulated eye velocity changes and they could potentially be used for efficiently coding head rotational signals in future vestibular neural prostheses.

Astigmatism in Monkeys with Experimentally Induced Myopia or Hyperopia

PubMed Central

KEE, CHEA-SU; HUNG, LI-FANG; QIAO-GRIDER, YING; RAMAMIRTHAM, RAMKUMAR; SMITH, EARL L.

2006-01-01

Purpose Astigmatism is the most common ametropia found in humans and is often associated with large spherical ametropias. However, little is known about the etiology of astigmatism or the reason(s) for the association between spherical and astigmatic refractive errors. This study examines the frequency and characteristics of astigmatism in infant monkeys that developed axial ametropias as a result of altered early visual experience. Methods Data were obtained from 112 rhesus monkeys that experienced a variety of lens-rearing regimens that were intended to alter the normal course of emmetropization. These visual manipulations included form deprivation (n = 13); optically imposed defocus (n = 48); and continuous ambient lighting with (n = 6) or without optically imposed defocus (n = 6). In addition, data from 19 control monkeys and 39 infants reared with an optically imposed astigmatism were used for comparison purposes. The lens-rearing period started at approximately 3 weeks of age and ended by 4 to 5 months of age. Refractive development for all monkeys was assessed periodically throughout the treatment and subsequent recovery periods by retinoscopy, keratometry, and A-scan ultrasonography. Results In contrast to control monkeys, the monkeys that had experimentally induced axial ametropias frequently developed significant amounts of astigmatism (mean refractive astigmatism = 0.37 ± 0.33 D [control] vs. 1.24 ± 0.81 D [treated]; two-sample t-test, p < 0.0001), especially when their eyes exhibited relative hyperopic shifts in refractive error. The astigmatism was corneal in origin (Pearson’s r; p < 0.001 for total astigmatism and the JO and J45 components), and the axes of the astigmatism were typically oblique and bilaterally mirror symmetric. Interestingly, the astigmatism was not permanent; the majority of the monkeys exhibited substantial reductions in the amount of astigmatism at or near the end of the lens-rearing procedures. Conclusions In infant monkeys, visual conditions that alter axial growth can also alter corneal shape. Similarities between the astigmatic errors in our monkeys and some astigmatic errors in humans suggest that vision-dependent changes in eye growth may contribute to astigmatism in humans. PMID:15829845

Regenerating Fish Optic Nerves and a Regeneration-Like Response in Injured Optic Nerves of Adult Rabbits

NASA Astrophysics Data System (ADS)

Schwartz, M.; Belkin, M.; Harel, A.; Solomon, A.; Lavie, V.; Hadani, M.; Rachailovich, I.; Stein-Izsak, C.

1985-05-01

Regeneration of fish optic nerve (representing regenerative central nervous system) was accompanied by increased activity of regeneration-triggering factors produced by nonneuronal cells. A graft of regenerating fish optic nerve, or a ``wrap-around'' implant containing medium conditioned by it, induced a response associated with regeneration in injured optic nerves of adult rabbits (representing a nonregenerative central nervous system). This response was manifested by an increase of general protein synthesis and of selective polypeptides in the retinas and by the ability of the retina to sprout in culture.

Optic Nerve Imaging

MedlinePlus

... About Us Donate In This Section Optic Nerve Imaging email Send this article to a friend by ... may use one of these optic nerve computer imaging techniques as part of your glaucoma examination. By ...

Biochronometry; Proceedings of the Symposium, Friday Harbor, Wash., September 4-6, 1969.

NASA Technical Reports Server (NTRS)

Menaker, M.

1971-01-01

Topics discussed include circadian activity rhythms in birds and man, variation of circadian rhythms in monkeys, resetting of circadian eclosion rhythm in fruitflies, the effectiveness of mathematical models of circadian rhythms, the influence of ac electric fields on circadian rhythms in man, the relation between changes in the metabolic rate and circadian periodicity of the resistance of pocket mice to ionizing radiation, the relation between circadian organization and the photoperiodic time measurement in moths, the circadian rhythm of optic nerve potentials in the isolated eye of the sea hare, phasing of circadian temperature rhythms in the pocket mouse by specific spectral regions, the phase-shifting effect of light on circadian rhymicity in the fruifly, hormonal control of circadian rhythms in the fruitfly, metabolically controlled temperature compensation in the circadian rhythm of algae, and circadian rhythms in the chloroplasts of algae. Individual items are abstracted in this issue.

High-resolution matrix-assisted laser desorption ionization–imaging mass spectrometry of lipids in rodent optic nerve tissue

PubMed Central

Anderson, David M. G.; Mills, Daniel; Spraggins, Jeffrey; Lambert, Wendi S.; Calkins, David J.

2013-01-01

Purpose To develop a method for generating high spatial resolution (10 µm) matrix-assisted laser desorption ionization (MALDI) images of lipids in rodent optic nerve tissue. Methods Ice-embedded optic nerve tissue from rats and mice were cryosectioned across the coronal and sagittal axes of the nerve fiber. Sections were thaw mounted on gold-coated MALDI plates and were washed with ammonium acetate to remove biologic salts before being coated in 2,5-dihydroxybenzoic acid by sublimation. MALDI images were generated in positive and negative ion modes at 10 µm spatial resolution. Lipid identification was performed with a high mass resolution Fourier transform ion cyclotron resonance mass spectrometer. Results Several lipid species were observed with high signal intensity in MALDI images of optic nerve tissue. Several lipids were localized to specific structures including in the meninges surrounding the optic nerve and in the central neuronal tissue. Specifically, phosphatidylcholine species were observed throughout the nerve tissue in positive ion mode while sulfatide species were observed in high abundance in the meninges surrounding the optic nerve in negative ion mode. Accurate mass measurements and fragmentation using sustained off-resonance irradiation with a high mass resolution Fourier transform ion cyclotron resonance mass spectrometer instrument allowed for identification of lipid species present in the small structure of the optic nerve directly from tissue sections. Conclusions An optimized sample preparation method provides excellent sensitivity for lipid species present within optic nerve tissue. This allowed the laser spot size and fluence to be reduced to obtain a high spatial resolution of 10 µm. This new imaging modality can now be applied to determine spatial and molecular changes in optic nerve tissue with disease. PMID:23559852

Evaluation of acute radiation optic neuropathy by B-scan ultrasonography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lovato, A.A.; Char, D.H.; Quivey, J.M.

1990-09-15

We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography.more » In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes.« less

Optic neuritis

MedlinePlus

... optic neuritis is unknown. The optic nerve carries visual information from your eye to the brain. The nerve can swell when it becomes suddenly ... may include: Color vision testing MRI of the brain , including special images of the optic nerve Visual acuity testing Visual field testing Examination of the ...

Neurophysiological intraoperative monitoring during an optic nerve schwannoma removal.

PubMed

San-Juan, Daniel; Escanio Cortés, Manuel; Tena-Suck, Martha; Orozco Garduño, Adolfo Josué; López Pizano, Jesús Alejandro; Villanueva Domínguez, Jonathan; Fernández Gónzalez-Aragón, Maricarmen; Gómez-Amador, Juan Luis

2017-10-01

This paper reports the case of a patient with optic nerve schwannoma and the first use of neurophysiological intraoperative monitoring of visual evoked potentials during the removal of such tumor with no postoperative visual damage. Schwannomas are benign neoplasms of the peripheral nervous system arising from the neural crest-derived Schwann cells, these tumors are rarely located in the optic nerve and the treatment consists on surgical removal leading to high risk of damage to the visual pathway. Case report of a thirty-year-old woman with an optic nerve schwannoma. The patient underwent surgery for tumor removal on the left optic nerve through a left orbitozygomatic approach with intraoperative monitoring of left II and III cranial nerves. We used Nicolet Endeavour CR IOM (Carefusion, Middleton WI, USA) to performed visual evoked potentials stimulating binocularly with LED flash goggles with the patient´s eyes closed and direct epidural optic nerve stimulation delivering rostral to the tumor a rectangular current pulse. At follow up examinations 7 months later, the left eye visual acuity was 20/60; Ishihara score was 8/8 in both eyes; the right eye photomotor reflex was normal and left eye was mydriatic and arreflectic; optokinetic reflex and ocular conjugate movements were normal. In this case, the epidural direct electrical stimulation of optic nerve provided stable waveforms during optic nerve schwannoma resection without visual loss.

Monochromatic ocular wave aberrations in young monkeys

PubMed Central

Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Roorda, Austin; Smith, Earl L.

2006-01-01

High-order monochromatic aberrations could potentially influence vision-dependent refractive development in a variety of ways. As a first step in understanding the effects of wave aberration on refractive development, we characterized the maturational changes that take place in the high-order aberrations of infant rhesus monkey eyes. Specifically, we compared the monochromatic wave aberrations of infant and adolescent animals and measured the longitudinal changes in the high-order aberrations of infant monkeys during the early period when emmetropization takes place. Our main findings were that (1) adolescent monkey eyes have excellent optical quality, exhibiting total RMS errors that were slightly better than those for adult human eyes that have the same numerical aperture and (2) shortly after birth, infant rhesus monkeys exhibited relatively larger magnitudes of high-order aberrations predominately spherical aberration, coma, and trefoil, which decreased rapidly to assume adolescent values by about 200 days of age. The results demonstrate that rhesus monkey eyes are a good model for studying the contribution of individual ocular components to the eye’s overall aberration structure, the mechanisms responsible for the improvements in optical quality that occur during early ocular development, and the effects of high-order aberrations on ocular growth and emmetropization. PMID:16750549

Haemodilution and head-down tilting induce functional injury in the rat optic nerve: A model for peri-operative ischemic optic neuropathy.

PubMed

Roth, Steven; Dreixler, John; Newman, Nancy J

2018-05-15

Mechanisms of peri-operative ischaemic optic neuropathy remain poorly understood. Both specific pre-operative and intra-operative factors have been examined by retrospective studies, but no animal model currently exists. To develop a rodent model of peri-operative ischaemic optic neuropathy. In rats, we performed head-down tilt and/or haemodilution, theorising that the combination damages the optic nerve. Animal study. Laboratory. A total of 36 rats, in four groups, completed the functional examination of retina and optic nerve after the interventions. Anaesthetised groups (n>8) were supine (SUP) for 5 h, head-down tilted 70° for 5 h, head-down tilted/haemodiluted for 5 h or SUP/haemodiluted for 5 h. We measured blood pressure, heart rate, intra-ocular pressure and maintained constant temperature. Retinal function (electroretinography), scotopic threshold response (STR) (for retinal ganglion cells) and visual evoked potentials (VEP) (for transmission through the optic nerve). We imaged the optic nerve in vivo and evaluated retinal histology, apoptotic cells and glial activation in the optic nerve. Retinal and optic nerve function were followed to 14 and 28 days after experiments. At 28 days in head down tilted/haemodiluted rats, negative STR decreased (about 50% amplitude reduction, P = 0.006), VEP wave N2-P3 decreased (70% amplitude reduction, P = 0.01) and P2 latency increased (35%, P = 0.003), optic discs were swollen and glial activation was present in the optic nerve. SUP/haemodiluted rats had decreases in negative STR and increased VEP latency, but no glial activation. An injury partly resembling human ischaemic optic neuropathy can be produced in rats by combining haemodilution and head-down tilt. Significant functional changes were also present with haemodilution alone. Future studies with this partial optic nerve injury may enable understanding of mechanisms of peri-operative ischaemic optic neuropathy and could help discover preventive or treatment strategies.

Experimental poliomyelitis in bonnet monkey. Clinical features, virology and pathology.

PubMed

Samuel, B U; Ponnuraj, E; Rajasingh, J; John, T J

1993-01-01

We have investigated the distribution of virus and the pathology in the spinal cords of bonnet monkeys (Macaca radiata) with experimental paralytic poliomyelitis induced by inoculating poliovirus type 1 (Mahoney) into the right ulnar nerve. Viraemia and alimentary tract infection due to the inoculated virus were found in all monkeys. Between two and seven days after the onset of limb paralysis, the animals were killed and the spinal cord examined. Virus was isolated from the cervical enlargement, thoracic region and lumbar enlargement in titres ranging from 10(2.5) to 10(6.4) TCID50/gram of tissue. Cellular infiltrate, perivascular cuffing, early and late neuronal damage such as chromatolysis, nuclear pyknosis, retraction of the cytoplasm and neuronophagia were seen distributed throughout the spinal cord. This experimental animal model resembles human paralytic poliomyelitis clinically and pathologically.

Analysis of optic disc change using the heidelberg retina tomograph in an acquired pit of the optic nerve.

PubMed

Oh, Joo Youn; Park, Ki Ho

2004-01-01

A 51-year-old woman diagnosed as having normal-tension glaucoma developed an acquired pit of the optic nerve. The optic disc was viewed by the Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany) before and after development of an acquired pit of the optic nerve. HRT parameters and cross-sectional images of the optic disc were compared. Maximum cup depth at the site of the acquired pit of the optic nerve increased after development of the acquired pit of the optic nerve (from 1.200 to 2.432 mm). The neuroretinal rim area and volume in the inferotemporal octant were reduced (rim area from 0.070 to 0.010 mm2, rim volume from 0.009 to 0.001 mm3). The morphologic changes in the optic disc were also detected topographically and reflectively.

Optic Nerve Assessment Using 7-Tesla Magnetic Resonance Imaging.

PubMed

Singh, Arun D; Platt, Sean M; Lystad, Lisa; Lowe, Mark; Oh, Sehong; Jones, Stephen E; Alzahrani, Yahya; Plesec, Thomas

2016-04-01

The purpose of this study was to correlate high-resolution magnetic resonance imaging (MRI) and histologic findings in a case of juxtapapillary choroidal melanoma with clinical evidence of optic nerve invasion. With institutional review board approval, an enucleated globe with choroidal melanoma and optic nerve invasion was imaged using a 7-tesla MRI followed by histopathologic evaluation. Optical coherence tomography, B-scan ultrasonography, and 1.5-tesla MRI of the orbit (1-mm sections) could not detect optic disc invasion. Ex vivo, 7-tesla MRI detected optic nerve invasion, which correlated with histopathologic features. Our case demonstrates the potential to document the existence of optic nerve invasion in the presence of an intraocular tumor, a feature that has a major bearing on decision making, particularly for consideration of enucleation.

Eye Involvement in TSC

MedlinePlus

... what we see to the brain via the optic nerve. Retinal and optic nerve involvement in TSC are well known today, ... hamartomas (non-cancerous tumors) of the retina or optic nerve. The most common type of retinal hamartoma ...

Transnasal Endoscopic Optic Nerve Decompression in Post Traumatic Optic Neuropathy.

PubMed

Gupta, Devang; Gadodia, Monica

2018-03-01

To quantify the successful outcome in patients following optic nerve decompression in post traumatic unilateral optic neuropathy in form of improvement in visual acuity. A prospective study was carried out over a period of 5 years (January 2011 to June 2016) at civil hospital Ahmedabad. Total 20 patients were selected with optic neuropathy including patients with direct and indirect trauma to unilateral optic nerve, not responding to conservative management, leading to optic neuropathy and subsequent impairment in vision and blindness. Decompression was done via Transnasal-Ethmo-sphenoidal route and outcome was assessed in form of post-operative visual acuity improvement at 1 month, 6 months and 1 year follow up. After surgical decompression complete recovery of visual acuity was achieved in 16 (80%) patients and partial recovery in 4 (20%). Endoscopic transnasal approach is beneficial in traumatic optic neuropathy not responding to steroid therapy and can prevent permanent disability if earlier intervention is done prior to irreversible damage to the nerve. Endoscopic optic nerve surgery can decompress the traumatic and oedematous optic nerve with proper exposure of orbital apex and optic canal without any major intracranial, intraorbital and transnasal complications.

Ultrastructure of free-ending nerve fibres in oesophageal epithelium.

PubMed Central

Robles-Chillida, E M; Rodrigo, J; Mayo, I; Arnedo, A; Gómez, A

1981-01-01

For the first time, at the ultrastructural level, the existence of free-ending, intraepithelial nerve fibres has been demonstrated in the oesophagus wall of adult cats and monkeys. Their form, the way they penetrate the epithelium, their location within the epithelium and their relationships with neighbouring cells have been established. A sensory function is suggested for this type of ending. Images Figs. 1-4 Figs. 5-6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Figs. 14-15 Figs. 16-17 PMID:7333951

Meningiomas involving the optic nerve: technical aspects and outcomes for a series of 50 patients.

PubMed

Margalit, Nevo S; Lesser, Jonathan B; Moche, Jason; Sen, Chandranath

2003-09-01

Surgical strategies and results for 50 patients with meningiomas involving the optic nerves are discussed and evaluated. Factors affecting the degree of resection and patient outcomes are presented. We emphasize our surgical techniques for resection of these tumors and we discuss the advantages of different approaches, depending on the relationship of the tumor to the optic nerves. Data for 50 patients with meningiomas involving the optic nerves who were surgically treated between 1991 and 2002 were reviewed, by using patient files, operative notes, and pre- and postoperative imaging and ophthalmological examination findings. Thirty-one female patients and 19 male patients, with a mean age of 53 years, were treated. Thirty-one patients (62%) underwent complete tumor removal (Simpson Grade 1 or 2), and 19 patients underwent subtotal removal (Grade 4). Factors affecting the grade of resection were tumor size (P = 0.01), location (P = 0.007), and internal carotid artery encasement (P = 0.019). Patients who underwent Grade 1 or 2 resection exhibited a mean tumor size of 3.0 cm, and patients who underwent Grade 4 resection exhibited a mean tumor size of 4.1 cm. Only three patients had residual tumor on the optic nerve; all others had tumor in the cavernous sinus or at the orbital apex or exhibited vascular involvement. Visual outcomes were influenced predominantly by tumor size, preoperative visual function, and optic nerve encasement. Meningiomas that involve the optic nerves require special considerations and surgical techniques. Early decompression of the optic nerve within the bony canal allows identification and separation of the tumor from the nerve, permitting removal of the tumor from this area with minimal manipulation of the optic nerve.

Magnetic resonance diffusion tensor imaging of optic nerve and optic radiation in healthy adults at 3T.

PubMed

Sun, Hong-Hong; Wang, Dong; Zhang, Qiu-Juan; Bai, Zhi-Lan; He, Ping

2013-01-01

To investigate the diffusion characteristics of water of optic nerve and optic radiation in healthy adults and its related factors by diffusion tensor imaging (DTI) at 3T. A total of 107 healthy volunteers performed head conventional MRI and bilateral optic nerve and optic radiation DTI. The primary data of DTI was processed by post-processing software of DTI studio 2.3, obtaining fractional anisotropy value, mean diffusivity value, principal engine value, orthogonal engine value by measuring, and analyzed by the SPSS13.0 statistical software. The bilateral optic nerve and optic radiation fibers presented green color in directional encoded color (DEC) maps and presented high signal in fractional anisotropy (FA) maps. The FA value of the left optic nerve was 0.598±0.069 and the right was 0.593±0.065; the mean diffusivity (MD) value of the left optic nerve was (1.324±0.349)×10(-3)mm(2)/s and the right was (1.312±0.350)×10(-3)mm(2)/s; the principal engine value (λ‖) of the left optic nerve was (2.297±0.522)×10(-3)mm(2)/s and the right was (2.277±0.526)×10(-3)mm(2)/s; the orthogonal engine value (λ⊥) of the left optic nerve was (0.838±0.285)×10(-3)mm(2)/s and the right was (0.830±0.280)×10(-3)mm(2)/s; the FA value of the left optic radiation was 0.636±0.057 and the right was 0.628±0.056; the mean diffusivity (MD) value of the left optic radiation was (0.907±0.103)×10(-3)mm(2)/s and the right was (0.889±0.125)×10(-3)mm(2)/s; the principal eigenvalue (λ‖) of the left optic radiation was (1.655±0.210)×10(-3)mm(2)/s and the right was (1.614±0.171)×10(-3)mm(2)/s; the orthogonal enginvalue (λ⊥) of the left optic radiation was (0.531±0.103)×10(-3)mm(2)/s and the right was (0.524±0.152)×10(-3)mm(2)/s. There was no obvious difference between the FA, MD, λ‖, λ⊥ of the bilateral optic radiation and the bilateral optic nerve (P>0.05) and no obvious difference between male and female group. The FA, MD, λ‖, λ⊥ of the bilateral optic radiation and the bilateral optic nerve had no obvious correlations to the age. DTI is sensitive to the optic nerve and radiation and the relevant DTI parameters of the optic nerve and radiation are established preliminarily in this study.

Nicotine-mediated improvement in L-dopa-induced dyskinesias in MPTP-lesioned monkeys is dependent on dopamine nerve terminal function.

PubMed

Quik, Maryka; Mallela, Archana; Chin, Matthew; McIntosh, J Michael; Perez, Xiomara A; Bordia, Tanuja

2013-02-01

L-dopa-induced dyskinesias (LIDs) are abnormal involuntary movements that develop with long term L-dopa therapy for Parkinson's disease. Studies show that nicotine administration reduced LIDs in several parkinsonian animal models. The present work was done to understand the factors that regulate the nicotine-mediated reduction in LIDs in MPTP-lesioned nonhuman primates. To approach this, we used two groups of monkeys, one with mild-moderate and the other with more severe parkinsonism rendered dyskinetic using L-dopa. In mild-moderately parkinsonian monkeys, nicotine pretreatment (300 μg/ml via drinking water) prevented the development of LIDs by ~75%. This improvement was maintained when the nicotine dose was lowered to 50 μg/ml but was lost with nicotine removal. Nicotine re-exposure again decreased LIDs. By contrast, nicotine treatment did not reduce LIDs in monkeys with more severe parkinsonism. We next determined how nicotine's ability to reduce LIDs correlated with lesion-induced changes in the striatal dopamine transporter and (3)H-dopamine release in these two groups of monkeys. The striatal dopamine transporter was reduced to 54% and 28% of control in mild-moderately and more severely parkinsonian monkeys, respectively. However, basal, K(+), α4β2* and α6β2* nAChR-evoked (3)H-dopamine release were near control levels in striatum of mild-moderately parkinsonian monkeys. By contrast, these same release measures were reduced to a significantly greater extent in striatum of more severely parkinsonian monkeys. Thus, nicotine best improves LIDs in lesioned monkeys in which striatal dopamine transmission is still relatively intact. These data suggest that nicotine treatment would most effectively reduce LIDs in patients with mild to moderate Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Astrocytes in the optic nerve head express putative mechanosensitive channels

PubMed Central

Choi, Hee Joo; Sun, Daniel

2015-01-01

Purpose To establish whether optic nerve head astrocytes express candidate molecules to sense tissue stretch. Methods We used conventional PCR, quantitative PCR, and single-cell reverse transcription PCR (RT–PCR) to assess the expression of various members of the transient receptor potential (TRP) channel family and of the recently characterized mechanosensitive channels Piezo1 and 2 in optic nerve head tissue and in single, isolated astrocytes. Results Most TRP subfamilies (TRPC, TRPM, TRPV, TRPA, and TRPP) and Piezo1 and 2 were expressed in the optic nerve head of the mouse. Quantitative real-time PCR analysis showed that TRPC1, TRPM7, TRPV2, TRPP2, and Piezo1 are the dominant isoforms in each subfamily. Single-cell RT–PCR revealed that many TRP isoforms, TRPC1–2, TRPC6, TRPV2, TRPV4, TRPM2, TRPM4, TRPM6–7, TRPP1–2, and Piezo1–2, are expressed in astrocytes of the optic nerve head, and that most astrocytes express TRPC1 and TRPP1–2. Comparisons of the TRPP and Piezo expression levels between different tissue regions showed that Piezo2 expression was higher in the optic nerve head and the optic nerve proper than in the brain and the corpus callosum. TRPP2 also showed higher expression in the optic nerve head. Conclusions Astrocytes in the optic nerve head express multiple putative mechanosensitive channels, in particular the recently identified channels Piezo1 and 2. The expression of putative mechanosensitive channels in these cells may contribute to their responsiveness to traumatic or glaucomatous injury. PMID:26236150

Expansions of the Neurovascular Scleral Canal and Contained Optic Nerve Occur Early in the Hypertonic Saline Rat Experimental Glaucoma Model

PubMed Central

Pazos, Marta; Yang, Hongli; Gardiner, Stuart K.; Cepurna, W.O.; Johnson, E.C.; Morrison, J.C.; Burgoyne, Claude F.

2015-01-01

Purpose To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Methods Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONH’s with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Results Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p<.0022), and in 7 of 8 EG eyes (p<.005). In at least 5 EG eyes, significant expansions (p<.005) in Bruch’s membrane opening (range 3–10%), the anterior and posterior scleral canal openings (8–21% and 5–21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11–30% and 8–41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R= 0.768, P=.042). Conclusion In the rat ONH, the optic nerve and surrounding Bruch’s membrane opening and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. PMID:26500195

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model.

PubMed

Pazos, Marta; Yang, Hongli; Gardiner, Stuart K; Cepurna, William O; Johnson, Elaine C; Morrison, John C; Burgoyne, Claude F

2016-04-01

To characterize early optic nerve head (ONH) structural change in rat experimental glaucoma (EG). Unilateral intraocular pressure (IOP) elevation was induced in Brown Norway rats by hypertonic saline injection into the episcleral veins and animals were sacrificed 4 weeks later by perfusion fixation. Optic nerve cross-sections were graded from 1 (normal) to 5 (extensive injury) by 5 masked observers. ONHs with peripapillary retina and sclera were embedded, serial sectioned, 3-D reconstructed, delineated, and quantified. Overall and animal-specific EG versus Control eye ONH parameter differences were assessed globally and regionally by linear mixed effect models with significance criteria adjusted for multiple comparisons. Expansions of the optic nerve and surrounding anterior scleral canal opening achieved statistical significance overall (p < 0.0022), and in 7 of 8 EG eyes (p < 0.005). In at least 5 EG eyes, significant expansions (p < 0.005) in Bruch's membrane opening (BMO) (range 3-10%), the anterior and posterior scleral canal openings (8-21% and 5-21%, respectively), and the optic nerve at the anterior and posterior scleral canal openings (11-30% and 8-41%, respectively) were detected. Optic nerve expansion was greatest within the superior and inferior quadrants. Optic nerve expansion at the posterior scleral canal opening was significantly correlated to optic nerve damage (R = 0.768, p = 0.042). In the rat ONH, the optic nerve and surrounding BMO and neurovascular scleral canal expand early in their response to chronic experimental IOP elevation. These findings provide phenotypic landmarks and imaging targets for detecting the development of experimental glaucomatous optic neuropathy in the rat eye. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optic Nerve Assessment Using 7-Tesla Magnetic Resonance Imaging

PubMed Central

Singh, Arun D.; Platt, Sean M.; Lystad, Lisa; Lowe, Mark; Oh, Sehong; Jones, Stephen E.; Alzahrani, Yahya; Plesec, Thomas

2016-01-01

Purpose The purpose of this study was to correlate high-resolution magnetic resonance imaging (MRI) and histologic findings in a case of juxtapapillary choroidal melanoma with clinical evidence of optic nerve invasion. Methods With institutional review board approval, an enucleated globe with choroidal melanoma and optic nerve invasion was imaged using a 7-tesla MRI followed by histopathologic evaluation. Results Optical coherence tomography, B-scan ultrasonography, and 1.5-tesla MRI of the orbit (1-mm sections) could not detect optic disc invasion. Ex vivo, 7-tesla MRI detected optic nerve invasion, which correlated with histopathologic features. Conclusions Our case demonstrates the potential to document the existence of optic nerve invasion in the presence of an intraocular tumor, a feature that has a major bearing on decision making, particularly for consideration of enucleation. PMID:27239461

Endoscopic Endonasal Optic Nerve Decompression for Fibrous Dysplasia

PubMed Central

DeKlotz, Timothy R.; Stefko, S. Tonya; Fernandez-Miranda, Juan C.; Gardner, Paul A.; Snyderman, Carl H.; Wang, Eric W.

2016-01-01

Objective To evaluate visual outcomes and potential complications for optic nerve decompression using an endoscopic endonasal approach (EEA) for fibrous dysplasia. Design Retrospective chart review of patients with fibrous dysplasia causing extrinsic compression of the canalicular segment of the optic nerve that underwent an endoscopic endonasal optic nerve decompression at the University of Pittsburgh Medical Center from 2010 to 2013. Main Outcome Measures The primary outcome measure assessed was best-corrected visual acuity (BCVA) with secondary outcomes, including visual field testing, color vision, and complications associated with the intervention. Results A total of four patients and five optic nerves were decompressed via an EEA. All patients were symptomatic preoperatively and had objective findings compatible with compressive optic neuropathy: decreased visual acuity was noted preoperatively in three patients while the remaining patient demonstrated an afferent pupillary defect. BCVA improved in all patients postoperatively. No major complications were identified. Conclusion EEA for optic nerve decompression appears to be a safe and effective treatment for patients with compressive optic neuropathy secondary to fibrous dysplasia. Further studies are required to identify selection criteria for an open versus an endoscopic approach. PMID:28180039

Visual abnormalities associated with enhanced optic nerve myelination.

PubMed

Yu, Minzhong; Narayanan, S Priyadarshini; Wang, Feng; Morse, Emily; Macklin, Wendy B; Peachey, Neal S

2011-02-16

Expression of the constitutively active serine/threonine kinase Akt in oligodendrocytes results in enhanced myelination in the CNS. Here, we have examined the effects of this Akt overexpression on optic nerve structure and on optic nerve function, assessed using the visual evoked potential (VEP). Transgenic mice have been generated with the Plp promoter driving expression of a modified form of Akt, in which aspartic acids are substituted for Thr308 and Ser473. These Plp-Akt-DD (Akt-DD) mice, and littermate controls, were studied at different ages. Optic nerves were examined anatomically at 2 and 6 months of age. At 2 months of age, optic nerves were substantially thicker in Akt-DD mice, reflecting an increase in myelination of optic nerve axons. By electron microscopy, myelin thickness was increased in Akt-DD optic nerve, with extended paranodal domains having excess paranodal loops, and the density of nodes of Ranvier was reduced, relative to control mice. We recorded VEPs in response to strobe flash ganzfeld stimuli presented after overnight dark- and light-adapted conditions at ages ranging from 1 to 10 months. It was possible to record a clear VEP from Akt-DD mice at all ages examined. At 1 month of age, VEP implicit times were somewhat shorter in Akt-DD transgenic mice than in control animals. Beyond 6months of age, VEP latencies were consistently delayed in Akt-DD transgenic mice. These abnormalities did not reflect an alteration in retinal function as there were no significant differences between ERGs obtained from control or Akt-DD transgenic mice. In young mice, the somewhat faster responses may reflect improved transmission due to increased myelination of optic nerve axons. In older mice, where the Akt-DD optic nerve is markedly thicker than control, it is remarkable that optic nerves continue to function. Copyright © 2010 Elsevier B.V. All rights reserved.

Optic nerve involvement in childhood onset systemic lupus erythematosus: Three cases and a review of the literature.

PubMed

Suri, D; Abujam, B; Gupta, A; Rawat, A; Saikia, B; Walker Minz, R; Gupta, V; Bansal, R; Kaushik, S; Singh, S

2016-01-01

The ocular system can be affected in systemic lupus erythematosus (SLE) in one third of patients. However, optic nerve involvement is relatively uncommon, but is more so in pediatric SLE patients, where it can occur in 1% of cases. We report three children with SLE who presented with optic nerve involvement. Two children had optic neuritis, with optic neuritis being the first manifestation in one child. The third child had ischaemic optic neuropathy secondary to antiphospholipid syndrome. A careful work up for SLE should be performed in every child with optic nerve disease. Prompt diagnosis and early treatment results in a better prognosis. © The Author(s) 2015.

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

2009-02-01

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

Species and sex differences in susceptibility to olfactory lesions among the mouse, rat and monkey following an intravenous injection of vincristine sulphate.

PubMed

Kai, Kiyonori; Sahto, Hiroshi; Yoshida, Mitsuyoshi; Suzuki, Takami; Shikanai, Yukari; Kajimura, Tetsuyo; Furuhama, Kazuhisa

2006-01-01

Species and sex differences in susceptibility to vincristine sulphate (VCR)-induced olfactory epithelial lesions were investigated among the BALB/c mice, Crj: CD(SD) IGS rats and common marmoset monkeys following a single intravenous administration on day 1. As dosage levels, the 0.17-fold LD10, 0.6-fold LD10 and LD10 were used for mice and rats, and a maximum tolerated dose (MTD) was chosen only for monkeys. The order of strength of VCR action on peripheral neuropathic signs, body weight gain, and hematological parameters was mice > rats > monkeys, without clear sex differences. Histopathologically, on day 2, single cell death in the olfactory epithelium and vomeronasal organ was observed only in male mice at LD10, and in female mice at 0.6-fold LD10 or more. On day 5, the olfactory epithelium in these mice showed regenerative proliferation suggesting a sign of recovery. On day 10, axonopathy and demyelination in the sciatic and trigeminal nerves were noted in mice of both sexes at 0.6-fold LD10 or more. In rats and monkeys of either sex, however, no morphological changes were observed at any dose level. In conclusion, mice, particularly females, were shown to be more susceptible to VCR-induced apoptosis in the olfactory epithelium than rats and monkeys.

Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parsons, J.T.; Bova, F.J.; Million, R.R.

1994-11-15

To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 andmore » 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.« less

Axonal loss from acute optic neuropathy documented by scanning laser polarimetry

PubMed Central

Meier, F M; Bernasconi, P; Stürmer, J; Caubergh, M-J; Landau, K

2002-01-01

Background/aims: Retinal nerve fibre layer analysis by scanning laser polarimetry has been shown to facilitate diagnosis of glaucoma while its role in glaucoma follow up is still unclear. A major difficulty is the slow reduction of retinal nerve fibre layer thickness in glaucomatous optic neuropathy. Eyes of patients were studied after acute retrobulbar optic nerve lesion in order to evaluate the usefulness of scanning laser polarimetry in documenting retinal nerve fibre layer loss over time. Methods: Five patients who suffered severe retrobulbar optic neuropathy have had repeated measurements of the retinal nerve fibre layer using scanning laser polarimetry at various intervals, the first examination being within 1 week of injury. Results: All eyes showed a marked decrease in peripapillary retinal nerve fibre layer thickness, which followed an exponential curve and occurred predominantly within 8 weeks of injury. Compared to a previous study using red-free photographs, scanning laser polarimetry showed retinal nerve fibre layer loss earlier in the course of descending atrophy. Conclusion: Scanning laser polarimetry is useful for early detection and documentation of retinal nerve fibre layer loss following acute injury to the retrobulbar optic nerve. It seems to be a promising tool for follow up of individual glaucoma patients. PMID:11864884

Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms

PubMed Central

Parrilla, Marta; León-Lobera, Fernando; Lillo, Concepción; Arévalo, Rosario; Aijón, José; Lara, Juan Manuel; Velasco, Almudena

2016-01-01

The mammalian central nervous system (CNS) is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP), as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes. PMID:27149509

Different effects of astrocytes and Schwann cells on regenerating retinal axons.

PubMed

Campbell, Gregor; Kitching, Juliet; Anderson, Patrick N; Lieberman, A Robert

2003-11-14

Following a crush injury of the optic nerve in adult rats, the axons of retinal ganglion cells, stimulated to regenerate by a lens injury and growing within the optic nerve, are associated predominantly with astrocytes: they remain of small diameter (0.1-0.5 microm) and unmyelinated for > or = 2 months after the operation. In contrast, when the optic nerve is cut and a segment of a peripheral nerve is grafted to the ocular stump of the optic nerve, the regenerating retinal axons are associated predominantly with Schwann cells: they are of larger diameter than in the previous experiment and include unmyelinated axons (0.2-2.5 microm) and myelinated axons (mean diameter 2.3 microm). Thus, the grafted peripheral nerve, and presumably its Schwann cells, stimulate enlargement of the regenerating retinal axons leading to partial myelination, whereas the injured optic nerve itself, and presumably its astrocytes, does not. The result points to a marked difference of peripheral (Schwann cells) and central (astrocytes) glia in their effect on regenerating retinal axons.

Astrocytes as gate-keepers in optic nerve regeneration--a mini-review.

PubMed

García, Dana M; Koke, Joseph R

2009-02-01

Animals that develop without extra-embryonic membranes (anamniotes--fish, amphibians) have impressive regenerative capacity, even to the extent of replacing entire limbs. In contrast, animals that develop within extra-embryonic membranes (amniotes--reptiles, birds, mammals) have limited capacity for regeneration as adults, particularly in the central nervous system (CNS). Much is known about the process of nerve development in fish and mammals and about regeneration after lesions in the CNS in fish and mammals. Because the retina of the eye and optic nerve are functionally part of the brain and are accessible in fish, frogs, and mice, optic nerve lesion and regeneration (ONR) has been extensively used as a model system for study of CNS nerve regeneration. When the optic nerve of a mouse is severed, the axons leading into the brain degenerate. Initially, the cut end of the axons on the proximal, eye-side of the injury sprout neurites which begin to grow into the lesion. Simultaneously, astrocytes of the optic nerve become activated to initiate wound repair as a first step in reestablishing the structural integrity of the optic nerve. This activation appears to initiate a cascade of molecular signals resulting in apoptotic cell death of the retinal ganglion cells axons of which make up the neural component of the optic nerve; regeneration fails and the injury is permanent. Evidence specifically implicating astrocytes comes from studies showing selective poisoning of astrocytes at the optic nerve lesion, along with activation of a gene whose product blocks apoptosis in retinal ganglion cells, creates conditions favorable to neurites sprouting from the cut proximal stump, growing through the lesion and into the distal portion of the injured nerve, eventually reaching appropriate targets in the brain. In anamniotes, astrocytes ostensibly present no such obstacle since optic nerve regeneration occurs without intervention; however, no systematic study of glial involvement has been done. In fish, vigorously growing neurites sprout from the cut axons and within a few days begin to re-enervate the brain. This review offers a new perspective on the role of glia, particularly astrocytes, as "gate-keepers;" i.e., as being permissive or inhibitory, by comparison between fish and mammals of glial function during ONR.

Evolution of optic nerve photography for glaucoma screening: a review.

PubMed

Myers, Jonathan S; Fudemberg, Scott J; Lee, Daniel

2018-03-01

Visual evaluation of the optic nerve has been one of the earliest and most widely used methods to evaluate patients for glaucoma. Photography has proven very useful for documentation of the nerve's appearance at a given time, allowing more detailed scrutiny then, and later comparison for change. Photography serves as the basis for real-time or non-simultaneous review in telemedicine and screening events allowing fundus and optic nerve evaluation by experts elsewhere. Expert evaluation of disc photographs has shown diagnostic performance similar to other methods of optic nerve evaluation for glaucoma. Newer technology has made optic nerve photography simpler, cheaper and more portable creating opportunities for broader utilization in screening in underserved populations by non-physicians. Recent investigations suggest that non-physicians or software algorithms for disc photograph evaluation have promise to allow more screening to be done with fewer experts. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

High resolution ultrasound and magnetic resonance imaging of the optic nerve and the optic nerve sheath: anatomic correlation and clinical importance.

PubMed

Steinborn, M; Fiegler, J; Kraus, V; Denne, C; Hapfelmeier, A; Wurzinger, L; Hahn, H

2011-12-01

We performed a cadaver study to evaluate the accuracy of measurements of the optic nerve and the optic nerve sheath for high resolution US (HRUS) and magnetic resonance imaging (MRI). Five Thiel-fixated cadaver specimens of the optic nerve were examined with HRUS and MRI. Measurements of the optic nerve and the ONSD were performed before and after the filling of the optic nerve sheath with saline solution. Statistical analysis included the calculation of the agreement of measurements and the evaluation of the intraobserver and interobserver variation. Overall a good correlation of measurement values between HRUS and MRI can be found (mean difference: 0.02-0.97 mm). The repeatability coefficient (RC) and concordance correlation coefficient (CCC) values were good to excellent for most acquisitions (RC 0.2-1.11 mm; CCC 0.684-0.949). The highest variation of measurement values was found for transbulbar sonography (RC 0.58-1.83 mm; CCC 0.615/0.608). If decisive anatomic structures are clearly depicted and the measuring points are set correctly, there is a good correlation between HRUS and MRI measurements of the optic nerve and the ONSD even on transbulbar sonography. As most of the standard and cut-off values that have been published for ultrasound are significantly lower than the results obtained with MRI, a reevaluation of sonographic ONSD measurement with correlation to MRI is necessary. © Georg Thieme Verlag KG Stuttgart · New York.

Acquired pit of the optic nerve: a risk factor for progression of glaucoma.

PubMed

Ugurlu, S; Weitzman, M; Nduaguba, C; Caprioli, J

1998-04-01

To examine acquired pit of the optic nerve as a risk factor for progression of glaucoma. In a retrospective longitudinal study, 25 open-angle glaucoma patients with acquired pit of the optic nerve were compared with a group of 24 open-angle glaucoma patients without acquired pit of the optic nerve. The patients were matched for age, mean intraocular pressure, baseline ratio of neuroretinal rim area to disk area, visual field damage, and duration of follow-up. Serial optic disk photographs and visual fields of both groups were evaluated by three independent observers for glaucomatous progression. Of 46 acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk damage occurred in 16 patients (64%) in the group with acquired pit and in three patients (12.5%) in the group without acquired pit (P < .001). Progression of visual field loss occurred in 14 patients (56%) in the group with acquired pit and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more frequently in the group with acquired pit (10 eyes, 40%) compared with the group without pit (two eyes, 8%; P=.02). Among patients with glaucoma, patients with acquired pit of the optic nerve represent a subgroup who are at increased risk for progressive optic disk damage and visual field loss.

Long-term optical imaging of intrinsic signals in anesthetized and awake monkeys

NASA Astrophysics Data System (ADS)

Roe, Anna W.

2007-04-01

Some exciting new efforts to use intrinsic signal optical imaging methods for long-term studies in anesthetized and awake monkeys are reviewed. The development of such methodologies opens the door for studying behavioral states such as attention, motivation, memory, emotion, and other higher-order cognitive functions. Long-term imaging is also ideal for studying changes in the brain that accompany development, plasticity, and learning. Although intrinsic imaging lacks the temporal resolution offered by dyes, it is a high spatial resolution imaging method that does not require application of any external agents to the brain. The bulk of procedures described here have been developed in the monkey but can be applied to the study of surface structures in any in vivo preparation.

Supraorbital keyhole surgery for optic nerve decompression and dura repair.

PubMed

Chen, Yuan-Hao; Lin, Shinn-Zong; Chiang, Yung-Hsiao; Ju, Da-Tong; Liu, Ming-Ying; Chen, Guann-Juh

2004-07-01

Supraorbital keyhole surgery is a limited surgical procedure with reduced traumatic manipulation of tissue and entailing little time in the opening and closing of wounds. We utilized the approach to treat head injury patients complicated with optic nerve compression and cerebrospinal fluid leakage (CSF). Eleven cases of basal skull fracture complicated with either optic nerve compression and/or CSF leakage were surgically treated at our department from February 1995 to June 1999. Six cases had primary optic nerve compression, four had CSF leakage and one case involved both injuries. Supraorbital craniotomy was carried out using a keyhole-sized burr hole plus a small craniotomy. The size of craniotomy approximated 2 x 3 cm2. The optic nerve was decompressed via removal of the optic canal roof and anterior clinoid process with high-speed drills. The defect of dura was repaired with two pieces of tensa fascia lata that were attached on both sides of the torn dural defect with tissue glue. Seven cases with optic nerve injury included five cases of total blindness and two cases of light perception before operation. Vision improved in four cases. The CSF leakage was stopped successfully in all four cases without complication. As optic nerve compression and CSF leakage are skull base lesions, the supraorbital keyhole surgery constitutes a suitable approach. The supraorbital keyhole surgery allows for an anterior approach to the skull base. This approach also allows the treatment of both CSF leakage and optic nerve compression. Our results indicate that supraorbital keyhole operation is a safe and effective method for preserving or improving vision and attenuating CSF leakage following injury.

AN ELECTRON MICROSCOPE STUDY OF NERVES INFECTED WITH HUMAN POLIOMYELITIS VIRUS

PubMed Central

De Robertis, E.; Schmitt, F. O

1949-01-01

Sciatic nerves of rhesus monkeys infected with CAM and Wis. '45 strains of human poliomyelitis virus were fixed in formalin, sectioned, fragmented, and examined in the electron microscope. Most of the neurotubules of nerves infected with the CAM strain have normal appearance but a very small number show the presence of dense particles irregularly aligned within the edges of the neurotubules. The diameters of the particles range between 160 and 500 Å, the mean being 330 Å. The particles were found in regions along the nerve which varied with the time after infection, indicating a central movement of the morphological alteration of the order of 2 mm. per hour. Relatively abundant dense particulate material was found in nerves infected with Wis. '45 strain virus and the particles were chiefly attached to the edges of the neurotubules and in the adjacent areas of the field. The dense particles appear to be associated with the virus infection but no further characterization is possible at this time. PMID:18140661

Anomalous optic discs in a patient with a Dandy-Walker cyst.

PubMed

Orcutt, J C; Bunt, A H

1982-03-01

A 19-month-old female infant with a Dandy-Walker cyst had anomalous optic discs, each of which appeared to divide to form an accessory optic nerve. The discs probably lie within the spectrum of anomalous discs including optic nerve aplasia and hypoplasia, megallopapillae, morning glory disc, optic disc dysplasia, and optic nerve colobomas. The association of anomalous optic discs with a Dandy-Walker cyst has not been previously recognized. The ocular and brain malformations in this patient likely occurred during the fourth to eighth week of gestation, when the retinal ganglion cell axons were penetrating the optic nerve, and the rhombic lips were enlarging in early cerebellar development. The etiology of these anomalies is not known; however, teratogens, sporadic events, and genetic disorders should be considered.

Optic nerve axons and acquired alterations in the appearance of the optic disc.

PubMed Central

Wirtschafter, J D

1983-01-01

The pathophysiologic events in optic nerve axons have recently been recognized as crucial to an understanding of clinically significant acquired alterations in the ophthalmoscopic appearance of the optic disc. Stasis and related abnormalities of axonal transport appear to explain most aspects of optic nerve head swelling, including optic disc drusen and retinal cottonwool spots. Loss of axoplasm and axonal death can be invoked to interpret optic disc pallor, thinning and narrowing of rim tissue, changes in the size and outline of the optic cup, laminar dots, atrophy of the retinal nerve fiber layer, and acquired demyelination and myelination of the retinal nerve fiber layer. It is speculated that the axons may also play a role in the mechanical support of the lamina cribrosa in resisting the pressure gradient across the pars scleralis of the optic nerve head. Axons and their associated glial cells may be involved in those cases where "reversibility" of cupping of the optic disc has been reported. The structure, physiology, and experimental pathologic findings of the optic nerve head have been reviewed. Many aspects concerning the final anatomic appearance of the optic nerve head have been explained. However, many questions remain concerning the intermediate mechanisms by which increased intracranial pressure retards the various components of axonal transport in papilledema and by which increased IOP causes axonal loss in glaucoma. Investigation of the molecular biology of axonal constituents and their responses to abnormalities in their physical and chemical milieu could extend our understanding of the events that result from mechanical compression and local ischemia. Moreover, we have identified a need to further explore the role of axons in the pathophysiology of optic disc cupping. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 11 FIGURE 12 FIGURE 13 PMID:6203209

A Multidisciplinary Approach to Educating Preschool Children with Optic Nerve Hypoplasia and Septo-Optic Nerve Dysplasia.

ERIC Educational Resources Information Center

Bahar, Cheryl; Brody, Jill; McCann, Mary Ellen; Mendiola, Rosalinda; Slott, Gayle

2003-01-01

This article discusses the observations and experiences of a multidisciplinary team at the Blind Childrens Center in Los Angeles, which works specifically with children from birth to 5 years of age who have been diagnosed with optic nerve hypoplasia and may have septo-optic displasia. Strategies for educational interventions are explained.…

Intracanalicular Optic Nerve Swelling and Signal Change in Fulminant Untreated Idiopathic Intracranial Hypertension.

PubMed

Moodley, Anand A; Dlwati, Mahlubonke S; Durand, Miranda

2017-04-01

The role of the optic canal in the pathogenesis of papilloedema has been under scrutiny recently. Whether a larger canal precedes more severe papilloedema or is the result of bone remodelling from chronically raised pressure across a pressure gradient is not clear. The authors present the magnetic resonance imaging findings of a 29-year-old female with fulminant and untreated idiopathic intracranial hypertension. Imaging showed focal expansion and intrinsic signal changes of the intracanalicular optic nerve. The authors discuss the possibility of either fluid accumulation within the optic nerves from a water hammer effect across blocked optic canals resulting from the steep pressure gradient or opticomalacia (optic nerve softening) from chronic ischaemia.

Crystalline lens MTF measurement during simulated accommodation

NASA Astrophysics Data System (ADS)

Borja, David; Takeuchi, Gaku; Ziebarth, Noel; Acosta, Ana C.; Manns, Fabrice; Parel, Jean-Marie

2005-04-01

Purpose: To design and test an optical system to measure the optical quality of post mortem lenses during simulated accommodation. Methods: An optical bench top system was designed to measure the point spread function and calculate the modulation transfer function (MTF) of monkey and human ex-vivo crystalline lenses. The system consists of a super luminescent diode emitting at 850nm, collimated into a 3mm beam which is focused by the ex-vivo lens under test. The intensity distribution at the focus (point spread function) is re-imaged and magnified onto a beam profiler CCD camera. The optical quality in terms of spatial frequency response (modulation transfer function) is calculated by Fourier transform of the point spread function. The system was used on ex-vivo lenses with attached zonules, ciliary body and sclera. The sclera was glued to 8 separate PMMA segments and stretched radial by 5mm on an accommodation simulating lens stretching device. The point spread function was measured for each lens in the relaxed and stretched state for 5 human (ages 38-86 years) and 5 cynomolgus monkey (ages 53 - 67 months) fresh post mortem crystalline lenses. Results: Stretching induced measurable changes in the MTF. The cutoff frequency increased from 54.4+/-13.6 lp/mm unstretched to 59.5+/-21.4 lp/mm stretched in the post-presbyopic human and from 51.9+/-24.7 lp/mm unstretched to 57.7+/-18.5 lp/mm stretched cynomolgus monkey lenses. Conclusion: The results demonstrate the feasibility of measuring the optical quality of ex-vivo human and cynomolgus monkey lenses during simulated accommodation. Additional experiments are underway to quantify changes in optical quality induced by stretching.

Imaging of the optic nerve and retinal nerve fiber layer: an essential part of glaucoma diagnosis and monitoring.

PubMed

Kotowski, Jacek; Wollstein, Gadi; Ishikawa, Hiroshi; Schuman, Joel S

2014-01-01

Because glaucomatous damage is irreversible early detection of structural changes in the optic nerve head and retinal nerve fiber layer is imperative for timely diagnosis of glaucoma and monitoring of its progression. Significant improvements in ocular imaging have been made in recent years. Imaging techniques such as optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy rely on different properties of light to provide objective structural assessment of the optic nerve head, retinal nerve fiber layer and macula. In this review, we discuss the capabilities of these imaging modalities pertinent for diagnosis of glaucoma and detection of progressive glaucomatous damage and provide a review of the current knowledge on the clinical performance of these technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

[Pay attention to the secondary optic neuropathy and the safe appropriate applications of optic neuroprotection].

PubMed

Zhong, Y

2016-12-11

Secondary optic neuropathy of optic nerve abnormalities is the leading cause of persistent visual impairment. Previous ocular neuroprotection studies have proved that the nerve growth factor and other agents are of significant in the preservation of optic nerve axon and retinal ganglion cells. However, finding novel safe and effective approach as well as the appropriate applications of optic neuroprotection should be highly emphasized and would be very helpful in the treatment of optic neuropathy. (Chin J Ophthalmol, 2016, 52: 881 - 884) .

Pulsed laser versus electrical energy for peripheral nerve stimulation

PubMed Central

Wells, Jonathon; Konrad, Peter; Kao, Chris; Jansen, E. Duco; Mahadevan-Jansen, Anita

2010-01-01

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods can selectively excite functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits some advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future. PMID:17537515

A polarization measurement method for the quantification of retardation in optic nerve fiber layer

NASA Astrophysics Data System (ADS)

Fukuma, Yasufumi; Okazaki, Yoshio; Shioiri, Takashi; Iida, Yukio; Kikuta, Hisao; Ohnuma, Kazuhiko

2008-02-01

The thickness measurement of the optic nerve fiber layer is one of the most important evaluations for carrying out glaucoma diagnosis. Because the optic nerve fiber layer has birefringence, the thickness can be measured by illuminating eye optics with circular polarized light and analyzing the elliptical rate of the detected polarized light reflected from the optic nerve fiber layer. In this method, the scattering light from the background and the retardation caused by the cornea disturbs the precise measurement. If the Stokes vector expressing the whole state of polarization can be detected, we can eliminate numerically the influence of the background scattering and of the retardation caused by the cornea. Because the retardation process of the eye optics can be represented by a numerical equation using the retardation matrix of each component and also the nonpolarized background scattering light, it can be calculated by using the Stokes vector. We applied a polarization analysis system that can detect the Stokes vector onto the fundus camera. The polarization analysis system is constructed with a CCD area image sensor, a linear polarizing plate, a micro phase plate array, and a circularly polarized light illumination unit. With this simply constructed system, we can calculate the retardation caused only by the optic nerve fiber layer and it can predict the thickness of the optic nerve fiber layer. We report the method and the results graphically showing the retardation of the optic nerve fiber layer without the retardation of the cornea.

Blindness associated with nasal/paranasal lymphoma in a stallion.

PubMed

Sano, Yuto; Okamoto, Minoru; Ootsuka, Youhei; Matsuda, Kazuya; Yusa, Shigeki; Taniyama, Hiroyuki

2017-03-23

A 29-year-old stallion presented with bilateral blindness following the chronic purulent nasal drainage. The mass occupied the right caudal nasal cavity and right paranasal sinuses including maxillary, palatine and sphenoidal sinuses, and the right-side turbinal and paranasal septal bones, and cribriform plate of ethmoid bone were destructively replaced by the mass growth. The right optic nerve was invaded and involved by the mass, and the left optic nerve and optic chiasm were compressed by the mass which was extended and invaded the skull base. Histologically, the optic nerves and optic chiasm were degenerated, and the mass was diagnosed as lymphoma which was morphologically and immunohistochemically classified as a diffuse large B-cell lymphoma. Based on these findings, the cause of the blindness in the stallion was concluded to be due to the degeneration of the optic nerves and chiasm associated with lymphoma occurring in the nasal and paranasal cavities. To the best of our knowledge, this is the first report of the equine blindness with optic nerve degeneration accompanied by lymphoma.

Inflammatory Papillitis in Uveitis: Response to Treatment and Use of Optic Nerve Optical Coherence Tomography for Monitoring.

PubMed

Cho, Heeyoon; Pillai, Parvathy; Nicholson, Laura; Sobrin, Lucia

2016-01-01

To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 µm (p = 0.01). Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.

Age-related posterior ciliary muscle restriction – A link between trabecular meshwork and optic nerve head pathophysiology

PubMed Central

Lütjen-Drecoll, Elke; Kaufman, Paul L.

2016-01-01

The ciliary muscle plays a major role in controlling both accommodation and outflow facility in primates. The ciliary muscle and the choroid functionally form an elastic network that extends from the trabecular meshwork all the way to the back of the eye and ultimately attaches to the elastic fiber ring that surrounds the optic nerve and to the lamina cribrosa through which the nerve passes. The ciliary muscle governs the accommodative movement of the elastic network. With age ciliary muscle mobility is restricted by progressively inelastic posterior attachments and the posterior restriction makes the contraction progressively isometric; placing increased tension on the optic nerve region. In addition, outflow facility also declines with age and limbal corneoscleral contour bows inward. Age-related loss in muscle movement and altered limbal corneoscleral contour could both compromise the basal function of the trabecular meshwork. Further, recent studies in non-human primates show that the central vitreous moves posteriorly all the way back to the optic nerve region, suggesting a fluid current and a pressure gradient toward the optic nerve. Thus, there may be pressure and tension spikes on the optic nerve region during accommodation and these pressure and tension spikes may increase with age. This constellation of events could be relevant to glaucomatous optic neuropathy. In summary, our hypothesis is that glaucoma and presbyopia may be literally linked to each other, via the choroid, and that damage to the optic nerve may be inflicted by accommodative intraocular pressure and choroidal tension “spikes”, which may increase with age. PMID:27453343

Age-related posterior ciliary muscle restriction - A link between trabecular meshwork and optic nerve head pathophysiology.

PubMed

Croft, Mary Ann; Lütjen-Drecoll, Elke; Kaufman, Paul L

2017-05-01

The ciliary muscle plays a major role in controlling both accommodation and outflow facility in primates. The ciliary muscle and the choroid functionally form an elastic network that extends from the trabecular meshwork all the way to the back of the eye and ultimately attaches to the elastic fiber ring that surrounds the optic nerve and to the lamina cribrosa through which the nerve passes. The ciliary muscle governs the accommodative movement of the elastic network. With age ciliary muscle mobility is restricted by progressively inelastic posterior attachments and the posterior restriction makes the contraction progressively isometric; placing increased tension on the optic nerve region. In addition, outflow facility also declines with age and limbal corneoscleral contour bows inward. Age-related loss in muscle movement and altered limbal corneoscleral contour could both compromise the basal function of the trabecular meshwork. Further, recent studies in non-human primates show that the central vitreous moves posteriorly all the way back to the optic nerve region, suggesting a fluid current and a pressure gradient toward the optic nerve. Thus, there may be pressure and tension spikes on the optic nerve region during accommodation and these pressure and tension spikes may increase with age. This constellation of events could be relevant to glaucomatous optic neuropathy. In summary, our hypothesis is that glaucoma and presbyopia may be literally linked to each other, via the choroid, and that damage to the optic nerve may be inflicted by accommodative intraocular pressure and choroidal tension "spikes", which may increase with age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

PubMed

Eltony, Sohair A; Abdelhameed, Sally Y

2017-04-01

Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optic nerve lesion following neuroborreliosis: a case report.

PubMed

Burkhard, C; Gleichmann, M; Wilhelm, H

2001-01-01

Neuroborreliosis may cause various neuro-ophthalmological complications. We describe a case with a bilateral optic neuropathy. A 58-year-old female developed facial paresis six weeks after an insect bite. One week later she developed bilateral optic disc swelling with haemorrhages and nerve fibre bundle defects in the lower visual field of the left eye. In CSF and serum, raised IgM and IgG titres to Borrelia burgdorferi were found. Systemic antibiotic treatment led to improvement of the vision and facial paresis, but not all visual field defects resolved, probably due to ischemic lesions of the optic disc. In optic nerve lesions due to neuroborreliosis it is difficult to distinguish between inflammatory and ischemic lesions. This patient demonstrated features of an ischemic optic nerve lesion.

Intracanalicular Optic Nerve Swelling and Signal Change in Fulminant Untreated Idiopathic Intracranial Hypertension

PubMed Central

Moodley, Anand A.; Dlwati, Mahlubonke S.; Durand, Miranda

2017-01-01

ABSTRACT The role of the optic canal in the pathogenesis of papilloedema has been under scrutiny recently. Whether a larger canal precedes more severe papilloedema or is the result of bone remodelling from chronically raised pressure across a pressure gradient is not clear. The authors present the magnetic resonance imaging findings of a 29-year-old female with fulminant and untreated idiopathic intracranial hypertension. Imaging showed focal expansion and intrinsic signal changes of the intracanalicular optic nerve. The authors discuss the possibility of either fluid accumulation within the optic nerves from a water hammer effect across blocked optic canals resulting from the steep pressure gradient or opticomalacia (optic nerve softening) from chronic ischaemia. PMID:28348630

Bedside Optic Nerve Sheath Diameter Assessment in the Identification of Increased Intracranial Pressure in Suspected Idiopathic Intracranial Hypertension.

PubMed

Irazuzta, Jose E; Brown, Martha E; Akhtar, Javed

2016-01-01

We determined whether the bedside assessment of the optic nerve sheath diameter could identify elevated intracranial pressure in individuals with suspected idiopathic intracranial hypertension. This was a single-center, prospective, rater-blinded study performed in a freestanding pediatric teaching hospital. Patients aged 12 to 18 years scheduled for an elective lumbar puncture with the suspicion of idiopathic intracranial hypertension were eligible to participate. Optic nerve sheath diameter was measured via ultrasonography before performing a sedated lumbar puncture for measuring cerebrospinal fluid opening pressure. Abnormal measurements were predefined as optic nerve sheath diameter ≥4.5 mm and a cerebrospinal fluid opening pressure greater than 20 cmH2O. Thirteen patients participated in the study, 10 of whom had elevated intracranial pressure. Optic nerve sheath diameter was able to predict or rule out elevated intracranial pressure in all patients. Noninvasive assessment of the optic nerve sheath diameter could help to identify patients with elevated intracranial pressure when idiopathic intracranial hypertension is suspected. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma.

PubMed

Wasyluk, Jaromir T; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona

2012-03-01

We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18-70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in µm) differ significantly between GDx and all OCT devices. Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients.

Wave aberrations in rhesus monkeys with vision-induced ametropias

PubMed Central

Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Huang, Juan; Roorda, Austin; Smith, Earl L.

2007-01-01

The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development. PMID:17825347

Optic Nerve Sheath Mechanics in VIIP Syndrome

NASA Technical Reports Server (NTRS)

Raykin, Julia; Feola, Andrew; Gleason, Rudy; Mulugeta, Lealem; Myers, Jerry; Nelson, Emily; Samuels, Brian; Ethier, C. Ross

2015-01-01

Visual Impairment and Intracranial Pressure (VIIP) syndrome results in a loss of visual function and occurs in astronauts following long-duration spaceflight. Understanding the mechanisms that lead to the ocular changes involved in VIIP is of critical importance for space medicine research. Although the exact mechanisms of VIIP are not yet known, it is hypothesized that microgravity-induced increases in intracranial pressures (ICP) drive the remodeling of the optic nerve sheath, leading to compression of the optic nerve which in turn may reduce visual acuity. Some astronauts present with a kink in the optic nerve after return to earth, suggesting that tissue remodeling in response to ICP increases may be taking place. The goal of this work is to characterize the mechanical properties of the optic nerve sheath (dura mater) to better understand its biomechanical response to increased ICP.

A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Steven L

2015-12-01

Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION.

Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury

PubMed Central

CHUNG, SOKJOONG; RHO, SEUNGSOO; KIM, GIJIN; KIM, SO-RA; BAEK, KWANG-HYUN; KANG, MYUNGSEO; LEW, HELEN

2016-01-01

The use of mesenchymal stem cells (MSCs) in cell therapy in regenerative medicine has great potential, particularly in the treatment of nerve injury. Umbilical cord blood (UCB) reportedly contains stem cells, which have been widely used as a hematopoietic source and may have therapeutic potential for neurological impairment. Although ongoing research is dedicated to the management of traumatic optic nerve injury using various measures, novel therapeutic strategies based on the complex underlying mechanisms responsible for optic nerve injury, such as inflammation and/or ischemia, are required. In the present study, a rat model of optic nerve crush (ONC) injury was established in order to examine the effects of transplanting human chorionic plate-derived MSCs (CP-MSCs) isolated from the placenta, as well as human UCB mononuclear cells (CB-MNCs) on compressed rat optic nerves. Expression markers for inflammation, apoptosis, and optic nerve regeneration were analyzed, as well as the axon survival rate by direct counting. Increased axon survival rates were observed following the injection of CB-MNCs at at 1 week post-transplantation compared with the controls. The levels of growth-associated protein-43 (GAP-43) were increased after the injection of CB-MNCs or CP-MSCs compared with the controls, and the expression levels of hypoxia-inducible factor-1α (HIF-1α) were also significantly increased following the injection of CB-MNCs or CP-MSCs. ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP-MSC-injected rats with ONC injury. The findings of our study suggest that the administration of CB-MNCs or CP-MSCs may promote axon survival through systemic concomitant mechanisms involving GAP-43 and HIF-1α. Taken together, these findings provide further understanding of the mechanisms repsonsible for optic nerve injury and may aid in the development of novel cell-based therapeutic strategies with future applications in regenerative medicine, particularly in the management of optic nerve disorders. PMID:26986762

[Raman spectra of monkey cerebral cortex tissue].

PubMed

Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

2010-01-01

Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans.

PubMed

Polska, Elzbieta; Ehrlich, Paulina; Luksch, Alexandra; Fuchsjäger-Mayrl, Gabriele; Schmetterer, Leopold

2003-07-01

There is evidence from a variety of animal studies that the adenosine system plays a role in the control of intraocular pressure (IOP) and ocular blood flow. However, human data on the effect of adenosine on IOP and choroidal and optic nerve blood flow are not available. The effect of stepwise increases in doses of adenosine (10, 20, and 40 micro g/kg per minute, 30 minutes per infusion step) on optic nerve head blood flow, choroidal blood flow, and IOP was determined in a placebo-controlled double-masked clinical trial in 12 healthy male volunteers. Blood flow in the optic nerve head and choroid was measured with laser Doppler flowmetry. In addition, fundus pulsation amplitude in the macula (FPAM) and the optic nerve head (FPAO) were assessed with laser interferometry. Adenosine induced a small but significant decrease in IOP (at 40 microg/kg per minute: 12% +/- 13%), which was significant versus placebo (P = 0.046). In addition, adenosine induced a significant increase in choroidal blood flow (P < 0.001) and optic nerve head blood flow (P = 0.037), and FPAM (P = 0.0014) and tended to increase FPAO (P = 0.057). At the highest administered dose, the effect on choroidal hemodynamic parameters between 14% and 17%, whereas the effect on optic nerve hemodynamic parameters was between 3% and 11%. These data are consistent with adenosine inducing choroidal and optic nerve head vasodilatation and reducing IOP in healthy humans. Considering the neuroprotective properties of adenosine described in previous animal experiments the adenosine system is an attractive target system for therapeutic approaches in glaucoma.

The effects of rearing light level and duration differences on the optic nerve, brain, and associated structures in developing zebrafish larvae: a light and transmission electron microscope study.

PubMed

Chapman, George B; Tarboush, Rania; Connaughton, Victoria P

2012-03-01

The ultrastructure of the optic nerve, brain, and some associated structures of larval zebrafish, grown under three different light regimens were studied. Fish grown under cyclic light (control), constant dark (CD), and constant light (CL) were studied for 4 and 8 days postfertilization (dpf). We also studied the control and CD fish at 15 dpf. The brains of the control and CL fish were larger at 4 dpf than at 8 dpf. In all 4 dpf fish, the brain occupied the entire expanse between the two retinas and the optic nerve extended the shortest distance between the retina and the brain. The 15 dpf zebrafish had the smallest brain size. Groups of skeletal muscle cells associated with the optic nerves became visible in all older larvae. In the 15 dpf larvae, bulges and dilations in the optic nerve occurred as it reached the brain and optic chiasms occurred proximal to the brain. Electron microscopy yielded information about myelinated and unmyelinated axons in the optic nerve, the dimensions of neurotubules, neurofilaments, and myofilaments, including a unique variation in actin myofilaments, and a confirmation of reported myosin myofilament changes (but with dimensions). We also describe the ultrastructure of a sheath-like structure that is confluent over the optic nerve and the brain, which has not been described before in zebrafish. Also presented are images of associated fibroblasts, epithelial cells lining the mouth, cartilage plates, blood vessels, nerve bundles, and skeletal muscle cells, most of which have not been previously described in the literature. Copyright © 2012 Wiley Periodicals, Inc.

Optic chiasm in the species of order Clupeiformes, family Clupeidae: optic chiasm of Spratelloides gracilis shows an opposite laterality to that of Etrumeus teres.

PubMed

Mogi, Kazue; Misawa, Kazuya; Utsunomiya, Kentaro; Kawada, Yuta; Yamazaki, Toshihisa; Takeuchi, Shigeo; Toyoizumi, Ryuji

2009-09-01

In most teleost fishes, the optic nerves decussate completely as they project to the mesencephalic region. Examination of the decussation pattern of 25 species from 11 different orders in Pisces revealed that each species shows a specific chiasmic type. In 11 species out of the 25, laterality of the chiasmic pattern was not determined; in half of the individuals examined, the left optic nerve ran dorsally to the right optic nerve, while in the other half, the right optic nerve was dorsal. In eight other species the optic nerves from both eyes branched into several bundles at the chiasmic point, and intercalated to form a complicated decussation pattern. In the present study we report our findings that Spratelloides gracilis, of the order Clupeiformes, family Clupeidae, shows a particular laterality of decussation: the left optic nerve ran dorsally to the right (n=200/202). In contrast, Etrumeus teres, of the same order and family, had a strong preference of the opposite (complementary) chiasmic pattern to that of S. gracilis (n=59/59), revealing that these two species display opposite left-right optic chiasm patterning. As far as we investigated, other species of Clupeiformes have not shown left-right preference in the decussation pattern. We conclude that the opposite laterality of the optic chiasms of these two closely related species, S. gracilis and E. teres, enables investigation of species-specific laterality in fishes of symmetric shapes.

Optic chiasm in the species of order Clupeiformes, family Clupeidae: Optic chiasm of Spratelloides gracilis shows an opposite laterality to that of Etrumeus teres

PubMed Central

Mogi, Kazue; Misawa, Kazuya; Utsunomiya, Kentaro; Kawada, Yuta; Yamazaki, Toshihisa; Takeuchi, Shigeo; Toyoizumi, Ryuji

2009-01-01

In most teleost fishes, the optic nerves decussate completely as they project to the mesencephalic region. Examination of the decussation pattern of 25 species from 11 different orders in Pisces revealed that each species shows a specific chiasmic type. In 11 species out of the 25, laterality of the chiasmic pattern was not determined; in half of the individuals examined, the left optic nerve ran dorsally to the right optic nerve, while in the other half, the right optic nerve was dorsal. In eight other species the optic nerves from both eyes branched into several bundles at the chiasmic point, and intercalated to form a complicated decussation pattern. In the present study we report our findings that Spratelloides gracilis, of the order Clupeiformes, family Clupeidae, shows a particular laterality of decussation: the left optic nerve ran dorsally to the right (n = 200/202). In contrast, Etrumeus teres, of the same order and family, had a strong preference of the opposite (complementary) chiasmic pattern to that of S. gracilis (n = 59/59), revealing that these two species display opposite left–right optic chiasm patterning. As far as we investigated, other species of Clupeiformes have not shown left–right preference in the decussation pattern. We conclude that the opposite laterality of the optic chiasms of these two closely related species, S. gracilis and E. teres, enables investigation of species-specific laterality in fishes of symmetric shapes. PMID:19229672

Patients affected by endemic pemphigus foliaceus in Colombia, South America exhibit autoantibodies to optic nerve sheath envelope cell junctions.

PubMed

Abreu-Velez, Ana Maria; Gao, Wendy; Howard, Michael S

2018-01-01

The majority of the patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre EPF or pemphigus Abreu-Manu), have experienced vision problems; we have previously reported several ocular abnormalities. Here, we aimed to investigate reactivity to optic nerves in these patients. We utilized bovine, rat and mouse optic nerves, and performed immunofluorescence and confocal microscopy to test for optical nerve autoreactivity. We tested 45 patients affected by this disease and 45 controls from the endemic area matched by age, sex and work activity. Overall, 37 of the 45 patient sera reacted to the optic nerve envelope that is composed of leptomeninges; the reactivity was polyclonal and present mostly at the cell junctions (P < 0.001). The immune response was directed against optic nerve sheath cell junctions and the vessels inside it, as well as other molecules inside the nerve. No control cases were positive. Of interest, all the patient autoantibodies co-localized with commercial antibodies to desmoplakins I-II, myocardium-enriched zonula occludens-1- associated protein (MYZAP), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and plakophilin-4 (p0071) from Progen Biotechnik (P < 0.001). We conclude that the majority of the patients affected by pemphigus Abreu-Manu have autoantibodies to optic nerve sheath envelope cell junctions. These antibodies also co-localize with armadillo repeat gene deleted in velo-cardio-facial syndrome, p0071 and desmoplakins I-II. The clinical significance of our findings remains unknown.

Comparative study of the retinal nerve fibre layer thickness performed with optical coherence tomography and GDx scanning laser polarimetry in patients with primary open-angle glaucoma

PubMed Central

Wasyluk, Jaromir T.; Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona

2012-01-01

Summary Background We compared the parameters of retinal nerve fibre layer in patients with advanced glaucoma with the use of different OCT (Optical Coherence Tomograph) devices in relation to analogical measurements performed with GDx VCC (Nerve Fiber Analyzer with Variable Corneal Compensation) scanning laser polarimetry. Material/Methods Study subjects had advanced primary open-angle glaucoma, previously treated conservatively, diagnosed and confirmed by additional examinations (visual field, ophthalmoscopy of optic nerve, gonioscopy), A total of 10 patients were enrolled (9 women and 1 man), aged 18–70 years of age. Nineteen eyes with advanced glaucomatous neuropathy were examined. 1) Performing a threshold perimetry Octopus, G2 strategy and ophthalmoscopy of optic nerve to confirm the presence of advanced primary open-angle glaucoma; 2) performing a GDx VCC scanning laser polarimetry of retinal nerve fibre layer; 3) measuring the retinal nerve fibre layer thickness with 3 different optical coherence tomographs. Results The parameters of the retinal nerve fibre layer thickness are highly correlated between the GDx and OCT Stratus and 3D OCT-1000 devices in mean retinal nerve fibre layer thickness, retinal nerve fibre layer thickness in the upper sector, and correlation of NFI (GDx) with mean retinal nerve fibre layer thickness in OCT examinations. Absolute values of the retinal nerve fibre layer thickness (measured in μm) differ significantly between GDx and all OCT devices. Conclusions Examination with OCT devices is a sensitive diagnostic method of glaucoma, with good correlation with the results of GDx scanning laser polarimetry of the patients. PMID:22367131

Birefringence measurement of retinal nerve fiber layer using polarization-sensitive spectral domain optical coherence tomography with Jones matrix based analysis

NASA Astrophysics Data System (ADS)

Yamanari, Masahiro; Miura, Masahiro; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

2007-02-01

Birefringence of retinal nerve fiber layer is measured by polarization-sensitive spectral domain optical coherence tomography using the B-scan-oriented polarization modulation method. Birefringence of the optical fiber and the cornea is compensated by Jones matrix based analysis. Three-dimensional phase retardation map around the optic nerve head and en-face phase retardation map of the retinal nerve fiber layer are shown. Unlike scanning laser polarimetry, our system can measure the phase retardation quantitatively without using bow-tie pattern of the birefringence in the macular region, which enables diagnosis of glaucoma even if the patients have macular disease.

Bilateral vision loss in a captive cheetah (Acinonyx jubatus).

PubMed

Walser-Reinhardt, Ladina; Wernick, Morena B; Hatt, Jean-Michel; Spiess, Bernhard M

2010-09-01

The following case report describes a 1-year-old female cheetah (Acinonyx jubatus) with bilateral blindness and unresponsive pupils. For comparison, a second healthy 2.5-year-old male cheetah without visual deficits was also examined. Clinical examination of both animals included biomicroscopy, indirect ophthalmoscopy, tonometry, and electroretinography. The young female cheetah showed no menace response, no direct or indirect pupillary light reflex, and no dazzle reflex in either eye. Fundus lesions, as detected by indirect ophthalmoscopy, are described for the female animal. In both eyes, the fundus color was green/turquoise/yellow with multiple hyperpigmented linear lesions in the tapetal area around the optic nerve. The optic nerve head was dark gray and about half the normal size suggesting bilateral optic nerve hypoplasia and retinal dysplasia or differentially optic nerve atrophy and chorioretinal scarring. The ERG had low amplitudes in the right eye but appeared normal in the left eye compared with the male cheetah. Blood levels did not suggest current taurine deficiency. This is addressed to some degree in the discussion. Bilateral optic nerve hypoplasia or optic nerve atrophy is a rare anomaly in cats and has not yet been described in a cheetah.

Coincidental Optic Nerve Meningioma and Thyroid Eye Disease.

PubMed

Garg, Aakriti; Patel, Payal; Lignelli, Angela; Baron, Edward; Kazim, Michael

2015-01-01

A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist.

Evidence that the extraocular motor nuclei innervate monkey palisade endings.

PubMed

Zimmermann, Lars; May, Paul J; Pastor, Angel M; Streicher, Johannes; Blumer, Roland

2011-02-04

Palisade endings are found in the extraocular muscles (EOMs) of almost every mammalian species, including primates. These nerve specializations surrounding the muscle fiber insertion have been postulated to be the proprioceptors of the EOMs. However, it was recently demonstrated that palisade endings have a cholinergic nature, which reopened the question of whether palisade endings are motor or sensory structures. In this work, we examined whether the cell bodies of palisade endings lie in EOM motor nuclei by injecting an anterograde tracer, biotinylated dextran amine, into the abducens nucleus of a macaque monkey. Tracer visualization in the lateral rectus muscle was combined with choline acetyltransferase (ChAT) and α-bungarotoxin staining. Analysis of the samples was performed by conventional light microscopy and confocal laser scanning microscopy. About 30% of the nerve fibers innervating the muscle were tracer positive. These were ChAT positive as well. Tracer positive nerve fibers established motor contacts on singly and multiply innervated muscle fibers, which were confirmed by α-bungarotoxin staining. At the transition between muscle and distal tendon, we found palisade endings that contained tracer. Palisade endings exhibited the classic morphology: axons arising from the muscle extend onto the tendon, then turn back 180° and terminate in a cuff of terminals around an individual muscle fiber tip. This finding suggests that the cell bodies of palisade endings lie in the EOM motor nuclei, which complements prior studies demonstrating a cholinergic, and possibly motor, phenotype for palisade endings. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Evidence that the extraocular motor nuclei innervate monkey palisade endings

PubMed Central

Zimmermann, Lars; May, Paul J.; Pastor, Ángel M.; Streicher, Johannes; Blumer, Roland

2011-01-01

Palisade endings are found in the extraocular muscles (EOMs) of almost every mammalian species, including primates. These nerve specializations surrounding the muscle fiber insertion have been postulated to be the proprioceptors of the EOMs. However, it was recently demonstrated that palisade endings have a cholinergic nature, which reopened the question of whether palisade endings are motor or sensory structures. In this work, we examined whether the cell bodies of palisade endings lie in EOM motor nuclei by injecting an anterograde tracer, biotinylated dextran amine, into the abducens nucleus of a macaque monkey. Tracer visualization in the lateral rectus muscle was combined with choline acetyltransferase (ChAT) and α-bungarotoxin staining. Analysis of the samples was performed by conventional light microscopy and confocal laser scanning microscopy. About 30% of the nerve fibers innervating the muscle were tracer positive. These were ChAT positive as well. Tracer positive nerve fibers established motor contacts on singly and multiply innervated muscle fibers, which were confirmed by α-bungarotoxin staining. At the transition between muscle and distal tendon, we found palisade endings that contained tracer. Palisade endings exhibited the classic morphology: axons arising from the muscle extend onto the tendon, then turn back 180° and terminate in a cuff of terminals around an individual muscle fiber tip. This finding suggests that the cell bodies of palisade endings lie in the EOM motor nuclei, which complements prior studies demonstrating a cholinergic, and possibly motor, phenotype for palisade endings. PMID:21138754

Viewing speech modulates activity in the left SI mouth cortex.

PubMed

Möttönen, Riikka; Järveläinen, Juha; Sams, Mikko; Hari, Riitta

2005-02-01

The ability to internally simulate other persons' actions is important for social interaction. In monkeys, neurons in the premotor cortex are activated both when the monkey performs mouth or hand actions and when it views or listens to actions made by others. Neuronal circuits with similar "mirror-neuron" properties probably exist in the human Broca's area and primary motor cortex. Viewing other person's hand actions also modulates activity in the primary somatosensory cortex SI, suggesting that the SI cortex is related to the human mirror-neuron system. To study the selectivity of the SI activation during action viewing, we stimulated the lower lip (with tactile pulses) and the median nerves (with electric pulses) in eight subjects to activate their SI mouth and hand cortices while the subjects either rested, listened to other person's speech, viewed her articulatory gestures, or executed mouth movements. The 55-ms SI responses to lip stimuli were enhanced by 16% (P<0.01) in the left hemisphere during speech viewing whereas listening to speech did not modulate these responses. The 35-ms responses to median-nerve stimulation remained stable during speech viewing and listening. Own mouth movements suppressed responses to lip stimuli bilaterally by 74% (P<0.001), without any effect on responses to median-nerve stimuli. Our findings show that viewing another person's articulatory gestures activates the left SI cortex in a somatotopic manner. The results provide further evidence for the view that SI is involved in "mirroring" of other persons' actions.

Enhancing effects of saccharin on gustatory responses to D-phenylalanine in monkey single chorda tympani fibers.

PubMed

Ninomiya, Y; Hellekant, G

1994-01-28

Taste enhancing effects of sodium saccharin (Sac) on D-phenylalanine (D-Phe), first found in mice, were examined by comparing single fiber responses to various taste stimuli in the monkey chorda tympani nerve. Fifteen fibers sampled were divided into the following 5 groups according to their responsiveness to 5 prototypical taste stimuli; 8 sucrose-, 2 quinine-, 2 acid-, 2 NaCl- and one monosodium glutamate (MSG)-best fibers. Out of 8 sucrose-best fibers, 5 fibers showed enhancement of D-Phe responses after the stimulation with Sac, but neither the remaining 3 sucrose-best fibers nor other fibers showed the enhancement. These results suggest that (1) the enhancement of D-Phe responses by Sac also occurs in the monkey peripheral taste system, and (2) there exist distinct receptor sites for D-Phe responsible for occurrence of the enhancement, and (3) taste cells possessing the D-Phe receptor site are innervated by a limited subpopulation of sucrose-best fibers.

Adeno-Associated Viral-Mediated Catalase Expression Suppresses Optic Neuritis in Experimental Allergic Encephalomyelitis

NASA Astrophysics Data System (ADS)

Guy, John; Qi, Xiaoping; Hauswirth, William W.

1998-11-01

Suppression of oxidative injury by viral-mediated transfer of the human catalase gene was tested in the optic nerves of animals with experimental allergic encephalomyelitis (EAE). EAE is an inflammatory autoimmune disorder of primary central nervous system demyelination that has been frequently used as an animal model for the human disease multiple sclerosis (MS). The optic nerve is a frequent site of involvement common to both EAE and MS. Recombinant adeno-associated virus containing the human gene for catalase was injected over the right optic nerve heads of SJL/J mice that were simultaneously sensitized for EAE. After 1 month, cell-specific catalase activity, evaluated by quantitation of catalase immunogold, was increased approximately 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the optic nerve. Effects of catalase on the histologic lesions of EAE were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), extent of the cellular infiltrate, extravasated serum albumin labeled by immunogold (for blood-brain barrier disruption), and in vivo H2O2 reaction product. Relative to control, contralateral optic nerves injected with the recombinant virus without a therapeutic gene, catalase gene inoculation reduced demyelination by 38%, optic nerve head swelling by 29%, cellular infiltration by 34%, disruption of the blood-brain barrier by 64%, and in vivo levels of H2O2 by 61%. Because the efficacy of potential treatments for MS are usually initially tested in the EAE animal model, this study suggests that catalase gene delivery by using viral vectors may be a therapeutic strategy for suppression of MS.

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice.

PubMed

Chao de la Barca, Juan Manuel; Simard, Gilles; Sarzi, Emmanuelle; Chaumette, Tanguy; Rousseau, Guillaume; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Ferré, Marc; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Gueguen, Naïg; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Amati-Bonneau, Patrizia; Procaccio, Vincent; Hamel, Christian; Lenaers, Guy; Reynier, Pascal; Prunier-Mirebeau, Delphine

2017-02-01

Dominant optic atrophy (MIM No. 165500) is a blinding condition related to mutations in OPA1, a gene encoding a large GTPase involved in mitochondrial inner membrane dynamics. Although several mouse models mimicking the disease have been developed, the pathophysiological mechanisms responsible for retinal ganglion cell degeneration remain poorly understood. Using a targeted metabolomic approach, we measured the concentrations of 188 metabolites in nine tissues, that is, brain, three types of skeletal muscle, heart, liver, retina, optic nerve, and plasma in symptomatic 11-month-old Opa1delTTAG/+ mice. Significant metabolic signatures were found only in the optic nerve and plasma of female mice. The optic nerve signature was characterized by altered concentrations of phospholipids, amino acids, acylcarnitines, and carnosine, whereas the plasma signature showed decreased concentrations of amino acids and sarcosine associated with increased concentrations of several phospholipids. In contrast, the investigation of 3-month-old presymptomatic Opa1delTTAG/+ mice showed no specific plasma signature but revealed a significant optic nerve signature in both sexes, although with a sex effect. The Opa1delTTAG/+ versus wild-type optic nerve signature was characterized by the decreased concentrations of 10 sphingomyelins and 10 lysophosphatidylcholines, suggestive of myelin sheath alteration, and by alteration in the concentrations of metabolites involved in neuroprotection, such as dimethylarginine, carnitine, spermine, spermidine, carnosine, and glutamate, suggesting a concomitant axonal metabolic dysfunction. Our comprehensive metabolomic investigations revealed in symptomatic as well as in presymptomatic Opa1delTTAG/+ mice, a specific sensitiveness of the optic nerve to Opa1 insufficiency, opening new routes for protective therapeutic strategies.

Temperature-controlled optical stimulation of the rat prostate cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Hutchens, Thomas C.; McClain, Michael A.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2013-06-01

Optical nerve stimulation (ONS) may be useful as a diagnostic tool for intraoperative identification and preservation of the prostate cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. Successful ONS requires elevating the nerve temperature to within a narrow range (˜42 to 47°C) for nerve activation without thermal damage to the nerve. This preliminary study explores a prototype temperature-controlled optical nerve stimulation (TC-ONS) system for maintaining a constant (±1°C) nerve temperature during short-term ONS of the rat prostate CNs. A 150-mW, 1455-nm diode laser was operated in continuous-wave mode, with and without temperature control, during stimulation of the rat CNs for 15 to 30 s through a fiber optic probe with a 1-mm-diameter spot. A microcontroller opened and closed an in-line mechanical shutter in response to an infrared sensor, with a predetermined temperature set point. With TC-ONS, higher laser power settings were used to rapidly and safely elevate the CNs to a temperature necessary for a fast intracavernous pressure response, while also preventing excessive temperatures that would otherwise cause thermal damage to the nerve. With further development, TC-ONS may provide a rapid, stable, and safe method for intraoperative identification and preservation of the prostate CNs.

Assessment of nerve ultrastructure by fibre-optic confocal microscopy.

PubMed

Cushway, T R; Lanzetta, M; Cox, G; Trickett, R; Owen, E R

1996-01-01

Fibre-optic technology combined with confocality produces a microscope capable of optical thin sectioning. In this original study, tibial nerves have been stained in a rat model with a vital dye, 4-(4-diethylaminostyryl)-N-methylpyridinium iodide, and analysed by fibre-optic confocal microscopy to produce detailed images of nerve ultrastructure. Schwann cells, nodes of Ranvier and longitudinal myelinated sheaths enclosing axons were clearly visible. Single axons appeared as brightly staining longitudinal structures. This allowed easy tracing of multiple signal axons within the nerve tissue. An accurate measurement of internodal lengths was easily accomplished. This technique is comparable to current histological techniques, but does not require biopsy, thin sectioning or tissue fixing. This study offers a standard for further in vivo microscopy, including the possibility of monitoring the progression of nerve regeneration following microsurgical neurorraphy.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Optic Nerve Sheath Mechanics in VIIP Syndrome

NASA Technical Reports Server (NTRS)

Raykin, Julia; Forte, Taylor E.; Wang, Roy; Feola, Andrew; Samuels, Brian; Myers, Jerry; Nelson, Emily; Gleason, Rudy; Ethier, C. Ross

2016-01-01

Visual Impairment Intracranial Pressure (VIIP) syndrome is a major concern in current space medicine research. While the exact pathology of VIIP is not yet known, it is hypothesized that the microgravity-induced cephalad fluid shift increases intracranial pressure (ICP) and drives remodeling of the optic nerve sheath. To investigate this possibility, we are culturing optic nerve sheath dura mater samples under different pressures and investigating changes in tissue composition. To interpret results from this work, it is essential to first understand the biomechanical response of the optic nerve sheath dura mater to loading. Here, we investigated the effects of mechanical loading on the porcine optic nerve sheath.Porcine optic nerves (number: 6) were obtained immediately after death from a local abattoir. The optic nerve sheath (dura mater) was isolated from the optic nerve proper, leaving a hollow cylinder of connective tissue that was used for biomechanical characterization. We developed a custom mechanical testing system that allowed for unconfined lengthening, twisting, and circumferential distension of the dura mater during inflation and under fixed axial loading. To determine the effects of variations in ICP, the sample was inflated (0-60 millimeters Hg) and circumferential distension was simultaneously recorded. These tests were performed under variable axial loads (0.6 grams - 5.6 grams at increments of 1 gram) by attaching different weights to one end of the dura mater. Results and Conclusions: The samples demonstrated nonlinear behavior, similar to other soft connective tissue (Figure 1). Large increases in diameter were observed at lower transmural pressures (approximately 0 to 5 millimeters Hg), whereas only small diameter changes were observed at higher pressures. Particularly interesting was the existence of a cross-over point at a pressure of approximately 11 millimeters Hg. At this pressure, the same diameter is obtained for all axial loads applied to the tissue; i.e., as the axial load is varied, the diameter of the dura mater remains constant. This cross-over in the pressure-diameter curves occurred in all optic nerve sheaths that were tested, and may correspond with in vivo ICP levels for pigs. These data suggest that diameter of the dura mater of the optic nerve remains nearly constant in vivo despite being stretched axially. This may be a homeostatic mechanism aimed at maintaining target stresses/strains on the cells in the dura mater, and deviations from these stresses may play an important role in optic nerve sheath remodeling. Future studies will involve subjecting the dura mater to varying pressures and axial tensions for extended periods of time, while monitoring changes in the biomechanical properties. The data can then be used to study the effects of changes in ICP on the remodeling of the dura mater.

Optical cuff for optogenetic control of the peripheral nervous system.

PubMed

Michoud, Frédéric; Sottas, Loïc; Browne, Liam E; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J; Lacour, Stéphanie P

2018-02-01

Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Here, we propose an optical peripheral nerve interface-an optocuff-, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

Optical cuff for optogenetic control of the peripheral nervous system

NASA Astrophysics Data System (ADS)

Michoud, Frédéric; Sottas, Loïc; Browne, Liam E.; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J.; Lacour, Stéphanie P.

2018-02-01

Objective. Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Approach. Here, we propose an optical peripheral nerve interface—an optocuff—, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Main results. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. Significance. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

[Clinical evaluation of the optic disc in glaucoma].

PubMed

Greslechner, R; Spiegel, D

2016-10-01

Glaucoma is defined as a progressive neuropathy of the optic nerve, characterized by specific changes of the optic disc, parapapillary region, and retinal nerve fiber layer. Characteristic glaucomatous changes of the optic disc, parapapillary region, and retinal nerve fiber layer are discussed and their ophthalmoscopic examination is described. A literature search in the PubMed database was conducted. A systematic step-by-step approach to a qualitative and quantitative ophthalmoscopic evaluation of the optic disc regarding glaucomatous damage is presented. A systematic, clinical, qualitative, and quantitative assessment of the optic disc can be performed with little effort and forms the basis for diagnosis and treatment of glaucoma.

Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ.

PubMed

Zarei, Kasra; Scheetz, Todd E; Christopher, Mark; Miller, Kathy; Hedberg-Buenz, Adam; Tandon, Anamika; Anderson, Michael G; Fingert, John H; Abràmoff, Michael David

2016-05-26

We have developed a publicly available tool, AxonJ, which quantifies the axons in optic nerve sections of rodents stained with paraphenylenediamine (PPD). In this study, we compare AxonJ's performance to human experts on 100x and 40x images of optic nerve sections obtained from multiple strains of mice, including mice with defects relevant to glaucoma. AxonJ produced reliable axon counts with high sensitivity of 0.959 and high precision of 0.907, high repeatability of 0.95 when compared to a gold-standard of manual assessments and high correlation of 0.882 to the glaucoma damage staging of a previously published dataset. AxonJ allows analyses that are quantitative, consistent, fully-automated, parameter-free, and rapid on whole optic nerve sections at 40x. As a freely available ImageJ plugin that requires no highly specialized equipment to utilize, AxonJ represents a powerful new community resource augmenting studies of the optic nerve using mice.

Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ

NASA Astrophysics Data System (ADS)

Zarei, Kasra; Scheetz, Todd E.; Christopher, Mark; Miller, Kathy; Hedberg-Buenz, Adam; Tandon, Anamika; Anderson, Michael G.; Fingert, John H.; Abràmoff, Michael David

2016-05-01

We have developed a publicly available tool, AxonJ, which quantifies the axons in optic nerve sections of rodents stained with paraphenylenediamine (PPD). In this study, we compare AxonJ’s performance to human experts on 100x and 40x images of optic nerve sections obtained from multiple strains of mice, including mice with defects relevant to glaucoma. AxonJ produced reliable axon counts with high sensitivity of 0.959 and high precision of 0.907, high repeatability of 0.95 when compared to a gold-standard of manual assessments and high correlation of 0.882 to the glaucoma damage staging of a previously published dataset. AxonJ allows analyses that are quantitative, consistent, fully-automated, parameter-free, and rapid on whole optic nerve sections at 40x. As a freely available ImageJ plugin that requires no highly specialized equipment to utilize, AxonJ represents a powerful new community resource augmenting studies of the optic nerve using mice.

Evolution of an Astrocytic Hamartoma of the Optic Nerve Head in a Patient with Retinitis Pigmentosa - Photographic Documentation over 2 Years of Follow-Up.

PubMed

Loukianou, Eleni; Kisma, Nacima; Pal, Bishwanathan

2011-02-02

To report photographically the evolution of an astrocytic hamartoma of the left optic nerve head over a 2-year follow-up in a patient with retinitis pigmentosa. A 14-year-old boy was seen in the medical retina clinic with a 3-year history of night blindness. Best corrected visual acuity was 6/18 in both eyes. Colour vision was normal in both eyes and confrontation fields showed peripheral constriction. Fundus examination revealed bone spicule pigmentary changes at the retinal mid periphery typical of retinitis pigmentosa and superficial globules at the margins of both optic nerve heads. Electrodiagnostic tests confirmed moderately severe rod cone dystrophy with macular involvement bilaterally. Two years later, the ocular examination was unchanged except for the appearance of the optic nerve head lesion in the left eye. There was an increase in the size of the lesion which was diagnosed as an astrocytic hamartoma. Further investigations were recommended to exclude neurofibromatosis and tuberous sclerosis. Astrocytic hamartomas of the optic nerve head and optic nerve head drusen have both been described in patients with retinitis pigmentosa. They can be a diagnostic dilemma although drusen are more common (10%). To differentiate these two entities it is very important to document any growth during the follow-up period which is suggestive of astrocytic hamartoma rather than optic disc drusen.

Ultrahigh-Speed Optical Coherence Tomography for Three-Dimensional and En Face Imaging of the Retina and Optic Nerve Head

PubMed Central

Srinivasan, Vivek J.; Adler, Desmond C.; Chen, Yueli; Gorczynska, Iwona; Huber, Robert; Duker, Jay S.; Schuman, Joel S.; Fujimoto, James G.

2009-01-01

Purpose To demonstrate ultrahigh-speed optical coherence tomography (OCT) imaging of the retina and optic nerve head at 249,000 axial scans per second and a wavelength of 1060 nm. To investigate methods for visualization of the retina, choroid, and optic nerve using high-density sampling enabled by improved imaging speed. Methods A swept-source OCT retinal imaging system operating at a speed of 249,000 axial scans per second was developed. Imaging of the retina, choroid, and optic nerve were performed. Display methods such as speckle reduction, slicing along arbitrary planes, en face visualization of reflectance from specific retinal layers, and image compounding were investigated. Results High-definition and three-dimensional (3D) imaging of the normal retina and optic nerve head were performed. Increased light penetration at 1060 nm enabled improved visualization of the choroid, lamina cribrosa, and sclera. OCT fundus images and 3D visualizations were generated with higher pixel density and less motion artifacts than standard spectral/Fourier domain OCT. En face images enabled visualization of the porous structure of the lamina cribrosa, nerve fiber layer, choroid, photoreceptors, RPE, and capillaries of the inner retina. Conclusions Ultrahigh-speed OCT imaging of the retina and optic nerve head at 249,000 axial scans per second is possible. The improvement of ∼5 to 10× in imaging speed over commercial spectral/Fourier domain OCT technology enables higher density raster scan protocols and improved performance of en face visualization methods. The combination of the longer wavelength and ultrahigh imaging speed enables excellent visualization of the choroid, sclera, and lamina cribrosa. PMID:18658089

Pediatric and adult vision restoration after optic nerve sheath decompression for idiopathic intracranial hypertension.

PubMed

Bersani, Thomas A; Meeker, Austin R; Sismanis, Dimitrios N; Carruth, Bryant P

2016-06-01

To compare presentations of idiopathic intracranial hypertension and efficacy of optic nerve sheath decompression between adult and pediatric patients, a retrospective cohort study was completed All idiopathic intracranial hypertension patients undergoing optic nerve sheath decompression by one surgeon between 1991 and 2012 were included. Pre-operative and post-operative visual fields, visual acuity, color vision, and optic nerve appearance were compared between adult and pediatric (<18 years) populations. Outcome measures included percentage of patients with complications or requiring subsequent interventions. Thirty-one adults (46 eyes) and eleven pediatric patients (18 eyes) underwent optic nerve sheath decompression for vision loss from idiopathic intracranial hypertension. Mean deviation on visual field, visual acuity, color vision, and optic nerve appearance significantly improved across all subjects. Pre-operative mean deviation was significantly worse in children compared to adults (p=0.043); there was no difference in mean deviation post-operatively (p=0.838). Significantly more pediatric eyes (6) presented with light perception only or no light perception than adult eyes (0) (p=0.001). Pre-operative color vision performance in children (19%) was significantly worse than in adults (46%) (p=0.026). Percentage of patients with complications or requiring subsequent interventions did not differ between groups. The consistent improvement after surgery and low rate of complications suggest optic nerve sheath decompression is safe and effective in managing vision loss due to adult and pediatric idiopathic intracranial hypertension. Given the advanced pre-operative visual deficits seen in children, one might consider a higher index of suspicion in diagnosing, and earlier surgical intervention in treating pediatric idiopathic intracranial hypertension.

Coronal Axis Measurement of the Optic Nerve Sheath Diameter Using a Linear Transducer.

PubMed

Amini, Richard; Stolz, Lori A; Patanwala, Asad E; Adhikari, Srikar

2015-09-01

The true optic nerve sheath diameter cutoff value for detecting elevated intracranial pressure is variable. The variability may stem from the technique used to acquire sonographic measurements of the optic nerve sheath diameter as well as sonographic artifacts inherent to the technique. The purpose of this study was to compare the traditional visual axis technique to an infraorbital coronal axis technique for assessing the optic nerve sheath diameter using a high-frequency linear array transducer. We conducted a cross-sectional study at an academic medical center. Timed optic nerve sheath diameter measurements were obtained on both eyes of healthy adult volunteers with a 10-5-MHz broadband linear array transducer using both traditional visual axis and coronal axis techniques. Optic nerve sheath diameter measurements were obtained by 2 sonologists who graded the difficulty of each technique and were blinded to each other's measurements for each participant. A total of 42 volunteers were enrolled, yielding 84 optic nerve sheath diameter measurements. There were no significant differences in the measurements between the techniques on either eye (P = .23 [right]; P = .99 [left]). Additionally, there was no difference in the degree of difficulty obtaining the measurements between the techniques (P = .16). There was a statistically significant difference in the time required to obtain the measurements between the traditional and coronal techniques (P < .05). Infraorbital coronal axis measurements are similar to measurements obtained in the traditional visual axis. The infraorbital coronal axis technique is slightly faster to perform and is not technically challenging. © 2015 by the American Institute of Ultrasound in Medicine.

Age related optic nerve axonal loss in adult Brown Norway rats.

PubMed

Cepurna, William O; Kayton, Robert J; Johnson, Elaine C; Morrison, John C

2005-06-01

The effect of age on the number and morphology of optic nerve axons in adult Brown Norway rats (5-31 months old) (n=29) was examined using transmission electron microscopy (TEM). By manually counting every axon in areas representing 60% of the optic nerve cross-section, we found a significant negative correlation between age and axon count (R(2)=0.18, P<0.05). However, when the oldest animals were omitted, the relationship was no longer statistically significant. Simultaneously, the proportion of spontaneously degenerating axons increased at an exponential rate (R(2)=0.79, P<0.05), with significantly more degeneration in the 31-month group than in 5-month-old animals (ANOVA, P<0.05). This study demonstrates, using quantitative TEM methods, that optic nerve axonal numbers are relatively constant throughout the majority of the adult life of the Brown Norway rat, an increasingly popular strain for glaucoma research. Total axonal loss with aging is substantially less than that reported for other strains. The reduction in axonal numbers and the rate of axonal degeneration do not appear significantly altered until the last few months of life, failing to support some studies that have concluded that optic nerve axon loss in adult rats is linear. However, they do agree with other studies in the rat, and a similar study performed in non-human primate eyes, that concluded that aging changes in the optic nerve and retina follow a complex pattern. Therefore, the impact of animal age must be considered when modeling the course and pathophysiology of experimental glaucomatous optic nerve damage in rats.

Applications of optical coherence tomography in pediatric clinical neuroscience.

PubMed

Avery, Robert A; Rajjoub, Raneem D; Trimboli-Heidler, Carmelina; Waldman, Amy T

2015-04-01

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve-the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions. Georg Thieme Verlag KG Stuttgart · New York.

High-resolution imaging of retinal nerve fiber bundles in glaucoma using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Ueda-Arakawa, Naoko; Yoshida, Sachiko; Akagi, Tadamichi; Ikeda, Hanako Ohashi; Nonaka, Atsushi; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2013-05-01

To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

Fourier-domain optical coherence tomography and adaptive optics reveal nerve fiber layer loss and photoreceptor changes in a patient with optic nerve drusen.

PubMed

Choi, Stacey S; Zawadzki, Robert J; Greiner, Mark A; Werner, John S; Keltner, John L

2008-06-01

New technology allows more precise definition of structural alterations of all retinal layers although it has not been used previously in cases of optic disc drusen. Using Stratus and Fourier domain (FD) optical coherence tomography (OCT) and adaptive optics (AO) through a flood-illuminated fundus camera, we studied the retinas of a patient with long-standing optic disc drusen and acute visual loss at high altitude attributed to ischemic optic neuropathy. Stratus OCT and FD-OCT confirmed severe thinning of the retinal nerve fiber layer (RNFL). FD-OCT revealed disturbances in the photoreceptor layer heretofore not described in optic disc drusen patients. AO confirmed the FD-OCT findings in the photoreceptor layer and also showed reduced cone density at retinal locations associated with reduced visual sensitivity. Based on this study, changes occur not only in the RNFL but also in the photoreceptor layer in optic nerve drusen complicated by ischemic optic neuropathy. This is the first reported application of FD-OCT and the AO to this condition. Such new imaging technology may in the future allow monitoring of disease progression more precisely and accurately.

Estimating a structural bottle neck for eye-brain transfer of visual information from 3D-volumes of the optic nerve head from a commercial OCT device

NASA Astrophysics Data System (ADS)

Malmberg, Filip; Sandberg-Melin, Camilla; Söderberg, Per G.

2016-03-01

The aim of this project was to investigate the possibility of using OCT optic nerve head 3D information captured with a Topcon OCT 2000 device for detection of the shortest distance between the inner limit of the retina and the central limit of the pigment epithelium around the circumference of the optic nerve head. The shortest distance between these boundaries reflects the nerve fiber layer thickness and measurement of this distance is interesting for follow-up of glaucoma.

Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

PubMed

Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A

1992-10-01

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened.

Stimulation of the human auditory nerve with optical radiation

NASA Astrophysics Data System (ADS)

Fishman, Andrew; Winkler, Piotr; Mierzwinski, Jozef; Beuth, Wojciech; Izzo Matic, Agnella; Siedlecki, Zygmunt; Teudt, Ingo; Maier, Hannes; Richter, Claus-Peter

2009-02-01

A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The finding is an important step for translating results from animal experiments to human and furthers the development of a novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the stimulation parameters.

Patterns of intraocular pressure elevation after aqueous humor outflow obstruction in rats.

PubMed

Jia, L; Cepurna, W O; Johnson, E C; Morrison, J C

2000-05-01

To determine the diural intraocular pressure (IOP) response of Brown Norway rat eyes after sclerosis of the aqueous humor outflow pathways and its relationship to optic nerve damage. Hypertonic saline was injected into a single episcleral vein in 17 animals and awake IOP measured in both the light and dark phases of the circadian cycle for 34 days. Mean IOP for light and dark phases during the experimental period were compared with the respective pressures of the uninjected fellow eyes. Optic nerve cross sections from each nerve were graded for injury by five independent masked observers. For fellow eyes, mean light- and dark-phase IOP was 21 +/- 1 and 31 +/- 1 mm Hg, respectively. For four experimental eyes, mean IOPs for both phases were not altered. Six eyes demonstrated significant mean IOP elevations only during the dark phase. Of these, five showed persistent, large circadian oscillations, and four had partial optic nerve lesions. The remaining seven eyes experienced significant IOP elevations during both phases, and all had extensive optic nerve damage. Episcleral vein injection of hypertonic saline is more likely to increase IOP during the dark phase than the light. This is consistent with aqueous outflow obstruction superimposed on a circadian rhythm of aqueous humor production. Because these periodic IOP elevations produced optic nerve lesions, both light- and dark-phase IOP determinations are necessary for accurate correlation of IOP history to optic nerve damage in animals housed in a light- dark environment.

Unilateral blindness with third cranial nerve palsy and abnormal enhancement of extraocular muscles on magnetic resonance imaging of orbit after the ingestion of methanol.

PubMed

Chung, Tae Nyoung; Kim, Sun Wook; Park, Yoo Seok; Park, Incheol

2010-05-01

Methanol is generally known to cause visual impairment and various systemic manifestations. There are a few reported specific findings for methanol intoxication on magnetic resonance imaging (MRI) of the brain. A case is reported of unilateral blindness with third cranial nerve palsy oculus sinister (OS) after the ingestion of methanol. Unilateral damage of the retina and optic nerve were confirmed by fundoscopy, flourescein angiography, visual evoked potential and electroretinogram. The optic nerve and extraocular muscles (superior rectus, medial rectus, inferior rectus and inferior oblique muscle) were enhanced by gadolinium-DTPA on MRI of the orbit. This is the first case report of permanent monocular blindness with confirmed unilateral damage of the retina and optic nerve, combined with third cranial nerve palsy after methanol ingestion.

Lost in the jungle: new hurdles for optic nerve axon regeneration.

PubMed

Pernet, Vincent; Schwab, Martin E

2014-07-01

The poor regenerative capacity of injured central nervous system (CNS) axons leads to permanent neurological deficits after brain, spinal cord, or optic nerve lesions. In the optic nerve, recent studies showed that stimulation of the cytokine or mammalian target of rapamycin (mTOR) signaling pathways potently enhances sprouting and regeneration of injured retinal ganglion cell axons in adult mice, but does not allow the majority of axons to reach their main cerebral targets. New analyses have revealed axon navigation defects in the optic nerve and at the optic chiasm under conditions of strong growth stimulation. We propose that a balanced growth stimulatory treatment will have to be combined with guidance factors and suppression of local growth inhibitory factors to obtain the full regeneration of long CNS axonal tracts. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Steven L.

2015-01-01

Purpose Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). Methods We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. Results A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. Conclusions A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION. PMID:26624498

A study of axonal degeneration in the optic nerves of aging mice

NASA Technical Reports Server (NTRS)

Johnson, J. E., Jr.; Philpott, D. E.; Miquel, J.

1978-01-01

The optic nerves of C57BL/6J mice ranging from 3 to 30 months were examined by electron microscopy. At all ages investigated, optic nerve axons contained enlarged mitochondria with abnormal cristae. With increasing age, a large number of necrotic axons were observed and were in the process of being phagocytized. The abnormal mitochondria may represent preliminary changes that eventually lead to necrosis of the axon.

Sodium channels in axons and glial cells of the optic nerve of Necturus maculosa.

PubMed

Tang, C M; Strichartz, G R; Orkand, R K

1979-11-01

Experiments investigating both the binding of radioactively labelled saxitoxin (STX) and the electrophysiological response to drugs that increase the sodium permeability of excitable membranes were conducted in an effort to detect sodium channels in glial cells of the optic nerve of Necturus maculosa, the mudpuppy. Glial cells in nerves from chronically enucleated animals, which lack optic nerve axons, show no saturable uptake of STX whereas a saturable uptake is clearly present in normal optic nerves. The normal nerve is depolarized by aconitine, batrachotoxin, and veratridine (10(-6)-10(-5) M), whereas the all-glial preparation is only depolarized by veratridine and at concentrations greater than 10(-3) M. Unlike the depolarization caused by veratridine in normal nerves, the response in the all-glial tissue is not blocked by tetrodotoxin nor enhanced by scorpion venom (Leiurus quinquestriatus). In glial cells of the normal nerve, where axons are also present, the addition of 10(-5) M veratridine does lead to a transient depolarization; however, it is much briefer than the axonal response to veratridine in this same tissue. This glial response to veratridine could be caused by the efflux of K+ from the drug-depolarized axons, and is similar to the glial response to extracellular K+ accumulation resulting from action potentials in the axon.

Sodium channels in axons and glial cells of the optic nerve of Necturus maculosa

PubMed Central

1979-01-01

Experiments investigating both the binding of radioactively labelled saxitoxin (STX) and the electrophysiological response to drugs that increase the sodium permeability of excitable membranes were conducted in an effort to detect sodium channels in glial cells of the optic nerve of Necturus maculosa, the mudpuppy. Glial cells in nerves from chronically enucleated animals, which lack optic nerve axons, show no saturable uptake of STX whereas a saturable uptake is clearly present in normal optic nerves. The normal nerve is depolarized by aconitine, batrachotoxin, and veratridine (10(-6)-10(-5) M), whereas the all-glial preparation is only depolarized by veratridine and at concentrations greater than 10(-3) M. Unlike the depolarization caused by veratridine in normal nerves, the response in the all-glial tissue is not blocked by tetrodotoxin nor enhanced by scorpion venom (Leiurus quinquestriatus). In glial cells of the normal nerve, where axons are also present, the addition of 10(-5) M veratridine does lead to a transient depolarization; however, it is much briefer than the axonal response to veratridine in this same tissue. This glial response to veratridine could be caused by the efflux of K+ from the drug- depolarized axons, and is similar to the glial response to extracellular K+ accumulation resulting from action potentials in the axon. PMID:512633

Optical Coherence Tomography in Glaucoma

NASA Astrophysics Data System (ADS)

Berisha, Fatmire; Hoffmann, Esther M.; Pfeiffer, Norbert

Retinal nerve fiber layer (RNFL) thinning and optic nerve head cupping are key diagnostic features of glaucomatous optic neuropathy. The higher resolution of the recently introduced SD-OCT offers enhanced visualization and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.

Retinal nerve fiber layer thickness measured with optical coherence tomography is related to visual function in glaucomatous eyes.

PubMed

El Beltagi, Tarek A; Bowd, Christopher; Boden, Catherine; Amini, Payam; Sample, Pamela A; Zangwill, Linda M; Weinreb, Robert N

2003-11-01

To determine the relationship between areas of glaucomatous retinal nerve fiber layer thinning identified by optical coherence tomography and areas of decreased visual field sensitivity identified by standard automated perimetry in glaucomatous eyes. Retrospective observational case series. Forty-three patients with glaucomatous optic neuropathy identified by optic disc stereo photographs and standard automated perimetry mean deviations >-8 dB were included. Participants were imaged with optical coherence tomography within 6 months of reliable standard automated perimetry testing. The location and number of optical coherence tomography clock hour retinal nerve fiber layer thickness measures outside normal limits were compared with the location and number of standard automated perimetry visual field zones outside normal limits. Further, the relationship between the deviation from normal optical coherence tomography-measured retinal nerve fiber layer thickness at each clock hour and the average pattern deviation in each visual field zone was examined by using linear regression (R(2)). The retinal nerve fiber layer areas most frequently outside normal limits were the inferior and inferior temporal regions. The least sensitive visual field zones were in the superior hemifield. Linear regression results (R(2)) showed that deviation from the normal retinal nerve fiber layer thickness at optical coherence tomography clock hour positions 6 o'clock, 7 o'clock, and 8 o'clock (inferior and inferior temporal) was best correlated with standard automated perimetry pattern deviation in visual field zones corresponding to the superior arcuate and nasal step regions (R(2) range, 0.34-0.57). These associations were much stronger than those between clock hour position 6 o'clock and the visual field zone corresponding to the inferior nasal step region (R(2) = 0.01). Localized retinal nerve fiber layer thinning, measured by optical coherence tomography, is topographically related to decreased localized standard automated perimetry sensitivity in glaucoma patients.

Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broomfield, C.A.; Maxwell, D.M.; Solana, R.P.

1991-12-31

Butyrylcholinesterase (BuChE) was examined as an in vivo exogenous scavenger for highly toxic organophosphorus (OP) poisons. Protection studies with equine BuChE were carried out in rhesus monkeys trained to perform a Serial Probe Recognition task. The pharmacokinetics of equine BuChE administered i.v. in rhesus monkeys revealed an elimination T1/2 of -620 hr. Animals given 503 nmol of BuChE i.v. and then challenged with 220 to 260 nmol of soman (two LD50; a lethal dose in untreated animals) all survived with no clinical signs of OP poisoning. Serial Probe Recognition performance was depressed after enzyme administration and at 1 hr postsoman.more » However, all monkeys performed the task at base-line levels at 8 hr after soman and throughout the remainder of the experimental period. Two different monkeys each were given two doses of sarin, 183 nmol/ dose (one LD50) after 460 nmol of BuChE. No signs were observed. A third group of monkeys given 253 or 340 nmol (three and four LD50, respectively) of soman after 460 nmol of BuChE required 1 mg/kg of atropine i.v. 1 0 min postsoman, but recovered completely within 24 hr. Our results indicate that BuChE has the required properties to function as a biological scavenger to protect against the pharmacological and behavioral toxicity of OP poisons. Exogenous scavenger, butyrylcholinesterase, nerve agent.« less

Study on the deformations of the lamina cribrosa during glaucoma.

PubMed

Tian, Hanjing; Li, Long; Song, Fan

2017-06-01

The lamina cribrosa is the primary site of optic nerve injury during glaucoma, and its deformations induced by elevated intraocular pressure are associated directly with the optic nerve injury and visual field defect. However, the deformations in a living body have been poorly understood yet so far. It is because that integral observation and precise measurement of the deformations in vivo are now almost impossible in the clinical diagnosis and treatment of glaucoma. In the present study, a new mechanical model of the lamina cribrosa is presented by using Reissner's thin plate theory. This model accurately displays the stress and deformation states in the lamina cribrosa under elevated intraocular pressure, in which the shear deformation is not presented by the previous models, however, is demonstrated to play a key role in the optic nerve injury. Further, the deformations of the structures, involving the optic nerve channels and the laminar sheets in the lamina cribrosa, are first investigated in detail. For example, the dislocation of the laminar sheets reaches 18.6μm under the intraocular pressure of 40mmHg, which is large enough to damage the optic nerve axons. The results here confirm some previously proposed clinical speculations on the deformations of the pore shape in the lamina cribrosa under elevated intraocular pressure during glaucoma. Finally, some essentially clinical questions existed during glaucoma, such as the pathological mechanism of the open-angle glaucoma with normal intraocular pressure, are discussed. The present study is beneficial to deeply understanding the optic nerve injury during glaucoma. The lamina cribrosa is the primary site of the optic nerve injury induced by elevated intraocular pressure during glaucoma. Under high intraocular pressure, the optic nerve channel near to the periphery of the lamina cribrosa (Channel A) is deformed to become into a tortuous elliptical horn from a straight cylinder, while the optic nerve channel near to the center of the lamina cribrosa (Channel B) is deformed to become into a straight horn from a straight cylinder. These deformations cause both the axoplasm flow obstacle in the axon fibers and the blocked blood flow in the capillaries which pass through the channels, and trigger the visual field defect during glaucoma. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of subacute pretreatment with carbamate together with acute adjunct pretreatment against nerve agent exposure. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, D.R.; Harris, L.W.; Lennox, W.J.

1991-12-31

Acute carbamate pretreatment, in conjunction with atropine pretreatment or followed by atropine and oxime therapy has been shown to protect rabbits, rats, guinea pigs and monkeys against multiple lethal doses of soman. In those experiments, pretreated animals were usually challenged with soman at the time of peak whole blood acetylcholinesterase (AChE) inhibition by the carbamate or when the concentration of carbamate in the blood was expected to be rapidly diminishing. However, soldiers in a chemical environment, having taken carbamate orally might well be exposed to nerve agent shortly thereafter. Thus, both active carbamate and nerve agent would be entering themore » blood simultaneously. In a recent study it was reported that subacute administration of physostigmine (Phy), via subcutaneously implanted 28 day osmotic minipump, afforded protection against an iv challenge of soman on the 27th day.« less

Evolution of an Astrocytic Hamartoma of the Optic Nerve Head in a Patient with Retinitis Pigmentosa – Photographic Documentation over 2 Years of Follow-Up

PubMed Central

Loukianou, Eleni; Kisma, Nacima; Pal, Bishwanathan

2011-01-01

Aim To report photographically the evolution of an astrocytic hamartoma of the left optic nerve head over a 2-year follow-up in a patient with retinitis pigmentosa. Methods A 14-year-old boy was seen in the medical retina clinic with a 3-year history of night blindness. Best corrected visual acuity was 6/18 in both eyes. Colour vision was normal in both eyes and confrontation fields showed peripheral constriction. Fundus examination revealed bone spicule pigmentary changes at the retinal mid periphery typical of retinitis pigmentosa and superficial globules at the margins of both optic nerve heads. Electrodiagnostic tests confirmed moderately severe rod cone dystrophy with macular involvement bilaterally. Results Two years later, the ocular examination was unchanged except for the appearance of the optic nerve head lesion in the left eye. There was an increase in the size of the lesion which was diagnosed as an astrocytic hamartoma. Further investigations were recommended to exclude neurofibromatosis and tuberous sclerosis. Conclusion Astrocytic hamartomas of the optic nerve head and optic nerve head drusen have both been described in patients with retinitis pigmentosa. They can be a diagnostic dilemma although drusen are more common (10%). To differentiate these two entities it is very important to document any growth during the follow-up period which is suggestive of astrocytic hamartoma rather than optic disc drusen. PMID:21347192

Effect of race, age, and axial length on optic nerve head parameters and retinal nerve fiber layer thickness measured by Cirrus HD-OCT.

PubMed

Knight, O'Rese J; Girkin, Christopher A; Budenz, Donald L; Durbin, Mary K; Feuer, William J

2012-03-01

To determine the effect of race, demographic, and ocular variables on optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements using spectral-domain optical coherence tomography. In a cross-sectional observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7 sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior RNFL thicknesses were calculated. The main outcome measures were associations between Cirrus HD-OCT optic nerve head and RNFL measurements and age, sex, and race. The 284 subjects self-identified as being of European (122), Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the effect of age, there was a statistically significant difference among racial groups for all optic nerve head and RNFL parameters (all P ≤ .005) except rim area (P = .22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and cup volume were moderately associated with disc area (r(2) = 0.15, 0.33, 0.33, and 0.37, respectively). After a linear adjustment for disc area, there was no statistically significant difference among racial groups for any optic nerve head parameter. Individuals of European descent had thinner RNFL measurements except in the temporal quadrant. There are racial differences in optic disc area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL thickness as measured by Cirrus HD-OCT. These differences should be considered when using Cirrus HD-OCT to assess for glaucomatous damage in differing population groups.

Effect of Race, Age, and Axial Length on Optic Nerve Head Parameters and Retinal Nerve Fiber Layer Thickness Measured by Cirrus HD-OCT

PubMed Central

Knight, O’Rese J.; Girkin, Christopher A.; Budenz, Donald L.; Durbin, Mary K.; Feuer, William J.

2017-01-01

Objective To determine the effect of race, demographic, and ocular variables on optic nerve head and retinal nerve fiber layer (RNFL) thickness measurements using spectral-domain optical coherence tomography. Methods In a cross-sectional observational study, 284 normal subjects aged 18 to 84 years were evaluated at 7 sites using Cirrus HD-OCT. Disc area, rim area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and average, temporal, superior, nasal, and inferior RNFL thicknesses were calculated. The main outcome measures were associations between Cirrus HD-OCT optic nerve head and RNFL measurements and age, sex, and race. Results The 284 subjects self-identified as being of European (122), Chinese (63), African (51), or Hispanic (35) descent. After adjusting for the effect of age, there was a statistically significant difference among racial groups for all optic nerve head and RNFL parameters (all P≤.005) except rim area (P=.22). Rim area, average cup-disc ratio, vertical cup-disc ratio, and cup volume were moderately associated with disc area (r2=0.15, 0.33, 0.33, and 0.37, respectively). After a linear adjustment for disc area, there was no statistically significant difference among racial groups for any optic nerve head parameter. Individuals of European descent had thinner RNFL measurements except in the temporal quadrant. Conclusions There are racial differences in optic disc area, average cup-disc ratio, vertical cup-disc ratio, cup volume, and RNFL thickness as measured by Cirrus HD-OCT. These differences should be considered when using Cirrus HD-OCT to assess for glaucomatous damage in differing population groups. PMID:22411660

Imaging of macrophage dynamics with optical coherence tomography in anterior ischemic optic neuropathy.

PubMed

Kokona, Despina; Häner, Nathanael U; Ebneter, Andreas; Zinkernagel, Martin S

2017-01-01

Anterior ischemic optic neuropathy (AION) is a relatively common cause of visual loss and results from hypoperfusion of the small arteries of the anterior portion of the optic nerve. AION is the leading cause of sudden optic nerve related vision loss with approximately 10 cases per 100'000 in the population over 50 years. To date there is no established treatment for AION and therefore a better understanding of the events occurring at the level of the optic nerve head (ONH) would be important to design future therapeutic strategies. The optical properties of the eye allow imaging of the optic nerve in vivo, which is a part of the CNS, during ischemia. Experimentally laser induced optic neuropathy (eLiON) displays similar anatomical features as anterior ischemic optic neuropathy in humans. After laser induced optic neuropathy we show that hyperreflective dots in optical coherence tomography correspond to mononuclear cells in histology. Using fluorescence-activated flow cytometry (FACS) we found these cells to peak one week after eLiON. These observations were translated to OCT findings in patients with AION, where similar dynamics of hyperreflective dots at the ONH were identified. Our data suggests that activated macrophages can be identified as hyperreflective dots in OCT. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

In vivo optical microscopy of peripheral nerve myelination with polarization sensitive-optical coherence tomography

PubMed Central

Henry, Francis P.; Wang, Yan; Rodriguez, Carissa L. R.; Randolph, Mark A.; Rust, Esther A. Z.; Winograd, Jonathan M.; de Boer, Johannes F.; Park, B. Hyle

2015-01-01

Abstract. Assessing nerve integrity and myelination after injury is necessary to provide insight for treatment strategies aimed at restoring neuromuscular function. Currently, this is largely done with electrical analysis, which lacks direct quantitative information. In vivo optical imaging with sufficient imaging depth and resolution could be used to assess the nerve microarchitecture. In this study, we examine the use of polarization sensitive-optical coherence tomography (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through measurements of birefringence after applying a nerve crush injury in a rat model. Initial loss of function and subsequent recovery were demonstrated by calculating the sciatic function index (SFI). We found that the PS-OCT phase retardation slope, which is proportional to birefringence, increased monotonically with the SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio shows that the PS-OCT slope is a good indicator of myelin health and recovery after injury. These results demonstrate that PS-OCT is capable of providing nondestructive and quantitative assessment of nerve health after injury and shows promise for continued use both clinically and experimentally in neuroscience. PMID:25858593

In vivo optical microscopy of peripheral nerve myelination with polarization sensitive-optical coherence tomography.

PubMed

Henry, Francis P; Wang, Yan; Rodriguez, Carissa L R; Randolph, Mark A; Rust, Esther A Z; Winograd, Jonathan M; de Boer, Johannes F; Park, B Hyle

2015-04-01

Assessing nerve integrity and myelination after injury is necessary to provide insight for treatment strategies aimed at restoring neuromuscular function. Currently, this is largely done with electrical analysis, which lacks direct quantitative information. In vivo optical imaging with sufficient imaging depth and resolution could be used to assess the nerve microarchitecture. In this study, we examine the use of polarization sensitive-optical coherence tomography (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through measurements of birefringence after applying a nerve crush injury in a rat model. Initial loss of function and subsequent recovery were demonstrated by calculating the sciatic function index (SFI). We found that the PS-OCT phase retardation slope, which is proportional to birefringence, increased monotonically with the SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio shows that the PS-OCT slope is a good indicator of myelin health and recovery after injury. These results demonstrate that PS-OCT is capable of providing nondestructive and quantitative assessment of nerve health after injury and shows promise for continued use both clinically and experimentally in neuroscience.

Palisade endings: cholinergic sensory organs or effector organs?

PubMed

Blumer, Roland; Konakci, Kadriye Zeynep; Pomikal, Christine; Wieczorek, Grazyna; Lukas, Julius-Robert; Streicher, Johannes

2009-03-01

This study aims to complement the authors' prior findings on palisade endings in extraocular muscles (EOMs) of monkeys, and to clarify whether palisade endings are cholinergic motor or cholinergic sensory. Macaque monkeys (Macaca fascicularis, n = 10) of both sexes were analyzed using three-dimensional (3D) reconstructions, confocal laser scanning microscopy (CLSM), and conventional/immuno transmission electron microscopy (TEM). For CLSM, we used three combinations of triple fluorescent labeling. EOM wholemounts were labeled with cholinergic markers, including choline acetyltransferase (ChAT), choline transporter (ChT), vesicular acetylcholine transporter (VAChT), and a classical postsynaptic marker for motor terminals, namely alpha-bungarotoxin. Muscle fibers were counterstained with phalloidin. 3D reconstructions were done of triple-labeled palisade endings. For immuno TEM, tissue was labeled with antibody against ChAT. Concordant with prior findings, the authors demonstrated that palisade endings at the muscle fiber tips arose from nerve fibers that are ChAT-positive. In 25% of the cases, axons forming palisade endings established multiple neuromuscular contacts outside the palisade complex. Such additional neuromuscular contacts were motor terminals, as demonstrated by alpha-bungarotoxin binding. All palisade endings established nerve terminals on the tendon. In 40% of the palisade endings, nerve terminals were observed on the muscle fiber as well. Neurotendinous contacts and neuromuscular contacts in palisade endings were ChT/ChAT/VAChT-immunoreactive. Neuromuscular contacts exhibited structural features of motor terminals and were also alpha-bungarotoxin positive. The present study ascertained that palisade endings are cholinergic motor organs. Therefore, it was concluded that palisade endings are not candidates to provide eye-position signals.

Biological applications and effects of optical masers

NASA Astrophysics Data System (ADS)

Ham, William T., Jr.; Mueller, Harold A.; Williams, Ray C.; Geeraets, Walter J.; Ruffolo, John J., Jr.

1988-02-01

Research experiments and projects pertaining to the ocular hazards of lasers and other optical sources are reviewed and discussed in some detail. Early studies to determine threshold retinal damage in the rabbit from ruby and neodymium lasers are described and followed by more elaborate experiments with monkeys using the He;Ne laser. A comparison between threshold retinal lesions in human volunteers, monkeys and rabbits is given. Retinal damage in the rhesus monkey is evaluated in terms of visual acuity. Quantitative data on solar retinitis as determined in the rhesus monkey are provided and the effects of wavelength on light toxicity are evaluated for eight monochromatic laser lines. Experiments performed at Los Alamos to evaluate the ocular effects and hazards of picosecond and nanosecond pulses of radiation from CO2 and HF lasers are described. A list of published papers describing the above research is included. The HF laser effects on the rabbit cornea were very similar to those caused by exposure to the CO2 laser. The energy from the CO2 and HF lasers is completely absorbed in the superficial layers of the cornea, creating a sharp sonic or shock wave which can disrupt the epithelial cells but does not penetrate to the stroma.

High resolution transbulbar sonography in children with suspicion of increased intracranial pressure.

PubMed

Steinborn, Marc; Friedmann, Melanie; Makowski, Christine; Hahn, Helmut; Hapfelmeier, Alexander; Juenger, Hendrik

2016-04-01

To evaluate the accuracy of high resolution transbulbar sonography for the estimation of intracranial pressure (ICP) in children. In children and adolescents with acute neurologic symptoms of various origin, transbulbar sonography was performed. Besides measurement of the optic nerve sheath diameter (ONSD), the ultrastructure of the subarachnoid space of the optic nerve sheath was evaluated. The results of transbulbar sonography were correlated with clinical data based on cross-sectional imaging, ICP measurement, and ophthalmologic examination. Eighty-one patients (age 3-17.8 years, mean 11.7 years) were included. In 25 children, cross-sectional imaging and ICP measurement revealed increased intracranial pressure. The mean ONSD was 6.85 ± 0.81 mm. Twenty patients (20/25, 80 %) had a microcystic appearance of the subarachnoid space of the optic nerve. In 56 children without evidence of increased intracranial pressure, the mean ONSD was 5.77 ± 0.48 mm. Forty-nine patients (49/56, 87.5 %) had a normal homogenous appearance of the subarachnoid space. The ONSD in children with increased intracranial pressure was significantly higher than in patients without (p < 0.001). High resolution transbulbar sonography of the optic nerve is a useful technique for the rapid and non-invasive estimation of intracranial pressure in children. Besides measurement of the optic nerve sheath diameter, evaluation of the ultrastructure of the subarachnoid space of the optic nerve is a helpful parameter.

Unilateral Loss of Spontaneous Venous Pulsations in an Astronaut

NASA Technical Reports Server (NTRS)

Mader, Thomas H.; Gibson, C. Robert; Lee, Andrew G.; Patel, Nimesh; Hart, Steven; Pettit, Donald R.

2014-01-01

Spontaneous venous pulsations seen on the optic nerve head (optic disc) are presumed to be caused by fluctuations in the pressure gradient between the intraocular and retrolaminar venous systems. The disappearance of previously documented spontaneous venous pulsations is a well-recognized clinical sign usually associated with a rise in intracranial pressure and a concomitant bilateral elevation of pressure in the subarachnoid space surrounding the optic nerves. In this correspondence we report the unilateral loss of spontaneous venous pulsations in an astronaut 5 months into a long duration space flight. We documented a normal lumbar puncture opening pressure 8 days post mission. The spontaneous venous pulsations were also documented to be absent 21 months following return to Earth.. We hypothesize that these changes may have resulted from a chronic unilateral rise in optic nerve sheath pressure caused by a microgravity-induced optic nerve sheath compartment syndrome.

Expanding the limits of endoscopic intraorbital tumor resection using 3-dimensional reconstruction.

PubMed

Gregorio, Luciano Lobato; Busaba, Nicolas Y; Miyake, Marcel M; Freitag, Suzanne K; Bleier, Benjamin S

2017-12-26

Endoscopic orbital surgery is a nascent field and new tools are required to assist with surgical planning and to ascertain the limits of the tumor resectability. We purpose to utilize three-dimensional radiographic reconstruction to define the theoretical lateral limit of endoscopic resectability of primary orbital tumors and to apply these boundary conditions to surgical cases. A three-dimensional orbital model was rendered in 4 representative patients presenting with primary orbital tumors using OsiriX open source imaging software. A 2-Dimensional plane was propagated between the contralateral nare and a line tangential to the long axis of the optic nerve reflecting the trajectory of a trans-septal approach. Any tumor volume falling medial to the optic nerve and/or within the space inferior to this plane of resectability was considered theoretically resectable regardless of how far it extended lateral to the optic nerve as nerve retraction would be unnecessary. Actual tumor volumes were then superimposed over this plan and correlated with surgical outcomes. Among the 4 lesions analyzed, two were fully medial to the optic nerve, one extended lateral to the optic nerve but remained inferior to the plane of resectability, and one extended both lateral to the optic nerve and superior to the plane of resectability. As predicted by the three-dimensional modeling, a complete resection was achieved in all lesions except one that transgressed the plane of resectability. No new diplopia or vision loss was observed in any patient. Three-dimensional reconstruction enhances preoperative planning for endoscopic orbital surgery. Tumors that extend lateral to the optic nerve may still be candidates for a purely endoscopic resection as long as they do not extend above the plane of resectability described herein. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Intrinsic-Signal Optical Imaging Reveals Cryptic Ocular Dominance Columns in Primary Visual Cortex of New World Owl Monkeys

PubMed Central

Kaskan, Peter M.; Lu, Haidong D.; Dillenburger, Barbara C.; Roe, Anna W.; Kaas, Jon H.

2007-01-01

A significant concept in neuroscience is that sensory areas of the neocortex have evolved the remarkable ability to represent a number of stimulus features within the confines of a global map of the sensory periphery. Modularity, the term often used to describe the inhomogeneous nature of the neocortex, is without a doubt an important organizational principle of early sensory areas, such as the primary visual cortex (V1). Ocular dominance columns, one type of module in V1, are found in many primate species as well as in carnivores. Yet, their variable presence in some New World monkey species and complete absence in other species has been enigmatic. Here, we demonstrate that optical imaging reveals the presence of ocular dominance columns in the superficial layers of V1 of owl monkeys (Aotus trivirgatus), even though the geniculate inputs related to each eye are highly overlapping in layer 4. The ocular dominance columns in owl monkeys revealed by optical imaging are circular in appearance. The distance between left eye centers and right eye centers is approximately 650 μm. We find no relationship between ocular dominance centers and other modular organizational features such as orientation pinwheels or the centers of the cytochrome oxidase blobs. These results are significant because they suggest that functional columns may exist in the absence of obvious differences in the distributions of activating inputs and ocular dominance columns may be more widely distributed across mammalian taxa than commonly suggested. PMID:18974855

In vivo thickness and birefringence determination of the human retinal nerve fiber layer using polarization-sensitive optical coherence tomography.

PubMed

Cense, B; Chen, T C; de Boer, J F

2006-01-01

Thinning of the retinal nerve fiber layer and changes in retinal nerve fiber layer birefringence may both precede clinically detectable glaucomatous vision loss. We present in vivo thickness and depth-resolved birefringence measurements of the human retinal nerve fiber layer (RNFL) by use of polarization-sensitive optical coherence tomography (PS-OCT). Using a fiber-based PS-OCT setup real-time images of the human retina in vivo were recorded, co-registered with retinal video images of the location of PS-OCT scans. PS-OCT scans around the optic nerve head (ONH) of two healthy young volunteers were made using 10 concentric circles of increasing radius. Both the mean retinal nerve fiber layer thickness and mean retinal nerve fiber birefringence for each of 48 sectors on a circle were determined. The retinal nerve fiber layer thickness and birefringence varied as a function of sector around the ONH. Measured double pass phase retardation per unit depth values around the ONH range between 0.10 and 0.35 degrees/microm. The retinal nerve fiber layer becomes thinner with increasing distance from the ONH. In contrast, the birefringence does not vary significantly with increasing distance from the ONH.

Indocyanine Green Videoangiography Transoptic Visualization and Clipping Confirmation of an Optic Splitting Ophthalmic Artery Aneurysm.

PubMed

Rustemi, Oriela; Cester, Giacomo; Causin, Francesco; Scienza, Renato; Della Puppa, Alessandro

2016-06-01

Ophthalmic artery aneurysms with medial and superior projection in exceptionally rare cases can split the optic nerve. Treatment of these aneurysms is challenging, because the aneurysm dome is hidden from the optic nerve, rendering its visualization and clipping confirmation difficult. In addition, optic nerve function should be preserved during surgical maneuvers. Preoperative detection of this growing feature is usually missing. We illustrate the first case of indocyanine green videoangiography (ICG-VA) application in an optic penetrating ophthalmic artery aneurysm treatment. A 57-year-old woman presented with temporal hemianopsia, slight right visual acuity deficit, and new onset of headache. The cerebral angiography detected a right ophthalmic artery aneurysm medially and superiorly projecting. The A1 tract of the ipsilateral anterior cerebral artery was elevated and curved, being suspicious for an under optic aneurysm growth. Surgery was performed. Initially the aneurysm was not visible. ICG-VA permitted the transoptic aneurysm visualization. After optic canal opening, the aneurysm was clipped and transoptic ICG-VA confirmed the aneurysm occlusion. ICG-VA showed also the slight improvement of the optic nerve pial vascularization. Postoperatively, the visual acuity was 10/10 and the hemianopsia did not worsen. The elevation and curve of the A1 tract in medially and superiorly projecting ophthalmic aneurysms may be an indirect sign of under optic growth, or optic splitting aneurysms. ICG-VA transoptic aneurysm detection and occlusion confirmation reduces the surgical maneuvers on the optic nerve, contributing to function preservation. Copyright © 2016 Elsevier Inc. All rights reserved.

Utility of coronal contrast-enhanced fat-suppressed FLAIR in the evaluation of optic neuropathy and atrophy.

PubMed

Boegel, Kevin H; Tyan, Andrew E; Iyer, Veena R; Rykken, Jeffrey B; McKinney, Alexander M

2017-01-01

Evaluating chronic sequelae of optic neuritis, such as optic neuropathy with or without optic nerve atrophy, can be challenging on whole brain MRI. This study evaluated the utility of dedicated coronal contrast-enhanced fat-suppressed FLAIR (CE-FS-FLAIR) MR imaging to detect optic neuropathy and optic nerve atrophy. Over 4.5 years, a 3 mm coronal CE-FS-FLAIR sequence at 1.5T was added to the routine brain MRIs of 124 consecutive patients, 102 of whom had suspected or known demyelinating disease. Retrospective record reviews confirmed that 28 of these 102 had documented onset of optic neuritis >4 weeks prior to the brain MRI. These 28 were compared to the other 22 ("controls") of the 124 patients who lacked a history of demyelinating disease or visual symptoms. Using coronal CE-FS-FLAIR, two neuroradiologists separately graded each optic nerve (n = 50 patients, 100 total nerves) as either negative, equivocal, or positive for optic neuropathy or atrophy. The scoring was later repeated. The mean time from acute optic neuritis onset to MRI was 4.1 ± 4.6 years (range 34 days-17.4 years). Per individual nerve grading, the range of sensitivity, specificity, and accuracy of coronal CE-FS-FLAIR in detecting optic neuropathy was 71.4-77.1%, 93.8-95.4%, and 85.5-89.0%, respectively, with strong interobserver (k = 0.667 - 0.678, p < 0.0001), and intraobserver (k = 0.706 - 0.763, p < 0.0001) agreement. For optic atrophy, interobserver agreement was moderate (k = 0.437 - 0.484, p < 0.0001), while intraobserver agreement was moderate-strong (k = 0.491 - 0.596, p < 0.0001). Coronal CE-FS-FLAIR is quite specific in detecting optic neuropathy years after the onset of acute optic neuritis, but is less useful in detecting optic nerve atrophy.

The optic nerve: A “mito-window” on mitochondrial neurodegeneration

PubMed Central

Maresca, Alessandra; la Morgia, Chiara; Caporali, Leonardo; Valentino, Maria Lucia; Carelli, Valerio

2013-01-01

Retinal ganglion cells (RGCs) project their long axons, composing the optic nerve, to the brain, transmitting the visual information gathered by the retina, ultimately leading to formed vision in the visual cortex. The RGC cellular system, representing the anterior part of the visual pathway, is vulnerable to mitochondrial dysfunction and optic atrophy is a very frequent feature of mitochondrial and neurodegenerative diseases. The start of the molecular era of mitochondrial medicine, the year 1988, was marked by the identification of a maternally inherited form of optic atrophy, Leber's hereditary optic neuropathy, as the first disease due to mitochondrial DNA point mutations. The field of mitochondrial medicine has expanded enormously over the last two decades and many neurodegenerative diseases are now known to have a primary mitochondrial etiology or mitochondrial dysfunction plays a relevant role in their pathogenic mechanism. Recent technical advancements in neuro-ophthalmology, such as optical coherence tomography, prompted a still ongoing systematic re-investigation of retinal and optic nerve involvement in neurodegenerative disorders. In addition to inherited optic neuropathies, such as Leber's hereditary optic neuropathy and dominant optic atrophy, and in addition to the syndromic mitochondrial encephalomyopathies or mitochondrial neurodegenerative disorders such as some spinocerebellar ataxias or familial spastic paraparesis and other disorders, we draw attention to the involvement of the optic nerve in classic age-related neurodegenerative disorders such as Parkinson and Alzheimer disease. We here provide an overview of optic nerve pathology in these different clinical settings, and we review the possible mechanisms involved in the pathogenesis of optic atrophy. This may be a model of general value for the field of neurodegeneration. This article is part of a Special Issue entitled ‘Mitochondrial function and dysfunction in neurodegeneration’. PMID:22960139

Auditory-nerve single-neuron thresholds to electrical stimulation from scala tympani electrodes.

PubMed

Parkins, C W; Colombo, J

1987-12-31

Single auditory-nerve neuron thresholds were studied in sensory-deafened squirrel monkeys to determine the effects of electrical stimulus shape and frequency on single-neuron thresholds. Frequency was separated into its components, pulse width and pulse rate, which were analyzed separately. Square and sinusoidal pulse shapes were compared. There were no or questionably significant threshold differences in charge per phase between sinusoidal and square pulses of the same pulse width. There was a small (less than 0.5 dB) but significant threshold advantage for 200 microseconds/phase pulses delivered at low pulse rates (156 pps) compared to higher pulse rates (625 pps and 2500 pps). Pulse width was demonstrated to be the prime determinant of single-neuron threshold, resulting in strength-duration curves similar to other mammalian myelinated neurons, but with longer chronaxies. The most efficient electrical stimulus pulse width to use for cochlear implant stimulation was determined to be 100 microseconds/phase. This pulse width delivers the lowest charge/phase at threshold. The single-neuron strength-duration curves were compared to strength-duration curves of a computer model based on the specific anatomy of auditory-nerve neurons. The membrane capacitance and resulting chronaxie of the model can be varied by altering the length of the unmyelinated termination of the neuron, representing the unmyelinated portion of the neuron between the habenula perforata and the hair cell. This unmyelinated segment of the auditory-nerve neuron may be subject to aminoglycoside damage. Simulating a 10 micron unmyelinated termination for this model neuron produces a strength-duration curve that closely fits the single-neuron data obtained from aminoglycoside deafened animals. Both the model and the single-neuron strength-duration curves differ significantly from behavioral threshold data obtained from monkeys and humans with cochlear implants. This discrepancy can best be explained by the involvement of higher level neurologic processes in the behavioral responses. These findings suggest that the basic principles of neural membrane function must be considered in developing or analyzing electrical stimulation strategies for cochlear prostheses if the appropriate stimulation of frequency specific populations of auditory-nerve neurons is the objective.

Optical stimulation of the facial nerve: a surgical tool?

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Teudt, Ingo Ulrik; Nevel, Adam E.; Izzo, Agnella D.; Walsh, Joseph T., Jr.

2008-02-01

One sequela of skull base surgery is the iatrogenic damage to cranial nerves. Devices that stimulate nerves with electric current can assist in the nerve identification. Contemporary devices have two main limitations: (1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue. Stimulation and screening of the nerve is possible without making physical contact. The gerbil facial nerve was irradiated with 250-μs-long pulses of 2.12 μm radiation delivered via a 600-μm-diameter optical fiber at a repetition rate of 2 Hz. Muscle action potentials were recorded with intradermal electrodes. Nerve samples were examined for possible tissue damage. Eight facial nerves were stimulated with radiant exposures between 0.71-1.77 J/cm2, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3-0.4 mV, 0.15-1.4 mV and 0.3-2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm2, but no apparent damage at radiant exposures of 2.0 J/cm2.

Human neural tuning estimated from compound action potentials in normal hearing human volunteers

NASA Astrophysics Data System (ADS)

Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

2015-12-01

The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

Analyzing Sub-Classifications of Glaucoma via SOM Based Clustering of Optic Nerve Images.

PubMed

Yan, Sanjun; Abidi, Syed Sibte Raza; Artes, Paul Habib

2005-01-01

We present a data mining framework to cluster optic nerve images obtained by Confocal Scanning Laser Tomography (CSLT) in normal subjects and patients with glaucoma. We use self-organizing maps and expectation maximization methods to partition the data into clusters that provide insights into potential sub-classification of glaucoma based on morphological features. We conclude that our approach provides a first step towards a better understanding of morphological features in optic nerve images obtained from glaucoma patients and healthy controls.

Regeneration-associated genes on optic nerve regeneration in fish retina.

PubMed

Ogai, Kazuhiro; Nishitani, Maki; Kuwana, Ayaka; Mawatari, Kazuhiro; Koriyama, Yoshiki; Sugitani, Kayo; Nakashima, Hiroshi; Kato, Satoru

2014-01-01

It has been well documented that fish central nervous system, including retina and optic nerve, can regenerate and recover its function after nerve injury. Within a few decades, a number of regeneration-associated genes (RAGs) have been identified in fish retina following optic nerve injury (ONI). RAGs can be classified into two groups: cell survival- and axonal outgrowth-related genes. In fish retina after ONI, cell survival-related genes were upregulated in 1-6 days after ONI, which corresponds to the preparation stage for cell survival and axonal sprouting. Subsequently, axonal outgrowth-related genes were upregulated in 1-6 weeks after ONI, which corresponds to the axonal regrowth stage. Recently, we've found a novel type of RAGs, dedifferentiation-related genes, that are upregulated in overlapping time between cell survival and axonal regrowth (3-10 days after ONI). In this chapter we summarize these three types of RAGs that promote optic nerve regeneration in the fish retina after ONI.

Modeling the Effects of Spaceflight on the Posterior Eye in VIIP

NASA Technical Reports Server (NTRS)

Ethier, C. R.; Feola, A. J.; Raykin, J.; Mulugeta, L.; Gleason, R.; Myers, J. G.; Nelson, E. S.; Samuels, B.

2015-01-01

Purpose: Visual Impairment and Intracranial Pressure (VIIP) syndrome is a new and significant health concern for long-duration space missions. Its etiology is unknown, but is thought to involve elevated intracranial pressure (ICP)that induces connective tissue changes and remodeling in the posterior eye (Alexander et al. 2012). Here we study the acute biomechanical response of the lamina cribrosa (LC) and optic nerve to elevations in ICP utilizing finite element (FE) modeling. Methods: Using the geometry of the posterior eye from previous axisymmetric FE models (Sigal et al. 2004), we added an elongated optic nerve and optic nerve sheath, including the pia and dura. Tissues were modeled as linear elastic solids. Intraocular pressure and central retinal vessel pressures were set at 15 mmHg and 55 mmHg, respectively. ICP varied from 0 mmHg (suitable for standing on earth) to 30 mmHg (representing severe intracranial hypertension, thought to occur in space flight). We focused on strains and deformations in the LC and optic nerve (within 1 mm of the LC) since we hypothesize that they may contribute to vision loss in VIIP. Results: Elevating ICP from 0 to 30 mmHg significantly altered the strain distributions in both the LC and optic nerve (Figure), notably leading to more extreme strain values in both tension and compression. Specifically, the extreme (95th percentile) tensile strains in the LC and optic nerve increased by 2.7- and 3.8-fold, respectively. Similarly, elevation of ICP led to a 2.5- and 3.3-fold increase in extreme (5th percentile) compressive strains in the LC and optic nerve, respectively. Conclusions: The elevated ICP thought to occur during spaceflight leads to large acute changes in the biomechanical environment of the LC and optic nerve, and we hypothesize that such changes can activate mechanosensitive cells and invoke tissue remodeling. These simulations provide a foundation for more comprehensive studies of microgravity effects on human vision, e.g. to guide biological studies in which cells and tissues are mechanically loaded in a ranger elevant for microgravity conditions.

Optic nerve sheath fenestration using a Raman-shifted alexandrite laser

PubMed Central

Kozub, John; Shen, Jin-H.; Joos, Karen M.; Prasad, Ratna; Hutson, M. Shane

2016-01-01

Background and Objective Optic nerve sheath fenestration is an established procedure for relief of potentially damaging overpressure on the optic nerve resulting from idiopathic intracranial hypertension. Prior work showed that a mid-IR free-electron laser could be delivered endoscopically and used to produce an effective fenestration. This study evaluates the efficacy of fenestration using a table-top mid-IR source based on a Raman-shifted alexandrite (RSA) laser. Study Design/Materials and Methods Porcine optic nerves were ablated using light from an RSA laser at wavelengths of 6.09, 6.27 and 6.43 μm and pulse energies up to 3 mJ using both free-space and endoscopic beam delivery through 250-μm I.D. hollow-glass waveguides. Waveguide transmission was characterized, ablation thresholds and etch rates were measured, and the efficacy of endoscopic fenestration was evaluated for ex vivo exposures using both optical coherence tomography and histological analysis. Results Using endoscopic delivery, the RSA laser can effectively fenestrate porcine optic nerves. Performance was optimized at a wavelength of 6.09 μm and delivered pulse energies of 0.5-0.8 mJ (requiring 1.5-2.5 mJ to be incident on the waveguide). Under these conditions, the ablation threshold fluence was 0.8 ± 0.2 J/cm2, the ablation rate was 1-4 μm/pulse, and the margins of ablation craters showed little evidence of thermal or mechanical damage. Nonetheless, nominally identical exposures yielded highly variable ablation rates. This led to fenestrations that ranged from too deep to too shallow – either damaging the underlying optic nerve or requiring additional exposure to cut fully through the sheath. Of 48 excised nerves subjected to fenestration at 6.09 μm, 16 ex vivo fenestrations were judged as good, 23 as too deep, and 9 as too shallow. Conclusions Mid-IR pulses from the RSA laser, propagated through a flexible hollow waveguide, are capable of cutting through porcine optic nerve sheaths in surgically relevant times with reasonable accuracy and low collateral damage. This can be accomplished at wavelengths of 6.09 or 6.27 μm, with 6.09 μm slightly preferred. The depth of ex vivo fenestrations was difficult to control, but excised nerves lack a sufficient layer of cerebrospinal fluid that would provide an additional margin of safety in actual patients. PMID:27020001

Locomotor recovery after spinal cord hemisection/contusion injures in bonnet monkeys: footprint testing--a minireview.

PubMed

Rangasamy, Suresh Babu

2013-07-01

Spinal cord injuries usually produce loss or impairment of sensory, motor and reflex function below the level of damage. In the absence of functional regeneration or manipulations that promote regeneration, spontaneous improvements in motor functions occur due to the activation of multiple compensatory mechanisms in animals and humans following the partial spinal cord injury. Many studies were performed on quantitative evaluation of locomotor recovery after induced spinal cord injury in animals using behavioral tests and scoring techniques. Although few studies on rodents have led to clinical trials, it would appear imperative to use nonhuman primates such as macaque monkeys in order to relate the research outcomes to recovery of functions in humans. In this review, we will discuss some of our research evidences concerning the degree of spontaneous recovery in bipedal locomotor functions of bonnet monkeys that underwent spinal cord hemisection/contusion lesions. To our knowledge, this is the first report to discuss on the extent of spontaneous recovery in bipedal locomotion of macaque monkeys through the application of footprint analyzing technique. In addition, the results obtained were compared with the published data on recovery of quadrupedal locomotion of spinally injured rodents. We propose that the mechanisms underlying spontaneous recovery of functions in spinal cord lesioned monkeys may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Moreover, based on analysis of motor functions observed in locomotion in these subjected monkeys, we understand that spinal automatism and development of responses by afferent stimuli from outside the cord could possibly contribute to recovery of paralyzed hindlimbs. This report also emphasizes the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed in partially lesioned cord of monkeys. Copyright © 2013 Wiley Periodicals, Inc.

FIBER-OPTIC BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

EPA Science Inventory

A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve
agents was developed. The basic element of this biosensor is organophosphorus hydrolase
immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber
bundle....

Neuroprotective Strategies for the Treatment of Blast-Induced Optic Neuropathy

DTIC Science & Technology

2016-09-01

will examine alterations in the amacrine cells and ganglion cells as well as therapeutic outcome measures including electroretinogram, visual evoked...nerve degeneration.1-3 This suggests that degeneration of the retinal ganglion cell (RGC) axons in the optic nerve is a secondary event. Secondary...for neurodegenerations from trauma extending beyond optic neuropathy. 2. Keywords: retinal ganglion cell (RGC), traumatic optic neuropathy

Torsional Eye Movements Evoked by Unilateral Labyrinthine Galvanic Polarizations in the Squirrel Monkey

NASA Technical Reports Server (NTRS)

Minor, Lloyd B.; Tomko, David L.; Paige, Gary D.

1995-01-01

Electrical stimulation of vestibular-nerve afferents innervating the semicircular canals has been used to identify the extraocular muscles receiving activation or inhibition by individual ampullary nerves. This technique was originally developed by Szentagothai (1950) and led to the description of three neuron reflex arcs that connect each semicircular canal through an interneuron traversing in the region of the medial longitudinal fasciculus to one ipsilateral and one contralateral eye muscle. Selective ampullary nerve stimulation was subsequently used by Cohen and colleagues (Cohen and Suzuki, 1963; Cohen et al., 1964; Suzuki et al., 1964; Cohen et al., 1966) to study movements of the eyes and activation of individual extraocular muscles in response to stimulation of combinations of ampullary nerves. This work led to a description of the now familiar relationships between activation of a semicircular canal ampullary nerves and the anticipated movement in each eye. Disconjugacy of eye movements induced by individual vertical canal stimulation and dependence of the pulling direction of vertical recti and oblique muscles on eye position were also defined in these experiments. Subsequent studies have defined the mechanisms by which externally applied galvanic currents result in a change in vestibular-nerve afferent discharge. The currents appear to act at the spike trigger site. Perilymphatic cathodal currents depolarize the trigger site and lead to excitation whereas anodal currents hyperpolarize and result in inhibition. Afferents innervating all five vestibular endorgans appear to be affected equally by the currents (Goldberg et al., 1984). Irregularly discharging afferents are about 5-10 times more sensitive than regularly discharging ones because of the steeper slope of the former's faster postspike recovery of excitability in encoder sensitivity (Smith and Goldberg, 1986). Response adaptation similar to that noted during acceleration steps is apparent for longer periods of current administration. This adaptation is manifested as a perstimulus return toward resting discharge and poststimulus after-response in the opposite direction (Goldberg et al., 1984; Minor and Goldberg, l991). Cathodal currents (with respect to the perilymphatic space of the vestibule) are excitatory whereas anodal currents are inhibitory. Horizontal eye movements evoked by unilateral galvanic polarizations administered through chronically implanted labyrinthine stimulating electrodes have been studied in alert squirrel monkeys (Minor and Goldberg, 1991). We sought to extend this analysis by recording three-dimensional eye movements during galvanic stimulation. As predicted based upon roughly equal stimulation of ampullary nerves innervating the vertical canals, a substantial torsional component to the nystagmus is noted. The trajectory of torsional slow phases and nystagmus profile after the polarization provide insight into the central mechanisms that influence these responses.

Congenital anomalies of the optic nerve

PubMed Central

Amador-Patarroyo, Manuel J.; Pérez-Rueda, Mario A.; Tellez, Carlos H.

2014-01-01

Congenital optic nerve head anomalies are a group of structural malformations of the optic nerve head and surrounding tissues, which may cause congenital visual impairment and blindness. Each entity in this group of optic nerve anomalies has individually become more prevalent as our ability to differentiate between them has improved due to better characterization of cases. Access to better medical technology (e.g., neuroimaging and genetic analysis advances in recent years) has helped to expand our knowledge of these abnormalities. However, visual impairment may not be the only problem in these patients, some of these entities will be related to ophthalmologic, neurologic and systemic features that will help the physician to identify and predict possible outcomes in these patients, which sometimes may be life-threatening. Herein we present helpful hints, associations and management (when plausible) for them. PMID:25859137

Reduced ventral cingulum integrity and increased behavioral problems in children with isolated optic nerve hypoplasia and mild to moderate or no visual impairment.

PubMed

Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

2013-01-01

To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified. Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed. Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = -0.52, p<0.02, r = -0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores. Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises questions as to the pathogenesis of these changes which will need to be addressed by future studies.

Quantitative relations between the eyeball, the optic nerve, and the optic canal important for intracranial pressure monitoring

PubMed Central

2014-01-01

Objective To find correlations between diameters of the optic nerve sheath (ONSD), the eyeball, and the optic canal that might be important for intracranial pressure monitoring. Methods In a prospective cohort study, the CT data of consecutive 400 adults (18+) with healthy eyes and optic nerves and absence of neurological diseases were collected and analyzed. When the CT scans were obtained, the diameters of the optic nerve sheath, the eyeball, and the optic canal were measured and statistically analyzed. The data obtained from the left and from the right eyeballs and optic nerves were compared. The correlation analysis was performed within these variables, with the gender, and the age. Results In healthy persons, the ONSD varies from 3.65 mm to 5.17 mm in different locations within the intraorbital space with no significant difference between sexes and age groups. There is a strong correlation between the eyeball transverse diameter (ETD) and ONSD that can be presented as ONSD/ETD index. In healthy subjects, the ONSD/ETD index equals 0.19. Conclusion The calculation of an index when ONSD is divided by the ETD of the eyeball presents precise normative database for ONSD intracranial pressure measurement technique. When the ONSD is measured for intracranial pressure monitoring, the most stable results can be obtained if the diameter is measured 10 mm from the globe. These data might serve as a normative database at emergency departments and in general neurological practice. PMID:25130267

Quantitative relations between the eyeball, the optic nerve, and the optic canal important for intracranial pressure monitoring.

PubMed

Vaiman, Michael; Gottlieb, Paul; Bekerman, Inessa

2014-08-17

To find correlations between diameters of the optic nerve sheath (ONSD), the eyeball, and the optic canal that might be important for intracranial pressure monitoring. In a prospective cohort study, the CT data of consecutive 400 adults (18+) with healthy eyes and optic nerves and absence of neurological diseases were collected and analyzed. When the CT scans were obtained, the diameters of the optic nerve sheath, the eyeball, and the optic canal were measured and statistically analyzed. The data obtained from the left and from the right eyeballs and optic nerves were compared. The correlation analysis was performed within these variables, with the gender, and the age. In healthy persons, the ONSD varies from 3.65 mm to 5.17 mm in different locations within the intraorbital space with no significant difference between sexes and age groups. There is a strong correlation between the eyeball transverse diameter (ETD) and ONSD that can be presented as ONSD/ETD index. In healthy subjects, the ONSD/ETD index equals 0.19. The calculation of an index when ONSD is divided by the ETD of the eyeball presents precise normative database for ONSD intracranial pressure measurement technique. When the ONSD is measured for intracranial pressure monitoring, the most stable results can be obtained if the diameter is measured 10 mm from the globe. These data might serve as a normative database at emergency departments and in general neurological practice.

[The neuroprotective effect of erigeron breviscapus (vant) hand-mazz on retinal ganglion cells after optic nerve crush injury].

PubMed

Jiang, Bing; Jiang, You-qin

2003-08-01

To investigate whether a Chinese herbal medicine, erigeron breviscapus (vant) hand-mazz (EBHM), can protect the retinal ganglion cells (RGC) damaged by calibrated optic nerve crush injury. Forty-two Sprague-Dawley rats were randomly divided into two groups. Calibrated optic nerve crush injury model was induced in the right eyes by a special designed optic nerve clip. The left eyes served as a control. All 42 rats were randomly divided into 2 groups. Group A consisted of the rats with calibrated optic nerve crush injury and group B consisted of rats with calibrated optic nerve crush injury treated with EBHM. In group B, EBHM solution was given once after the crush injury. According to the time interval between the optic nerve crush and the sacrifice, both groups A and B were further divided into three subgroups (day 4, day 14 and day 21). Therefore, there were 7 rats in each subgroup. Three days before sacrifice, 3% fast blue was injected into superior colliculi bilaterally. The eyes were enucleated after the rat was sacrificed, and flat mounts of the retina from both eyes were prepared on a slide and observed under a fluorescence microscope. Four photos with 400 x magnification were taken from each of the four quadrants of the retina 1 mm away from the optic disc. The labeled RGC were counted by a computerized image analyzer. The labeled RGC rate was used for statistical analysis (the labeled RGC rate = number of RGC in injured eye/control eye x 100%). In group A, the labeled RGC rate was (77.79 +/- 7.11)%, (63.76 +/- 3.79)% and (54.66 +/- 4.75)% on day 4, day 14 and day 21, respectively. In group B, the labeled RGC rate was (80.13 +/- 12.03)%, (78.17 +/- 9.19)% and (83.59 +/- 12.61)% on day 4, day 14 and day 21, respectively. In group B, which was treated with EBHM after injury, the labeled RGC rate was significantly higher than that of group A on day 14 and day 21. In the experimental optic nerve crush model in rats, EBHM therapy can increase the survival rate of the RGC and can rescue and/or restore the injured RGC.

Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity.

PubMed

Leibinger, Marco; Andreadaki, Anastasia; Golla, Renate; Levin, Evgeny; Hilla, Alexander M; Diekmann, Heike; Fischer, Dietmar

2017-07-03

Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3 S/A knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons. Conversely, genetic or shRNA-mediated conditional KO/knockdown of GSK3β reduced inhibitory phosphorylation of CRMP2 in RGCs and improved optic nerve regeneration. Accordingly, GSK3β KO-mediated neurite growth promotion and myelin disinhibition were abrogated by CRMP2 inhibition and largely mimicked in WT neurons upon expression of constitutively active CRMP2 (CRMP2 T/A ). These results underscore the prevalent requirement of active CRMP2 for optic nerve regeneration. Strikingly, expression of CRMP2 T/A in GSK3 S/A RGCs further boosted optic nerve regeneration, with axons reaching the optic chiasm within 3 wk. Thus, active GSK3 can also markedly promote axonal growth in central nerves if CRMP2 concurrently remains active. Similar to peripheral nerves, GSK3-mediated MAP1B phosphorylation/activation and the reduction of microtubule detyrosination contributed to this effect. Overall, these findings reconcile conflicting data on GSK3-mediated axon regeneration. In addition, the concept of complementary modulation of normally antagonistically targeted GSK3 substrates offers a therapeutically applicable approach to potentiate the regenerative outcome in the injured CNS.

Retinal nerve fiber layer changes after LASIK evaluated with optical coherence tomography.

PubMed

Dementyev, Dmitriy D; Kourenkov, Vyacheslav V; Rodin, Alexander S; Fadeykina, Tatyana L; Diaz Martines, Tatyana E

2005-01-01

To determine whether the increase in intraocular pressure (IOP) during LASIK suction can induce a decrease in retinal nerve fiber layer thickness assessed by optical coherence tomography (OCT). Nineteen patients (38 eyes) were enrolled in the study. Intraocular pressure was normal at all pre- and postoperative examinations. Retinal nerve fiber layer thickness was measured using OCT-3 Stratus prior to and 1 week and 3 months after LASIK. Laser in situ keratomileusis was performed using the Bausch & Lomb Hansatome microkeratome and the NIDEK EC-5000 excimer laser. Optical coherence tomography mean retinal nerve fiber layer thickness values before and after LASIK were compared using the Student paired t test. Mean patient age was 27.8 years (range: 18 to 33 years). Mean preoperative spherical equivalent refractive error was -4.9 diopters (D) (range: -2.0 to -8.5 D). Mean time of microkeratome suction was 30 seconds (range: 20 to 50 seconds). Preoperatively, the mean retinal nerve fiber layer thickness obtained by OCT was 104.2+/-9.0 microm; at 1 week postoperatively the mean thickness was 101.9+/-6.9 microm, and 106.7+/-6.1 microm at 3 months postoperatively. Mean retinal nerve fiber layer thicknesses obtained by OCT were not significantly different between preoperative and 1 week and 3 months after LASIK (P > or = .05). Laser in situ keratomileusis performed on young myopic patients does not have a significant effect on retinal nerve fiber layer thickness determined by OCT. Further studies are required to reveal the risk of possible optic nerve or retinal nerve fiber layer damage by elevated IOP during LASIK.

Peripapillary nerve fiber layer thickness measurement reproducibility using optical coherence tomography.

PubMed

Villain, Max A; Greenfield, David S

2003-01-01

To assess reproducibility of quadrantic and clock hour sectors of retinal nerve fiber layer thickness in normal eyes using optical coherence tomography. Normal eyes of healthy volunteers meeting eligibility criteria were imaged by two inexperienced operators. Six 360 degrees circular scans with a diameter of 3.4 mm centered on the optic disc were obtained during each scanning session, and a baseline image was formed using 3 high-quality images defined by the software. Images were obtained on three different days within a 4-week period. Variance and coefficient of variation (CV) were calculated for quadrantic and retinal nerve fiber layer clock hour sectors obtained from the baseline image. Five normal eyes were scanned. Intraoperator reproducibility was high. The mean (+/- SD) CV for total retinal nerve fiber layer thickness was 5.3 +/- 3.82% and 4.33 +/- 3.7% for operators 1 and 2, respectively. Interoperator reproducibility was good with statistically similar variance for all quadrantic and clock hour retinal nerve fiber layer parameters (P = .42 to .99). The nasal retinal nerve fiber layer was the most variable sector for both operators (mean CV: 10.42% and 7.83% for operators 1 and 2, respectively). Differences in mean total, nasal, temporal, and superior retinal nerve fiber layer thickness were not statistically significant between operators for all eyes; however, for inferior retinal nerve fiber layer thickness, there was a significant (P = .0007) difference between operators in one eye. Peripapillary retinal nerve fiber layer thickness assessments using optical coherence tomography have good intraoperator and interoperator reproducibility. Inexperienced operators can generate useful measurement data with acceptable levels of variance.

Axonal transport rate decreased at the onset of optic neuritis in EAE mice

PubMed Central

Lin, Tsen-Hsuan; Kim, Joong Hee; Perez-Torres, Carlos; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn2+ accumulation rate (in % signal change/hour) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn2+ transport rate (in mm/hour) by measuring the rate of change in optic nerve length enhanced by Mn2+. Compared to sham-treated healthy mice, Mn2+ accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn2+ was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis. PMID:24936685

Optic nerve head drusen and idiopathic intracranial hypertension in a 14-year-old girl.

PubMed

Granger, Robert H; Bonnelame, Thomas; Daubenton, John; Dreyer, Michael; McCartney, Paul

2009-01-01

A 14-year-old girl had a 3-month history of headache and blurred vision. Funduscopy showed bilateral optic disc edema. Findings on brain imaging were normal, and a diagnosis of idiopathic intracranial hypertension was confirmed after lumbar puncture showed an elevated opening pressure of 32 cm H(2)O. Optic nerve head drusen were noted on computed tomography scan and confirmed with B-scan ultrasound. After 2 years, resolution of symptoms coincided with variable compliance to treatment with acetazolamide and concomitant papilledema. In general, optic disc edema poses a clinical conundrum due to the more common occurrence of optic nerve head drusen, potentially resulting in delayed diagnosis and treatment of idiopathic intracranial hypertension. Copyright 2009, SLACK Incorporated.

Measurement of amino acid levels in the vitreous humor of rats after chronic intraocular pressure elevation or optic nerve transection.

PubMed

Levkovitch-Verbin, Hana; Martin, Keith R G; Quigley, Harry A; Baumrind, Lisa A; Pease, Mary Ellen; Valenta, Danielle

2002-10-01

To investigate whether the levels of free amino acids and protein in the vitreous of rat eyes are altered with chronic intraocular pressure (IOP) elevation or after optic nerve transection. The concentrations of 20 amino acids in the vitreous humor were measured by high-performance liquid chromatography in both eyes of 41 rats with unilateral IOP elevation induced by translimbal photocoagulation. Eyes were studied 1 day and 1, 2, 4, and 9 weeks after initial IOP elevation. The same amino acids were measured in 41 rats 1 day and 2, 4, and 9 weeks after unilateral transection of the orbital optic nerve. The intravitreal protein level was assayed in additional 22 rats with IOP elevation and 12 rats after nerve transection. Two masked observers evaluated the amount of optic nerve damage with a semiquantitative, light-microscopic technique. In rats with experimental glaucoma, amino acid concentrations were unchanged 1 day after treatment. At 1 week, 4 of 20 amino acids (aspartate, proline, alanine, and lysine) were higher than in control eyes ( < or = 0.01), but this difference was nonsignificant after Bonferroni correction for multiple simultaneous amino acid comparisons (none achieved < 0.0025). No amino acid was significantly different from control in the nerve transection groups (all > 0.05). Vitreous protein level was significantly higher in glaucomatous eyes than their paired controls at 1 day ( < 0.0001) and 1 week ( < 0.002). One day and 1 week after optic nerve transection, vitreal proteins were significantly elevated compared with control eyes from untreated animals ( < 0.0020 and < 0.0022, respectively), though not compared with their fellow eyes ( = 0.25 and 0.10). Chronic experimental glaucoma and transection of the optic nerve increase the amount of protein in the rat vitreous above control levels. In the vitreous of rats with experimental glaucoma, a number of free amino acids were transiently elevated to a modest degree, but no significant difference in vitreous glutamate concentration was detected ( > 0.01).

Optical coherence tomography platforms and parameters for glaucoma diagnosis and progression.

PubMed

Mwanza, Jean-Claude; Budenz, Donald L

2016-03-01

Optical coherence tomography (OCT) aids in the diagnosis and long-term monitoring of various ocular diseases, including glaucoma. Initially, the retinal nerve fiber layer was the only OCT structural parameter used in glaucoma. Subsequent research has resulted in more retinal and optic nerve head parameters. In addition, OCT is being investigated for its ability to assess ocular hemodynamics. This review summarizes these spectral domain-optical coherence tomography (SDOCT) parameters in the context of glaucoma. Several new SDOCT retinal nerve fiber layer, optic nerve head, and macular parameters with good glaucoma diagnostic ability have been added to existing ones recently. The combination of SDOCT and Doppler or angiography has also resulted in hemodynamic parameters that may prove to be useful in the functional assessment in glaucoma. OCT technology is advancing not only as a tool for structural assessment, but also as a multimodality tool to assess both structure and function to enhance our understanding of glaucoma, and ultimately clinical decisions.

Optic Nerve Atrophy Due to Long-Standing Compression by Planum Sphenoidale Meningioma.

PubMed

Di Somma, Alberto; Kaen, Ariel Matias; Cárdenas Ruiz-Valdepeñas, Eugenio; Cavallo, Luigi Maria

2018-05-01

In this study we report an uncommon endoscopic endonasal image of an atrophic optic nerve as seen after surgical removal of a suprasellar meningioma. The peculiarity of this case is the long-lasting underestimated ocular symptomatology of the patient who reported a 15-year history of impairment of vision on her left eye. A 51-year-old woman was admitted to our hospital complaining of a 15-year history of impairment of vision on her left eye. After making serendipitously the diagnosis of a suprasellar mass, we performed endoscopic endonasal surgery. The tumor was reached from below and removed safely, without manipulation of the optic pathways. At the end of tumor removal, the impressive left optic nerve atrophy due to enduring local tumor compression was visualized. To the best of our knowledge, no endoscopic endonasal image with such features has been provided in the pertinent literature. Possibly, this contribution will help identify damaged optic nerves during endoscopic endonasal surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Multi-modality imaging findings of huge intrachoroidal cavitation and myopic peripapillary sinkhole.

PubMed

Chen, Yutong; Ma, Xiaoli; Hua, Rui

2018-02-02

Peripapillary intrachoroidal cavitation was described as the presence of an asymptomatic, well-circumscribed, yellow-orange, peripapillary lesion at the inferior border of the myopic conus in eyes with high myopia. A 66-year-old myopic Chinese man was enrolled and his multi-color imaging examination showed a well-circumscribed, caesious, peripapillary lesion coalesced with the optic nerve head vertically rotated and obliquely tilted, together with an inferotemporal sinkhole in the myopic conus. The optical coherence tomography images showed an intrachoroidal hyporeflective space, schisis, an intracavitary septum located below the retinal pigment epithelium and inserted beneath the optic nerve head, as well as a sinkhole between the peripapillary intrachoroidal cavitation and the vitreous space. Both myopic colobomas and sinkhole in myopic conus may contribute the coalescence of intrachoroidal cavitation with optic nerve head. These qualitative and quantitative new findings will be beneficial for understanding its pathomorphological mechanism, and the impact on optic nerve tissue of myopic patients.

Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

PubMed Central

Raspanti, M; Marchini, M; Della Pasqua, V; Strocchi, R; Ruggeri, A

1992-01-01

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1295858

Stem Cell Ophthalmology Treatment Study (SCOTS): bone marrow-derived stem cells in the treatment of Leber's hereditary optic neuropathy

PubMed Central

Weiss, Jeffrey N.; Levy, Steven; Benes, Susan C.

2016-01-01

The Stem Cell Ophthalmology Treatment Study (SCOTS) is currently the largest-scale stem cell ophthalmology trial registered at ClinicalTrials.gov (identifier: NCT01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber's hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study (ETDRS) of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autologous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber's hereditary optic neuropathy may be a viable treatment option. PMID:27904503

Retinotopic and temporal organization of the optic nerve and tracts in the adult goldfish.

PubMed

Bunt, S M

1982-04-10

In order to investigate the role of the different factors controlling the pathways and termination sites of growing axons, selected optic fibers were traced from the eye to the tectum in adult goldfish either by filling them with HRP, or by severing a group of fibers and tracing their degeneration in 2 micrometers plastic sections stained with toluidine blue. Some fish received more than one lesion and others received both lesions and HRP applications. Two major rearrangements of the optic fibers were identified, one at the exit from the eye, the other within the optic tracts. Near the eye the optic fibers appear to be guided by the conformation of the underlying tissue planes that they encounter. The most recently added fibers, from the peripheral retina, grow over the vitread surface of the older fibers toward the blood vessel in the center of the optic nerve head. Behind the eye the fibers follow this blood vessel until it leaves the side of the optic nerve, and the fibers from peripheral retina are left as a single group on the ventral edge of the optic nerve cross section. As a consequence of this pattern of fiber growth the fibers form an orderly temporal sequence in the optic nerve, with the oldest fibers from the central retina on one side of the nerve and the youngest from peripheral retina on the other. In addition, the fibers are ordered topographically at right angles to this central-to-peripheral axis, with fibers from ventral retina on each edge of the nerve, dorsal fibers in the center, and nasal and temporal fibers in between. This arrangement of the optic fibers continues with only a little loss of precision up to the optic tracts. A more radical fiber rearrangement, seemingly incompatible with the fibers simply following tissue planes occurs within the optic tracts. Each newly arriving set of fibers grows over the surface of the optic tracts so that the older fibers come to lie deepest in the tracts. This segregation of fibers of different ages ensures that the rearrangement is limited to each layer of fibers. The abrupt reorganization of the fibers occurs as the tracts split around the nucleus rotundus to form the brachia of the optic tracts. The fibers are then arranged with temporal fibers nearest the nucleus rotundus and nasal fibers on the opposite edges of the brachia. From this point the fibers grow out over the tectal surface to their termination sites with only minimal rearrangements. Therefore the optic fiber rearrangements show evidence of several different sorts of constraints acting on the fibers at separate points in the optic pathway, each contributing to the final orderly arrangement of the fibers on the optic tectum.

Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

NASA Astrophysics Data System (ADS)

Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

2011-11-01

The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

Torsion Induced Traumatic Optic Neuropathy (TITON): Animal Model for Diagnostics, Drugs Delivery, and Therapeutics for Injuries to the Cental Nervous System

DTIC Science & Technology

2016-06-01

neck and the eye coils are actively decoupled. The following parameters will be used: slice thickness = 1 mm, TR = 4 s, TE = 13 ms, label duration... Eyes were removed with 3-5 mm of optic nerve intact taking care not to stretch or otherwise injure the nerve. Eyes were flash frozen in liquid...nitrogen, then stored at -80°C. The eyes were then sectioned through the optic nerve using a cryostat, then transferred to indium titanium oxide-coated

Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schimmenti, L.A.; Pierpont, M.E.; Carpenter, B.L.M.

1995-11-06

We describe a father and 3 sons with optic nerve colobomas, vesicoureteral reflux, and renal anomalies. The youngest son had congenital renal failure and ultimately underwent renal transplantation. The father and one son had high frequency hearing loss. There were no other affected relatives. We conclude that the association of optic nerve colobomas, renal anomalies, and vesicoureteral reflux comprises a unique autosomal dominant syndrome. Molecular investigations have determined this disorder to be associated with a single nucleotide deletion in the PAX2 gene. 16 refs., 3 figs.

Protection by an oral disubstituted hydroxylamine derivative against loss of retinal ganglion cell differentiation following optic nerve crush.

PubMed

Lindsey, James D; Duong-Polk, Karen X; Dai, Yi; Nguyen, Duy H; Leung, Christopher K; Weinreb, Robert N

2013-01-01

Thy-1 is a cell surface protein that is expressed during the differentiation of retinal ganglion cells (RGCs). Optic nerve injury induces progressive loss in the number of RGCs expressing Thy-1. The rate of this loss is fastest during the first week after optic nerve injury and slower in subsequent weeks. This study was undertaken to determine whether oral treatment with a water-soluble N-hydroxy-2,2,6,6-tetramethylpiperidine derivative (OT-440) protects against loss of Thy-1 promoter activation following optic nerve crush and whether this effect targets the earlier quick phase or the later slow phase. The retina of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) was imaged using a blue-light confocal scanning laser ophthalmoscope (bCSLO). These mice then received oral OT-440 prepared in cream cheese or dissolved in water, or plain vehicle, for two weeks and were imaged again prior to unilateral optic nerve crush. Treatments and weekly imaging continued for four more weeks. Fluorescent neurons were counted in the same defined retinal areas imaged at each time point in a masked fashion. When the counts at each time point were directly compared, the numbers of fluorescent cells at each time point were greater in the animals that received OT-440 in cream cheese by 8%, 27%, 52% and 60% than in corresponding control animals at 1, 2, 3 and 4 weeks after optic nerve crush. Similar results were obtained when the vehicle was water. Rate analysis indicated the protective effect of OT-440 was greatest during the first two weeks and was maintained in the second two weeks after crush for both the cream cheese vehicle study and water vehicle study. Because most of the fluorescent cells detected by bCSLO are RGCs, these findings suggest that oral OT-440 can either protect against or delay early degenerative responses occurring in RGCs following optic nerve injury.

Evaluation of Eyeball and Orbit in Relation to Gender and Age.

PubMed

Özer, Cenk Murat; Öz, Ibrahim Ilker; Şerifoğlu, Ismail; Büyükuysal, Mustafa Çağatay; Barut, Çağatay

2016-11-01

The orbital aperture is the entrance to the orbit in which most important visual structures such as the eyeball and the optic nerve are found. It is vital not only for the visual system but also for the evaluation and recognition of the face. Eyeball volume is essential for diagnosing microphthalmos or buphthalmos in several eye disorders. Knowing the length of the optic nerve is necessary in selecting the right instruments for enucleation. Therefore, the aim of this study was to evaluate eyeball volume, orbital aperture, and optic nerve dimensions for a morphological description in a Turkish population sample according to gender and body side.Paranasal sinus computed tomography (CT) scans of 198 individuals (83 females, 115 males) aged between 5 and 74 years were evaluated retrospectively. The dimensions of orbital aperture, axial length and volume of eyeball, and diameter and length of the intraorbital part of the optic nerve were measured. Computed tomography examinations were performed on an Activion 16 CT Scanner (Toshiba Medical Systems, 2008 Japan). The CT measurements were calculated by using OsiriX software on a personal computer. All parameters were evaluated according to gender and right/left sides. A statistically significant difference between genders was found with respect to axial length of eyeball, optic nerve diameter, dimensions of orbital aperture on both sides, and right optic nerve length. Furthermore, certain statistically significant side differences were also found. There were statistically significant correlations between age and the axial length of the eyeball, optic nerve diameter, and the transverse length of the orbital aperture on both sides for the whole study group.In this study we determined certain morphometric parameters of the orbit. These outcomes may be helpful in developing a database to determine normal orbit values for the Turkish population so that quantitative assessment of orbital disease and orbital deformities will be evaluated both for preoperative planning and for assessing postoperative outcomes.

Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study.

PubMed

Savini, G; Zanini, M; Carelli, V; Sadun, A A; Ross-Cisneros, F N; Barboni, P

2005-04-01

To investigate the correlation between retinal nerve fibre layer (RNFL) thickness and optic nerve head (ONH) size in normal white subjects by means of optical coherence tomography (OCT). 54 eyes of 54 healthy subjects aged between 15 and 54 underwent peripapillary RNFL thickness measurement by a series of three circular scans with a 3.4 mm diameter (Stratus OCT, RNFL Thickness 3.4 acquisition protocol). ONH analysis was performed by means of six radial scans centred on the optic disc (Stratus OCT, Fast Optic Disc acquisition protocol). The mean RNFL values were correlated with the data obtained by ONH analysis. The superior, nasal, and inferior quadrant RNFL thickness showed a significant correlation with the optic disc area (R = 0.3822, p = 0.0043), (R = 0.3024, p = 0.026), (R = 0.4048, p = 0.0024) and the horizontal disc diameter (R = 0.2971, p = 0.0291), (R = 0.2752, p = 0.044), (R = 0.3970, p = 0.003). The superior and inferior quadrant RNFL thickness was also positively correlated with the vertical disc diameter (R = 0.3774, p = 0.0049), (R = 0.2793, p = 0.0408). A significant correlation was observed between the 360 degrees average RNFL thickness and the optic disc area and the vertical and horizontal disc diameters of the ONH (R = 0.4985, p = 0.0001), (R = 0.4454, p = 0.0007), (R = 0.4301, p = 0.0012). RNFL thickness measurements obtained by Stratus OCT increased significantly with an increase in optic disc size. It is not clear if eyes with large ONHs show a thicker RNFL as a result of an increased amount of nerve fibres or to the shorter distance between the circular scan and the optic disc edge.

A common-path optical coherence tomography based electrode for structural imaging of nerves and recording of action potentials

NASA Astrophysics Data System (ADS)

Islam, M. Shahidul; Haque, Md. Rezuanul; Oh, Christian M.; Wang, Yan; Park, B. Hyle

2013-03-01

Current technologies for monitoring neural activity either use different variety of electrodes (electrical recording) or require contrast agents introduced exogenously or through genetic modification (optical imaging). Here we demonstrate an optical method for non-contact and contrast agent free detection of nerve activity using phase-resolved optical coherence tomography (pr-OCT). A common-path variation of the pr-OCT is recently implemented and the developed system demonstrated the capability to detect rapid transient structural changes that accompany neural spike propagation. No averaging over multiple trials was required, indicating its capability of single-shot detection of individual impulses from functionally stimulated Limulus optic nerve. The strength of this OCT-based optical electrode is that it is a contactless method and does not require any exogenous contrast agent. With further improvements in accuracy and sensitivity, this optical electrode will play a complementary role to the existing recording technologies in future.

[Flicker comparison of optic disc photographs: sensitivity and specificity].

PubMed

Funk, Jens; Lagrèze, Wolf; Zeyen, Thierry

2002-12-01

Examination and documentation of the optic nerve head are essential in monitoring glaucoma patients. Even minor changes in optic nerve head morphology can be visualised using the so-called flicker test: Two optic nerve head photographs, taken at consecutive examinations, are superimposed by projection. When occluding the pictures in a rapid alternating fashion, changes in optic nerve head morphology appear as motion. In this study, we evaluated sensitivity and specificity of the flicker test. A set of 33 pairs of serial optic disc slides was used as gold standard. These 33 pairs had been classified earlier by 3 independent groups of experts. 23 had been classified as "no change over time", 10 had been classified as "change". All 33 pairs were now evaluated by flicker comparison in a masked fashion. Flicker comparison usually took 1 minute per pair of slides. Sensitivity was 90 %, specificity was 65 %. The sensitivity was reasonably high. The moderate specificity was due to some cases showing "change" with the flicker comparison which might have been overlooked by the expert groups. Flicker comparison is an easy, fast and reliable technique to evaluate pairs of consecutive optic disc photographs.

Virtual Instrumentation for a Fiber-Optics-Based Artificial Nerve

NASA Technical Reports Server (NTRS)

Lyons, Donald R.; Kyaw, Thet Mon; Griffin, DeVon (Technical Monitor)

2001-01-01

A LabView-based computer interface for fiber-optic artificial nerves has been devised as a Masters thesis project. This project involves the use of outputs from wavelength multiplexed optical fiber sensors (artificial nerves), which are capable of producing dense optical data outputs for physical measurements. The potential advantages of using optical fiber sensors for sensory function restoration is the fact that well defined WDM-modulated signals can be transmitted to and from the sensing region allowing networked units to replace low-level nerve functions for persons desirous of "intelligent artificial limbs." Various FO sensors can be designed with high sensitivity and the ability to be interfaced with a wide range of devices including miniature shielded electrical conversion units. Our Virtual Instrument (VI) interface software package was developed using LabView's "Laboratory Virtual Instrument Engineering Workbench" package. The virtual instrument has been configured to arrange and encode the data to develop an intelligent response in the form of encoded digitized signal outputs. The architectural layout of our nervous system is such that different touch stimuli from different artificial fiber-optic nerve points correspond to gratings of a distinct resonant wavelength and physical location along the optical fiber. Thus, when an automated, tunable diode laser sends scans, the wavelength spectrum of the artificial nerve, it triggers responses that are encoded with different touch stimuli by way wavelength shifts in the reflected Bragg resonances. The reflected light is detected and a resulting analog signal is fed into ADC1 board and DAQ card. Finally, the software has been written such that the experimenter is able to set the response range during data acquisition.

Review: Tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain?

PubMed Central

Ho, Wing-Lau; Leung, Yen; Tsang, Andrea Wing-Ting; So, Kwok-Fai; Chiu, Kin

2012-01-01

Tau protein’s versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer’s disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve. PMID:23170062

Wavelet denoising during optical coherence tomography of the prostate nerves using the complex wavelet transform.

PubMed

Chitchian, Shahab; Fiddy, Michael; Fried, Nathaniel M

2008-01-01

Preservation of the cavernous nerves during prostate cancer surgery is critical in preserving sexual function after surgery. Optical coherence tomography (OCT) of the prostate nerves has recently been studied for potential use in nerve-sparing prostate surgery. In this study, the discrete wavelet transform and complex dual-tree wavelet transform are implemented for wavelet shrinkage denoising in OCT images of the rat prostate. Applying the complex dual-tree wavelet transform provides improved results for speckle noise reduction in the OCT prostate image. Image quality metrics of the cavernous nerves and signal-to-noise ratio (SNR) were improved significantly using this complex wavelet denoising technique.

Methods for determination of optic nerve blood flow.

PubMed Central

Glazer, L. C.

1988-01-01

A variety of studies have been conducted over the past two decades to determine if decreased optic nerve blood flow has a role in the etiology of glaucomatous nerve damage. Five basic methods have been employed in examining blood flow. Invasive studies, utilizing electrodes placed in the optic nerve head, represent one of the first attempts to measure blood flow. More recently, the methodologies have included axoplasmic flow analysis, microspheres, radioactive tracers such as iodoantipyrine, and laser doppler measurements. The results of these studies are inconclusive and frequently contradictory. When the studies are grouped by methodology, only the iodoantipyrine data are consistent. While each of the experimental techniques has limitations, iodoantipyrine appears to have better resolution than either invasive studies or microspheres. PMID:3284212

Continuous-wave optical stimulation of the rat prostate nerves using an all-single-mode 1455 nm diode laser and fiber system

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2011-03-01

Optical nerve stimulation (ONS) has recently been reported as a potential alternative to electrical nerve stimulation. Continuous-wave (CW) laser stimulation of the prostate cavernous nerves (CN) in a rat model, in vivo, has also been demonstrated in our previous studies. The objective of this study is to present a new all-single-mode-fiber configuration for ONS with the laser operating in CW mode for potential diagnostic applications. An infrared pigtailed single-mode diode laser (λ = 1455 nm) was used in this study for noncontact ONS. This new all-fiber approach introduces several advantages including: (1) a less expensive and more compact ONS system, (2) elimination of alignment of optical components, and (3) an improved spatial beam profile. Successful optical stimulation of the rat CN using this new design was observed after the CN reached a threshold temperature of ~ 41 °C with response times as short as 3 s. Upon further study, this configuration may be useful for identification and preservation of the cavernous nerves during prostate cancer surgery.

The use of Peer Optic Nerve Photographs for Teaching Direct Ophthalmoscopy

PubMed Central

Milani, Behrad Y.; Majdi, Mercede N.; Green, Wesley; Mehralian, Amir; Moarefi, Majid; Oh, Freddie S.; Riddle, Janet M.; Djalilian, Ali R.

2014-01-01

Objective To use a novel teaching exercise to encourage students to practice ophthalmoscopy and to measure the learning effect both subjectively and objectively. Design Comparative case series. Participants One-hundred thirty-one fourth-year medical students on their one-week ophthalmology rotations with 89 in the experimental group and 42 in the control group. Methods Those in the experimental group had one eye dilated and their optic nerve photographed on the first day. The next day, these students received an unlabeled optic nerve photograph belonging to one of their peers (typically 8–10 per group) and were given three days to identify the student matching the photograph. The students in the control group were simply encouraged to practice ophthalmoscopy on each other without the use of photographs. Main Outcome Measures Both objective and subjective changes from the beginning to the end of the rotation were measured and compared between the two groups. Results In the 89 students who used peer optic nerve photographs, 75 (84.3%) showed improvement in direct ophthalmoscopy skills over the course of the week. In contrast, only 12 (28.6%) of the 42 control students demonstrated an objective improvement (P < 0.001). The subjective confidence levels were likewise more improved in the students who took part in the optic nerve photograph exercise. Conclusions These results suggest that the task of matching an unknown optic nerve photograph to the correct eye of a peer leads to increased self-confidence and more proficient use of the direct ophthalmoscope. PMID:23246117

Optic nerve involvement in a borderline lepromatous leprosy patient on multidrug therapy.

PubMed

Prabha, Neel; Mahajan, Vikram K; Sharma, Surinder K; Sharma, Vikas; Chauhan, Pushpinder S; Mehta, Karaninder S; Abhinav, C; Khatri, Gaytri; Chander, Bal; Tuli, Rajiv

2013-12-01

Amidst the plethora of ocular complications of leprosy, involvement of the posterior segment or optic nerve is extremely rare. The mechanism of optic neuritis in leprosy is poorly understood. A 47 year-old man presented with a single lesion suggestive of mid-borderline (BB) leprosy over left periorbital region; the histology showed borderline lepromatous (BL) leprosy with a BI of 3+. After initial improvement with WHO MDT-MB and prednisolone (40 mg/d) he developed sudden and painless diminished vision in the left eye, about 3 weeks later. His visual acuity was 6/9 in the left and 6/6 in the right eye, and there was left optic disc edema, hyperemia and blurred disc margins. Treatment with prednisolone (60 mg/d) along with WHO MDT-MB continued. A month later he returned with painless diminished vision in the other eye as well. Visual acuity was 6/6 in the right and 6/12 in the left eye, and there was right optic disc edema and left optic disc atrophy. CT of the head and MRI of the brain were normal. Inflammatory edema of the orbital connective tissue or other surrounding structures, or direct infiltration of vasa nervosa with resultant vascular occlusion leading to optic nerve ischemia, seems the most plausible explanation of optic nerve involvement in this case.

Assessing the changes in the spatial stiffness of the posterior sclera as a function of IOP with air-pulse OCE

NASA Astrophysics Data System (ADS)

Singh, Manmohan; Nair, Achuth; Aglyamov, Salavat R.; Wu, Chen; Han, Zhaolong; Lafon, Ericka; Larin, Kirill V.

2017-02-01

The mechanophysiology of tissues in the posterior eye have been implicated for diseases such as myopia and glaucoma. For example, the eye-globe shape, and consequently optical axial length, can be affected by scleral stiffness. In glaucoma, an elevated intraocular pressure is the primary risk factor for glaucoma, which is the 2nd most prevalent known cause of blindness. Recent work has shown that biomechanical properties of the optic nerve are critical for the onset and progression of glaucoma because weak tissues cause large displacements in the optic nerve, causing tissue damage. In this work, we utilize air-pulse optical coherence elastography (OCE) to quantify the spatial distribution of biomechanical properties of the optic nerve, its surrounding tissues, and the posterior sclera. Air-pulse measurements were made in a grid on in situ porcine eyes in the whole eye-globe configuration as various IOPs. The OCE-measured displacement process was linked to tissue stiffness by a simple kinematic equation. The results show that the optic nerve and peripapillary sclera are much stiffer than the surrounding sclera, and the stiffness of the optic nerve and peripapillary sclera increased as a function of IOP. However, the stiffness of the surrounding sclera did not dramatically increase. Our results show that understanding the dynamics of the biomechanical properties of the eye are critical to understand the aforementioned diseases and may provide additional information for assessing visual health and integrity.

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). Conclusions. In nonhuman primates, PGJ2 administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ2 is neuroprotective when administered up to 5 hours after induction of pNAION. PMID:25298416

Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat.

PubMed

Martin, Keith R G; Levkovitch-Verbin, Hana; Valenta, Danielle; Baumrind, Lisa; Pease, Mary Ellen; Quigley, Harry A

2002-07-01

High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared 3 days and 1, 4, and 6 weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After 1 to 6 weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at 3 days (29.3% +/- 6.7%, P = 0.01), 1 week (55.5% +/- 13.6%, P = 0.02), 4 weeks (27.2% +/- 10.1%, P = 0.05), and 6 weeks (38.1% +/- 7.9%, P = 0.01; mean reduction +/- SEM, paired t-tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r(2) = 0.31, P = 0.01, linear regression). GLAST was significantly reduced (33.8% +/- 8.1%, mean +/- SEM) after 4 weeks of elevated IOP (P = 0.01, paired t-test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (P = 0.01, paired t-test, n = 15 animals). There was no significant change in GLAST after transection. GLT-1 and GLAST were significantly reduced in an experimental rat glaucoma model, a response that was not found after optic nerve transection. Reductions in GLT-1 and GLAST may increase the potential for glutamate-induced injury to RGC in glaucoma.

Determining degree of optic nerve edema from color fundus photography

NASA Astrophysics Data System (ADS)

Agne, Jason; Wang, Jui-Kai; Kardon, Randy H.; Garvin, Mona K.

2015-03-01

Swelling of the optic nerve head (ONH) is subjectively assessed by clinicians using the Frisén scale. It is believed that a direct measurement of the ONH volume would serve as a better representation of the swelling. However, a direct measurement requires optic nerve imaging with spectral domain optical coherence tomography (SD-OCT) and 3D segmentation of the resulting images, which is not always available during clinical evaluation. Furthermore, telemedical imaging of the eye at remote locations is more feasible with non-mydriatic fundus cameras which are less costly than OCT imagers. Therefore, there is a critical need to develop a more quantitative analysis of optic nerve swelling on a continuous scale, similar to SD-OCT. Here, we select features from more commonly available 2D fundus images and use them to predict ONH volume. Twenty-six features were extracted from each of 48 color fundus images. The features include attributes of the blood vessels, optic nerve head, and peripapillary retina areas. These features were used in a regression analysis to predict ONH volume, as computed by a segmentation of the SD-OCT image. The results of the regression analysis yielded a mean square error of 2.43 mm3 and a correlation coefficient between computed and predicted volumes of R = 0:771, which suggests that ONH volume may be predicted from fundus features alone.

3D papillary image capturing by the stereo fundus camera system for clinical diagnosis on retina and optic nerve

NASA Astrophysics Data System (ADS)

Motta, Danilo A.; Serillo, André; de Matos, Luciana; Yasuoka, Fatima M. M.; Bagnato, Vanderlei S.; Carvalho, Luis A. V.

2014-03-01

Glaucoma is the second main cause of the blindness in the world and there is a tendency to increase this number due to the lifetime expectation raise of the population. Glaucoma is related to the eye conditions, which leads the damage to the optic nerve. This nerve carries visual information from eye to brain, then, if it has damage, it compromises the visual quality of the patient. In the majority cases the damage of the optic nerve is irreversible and it happens due to increase of intraocular pressure. One of main challenge for the diagnosis is to find out this disease, because any symptoms are not present in the initial stage. When is detected, it is already in the advanced stage. Currently the evaluation of the optic disc is made by sophisticated fundus camera, which is inaccessible for the majority of Brazilian population. The purpose of this project is to develop a specific fundus camera without fluorescein angiography and red-free system to accomplish 3D image of optic disc region. The innovation is the new simplified design of a stereo-optical system, in order to make capable the 3D image capture and in the same time quantitative measurements of excavation and topography of optic nerve; something the traditional fundus cameras do not do. The dedicated hardware and software is developed for this ophthalmic instrument, in order to permit quick capture and print of high resolution 3D image and videos of optic disc region (20° field-of-view) in the mydriatic and nonmydriatic mode.

Characterizing Intraorbital Optic Nerve Changes on Diffusion Tensor Imaging in Thyroid Eye Disease Before Dysthyroid Optic Neuropathy.

PubMed

Lee, Hwa; Lee, Young Hen; Suh, Sang-Il; Jeong, Eun-Kee; Baek, Sehyun; Seo, Hyung Suk

The aim of this study was to determine whether the optic nerve is affected by thyroid eye disease (TED) before the development of dysthyroid optic neuropathy with diffusion-tensor imaging (DTI). Twenty TED patients and 20 controls were included. The mean, axial, and radial diffusivities and fractional anisotropy (FA) value were measured at the optic nerves in DTI. Extraocular muscle diameters were measured on computed tomography. The diffusivities and FA of the optic nerves were compared between TED and controls and between active and inactive stages of TED. The correlations between these DTI parameters and the clinical features were determined. The mean, axial, and radial diffusivities were lower in TED compared with the controls (P < 0.05). In contrast, FA was higher in TED (P = 0.001). Radial diffusivity was lower in the active stage of TED than the inactive stage (P = 0.035). The FA was higher in the TED group than in the control group (P = 0.021) and was positively correlated with clinical activity score (r = 0.364, P = 0.021), modified NOSPECS score (r = 0.469, P = 0.002), and extraocular muscle thickness (r = 0.325, P = 0.041) in the TED group. Radial diffusivity was negatively correlated with modified NOSPECS score (r = -0.384, P = 0.014), and axial diffusivity was positively correlated with exophthalmos degree (r = 0.363, P = 0.025). The diffusivities and FA reflected changes in the optic nerve before dysthyroid optic neuropathy in TED. The FA, in particular, reflected TED activity and severity.

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma.

PubMed

Howell, Gareth R; Soto, Ileana; Zhu, Xianjun; Ryan, Margaret; Macalinao, Danilo G; Sousa, Gregory L; Caddle, Lura B; MacNicoll, Katharine H; Barbay, Jessica M; Porciatti, Vittorio; Anderson, Michael G; Smith, Richard S; Clark, Abbot F; Libby, Richard T; John, Simon W M

2012-04-01

Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve.

Microgravity-Driven Optic Nerve/Sheath Biomechanics Simulations

NASA Technical Reports Server (NTRS)

Ethier, C. R.; Feola, A.; Myers, J. G.; Nelson, E.; Raykin, J.; Samuels, B.

2016-01-01

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Current thinking suggests that the ocular changes observed in VIIP syndrome are related to cephalad fluid shifts resulting in altered fluid pressures [1]. In particular, we hypothesize that increased intracranial pressure (ICP) drives connective tissue remodeling of the posterior eye and optic nerve sheath (ONS). We describe here finite element (FE) modeling designed to understand how altered pressures, particularly altered ICP, affect the tissues of the posterior eye and optic nerve sheath (ONS) in VIIP. METHODS: Additional description of the modeling methodology is provided in the companion IWS abstract by Feola et al. In brief, a geometric model of the posterior eye and optic nerve, including the ONS, was created and the effects of fluid pressures on tissue deformations were simulated. We considered three ICP scenarios: an elevated ICP assumed to occur in chronic microgravity, and ICP in the upright and supine positions on earth. Within each scenario we used Latin hypercube sampling (LHS) to consider a range of ICPs, ONH tissue mechanical properties, intraocular pressures (IOPs) and mean arterial pressures (MAPs). The outcome measures were biomechanical strains in the lamina cribrosa, optic nerve and retina; here we focus on peak values of these strains, since elevated strain alters cell phenotype and induce tissue remodeling. In 3D, the strain field can be decomposed into three orthogonal components, denoted as first, second and third principal strains. RESULTS AND CONCLUSIONS: For baseline material properties, increasing ICP from 0 to 20 mmHg significantly changed strains within the posterior eye and ONS (Fig. 1), indicating that elevated ICP affects ocular tissue biomechanics. Notably, strains in the lamina cribrosa and retina became less extreme as ICP increased; however, within the optic nerve, the occurrence of such extreme strains greatly increased as ICP was elevated (Fig. 2). In particular, c. 48 of simulations in the elevated ICP condition showed peak strains in the optic nerve that exceeded the strains expected on earth. Such extreme strains are likely important, since they represent a larger signal for mechano-responsive resident cells [2]. The models predicted little to no anterior motion of the prelaminar neural tissue (optic nerve swelling, or papilledema, secondary to axoplasmic stasis), typically seen with elevated ICP. Specialized FE models to capture axoplasmic stasis would be required to study papilledema. These results suggest that the most notable effect of elevated ICP may occur via direct optic nerve loading, rather than through connective tissue deformation. These FE models can inform the design of future studies designed to bridge the gap between biomechanics and pathophysiological function in VIIP.

Lamina Cribrosa Microarchitecture in Normal Monkey Eyes Part 1: Methods and Initial Results

PubMed Central

Lockwood, Howard; Reynaud, Juan; Gardiner, Stuart; Grimm, Jonathan; Libertiaux, Vincent; Downs, J. Crawford; Yang, Hongli; Burgoyne, Claude F.

2015-01-01

Purpose. To introduce quantitative postmortem lamina cribrosa (LC) microarchitecture (LMA) assessment and characterize beam diameter (BD), pore diameter (PD), and connective tissue volume fraction (CTVF) in 21 normal monkey eyes. Methods. Optic nerve heads (ONHs) underwent digital three-dimensional (3D) reconstruction and LC beam segmentation. Each beam and pore voxel was assigned a diameter based on the largest sphere that contained it before transformation to one of twelve 30° sectors in a common cylinder. Mean BD, PD, and CTVF within 12 central and 12 peripheral subsectors and within inner, middle, and outer LC depths were assessed for sector, subsector, and depth effects by analysis of variance using general estimating equations. Eye-specific LMA discordance (the pattern of lowest connective tissue density) was plotted for each parameter. Results. The ranges of mean BD, PD, and CTVF were 14.0 to 23.1 μm, 20.0 to 35.6 μm, and 0.247 to 0.638, respectively. Sector, subsector, and depth effects were significant (P < 0.01) for all parameters except subsector on CTVF. Beam diameter and CTVF were smaller and PD was larger within the superior-temporal (ST) and inferior-temporal (IT) sectors (P < 0.05). These differences were enhanced within the central versus peripheral subsectors. Beam diameter and CTVF were larger and PD was smaller (P < 0.05) within the middle LC layer. Lamina cribrosa microarchitecture discordance most commonly occurred within the ST and IT sectors, varied by eye, and generally diminished as CTVF increased. Conclusions. Our data support previous characterizations of diminished connective tissue density within the ST and IT ONH regions. The clinical importance of eye-specific LMA discordance warrants further study. PMID:25650423

Cranial nerve threshold for thermal injury induced by MRI-guided high-intensity focused ultrasound (MRgHIFU): preliminary results on an optic nerve model.

PubMed

Harnof, Sagi; Zibly, Zion; Cohen, Zvi; Shaw, Andrew; Schlaff, Cody; Kassel, Neal F

2013-04-01

Future clinical applications of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) are moving toward the management of different intracranial pathologies. We sought to validate the production, safety, and efficacy of thermal injury to cranial nerves generated by MRgHIFU. In this study, five female domestic pigs underwent a standard bifrontal craniectomy under general anesthesia. Treatment was then given using an MRgHIFU system to induce hyperthermic ablative sonication (6 to 10 s; 50 to 2000 J.) Histological analyses were done to confirm nerve damage; temperature measured on the optic nerve was approximately 53.4°C (range: 39°C to 70°C.) Histology demonstrated a clear definition between a necrotic, transitional zone, and normal tissue. MRgHIFU induces targeted thermal injury to nervous tissue within a specific threshold of 50°C to 60°C with the tissue near the sonication center yielding the greatest effect; adjacent tissue showed minimal changes. Additional studies utilizing this technology are required to further establish accurate threshold parameters for optic nerve thermo-ablation.

In-vivo imaging of retinal nerve fiber layer vasculature: imaging - histology comparison

PubMed Central

Scoles, Drew; Gray, Daniel C; Hunter, Jennifer J; Wolfe, Robert; Gee, Bernard P; Geng, Ying; Masella, Benjamin D; Libby, Richard T; Russell, Stephen; Williams, David R; Merigan, William H

2009-01-01

Background Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO) scanning laser ophthalmoscopy (SLO), that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed. Methods We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue. Results Superficial focus (innermost retina) at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs). However, at a deeper focus beneath the NFL, (toward outer retina) the polygonal pattern typical of the ganglion cell layer (inner) and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections. Conclusion This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal vascular disorders and other eye diseases, such as glaucoma. PMID:19698151

In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs

DTIC Science & Technology

2010-01-01

L.W.Harris, D.L. Stitcher , Reactivation of VX-inhibited cholinesterase by 2-PAM and HS-6 in rats, Drug Chem. Toxicol. 6 (1983) 235–240. [9] P.M. Lundy, T.-M...rat, monkey and human, Arch. Toxicol. 68 (1994) 648–655. 2 gical In [ [ 14 T.-M. Shih et al. / Chemico-Biolo27] L.W. Harris, W.C. Heyl, D.L. Stitcher

Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

von Bredow, J.; Corcoran, K.; Maitland, G.

1991-12-31

Pretreatment of nonhuman primates with physostigmine (Phy) and scopolamine or physostigmine and trihexyphenidyl 25 min before exposure to 2 LD50 soman im resulted in complete survival without convulsions or loss of consciousness. When identically pretreated animals were challenged with 5 LD50s of soman followed by atropine and 2-PAM therapy 1 min later, all animals experienced a loss of consciousness for approximately 10 min followed by functional recovery within an additional 20 min. These findings indicated that a pretreatment regimen composed of Phy and cholinolytic is capable of protecting primates from an absolute lethal dose of soman with rapid recovery frommore » incapacitation. Physostigmine, nerve agent pretreatment, cynomolgus monkeys soman (GD).« less

Tolerance of cranial nerves of the cavernous sinus to radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tishler, R.B.; Loeffler, J.S.; Alexander, E. III

1993-09-20

Stereotactic radiosurgery is becoming a more accepted treatment option for benign, deep seated intracranial lesions. However, little is known about the effects of large single fractions of radiation on cranial nerves. This study was undertaken to assess the effect of radiosurgery on the cranial nerves of the cavernous sinus. The authors examined the tolerance of cranial nerves (II-VI) following radiosurgery for 62 patients (42/62 with meningiomas) treated for lesions within or near the cavernous sinus. Twenty-nine patients were treated with a modified 6 MV linear accelerator (Joint Center for Radiation Therapy) and 33 were treated with the Gamma Knife (Universitymore » of Pittsburgh). Three-dimensional treatment plans were retrospectively reviewed and maximum doses were calculated for the cavernous sinus and the optic nerve and chiasm. Median follow-up was 19 months (range 3-49). New cranial neuropathies developed in 12 patients from 3-41 months following radiosurgery. Four of these complications involved injury to the optic system and 8 (3/8 transient) were the result of injury to the sensory or motor nerves of the cavernous sinus. There was no clear relationship between the maximum dose to the cavernous sinus and the development of complications for cranial nerves III-VI over the dose range used (1000-4000 cGy). For the optic apparatus, there was a significantly increased incidence of complications with dose. Four of 17 patients (24%) receiving greater than 800 cGy to any part of the optic apparatus developed visual complications compared with 0/35 who received less than 800 cGy (p = 0.009). Radiosurgery using tumor-controlling doses of up to 4000 cGy appears to be a relatively safe technique in treating lesions within or near the sensory and motor nerves (III-VI) of the cavernous sinus. The dose to the optic apparatus should be limited to under 800 cGy. 21 refs., 4 tabs.« less

Applications of Optical Coherence Tomography in Pediatric Clinical Neuroscience

PubMed Central

Avery, Robert A.; Rajjoub, Raneem D.; Trimboli-Heidler, Carmelina; Waldman, Amy T.

2015-01-01

For nearly two centuries, the ophthalmoscope has permitted examination of the retina and optic nerve—the only axons directly visualized by the physician. The retinal ganglion cells project their axons, which travel along the innermost retina to form the optic nerve, marking the beginning of the anterior visual pathway. Both the structure and function of the visual pathway are essential components of the neurologic examination as it can be involved in numerous acquired, congenital and genetic central nervous system conditions. The development of optical coherence tomography now permits the pediatric neuroscientist to visualize and quantify the optic nerve and retinal layers with unprecedented resolution. As optical coherence tomography becomes more accessible and integrated into research and clinical care, the pediatric neuroscientist may have the opportunity to utilize and/or interpret results from this device. This review describes the basic technical features of optical coherence tomography and highlights its potential clinical and research applications in pediatric clinical neuroscience including optic nerve swelling, optic neuritis, tumors of the visual pathway, vigabatrin toxicity, nystagmus, and neurodegenerative conditions. PMID:25803824

Morphological study of the eye and adnexa in capuchin monkeys (Sapajus sp.)

PubMed Central

Silva, Danielle Nascimento; Oriá, Arianne Pontes; Araujo, Nayone Lantyer; Martins-Filho, Emanoel; Muramoto, Caterina; Libório, Fernanda de Azevedo

2017-01-01

The objective of this study was to describe the anatomic and histologic features of the Sapajus sp. eye, comparing similarities and differences of humans and other species of non-human primates for biomedical research purposes. Computed tomography (CT) of adnexa, eye and orbit live animal, as well as formolized pieces of the same structures of Sapajus sp. for anatomical and histological study were also performed. The anatomical description of the eye and adnexa was performed using the techniques of topographic dissection and exenteration. Histological fragments were fixated in buffered formalin 10%, processed by the routine paraffin inclusion technique, stained with hematoxylin-eosin and special stains. CT scan evaluation showed no differences between the live animal and the formolized head on identification of visual apparatus structures. Anatomic and histologic evaluation revealed rounded orbit, absence of the supraorbital foramen and frontal notch, little exposure of the sclera, with slight pigmentation of the exposed area and marked pigmentation at the sclerocorneal junction. Masson's Trichrome revealed the Meibomian glands, the corneal epithelium and Bowman's membrane; in the choroid, melanocytes and Bruch's membrane were observed; and in the retina, cones and rods as well as, optic nerve, the lamina cribrosa of the nerve fibers bundles. Toluidine blue highlighted the membranes: Bowman, Descemet and the endothelium; in the choroid: melanocytes; and in the retina: nuclear layers and retinal pigment epithelium. In view of the observed results Sapajus sp. is an important experimental model for research in the ophthalmology field, which has been shown due to the high similarity of its anatomical and histological structures with the human species. PMID:29206882

Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

PubMed

Ward, Patricia J; Jones, Laura N; Mulligan, Amanda; Goolsby, William; Wilhelm, Jennifer C; English, Arthur W

2016-01-01

Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation) that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2), we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2) to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555) was greater in mice that received optical treatment. Thus, the acute (1 hour), one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-). We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

Three-dimensional digital mapping of the optic nerve head cupping in glaucoma

NASA Astrophysics Data System (ADS)

Mitra, Sunanda; Ramirez, Manuel; Morales, Jose

1992-08-01

Visualization of the optic nerve head cupping is clinically achieved by stereoscopic viewing of a fundus image pair of the suspected eye. A novel algorithm for three-dimensional digital surface representation of the optic nerve head, using fusion of stereo depth map with a linearly stretched intensity image of a stereo fundus image pair, is presented. Prior to depth map acquisition, a number of preprocessing tasks including feature extraction, registration by cepstral analysis, and correction for intensity variations are performed. The depth map is obtained by using a coarse to fine strategy for obtaining disparities between corresponding areas. The required matching techniques to obtain the translational differences in every step, uses cepstral analysis and correlation-like scanning technique in the spatial domain for the finest details. The quantitative and precise representation of the optic nerve head surface topography following this algorithm is not computationally intensive and should provide more useful information than just qualitative stereoscopic viewing of the fundus as one of the diagnostic criteria for diagnosis of glaucoma.

Bilateral Traumatic Globe Luxation with Optic Nerve Transection

PubMed Central

Tok, Levent; Tok, Ozlem Yalcin; Argun, Tugba Cakmak; Yilmaz, Omer; Gunes, Alime; Unlu, Elif Nisa; Sezer, Sezgin; Ibisoglu, Seda; Argun, Mehmet

2014-01-01

Purpose The purpose of this study was to document clinical findings and management of a patient with bilateral globe luxation and optic nerve transection. Materials and Methods A 25-year-old female patient was admitted to the emergency department with bilateral traumatic globe luxation following a motor vehicle accident. Results Visual acuity testing showed no light perception. The right pupil was dilated and bilaterally did not react to light. The globes were bilaterally intact. A computed tomography scan revealed Le Fort type II fractures, bilateral optic nerve transection and disruption of all extraocular muscles. The globes of the patient were bilaterally reduced into the orbit. However, the patient developed phthisis bulbi in the right eye at month 3. Conclusion Globe luxation presents a dramatic clinical picture, and may lead to the development of severe complications due to the concomitance of complete optic nerve dissection and multiple traumas. Even if the luxated globe is repositioned into the orbit, there is still an increased risk of the development of phthisis due to ischemia. PMID:25606034

Transdermal optogenetic peripheral nerve stimulation

NASA Astrophysics Data System (ADS)

Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

2017-06-01

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Transcranial photoacoustic tomography of the monkey brain

NASA Astrophysics Data System (ADS)

Nie, Liming; Huang, Chao; Guo, Zijian; Anastasio, Mark; Wang, Lihong V.

2012-02-01

A photoacoustic tomography (PAT) system using a virtual point ultrasonic transducer was developed for transcranial imaging of monkey brains. The virtual point transducer provided a 10 times greater field-of-view (FOV) than finiteaperture unfocused transducers, which enables large primate imaging. The cerebral cortex of a monkey brain was accurately mapped transcranially, through up to two skulls ranging from 4 to 8 mm in thickness. The mass density and speed of sound distributions of the skull were estimated from adjunct X-ray CT image data and utilized with a timereversal algorithm to mitigate artifacts in the reconstructed image due to acoustic aberration. The oxygenation saturation (sO2) in blood phantoms through a monkey skull was also imaged and quantified, with results consistent with measurements by a gas analyzer. The oxygenation saturation (sO2) in blood phantoms through a monkey skull was also imaged and quantified, with results consistent with measurements by a gas analyzer. Our experimental results demonstrate that PAT can overcome the optical and ultrasound attenuation of a relatively thick skull, and the imaging aberration caused by skull can be corrected to a great extent.

Evaluation of retinal nerve fiber layer thickness in the area of apparently normal hemifield in glaucomatous eyes with optical coherence tomography.

PubMed

Kee, Changwon; Cho, Changhwan

2003-06-01

The authors investigated the correlation between visual field defects detected by automated perimetry and the thickness of the retinal nerve fiber layer measured with optical coherence tomography, and examined whether there is a decrease in retinal nerve fiber layer thickness in the apparently normal hemifield of glaucomatous eyes. Forty-one patients with glaucoma and 41 normal control subjects were included in this study. Statistical correlations between the sum of the total deviation of 37 stimuli of each hemifield and the ratio of decrease in retinal nerve fiber layer thickness were evaluated. The statistical difference between the retinal nerve fiber layer thickness of the apparently normal hemifield in glaucomatous eyes and that of the corresponding hemifield in normal subjects was also evaluated. There was a statistically significant correlation in the sum of the total deviation and retinal nerve fiber layer thickness decrease ratio (superior hemifield, P = 0.001; inferior hemifield, P = 0.003). There was no significant decrease in retinal nerve fiber layer thickness in the area that corresponded to the normal visual field in the hemifield defect with respect to the horizontal meridian in glaucomatous eyes (superior side, P = 0.148; inferior side, P = 0.341). Optical coherence tomography was capable of demonstrating and measuring retinal nerve fiber layer abnormalities. No changes in the retinal nerve fiber layer thickness of the apparently normal hemifield were observed in glaucomatous eyes.

Optic Nerve Sheath Meningocele: A Case Report

PubMed Central

Halimi, E.; Wavreille, O.; Rosenberg, R.; Bouacha, I.; Lejeune, J.-P.; Defoort-Dhellemmes, S.

2013-01-01

Abstract Isolated optic nerve sheath meningocele is a rare affection defined as the cystic enlargement of the optic nerve sheath filled with cerebrospinal fluid. We report the case of a 39-year-old woman presenting with bilateral meningocele uncovered during a routine examination for headache complaints. A 5-year follow-up validated the lesion’s clinical and imaging stability. Magnetic resonance imaging (MRI) is an essential tool in the diagnosis of this pathology, alongside characteristic symptoms indicating that the meningocele might have progressively expanded into the orbit. In this case we present a therapeutic approach based on pathophysiological hypotheses and review of the literature. PMID:28163760

Is the term "fasciculus opticus cerebralis" more justifiable than the term "optic nerve"?

PubMed

Vojniković, Bojo; Bajek, Snjezana; Bajek, Goran; Strenja-Linić, Ines; Grubesić, Aron

2013-04-01

The terminology of the optic nerve had already been changed three times, since 1895 until 1955 when the term "nervus opticus" was introduced in the "Terminologia Anatomica". Following our study we claim that, from the aspect of phylogenetic evolution of binocular vision development as well as optical embryogenesis where opticus is evidently presented as a product of diencephalic structures, the addition of the term "nervus" to opticus is not adequate and justified. From the clinical aspect the term "nervus opticus" is also inadequate, both as a "nerve" that has no functional regenerative properties, unlike other cranial nerves, as well as from a pedagogical and didactical aspect of educating future physicians. We suggest that the term "Fasciculus Opticus Cerebralis" should be used as it much better explains the origin as well as its affiliation to the central nervous system.

ImagePAD, a Novel Counting Application for the Apple iPad®, Used to Quantify Axons in the Mouse Optic Nerve

PubMed Central

Templeton, Justin P.; Struebing, Felix L.; Lemmon, Andrew; Geisert, Eldon E.

2014-01-01

The present article introduces a new and easy to use counting application for the Apple iPad. The application “ImagePAD” takes advantage of the advanced user interface features offered by the Apple iOS® platform, simplifying the rather tedious task of quantifying features in anatomical studies. For example, the image under analysis can be easily panned and zoomed using iOS-supported multi-touch gestures without losing the spatial context of the counting task, which is extremely important for ensuring count accuracy. This application allows one to quantify up to 5 different types of objects in a single field and output the data in a tab-delimited format for subsequent analysis. We describe two examples of the use of the application: quantifying axons in the optic nerve of the C57BL/6J mouse and determining the percentage of cells labeled with NeuN or ChAT in the retinal ganglion cell layer. For the optic nerve, contiguous images at 60× magnification were taken and transferred onto an Apple iPad®. Axons were counted by tapping on the touch-sensitive screen using ImagePAD. Nine optic nerves were sampled and the number of axons in the nerves ranged from 38872 axons to 50196 axons with an average of 44846 axons per nerve (SD = 3980 axons). PMID:25281829

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration

PubMed Central

Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S.; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J.; Benowitz, Larry

2017-01-01

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn2+) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn2+ accumulation in amacrine cell processes involves the Zn2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn2+ chelation extends for several days after nerve injury. These results show that retinal Zn2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration. PMID:28049831

Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

PubMed

Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J; Rosenberg, Paul A; Benowitz, Larry

2017-01-10

Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn 2+ ) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn 2+ increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn 2+ accumulation in amacrine cell processes involves the Zn 2+ transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn 2+ chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn 2+ chelation extends for several days after nerve injury. These results show that retinal Zn 2+ dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn 2+ chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

Effect of the menstrual cycle on the optic nerve head in diabetes: analysis by confocal scanning laser ophthalmoscopy.

PubMed

Akar, Munire Erman; Yucel, Iclal; Erdem, Uzeyir; Taskin, Omur; Ozel, Alper; Akar, Yusuf

2005-04-01

The purpose of this study was to examine and compare menstrual-cycle-dependent topographic changes in the optic nerve head of normally menstruating women with different grades of type 2 diabetes mellitus. We studied the right eyes of 123 normally menstruating women (36 with severe nonproliferative diabetic retinopathy [NPDR], 42 with mild NPDR and 45 healthy subjects). All subjects underwent a complete ocular examination at baseline. At 4 hormonally distinct phases of the menstrual cycle (early follicular, late follicular, mid-luteal and late luteal), we analysed the topography of the optic nerve head, using a confocal scanning laser ophthalmoscope, and measured the serum levels of estradiol, progesterone and luteinizing hormone. We excluded from analysis the data for 8 patients with severe NPDR, 10 patients with mild NPDR and 15 control subjects who were lost to follow-up examinations during the menstrual cycle. The mean age and optic disc area did not differ significantly among the 3 groups. The duration of diabetes was significantly longer in the patients with severe NPDR than in those with mild NPDR (p < 0.05). The women with severe NPDR had a significantly increased neuroretinal rim area and a significantly decreased cup-shape measure, linear cup/disc ratio, cup/disc area ratio and cup area in the late luteal phase compared with the other phases of the menstrual cycle (p < 0.05). Those with mild NPDR or a normal retina had no significant topographic changes in the optic nerve head during the menstrual cycle. Severe NPDR is associated with significant topographic changes in the rim and cup of the optic nerve head during the menstrual cycle. This must be considered in the evaluation of women with both diabetes and glaucoma. The normal fluctuations in serum sex hormone levels during the menstrual cycle of diabetic women seem to affect the optic nerve head more when the disease is advanced.

Bilateral optic disc drusen mimicking papilledema.

PubMed

Sahin, Alparslan; Cingü, Abdullah Kürşat; Ari, Seyhmus; Cinar, Yasin; Caça, Ihsan

2012-06-01

Optic disc drusen, which are calcified deposits that form anterior to the lamina cribrosa in the optic nerve, may mimic papilledema. We report herein three cases referred to us with suspicion of disc swelling and papilledema. Following ophthalmologic evaluation with B-scan ultrasound, red-free fundus photography, and computed tomography, the diagnosis of papilledema was excluded in all cases and optic disc drusen was diagnosed. Clinical suspicion of optic disc drusen in cases presenting with swelling of the optic nerve head is important in order to avoid unnecessary interventions and anxiety. The reported cases highlight the commonly encountered clinical presentations and the practical aspects of diagnosis and management of optic disc drusen.

Hydrogen-rich saline promotes survival of retinal ganglion cells in a rat model of optic nerve crush.

PubMed

Sun, Jing-chuan; Xu, Tao; Zuo, Qiao; Wang, Ruo-bing; Qi, Ai-qing; Cao, Wen-luo; Sun, Ai-jun; Sun, Xue-jun; Xu, Jiajun

2014-01-01

To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC). We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) could be protected by H₂. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated. H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H₂ group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR. These results demonstrated that H₂ protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

PubMed Central

Howell, Gareth R.; Soto, Ileana; Zhu, Xianjun; Ryan, Margaret; Macalinao, Danilo G.; Sousa, Gregory L.; Caddle, Lura B.; MacNicoll, Katharine H.; Barbay, Jessica M.; Porciatti, Vittorio; Anderson, Michael G.; Smith, Richard S.; Clark, Abbot F.; Libby, Richard T.; John, Simon W.M.

2012-01-01

Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve. PMID:22426214

Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction.

PubMed

Bertin, Jonathan; Dury, Alain Y; Ouellet, Johanne; Pelletier, Georges; Labrie, Fernand

2014-08-01

To better understand the mechanisms underlying the beneficial effects of the intravaginal administration of dehydroepiandrosterone (DHEA) observed in postmenopausal women on sexual dysfunction. To identify the distribution of the androgen-synthesizing enzymes as well as androgen receptor (AR) and measure steroid levels in the monkey vagina. The cynomolgus monkey (Macaca fascicularis), the closest model to the human, has been used to measure the expression levels of steroidogenic enzymes and androgen receptor by quantitative reverse transcription polymerase chain reaction (n=4), confirmed by immunohistochemistry, and immunofluorescence (n=3). DHEA and its androgenic metabolites were quantified by LC-MS/MS (n=4). The presence of SRD5A1, SRD5A2, HSD17B3, AR as well as nerve fibers (PGP 9.5) was investigated, and steroid levels were measured. AR is widely distributed within the vaginal epithelium and also in the lamina propria with a lower expression in the muscularis layer and blood vessel walls. Androgen-forming enzymes, on the other hand, are expressed in the vaginal stratified squamous epithelium at a relatively high level where they are uniformly distributed from the basal membrane up to the superficial keratinized cells. The enzymes are at a lower level in blood vessel walls and zona muscularis where nerve fibers are localized. DHEA and its androgen metabolites are present at biologically significant concentrations in the monkey vagina. The enzymes responsible for androgen formation as well as AR are at the highest level in the superficial layer of the stratified epithelium and muscularis layers of the vagina. These data provide a potential explanation for the described role of androgens in regulating vaginal lubrication, smooth muscle activity, blood flow, and the neuronal activity potentially involved in the correction of sexual dysfunction. © 2014 International Society for Sexual Medicine.

Prevalence of Split Nerve Fiber Layer Bundles in Healthy People Imaged with Spectral Domain Optical Coherence Tomography.

PubMed

Gür Güngör, Sirel; Akman, Ahmet; Sarıgül Sezenöz, Almila; Tanrıaşıkı, Gülşah

2016-12-01

The presence of retinal nerve fiber layer (RNFL) split bundles was recently described in normal eyes scanned using scanning laser polarimetry and by histologic studies. Split bundles may resemble RNFL loss in healthy eyes. The aim of our study was to determine the prevalence of nerve fiber layer split bundles in healthy people. We imaged 718 eyes of 359 healthy persons with the spectral domain optical coherence tomography in this cross-sectional study. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program). In our study, a bundle was defined as 'split' when there is localized defect not resembling a wedge defect in the RNFL deviation map with a symmetrically divided RNFL appearance on the RNFL thickness map. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification. Inter-observer consensus was reached in all cases. Bilateral superior split bundles were seen in 19 cases (5.29%) and unilateral superior split was observed in 15 cases (4.16%). In 325 cases (90.52%) there was no split bundle. Split nerve fiber layer bundles, in contrast to single nerve fiber layer bundles, are not common findings in healthy eyes. In eyes with normal optic disc appearance, especially when a superior RNFL defect is observed in RNFL deviation map, the RNLF thickness map and graphs should also be examined for split nerve fiber layer bundles.

Pilot Study of Optical Coherence Tomography Measurement of Retinal Blood Flow in Retinal and Optic Nerve Diseases

PubMed Central

Wang, Yimin; Fawzi, Amani A.; Varma, Rohit; Sadun, Alfredo A.; Zhang, Xinbo; Tan, Ou; Izatt, Joseph A.

2011-01-01

Purpose. To investigate blood flow changes in retinal and optic nerve diseases with Doppler Fourier domain optical coherence tomography (OCT). Methods. Sixty-two participants were divided into five groups: normal, glaucoma, nonarteritic ischemic optic neuropathy (NAION), treated proliferative diabetic retinopathy (PDR), and branch retinal vein occlusion (BRVO). Doppler OCT was used to scan concentric circles of 3.4- and 3.75-mm diameters around the optic nerve head. Flow in retinal veins was calculated from the OCT velocity profiles. Arterial and venous diameters were measured from OCT Doppler and reflectance images. Results. Total retinal blood flow in normal subjects averaged 47.6 μL/min. The coefficient of variation of repeated measurements was 11% in normal eyes and 14% in diseased eyes. Eyes with glaucoma, NAION, treated PDR, and BRVO had significantly decreased retinal blood flow compared with normal eyes (P < 0.001). In glaucoma patients, the decrease in blood flow was highly correlated with the severity of visual field loss (P = 0.003). In NAION and BRVO patients, the hemisphere with more severe disease also had lower blood flow. Conclusions. Doppler OCT retinal blood flow measurements showed good repeatability and excellent correlation with visual field and clinical presentations. This approach could enhance our understanding of retinal and optic nerve diseases and facilitate the development of new therapies. PMID:21051715

Optical coherence tomography measurement of the retinal nerve fiber layer in normal and juvenile glaucomatous eyes.

PubMed

Mrugacz, Malgorzata; Bakunowicz-Lazarczyk, Alina

2005-01-01

The aim of this study was to quantitatively assess and compare the thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes of children using the optical coherence tomograph. The mean RNFL thickness of normal eyes (n=26) was compared with that of glaucomatous eyes (n=26). The eyes were classified into diagnostic groups based on conventional ophthalmological physical examination, Humphrey 30-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. The mean RNFL was significantly thinner in glaucomatous eyes than in normal eyes: 95+/-26.3 and 132+/-24.5 microm, respectively. More specifically, the RNFL was significantly thinner in glaucomatous eyes than in normal eyes in the inferior quadrant: 87+/-23.5 and 122+/-24.2 microm, respectively. The mean and inferior quadrant RFNL thicknesses as measured by the optical coherence tomograph showed a statistically significant correlation with glaucoma. Optical coherence tomography may contribute to tracking of juvenile glaucoma progression. Copyright (c) 2005 S. Karger AG, Basel.

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

PubMed

Cuneo, K C; Zagar, T M; Brizel, D M; Yoo, D S; Hoang, J K; Chang, Z; Wang, Z; Yin, F F; Das, S K; Green, S; Ready, N; Bhatti, M T; Kaylie, D M; Becker, A; Sampson, J H; Kirkpatrick, J P

2012-06-01

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm for each case examined.

White matter changes linked to visual recovery after nerve decompression

PubMed Central

Paul, David A.; Gaffin-Cahn, Elon; Hintz, Eric B.; Adeclat, Giscard J.; Zhu, Tong; Williams, Zoë R.; Vates, G. Edward; Mahon, Bradford Z.

2015-01-01

The relationship between the integrity of white matter tracts and cortical function in the human brain remains poorly understood. Here we use a model of reversible white matter injury, compression of the optic chiasm by tumors of the pituitary gland, to study the structural and functional changes that attend spontaneous recovery of cortical function and visual abilities after surgical tumor removal and subsequent decompression of the nerves. We show that compression of the optic chiasm leads to demyelination of the optic tracts, which reverses as quickly as 4 weeks after nerve decompression. Furthermore, variability across patients in the severity of demyelination in the optic tracts predicts visual ability and functional activity in early cortical visual areas, and pre-operative measurements of myelination in the optic tracts predicts the magnitude of visual recovery after surgery. These data indicate that rapid regeneration of myelin in the human brain is a significant component of the normalization of cortical activity, and ultimately the recovery of sensory and cognitive function, after nerve decompression. More generally, our findings demonstrate the utility of diffusion tensor imaging as an in vivo measure of myelination in the human brain. PMID:25504884

Comparative quantitative study of astrocytes and capillary distribution in optic nerve laminar regions.

PubMed

Balaratnasingam, Chandrakumar; Kang, Min H; Yu, Paula; Chan, Geoffrey; Morgan, William H; Cringle, Stephen J; Yu, Dao-Yi

2014-04-01

Retinal ganglion cell (RGC) axonal structure and function in the optic nerve head (ONH) is predominantly supported by astrocytes and capillaries. There is good experimental evidence to demonstrate that RGC axons are perturbed in a non-uniform manner following ONH injury and it is likely that the pattern of RGC axonal modification bears some correlation with the quantitative properties of astrocytes and capillaries within laminar compartments. Although there have been some excellent topographic studies concerning glial and microvascular networks in the ONH our knowledge regarding the quantitative properties of these structures are limited. This report is an in-depth quantitative, structural analysis of astrocytes and capillaries in the pre laminar, lamina cribrosa and post laminar compartments of the ONH. 49 optic nerves from human (n = 10), pig (n = 12), horse (n = 6), rat (n = 11) and rabbit (n = 10) eyes are studied. Immunohistochemical and high-magnification confocal microscopy techniques are used to co-localise astrocytes, capillaries and nuclei in the mid-portion of the optic nerve. Quantitative methodology is used to determine the area occupied by astrocyte processes, microglia processes, nuclei density and the area occupied by capillaries in each laminar compartment. Comparisons are made within and between species. Relationships between ONH histomorphometry and astrocyte-capillary constitution are also explored. This study demonstrates that there are significant differences in the quantitative properties of capillaries and astrocytes between the laminar compartments of the human ONH. Astrocyte processes occupied the greatest area in the lamina cribrosa compartment of the human ONH implicating it as an area of great metabolic demands. Microglia were found to occupy only a small proportion of tissue in the rat, rabbit and pig optic nerve suggesting that the astrocyte is the predominant glia cell type in the optic nerve. This study also demonstrates that there is significant uniformity, with respect to astrocyte and capillary constitution, in the post laminar region of species with an unmyelinated anterior optic nerve. This implicates an important role served by oligodendrocytes and myelin in governing the structural characteristics of the post laminar optic nerve. Finally, this study demonstrates that eyes with similar lamina cribrosa structure do not necessarily share an identical cellular constitution with respect to astrocytes. The quantitative properties of astrocytes in the pre laminar and lamina cribrosa regions of the rat, which has a rudimentary lamina cribrosa with only a few collagenous beams, shared more similarities to the human eye than the pig or horse. The quantitative properties of astrocytes and capillaries in the laminar compartments of the ONH provide a basis for understanding the pathogenic mechanisms that are involved in diseases such as glaucoma and ischemic optic neuropathy. The findings in this study also provide valuable information about the distinct advantages of different animal models for studying human optic nerve diseases. Utilisation of structural data provided in this report together with emerging in vivo technology may potentially permit the early identification of RGC axonal injury by quantifying changes in ONH capillaries and astrocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Virtual tissue engineering and optic pathways: plotting the course of the axons in the retinal nerve fiber layer.

PubMed

Carreras, Francisco Javier; Medina, Javier; Ruiz-Lozano, Mariola; Carreras, Ignacio; Castro, Juan Luis

2014-04-17

As part of a larger project on virtual tissue engineering of the optic pathways, we describe the conditions that guide axons extending from the retina to the optic nerve head and formulate algorithms that meet such conditions. To find the entrance site on the optic nerve head of each axon, we challenge the fibers to comply with current models of axonal pathfinding. First, we build a retinal map using a single type of retinal ganglion cell (RGC) using density functions from the literature. Dendritic arbors are equated to receptive fields. Shape and size of retinal surface and optic nerve head (ONH) are defined. A computer model relates each soma to the corresponding entry point of its axon into the optic disc. Weights are given to the heuristics that guide the preference entry order in the nerve. Retinal ganglion cells from the area centralis saturate the temporal section of the disc. Retinal ganglion cells temporal to the area centralis curve their paths surrounding the fovea; some of these cells enter the disc centrally rather than peripherally. Nasal regions of the disc receive mixed axons from the far periphery of the temporal hemiretina, together with axons from the nasal half. The model plots the course of the axon using Bezier curves and compares them with clinical data, for a coincidence level of 86% or higher. Our model is able to simulate basic data of the early optic pathways including certain singularities and to mimic mechanisms operating during development, such as timing and fasciculation. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

PubMed

Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

1991-04-22

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

[Squirrel monkey--an ideal primate (correction of prmate) model of space physiology].

PubMed

Matsunami, K

1997-06-01

Investigation of the vestibulo-ocular system of the squirrel monkey was reviewed in consideration of space motion sickness (SMS), or which is recently more often termed as space adaptation syndrome (SAS). Since the first launching of the space satellite, Sputnik [correction of Sputonik] in October 1957, many experiments were carried out in biological and medical fields. A various kind of creatures were used as experimental models from protozoa to human beings. Rats and monkeys are most favorite animals, particularly the non-human primate seems to be the one, because of its phylogenetic relatives akin to the human beings. Chimpanzees, rhesus monkeys, pig tailed-monkeys, red-faced monkeys and squirrel monkeys have been used mostly in American space experiments. Russian used rhesus monkeys. Among these, however, the squirrel monkey has an advantage of the small size of the body, ranging from 600- l000g in adult. This small size as a primate is very advantageous in experiments conducted in a narrow room of the space satellite or shuttle because of its space-saving. The squirrel monkey has another advantage to rear easily as is demonstrated to keep it as a pet. Accordingly, this petit animal provides us a good animal model in biological and medical experiments in space craft. The size of the brain of the squirrel monkey is extraordinary large relative to the body size, which is even superior to that of the human beings. This is partly owed to enlargement of the occipito-temporal cortices, which are forced to well develop for processing a huge amount of audio-visual information indispensable to the arboreal habitant to survive in tropical forest. The vestibular system of the squirrel monkey seems to be the most superior as well, when judged from it relative size of the vestibular nuclear complex. Balancing on swinging twigs or jumping from tree to tree developed the capability of this equilibrium system. Fernandez, Goldberg and his collaborators used the squirrel monkey to elucidate functions of the peripheral vestibular system. A transfer function was proposed to explain the behaviors of regular and irregular unit activity of vestibular nerve fibers. The physiologic characteristics of the second order vestibular neuron was investigated in combination of electrophysiological and micro-morphological way, with using WGA-HRP methods, in relation to somato-motor and eye movements. Interconnections between vestibular neurons and cerebellum, interstitial nucleus of Cajal, oculomotor nuclear complex, superior colliculus and cervical spinal cord were elucidated. In physiological field of the vestibular system, the vestibulo-ocular reflex is well studied and results obtained from the squirrel monkey experiments were reviewed. The squirrel monkey, particularly the Bolivian, is a unique animal in that it is vulnerable to motion sickness induced by visual-motion stimulation with phase mismatch of the two stimuli. Experimental results of labyrinthectomy or bilateral ablation of the maculae staticae led to the conclusion that both semicircular and otolith organs are involved in the genesis of space motion sickness. On the other hand, destruction of the area postrema, acknowledged as the vomiting center to chemical stimulants, produced controversial results. However, it must be pointed out that the a human subject underwent to resection of the area postrema, became insensitive to administration of apomorphine, a well known chemical stimulant of vomiting. Finally the experiments in space revealed the presence of at least two origins of caloric nystagmus, that is, attributable to convection and non-convection current of the endolymphatic fluid.

High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia

PubMed Central

Pilat, Anastasia; Sibley, Daniel; McLean, Rebecca J.; Proudlock, Frank A.; Gottlob, Irene

2015-01-01

Purpose To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT). Design Prospective, cross-sectional, observational study. Subjects A total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls. Methods High-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula. Main Outcome Measures Horizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls. Results Patients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%. Conclusions Our study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis. PMID:25939636

Optic neuropathies: the tip of the neurodegeneration iceberg

PubMed Central

Carelli, Valerio; La Morgia, Chiara; Ross-Cisneros, Fred N.; Sadun, Alfredo A.

2017-01-01

Abstract The optic nerve and the cells that give origin to its 1.2 million axons, the retinal ganglion cells (RGCs), are particularly vulnerable to neurodegeneration related to mitochondrial dysfunction. Optic neuropathies may range from non-syndromic genetic entities, to rare syndromic multisystem diseases with optic atrophy such as mitochondrial encephalomyopathies, to age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease where optic nerve involvement has, until recently, been a relatively overlooked feature. New tools are available to thoroughly investigate optic nerve function, allowing unparalleled access to this part of the central nervous system. Understanding the molecular pathophysiology of RGC neurodegeneration and optic atrophy, is key to broadly understanding the pathogenesis of neurodegenerative disorders, for monitoring their progression in describing the natural history, and ultimately as outcome measures to evaluate therapies. In this review, the different layers, from molecular to anatomical, that may contribute to RGC neurodegeneration and optic atrophy are tackled in an integrated way, considering all relevant players. These include RGC dendrites, cell bodies and axons, the unmyelinated retinal nerve fiber layer and the myelinated post-laminar axons, as well as olygodendrocytes and astrocytes, looked for unconventional functions. Dysfunctional mitochondrial dynamics, transport, homeostatic control of mitobiogenesis and mitophagic removal, as well as specific propensity to apoptosis may target differently cell types and anatomical settings. Ultimately, we can envisage new investigative approaches and therapeutic options that will speed the early diagnosis of neurodegenerative diseases and their cure. PMID:28977448

A photon-driven micromotor can direct nerve fibre growth

NASA Astrophysics Data System (ADS)

Wu, Tao; Nieminen, Timo A.; Mohanty, Samarendra; Miotke, Jill; Meyer, Ronald L.; Rubinsztein-Dunlop, Halina; Berns, Michael W.

2012-01-01

Axonal path-finding is important in the development of the nervous system, nerve repair and nerve regeneration. The behaviour of the growth cone at the tip of the growing axon determines the direction of axonal growth and migration. We have developed an optical-based system to control the direction of growth of individual axons (nerve fibres) using laser-driven spinning birefringent spheres. One or two optical traps position birefringent beads adjacent to growth cones of cultured goldfish retinal ganglion cell axons. Circularly polarized light with angular momentum causes the trapped bead to spin. This creates a localized microfluidic flow generating an estimated 0.17 pN shear force against the growth cone that turns in response to the shear. The direction of axonal growth can be precisely manipulated by changing the rotation direction and position of this optically driven micromotor. A physical model estimating the shear force density on the axon is described.

Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs.

PubMed

Kanamori, Akiyasu; Nakamura, Makoto; Matsui, Noriko; Nagai, Azusa; Nakanishi, Yoriko; Kusuhara, Sentaro; Yamada, Yuko; Negi, Akira

2004-12-01

To analyze retinal nerve fiber layer (RNFL) thickness in eyes with band atrophy by use of optical coherence tomography (OCT) and to evaluate the ability of OCT to detect this characteristic pattern of RNFL loss. Cross-sectional, retrospective study. Thirty-four eyes of 18 patients with bitemporal hemianopia caused by optic chiasm compression by chiasmal tumors were studied. All eyes were divided into 3 groups according to visual field loss grading after Goldmann perimetry. Retinal nerve fiber layer thickness measurements with OCT. Retinal nerve fiber layer thickness around the optic disc was measured by OCT (3.4-mm diameter circle). Calculation of the changes in OCT parameters, including the horizontal (nasal + temporal quadrant RNFL thickness) and vertical values (superior + inferior quadrant RNFL thickness) was based on data from 160 normal eyes. Comparison between the 3 visual field grading groups was done with the analysis of variance test. The receiver operating characteristic (ROC) curve for the horizontal and vertical value were calculated, and the areas under the curve (AUC) were compared. Retinal nerve fiber layer thickness in eyes with band atrophy decreased in all OCT parameters. The reduction rate in average and temporal RNFL thickness and horizontal value was correlated with visual field grading. The AUC of horizontal value was 0.970+/-0.011, which was significantly different from AUC of vertical value (0.903+/-0.022). The degree of RNFL thickness reduction correlated with that of visual field defects. Optical coherence tomography was able to identify the characteristic pattern of RNFL loss in these eyes.

Neuro-Ophthalmology at a Tertiary Eye Care Centre in India.

PubMed

Dhiman, Rebika; Singh, Digvijay; Gantayala, Shiva P; Ganesan, Vaitheeswaran L; Sharma, Pradeep; Saxena, Rohit

2017-11-09

Neuro-ophthalmology as a specialty is underdeveloped in India. The aim of our study was to determine the spectrum and profile of patients presenting to a tertiary eye care center with neuro-ophthalmic disorders. A retrospective hospital-based study was conducted, and records of all patients seen at the neuro-ophthalmology clinic of Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India, over a 1-year period were retrieved and evaluated. Of a total of 30,111 patients referred to various specialty clinics in a span of 1 year, 1597 (5%) were referred for neuro-ophthalmology evaluation. The mean patient age was 30.8 ± 19.5 years, with a male dominance (M:F = 2.02:1). Among these patients, optic nerve disorders were noted in 63.8% (n = 1,020), cranial nerve palsy in 7% (n = 114), cortical visual impairment in 6.5% (n = 105), and others (eye/optic nerve hypophasia, blepharospasm, and optic disc drusen) in 6% (n = 95). Among the patients with optic nerve disorders, optic neuropathy without disc edema/(traumatic optic neuropathy, hereditary, tumor-related, retrobulbar neuritis, toxic, and idiopathic) was noted in 42.8% (n = 685) and optic neuropathy with disc edema (ischemic optic neuropathy, papilledema, post-papilledema optic atrophy, papillitis, neuroretinitis, and inflammatory optic neuropathy) in 20.9% (n = 335). Sixteen percent of patients (n = 263) were incorrect referrals. The neuro-ophthalmic clinic constitutes a significant referral unit in a tertiary eye care center in India. Traumatic and ischemic optic neuropathies are the most common diagnoses. Neuro-ophthalmology requires further development as a subspecialty in India to better serve the nation's population.

Multispectral photoacoustic imaging of nerves with a clinical ultrasound system

NASA Astrophysics Data System (ADS)

Mari, Jean Martial; West, Simeon; Beard, Paul C.; Desjardins, Adrien E.

2014-03-01

Accurate and efficient identification of nerves is of great importance during many ultrasound-guided clinical procedures, including nerve blocks and prostate biopsies. It can be challenging to visualise nerves with conventional ultrasound imaging, however. One of the challenges is that nerves can have very similar appearances to nearby structures such as tendons. Several recent studies have highlighted the potential of near-infrared optical spectroscopy for differentiating nerves and adjacent tissues, as this modality can be sensitive to optical absorption of lipids that are present in intra- and extra-neural adipose tissue and in the myelin sheaths. These studies were limited to point measurements, however. In this pilot study, a custom photoacoustic system with a clinical ultrasound imaging probe was used to acquire multi-spectral photoacoustic images of nerves and tendons from swine ex vivo, across the wavelength range of 1100 to 1300 nm. Photoacoustic images were processed and overlaid in colour onto co-registered conventional ultrasound images that were acquired with the same imaging probe. A pronounced optical absorption peak centred at 1210 nm was observed in the photoacoustic signals obtained from nerves, and it was absent in those obtained from tendons. This absorption peak, which is consistent with the presence of lipids, provides a novel image contrast mechanism to significantly enhance the visualization of nerves. In particular, image contrast for nerves was up to 5.5 times greater with photoacoustic imaging (0.82 +/- 0.15) than with conventional ultrasound imaging (0.148 +/- 0.002), with a maximum contrast of 0.95 +/- 0.02 obtained in photoacoustic mode. This pilot study demonstrates the potential of photoacoustic imaging to improve clinical outcomes in ultrasound-guided interventions in regional anaesthesia and interventional oncology.

Optic neuropathies--importance of spatial distribution of mitochondria as well as function.

PubMed

Yu Wai Man, C Y; Chinnery, P F; Griffiths, P G

2005-01-01

Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic atrophy and toxic amblyopia are an important cause of irreversible visual failure. Although they are associated with a defect of mitochondrial energy production, their pathogenesis is poorly understood. A common feature to all these disorders is relatively selective degeneration of the papillomacular bundle of retinal ganglion cells resulting central or caecocentral visual field defects. The striking similarity in the pattern of clinical involvement seen with these disparate disorders suggests a common pathway in their aetiology. The existing hypothesis that the optic nerve head has higher energy demands than other tissues making it uniquely dependent on oxidative phosporylation is not satisfactory. First, other ocular tissues such as photoreceptors, which are more dependent on oxidative phosporylation are not affected. Second, other mitochondrial disorders, which have a greater impact on mitochondrial energy function, do not affect the optic nerve. The optic nerve head has certain unique ultra structural features. Ganglion cell axons exit the eye through a perforated collagen plate, the lamina cribrosa. There is a sharp discontinuity in the density of mitochondria at the optic nerve head, with a very high concentration in the prelaminar nerve fibre layer and low concentration behind the lamina. This has previously been attributed to a mechanical hold up of axoplasmic flow, which has itself been proposed as a factor in the pathogenesis of a number of optic neuropathies. More recent evidence shows that mitochondrial distribution reflects the different energy requirements of the unmyelinated prelaminar axons in comparison to the myelinated retrolaminar axons. The heterogeous distribution of mitochondria is actively maintained to support conduction through the optic nerve head. We propose that factors that disrupt the heterogeneous distribution of mitochondria can result in ganglion cell death. Evidence for this comes from studies of cultured cells with the dominant optic atrophy mutation in which mitochondrial distribution is altered and from some forms of hereditary spastic paraparesis which are associated with optic atrophy. The responsible mutations do not affect ATP production until late in the disease but do affect mitochondrial arrangement, again showing that mitochondrial distribution as well as energy production by individual mitochondria may be important in the pathogenesis of ganglion cell death. Greater understanding of the factors localising mitochondria within the ganglion cell axon in particular the interaction with cytoskeleton is required to formulate new treatments. Boosting energy production alone may not be an effective treatment.

Non-invasive detection of animal nerve impulses with an atomic magnetometer operating near quantum limited sensitivity

PubMed Central

Jensen, Kasper; Budvytyte, Rima; Thomas, Rodrigo A.; Wang, Tian; Fuchs, Annette M.; Balabas, Mikhail V.; Vasilakis, Georgios; Mosgaard, Lars D.; Stærkind, Hans C.; Müller, Jörg H.; Heimburg, Thomas; Olesen, Søren-Peter; Polzik, Eugene S.

2016-01-01

Magnetic fields generated by human and animal organs, such as the heart, brain and nervous system carry information useful for biological and medical purposes. These magnetic fields are most commonly detected using cryogenically-cooled superconducting magnetometers. Here we present the first detection of action potentials from an animal nerve using an optical atomic magnetometer. Using an optimal design we are able to achieve the sensitivity dominated by the quantum shot noise of light and quantum projection noise of atomic spins. Such sensitivity allows us to measure the nerve impulse with a miniature room-temperature sensor which is a critical advantage for biomedical applications. Positioning the sensor at a distance of a few millimeters from the nerve, corresponding to the distance between the skin and nerves in biological studies, we detect the magnetic field generated by an action potential of a frog sciatic nerve. From the magnetic field measurements we determine the activity of the nerve and the temporal shape of the nerve impulse. This work opens new ways towards implementing optical magnetometers as practical devices for medical diagnostics. PMID:27417378

Non-invasive detection of animal nerve impulses with an atomic magnetometer operating near quantum limited sensitivity

NASA Astrophysics Data System (ADS)

Jensen, Kasper; Budvytyte, Rima; Thomas, Rodrigo A.; Wang, Tian; Fuchs, Annette M.; Balabas, Mikhail V.; Vasilakis, Georgios; Mosgaard, Lars D.; Stærkind, Hans C.; Müller, Jörg H.; Heimburg, Thomas; Olesen, Søren-Peter; Polzik, Eugene S.

2016-07-01

Magnetic fields generated by human and animal organs, such as the heart, brain and nervous system carry information useful for biological and medical purposes. These magnetic fields are most commonly detected using cryogenically-cooled superconducting magnetometers. Here we present the first detection of action potentials from an animal nerve using an optical atomic magnetometer. Using an optimal design we are able to achieve the sensitivity dominated by the quantum shot noise of light and quantum projection noise of atomic spins. Such sensitivity allows us to measure the nerve impulse with a miniature room-temperature sensor which is a critical advantage for biomedical applications. Positioning the sensor at a distance of a few millimeters from the nerve, corresponding to the distance between the skin and nerves in biological studies, we detect the magnetic field generated by an action potential of a frog sciatic nerve. From the magnetic field measurements we determine the activity of the nerve and the temporal shape of the nerve impulse. This work opens new ways towards implementing optical magnetometers as practical devices for medical diagnostics.

Bilateral Optic Disc Drusen Mimicking Papilledema

PubMed Central

Cingü, Abdullah Kürşat; Ari, Şeyhmus; Çinar, Yasin; Çaça, İhsan

2012-01-01

Background Optic disc drusen, which are calcified deposits that form anterior to the lamina cribrosa in the optic nerve, may mimic papilledema. Case Report We report herein three cases referred to us with suspicion of disc swelling and papilledema. Following ophthalmologic evaluation with B-scan ultrasound, red-free fundus photography, and computed tomography, the diagnosis of papilledema was excluded in all cases and optic disc drusen was diagnosed. Conclusions Clinical suspicion of optic disc drusen in cases presenting with swelling of the optic nerve head is important in order to avoid unnecessary interventions and anxiety. The reported cases highlight the commonly encountered clinical presentations and the practical aspects of diagnosis and management of optic disc drusen. PMID:22787500

Optical signature of nerve tissue-Exploratory ex vivo study comparing optical, histological, and molecular characteristics of different adipose and nerve tissues.

PubMed

Balthasar, Andrea J R; Bydlon, Torre M; Ippel, Hans; van der Voort, Marjolein; Hendriks, Benno H W; Lucassen, Gerald W; van Geffen, Geert-Jan; van Kleef, Maarten; van Dijk, Paul; Lataster, Arno

2018-05-14

During several anesthesiological procedures, needles are inserted through the skin of a patient to target nerves. In most cases, the needle traverses several tissues-skin, subcutaneous adipose tissue, muscles, nerves, and blood vessels-to reach the target nerve. A clear identification of the target nerve can improve the success of the nerve block and reduce the rate of complications. This may be accomplished with diffuse reflectance spectroscopy (DRS) which can provide a quantitative measure of the tissue composition. The goal of the current study was to further explore the morphological, biological, chemical, and optical characteristics of the tissues encountered during needle insertion to improve future DRS classification algorithms. To compare characteristics of nerve tissue (sciatic nerve) and adipose tissues, the following techniques were used: histology, DRS, absorption spectrophotometry, high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy, and solution 2D 13 C- 1 H heteronuclear single-quantum coherence spectroscopy. Tissues from five human freshly frozen cadavers were examined. Histology clearly highlights a higher density of cellular nuclei, collagen, and cytoplasm in fascicular nerve tissue (IFAS). IFAS showed lower absorption of light around 1200 nm and 1750 nm, higher absorption around 1500 nm and 2000 nm, and a shift in the peak observed around 1000 nm. DRS measurements showed a higher water percentage and collagen concentration in IFAS and a lower fat percentage compared to all other tissues. The scattering parameter (b) was highest in IFAS. The HR-MAS NMR data showed three extra chemical peak shifts in IFAS tissue. Collagen, water, and cellular nuclei concentration are clearly different between nerve fascicular tissue and other adipose tissue and explain some of the differences observed in the optical absorption, DRS, and HR-NMR spectra of these tissues. Some differences observed between fascicular nerve tissue and adipose tissues cannot yet be explained but may be helpful in improving the discriminatory capabilities of DRS in anesthesiology procedures. Lasers Surg. Med. 9999:1-13, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury.

PubMed

Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

2013-11-15

To investigate the potential therapeutic benefit of intravitreally implanted dental pulp stem cells (DPSCs) on axotomized adult rat retinal ganglion cells (RGCs) using in vitro and in vivo neural injury models. Conditioned media collected from cultured rat DPSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were assayed for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) secretion using ELISA. DPSCs or BMSCs were cocultured with retinal cells, with or without Fc-TrK inhibitors, in a Transwell system, and the number of surviving βIII-tubulin⁺ retinal cells and length/number of βIII-tubulin⁺ neurites were quantified. For the in vivo study, DPSCs or BMSCs were transplanted into the vitreous body of the eye after a surgically induced optic nerve crush injury. At 7, 14, and 21 days postlesion (dpl), optical coherence tomography (OCT) was used to measure the retinal nerve fiber layer thickness as a measure of axonal atrophy. At 21 dpl, numbers of Brn-3a⁺ RGCs in parasagittal retinal sections and growth-associated protein-43⁺ axons in longitudinal optic nerve sections were quantified as measures of RGC survival and axon regeneration, respectively. Both DPSCs and BMSCs secreted NGF, BDNF, and NT-3, with DPSCs secreting significantly higher titers of NGF and BDNF than BMSCs. DPSCs, and to a lesser extent BMSCs, promoted statistically significant survival and neuritogenesis/axogenesis of βIII-tubulin⁺ retinal cells in vitro and in vivo where the effects were abolished after TrK receptor blockade. Intravitreal transplants of DPSCs promoted significant neurotrophin-mediated RGC survival and axon regeneration after optic nerve injury.

ImagePAD, a novel counting application for the Apple iPad, used to quantify axons in the mouse optic nerve.

PubMed

Templeton, Justin P; Struebing, Felix L; Lemmon, Andrew; Geisert, Eldon E

2014-11-01

The present article introduces a new and easy to use counting application for the Apple iPad. The application "ImagePAD" takes advantage of the advanced user interface features offered by the Apple iOS platform, simplifying the rather tedious task of quantifying features in anatomical studies. For example, the image under analysis can be easily panned and zoomed using iOS-supported multi-touch gestures without losing the spatial context of the counting task, which is extremely important for ensuring count accuracy. This application allows one to quantify up to 5 different types of objects in a single field and output the data in a tab-delimited format for subsequent analysis. We describe two examples of the use of the application: quantifying axons in the optic nerve of the C57BL/6J mouse and determining the percentage of cells labeled with NeuN or ChAT in the retinal ganglion cell layer. For the optic nerve, contiguous images at 60× magnification were taken and transferred onto an Apple iPad. Axons were counted by tapping on the touch-sensitive screen using ImagePAD. Nine optic nerves were sampled and the number of axons in the nerves ranged from 38,872 axons to 50,196 axons with an average of 44,846 axons per nerve (SD = 3980 axons). Copyright © 2014 Elsevier Ltd. All rights reserved.

Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

NASA Technical Reports Server (NTRS)

Fernandez, C.; Lysakowski, A.; Goldberg, J. M.

1995-01-01

1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx endings to type I hair cells and bouton endings to type II hair cells. Long intraepithelial fibers are calyx and dimorphic units, whose terminal fields are similar to those of other fibers. The central zone is innervated by calyx and dimorphic fibers; the peripheral zone, by bouton and dimorphic fibers; and the intermediate zone, by all three kinds of fibers. Internal (axon) diameters are largest for calyx fibers and smallest for bouton fibers. Of the entire sample of 286 labeled fibers, 52% were dimorphic units, 40% were calyx units, and 8% were bouton units.(ABSTRACT TRUNCATED AT 400 WORDS).

Scanning laser topography and scanning laser polarimetry: comparing both imaging methods at same distances from the optic nerve head.

PubMed

Kremmer, Stephan; Keienburg, Marcus; Anastassiou, Gerasimos; Schallenberg, Maurice; Steuhl, Klaus-Peter; Selbach, J Michael

2012-01-01

To compare the performance of scanning laser topography (SLT) and scanning laser polarimetry (SLP) on the rim of the optic nerve head and its surrounding area and thereby to evaluate whether these imaging technologies are influenced by other factors beyond the thickness of the retinal nerve fiber layer (RNFL). A total of 154 eyes from 5 different groups were examined: young healthy subjects (YNorm), old healthy subjects (ONorm), patients with normal tension glaucoma (NTG), patients with open-angle glaucoma and early glaucomatous damage (OAGE) and patients with open-angle glaucoma and advanced glaucomatous damage (OAGA). SLT and SLP measurements were taken. Four concentric circles were superimposed on each of the images: the first one measuring at the rim of the optic nerve head (1.0 ONHD), the next measuring at 1.25 optic nerve head diameters (ONHD), at 1.5 ONHD and at 1.75 ONHD. The aligned images were analyzed using GDx/NFA software. Both methods showed peaks of RNFL thickness in the superior and inferior segments of the ONH. The maximum thickness, registered by the SLT device was at the ONH rim where the SLP device tended to measure the lowest values. SLT measurements at the ONH were influenced by other tissues besides the RNFL like blood vessels and glial tissues. SLT and SLP were most strongly correlated at distances of 1.25 and 1.5 ONHD. While both imaging technologies are valuable tools in detecting glaucoma, measurements at the ONH rim should be interpreted critically since both methods might provide misleading results. For the assessment of the retinal nerve fiber layer we would like to recommend for both imaging technologies, SLT and SLP, measurements in 1.25 and 1.5 ONHD distance of the rim of the optic nerve head.

Analysis of macular and nerve fiber layer thickness in multiple sclerosis patients according to severity level and optic neuritis episodes.

PubMed

Soler García, A; Padilla Parrado, F; Figueroa-Ortiz, L C; González Gómez, A; García-Ben, A; García-Ben, E; García-Campos, J M

2016-01-01

Quantitative assessment of macular and nerve fibre layer thickness in multiple sclerosis patients with regard to expanded disability status scale (EDSS) and presence or absence of previous optic neuritis episodes. We recruited 62 patients with multiple sclerosis (53 relapsing-remitting and 9 secondary progressive) and 12 disease-free controls. All patients underwent an ophthalmological examination, including quantitative analysis of the nerve fibre layer and macular thickness using optical coherence tomography. Patients were classified according to EDSS as A (lower than 1.5), B (between 1.5 and 3.5), and C (above 3.5). Mean nerve fibre layer thickness in control, A, B, and C groups was 103.35±12.62, 99.04±14.35, 93.59±15.41, and 87.36±18.75μm respectively, with statistically significant differences (P<.05). In patients with no history of optic neuritis, history of episodes in the last 3 to 6 months, or history longer than 6 months, mean nerve fibre layer thickness was 99.25±13.71, 93.92±13.30 and 80.07±15.91μm respectively; differences were significant (P<.05). Mean macular thickness in control, A, B, and C groups was 220.01±12.07, 217.78±20.02, 217.68±20.77, and 219.04±24.26μm respectively. Differences were not statistically significant. The mean retinal nerve fibre layer thickness in multiple sclerosis patients is related to the EDSS level. Patients with previous optic neuritis episodes have a thinner retinal nerve fibre layer than patients with no history of these episodes. Mean macular thickness is not correlated to EDSS level. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Finite Element Modeling of the Posterior Eye in Microgravity

NASA Technical Reports Server (NTRS)

Feola, Andrew; Raykin, Julia; Mulugeta, Lealem; Gleason, Rudolph; Myers, Jerry G.; Nelson, Emily S.; Samuels, Brian; Ethier, C. Ross

2015-01-01

Microgravity experienced during spaceflight affects astronauts in various ways, including weakened muscles and loss of bone density. Recently, visual impairment and intracranial pressure (VIIP) syndrome has become a major concern for space missions lasting longer than 30 days. Astronauts suffering from VIIP syndrome have changes in ocular anatomical and visual impairment that persist after returning to earth. It is hypothesized that a cephalad fluid shift in microgravity may increase the intracranial pressure (ICP), which leads to an altered biomechanical environment of the posterior globe and optic nerve sheath (ONS).Currently, there is a lack of knowledge of how elevated ICP may lead to vision impairment and connective tissue changes in VIIP. Our goal was to develop a finite element model to simulate the acute effects of elevated ICP on the posterior eye and optic nerve sheath. We used a finite element (FE) analysis approach to understand the response of the lamina cribrosa and optic nerve to the elevations in ICP thought to occur in microgravity and to identify which tissue components have the greatest impact on strain experienced by optic nerve head tissues.

Transbulbar B-Mode Sonography in Multiple Sclerosis: Clinical and Biological Relevance.

PubMed

De Masi, Roberto; Orlando, Stefania; Conte, Aldo; Pasca, Sergio; Scarpello, Rocco; Spagnolo, Pantaleo; Muscella, Antonella; De Donno, Antonella

2016-12-01

Optic nerve sheath diameter quantification by transbulbar B-mode sonography is a recently validated technique, but its clinical relevance in relapse-free multiple sclerosis patients remains unexplored. In an open-label, comparative, cross-sectional study, we aimed to assess possible differences between patients and healthy controls in terms of optic nerve sheath diameter and its correlation with clinical/paraclinical parameters in this disease. Sixty unselected relapse-free patients and 35 matched healthy controls underwent transbulbar B-mode sonography. Patients underwent routine neurologic examination, brain magnetic resonance imaging and visual evoked potential tests. The mean optic nerve sheath diameter 3 and 5 mm from the eyeball was 22-25% lower in patients than controls and correlated with the Expanded Disability Status Scale (r = -0.34, p = 0.048, and r = -0.32, p = 0.042, respectively). We suggest that optic nerve sheath diameter quantified by transbulbar B-mode sonography should be included in routine assessment of the disease as an extension of the neurologic examination. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Traumatic lesion of the optic nerve head by flying fish: a case report].

PubMed

Martin, M; Orgül, S; Robertson, A; Flammer, J

2004-05-01

Traumatic lesion to the optic nerve often leads to severe and persistent functional loss. A male patient was transferred to our hospital from the University Eye Clinic of Guadeloupe 5 days after ocular injury caused by a flying fish. Visual function was light perception. The anterior part of the eye and retina were unremarkable. A computer tomography disclosed a fracture of the sphenoid sinus, with a little bone fragment (DD: foreign body) located close to the optic nerve. Therapy had been started with Aminopenicillin combined with clavulan acid (Augmentin) i. v., 500 ml methylprednisolone (Solumedrol) i. v., lysine-acetyl salicylate (Aspegic) and topical application of dexamethasone combined with neomycin/polymyxin B (Maxitrol). We continued this therapy and intensified it by adding nimodipine (Nimotop) 30 1-1-1 and acetazolamide retard (Diamox sustet) 1-0-1. Unfortunately visual function did not recover under therapy. Traumatic lesions of the optic nerve head, especially when due to axial or tangential forces, can lead to severe and irreversible functional loss. Severe traumatic lesions, even bone fractures induced by flying fish are not a seldom encounter in the Caribbean Sea.

Assessment of rat optic nerve damage due to microbeam radiation therapy in the treatment of glioblastomas.

PubMed

Mohamed, A; Worobec, S; Schultke, E

2008-01-01

Glioblastomas are the most common and aggressive subtype of human primary brain tumors. Due to their uncontrolled cellular proliferation, intense invasion, and lack of apoptosis, they are extremely difficult to treat. Currently, different approaches such as surgery, chemotherapy and radiation therapy have been employed as possible treatments however thus far; these treatments are not curative. Currently, microbeam radiation therapy (MRT) is being trialed in animal models of malignant brain tumors (rats) to aid in treatment. Some of the protocols tested have been shown to significantly increase survival rates. However, due to the high x-ray doses uses in MRT, the surrounding tissue of the targeted Glioblastomas may be irreversibly damaged. In previous studies, lens damage and clouding of the cornea have been observed in microbeam exposed eyes. However, to date no studies have assessed optic nerve damage. Therefore, this study examines the potential rat optic nerve damage following exposure to microbeam radiation therapy in the treatment of Glioblastomas. Although there appears to be no significant damage to the optic nerve, slight inflammation was observed within the extra ocular muscle.

Optic nerve regeneration in the mouse is a complex trait modulated by genetic background

PubMed Central

Wang, Jiaxing; Li, Ying; King, Rebecca; Struebing, Felix L.

2018-01-01

Purpose The present study is designed to identify the influences of genetic background on optic nerve regeneration using the two parental strains (C57BL/6J and DBA/2J) and seven BXD recombinant inbred mouse strains. Methods To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using adenoassociated virus (AAV) delivery of shRNA, and a mild inflammatory response was induced with an intravitreal injection of zymosan with CPT-cAMP. The axons of the retinal ganglion cells were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by cholera toxin B, and 2 days later, the regenerating axons within the optic nerve were examined. The number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we measured the distance that five axons had grown down the nerve and the longest distance a single axon reached. Results The analysis revealed a considerable amount of differential axonal regeneration across the seven BXD strains and the parental strains. There was a statistically significant difference (p=0.014 Mann–Whitney U test) in the regenerative capacity in the number of axons reaching 0.5 mm from a low of 236.1±24.4 axons in the BXD102 mice to a high of 759.8±79.2 axons in the BXD29 mice. There were also statistically significant differences (p=0.014 Mann–Whitney U test) in the distance axons traveled. Looking at a minimum of five axons, the shortest distance was 787.2±46.5 µm in the BXD102 mice, and the maximum distance was 2025.5±223.3 µm in the BXD29 mice. Conclusions Differences in genetic background can have a profound effect on axonal regeneration causing a threefold increase in the number of regenerating axons at 0.5 mm from the crush site and a 2.5-fold increase in the distance traveled by at least five axons in the damaged optic nerve. PMID:29463955

Retinal ganglion cell damage in an experimental rodent model of blast-mediated traumatic brain injury.

PubMed

Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H; Harper, Matthew M

2013-05-15

To evaluate retina and optic nerve damage following experimental blast injury. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify.

Twelve-hour reproducibility of retinal and optic nerve blood flow parameters in healthy individuals.

PubMed

Luksch, Alexandra; Lasta, Michael; Polak, Kaija; Fuchsjäger-Mayrl, Gabriele; Polska, Elzbieta; Garhöfer, Gerhard; Schmetterer, Leopold

2009-11-01

The aim of the present study was to investigate the reproducibility and potential diurnal variation of optic nerve head and retinal blood flow parameters in healthy individuals over a period of 12 hr. We measured optic nerve head and retinal blood flow parameters in 16 healthy male non-smoking individuals at five time-points during the day (08:00, 11:00, 14:00, 17:00 and 20:00 hr). Outcome parameters were perimacular white blood cell flux (as assessed with the blue field entoptic technique), blood velocities in retinal veins (as assessed with bi-directional laser Doppler velocimetry), retinal arterial and venous diameters (as assessed with the retinal vessel analyser), optic nerve head blood flow, volume and velocity (as assessed with single point and scanning laser Doppler flowmetry) and blood velocities in the central retinal artery (as assessed with colour Doppler imaging). The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. No diurnal variation in optic nerve head or retinal blood flow was observed with any of the techniques employed. Coefficients of variation were between 1.6% and 18.5% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 3.7% to 78.2%. Our data indicate that in healthy individuals the selected techniques provide adequate reproducibility to be used in clinical studies. However, in patients with eye diseases and reduced vision the reproducibility may be considerably worse.

GlyCAM1 negatively regulates monocyte entry into the optic nerve head and contributes to radiation-based protection in glaucoma.

PubMed

Williams, Pete A; Braine, Catherine E; Foxworth, Nicole E; Cochran, Kelly E; John, Simon W M

2017-04-26

We previously reported a profound long-term neuroprotection subsequent to a single radiation-therapy in the DBA/2J mouse model of glaucoma. This neuroprotection prevents entry of monocyte-like immune cells into the optic nerve head during glaucoma. Gene expression studies in radiation-treated mice implicated Glycam1 in this protection. Glycam1 encodes a proteoglycan ligand for L-selectin and is an excellent candidate to modulate immune cell entry into the eye. Here, we experimentally test the hypothesis that radiation-induced over-expression of Glycam1 is a key component of the neuroprotection. We generated a null allele of Glycam1 on a DBA/2J background. Gene and protein expression of Glycam1, monocyte entry into the optic nerve head, retinal ganglion cell death, and axon loss in the optic nerve were assessed. Radiation therapy potently inhibits monocyte entry into the optic nerve head and prevents retinal ganglion cell death and axon loss. DBA/2J mice carrying a null allele of Glycam1 show increased monocyte entry and increased retinal ganglion cell death and axon loss following radiation therapy, but the majority of optic nerves were still protected by radiation therapy. Although GlyCAM1 is an L-selectin ligand, its roles in immunity are not yet fully defined. The current study demonstrates a partial role for GlyCAM1 in radiation-mediated protection. Furthermore, our results clearly show that GlyCAM1 levels modulate immune cell entry from the vasculature into neural tissues. As Glycam1 deficiency has a more profound effect on cell entry than on neurodegeneration, further experiments are needed to precisely define the role of monocyte entry in DBA/2J glaucoma. Nevertheless, GlyCAM1's function as a negative regulator of extravasation may lead to novel therapeutic strategies for an array of common conditions involving inflammation.

Optic nerve head blood flow response to reduced ocular perfusion pressure by alteration of either the blood pressure or intraocular pressure.

PubMed

Wang, Lin; Cull, Grant A; Fortune, Brad

2015-04-01

To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Twelve normal non-human primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n = 6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n = 6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. The optic nerve head blood flow showed significant difference between the two groups (p = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (p < 0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (p = 0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence related to the hemodynamic pathophysiology in glaucoma.

High-resolution imaging of the retinal nerve fiber layer in normal eyes using adaptive optics scanning laser ophthalmoscopy.

PubMed

Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Arakawa, Naoko; Oshima, Susumu; Shibata, Naohisa; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

2012-01-01

To conduct high-resolution imaging of the retinal nerve fiber layer (RNFL) in normal eyes using adaptive optics scanning laser ophthalmoscopy (AO-SLO). AO-SLO images were obtained in 20 normal eyes at multiple locations in the posterior polar area and a circular path with a 3-4-mm diameter around the optic disc. For each eye, images focused on the RNFL were recorded and a montage of AO-SLO images was created. AO-SLO images for all eyes showed many hyperreflective bundles in the RNFL. Hyperreflective bundles above or below the fovea were seen in an arch from the temporal periphery on either side of a horizontal dividing line to the optic disc. The dark lines among the hyperreflective bundles were narrower around the optic disc compared with those in the temporal raphe. The hyperreflective bundles corresponded with the direction of the striations on SLO red-free images. The resolution and contrast of the bundles were much higher in AO-SLO images than in red-free fundus photography or SLO red-free images. The mean hyperreflective bundle width around the optic disc had a double-humped shape; the bundles at the temporal and nasal sides of the optic disc were narrower than those above and below the optic disc (P<0.001). RNFL thickness obtained by optical coherence tomography correlated with the hyperreflective bundle widths on AO-SLO (P<0.001) AO-SLO revealed hyperreflective bundles and dark lines in the RNFL, believed to be retinal nerve fiber bundles and Müller cell septa. The widths of the nerve fiber bundles appear to be proportional to the RNFL thickness at equivalent distances from the optic disc.

Neurogenic regulation of renal tubular sodium reabsorption.

PubMed

DiBona, G F

1977-08-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies have demonstrated adrenergic nerve terminals in direct contact with basement membranes of mammalian (rat, dog, and monkey) renal tubular epithelial cells. Low-level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Antinatriuresis was prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Rat kidney micropuncture studies have localized a site of enhanced tubular sodium reabsorption to the proximal tubule. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney on renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. The possible effects of anesthesia and uncertainties about the completeness of surgical renal denervation and other tubular segmental sites of action are critically analyzed. The clinical implications of this mechanism in pathologic conditions of sodium and water retention are discussed and and a prospectus for future work is presented.

Probabilistic Modeling Of Ocular Biomechanics In VIIP: Risk Stratification

NASA Technical Reports Server (NTRS)

Feola, A.; Myers, J. G.; Raykin, J.; Nelson, E. S.; Mulugeta, L.; Samuels, B.; Ethier, C. R.

2016-01-01

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a major health concern for long-duration space missions. Currently, it is thought that a cephalad fluid shift in microgravity causes elevated intracranial pressure (ICP) that is transmitted along the optic nerve sheath (ONS). We hypothesize that this in turn leads to alteration and remodeling of connective tissue in the posterior eye which impacts vision. Finite element (FE) analysis is a powerful tool for examining the effects of mechanical loads in complex geometries. Our goal is to build a FE analysis framework to understand the response of the lamina cribrosa and optic nerve head to elevations in ICP in VIIP. To simulate the effects of different pressures on tissues in the posterior eye, we developed a geometric model of the posterior eye and optic nerve sheath and used a Latin hypercubepartial rank correlation coef-ficient (LHSPRCC) approach to assess the influence of uncertainty in our input parameters (i.e. pressures and material properties) on the peak strains within the retina, lamina cribrosa and optic nerve. The LHSPRCC approach was repeated for three relevant ICP ranges, corresponding to upright and supine posture on earth, and microgravity [1]. At each ICP condition we used intraocular pressure (IOP) and mean arterial pressure (MAP) measurements of in-flight astronauts provided by Lifetime Surveillance of Astronaut Health Program, NASA Johnson Space Center. The lamina cribrosa, optic nerve, retinal vessel and retina were modeled as linear-elastic materials, while other tissues were modeled as a Mooney-Rivlin solid (representing ground substance, stiffness parameter c1) with embedded collagen fibers (stiffness parameters c3, c4 and c5). Geometry creationmesh generation was done in Gmsh [2], while FEBio was used for all FE simulations [3]. The LHSPRCC approach resulted in correlation coefficients in the range of 1. To assess the relative influence of the uncertainty in an input parameter on the peak strains, we ranked and then normalized these coefficients, considering that normalized values 0.5 implied a substantial influence on the range of the peak strains in the optic nerve head (ONH). IOP and ICP were found to have a major influence on the peak strains in the ONH, as did optic nerve and LC stiffness. Interestingly, the stiffness of the sclera far from the scleral canal did not have a large influence on peak strains in ONH tissues; however, the collagen fiber stiffness in the peripapillary sclera and annular ring both influenced the peak strains within the ONH. We have created a physiologically relevant model that incorporated collagen fibers to study the effects of elevated ICP. Elevated ICP resulted in strains in the optic nerve that are not predicted to occur on earth: the upright or supine conditions. We found that IOP, ICP, lamina cribrosa stiffness and optic nerve stiffness had the highest association with these extreme strains in the ONH. These extreme strains may activate mechanosensitive cells that induce tissue remodeling and are a risk factor for the development of VIIP.

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa.

PubMed

Ikeda, Yasuhiro; Nishiguchi, Koji M; Miya, Fuyuki; Shimozawa, Nobuhiro; Funatsu, Jun; Nakatake, Shunji; Fujiwara, Kohta; Tachibana, Takashi; Murakami, Yusuke; Hisatomi, Toshio; Yoshida, Shigeo; Yasutomi, Yasuhiro; Tsunoda, Tatsuhiko; Nakazawa, Toru; Ishibashi, Tatsuro; Sonoda, Koh-Hei

2018-02-01

To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach

PubMed Central

Shaylor, Lara A.; Hwang, Sung Jin; Sanders, Kenton M.

2016-01-01

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1−/−) and P2Y1 receptors (P2ry1−/−) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1−/− mice IJPs and relaxations persisted whereas in P2ry1−/− mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species. PMID:27634009

Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach.

PubMed

Shaylor, Lara A; Hwang, Sung Jin; Sanders, Kenton M; Ward, Sean M

2016-11-01

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase (Nos1 -/- ) and P2Y1 receptors (P2ry1 -/- ) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1 -/- mice IJPs and relaxations persisted whereas in P2ry1 -/- mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species. Copyright © 2016 the American Physiological Society.

Speckle reduction during all-fiber common-path optical coherence tomography of the cavernous nerves

NASA Astrophysics Data System (ADS)

Chitchian, Shahab; Fiddy, Michael; Fried, Nathaniel M.

2009-02-01

Improvements in identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery, which are responsible for erectile function, may improve nerve preservation and postoperative sexual potency. In this study, we use a rat prostate, ex vivo, to evaluate the feasibility of optical coherence tomography (OCT) as a diagnostic tool for real-time imaging and identification of the cavernous nerves. A novel OCT system based on an all single-mode fiber common-path interferometer-based scanning system is used for this purpose. A wavelet shrinkage denoising technique using Stein's unbiased risk estimator (SURE) algorithm to calculate a data-adaptive threshold is implemented for speckle noise reduction in the OCT image. The signal-to-noise ratio (SNR) was improved by 9 dB and the image quality metrics of the cavernous nerves also improved significantly.

Orbital and Intracranial Effects of Microgravity: 3T MRI Findings

NASA Technical Reports Server (NTRS)

Kramer, L. A.; Sargsyan, A.; Hasan, K. M.; Polk, J. D.; Hamilton, D. R.

2012-01-01

Goals and Objectives of this presentation are: 1. To briefly describe a newly discovered clinical entity related to space flight. 2. To describe normal anatomy and pathologic changes of the optic nerve, posterior globe, optic nerve sheath and pituitary gland related to exposure to microgravity. 3. To correlate imaging findings with known signs of intracranial hypertension.

Somatostatin Receptor SPECT/CT using 99mTc Labeled HYNIC-TOC Aids in Diagnosis of Primary Optic Nerve Sheath Meningioma.

PubMed

Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

2017-01-01

Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99m Tc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

PubMed Central

Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

2014-01-01

Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

PubMed

Garcia-Martin, Elena; Ara, Jose R; Martin, Jesus; Almarcegui, Carmen; Dolz, Isabel; Vilades, Elisa; Gil-Arribas, Laura; Fernandez, Francisco J; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

2017-05-01

To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Observational and longitudinal study. One hundred patients with relapsing-remitting MS and 50 healthy controls. All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

African Descent and Glaucoma Evaluation Study (ADAGES)

PubMed Central

Girkin, Christopher A.; Sample, Pamela A.; Liebmann, Jeffrey M.; Jain, Sonia; Bowd, Christopher; Becerra, Lida M.; Medeiros, Felipe A.; Racette, Lyne; Dirkes, Keri A.; Weinreb, Robert N.; Zangwill, Linda M.

2010-01-01

Objective To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES). Methods Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate. Results The AD participants had significantly greater optic disc area on HRT (2.06 mm2; P<.001) and OCT (2.47 mm2; P<.001) and a deeper HRT cup depth than the ED group (P<.001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group. Conclusions Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status. PMID:20457974

A Comparative Morphometric Analysis of Three Cranial Nerves in Two Phocids: The Hooded Seal (Cystophora cristata) and the Harbor Seal (Phoca vitulina).

PubMed

Wohlert, Dennis; Kröger, Jürgen; Witt, Martin; Schmitt, Oliver; Wree, Andreas; Czech-Damal, Nicole; Siebert, Ursula; Folkow, Lars; Hanke, Frederike D

2016-03-01

While our knowledge about the senses of pinnipeds has increased over the last decades almost nothing is known about the organization of the neuroanatomical pathways. In a first approach to this field of research, we assessed the total number of myelinated axons of three cranial nerves (CNs) in the harbor (Phoca vitulina, Pv) and hooded seal (Cystophora cristata, Cc). Axons were counted in semithin sections of the nerves embedded in Epon and stained with toluidine blue. In both species, the highest axon number was found within the optic nerve (Pv 187,000 ± 8,000 axons, Cc 481,600 ± 1,300 axons). Generally, considering absolute axon numbers, far more axons were counted within the optic and trigmenial nerve (Pv 136,700 ± 2,500 axons, Cc 179,300 ± 6,900 axons) in hooded in comparison to harbor seals. The axon counts of the vestibulocochlear nerve are nearly identical for both species (Pv 87,100 ± 8,100 axons, Cc 86,600 ± 2,700 axons). However, when comparing cell density, the cell density is almost equal for all nerves for both species except for the optic nerve in which cell density was particularly higher than in the other nerves and higher in hooded in comparison to harbor seals. We here present the first comparative analysis of three CNs in two phocid seals. While the CNs of these closely related species share some general characteristics, pronounced differences in axon numbers/densities are apparent. These differences seem to reflect differences in e.g. size, habitat, and/or functional significance of the innervated sensory systems. © 2015 Wiley Periodicals, Inc.

A glial palisade delineates the ipsilateral optic projection in Monodelphis.

PubMed

MacLaren, R E

1998-01-01

In developing marsupials, the path taken through the optic chiasm by ipsilaterally projecting retinal ganglion cells is complicated. Just prior to entry into the chiasm, ganglion cells destined for the ipsilateral optic tract separate from the remainder of axons by turning abruptly downwards to take a position in the ventral part of the optic nerve. In this report, it is shown that a discrete population of about 10-15 large glial cells transiently form a linear array across the prechiasmatic part of the optic nerve, precisely at this axon turning point. The distinct morphology of these cells and their novel location may reflect a specialized role in axon guidance.

Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys.

PubMed

Neuringer, Martha; Sandstrom, Marita M; Johnson, Elizabeth J; Snodderly, D Max

2004-09-01

The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment (MP) and may protect the macula from age-related degeneration (AMD). In this study, L or Z was fed to rhesus monkeys reared on xanthophyll-free diets to follow the accumulation of serum carotenoids and MP over time. Eighteen rhesus monkeys were fed xanthophyll-free semipurified diets from birth until 7 to 16 years. The diets of six were then supplemented with pure L and six with pure Z at 3.9 micromol/kg per day (2.2 mg/kg per day) for 24 to 56 weeks. At baseline and 4- to 12-week intervals during supplementation, serum carotenoids were measured by HPLC, and MP density was estimated by two-wavelength reflectometry. Serum carotenoids and MP were also measured in monkeys fed a stock diet. Monkeys fed xanthophyll-free diets had no L or Z in serum and no detectable MP. During supplementation, serum L or Z increased rapidly over the first 4 weeks and from 16 weeks onward maintained similar levels, both several times higher than in stock-diet-fed monkeys. The central peak of MP optical density increased to a relatively steady level by 24 to 32 weeks in both L- and Z-fed groups. Rhesus monkeys fed a stock diet had lower blood concentrations of L than those found in humans and other nonhuman primates. Rhesus monkeys respond to either dietary L or Z supplementation with increases in serum xanthophylls and MP, even after life-long xanthophyll deficiency. These animals provide a potential model to study mechanisms of protection from AMD. Copyright Association for Research in Vision and Ophthalmology

Mucocele in an Onodi cell with simultaneous bilateral visual disturbance.

PubMed

Fukuda, Yoichiro; Chikamatsu, Kazuaki; Ninomiya, Hiroshi; Yasuoka, Yoshihito; Miyashita, Motoaki; Furuya, Nobuhiko

2006-06-01

The Onodi cell is a large pneumatized posterior ethmoid cell and closely related to optic nerve. We present an extremely rare case of retrobulbar optic neuropathy caused by mucocele in an Onodi cell. A 79-year-old man complained of headaches and simultaneous bilateral visual disturbance. A computed tomography (CT) scan demonstrated a mucocele in an Onodi cell, which involved bilateral optic nerves. The surgical treatment with a transnasal endoscopic approach was performed, resulting in the improving of visual acuity. The bilateral optic nerves were identified along each lateral wall into an Onodi cell accompanied with bone defect. In an Onodi cell, even if the lesion is isolated and/or small, it may be closely related to ocular symptoms. Imaging studies should be considered for the differential diagnosis because early diagnosis and prompt surgical treatment for mucocele are needed for recovery of visual impairment.

Optic neuropathy after anterior communicating artery aneurysm clipping: 3 cases and techniques to address a correctable pitfall.

PubMed

Linzey, Joseph R; Chen, Kevin S; Savastano, Luis; Thompson, B Gregory; Pandey, Aditya S

2018-06-01

Brain shifts following microsurgical clip ligation of anterior communicating artery (ACoA) aneurysms can lead to mechanical compression of the optic nerve by the clip. Recognition of this condition and early repositioning of clips can lead to reversal of vision loss. The authors identified 3 patients with an afferent pupillary defect following microsurgical clipping of ACoA aneurysms. Different treatment options were used for each patient. All patients underwent reexploration, and the aneurysm clips were repositioned to prevent clip-related compression of the optic nerve. Near-complete restoration of vision was achieved at the last clinic follow-up visit in all 3 patients. Clip ligation of ACoA aneurysms has the potential to cause clip-related compression of the optic nerve. Postoperative visual examination is of utmost importance, and if any changes are discovered, reexploration should be considered as repositioning of the clips may lead to resolution of visual deterioration.

Leber's Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited.

PubMed

Abu-Amero, Khaled K

2011-01-01

Our current understanding of Leber's hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

Nerve Fiber Flux Analysis Using Wide-Field Swept-Source Optical Coherence Tomography.

PubMed

Tan, Ou; Liu, Liang; Liu, Li; Huang, David

2018-02-01

To devise a method to quantify nerve fibers over their arcuate courses over an extended peripapillary area using optical coherence tomography (OCT). Participants were imaged with 8 × 8-mm volumetric OCT scans centered at the optic disc. A new quantity, nerve fiber flux (NFF), represents the cross-sectional area transected perpendicular to the nerve fibers. The peripapillary area was divided into 64 tracks with equal flux. An iterative algorithm traced the trajectory of the tracks assuming that the relative distribution of the NFF was conserved with compensation for fiber connections to ganglion cells on the macular side. Average trajectory was averaged from normal eyes and use to calculate the NFF maps for glaucomatous eyes. The NFF maps were divided into eight sectors that correspond to visual field regions. There were 24 healthy and 10 glaucomatous eyes enrolled. The algorithm converged on similar patterns of NFL tracks for all healthy eyes. In glaucomatous eyes, NFF correlated with visual field sensitivity in the arcuate sectors (Spearman ρ = 0.53-0.62). Focal nerve fiber loss in glaucomatous eyes appeared as uniform tracks of NFF defects that followed the expected arcuate fiber trajectory. Using an algorithm based on the conservation of flux, we derived nerve fiber trajectories in the peripapillary area. The NFF map is useful for the visualization of focal defects and quantification of sector nerve fiber loss from wide-area volumetric OCT scans. NFF provides a cumulative measure of volumetric loss along nerve fiber tracks and could improve the detection of focal glaucoma damage.

Adaptive optics ophthalmoscopy: results and applications.

PubMed

Pallikaris, A

2005-01-01

The living human eye's optical aberrations set a limit to retinal imaging in the clinical setting. Progress in the field of adaptive optics has offered unique solutions to this problem. The purpose of this review is to summarize the most recent advances in adaptive optics ophthalmoscopy. Adaptive optics technology has been combined with flood illumination imaging, confocal scanning laser ophthalmoscopy, and optical coherence tomography for the high resolution imaging of the retina. The advent of adaptive optics technology has provided the technical platform for the compensation of the eye's aberration and made possible the observation of single cones, small capillaries, nerve fibers, and leukocyte dynamics as well as the ultrastructure of the optic nerve head lamina cribrosa in vivo. Detailed imaging of retinal infrastructure provides valuable information for the study of retinal physiology and pathology.

The Role of Heparan Sulfate Proteoglycans in Optic Disc and Stalk Morphogenesis

PubMed Central

Cai, Zhigang; Grobe, Kay; Zhang, Xin

2014-01-01

Background Heparan sulfate proteoglycans (HSPG) are important for embryonic development via the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma and optic nerve hypoplasia. Results To study HSPG-dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV-specific mutations in the heparan sulfate (HS) N-sulfotransferase genes (Ndst1 and Ndst2) and HS O-sulfotransferase genes (Hs2st, Hs6st1 and Hs6st2) in mice. Interestingly, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down-regulated in Ndst mutants, and consistent with this, HS-related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. PMID:24753163

Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves.

PubMed

Klein, Amanda H; Vyshnevska, Alina; Hartke, Timothy V; De Col, Roberto; Mankowski, Joseph L; Turnquist, Brian; Bosmans, Frank; Reeh, Peter W; Schmelz, Martin; Carr, Richard W; Ringkamp, Matthias

2017-05-17

Voltage-gated sodium (Na V ) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine Na V channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na V 1.1-Na V 1.4, Na V 1.6-Na V 1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na V 1.8 and Na V 1.9) inhibited by millimolar concentrations, with Na V 1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys ( Macaca nemestrina ). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na V 1.9 -/- mice. In nerves from Na V 1.8 -/- mice, TTX-r C-CAPs could not be detected. These data indicate that Na V 1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na V 1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na V 1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin. SIGNIFICANCE STATEMENT It is unclear whether individual sodium channel isoforms exert differential roles in action potential conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve fibers, but clarifying the role of sodium channel subtypes in different axonal segments may be useful for the development of novel analgesic strategies. Here, we provide evidence from mice and nonhuman primates that a substantial portion of the C-fiber compound action potential in distal peripheral nerves, but not proximal nerves or dorsal roots, is resistant to tetrodotoxin and that, in mice, this effect is mediated solely by voltage-gated sodium channel 1.8 (Na V 1.8). The functional prominence of Na V 1.8 within the axonal compartment immediately proximal to its termination may affect strategies targeting pain of peripheral origin. Copyright © 2017 the authors 0270-6474/17/375205-11$15.00/0.

Research notes : can bridges have nerves? new technology developing for 'smart' infrastructure.

DOT National Transportation Integrated Search

1998-05-21

In the nerve system, the optical fibers are the information carrier and along their length are the fiber sensors, or nerve endings, which are used to sense the environment. They can be readily incorporated into new construction or retrofitted into ex...

Innervation of the cow's inner ear derived from micro-computed tomography

NASA Astrophysics Data System (ADS)

Costeur, Loic; Mennecart, Bastien; Khimchenko, Anna; Müller, Bert; Schulz, Georg

2017-09-01

The innervation of the inner ear has been thoroughly investigated in humans and in some animal models such as the guinea pig, the rabbit, the cat, the dog, the rat, the pig and some monkeys. Ruminant inner ears are still poorly known and their innervation was never investigated despite its potential interest in phylogenetic reconstructions. Following earlier works on the ontogeny of the cow's ear, we expand our understanding of this structure by reconstructing the fine innervation pattern of the inner ear of the cow in two ontogenetic stages, at 7 months gestation and at an adult age. Since we work on dry skeletal specimens, only the endocast of the innervation inside the petrosal bone was reconstructed up to the internal acoustic meatus. The paths of the facial and vestibulocochlear nerves could be reconstructed together with that of the spiral ganglion canal. The nerves have a very fibrous pattern. The bony cavities of the ampular and utricular branches of the vestibulocochlear nerve could also be reconstructed. Our observations confirm that not all bony structures are present in foetal stages since the branch of cranial nerve VII is not visible on the foetus but very broad on the adult stage. The fibrous pattern within the modiolus connecting the spiral canal to the cochlear nerve is also less dense than in the adult stage. The shape of the branch of cranial nerve VII is very broad in the cow ending in a large hiatus Fallopii; this, together with the above-mentioned particularities, could constitute relevant observations for phylogenetical purposes when more data will be made available.

Development of regenerative peripheral nerve interfaces for motor control of neuroprosthetic devices

NASA Astrophysics Data System (ADS)

Kemp, Stephen W. P.; Urbanchek, Melanie G.; Irwin, Zachary T.; Chestek, Cynthia A.; Cederna, Paul S.

2017-05-01

Traumatic peripheral nerve injuries suffered during amputation commonly results in debilitating neuropathic pain in the affected limb. Modern prosthetic technologies allow for intuitive, simultaneous control of multiple degrees of freedom. However, these state-of-the-art devices require separate, independent control signals for each degree of freedom, which is currently not possible. As a result, amputees reject up to 75% of myoelectric devices preferring instead to use body-powered artificial limbs which offer subtle sensory feedback. Without meaningful and intuitive sensory feedback, even the most advanced myoelectric prostheses remain insensate, burdensome, and are associated with enormous cognitive demand and mental fatigue. The ideal prosthetic device is one which is capable of providing intuitive somatosensory feedback essential for interaction with the environment. Critical to the design of such a bioprosthetic device is the development of a reliable biologic interface between human and machine. This ideal patient-prosthetic interface allows for transmission of both afferent somatosensory information and efferent motor signals for a closed-loop feedback system of neural control. Our lab has developed the Regenerative Peripheral Nerve Interface (RPNI) as a biologic nerve interface designed for stable integration of a prosthetic device with transected peripheral nerves in a residual limb. The RPNI is constructed by surgically implanting the distal end of a transected peripheral nerve into an autogenous muscle graft. Animal experiments in our lab have shown recording of motor signals from RPNI's implanted into both rodents and monkeys. Here, we achieve high amplitude EMG signals with a high signal to noise (SNR) ratio.

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

PubMed

Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse

PubMed Central

Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Brown, Angus M.

2017-01-01

ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood–brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS). PMID:28798954

Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.

PubMed

Weber, Arthur J; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine D

2010-01-01

To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone. Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally. Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so. Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.

Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters

PubMed Central

Akçam, H T; Capraz, I Y; Aktas, Z; Batur Caglayan, H Z; Ozhan Oktar, S; Hasanreisoglu, M; Irkec, C

2014-01-01

Purpose To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. Methods This is an observational case–control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's correlation test. Results The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. Conclusions In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found. PMID:25081285

Multiple Cranial Nerve Palsies in Giant Cell Arteritis.

PubMed

Ross, Michael; Bursztyn, Lulu; Superstein, Rosanne; Gans, Mark

2017-12-01

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large arteries often with ophthalmic involvement, including ischemic optic neuropathy, retinal artery occlusion, and ocular motor cranial nerve palsies. This last complication occurs in 2%-15% of patients, but typically involves only 1 cranial nerve. We present 2 patients with biopsy-proven GCA associated with multiple cranial nerve palsies.

Segmentation of optical coherence tomography images for differentiation of the cavernous nerves from the prostate gland

NASA Astrophysics Data System (ADS)

Chitchian, Shahab; Weldon, Thomas P.; Fried, Nathaniel M.

2009-07-01

The cavernous nerves course along the surface of the prostate and are responsible for erectile function. Improvements in identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery may improve nerve preservation and postoperative sexual potency. Two-dimensional (2-D) optical coherence tomography (OCT) images of the rat prostate were segmented to differentiate the cavernous nerves from the prostate gland. To detect these nerves, three image features were employed: Gabor filter, Daubechies wavelet, and Laws filter. The Gabor feature was applied with different standard deviations in the x and y directions. In the Daubechies wavelet feature, an 8-tap Daubechies orthonormal wavelet was implemented, and the low-pass sub-band was chosen as the filtered image. Last, Laws feature extraction was applied to the images. The features were segmented using a nearest-neighbor classifier. N-ary morphological postprocessing was used to remove small voids. The cavernous nerves were differentiated from the prostate gland with a segmentation error rate of only 0.058+/-0.019. This algorithm may be useful for implementation in clinical endoscopic OCT systems currently being studied for potential intraoperative diagnostic use in laparoscopic and robotic nerve-sparing prostate cancer surgery.

Segmentation of optical coherence tomography images for differentiation of the cavernous nerves from the prostate gland.

PubMed

Chitchian, Shahab; Weldon, Thomas P; Fried, Nathaniel M

2009-01-01

The cavernous nerves course along the surface of the prostate and are responsible for erectile function. Improvements in identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery may improve nerve preservation and postoperative sexual potency. Two-dimensional (2-D) optical coherence tomography (OCT) images of the rat prostate were segmented to differentiate the cavernous nerves from the prostate gland. To detect these nerves, three image features were employed: Gabor filter, Daubechies wavelet, and Laws filter. The Gabor feature was applied with different standard deviations in the x and y directions. In the Daubechies wavelet feature, an 8-tap Daubechies orthonormal wavelet was implemented, and the low-pass sub-band was chosen as the filtered image. Last, Laws feature extraction was applied to the images. The features were segmented using a nearest-neighbor classifier. N-ary morphological postprocessing was used to remove small voids. The cavernous nerves were differentiated from the prostate gland with a segmentation error rate of only 0.058+/-0.019. This algorithm may be useful for implementation in clinical endoscopic OCT systems currently being studied for potential intraoperative diagnostic use in laparoscopic and robotic nerve-sparing prostate cancer surgery.

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

PubMed

Kolbe, Scott C; van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F; Kilpatrick, Trevor J

2016-01-01

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis

PubMed Central

van der Walt, Anneke; Butzkueven, Helmut; Klistorner, Alexander; Egan, Gary F.; Kilpatrick, Trevor J.

2016-01-01

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = −0.428, p = 0.009; MD: R = −0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage. PMID:27555964

Diffusion tensor imaging of the optic tracts in multiple sclerosis: association with retinal thinning and visual disability.

PubMed

Dasenbrock, Hormuzdiyar H; Smith, Seth A; Ozturk, Arzu; Farrell, Sheena K; Calabresi, Peter A; Reich, Daniel S

2011-04-01

Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P=.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=.51, P=.003) and total-macular-volume reduction (r=.59, P=.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. Copyright © 2010 by the American Society of Neuroimaging.

Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability

PubMed Central

Dasenbrock, Hormuzdiyar H.; Smith, Seth A.; Ozturk, Arzu; Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.

2009-01-01

Background and purpose Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. Methods Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. Results After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (p=0.002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r=0.51, p=0.003) and total-macular-volume reduction (r=0.59, p=0.002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. Conclusions Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. PMID:20331501

Central amaurosis induced by an intraocular, posttraumatic fibrosarcoma in a cat.

PubMed

Barrett, P M; Merideth, R E; Alarcon, F L

1995-01-01

A 12-year-old, castrated male, domestic shorthair cat with a previous penetrating trauma to the left globe which progressed to a phthisical eye presented for acute blindness. Ophthalmic examination and electroretinography of the right eye were found to be normal. Following euthanasia, gross and microscopic examinations were completed. A left intraocular, posttraumatic fibrosarcoma with extension to the optic nerve and chiasm and induced right optic nerve fiber degeneration at the optic chiasm with necrosis leading to central amaurosis were diagnosed.

The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice

PubMed Central

Harder, Jeffrey M.; Fernandes, Kimberly A.; Libby, Richard T.

2012-01-01

Axonal insult induces retinal ganglion cell (RGC) death through a BAX-dependent process. The pro-apoptotic Bcl-2 family member BIM is known to induce BAX activation. BIM expression increased in RGCs after axonal injury and its induction was dependent on JUN. Partial and complete Bim deficiency delayed RGC death after mechanical optic nerve injury. However, in a mouse model of glaucoma, DBA/2J mice, Bim deficiency did not prevent RGC death in eyes with severe optic nerve degeneration. In a subset of DBA/2J mice, Bim deficiency altered disease progression resulting in less severe nerve damage. Bim deficient mice exhibited altered optic nerve head morphology and significantly lessened intraocular pressure elevation. Thus, a decrease in axonal degeneration in Bim deficient DBA/2J mice may not be caused by a direct role of Bim in RGCs. These data suggest that BIM has multiple roles in glaucoma pathophysiology, potentially affecting susceptibility to glaucoma through several mechanisms. PMID:22833783

Extracellular Recording of Light Responses from Optic Nerve Fibers and the Caudal Photoreceptor in the Crayfish

PubMed Central

Nesbit, Steven C.; Van Hoof, Alexander G.; Le, Chi C.; Dearworth, James R.

2015-01-01

Few laboratory exercises have been developed using the crayfish as a model for teaching how neural processing is done by sensory organs that detect light stimuli. This article describes the dissection procedures and methods for conducting extracellular recording from light responses of both the optic nerve fibers found in the animal’s eyestalk and from the caudal photoreceptor located in the ventral nerve cord. Instruction for ADInstruments’ data acquisition system is also featured for the data collection and analysis of responses. The comparison provides students a unique view on how spike activities measured from neurons code image-forming and non-image-forming processes. Results from the exercise show longer latency and lower frequency of firing by the caudal photoreceptor compared to optic nerve fibers to demonstrate evidence of different functions. After students learn the dissection, recording procedure, and the functional anatomy, they can develop their own experiments to learn more about the photoreceptive mechanisms and the sensory integration of modalities by these light-responsive interneurons. PMID:26557793

Nerve Fiber Layer Thickness and Characteristics Associated with Glaucoma in Community Living Older Adults: Prelude to a Screening Trial?

PubMed

Klein, Barbara E K; Johnson, Chris A; Meuer, Stacy M; Lee, Kyungmoo; Wahle, Andreas; Lee, Kristine E; Kulkarni, Amruta; Sonka, Milan; Abràmoff, Michael D; Klein, Ronald

2017-04-01

To examine the associations of nerve fiber layer (NFL) thickness with other ocular characteristics in older adults. Participants in the Beaver Dam Eye Study (2008-2010) underwent spectral domain optical coherence tomography (SD-OCT) scans of the optic nerve head, imaging of optic discs, frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP), and an interview concerning their history of glaucoma and use of drops to lower eye pressure. Self-reported histories of glaucoma and the use of drops to lower eye pressure were obtained at follow-up examinations (2014-2016). NFL thickness measured on OCTs varied by location around the optic nerve. Age was associated with mean NFL thickness. Mean NFL was thinnest in eyes with larger cup/disc (C/D) ratios. Horizontal hemifield defects or other optic nerve-field defects were associated with thinner NFL. NFL in persons who reported taking eye drops for high intraocular pressure was thinner compared to those not taking drops. After accounting for the presence of high intraocular pressure, large C/D ratios or hemifield defects, eyes with thinner NFL in the arcades were more likely (OR = 2.3 for 30 micron thinner NFL, p = 0.04) to have incident glaucoma at examination 5 years later. Retinal NFL thickness was associated with a new history of self-reported glaucoma 5 years later. A trial testing the usefulness of NFL as part of a screening battery for predicting glaucoma in those previously undiagnosed might lead to improved case finding and, ultimately, to diminishing the risk of visual field loss.

Retinal Ganglion Cell Damage in an Experimental Rodent Model of Blast-Mediated Traumatic Brain Injury

PubMed Central

Mohan, Kabhilan; Kecova, Helga; Hernandez-Merino, Elena; Kardon, Randy H.; Harper, Matthew M.

2013-01-01

Purpose. To evaluate retina and optic nerve damage following experimental blast injury. Methods. Healthy adult mice were exposed to an overpressure blast wave using a custom-built blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. Results. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. Conclusions. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify. PMID:23620426

Elevated intracranial pressure causes optic nerve and retinal ganglion cell degeneration in mice.

PubMed

Nusbaum, Derek M; Wu, Samuel M; Frankfort, Benjamin J

2015-07-01

The purpose of this study was to develop a novel experimental system for the modulation and measurement of intracranial pressure (ICP), and to use this system to assess the impact of elevated ICP on the optic nerve and retinal ganglion cells (RGCs) in CD1 mice. This system involved surgical implantation of an infusion cannula and a radiowave based pressure monitoring probe through the skull and into the subarachnoid space. The infusion cannula was used to increase ICP, which was measured by the probe and transmitted to a nearby receiver. The system provided robust and consistent ICP waveforms, was well tolerated, and was stable over time. ICP was elevated to approximately 30 mmHg for one week, after which we assessed changes in optic nerve structure with transmission electron microscopy in cross section and RGC numbers with antibody staining in retinal flat mounts. ICP elevation resulted in optic nerve axonal loss and disorganization, as well as RGC soma loss. We conclude that the controlled manipulation of ICP in active, awake mice is possible, despite their small size. Furthermore, ICP elevation results in visual system phenotypes of optic nerve and RGC degeneration, suggesting that this model can be used to study the impact of ICP on the visual system. Potentially, this model can also be used to study the relationship between ICP and IOP, as well diseases impacted by ICP variation such as glaucoma, idiopathic intracranial hypertension, and the spaceflight-related visual impairment intracranial pressure syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnostic value of neuro-ophthalmological signs in cases of Chiari I malformation.

PubMed

Bekerman, Inessa; Sigal, Tal; Kimiagar, Itzhak; Almer, Zina Evy; Vaiman, Michael

2016-12-01

Our purpose was to evaluate the diagnostic value of measuring diameters of optic nerve sheath (ONSD), presence/absence of papilledema, tortuosity of the optic nerve, flattening of the posterior sclera, and intraocular protrusion of the prelaminar optic nerve for intracranial pressure assessment in cases of Chiari I malformation. In a retrospective study, MRI data of 37 consecutive pediatric patients with Chiari malformation and data of 400 patients without intracranial pathology were compared and analyzed. ONSDs were measured at the point where the ophthalmic artery crosses the optic nerve (anatomical landmark). The correlation analysis was performed with clinical findings, gender, age, papilledema, and other neuro-ophthalmological findings. ONSD was enlarged in 38 % of cases of Chiari malformation. The enlargement was bilateral, no correlation with age or gender was found (p = 0.67 and p = 0.76, respectively). The presence of papilledema was detected in 19 % of cases presenting less valuable diagnostic sign if compared with ONSD. The tortuosity of the optic nerve was found in 22 % of cases, but in three patients, it was unilateral. All patients with enlarged ONSD and other neuro-ophthalmological signs present were treated surgically, while most of the patients without these signs (20/23) were treated conservatively. In majority of pediatric cases of Chiari malformation, the ONSD is not enlarged and other neuro-ophthalmological signs are not present. Detecting the enlarged ONSD and other neuro-ophthalmological signs in cases of Chiari malformation may indicate the elevated intracranial pressure and necessity for urgent surgical intervention.

Leukemic optic neuropathy.

PubMed

Brown, G C; Shields, J A; Augsburger, J J; Serota, F T; Koch, P

1981-03-01

The clinical course and ophthalmic manifestations of an eight year old child with acute undifferentiated leukemia and unilateral blindness secondary to leukemic optic nerve head infiltration are described. At autopsy the involved nerve head and peripapillary retina demonstrated massive leukemic cell infiltration and hemorrhagic necrosis. This manifestation of leukemia is quite uncommon and prognosis for life in such cases is poor with existing methods of therapy.

Vision Integrating Strategies in Ophthalmology and Neurochemistry (VISION)

DTIC Science & Technology

2016-08-01

ocular hypertension ). We have developed techniques to quantify damage to the retina, optic nerve, and visual axis in the brain (i.e. superior...injury with different injury-initiating mechanisms (i.e. optic nerve crush, retinal ischemia/reperfusion, and chronic ocular hypertension ). We...protected retinal ganglion cells from ocular hypertension induced damage and appeared to stimulate axonal regeneration. Sigma-1 receptor agonists and

A Unique Way of Learning: Teaching Young Children with Optic Nerve Hypoplasia

ERIC Educational Resources Information Center

Mendiola, Rosalinda; Bahar, Cheryl; Brody, Jill; Slott, Gayle L.

2005-01-01

This booklet was inspired by the need of educators and therapists of preschool students who are blind and visually impaired to share their observations of children with Optic Nerve Hypoplasia (ONH) and the therapies found to be helpful when working with these children. The work done at the Blind Childrens Center is very rewarding, and these…

Clinical Validation of a Smartphone-Based Adapter for Optic Disc Imaging in Kenya.

PubMed

Bastawrous, Andrew; Giardini, Mario Ettore; Bolster, Nigel M; Peto, Tunde; Shah, Nisha; Livingstone, Iain A T; Weiss, Helen A; Hu, Sen; Rono, Hillary; Kuper, Hannah; Burton, Matthew

2016-02-01

Visualization and interpretation of the optic nerve and retina are essential parts of most physical examinations. To design and validate a smartphone-based retinal adapter enabling image capture and remote grading of the retina. This validation study compared the grading of optic nerves from smartphone images with those of a digital retinal camera. Both image sets were independently graded at Moorfields Eye Hospital Reading Centre. Nested within the 6-year follow-up (January 7, 2013, to March 12, 2014) of the Nakuru Eye Disease Cohort in Kenya, 1460 adults (2920 eyes) 55 years and older were recruited consecutively from the study. A subset of 100 optic disc images from both methods were further used to validate a grading app for the optic nerves. Data analysis was performed April 7 to April 12, 2015. Vertical cup-disc ratio for each test was compared in terms of agreement (Bland-Altman and weighted κ) and test-retest variability. A total of 2152 optic nerve images were available from both methods (also 371 from the reference camera but not the smartphone, 170 from the smartphone but not the reference camera, and 227 from neither the reference camera nor the smartphone). Bland-Altman analysis revealed a mean difference of 0.02 (95% CI, -0.21 to 0.17) and a weighted κ coefficient of 0.69 (excellent agreement). The grades of an experienced retinal photographer were compared with those of a lay photographer (no health care experience before the study), and no observable difference in image acquisition quality was found. Nonclinical photographers using the low-cost smartphone adapter were able to acquire optic nerve images at a standard that enabled independent remote grading of the images comparable to those acquired using a desktop retinal camera operated by an ophthalmic assistant. The potential for task shifting and the detection of avoidable causes of blindness in the most at-risk communities makes this an attractive public health intervention.

Expression of Membrane-Bound Human AminopeptidaseP as a Soluble Enzyme and an Investigation into Its Efficacy Towards Offering Protection Against the Toxicity of Chemical Warfare Nerve Agents

DTIC Science & Technology

2016-09-01

survival rate of guinea pigs from GF toxicity [31]. The overall catalytic efficiency of II-G1 reported by Worek against GF was 8.4 × 107 M-1 min-1 and...al., Protection against soman or VX poisoning by human butyrylcholinesterase in guinea pigs and cynomolgus monkeys. Chem Biol Interact, 2005. 157...97-102. 30. Valiyaveettil, M., et al., Protective efficacy of catalytic bioscavenger, paraoxonase 1 against sarin and soman exposure in guinea pigs

[Devic disease: a rare cause of retrobulbar optic neuritis: a case report].

PubMed

Sempińska-Szewczyk, J; Weglewski, A; Juryńczyk, J; Cybulska, B

2000-01-01

A case of 58-year-old woman with recurrent retrobulbar optic neuritis (ron) and transverse myelitis is presented. The patient was admitted to the opthalmology unit because of acute right retrobulbar optic neuritis. In 1997 she complained of left retrobulbar optic neuritis. One year later transverse myelitis of thoracic spine with spastic paraparesis occurred. MRI examination showed T2 hyperintensive focus in the thoracic spine (Th8-Th9, probably demyelinisation). Nowadays MRI examination of the optic nerves and brain showed demyelinisation focus in the right optic nerve. There was no pathological changes in the brain. The diagnosis of Devic disease was established. Treatment with intravenous methyloprednisolon was administered with slight improvement. The pathology and clinical course of Devic disease are discussed.

A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus-Merzbacher disease: A new MRI finding.

PubMed

Pavlidou, Efterpi; Ramachandran, Vijaya; Govender, Veronica; Wilson, Clare; Das, Rini; Vlachou, Victoria; Pavlou, Evangelos; Saggar, Anand; Mankad, Kshitij; Kinali, Maria

2017-03-01

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients. Copyright © 2016 The Japanese Society of Child Neurology. All rights reserved.

Patulous Subarachnoid Space of the Optic Nerve Associated with X-Linked Hypophosphatemic Rickets.

PubMed

Galvez-Ruiz, Alberto; Chaudhry, Imtiaz

2013-01-01

Although the deficiency forms are the most common manifestations of rickets, there are other forms of rickets that are resistant to vitamin D. Of these, the most common is X-linked hypophosphatemic rickets. Rickets represents a group of multiple cranial bone disorders-craniosynostosis and the presence of Chari I malformation being the most notable-that explain the increase in intracranial pressure. We present a 4-year-old patient with an unusual association of X-linked hypophosphataemic rickets, bilateral proptosis, and prominent bilateral widening of the optic nerve sheaths. Although the association between intracranial hypertension and rickets is known, to the best of our knowledge, such a prominent distention of the subarachnoid space of the optic nerve without papilloedema has not been previously described.

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

PubMed Central

Springelkamp, Henriët; Iglesias, Adriana I.; Mishra, Aniket; Höhn, René; Wojciechowski, Robert; Khawaja, Anthony P.; Nag, Abhishek; Wang, Ya Xing; Wang, Jie Jin; Cuellar-Partida, Gabriel; Gibson, Jane; Bailey, Jessica N. Cooke; Vithana, Eranga N.; Gharahkhani, Puya; Boutin, Thibaud; Ramdas, Wishal D.; Zeller, Tanja; Luben, Robert N.; Yonova-Doing, Ekaterina; Viswanathan, Ananth C.; Yazar, Seyhan; Cree, Angela J.; Haines, Jonathan L.; Koh, Jia Yu; Souzeau, Emmanuelle; Wilson, James F.; Amin, Najaf; Müller, Christian; Venturini, Cristina; Kearns, Lisa S.; Kang, Jae Hee; Tham, Yih Chung; Zhou, Tiger; van Leeuwen, Elisabeth M.; Nickels, Stefan; Sanfilippo, Paul; Liao, Jiemin; van der Linde, Herma; Zhao, Wanting; van Koolwijk, Leonieke M.E.; Zheng, Li; Rivadeneira, Fernando; Baskaran, Mani; van der Lee, Sven J.; Perera, Shamira; de Jong, Paulus T.V.M.; Oostra, Ben A.; Uitterlinden, André G.; Fan, Qiao; Hofman, Albert; Tai, E-Shyong; Vingerling, Johannes R.; Sim, Xueling; Wolfs, Roger C.W.; Teo, Yik Ying; Lemij, Hans G.; Khor, Chiea Chuen; Willemsen, Rob; Lackner, Karl J.; Aung, Tin; Jansonius, Nomdo M.; Montgomery, Grant; Wild, Philipp S.; Young, Terri L.; Burdon, Kathryn P.; Hysi, Pirro G.; Pasquale, Louis R.; Wong, Tien Yin; Klaver, Caroline C.W.; Hewitt, Alex W.; Jonas, Jost B.; Mitchell, Paul; Lotery, Andrew J.; Foster, Paul J.; Vitart, Veronique; Pfeiffer, Norbert; Craig, Jamie E.; Mackey, David A.; Hammond, Christopher J.; Wiggs, Janey L.; Cheng, Ching-Yu; van Duijn, Cornelia M.; MacGregor, Stuart

2017-01-01

Abstract Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk. PMID:28073927

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia.

PubMed

Mendoza-Santiesteban, Carlos E; Palma, Jose-Alberto; Hedges, Thomas R; Laver, Nora V; Farhat, Nada; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

2017-03-01

Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Role of Retinal Nerve Fiber Layer Thickness and Optic Disk Measurement by OCT on Early Diagnosis of Glaucoma.

PubMed

Hua, Zanmei; Fang, Qiuyun; Sha, Xiangyin; Yang, Ruiming; Hong, Zuopeng

2015-03-01

Glaucoma is an eye disease that can lead to irreversible optic nerve damage and cause blindness. Optical coherence tomography (OCT) allows an early diagnosis of glaucoma by the measurements of the retinal nerve fiber and optic disc parameters. A retrospective study was designed to analyze the effects of the measurement of the retinal nerve fiber layer (RNFL) thickness and the optic disc tomography by spectral-domain OCT on the early diagnosis of suspected glaucoma and primary open angle glaucoma (POAG). This was a clinical case-control study. The RNFL thickness around the optic disc and optic disk tomographic parameters of the control (n = 51, 98 eyes), suspected glaucoma (n = 81, 146 eyes), and POAG groups (n = 55, 106 eyes) were measured by OCT. The parameters included superior, inferior, nasal and temporal mean RNFL thickness, disc area (DA), cup area (CA), rim area (RA), disc volume (DV), cup volume (CV), rim volume (RV), cup/disc area ratio (CA/DA), rim/disc area ratio (RA/DA), cup/disc volume ratio (CV/DV) and rim/disc volume ratio (RV/DV). Superior, nasal, and mean RNFL parameters, DA, CA,RA, DV, CV, CA/DA, RA/DA, CV/DV and RV/DV significantly differed among three groups by single-factorial ANOVA. Inferior and temporal RNFL thickness significantly differed between the control and POAG groups. No significant difference was observed in RV among three groups. In the POAG group, the maximum area under the ROC curve (AROC) of mean RNFL thickness was 0.845. The maximum AROC of optic disk parameters was RA/DA (0.998), followed by CA/DA (0.997). The AROC of CA, RA, CV, and DV were all > 0.900. OCT may serve as a useful diagnostic modality in distinguishing suspected glaucoma from POAG.

Influence of optic disc leakage on objective optic nerve head assessment in patients with uveitis.

PubMed

Heinz, Carsten; Kogelboom, Katy; Heiligenhaus, Arnd

2016-02-01

Secondary glaucoma is a common complication in patients with uveitis. Heidelberg Retina Tomography (HRT) and retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT) are widely used for examining optic nerve head changes. We evaluated these parameters in patients with uveitis and secondary glaucoma and with inflammatory papillary leakage on fluorescein angiography. Prospective single-center analysis of patients with uveitis, evaluating the impact of optic disc leakage on objective optic disc imaging parameters. Overall, 96 eyes of 59 patients were included. Papillary leakage was found in 42 eyes (43.8 %), and secondary glaucoma was found in 41 eyes (42.7 %). Glaucoma and papillary leakage were present in 12 (29 %) eyes with leakage and in 29 (54 %) eyes without leakage (p = 0.023). Neuroretinal rim area (p = 0.004), rim volume on HRT (p = 0.004), and RNFL thickness on OCT (p = 0.0008) were significantly increased in eyes with papillary leakage, while RNFL on HRT was unchanged (p = 0.255). When only eyes with normal IOP were examined, all objective parameters on OCT and HRT were significantly increased, whereas in eyes with secondary glaucoma, there was only a trend in the same direction, which did not reach significance. A comparison of eyes with secondary glaucoma and optic disc leakage to normal eyes with no glaucoma or leakage revealed no difference in any of the parameters. The objective parameters of optic nerve head imaging tools are significantly influenced by papillary leakage. In patients with secondary glaucoma and papillary leakage, these techniques are unable to detect and monitor glaucomatous damage.

Integrated Model of the Eye/Optic Nerve Head Biomechanical Environment

NASA Technical Reports Server (NTRS)

Ethier, C. R.; Feola, A.; Myers, J. G.; Nelson, E.; Raykin, J.; Samuels, B.

2017-01-01

Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Previously, it has been suggested that ocular changes observed in VIIP syndrome are related to the cephalad fluid shift that results in altered fluid pressures [1]. We are investigating the impact of changes in intracranial pressure (ICP) using a combination of numerical models, which simulate the effects of various environment conditions, including finite element (FE) models of the posterior eye. The specific interest is to understand how altered pressures due to gravitational changes affect the biomechanical environment of tissues of the posterior eye and optic nerve sheath. METHODS: Additional description of the numerical modeling is provided in the IWS abstract by Nelson et al. In brief, to simulate the effects of a cephalad fluid shift on the cardiovascular and ocular systems, we utilized a lumped-parameter compartment model of these systems. The outputs of this lumped-parameter model then inform boundary conditions (pressures) for a finite element model of the optic nerve head (Figure 1). As an example, we show here a simulation of postural change from supine to 15 degree head-down tilt (HDT), with primary outcomes being the predicted change in strains at the optic nerve head (ONH) region, specifically in the lamina cribrosa (LC), retrolaminar optic nerve, and prelaminar neural tissue (PLNT). The strain field can be decomposed into three orthogonal components, denoted as the first, second and third principal strains. We compare the peak tensile (first principal) and compressive (third principal) strains, since elevated strain alters cell phenotype and induces tissue remodeling. RESULTS AND CONCLUSIONS: Our lumped-parameter model predicted an IOP increase of c. 7 mmHg after 21 minutes of 15 degree HDT, which agreed with previous reports of IOP in HDT [1]. The corresponding FEM simulations predicted a relative increase in the magnitudes of the peak tensile and compressive strains in the lamina cribrosa of 42 and 43, respectively (Fig. 2). The corresponding changes in the optic nerve strains were 17 and 39, while in the PLNT they were 47 and 43. These magnitudes of relative elevations in peak strains may induce a phenotypic response in resident mechano-responsive resident cells [2]. This approach may be expanded to investigate other environmental changes (e.g. parabolic flight). Through our VIIP SCHOLAR project, we will validate and improve these integrated models by measuring patient-specific changes in optic nerve sheath geometry in patients with idiopathic intracranial hypertension before and after lumbar puncture and CSF removal.

Glaucoma drops control intraocular pressure and protect optic nerves in a rat model of glaucoma.

PubMed

Morrison, J C; Nylander, K B; Lauer, A K; Cepurna, W O; Johnson, E

1998-03-01

To determine whether chronic topical glaucoma therapy can control intraocular pressure (IOP) and protect nerve fibers in a rat model of pressure-induced optic nerve damage. Sixteen adult Brown Norway rats were-administered unilateral episcleral vein injections of hypertonic saline to produce scarring of the aqueous humor outflow pathways. Twice daily applications of either artificial tears (n = 6), 0.5% betaxolol (n = 5), or 0.5% apraclonidine (n = 5) were delivered to both eyes, and awake pressures were monitored with a TonoPen XL tonometer for 17 days before the rats were killed. For animals administered artificial tears, the mean IOP of the experimental eyes was 39 +/- 2 mm Hg compared with 29 +/- 1 mm Hg for the control eyes. This difference was statistically significant (P < 0.001). Mean IOPs in the experimental eyes of animals administered betaxolol and apraclonidine were 29 +/- 7 and 29 +/- 4 mm Hg, respectively, whereas the mean IOP in the control eyes was 28 +/- 1 mm Hg for both groups. There was no statistically significant difference among these values. The mean IOP for the experimental eyes in the betaxolol and apraclonidine groups was lower than that in animals administered artificial tears (P = 0.003). Quantitative histologic analysis of optic nerve damage in experimental eyes showed that four of the six animals administered artificial tears had damage involving 100% of the neural area. This degree of damage appeared in only 3 of 10 animals administered glaucoma therapy. Optic nerve protection was closely correlated with IOP history because damage was limited to less than 10% of the cross-sectional area in all animals in which the maximal IOP was less than or equal to 39 mm Hg, more than 2 SD below the mean value for eyes administered artificial tears. Topical glaucoma therapy in this model can prevent IOP elevation and protect optic nerve fibers.

Stem Cell Ophthalmology Treatment Study II

ClinicalTrials.gov

2018-02-01

Retinal Disease; Age-Related Macular Degeneration; Retinitis Pigmentosa; Stargardt Disease; Optic Neuropathy; Nonarteritic Ischemic Optic Neuropathy; Optic Atrophy; Optic Nerve Disease; Glaucoma; Leber Hereditary Optic Neuropathy; Blindness; Vision Loss Night; Vision Loss Partial; Vision, Low; Retinopathy; Maculopathy; Macular Degeneration; Retina Atrophy

Regional Retinal Ganglion Cell Axon Loss in a Murine Glaucoma Model

PubMed Central

Schaub, Julie A.; Kimball, Elizabeth C.; Steinhart, Matthew R.; Nguyen, Cathy; Pease, Mary E.; Oglesby, Ericka N.; Jefferys, Joan L.; Quigley, Harry A.

2017-01-01

Purpose To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve. Methods Experimental glaucoma was induced for 6 weeks with a microbead injection model in CD1 (n = 78) and C57BL/6 (B6, n = 68) mice. From epoxy-embedded sections of optic nerve 1 to 2 mm posterior to the globe, total nerve area and regional axon density (axons/1600 μm2) were measured in superior, inferior, nasal, and temporal zones. Results Control eyes of CD1 mice have higher axon density and more total RGCs than control B6 mice eyes. There were no significant differences in control regional axon density in all mice or by strain (all P > 0.2, mixed model). Exposure to elevated IOP caused loss of RGC in both strains. In CD1 mice, axon density declined without significant loss of nerve area, while B6 mice had less density loss, but greater decrease in nerve area. Axon density loss in glaucoma eyes was not significantly greater in any region in either mouse strain (both P > 0.2, mixed model). In moderately damaged CD1 glaucoma eyes, and CD1 eyes with the greatest IOP elevation exposure, density loss differed by region (P = 0.05, P = 0.03, mixed model) with the greatest loss in the temporal and superior regions, while in severely injured B6 nerves superior loss was greater than inferior loss (P = 0.01, mixed model, Bonferroni corrected). Conclusions There was selectively greater loss of superior and temporal optic nerve axons of RGCs in mouse glaucoma at certain stages of damage. Differences in nerve area change suggest non-RGC responses differ between mouse strains. PMID:28549091

Lower corneal hysteresis in glaucoma patients with acquired pit of the optic nerve (APON).

PubMed

Bochmann, Frank; Ang, Ghee S; Azuara-Blanco, Augusto

2008-05-01

Acquired pit-like changes of the optic nerve head (APON) are characteristic of glaucomatous damage and may be a sign of a localized susceptibility of the optic nerve. Thus, it is possible that biomechanical properties of the ocular tissues may play a pressure-independent role in the pathogenesis of glaucoma. Corneal hysteresis (CH) appears to provide information of the biomechanical properties of the ocular hull tissues. The purpose of this study was to compare CH of patients with primary open angle glaucoma (POAG) with and without APON. A prospective case control study was done. POAG patients with and without APON were measured using the Ocular Response Analyzer by masked investigators. Patients in both groups were matched for sex, age, corneal thickness, and type of glaucoma according to maximal IOP (NTG or POAG). Statistical analysis was done using ANOVA. Corneal hysteresis of 16 glaucomatous eyes with APON and 32 controls (glaucoma without APON) was measured. The mean (+/-SD) CH in the APON group was 8.89 (+/-1.53) and 10.2 (+/-1.05) in the control group. The difference is statistically significant (p=0.005). Corneal hysteresis in POAG patients with APON was significantly lower than in patients that did not have such structural changes of the optic disc. These findings may reflect pressure-independent mechanisms involved in the pathogenesis of such glaucomatous optic nerve changes.

Microsurgical Resection of Lateral Tuberculum Sellae Meningioma: Operative Video.

PubMed

Cândido, Duarte N C; Nakashima, Paulo E H; de Oliveira, Jean Gonçalves; Borba, Luis A B

2018-02-01

Tuberculum Sellae Meningiomas (TSMs) are lesions dramatically related to the optic apparatus once the principal clinical complain remains on visual alterations. This is the main picture on decision making to evaluate the best time, risk-benefit, and surgical approaches to the patient treatment. In this video, we present a 65 years old female with 30 days complaint of unilateral (right) complete blindness and complete impaired right eye field test. On physical examination, there were normal pupillary function to light tests. The scans demonstrated the presence of a TSM mostly related to the right optic nerve and encasing it altogether with the right internal carotid artery. Promptly, surgery was addressed using a modified one piece cranio-orbital-zygomatic approach with extra-dural anterior clinoidectomy, as this is the procedure of choice of the senior author (LB), with easy access to decompression of the optic canal and nerve. As demonstrated on the video, the optic nerve was encased by the tumor and pushed upwards against the falciform ligament. Complete resection and decompression was established with step by step dissection, starting unroofing the optic canal, opening the ligament and finally with carefully tumor debulking. Pathology demonstrated a grade one meningioma. The patient improved remarkably her visual acuity and visual field tests on the postoperative period, emphasizing the importance of early treatment for nerve function outcome. The link to the video can be found at: https://youtu.be/pALZqDUkltQ .

Silicone oil migration along the optic nerve after intraocular tamponade.

PubMed

Gargallo Vaamonde, Á; Ibáñez Muñoz, D; Salceda Artola, J; Garatea Aznar, P; Zalazar, R; Yanguas Barea, N

2016-11-01

We present a case of silicone oil migration trough the optic nerve in a diabetic patient with retinal detachment and review the etiologic mechanism and clinical implications. Intracranial silicone oil migration is an uncommon complication associated with silicone oil tamponade. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Orbital cerebrospinal fluid space in glaucoma: the Beijing intracranial and intraocular pressure (iCOP) study.

PubMed

Wang, Ningli; Xie, Xiaobin; Yang, Diya; Xian, Junfang; Li, Yong; Ren, Ruojin; Peng, Xiaoxia; Jonas, Jost B; Weinreb, Robert N

2012-10-01

Low cerebrospinal fluid pressure (CSF-P) may be involved in the pathogenesis of glaucoma. We measured the optic nerve subarachnoid space width (ONSASW) as a surrogate for orbital CSF-P in patients with primary open-angle glaucoma (POAG) with normal and high pressure and a control group. Prospective observational study. The study included 39 patients with POAG; 21 patients had normal pressure (intraocular pressure [IOP] 21 mmHg), and 18 patients had high pressure (IOP >21 mmHg); 21 subjects formed the control group. By using magnetic resonance imaging (MRI) with fat-suppressed fast recovery fast spin echo (FRFSE) T2-weighted sequence, we determined the ONSASW at 3, 9, and 15 mm posterior to the globe. The ONSASW and optic nerve diameter. At all 3 measurement locations of 3, 9, and 15 mm, the ONSASW was significantly (P<0.001, P<0.001, and P = 0.003, respectively) narrower in the normal-pressure group (0.67±0.16, 0.55±0.09, and 0.51±0.12 mm, respectively) than in the high-pressure group (0.93±0.21, 0.70±0.12, and 0.62±0.11 mm, respectively) or the control group (0.87±0.15, 0.67±0.07, and 0.61±0.07 mm, respectively). The high-pressure and control groups did not vary significantly at 3, 9, and 15 mm (P = 0.31, P = 0.39, and P = 0.44, respectively). At all 3 measurement locations, ONSASW was narrower in the normal-pressure group compared with the high-pressure and control groups after adjustment for optic nerve diameter (P<0.01). Correspondingly, the width of the optic nerve subarachnoid space measured at 3, 9, and 15 mm behind the globe, respectively, was significantly (all P<0.05) associated with IOP after adjustment for optic nerve diameter and visual field defect. The narrower orbital optic nerve subarachnoid space in patients with POAG with normal pressure compared with high pressure suggests a lower orbital CSF-P in patients with POAG with normal pressure. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology

NASA Technical Reports Server (NTRS)

Myers, J. G.; Feola, A.; Werner, C.; Nelson, E. S.; Raykin, J.; Samuels, B.; Ethier, C. R.

2016-01-01

The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.

Optical coherence tomography angiography in acute arteritic and non-arteritic anterior ischemic optic neuropathy.

PubMed

Balducci, Nicole; Morara, Mariachiara; Veronese, Chiara; Barboni, Piero; Casadei, Nicoletta Lelli; Savini, Giacomo; Parisi, Vincenzo; Sadun, Alfredo A; Ciardella, Antonio

2017-11-01

The purpose of our study was to describe the feature of acute non-arteritic or arteritic anterior ischemic optic neuropathy (NA-AION and A-AION) using optical coherence tomography angiography (OCT-A) and to compare it with fluorescein angiography (FA) and indocyanine green angiography (ICGA). In this retrospective, observational case-control study four NA-AION patients and one A-AION patient were examined by FA, ICGA and OCT-A within 2 weeks from disease presentation. The characteristics of the images were analyzed. Optic nerve head (ONH) and radial peripapillary capillaries (RPC) vessel densities (VDs) were compared between NA-AION and controls. In two of four NA-AION cases and in the A-AION patient, OCT-A clearly identified the boundary of the ischemic area at the level of the optic nerve head, which was comparable to optic disc filling defects detected by FA. In the other two NA-AION cases, a generalized leakage from the disc was visible with FA, yet OCT-A still demonstrated sectorial peripapillary capillary network reduction. Both ONH and RPC VDs were reduced in NA-AION patients, when compared to controls. OCT-A was able to identify microvascular defects and VD reduction in cases of acute optic disc edema due to NA-AION and A-AION. OCT-A provides additional information in ischemic conditions of the optic nerve head.

Molecular mechanisms of optic axon guidance

NASA Astrophysics Data System (ADS)

Inatani, Masaru

2005-12-01

Axon guidance is one of the critical processes during vertebrate central nervous system (CNS) development. The optic nerve, which contains the axons of retinal ganglion cells, has been used as a powerful model to elucidate some of the mechanisms underlying axon guidance because it is easily manipulated experimentally, and its function is well understood. Recent molecular biology studies have revealed that numerous guidance molecules control the development of the visual pathway. This review introduces the molecular mechanisms involved in each critical step during optic axon guidance. Axonal projections to the optic disc are thought to depend on adhesion molecules and inhibitory extracellular matrices such as chondroitin sulfate. The formation of the head of the optic nerve and the optic chiasm require ligand-receptor interactions between netrin-1 and the deleted in colorectal cancer receptor, and Slit proteins and Robo receptors, respectively. The gradient distributions of ephrin ligands and Eph receptors are essential for correct ipsilateral projections at the optic chiasm and the topographic mapping of axons in the superior colliculus/optic tectum. The precise gradient is regulated by transcription factors determining the retinal dorso-ventral and nasal-temporal polarities. Moreover, the axon guidance activities by Slit and semaphorin 5A require the existence of heparan sulfate, which binds to numerous guidance molecules. Recent discoveries about the molecular mechanisms underlying optic nerve guidance will facilitate progress in CNS developmental biology and axon-regeneration therapy.

Inactivation of the Parietal Reach Region Causes Optic Ataxia, Impairing Reaches but Not Saccades

PubMed Central

Hwang, Eun Jung; Hauschild, Markus; Wilke, Melanie; Andersen, Richard A.

2013-01-01

SUMMARY Lesions in human posterior parietal cortex can cause optic ataxia (OA), in which reaches but not saccades to visual objects are impaired, suggesting separate visuomotor pathways for the two effectors. In monkeys, one potentially crucial area for reach control is the parietal reach region (PRR), in which neurons respond preferentially during reach planning as compared to saccade planning. However, direct causal evidence linking the monkey PRR to the deficits observed in OA is missing. We thus inactivated part of the macaque PRR, in the medial wall of the intraparietal sulcus, and produced the hallmarks of OA, misreaching for peripheral targets but unimpaired saccades. Furthermore, reach errors were larger for the targets preferred by the neural population local to the injection site. These results demonstrate that PRR is causally involved in reach-specific visuomotor pathways, and reach goal disruption in PRR can be a neural basis of OA. PMID:23217749

Peripheral Sensory Neurons Expressing Melanopsin Respond to Light

PubMed Central

Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping; Blixt, Frank W.; Parikh, Sachin; Kessler, Jason; Pérez de Sevilla Müller, Luis; Habib, Samer; Kim, Paul; Wang, Zhe Z.; Rodriguez, Allen; Charles, Andrew; Nusinowitz, Steven; Edvinsson, Lars; Barnes, Steven; Brecha, Nicholas C.; Gorin, Michael B.

2016-01-01

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior. PMID:27559310

Diffuse reflectance spectroscopy for optical nerve identification. Preliminary ex vivo results for feedback controlled oral and maxillofacial laser surgery

NASA Astrophysics Data System (ADS)

Stelzle, Florian; Zam, Azhar; Adler, Werner; Douplik, Alexandre; Tangermann-Gerk, Katja; Nkenke, Emeka; Neukam, Friedrich Wilhelm; Schmidt, Michael

Objective: Laser surgery has many advantages. However, due to a lack of haptic feedback it is accompanied by the risk of iatrogenic nerve damage. The aim of this study was to evaluate the possibilities of optical nerve identification by diffuse reflectance spectroscopy to set the base for a feedback control system to enhance nerve preservation in oral and maxillofacial laser surgery. Materials and Methods: Diffuse reflectance spectra of nerve tissue, skin, mucosa, fat tissue, muscle, cartilage and bone (15120 spectra) of ex vivo pig heads were acquired in the wavelength range of 350-650 nm. Tissue differentiation was performed by principal components analysis (PCA) followed by linear discriminant analysis (LDA). Specificity and sensitivity were calculated by receiver operating characteristic (ROC) analysis and the area under curve (AUC). Results: Nerve tissue could correctly be identified and differed from skin, mucosa, fat tissue, muscle, cartilage and bone in more than 90% of the cases (AUC results) with a specificity of over 78% and a sensitivity of more than 86%. Conclusion: Nerve tissue can be identified by diffuse reflectance spectroscopy with high precision and reliability. The results may set the base for a feedback system to prevent iatrogenic nerve damage performing oral and maxillofacial laser surgery.

Visualization of prostatic nerves by polarization-sensitive optical coherence tomography

PubMed Central

Yoon, Yeoreum; Jeon, Seung Hwan; Park, Yong Hyun; Jang, Won Hyuk; Lee, Ji Youl; Kim, Ki Hean

2016-01-01

Preservation of prostatic nerves is critical to recovery of a man’s sexual potency after radical prostatectomy. A real-time imaging method of prostatic nerves will be helpful for nerve-sparing radical prostatectomy (NSRP). Polarization-sensitive optical coherence tomography (PS-OCT), which provides both structural and birefringent information of tissue, was applied for detection of prostatic nerves in both rat and human prostate specimens, ex vivo. PS-OCT imaging of rat prostate specimens visualized highly scattering and birefringent fibrous structures superficially, and these birefringent structures were confirmed to be nerves by histology or multiphoton microscopy (MPM). PS-OCT could easily distinguish these birefringent structures from surrounding other tissue compartments such as prostatic glands and fats. PS-OCT imaging of human prostatectomy specimens visualized two different birefringent structures, appearing fibrous and sheet-like. The fibrous ones were confirmed to be nerves by histology, and the sheet-like ones were considered to be fascias surrounding the human prostate. PS-OCT imaging of human prostatectomy specimens along the perimeter showed spatial variation in the amount of birefringent fibrous structures which was consistent with anatomy. These results demonstrate the feasibility of PS-OCT for detection of prostatic nerves, and this study will provide a basis for intraoperative use of PS-OCT. PMID:27699090

Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure

PubMed Central

Liu, P.; Zhang, M.; Shoeb, M.; Hogan, D.; Tang, Luosheng; Syed, M. F.; Wang, C. Z.; Campbell, G.A.; Ansari, N.H.

2014-01-01

Since as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methyl sulfonyl methane (MSM) applied topically on the eye to determine if this non-invasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected in the anterior chamber of the rat eye to elevate the IOP. EDTA-MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein-lipid aldehyde adducts, and cyclooxygnease-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA-MSM treatment. However oxidative damage and inflammation were ameliorated as reflected by decrease in formation of protein-lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA-MSM treatment increased retinal ganglion cell survival and decreased demyelinization of optic nerve compared with untreated eyes. Chelation treatment with EDTA-MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Since most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA-MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells. PMID:24509160

Phenotype analysis of early risk factors from electronic medical records improves image-derived diagnostic classifiers for optic nerve pathology

NASA Astrophysics Data System (ADS)

Chaganti, Shikha; Nabar, Kunal P.; Nelson, Katrina M.; Mawn, Louise A.; Landman, Bennett A.

2017-03-01

We examine imaging and electronic medical records (EMR) of 588 subjects over five major disease groups that affect optic nerve function. An objective evaluation of the role of imaging and EMR data in diagnosis of these conditions would improve understanding of these diseases and help in early intervention. We developed an automated image processing pipeline that identifies the orbital structures within the human eyes from computed tomography (CT) scans, calculates structural size, and performs volume measurements. We customized the EMR-based phenome-wide association study (PheWAS) to derive diagnostic EMR phenotypes that occur at least two years prior to the onset of the conditions of interest from a separate cohort of 28,411 ophthalmology patients. We used random forest classifiers to evaluate the predictive power of image-derived markers, EMR phenotypes, and clinical visual assessments in identifying disease cohorts from a control group of 763 patients without optic nerve disease. Image-derived markers showed more predictive power than clinical visual assessments or EMR phenotypes. However, the addition of EMR phenotypes to the imaging markers improves the classification accuracy against controls: the AUC improved from 0.67 to 0.88 for glaucoma, 0.73 to 0.78 for intrinsic optic nerve disease, 0.72 to 0.76 for optic nerve edema, 0.72 to 0.77 for orbital inflammation, and 0.81 to 0.85 for thyroid eye disease. This study illustrates the importance of diagnostic context for interpretation of image-derived markers and the proposed PheWAS technique provides a flexible approach for learning salient features of patient history and incorporating these data into traditional machine learning analyses.

Transplantation of BDNF-Secreting Mesenchymal Stem Cells Provides Neuroprotection in Chronically Hypertensive Rat Eyes

PubMed Central

Harper, Matthew M.; Grozdanic, Sinisa D.; Blits, Bas; Kuehn, Markus H.; Zamzow, Daniel; Buss, Janice E.; Kardon, Randy H.; Sakaguchi, Donald S.

2011-01-01

Purpose. To evaluate the ability of mesenchymal stem cells (MSCs) engineered to produce and secrete brain-derived neurotrophic factor (BDNF) to protect retinal function and structure after intravitreal transplantation in a rat model of chronic ocular hypertension (COH). Methods. COH was induced by laser cauterization of trabecular meshwork and episcleral veins in rat eyes. COH eyes received an intravitreal transplant of MSCs engineered to express BDNF and green fluorescent protein (BDNF-MSCs) or just GFP (GFP-MSCs). Computerized pupillometry and electroretinography (ERG) were performed to assess optic nerve and retinal function. Quantification of optic nerve damage was performed by counting retinal ganglion cells (RGCs) and evaluating optic nerve cross-sections. Results. After transplantation into COH eyes, BDNF-MSCs preserved significantly more retina and optic nerve function than GFP-MSC–treated eyes when pupil light reflex (PLR) and ERG function were evaluated. PLR analysis showed significantly better function (P = 0.03) in BDNF-MSC–treated eyes (operated/control ratio = 63.00% ± 11.39%) than GFP-MSC–treated eyes (operated/control ratio = 31.81% ± 9.63%) at 42 days after surgery. The BDNF-MSC–transplanted eyes also displayed a greater level of RGC preservation than eyes that received the GFP-MSCs only (RGC cell counts: BDNF-MSC–treated COH eyes, 112.2 ± 19.39 cells/section; GFP-MSC–treated COH eyes, 52.21 ± 11.54 cells/section; P = 0.01). Conclusions. The authors have demonstrated that lentiviral-transduced BDNF-producing MSCs can survive in eyes with chronic hypertension and can provide retina and optic nerve functional and structural protection. Transplantation of BDNF-producing stem cells may be a viable treatment strategy for glaucoma. PMID:21498611

Canine orbital meningiomas: a review of 22 cases.

PubMed

Mauldin, E.A.; Deehr, A.J.; Hertzke, D.; Dubielzig, R.R.

2000-01-01

Clinical and pathologic features of primary orbital meningiomas in the dog were reviewed. Twenty-two meningiomas, confined to the orbit, were identified from the Comparative Ophthalmic Pathology Laboratory of Wisconsin from 1981 to 1997. The dogs ranged in age from 3 to 17 years (mean = 9.2 years). The clinical presentation, reported in 20 cases, was indicative of a retrobulbar mass and included exophthalmos and orbital swelling (18/20), and papilledema or abnormalities of the posterior segment (7/20). Visual acuity was reported in 15 cases; of those, 12 dogs were blind in the affected eye. Follow-up information was obtained on 17 cases; six dogs developed local recurrence of the neoplasm. Two dogs with recurrent neoplasms simultaneously developed blindness in the opposite eye. Extension along the optic nerve to the optic chiasm was suspected. No metastasis was found at the time of the study. Enucleation with excisional biopsy was effective therapy to date in 11 cases (0.2-4.5 years follow-up time). All neoplasms were located within the vicinity of the optic nerve and, when sectioned through the optic nerve head, appeared to completely envelope the nerve. The neoplastic cells were arranged in tight whorls and bundles characteristic of meningiomas. Most tumors had islands of chondroid and osseous metaplasia (17/22). Ocular invasion was limited to small foci in the posterior choroid or optic nerve head of six dogs. Immunoperoxidase stains on 10 cases were positive for vimentin and S-100, but negative for cytokeratin. Electron microscopy revealed complex interdigitations between cell membranes and few desmosomal intercellular attachments. Primary orbital meningiomas have a characteristic histologic appearance and may recur locally after surgical excision.

Glioprotection of Retinal Astrocytes After Intravitreal Administration of Memantine in the Mouse Optic Nerve Crush Model.

PubMed

Maciulaitiene, Ruta; Pakuliene, Giedre; Kaja, Simon; Pauza, Dainius Haroldas; Kalesnykas, Giedrius; Januleviciene, Ingrida

2017-03-07

BACKGROUND In glaucoma, non-intraocular pressure (IOP)-related risk factors can result in increased levels of extracellular glutamate, which triggers a cascade of neurodegeneration characterized by the excessive activation of N-methyl-D-aspartate (NMDA). The purpose of our study was to evaluate the glioprotective effects of memantine as a prototypic uncompetitive NMDA blocker on retinal astrocytes in the optic nerve crush (ONC) mouse model for glaucoma. MATERIAL AND METHODS Optic nerve crush was performed on all of the right eyes (n=8), whereas left eyes served as contralateral healthy controls (n=8) in Balb/c/Sca mice. Four randomly assigned mice received 2-µl intravitreal injections of memantine (1 mg/ml) after ONC in the experimental eye. One week after the experiment, optic nerves were dissec-ted and stained with methylene blue. Retinae were detached from the sclera. The tissue was immunostained. Whole-mount retinae were investigated by fluorescent microscopy. Astrocyte counts for each image were performed manually. RESULTS Histological sections of crushed optic nerves showed consistently moderate tissue damage in experimental groups. The mean number of astrocytes per image in the ONC group was significantly lower than in the healthy control group (7.13±1.5 and 10.47±1.9, respectively). Loss of astrocytes in the memantine-treated group was significantly lower (8.83±2.2) than in the ONC group. Assessment of inter-observer reliability showed excellent agreement among observations in control, ONC, and memantine groups. CONCLUSIONS The ONC is an effective method for investigation of astrocytic changes in mouse retina. Intravitreally administered memantine shows a promising glioprotective effect on mouse retinal astrocytes by preserving astrocyte count after ONC.

Neuromuscular ultrasound of cranial nerves.

PubMed

Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

2015-04-01

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Direct Surgery of Previously Coiled Large Internal Carotid Ophthalmic Aneurysm for the Purpose of Optic Nerve Decompression

PubMed Central

Kawabata, Shuhei; Toyota, Shingo; Kumagai, Tetsuya; Goto, Tetsu; Mori, Kanji; Taki, Takuyu

2017-01-01

Background Progressive visual loss after coil embolization of a large internal carotid ophthalmic aneurysm has been widely reported. It is generally accepted that the primary strategy for this complication should be conservative, including steroid therapy; however, it is not well known as to what approach to take when the conservative therapy is not effective. Case Presentation We report a case of a 55-year-old female presenting with progressive visual loss after the coiling of a ruptured large internal carotid ophthalmic aneurysm. As the conservative therapy had not been effective, we performed neck clipping of the aneurysm with optic canal unroofing, anterior clinoidectomy, and partial removal of the embolized coils for the purpose of optic nerve decompression. After the surgery, the visual symptom was improved markedly. Conclusions It is suggested that direct surgery for the purpose of optic nerve decompression may be one of the options when conservative therapy is not effective for progressive visual disturbance after coil embolization. PMID:28229036

Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection.

PubMed

Khalilpour, Saba; Latifi, Shahrzad; Behnammanesh, Ghazaleh; Majid, Amin Malik Shah Abdul; Majid, Aman Shah Abdul; Tamayol, Ali

2017-04-15

Optic neuropathy is a neurodegenerative disease which involves optic nerve injury. It is caused by acute or intermittent insults leading to visual dysfunction. There are number of factors, responsible for optic neuropathy, and the optic nerve axon is affected in all type which causes the loss of retinal ganglion cells. In this review we will highlight various mechanisms involved in the cell loss cascades during axonal degeneration as well as ischemic optic neuropathy. These mechanisms include oxidative stress, excitotoxicity, angiogenesis, neuroinflammation and apoptosis following retinal ischemia. We will also discuss the effect of neuroprotective agents in attenuation of the negative effect of factors involve in the disease occurrence and progression. Copyright © 2016. Published by Elsevier B.V.

Tracking the eye non-invasively: simultaneous comparison of the scleral search coil and optical tracking techniques in the macaque monkey

PubMed Central

Kimmel, Daniel L.; Mammo, Dagem; Newsome, William T.

2012-01-01

From human perception to primate neurophysiology, monitoring eye position is critical to the study of vision, attention, oculomotor control, and behavior. Two principal techniques for the precise measurement of eye position—the long-standing sclera-embedded search coil and more recent optical tracking techniques—are in use in various laboratories, but no published study compares the performance of the two methods simultaneously in the same primates. Here we compare two popular systems—a sclera-embedded search coil from C-N-C Engineering and the EyeLink 1000 optical system from SR Research—by recording simultaneously from the same eye in the macaque monkey while the animal performed a simple oculomotor task. We found broad agreement between the two systems, particularly in positional accuracy during fixation, measurement of saccade amplitude, detection of fixational saccades, and sensitivity to subtle changes in eye position from trial to trial. Nonetheless, certain discrepancies persist, particularly elevated saccade peak velocities, post-saccadic ringing, influence of luminance change on reported position, and greater sample-to-sample variation in the optical system. Our study shows that optical performance now rivals that of the search coil, rendering optical systems appropriate for many if not most applications. This finding is consequential, especially for animal subjects, because the optical systems do not require invasive surgery for implantation and repair of search coils around the eye. Our data also allow laboratories using the optical system in human subjects to assess the strengths and limitations of the technique for their own applications. PMID:22912608

A Subset of Palisade Endings Only in the Medial and Inferior Rectus Muscle in Monkey Contain Calretinin

PubMed Central

Lienbacher, Karoline; Ono, Seiji; Fleuriet, Jérome; Mustari, Michael; Horn, Anja K. E.

2018-01-01

Purpose To further chemically characterize palisade endings in extraocular muscles in rhesus monkeys. Methods Extraocular muscles of three rhesus monkeys were studied for expression of the calcium-binding protein calretinin (CR) in palisade endings and multiple endings. The complete innervation was visualized with antibodies against the synaptosomal-associated protein of 25 kDa and combined with immunofluorescence for CR. Six rhesus monkeys received tracer injections of choleratoxin subunit B or wheat germ agglutinin into either the belly or distal myotendinous junction of the medial or inferior rectus muscle to allow retrograde tracing in the C-group of the oculomotor nucleus. Double-immunofluorescence methods were used to study the CR content in retrogradely labeled neurons in the C-group. Results A subgroup of palisade and multiple endings was found to express CR, only in the medial and inferior rectus muscle. In contrast, the en plaque endings lacked CR. Accordingly, within the tracer-labeled neurons of the C-group, a subgroup expressed CR. Conclusions The study indicates that two different neuron populations targeting nontwitch muscle fibers are present within the C-group for inferior rectus and medial rectus, respectively, one expressing CR, one lacking CR. It is possible that the CR-negative neurons represent the basic population for all extraocular muscles, whereas the CR-positive neurons giving rise to CR-positive palisade endings represent a specialized, perhaps more excitable type of nerve ending in the medial and inferior rectus muscles, being more active in vergence. The malfunction of this CR-positive population of neurons that target nontwitch muscle fibers could play a significant role in strabismus.

Change of Retinal Nerve Layer Thickness in Non-Arteritic Anterior Ischemic Optic Neuropathy Revealed by Fourier Domain Optical Coherence Tomography.

PubMed

Han, Mei; Zhao, Chen; Han, Quan-Hong; Xie, Shiyong; Li, Yan

2016-08-01

To examine the changes of non-arteritic anterior ischemic optic neuropathy (NAION) by serial morphometry using Fourier domain optical coherence tomography (FD-OCT). Retrospective study in patients with newly diagnosed NAION (n=33, all unilateral) and controls (n=75 unilateral NAION patients with full contralateral eye vision) who underwent FD-OCT of the optic disk, optic nerve head (ONH), and macula within 1 week of onset and again 1, 3, 6, and 12 months later. The patients showed no improvement in vision during follow-up. Within 1 week of onset, all NAION eyes exhibited severe ONH fiber crowding and peripapillary retinal nerve fiber layer (RNFL) edema. Four had subretinal fluid accumulation and 12 had posterior vitreous detachment (PVD) at the optic disc surface. Ganglion cell complex (GCC) and RNFL thicknesses were reduced at 1 and 3 months (p < 0.05), with no deterioration thereafter. Initial RNFL/GCC contraction magnitude in the superior hemisphere correlated with the severity of inferior visual field deficits. NAION progression is characterized by an initial phase of accelerated RNFL and GCC deterioration. These results reveal that the kinetic change of neural retina in NAION and may have implication on the time window for treatment of NAION. FD-OCT is useful in the evaluation of NAION.

Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy and compressive optic neuropathy

PubMed Central

Jayaraman, Manju; Gandhi, Rashmin Anilkumar; Ravi, Priya; Sen, Parveen

2014-01-01

Purpose: To investigate the effect of optic neuritis (ON), ischemic optic neuropathy (ION) and compressive optic neuropathy (CON) on multifocal visual evoked potential (mfVEP) amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes), ischemic optic neuropathy (ION, n = 14 eyes), and compressive optic neuropathy (CON, n = 13 eyes). The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT). Results: Median of mfVEP amplitude (log SNR) averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33)), ION (0.14 (0.12-0.21)) and CON (0.21 (0.14-0.30)) when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50) ms and 5.73 (2.67-14.14) ms respectively compared to ION group (2.06 (-4.09-13.02)). The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect. PMID:24088641

Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease.

PubMed

Moro, Cécile; El Massri, Nabil; Darlot, Fannie; Torres, Napoleon; Chabrol, Claude; Agay, Diane; Auboiroux, Vincent; Johnstone, Daniel M; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis

2016-10-01

We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of vascularization and myelination following peripheral nerve repair using angiographic and polarization sensitive optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nam, Ahhyun S.; Chico-Calero, Isabel; Easow, Jeena M.; Villiger, Martin; Welt, Jonathan; Winograd, Jonathan M.; Randolph, Mark A.; Redmond, Robert W.; Vakoc, Benjamin J.

2017-02-01

A severe traumatic injury to a peripheral nerve often requires surgical graft repair. However, functional recovery after these surgical repairs is often unsatisfactory. To improve interventional procedures, it is important to understand the regeneration of the nerve grafts. The rodent sciatic nerve is commonly used to investigate these parameters. However, the ability to longitudinally assess the reinnervation of injured nerves are limited, and to our knowledge, no methods currently exist to investigate the timing of the revascularization in functional recovery. In this work, we describe the development and use of angiographic and polarization-sensitive (PS) optical coherence tomography (OCT) to visualize the vascularization, demyelination and remyelination of peripheral nerve healing after crush and transection injuries, and across a variety of graft repair methods. A microscope was customized to provide 3.6 cm fields of view along the nerve axis with a capability to track the nerve height to maintain the nerve within the focal plane. Motion artifact rejection was implemented in the angiography algorithm to reduce degradation by bulk respiratory motion in the hindlimb site. Vectorial birefringence imaging methods were developed to significantly enhance the accuracy of myelination measurements and to discriminate birefringent contributions from the myelin and epineurium. These results demonstrate that the OCT platform has the potential to reveal new insights in preclinical studies and may ultimately provide a means for clinical intra-surgical assessment of peripheral nerve function.

Ocular Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to Investigate NGF Neuroprotective and Reparative Actions.

PubMed

Tirassa, Paola; Rosso, Pamela; Iannitelli, Angela

2018-01-01

The eye is a central nervous system structure that is uniquely accessible to local treatment. Through the ocular surface, it is possible to access the retina, optic nerve, and brain. Animal models of retina degeneration or optic nerve crush could thus serve as tools to investigate whether and how factors, which are anterogradely or retrogradely transported through the optic nerve, might contribute to activate neuroprotection and eventually regeneration. Among these factors, nerve growth factor (NGF) plays a crucial role during development of the visual system, as well as during the entire life span, and in pathological conditions. The ability of NGF to exert survival and trophic actions on the retina and brain cells when applied intraocularly and topically as eye drops is critically reviewed here, together with the effects of ocular neurotrophins on neuronal pathways influencing body rhythm, cognitions, and behavioral functions. The latest data from animal models and humans are presented, and the mechanism of action of ocularly administered NGF is discussed. NGF eye drops are proposed as an experimental strategy to investigate the role and cellular targets of neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and their involvement in the regulation of neurological and behavioral dysfunctions.

Optical coherence tomography in retinitis pigmentosa: reproducibility and capacity to detect macular and retinal nerve fiber layer thickness alterations.

PubMed

Garcia-Martin, Elena; Pinilla, Isabel; Sancho, Eva; Almarcegui, Carmen; Dolz, Isabel; Rodriguez-Mena, Diego; Fuertes, Isabel; Cuenca, Nicolas

2012-09-01

To evaluate the ability of time-domain and Fourier-domain optical coherence tomographies (OCTs) to detect macular and retinal nerve fiber layer atrophies in retinitis pigmentosa (RP). To test the intrasession reproducibility using three OCT instruments (Stratus, Cirrus, and Spectralis). Eighty eyes of 80 subjects (40 RP patients and 40 healthy subjects) underwent a visual field examination, together with 3 macular scans and 3 optic disk evaluations by the same experienced examiner using 3 OCT instruments. Differences between healthy and RP eyes were compared. The relationship between measurements with each OCT instrument was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. Macular and retinal nerve fiber layer atrophies were detected in RP patients for all OCT parameters. Macular and retinal nerve fiber layer thicknesses, as determined by the different OCTs, were correlated but significantly different (P < 0.05). Reproducibility was moderately high using Stratus, good using Cirrus and Spectralis, and excellent using the Tru-track technology of Spectralis. In RP eyes, measurements showed higher variability compared with healthy eyes. Differences in thickness measurements existed between OCT instruments, despite there being a high degree of correlation. Fourier-domain OCT can be considered a valid and repeatability technique to detect retinal nerve fiber layer atrophy in RP patients.

Object localization, discrimination, and grasping with the optic nerve visual prosthesis.

PubMed

Duret, Florence; Brelén, Måten E; Lambert, Valerie; Gérard, Benoît; Delbeke, Jean; Veraart, Claude

2006-01-01

This study involved a volunteer completely blind from retinis pigmentosa who had previously been implanted with an optic nerve visual prosthesis. The aim of this two-year study was to train the volunteer to localize a given object in nine different positions, to discriminate the object within a choice of six, and then to grasp it. In a closed-loop protocol including a head worn video camera, the nerve was stimulated whenever a part of the processed image of the object being scrutinized matched the center of an elicitable phosphene. The accessible visual field included 109 phosphenes in a 14 degrees x 41 degrees area. Results showed that training was required to succeed in the localization and discrimination tasks, but practically no training was required for grasping the object. The volunteer was able to successfully complete all tasks after training. The volunteer systematically performed several left-right and bottom-up scanning movements during the discrimination task. Discrimination strategies included stimulation phases and no-stimulation phases of roughly similar duration. This study provides a step towards the practical use of the optic nerve visual prosthesis in current daily life.

Acute Blindness.

PubMed

Meekins, Jessica M

2015-09-01

Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Cranial Nerve II

PubMed Central

Gillig, Paulette Marie; Sanders, Richard D.

2009-01-01

This article contains a brief review of the anatomy of the visual system, a survey of diseases of the retina, optic nerve and lesions of the optic chiasm, and other visual field defects of special interest to the psychiatrist. It also includes a presentation of the corticothalamic mechanisms, differential diagnosis, and various manifestations of visual illusions, and simple and complex visual hallucinations, as well as the differential diagnoses of these various visual phenomena. PMID:19855858

In vitro imaging of ophthalmic tissue by digital interference holography

NASA Astrophysics Data System (ADS)

Potcoava, Mariana C.; Kay, Christine N.; Kim, Myung K.; Richards, David W.

2010-01-01

We used digital interference holography (DIH) for in vitro imaging of human optic nerve head and retina. Samples of peripheral retina, macula, and optic nerve head from two formaldehyde-preserved human eyes were dissected and mounted onto slides. Holograms were captured by a monochrome CCD camera (Sony XC-ST50, with 780 × 640 pixels and pixel size of ∼9 µm). Light source was a solid-state pumped dye laser with tunable wavelength range of 560-605 nm. Using about 50 wavelengths in this band, holograms were obtained and numerically reconstructed using custom software based on NI LabView. Tomographic images were produced by superposition of holograms. Holograms of all tissue samples were obtained with a signal-to-noise ratio of approximately 50 dB. Optic nerve head characteristics (shape, diameter, cup depth, and cup width) were quantified with a few micron resolution (4.06-4.8 µm). Multiple layers were distinguishable in cross-sectional images of the macula. To our knowledge, this is the first report of DIH use to image human macular and optic nerve tissue. DIH has the potential to become a useful tool for researchers and clinicians in the diagnosis and treatment of many ocular diseases, including glaucoma and a variety of macular diseases.

Subsurface optical stimulation of rat prostate cavernous nerves using a continuous wave, single mode, 1490 nm diode laser

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Stahl, Charlotte S. D.; Hutchens, Thomas C.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2013-03-01

Successful identification of the cavernous nerves (CN's) during radical prostatectomy requires detection of the CN's through a thin layer of overlying fascia. This study explores the 1490 nm infrared (IR) diode laser wavelength for rapid and deep subsurface CN stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth of 520 μm was used to stimulate the CN's in 8 rats through a single mode fiber optic probe with 1-mm-diameter spot and 15 s irradiation time. Successful ONS was judged by an intracavernous pressure response (ICP) in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 and 1550 nm IR diode laser wavelengths. ONS was observed through fascia layers up to 380 μm thick using an incident laser power of 50 mW. ICP response times as short as 4.6 +/- 0.2 s were recorded using higher laser powers bust still below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper optical penetration than 1455 nm and more rapid and efficient nerve stimulation than 1550 nm.

A compact, inexpensive infrared laser system for continuous-wave optical stimulation of the rat prostate cavernous nerves

NASA Astrophysics Data System (ADS)

Perkins, William C.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2014-03-01

Optical nerve stimulation (ONS) has been commonly performed in the laboratory using high-power, pulsed, infrared (IR) lasers including Holmium:YAG, diode, and Thulium fiber lasers. However, the relatively high cost of these lasers in comparison with conventional electrical nerve stimulation (ENS) equipment may represent a significant barrier to widespread adoption of ONS. Optical stimulation of the prostate cavernous nerves (CN's) has recently been reported using lower cost, continuous-wave (CW), all-fiber-based diode lasers. This preliminary study describes further miniaturization and cost reduction of the ONS system in the form of a compact, lightweight, cordless, and inexpensive IR laser. A 140-mW, 1560-nm diode laser was integrated with a green aiming beam and delivery optics into a compact ONS system. Surface and subsurface ONS was performed in a total of 5 rats, in vivo, with measurement of an intracavernous pressure (ICP) response during CW laser irradiation for 30 s with a spot diameter of 0.7 mm. Short-term, CW ONS of the prostate CN's is feasible using a compact, inexpensive, batterypowered IR laser diode system. This ONS system may represent an alternative to ENS for laboratory studies, and with further development, a handheld option for ONS in the clinic to identify and preserve the CN's during prostate cancer surgery.

Effect of spectrum bias on the diagnostic accuracy of spectral-domain optical coherence tomography in glaucoma.

PubMed

Rao, Harsha L; Kumbar, Tukaram; Addepalli, Uday K; Bharti, Neha; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2012-02-29

To evaluate the influence of a control group on the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) in early glaucoma. In a diagnostic, case-control study, 119 eyes of 60 normal subjects with no findings suspicious for glaucoma (control cohort 1); 76 eyes of 41 subjects referred by general ophthalmologists as glaucoma suspects based on optic disc morphology, but found by glaucoma experts to be normal but with physiological variations in their optic nerves (control cohort 2); and 65 eyes of 46 early-glaucoma patients (cases) underwent imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) by SD-OCT. Areas under the receiver operating characteristic curves (AUC) of ONH parameters discriminating glaucomatous eyes from normal eyes of control cohort 2 were significantly lesser (P < 0.001) than those discriminating glaucomatous eyes from normal eyes of control cohort 1. AUCs of RNFL parameters discriminating glaucomatous eyes from normal eyes of control cohorts 2 and 1 were comparable. Although the AUCs of GCC thickness parameters were comparable, AUCs of GCC focal and global loss volume in control cohort 2 (0.684 and 0.671. respectively) were significantly less (P < 0.05) than in control cohort 1 (0.881 and 0.841, respectively). The effectiveness of most SD-OCT parameters in detecting glaucoma significantly decreased when evaluated against a clinically relevant control group with suspicious-looking optic nerves compared with that against a control group consisting of normal subjects with no findings suspicious for glaucoma.

Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy.

PubMed

Weiss, Jeffrey N; Levy, Steven; Benes, Susan C

2015-09-01

We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and intravitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

Interleaved 3D-CNNs for joint segmentation of small-volume structures in head and neck CT images.

PubMed

Ren, Xuhua; Xiang, Lei; Nie, Dong; Shao, Yeqin; Zhang, Huan; Shen, Dinggang; Wang, Qian

2018-05-01

Accurate 3D image segmentation is a crucial step in radiation therapy planning of head and neck tumors. These segmentation results are currently obtained by manual outlining of tissues, which is a tedious and time-consuming procedure. Automatic segmentation provides an alternative solution, which, however, is often difficult for small tissues (i.e., chiasm and optic nerves in head and neck CT images) because of their small volumes and highly diverse appearance/shape information. In this work, we propose to interleave multiple 3D Convolutional Neural Networks (3D-CNNs) to attain automatic segmentation of small tissues in head and neck CT images. A 3D-CNN was designed to segment each structure of interest. To make full use of the image appearance information, multiscale patches are extracted to describe the center voxel under consideration and then input to the CNN architecture. Next, as neighboring tissues are often highly related in the physiological and anatomical perspectives, we interleave the CNNs designated for the individual tissues. In this way, the tentative segmentation result of a specific tissue can contribute to refine the segmentations of other neighboring tissues. Finally, as more CNNs are interleaved and cascaded, a complex network of CNNs can be derived, such that all tissues can be jointly segmented and iteratively refined. Our method was validated on a set of 48 CT images, obtained from the Medical Image Computing and Computer Assisted Intervention (MICCAI) Challenge 2015. The Dice coefficient (DC) and the 95% Hausdorff Distance (95HD) are computed to measure the accuracy of the segmentation results. The proposed method achieves higher segmentation accuracy (with the average DC: 0.58 ± 0.17 for optic chiasm, and 0.71 ± 0.08 for optic nerve; 95HD: 2.81 ± 1.56 mm for optic chiasm, and 2.23 ± 0.90 mm for optic nerve) than the MICCAI challenge winner (with the average DC: 0.38 for optic chiasm, and 0.68 for optic nerve; 95HD: 3.48 for optic chiasm, and 2.48 for optic nerve). An accurate and automatic segmentation method has been proposed for small tissues in head and neck CT images, which is important for the planning of radiotherapy. © 2018 American Association of Physicists in Medicine.

Effects of environmental enrichment on blood vessels in the optic tract of malnourished rats: A morphological and morphometric analysis.

PubMed

Barbosa, Everton Horiquini; Soares, Roberto Oliveira; Braga, Natália Nassif; Almeida, Sebastião de Sousa; Lachat, João-José

2016-06-01

This study aimed to compare the effects of environmental enrichment in nourished (on a diet containing 16% protein) and malnourished (on a diet containing 6% protein) rats during the critical period of brain development, specifically focusing on the optic nerve. By means of morphologic and morphometric assessment of the optic nerve, we analyzed the changes caused by diet and stimulation (environmental enrichment) on postnatal day 35, a time point ideal for such morphological analysis since developmental processes are considered complete at this age. Malnourished animals presented low body and brain weights and high body-to-brain weight ratio compared to well-nourished rats. Furthermore, malnourished animals showed morphological changes in the optic nerve such as edema and vacuolization characterized by increased interstitial space. The malnourished-stimulated group presented lesions characteristic of early protein malnutrition but were milder than lesions exhibited by malnourished-non-stimulated group. The morphometric analysis revealed no difference in glial cell density between groups, but there was significantly higher blood vessel density in the stimulated rats, independent of their nutritional condition. Our data indicate that protein malnutrition imposed during the critical period of brain development alters the cytoarchitecture of the optic nerve. In addition, we affirm that a 1-hour exposure to an enriched environment everyday was sufficient for tissue preservation in rats maintained on a low-protein diet. This protective effect might be related to angiogenesis, as confirmed by the increased vascular density observed in morphometric analyses.

Peripheral Defocus of the Monkey Crystalline Lens With Accommodation in a Lens Stretcher

PubMed Central

Maceo Heilman, Bianca; Manns, Fabrice; Ruggeri, Marco; Ho, Arthur; Gonzalez, Alex; Rowaan, Cor; Bernal, Andres; Arrieta, Esdras; Parel, Jean-Marie

2018-01-01

Purpose To characterize the peripheral defocus of the monkey crystalline lens and its changes with accommodation. Methods Experiments were performed on 15 lenses from 11 cynomolgus monkey eyes (age: 3.8–12.4 years, postmortem time: 33.5 ± 15.3 hours). The tissue was mounted in a motorized lens stretcher to allow for measurements of the lens in the accommodated (unstretched) and unaccommodated (stretched) states. A custom-built combined laser ray tracing and optical coherence tomography system was used to measure the paraxial on-axis and off-axis lens power for delivery angles ranging from −20° to +20° (in air). For each delivery angle, peripheral defocus was quantified as the difference between paraxial off-axis and on-axis power. The peripheral defocus of the lens was compared in the unstretched and stretched states. Results On average, the paraxial on-axis lens power was 52.0 ± 3.4 D in the unstretched state and 32.5 ± 5.1 D in the stretched state. In both states, the lens power increased with increasing delivery angle. From 0° to +20°, the relative peripheral lens power increased by 10.7 ± 1.4 D in the unstretched state and 7.5 ± 1.6 D in the stretched state. The change in field curvature with accommodation was statistically significant (P < 0.001), indicating that the unstretched (accommodated) lens has greater curvature or relative peripheral power. Conclusions The cynomolgus monkey lens has significant accommodation-dependent curvature of field, which suggests that the lens asserts a significant contribution to the peripheral optical performance of the eye that also varies with the state of accommodation.

[Congenital mydriasis as an initial sign of septo-optic dysplasia].

PubMed

Carrascosa-Romero, M C; Ruiz-Cano, R; Martínez-López, F; Alfaro-Ponce, B; Pérez-Pardo, A

2013-10-01

Septo-optic dysplasia (SOD)[MIM182230] consisting of a heterogeneous and uncommon condition characterised by the classictriad: optic nerve hypoplasia, abnormalities of pituitary hormone, and defects of thebrain midline (including agenesis of the septum pellucidum and/or the corpus callosum; ithas also been described associated cortical malformations, it was referred to as SOD plus syndrome).We report the first known case in which the initial diagnostic sign of SOD was a bilateralmydriasis as a manifestation ofhypoplasia of both optic nerves, pituitary hypoplasia andcerebral dysgenesis with neuronal migration disorder.We discuss thedifferential diagnosis of congenital mydriasis. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Analysis of the variation in OCT measurements of a structural bottle neck for eye-brain transfer of visual information from 3D-volumes of the optic nerve head, PIMD-Average [02π

NASA Astrophysics Data System (ADS)

Söderberg, Per G.; Malmberg, Filip; Sandberg-Melin, Camilla

2016-03-01

The present study aimed to analyze the clinical usefulness of the thinnest cross section of the nerve fibers in the optic nerve head averaged over the circumference of the optic nerve head. 3D volumes of the optic nerve head of the same eye was captured at two different visits spaced in time by 1-4 weeks, in 13 subjects diagnosed with early to moderate glaucoma. At each visit 3 volumes containing the optic nerve head were captured independently with a Topcon OCT- 2000 system. In each volume, the average shortest distance between the inner surface of the retina and the central limit of the pigment epithelium around the optic nerve head circumference, PIMD-Average [02π], was determined semiautomatically. The measurements were analyzed with an analysis of variance for estimation of the variance components for subjects, visits, volumes and semi-automatic measurements of PIMD-Average [0;2π]. It was found that the variance for subjects was on the order of five times the variance for visits, and the variance for visits was on the order of 5 times higher than the variance for volumes. The variance for semi-automatic measurements of PIMD-Average [02π] was 3 orders of magnitude lower than the variance for volumes. A 95 % confidence interval for mean PIMD-Average [02π] was estimated to 1.00 +/-0.13 mm (D.f. = 12). The variance estimates indicate that PIMD-Average [02π] is not suitable for comparison between a onetime estimate in a subject and a population reference interval. Cross-sectional independent group comparisons of PIMD-Average [02π] averaged over subjects will require inconveniently large sample sizes. However, cross-sectional independent group comparison of averages of within subject difference between baseline and follow-up can be made with reasonable sample sizes. Assuming a loss rate of 0.1 PIMD-Average [02π] per year and 4 visits per year it was found that approximately 18 months follow up is required before a significant change of PIMDAverage [02π] can be observed with a power of 0.8. This is shorter than what has been observed both for HRT measurements and automated perimetry measurements with a similar observation rate. It is concluded that PIMDAverage [02π] has the potential to detect deterioration of glaucoma quicker than currently available primary diagnostic instruments. To increase the efficiency of PIMD-Average [02π] further, the variation among visits within subject has to be reduced.

Genetics Home Reference: septo-optic dysplasia

MedlinePlus

... have been associated with septo-optic dysplasia , although mutations in these genes appear to be rare causes ... brain (the forebrain) such as the optic nerves . Mutations in any of these genes disrupt the early ...

Probabilistic Modeling of Intracranial Pressure Effects on Optic Nerve Biomechanics

NASA Technical Reports Server (NTRS)

Ethier, C. R.; Feola, Andrew J.; Raykin, Julia; Myers, Jerry G.; Nelson, Emily S.; Samuels, Brian C.

2016-01-01

Altered intracranial pressure (ICP) is involved/implicated in several ocular conditions: papilledema, glaucoma and Visual Impairment and Intracranial Pressure (VIIP) syndrome. The biomechanical effects of altered ICP on optic nerve head (ONH) tissues in these conditions are uncertain but likely important. We have quantified ICP-induced deformations of ONH tissues, using finite element (FE) and probabilistic modeling (Latin Hypercube Simulations (LHS)) to consider a range of tissue properties and relevant pressures.

Developing Extracellular Matrix Technology to Treat Retinal or Optic Nerve Injury

PubMed Central

van der Merwe, Yolandi

2015-01-01

Abstract Adult mammalian CNS neurons often degenerate after injury, leading to lost neurologic functions. In the visual system, retinal or optic nerve injury often leads to retinal ganglion cell axon degeneration and irreversible vision loss. CNS axon degeneration is increasingly linked to the innate immune response to injury, which leads to tissue-destructive inflammation and scarring. Extracellular matrix (ECM) technology can reduce inflammation, while increasing functional tissue remodeling, over scarring, in various tissues and organs, including the peripheral nervous system. However, applying ECM technology to CNS injuries has been limited and virtually unstudied in the visual system. Here we discuss advances in deriving fetal CNS-specific ECMs, like fetal porcine brain, retina, and optic nerve, and fetal non-CNS-specific ECMs, like fetal urinary bladder, and the potential for using tissue-specific ECMs to treat retinal or optic nerve injuries in two platforms. The first platform is an ECM hydrogel that can be administered as a retrobulbar, periocular, or even intraocular injection. The second platform is an ECM hydrogel and polymer “biohybrid” sheet that can be readily shaped and wrapped around a nerve. Both platforms can be tuned mechanically and biochemically to deliver factors like neurotrophins, immunotherapeutics, or stem cells. Since clinical CNS therapies often use general anti-inflammatory agents, which can reduce tissue-destructive inflammation but also suppress tissue-reparative immune system functions, tissue-specific, ECM-based devices may fill an important need by providing naturally derived, biocompatible, and highly translatable platforms that can modulate the innate immune response to promote a positive functional outcome. PMID:26478910

Spectral domain polarization-sensitive optical coherence tomography at 850 nm

NASA Astrophysics Data System (ADS)

Cense, Barry; Chen, Teresa C.; Mujat, Mircea; Joo, Chulmin; Akkin, Taner; Park, B. H.; Pierce, Mark C.; Yun, Andy; Bouma, Brett E.; Tearney, Guillermo J.; de Boer, Johannes F.

2005-04-01

Spectral-Domain Polarization-Sensitive Optical Coherence Tomography (SD-PS-OCT) is a technique developed to measure the thickness and birefringence of the nerve fiber layer in vivo as a tool for the early diagnosis of glaucoma. A clinical SD-PS-OCT system was developed and scans were made around the optic nerve head (ONH) using ten concentric circles of increasing diameter. One healthy volunteer was imaged. Retinal nerve fiber layer thickness and birefringence information was extracted from the data. Polarization-sensitive OCT images were acquired at video rate (29 frames per second (fps), 1000 A-lines / frame) and at 7 fps (1000 A-lines / frame). The last setting improved the signal to noise ratio by approximately 6 dB. Birefringence measurements on the healthy volunteer gave similar results as earlier reported values that were obtained with a time-domain setup. The measurement time was reduced from more than a minute to less than a second.

Optic Nerve Head Biomechanics in Aging and Disease

PubMed Central

Downs, J. Crawford

2015-01-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451

Update on treatment modalities for optic nerve sheath meningiomas.

PubMed

Liu, James K; Forman, Scott; Moorthy, Chitti R; Benzil, Deborah L

2003-05-15

Optic nerve sheath meningiomas (ONSMs) represent 1 to 2% of all meningiomas and one third of all optic nerve tumors. The management of ONSMs is controversial. Traditional surgical removal often results in postoperative blindness in the affected eye and thus has been abandoned as a treatment option in most patients. Surgery may be unnecessarily aggressive, especially if the patient has useful vision. When these tumors are left untreated, however, ensuing progressive visual impairment may lead to complete blindness. More recently, radiotherapy has gained wider acceptance as a treatment for these lesions. The authors of some reports have suggested that fractionated stereotactic radiosurgery (SRS) may be the best option for treating primary ONSMs. In patients with documented progressive visual deterioration, fractionated SRS may be effective in improving or stabilizing remaining functional vision. The authors review the clinical presentation, radiographic characteristics, and management of ONSMs, emphasizing the use of fractionated SRS.

A circadian rhythm in optic nerve impulses from an isolated eye in darkness.

NASA Technical Reports Server (NTRS)

Jacklet, J. W.

1971-01-01

Study of the circadian rhythm of optic nerve potentials recorded from the isolated eye of the sea hare Aplysia. The optic nerve activity in constant conditions is found to be clearly circadian and to obey the circadian rule for diurnal animals. In addition, the period length depends on the in vitro culturing solution. In seawater it is about 22 hr, but in culture medium it is 27 hr. The rhythm can be completely phase-shifted in one trial if the phase of the LD 12:12 Zeitgeber is advanced or delayed 4 hr. The rhythm in one eye can be phase-shifted in vivo independently of the other eye and in vitro independently of the rest of the animal. Thus, in the animal, the eye oscillators are, at most, only slightly influenced by each other or by other oscillators in the animal.

[Effectiveness of magnetotherapy in optic nerve atrophy. A preliminary study].

PubMed

Zobina, L V; Orlovskaia, L S; Sokov, S L; Sabaeva, G F; Kondé, L A; Iakovlev, A A

1990-01-01

Magnetotherapy effects on visual functions (vision acuity and field), on retinal bioelectric activity, on conductive vision system, and on intraocular circulation were studied in 88 patients (160 eyes) with optic nerve atrophy. A Soviet Polyus-1 low-frequency magnetotherapy apparatus was employed with magnetic induction of about 10 mT, exposure 7-10 min, 10-15 sessions per course. Vision acuity of patients with its low (below 0.04 diopters) values improved in 50 percent of cases. The number of patients with vision acuity of 0.2 diopters has increased from 46 before treatment to 75. Magnetotherapy improved ocular hemodynamics in patients with optic nerve atrophy, it reduced the time of stimulation conduction along the vision routes and stimulated the retinal ganglia cells. The maximal effect was achieved after 10 magnetotherapy sessions. A repeated course carried out in 6-8 months promoted a stabilization of the process.

Current perspective of neuroprotection and glaucoma

PubMed Central

Tian, Kailin; Shibata-Germanos, Shannon; Pahlitzsch, Milena; Cordeiro, M Francesca

2015-01-01

Glaucoma is the second leading cause of blindness worldwide and is most notably characterized by progressive optic nerve atrophy and advancing loss of retinal ganglion cells (RGCs). The main concomitant factor is the elevated intraocular pressure (IOP). Existing treatments are focused generally on lowering IOP. However, both RGC loss and optic nerve atrophy can independently occur with IOP at normal levels. In recent years, there has been substantial progress in the development of neuroprotective therapies for glaucoma in order to restore vital visual function. The present review intends to offer a brief insight into conventional glaucoma treatments and discuss exciting current developments of mostly preclinical data in novel neuroprotective strategies for glaucoma that include recent advances in noninvasive diagnostics going beyond IOP maintenance for an enhanced global view. Such strategies now target RGC loss and optic nerve damage, opening a critical therapeutic window for preventative monitoring and treatment. PMID:26635467

Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

PubMed Central

Mulder, Jan; Hökfelt, Tomas; Knuepfer, Mark M.

2013-01-01

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation. PMID:23408032

Preoperative Visualization of Cranial Nerves in Skull Base Tumor Surgery Using Diffusion Tensor Imaging Technology.

PubMed

Ma, Jun; Su, Shaobo; Yue, Shuyuan; Zhao, Yan; Li, Yonggang; Chen, Xiaochen; Ma, Hui

2016-01-01

To visualize cranial nerves (CNs) using diffusion tensor imaging (DTI) with special parameters. This study also involved the evaluation of preoperative estimates and intraoperative confirmation of the relationship between nerves and tumor by verifying the accuracy of visualization. 3T magnetic resonance imaging scans including 3D-FSPGR, FIESTA, and DTI were used to collect information from 18 patients with skull base tumor. DTI data were integrated into the 3D slicer for fiber tracking and overlapped anatomic images to determine course of nerves. 3D reconstruction of tumors was achieved to perform neighboring, encasing, and invading relationship between lesion and nerves. Optic pathway including the optic chiasm could be traced in cases of tuberculum sellae meningioma and hypophysoma (pituitary tumor). The oculomotor nerve, from the interpeduncular fossa out of the brain stem to supraorbital fissure, was clearly visible in parasellar meningioma cases. Meanwhile, cisternal parts of trigeminal nerve and abducens nerve, facial nerve were also imaged well in vestibular schwannomas and petroclival meningioma cases. The 3D-spatial relationship between CNs and skull base tumor estimated preoperatively by tumor modeling and tractography corresponded to the results determined during surgery. Supported by DTI and 3D slicer, preoperative 3D reconstruction of most CNs related to skull base tumor is feasible in pathological circumstances. We consider DTI Technology to be a useful tool for predicting the course and location of most CNs, and syntopy between them and skull base tumor.

Electrical stimulation vs. pulsed and continuous-wave optical stimulation of the rat prostate cavernous nerves, in vivo

NASA Astrophysics Data System (ADS)

Perkins, William C.; Lagoda, Gwen A.; Burnett, Arthur; Fried, Nathaniel M.

2015-07-01

Identification and preservation of the cavernous nerves (CNs) during prostate cancer surgery is critical for post-operative sexual function. Electrical nerve stimulation (ENS) mapping has previously been tested as an intraoperative tool for CN identification, but was found to be unreliable. ENS is limited by the need for electrode-tissue contact, poor spatial precision from electrical current spreading, and stimulation artifacts interfering with detection. Alternatively, optical nerve stimulation (ONS) provides noncontact stimulation, improved spatial selectivity, and elimination of stimulation artifacts. This study compares ENS to pulsed/CW ONS to explore the ONS mechanism. A total of eighty stimulations were performed in 5 rats, in vivo. ENS (4 V, 5 ms, 10 Hz) was compared to ONS using a pulsed diode laser nerve stimulator (1873 nm, 5 ms, 10 Hz) or CW diode laser nerve stimulator (1455 nm). Intracavernous pressure (ICP) response and nerve compound action potentials (nCAPs) were measured. All three stimulation modes (ENS, ONS-CW, ONS-P) produced comparable ICP magnitudes. However, ENS demonstrated more rapid ICP response times and well defined nCAPs compared to unmeasurable nCAPs for ONS. Further experiments measuring single action potentials during ENS and ONS are warranted to further understand differences in the ENS and ONS mechanisms.

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han; Sunwoo, Il-Nam

2012-03-01

Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Optic Disc and Optic Cup Segmentation Methodologies for Glaucoma Image Detection: A Survey

PubMed Central

Almazroa, Ahmed; Burman, Ritambhar; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

2015-01-01

Glaucoma is the second leading cause of loss of vision in the world. Examining the head of optic nerve (cup-to-disc ratio) is very important for diagnosing glaucoma and for patient monitoring after diagnosis. Images of optic disc and optic cup are acquired by fundus camera as well as Optical Coherence Tomography. The optic disc and optic cup segmentation techniques are used to isolate the relevant parts of the retinal image and to calculate the cup-to-disc ratio. The main objective of this paper is to review segmentation methodologies and techniques for the disc and cup boundaries which are utilized to calculate the disc and cup geometrical parameters automatically and accurately to help the professionals in the glaucoma to have a wide view and more details about the optic nerve head structure using retinal fundus images. We provide a brief description of each technique, highlighting its classification and performance metrics. The current and future research directions are summarized and discussed. PMID:26688751

Neurofibromatosis: an update of ophthalmic characteristics and applications of optical coherence tomography

PubMed Central

Abdolrahimzadeh, Barmak; Piraino, Domenica Carmen; Albanese, Giorgio; Cruciani, Filippo; Rahimi, Siavash

2016-01-01

Neurofibromatosis (NF) is a multisystem disorder and tumor predisposition syndrome caused by genetic mutation on chromosome 17-17q11.2 in NF type 1 (NF1), and on chromosome 22-22q12.2 in NF type 2. The disorder is characterized by considerable heterogeneity of clinical expression. NF1 is the form with the most characteristic ocular manifestations. Lisch nodules of the iris are among the well-known diagnostic criteria for the disease. Glaucoma and associated globe enlargement have been described in a significant proportion of patients with NF1 and orbital–facial involvement. Optic nerve glioma may cause strabismus and proptosis, and palpebral neurofibroma may reach considerable size and occasionally show malignant transformation. Near infrared reflectance has greatly contributed to enhancing our knowledge on choroidal alterations in NF1. Indeed, some authors have proposed to include these among the diagnostic criteria. Optical coherence tomography has given new insight on retinal alterations and is a noninvasive tool in the management of optic nerve gliomas in children. Ocular manifestations in NF type 2 can range from early-onset cataracts in up to 80% of cases to optic nerve hamartomas and combined pigment epithelial and retinal hamartomas. PMID:27257370

Premise and Prediction – How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

PubMed Central

Burgoyne, Claude F.; Downs, J. Crawford

2009-01-01

We propose that age-related alterations in optic nerve head (ONH) biomechanics underlie the clinical behavior and increased susceptibility of the aged ONH to glaucomatous damage. The literature which suggests that the aged ONH is more susceptible to glaucomatous damage at all levels of intraocular pressure is reviewed. The relevant biomechanics of the aged ONH are discussed and a biomechanical explanation for why, on average, the stiffened peripapillary scleral and lamina cribrosa connective tissues of the aged eye should lead to a shallow (senile sclerotic) form of cupping is proposed. A logic for why age-related axon loss and the optic neuropathy of glaucoma in the aged eye may overlap is discussed. Finally, we argue for a need to characterize all forms of clinical cupping into prelaminar and laminar components so as to add precision to the discussion of clinical cupping which does not currently exist. Such characterization may lead to the early detection of ONH axonal and connective tissue pathology in ocular hypertension and eventually aid in the assessment of etiology in all forms of optic neuropathy including those that may be purely age-related. PMID:18552618

Hierarchical structural health monitoring system combining a fiber optic spinal cord network and distributed nerve cell devices

NASA Astrophysics Data System (ADS)

Minakuchi, Shu; Tsukamoto, Haruka; Takeda, Nobuo

2009-03-01

This study proposes novel hierarchical sensing concept for detecting damages in composite structures. In the hierarchical system, numerous three-dimensionally structured sensor devices are distributed throughout the whole structural area and connected with the optical fiber network through transducing mechanisms. The distributed "sensory nerve cell" devices detect the damage, and the fiber optic "spinal cord" network gathers damage signals and transmits the information to a measuring instrument. This study began by discussing the basic concept of the hierarchical sensing system thorough comparison with existing fiber optic based systems and nerve systems in the animal kingdom. Then, in order to validate the proposed sensing concept, impact damage detection system for the composite structure was proposed. The sensor devices were developed based on Comparative Vacuum Monitoring (CVM) system and the Brillouin based distributed strain sensing was utilized to gather the damage signals from the distributed devices. Finally a verification test was conducted using prototype devices. Occurrence of barely visible impact damage was successfully detected and it was clearly indicated that the hierarchical system has better repairability, higher robustness, and wider monitorable area compared to existing systems utilizing embedded optical fiber sensors.

Expression of inducible heat shock proteins Hsp27 and Hsp70 in the visual pathway of rats subjected to various models of retinal ganglion cell injury.

PubMed

Chidlow, Glyn; Wood, John P M; Casson, Robert J

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and -70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and -70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration.

In vivo three-dimensional imaging of human corneal nerves using Fourier-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Shin, Jun Geun; Hwang, Ho Sik; Eom, Tae Joong; Lee, Byeong Ha

2017-01-01

We have employed Fourier-domain optical coherence tomography (FD-OCT) to achieve corneal nerve imaging, which could be useful in surgical planning and refractive surgery. Because the three-dimensional (3-D) images of the corneal nerves were acquired in vivo, unintentional movement of the subject during the measurement led to imaging artifacts. These artifacts were compensated for with a series of signal processing techniques, namely realigning A-scan images to flatten the boundary and cross-correlating adjacent B-scan images. To overcome the undesirably large signal from scattering at the corneal surface and iris, volume rendering and maximum intensity projections were performed with only the data taken in the stromal region of the cornea, which is located between 200 and 500 μm from the corneal surface. The 3-D volume imaging of a 10×10 mm2 area took 9.8 s, which is slightly shorter than the normal tear breakup time. This allowed us to image the branched and threadlike corneal nerve bundles within the human eye. The experimental results show that FD-OCT systems have the potential to be useful in clinical investigations of corneal nerves and by minimizing nerve injury during clinical or surgical procedures.

Peripapillary retinal nerve fiber layer thickness in a population of 6-year-old children: findings by optical coherence tomography.

PubMed

Huynh, Son C; Wang, Xiu Ying; Rochtchina, Elena; Mitchell, Paul

2006-09-01

To study the distribution of retinal nerve fiber layer (RNFL) thickness by ocular and demographic variables in a population-based study of young children. Population-based cross-sectional study. One thousand seven hundred sixty-five of 2238 (78.9%) eligible 6-year-old children participated in the Sydney Childhood Eye Study between 2003 and 2004. Mean age was 6.7 years (50.9% boys). Detailed examination included cycloplegic autorefraction and measurement of axial length. Retinal nerve fiber layer scans using an optical coherence tomographer were performed with a circular scan pattern of 3.4-mm diameter. Multivariate analyses were performed to examine the distribution of RNFL parameters with gender, ethnicity, axial length, and refraction. Peripapillary RNFL thickness and RNFL(estimated integral) (RNFL(EI)), which measures the total cross-sectional area of ganglion cell axons converging onto the optic nerve head. Peripapillary RNFL thickness and RNFL(EI) were normally distributed. The mean+/-standard deviation RNFL average thickness was 103.7+/-11.4 microm and RNFL(EI) was 1.05+/-0.12 mm2. Retinal nerve fiber layer thickness was least for the temporal quadrant (75.7+/-14.7 microm), followed by the nasal (81.7+/-19.6 microm), inferior (127.8+/-20.5 microm), and superior (129.5+/-20.6 microm) quadrants. Multivariate adjusted RNFL average thickness was marginally greater in boys than in girls (104.7 microm vs. 103.2 microm; P = 0.007) and in East Asian than in white children (107.7 microm vs. 102.7 microm; P<0.0001). The RNFL was thinner with greater axial length (P(trend)<0.0001) and less positive spherical equivalent refractions (P(trend) = 0.004). Retinal nerve fiber layer average thickness and RNFL(EI) followed a normal distribution. Retinal nerve fiber layer thickness varied marginally with gender, but differences were more marked between white and East Asian children. Retinal nerve fiber layer thinning was associated with increasing axial length and less positive refractions.

Rapid diagnosis of retina and optic nerve abnormalities in canine patients with and without cataracts using chromatic pupil light reflex testing.

PubMed

Grozdanic, Sinisa D; Kecova, Helga; Lazic, Tatjana

2013-09-01

To develop fast and reliable testing routines for diagnosing retina and optic nerve diseases in canine cataract patients based on chromatic properties of the pupillary light reflex response. Seventy-seven canine patients with a history of cataract and decreased vision (43 patients with cataracts and no evidence of retina or optic nerve disease, 21 patients with cataracts and retinal degeneration [RD], 13 patients with cataracts and retinal detachment [RDT]), 11 canine patients with optic neuritis (ON) and 23 healthy dogs were examined using chromatic pupillary light reflex (cPLR) analysis with red and blue light and electroretinography. Electroretinography analysis showed statistically significant deficits in a- and b-wave amplitudes in dogs with cataracts and RD, or cataracts and RDT, when compared to dogs with cataracts without evidence of retinal abnormalities. Evaluation of b-wave amplitudes showed that presence of 78.5-μV (or lower) amplitudes had high sensitivity of 100% (95% CI: 87.2-100%) and high specificity of 96.7% (95% CI: 88.4-100%) in RD and RDT. Evaluation of cPLR responses using red light showed that presence of the pupil end constriction diameter of 5.5 mm (or higher) had moderately high sensitivity of 76.5% (95% CI: 50.1-93.2%) and high specificity of 100% (95% CI: 91.2-100%) in detecting RD and RDT. Optic neuritis patients had absent cPLR responses, regardless of the visual status. Chromatic evaluation of the pupillary light reflex is a rapid and accurate test for diagnosing retina and optic nerve diseases in canine patients. © 2012 American College of Veterinary Ophthalmologists.

Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy.

PubMed

Touitou, Valerie; Johnson, Mary A; Guo, Yan; Miller, Neil R; Bernstein, Steven L

2013-11-11

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both. TOXICITY was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed. IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers. IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION. A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

Optical imaging of neural and hemodynamic brain activity

NASA Astrophysics Data System (ADS)

Schei, Jennifer Lynn

Optical imaging technologies can be used to record neural and hemodynamic activity. Neural activity elicits physiological changes that alter the optical tissue properties. Specifically, changes in polarized light are concomitant with neural depolarization. We measured polarization changes from an isolated lobster nerve during action potential propagation using both reflected and transmitted light. In transmission mode, polarization changes were largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. To overcome irregular cell orientation found in the brain, we measured polarization changes from a nerve tied in a knot. Our results show that neural activation produces polarization changes that can be imaged even without regular cell orientations. Neural activation expends energy resources and elicits metabolic delivery through blood vessel dilation, increasing blood flow and volume. We used spectroscopic imaging techniques combined with electrophysiological measurements to record evoked neural and hemodynamic responses from the auditory cortex of the rat. By using implantable optics, we measured responses across natural wake and sleep states, as well as responses following different amounts of sleep deprivation. During quiet sleep, evoked metabolic responses were larger compared to wake, perhaps because blood vessels were more compliant. When animals were sleep deprived, evoked hemodynamic responses were smaller following longer periods of deprivation. These results suggest that prolonged neural activity through sleep deprivation may diminish vascular compliance as indicated by the blunted vascular response. Subsequent sleep may allow vessels to relax, restoring their ability to deliver blood. These results also suggest that severe sleep deprivation or chronic sleep disturbances could push the vasculature to critical limits, leading to metabolic deficit and the potential for tissue trauma.

Relative peripheral hyperopic defocus alters central refractive development in infant monkeys

PubMed Central

Smith, Earl L.; Hung, Li-Fang; Huang, Juan

2009-01-01

Understanding the role of peripheral defocus on central refractive development is critical because refractive errors can vary significantly with eccentricity and peripheral refractions have been implicated in the genesis of central refractive errors in humans. Two rearing strategies were used to determine whether peripheral hyperopia alters central refractive development in rhesus monkeys. In intact eyes, lens-induced relative peripheral hyperopia produced central axial myopia. Moreover, eliminating the fovea by laser photoablation did not prevent compensating myopic changes in response to optically imposed hyperopia. These results show that peripheral refractive errors can have a substantial impact on central refractive development in primates. PMID:19632261

[Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge].

PubMed

Ďuďáková, Ľ; Kousal, B; Kolářová, H; Hlavatá, L; Lišková, P

The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.

Magnetic resonance in studies of glaucoma

PubMed Central

Fiedorowicz, Michał; Dyda, Wojciech; Rejdak, Robert; Grieb, Paweł

2011-01-01

Summary Glaucoma is the second leading cause of blindness. It affects retinal ganglion cells and the optic nerve. However, there is emerging evidence that glaucoma also affects other components of the visual pathway and visual cortex. There is a need to employ new methods of in vivo brain evaluation to characterize these changes. Magnetic resonance (MR) techniques are well suited for this purpose. We review data on the MR evaluation of the visual pathway and the use of MR techniques in the study of glaucoma, both in humans and in animal models. These studies demonstrated decreases in optic nerve diameter, localized white matter loss and decrease in visual cortex density. Studies on rats employing manganese-enhanced MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor MRI revealed signs of degeneration of the optic pathway. Functional MRI showed decreased response of the visual cortex after stimulation of the glaucomatous eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in the visual cortex in a rat model of glaucoma, although not in glaucoma patients. Further applications of MR techniques in studies of glaucomatous brains are indicated. PMID:21959626

Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients.

PubMed

Garcia-Martin, Elena; Pueyo, Victoria; Almarcegui, Carmen; Martin, Jesus; Ara, Jose R; Sancho, Eva; Pablo, Luis E; Dolz, Isabel; Fernandez, Javier

2011-11-01

To quantify structural and functional degeneration in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS) over a 2-year time period, and to analyse the effect of prior optic neuritis (ON) as well as the duration and incidence of MS relapses. 166 MS patients and 120 healthy controls underwent assessment of visual acuity and colour vision, visual field examination, optical coherence tomography, scanning laser polarimetry and visual evoked potentials (VEPs). All subjects were re-evaluated after a period of 12 and 24 months. Changes in the optic nerve were detected by structural measurements but not by functional assessments. Changes registered in MS patients were greater than changes in healthy controls (p<0.05). Eyes with previous ON showed a greater reduction of parameters in the baseline evaluation, but RNFL atrophy was not significantly greater in the longitudinal study. Patients with MS relapses showed a greater reduction of RNFL thickness and VEP amplitude compared with non-relapsing cases. Patients with and without treatment showed similar measurement reduction, but the non-treated group had a significantly higher increase in Expanded Disability Status Scale (p=0.029). MS causes progressive axonal loss in the optic nerve, regardless of a history of ON. This ganglion cell atrophy occurs in all eyes but is more marked in MS eyes than in healthy eyes.

Primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse epibulbar extension and focal infiltration of the optic nerve and meninges, clinically presented as uveitis masquerade syndrome: a case report.

PubMed

Rasić, D M; Stanković, Z; Terzić, T; Kovacević, D; Koturović, Z; Marković, V

2010-09-01

To report a clinical, histopathological and immunohistochemical findings in a case of primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse extraocular episcleral extension and focal infiltration of the optic nerve and meninges, clinically presented as longstanding uveitis masquerade syndrome. Interventional case reports with histopathological correlation. We describe a 80-year-old male patient with a 3-year history of chronic recurrent hypertensive (pan) uveitis associated with ocular pain, unresponsive to topical and systemic anti-inflammatory, immunosuppressive, antibiotic/antiviral and antiglaucomatous therapy. Because the eye was not salvageable with conservative treatment, enucleation of blind and painful eye was performed. Findings from histopathological and immunohistochemistry examination of the enucleated eye showed an extranodal marginal zone lymphoma of the uveal tract with massive epibulbar extension and optic nerve and meningeal penetration. During almost 3 years of clinical course and 6 months after the enucleation, there were no systemic manifestations of lymphoma, and patient has not required subsequent treatment. Primary lymphoproliferative lesions of the uvea, comprising the iris, ciliary body and choroid are very rare, associated with epibulbar extension extremely and with optic nerve and menigeal penetration exceptionally. Despite its rarity, primary lymphoma of the uvea should be included in the differential diagnosis particularly in older patients with longstanding recurrent uveitis.

Surgical decompression in endocrine orbitopathy. Visual evoked potential evaluation and effect on the optic nerve.

PubMed

Clauser, Luigi C; Tieghi, Riccardo; Galie', Manlio; Franco, Filippo; Carinci, Francesco

2012-10-01

Endocrine orbitopathy (EO) represents the most frequent and important extrathyroidal stigma of Graves disease. This chronic autoimmune condition involves the orbital contents, including extraocular muscles, periorbital connective-fatty tissue and lacrimal gland. The increase of fat tissue and the enlargement of extraocular muscles within the bony confines of the orbit leads to proptosis, and in the most severe cases optic neuropathy, caused by compression and stretching of the optic nerve. The congestion and the pressure of the enlarged muscles, constrict the nerve and can lead to reduced sight or loss of vision with the so called "orbital apex syndrome". Generally surgical treatment of EO, based on fat and/or orbital wall expansion, is possible and effective in improving exophthalmos and diplopia. Since there are limited reports focussing on optic neuropathy recovery after fat and/or orbital walls decompression the Authors decided to perform a retrospective analysis on a series of patients affected by EO. The study population was composed of 10 patients affected by EO and presenting to the Unit of Cranio Maxillofacial Surgery, Center for Craniofacial Deformities & Orbital Surgery St. Anna Hospital and University, Ferrara, Italy, for evaluation and treatment. A complete Visual Evoked Potentials (VEP) evaluation was performed. There were seven women and three men with a median age of 55 years. Optic nerve VEP amplitude and latency were recorded as normal or pathological. Abnormal results were scored as moderate, mild and severe. Differences in VEP pre and post-operatively were recorded as present or absent (i.e. VEP Delta). Pearson chi square test was applied. There were 20 operated orbits. The first VEP evaluation was performed 3.2 months before surgery and post-operative VEP control was done after a mean of 18.7 months. Fat decompression was performed in all cases and eight patients had also bony decompression. VEP amplitude and latency were affected in 10 and 15 cases before operation and six and nine after surgery, respectively. VEP amplitude and latency significantly improved after orbital decompression. Fat and orbital wall decompression are of paramount importance not only to improve exophthalmos and diplopia in patients affected by EO but also as rescue surgery for severe cases where optic neuropathy caused by stretching of the optical nerve is detected by VEP. Imaging and functional nerve evaluation are mandatory in all cases of EO. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Syringomyelia presenting with unilateral optic neuropathy: a case report.

PubMed

Ngoo, Qi Zhe; Tai, Evelyn Li Min; Wan Hitam, Wan Hazabbah

2017-01-01

In this case report, we present two cases of syringomyelia with optic neuropathy. In Case 1, a 36-year-old Malay lady presented to our clinic with acute onset of blurring of vision in her left eye that she experienced since past 1 month. She was diagnosed with syringomyelia 12 years ago and was on conservative management. Her visual acuity was 6/6 in the right eye and counting fingers at 1 m in the left. There was a positive relative afferent pupillary defect in her left eye. Optic nerve functions of her left eye were reduced. Visual field showed a left inferior field defect. Her extraocular muscle movements were full. Magnetic resonance imaging of the brain and spine showed syringomyelia at the level of C2-C6 and T2-T9. Both of her optic nerves were normal. Her condition improved with intravenous and oral corticosteroids. In Case 2, a 44-year-old Malay lady presented to our clinic with a progressive central scotoma in her right eye that she experienced since past 1 month. She had previous history of recurrent episodes of weakness in both of her lower limbs from past 8 months. Visual acuity in her right and left eye was 6/9 and 6/6, respectively. The relative afferent pupillary defect in her right eye was positive. Optic nerve functions of her right eye were affected. Visual field showed a central scotoma in her right eye. Her extraocular muscle movements were full. Fundoscopy of her right eye showed a pale optic disc. Her left eye fundus was normal. Magnetic resonance imaging of the brain and spine showed syringomyelia at T3-T6. Both of her optic nerves were normal. A diagnosis of syringomyelia with right optic atrophy was performed. Her condition improved with intravenous and oral corticosteroids. Optic neuropathy is a rare neuro-ophthalmic manifestation in patients with syringomyelia. Prompt diagnosis and timely management are essential to avoid a poor visual outcome. Intravenous corticosteroids are beneficial in the treatment of early optic neuropathy in syringomyelia.

Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis

PubMed Central

Lin, Tsen-Hsuan; Spees, William M.; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further elucidate the interplay of underlying pathologies and functional impairments. Previously, we demonstrated a significant 27% activation-associated decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) in normal C57BL/6 mouse optic nerve with visual stimulation using diffusion fMRI. Here we apply this approach to explore the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis. Visual stimulation produced a significant 25% (vs. baseline) ADC⊥ decrease in sham EAE optic nerves, while only a 7% (vs. baseline) ADC⊥ decrease was seen in EAE mice with acute optic neuritis. The reduced activation-associated ADC⊥ response correlated with post-MRI immunohistochemistry determined pathologies (including inflammation, demyelination, and axonal injury). The negative correlation between activation-associated ADC⊥ response and visual acuity was also found when pooling EAE-affected and sham groups under our experimental criteria. Results suggest that reduction in diffusion fMRI directly reflects impaired axonal-activation in EAE mice with optic neuritis. Diffusion fMRI holds promise for directly gauging in vivo white-matter dysfunction or therapeutic responses in MS patients. PMID:24632420

Influence of myelinated retinal nerve fibers on retinal vessel density measurement with AngioVue OCT angiography.

PubMed

Holló, Gábor

2016-12-01

Myelinated retinal nerve fibers (MRNF) represent an asymptomatic developmental anomaly in which myelin sheaths extend to a group of retinal nerve fibers along their intraocular portion. The additional volume of the myelin sheaths causes displacement of the axons toward the vitreous body. We investigated the effect of localized MRNF on peripapillary vessel density measurement results using optical coherence tomography (OCT) angiography. Peripapillary angioflow density measurements (PAFD, % of the analyzed retinal area) were made with the AngioVue OCT (Optovue Inc., Fremont, USA). In both cases, the predominant position of MRNF was inferonasal to the disk. Vessel density was clearly greater in the area of the MRNF than in the surrounding retina in the optic nerve head (ONH) level, but it was lower than in the surrounding retina in the retinal nerve fiber layer (RNFL) level. In the ONH level, PAFD was higher in the MRNF area than in the spatially corresponding superonasal area (Case 1: 64.6 vs. 57.6 %; Case 2: 65.8 vs. 56.3 %). In contrast, in the RNFL level, PAFD was lower in the MRNF area than in the corresponding superonasal area (Case 1: 60.1 vs. 65.4 %; Case 2: 46.5 vs. 58.5 %). Our cases show that the effect of MRNF on OCT angiography vessel density is different in the different measurement layers. Clinicians may separate decreased vessel density caused by anterior RNFL displacement in MRNF areas from that caused by nerve fiber damage in optic neuropathies by evaluating PAFD in both the ONH and RNFL levels.

An Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Children With Epilepsy Receiving Treatment of Valproic Acid.

PubMed

Dereci, Selim; Koca, Tuğba; Akçam, Mustafa; Türkyilmaz, Kemal

2015-07-01

We investigated the peripapillary retinal nerve fiber layer thickness with optical coherence tomography in epileptic children receiving valproic acid monotherapy. The study was conducted on children aged 8-16 years who were undergoing valproic acid monotherapy for epilepsy. The study group comprised a total of 40 children who met the inclusion criteria and 40 healthy age- and sex-matched children as a control group. Children with at least a 1-year history of epilepsy and taking 10-40 mg/kg/day treatment were included in the study. Peripapillary retinal nerve fiber layer thickness measurements were performed using Cirrus HD optical coherence tomography. All children and parents were informed about the study and informed consent was obtained from the parents of all the participants. The study group included 21 girls and 19 boys with a mean age of 10.6 ± 2.3 years. According to the results of optical coherence tomography measurements, the mean peripapillary retinal nerve fiber layer thickness was 91.6 ± 9.7 in the patient group and 95.5 ± 7.4 μm in the control group (P < 0.05). The superior peripapillary retinal nerve fiber layer thickness was 112.0 ± 13.2 in the patient group and 120.0 ± 14.7 μm in the control group (P < 0.02). According to the results of both measurements, the peripapillary retinal nerve fiber layer thickness was significantly lower in the patient group. Neither color vision loss nor visual field examination abnormality could be documented. According to the optical coherence tomography measurements, the average and superior peripapillary retinal nerve fiber layer thicknesses were thinner in patients with epilepsy who were receiving valproic acid monotherapy compared with healthy children. This situation can lead to undesirable results in terms of eye health. New studies are needed to investigate whether these findings are the result of epilepsy or can be attributed to valproic acid and whether there are adverse effects of valproic acid later in life. Copyright © 2015 Elsevier Inc. All rights reserved.

Glaucoma risk index: automated glaucoma detection from color fundus images.

PubMed

Bock, Rüdiger; Meier, Jörg; Nyúl, László G; Hornegger, Joachim; Michelson, Georg

2010-06-01

Glaucoma as a neurodegeneration of the optic nerve is one of the most common causes of blindness. Because revitalization of the degenerated nerve fibers of the optic nerve is impossible early detection of the disease is essential. This can be supported by a robust and automated mass-screening. We propose a novel automated glaucoma detection system that operates on inexpensive to acquire and widely used digital color fundus images. After a glaucoma specific preprocessing, different generic feature types are compressed by an appearance-based dimension reduction technique. Subsequently, a probabilistic two-stage classification scheme combines these features types to extract the novel Glaucoma Risk Index (GRI) that shows a reasonable glaucoma detection performance. On a sample set of 575 fundus images a classification accuracy of 80% has been achieved in a 5-fold cross-validation setup. The GRI gains a competitive area under ROC (AUC) of 88% compared to the established topography-based glaucoma probability score of scanning laser tomography with AUC of 87%. The proposed color fundus image-based GRI achieves a competitive and reliable detection performance on a low-priced modality by the statistical analysis of entire images of the optic nerve head. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Shared-hole graph search with adaptive constraints for 3D optic nerve head optical coherence tomography image segmentation

PubMed Central

Yu, Kai; Shi, Fei; Gao, Enting; Zhu, Weifang; Chen, Haoyu; Chen, Xinjian

2018-01-01

Optic nerve head (ONH) is a crucial region for glaucoma detection and tracking based on spectral domain optical coherence tomography (SD-OCT) images. In this region, the existence of a “hole” structure makes retinal layer segmentation and analysis very challenging. To improve retinal layer segmentation, we propose a 3D method for ONH centered SD-OCT image segmentation, which is based on a modified graph search algorithm with a shared-hole and locally adaptive constraints. With the proposed method, both the optic disc boundary and nine retinal surfaces can be accurately segmented in SD-OCT images. An overall mean unsigned border positioning error of 7.27 ± 5.40 µm was achieved for layer segmentation, and a mean Dice coefficient of 0.925 ± 0.03 was achieved for optic disc region detection. PMID:29541497

The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

NASA Technical Reports Server (NTRS)

Fox, Robert A.; Sutton, R. L.; Mckenna, Susan

1991-01-01

Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

Visualization of Sliding and Deformation of Orbital Fat During Eye Rotation

PubMed Central

Hötte, Gijsbert J.; Schaafsma, Peter J.; Botha, Charl P.; Wielopolski, Piotr A.; Simonsz, Huibert J.

2016-01-01

Purpose Little is known about the way orbital fat slides and/or deforms during eye movements. We compared two deformation algorithms from a sequence of MRI volumes to visualize this complex behavior. Methods Time-dependent deformation data were derived from motion-MRI volumes using Lucas and Kanade Optical Flow (LK3D) and nonrigid registration (B-splines) deformation algorithms. We compared how these two algorithms performed regarding sliding and deformation in three critical areas: the sclera-fat interface, how the optic nerve moves through the fat, and how the fat is squeezed out under the tendon of a relaxing rectus muscle. The efficacy was validated using identified tissue markers such as the lens and blood vessels in the fat. Results Fat immediately behind the eye followed eye rotation by approximately one-half. This was best visualized using the B-splines technique as it showed less ripping of tissue and less distortion. Orbital fat flowed around the optic nerve during eye rotation. In this case, LK3D provided better visualization as it allowed orbital fat tissue to split. The resolution was insufficient to visualize fat being squeezed out between tendon and sclera. Conclusion B-splines performs better in tracking structures such as the lens, while LK3D allows fat tissue to split as should happen as the optic nerve slides through the fat. Orbital fat follows eye rotation by one-half and flows around the optic nerve during eye rotation. Translational Relevance Visualizing orbital fat deformation and sliding offers the opportunity to accurately locate a region of cicatrization and permit an individualized surgical plan. PMID:27540495

Proton beam irradiation: a safe procedure in post-equatorial extraocular extension from uveal melanoma.

PubMed

Seibel, Ira; Riechardt, Aline I; Erb-Eigner, Katharina; Böker, Alexander; Cordini, Dino; Heufelder, Jens; Joussen, Antonia M

2018-04-12

This study was performed to show long-term outcomes concerning metastasis rates and local recurrence rates after primary proton beam therapy in uveal melanoma with posterior extraocular extension (EOE) with the main focus on optic nerve invasion. Retrospective case series METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma with posterior EOE between July 1998 and August 2010 were included. EOE was either detected upon sonography at primary examination or during the surgical application of tantalum clips onto the sclera. Ultrasound was performed in each patient before surgery, and if EOE was detected, a magnetic resonance imaging (MRI) scan was performed to confirm EOE. All patients with tumors exceeding 6 mm in thickness or abutting the optic disc received a 1.5 Tesla MRI scan after clip surgery. To asses EOE during follow-up, either ultrasound examinations or-if initially detected only by MRI-MRI scans were performed during follow-up. A total of 27 patients underwent primary proton beam therapy. The EOE was separated into 3 growth types: Optic nerve infiltration in 10 patients, vortex vein infiltration in 9 patients, and transscleral growth post-equatorially in 8 patients. No local recurrences were found during the overall median follow-up of 80 months (11-168 months). Metastasis rates correlated with AJCC stages but not EOE volume. This study shows that posterior EOE can safely be treated by proton beam therapy, even if the optic nerve is infiltrated. MRI enables safe detection of optic nerve invasion. Copyright © 2018 Elsevier Inc. All rights reserved.

Isolated optic nerve gliomas: a multicenter historical cohort study.

PubMed

Shofty, Ben; Ben-Sira, Liat; Kesler, Anat; Jallo, George; Groves, Mari L; Iyer, Rajiv R; Lassaletta, Alvaro; Tabori, Uri; Bouffet, Eric; Thomale, Ulrich-Wilhelm; Hernáiz Driever, Pablo; Constantini, Shlomi

2017-12-01

OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway gliomas (OPGs). Due to the rarity of this condition and the difficulty in differentiating IONGs from other types of OPGs in most clinical series, little is known about these tumors. Currently, due to lack of evidence, they are managed the same as any other OPG. METHODS The authors conducted a multicenter retrospective cohort study aimed at determining the natural history of IONGs. Included were patients with clear-cut glioma of the optic nerve without posterior (chiasmatic/hypothalamic) involvement. At least 1 year of follow-up, 2 MRI studies, and 2 neuro-ophthalmological examinations were required for inclusion. RESULTS Thirty-six patients with 39 tumors were included in this study. Age at diagnosis ranged between 6 months and 16 years (average 6 years). The mean follow-up time was 5.6 years. Twenty-five patients had neurofibromatosis Type 1. During the follow-up period, 59% of the tumors progressed, 23% remained stable, and 18% (all with neurofibromatosis Type 1) displayed some degree of spontaneous regression. Fifty-one percent of the patients presented with visual decline, of whom 90% experienced further deterioration. Nine patients were treated with chemotherapy, 5 of whom improved visually. Ten patients underwent operation, and no local or distal recurrence was noted. CONCLUSIONS Isolated optic nerve gliomas are highly dynamic tumors. Radiological progression and visual deterioration occur in greater percentages than in the general population of patients with OPGs. Response to chemotherapy may be better in this group, and its use should be considered early in the course of the disease.

Optical Magnification Should Be Mandatory for Microsurgery: Scientific Basis and Clinical Data Contributing to Quality Assurance

PubMed Central

Schoeffl, Harald; Lazzeri, Davide; Schnelzer, Richard; Froschauer, Stefan M.

2013-01-01

Background Microsurgical techniques are considered standard procedures in reconstructive surgery. Although microsurgery by itself is defined as surgery aided by optical magnification, there are no guidelines for determining in which clinical situations a microscope or loupe should be used. Therefore, we conducted standardized experiments to objectively assess the impact of optical magnification in microsurgery. Methods Sixteen participants of microsurgical training courses had to complete 2 sets of experiments. Each set had to be performed with an unaided eye, surgical loupes, and a regular operating microscope. The first set of experiments included coaptation of a chicken femoral nerve, and the second set consisted of anastomosing porcine coronary arteries. Evaluation of the sutured nerves and vessels were performed by 2 experienced microsurgeons using an operating microscope. Results The 16 participants of the study completed all of the experiments. The nerve coaptation and vascular anastomoses exercises showed a direct relationship of error frequency and lower optical magnification, meaning that the highest number of microsurgical errors occurred with the unaided eye. For nerve coaptation, there was a strong relationship (P<0.05) between the number of mistakes and magnification, and this relationship was very strong (P<0.01) for vascular anastomoses. Conclusions We were able to prove that microsurgical success is directly related to optical magnification. The human eye's ability to discriminate potentially important anatomical structures is limited, which might be detrimental for clinical results. Although not legally mandatory, surgeries such as reparative surgery after hand trauma should be conducted with magnifying devices for achieving optimal patient outcomes. PMID:23532716

Oral Microbiome Link to Neurodegeneration in Glaucoma

PubMed Central

Astafurov, Konstantin; Elhawy, Eman; Ren, Lizhen; Dong, Cecilia Q.; Igboin, Christina; Hyman, Leslie; Griffen, Ann; Mittag, Thomas; Danias, John

2014-01-01

Background Glaucoma is a progressive optic nerve degenerative disease that often leads to blindness. Local inflammatory responses are implicated in the pathology of glaucoma. Although inflammatory episodes outside the CNS, such as those due to acute systemic infections, have been linked to central neurodegeneration, they do not appear to be relevant to glaucoma. Based on clinical observations, we hypothesized that chronic subclinical peripheral inflammation contributes to neurodegeneration in glaucoma. Methods Mouthwash specimens from patients with glaucoma and control subjects were analyzed for the amount of bacteria. To determine a possible pathogenic mechanism, low-dose subcutaneous lipopolysaccharide (LPS) was administered in two separate animal models of glaucoma. Glaucomatous neurodegeneration was assessed in the retina and optic nerve two months later. Changes in gene expression of toll-like receptor 4 (TLR4) signaling pathway and complement as well as changes in microglial numbers and morphology were analyzed in the retina and optic nerve. The effect of pharmacologic blockade of TLR4 with naloxone was determined. Findings Patients with glaucoma had higher bacterial oral counts compared to control subjects (p<0.017). Low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage. Conclusions The above findings suggest that the oral microbiome contributes to glaucoma pathophysiology. A plausible mechanism by which increased bacterial loads can lead to neurodegeneration is provided by experiments in animal models of the disease and involves activation of microglia in the retina and optic nerve, mediated through TLR4 signaling and complement upregulation. The finding that commensal bacteria may play a role in the development and/or progression of glaucomatous pathology may also be relevant to other chronic neurodegenerative disorders. PMID:25180891

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

PubMed

Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy

PubMed Central

KÖŞKDERELİOĞLU, Aslı; ORTAN, Pınar; ARI, Alpay; GEDİZLİOĞLU, Muhteşem

2016-01-01

Introduction To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Methods Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Results Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Conclusion Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type. PMID:28360761

Compartmental Innervation of the Superior Oblique Muscle in Mammals.

PubMed

Le, Alan; Poukens, Vadims; Ying, Howard; Rootman, Daniel; Goldberg, Robert A; Demer, Joseph L

2015-10-01

Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-μm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action.

Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase.

PubMed

Worek, Franz; Aurbek, Nadine; Wille, Timo; Eyer, Peter; Thiermann, Horst

2011-01-15

Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneous and oxime-induced reactivation kinetics of the pesticide paraoxon, serving as a model compound for diethyl-OP, and the oximes obidoxime, pralidoxime, HI 6 and MMB-4 with human, Rhesus monkey, swine, rabbit, rat and guinea pig erythrocyte AChE. Comparable results were obtained with human and monkey AChE. Differences between human, swine, rabbit, rat and guinea pig AChE were determined for the inhibition and reactivation kinetics. A six-fold difference of the inhibitory potency of paraoxon with human and guinea pig AChE was recorded while only moderate differences of the reactivation constants between human and animal AChE were determined. Obidoxime was by far the most effective reactivator with all tested species. Only minor species differences were found for the aging and spontaneous reactivation kinetics. The results of the present study underline the necessity to determine the inhibition, aging and reactivation kinetics in vitro as a basis for the development of meaningful therapeutic animal models, for the proper assessment of in vivo animal data and for the extrapolation of animal data to humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Alterations of the outer retina in non-arteritic anterior ischaemic optic neuropathy detected using spectral-domain optical coherence tomography.

PubMed

Ackermann, Philipp; Brachert, Maike; Albrecht, Philipp; Ringelstein, Marius; Finis, David; Geerling, Gerd; Aktas, Orhan; Guthoff, Rainer

2017-07-01

A characteristic disease pattern may be reflected by retinal layer thickness changes in non-arteritic anterior ischaemic optic neuropathy measured using spectraldomain optical coherence tomography. Retinal layer segmentation is enabled by advanced software. In this study, retinal layer thicknesses in acute and chronic non-arteritic anterior ischaemic optic neuropathy were compared. A single-centre cross-sectional analysis was used. A total of 27 patients (20 age-matched healthy eyes) were included: 14 with acute (<7 days) and 13 patients with chronic non-arteritic anterior ischaemic optic neuropathy. Macular volume and 12° peripapillary ring optical coherence tomography scans were used. The peripapillary thicknesses of the following layers were determined by manual segmentation: retinal nerve fibres, ganglion cells + inner plexiform layer, inner nuclear layer + outer plexiform layer, outer nuclear layer + inner segments of the photoreceptors and outer segments of the photoreceptors to Bruch's membrane. Macular retinal layer thicknesses were automatically determined in volume cubes centred on the fovea. Peripapillary retinal swelling in acute nonarteritic anterior ischaemic optic neuropathy was attributable to retinal nerve fibre layer, ganglion cell layer/inner plexiform layer and outer nuclear layer/segments of the photoreceptors thickening. In chronic cases, peripapillary retinal nerve fibre layer, macular ganglion cell layer and inner plexiform layer thinning were observed. In acute non-arteritic anterior ischaemic optic neuropathy, the inner and outer peripapillary retinal layers are affected by thickness changes. In chronic cases, atrophy of the ganglion cells and their axons and dendrites is evident by inner retinal layer thinning. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

Optical coherence tomography guided dental drill

DOEpatents

DaSilva, Luiz B.; Colston, Jr., Bill W.; James, Dale L.

2002-01-01

A dental drill that has one or multiple single mode fibers that can be used to image in the vicinity of the drill tip. It is valuable to image below the surface being drilled to minimize damage to vital or normal tissue. Identifying the boundary between decayed and normal enamel (or dentine) would reduce the removal of viable tissue, and identifying the nerve before getting too close with the drill could prevent nerve damage. By surrounding a drill with several optical fibers that can be used by an optical coherence domain reflectometry (OCDR) to image several millimeters ahead of the ablation surface will lead to a new and improved dental treatment device.

Differences in Optic Nerve Head, Retinal Nerve Fiber Layer, and Ganglion Cell Complex Parameters Between Caucasian and Chinese Subjects.

PubMed

Chansangpetch, Sunee; Huang, Guofu; Coh, Paul; Oldenburg, Catherine; Amoozgar, Behzad; He, Mingguang; Lin, Shan C

2018-04-01

To compare optic nerve head, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell complex (GCC) parameters between Caucasian and ethnic Chinese. Normal subjects above 40 years old and self-identified as being Caucasian and Chinese were recruited. They were evaluated with spectral-domain optical coherence tomography (RTVue-100). Parameters related to the optic nerve head, pRNFL, and GCC analysis protocols were acquired. Multivariable linear regression was performed adjusting for potential confounders. Data from 116 Caucasian and 130 Chinese subjects were available for analysis. Mean age of all participants was 66.72 (SD 10.82) years. There were statistically significant differences for disc area (DA), area cup-to-disc, vertical cup-to-disc, and cup volume (P=0.02, 0.004, 0.02, and 0.03, respectively), greater in Chinese. After adjusting for age, sex, axial length (AL), intraocular pressure (IOP), DA, and GCC thickness, Chinese subjects had significantly greater thickness in all pRNFL parameters (mean differences ranged between 4.29 and 9.93 μm; all P<0.001) except the nasal quadrant. GCC outcomes were also adjusted for DA and pRNFL; Caucasians had significantly higher average GCC and inferior GCC (mean difference 2.97 and 3.45 μm, respectively; P<0.01), whereas the Chinese group had significantly higher ganglion cell global loss volume (mean difference 2.47 %, P<0.001). This study suggests there is significantly greater pRNFL thickness in Chinese, which were independent of age, AL, IOP, and DA, and possibly greater GCC in Caucasians after adjustment for age, AL, IOP, DA, and pRNFL thickness.

Unilateral optic disk edema with central retinal artery and vein occlusions as the presenting signs of relapse in acute lymphoblastic leukemia.

PubMed

Salazar Méndez, R; Fonollá Gil, M

2014-11-01

A 39-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (LAL Ph+) developed progressive vision loss to no light perception in his right eye. He had optic disk edema and later developed central artery and vein occlusions. Pan-photocoagulation, as well as radiotherapy of the whole brain were performed in several fractions. Unfortunately the patient died of hematological relapse 4 months later. Optic nerve infiltration may appear as an isolated sign of a leukemia relapse, even before a hematological relapse occurs. Leukemic optic neuropathy is a critical sign, not only for vision, but also for life, and radiotherapy should be immediately performed before irreversible optic nerve damage occurs. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Intracranial pressure-induced optic nerve sheath response as a predictive biomarker for optic disc edema in astronauts.

PubMed

Wostyn, Peter; De Deyn, Peter Paul

2017-11-01

A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities. Understanding this syndrome, called visual impairment and intracranial pressure (VIIP), has become a high priority for National Aeronautics and Space Administration, especially in view of future long-duration missions (e.g., Mars missions). Moreover, to ensure selection of astronaut candidates who will be able to complete long-duration missions with low risk of the VIIP syndrome, it is imperative to identify biomarkers for VIIP risk prediction. Here, we hypothesize that the optic nerve sheath response to alterations in intracranial pressure may be a potential predictive biomarker for optic disc edema in astronauts. If confirmed, this biomarker could be used for preflight identification of astronauts at risk for developing VIIP-associated optic disc edema.

Development of Methods for the Real-Time and Rapid Identification and Detection of TSE in Living Animals Using Fluorescence Spectroscopy of the Eye

DTIC Science & Technology

2007-07-01

retina . Our experiments have so far been limited to sheep. Our experiments have been designed to address the following questions: 1. Can ocular spectra...components and reports that the cornea, lens, retina , and optic nerve show promise. Of these, the optic nerve showed the most potential for changes in...investigations so far suggest that the most promising part of the eye for revealing spectroscopic signatures of neurological disease is the retina . Our

External Factors, Produced by Growing Nerves, Trigger a Regenerative Response in a Non-Regenerative Central Nervous System: Purification and Mode of Action

DTIC Science & Technology

1989-06-01

regenerating optic nerve CNS - Central nervous system FCS - Fetal calf serum Galc - Galactocerebroside G AP - Glial fibriliary acidic protein NGF...nent confinment of the casualty to a wheel chair. Laceration in the upper spinal cord leads to paralysis of the four limbs and a cut in the optic...of microtiter plates in Dulbecco’s modified Eagle medium (DVIEM) containing 10% fetal calf serum (FCS). When the cells reached confluency the medium

Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

PubMed

Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

2010-12-15

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning. Copyright © 2010 Elsevier Inc. All rights reserved.

Real-time, label-free, intraoperative visualization of peripheral nerves and micro-vasculatures using multimodal optical imaging techniques

PubMed Central

Cha, Jaepyeong; Broch, Aline; Mudge, Scott; Kim, Kihoon; Namgoong, Jung-Man; Oh, Eugene; Kim, Peter

2018-01-01

Accurate, real-time identification and display of critical anatomic structures, such as the nerve and vasculature structures, are critical for reducing complications and improving surgical outcomes. Human vision is frequently limited in clearly distinguishing and contrasting these structures. We present a novel imaging system, which enables noninvasive visualization of critical anatomic structures during surgical dissection. Peripheral nerves are visualized by a snapshot polarimetry that calculates the anisotropic optical properties. Vascular structures, both venous and arterial, are identified and monitored in real-time using a near-infrared laser-speckle-contrast imaging. We evaluate the system by performing in vivo animal studies with qualitative comparison by contrast-agent-aided fluorescence imaging. PMID:29541506

Sequential Involvement of the Nervous System in Subacute Combined Degeneration

PubMed Central

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han

2012-01-01

Purpose Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. Materials and Methods In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. Results We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. Conclusion In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain. PMID:22318813

Craniopharyngioma

MedlinePlus

... pituitary gland. They often involve the third ventricle, optic nerve, and pituitary gland. Description Crangiopharyngiomas are localized ... tumor. Other symptoms result from pressure on the optic tract and pituitary gland. Obesity, delayed development, impaired ...

Functional near infrared spectroscopy for awake monkey to accelerate neurorehabilitation study

NASA Astrophysics Data System (ADS)

Kawaguchi, Hiroshi; Higo, Noriyuki; Kato, Junpei; Matsuda, Keiji; Yamada, Toru

2017-02-01

Functional near-infrared spectroscopy (fNIRS) is suitable for measuring brain functions during neurorehabilitation because of its portability and less motion restriction. However, it is not known whether neural reconstruction can be observed through changes in cerebral hemodynamics. In this study, we modified an fNIRS system for measuring the motor function of awake monkeys to study cerebral hemodynamics during neurorehabilitation. Computer simulation was performed to determine the optimal fNIRS source-detector interval for monkey motor cortex. Accurate digital phantoms were constructed based on anatomical magnetic resonance images. Light propagation based on the diffusion equation was numerically calculated using the finite element method. The source-detector pair was placed on the scalp above the primary motor cortex. Four different interval values (10, 15, 20, 25 mm) were examined. The results showed that the detected intensity decreased and the partial optical path length in gray matter increased with an increase in the source-detector interval. We found that 15 mm is the optimal interval for the fNIRS measurement of monkey motor cortex. The preliminary measurement was performed on a healthy female macaque monkey using fNIRS equipment and custom-made optodes and optode holder. The optodes were attached above bilateral primary motor cortices. Under the awaking condition, 10 to 20 trials of alternated single-sided hand movements for several seconds with intervals of 10 to 30 s were performed. Increases and decreases in oxy- and deoxyhemoglobin concentration were observed in a localized area in the hemisphere contralateral to the moved forelimb.

3D reconstruction of the optic nerve head using stereo fundus images for computer-aided diagnosis of glaucoma

NASA Astrophysics Data System (ADS)

Tang, Li; Kwon, Young H.; Alward, Wallace L. M.; Greenlee, Emily C.; Lee, Kyungmoo; Garvin, Mona K.; Abràmoff, Michael D.

2010-03-01

The shape of the optic nerve head (ONH) is reconstructed automatically using stereo fundus color images by a robust stereo matching algorithm, which is needed for a quantitative estimate of the amount of nerve fiber loss for patients with glaucoma. Compared to natural scene stereo, fundus images are noisy because of the limits on illumination conditions and imperfections of the optics of the eye, posing challenges to conventional stereo matching approaches. In this paper, multi scale pixel feature vectors which are robust to noise are formulated using a combination of both pixel intensity and gradient features in scale space. Feature vectors associated with potential correspondences are compared with a disparity based matching score. The deep structures of the optic disc are reconstructed with a stack of disparity estimates in scale space. Optical coherence tomography (OCT) data was collected at the same time, and depth information from 3D segmentation was registered with the stereo fundus images to provide the ground truth for performance evaluation. In experiments, the proposed algorithm produces estimates for the shape of the ONH that are close to the OCT based shape, and it shows great potential to help computer-aided diagnosis of glaucoma and other related retinal diseases.

Spatial and temporal variability in response to hybrid electro-optical stimulation

NASA Astrophysics Data System (ADS)

Duke, Austin R.; Lu, Hui; Jenkins, Michael W.; Chiel, Hillel J.; Jansen, E. Duco

2012-06-01

Hybrid electro-optical neural stimulation is a novel paradigm combining the advantages of optical and electrical stimulation techniques while reducing their respective limitations. However, in order to fulfill its promise, this technique requires reduced variability and improved reproducibility. Here we used a comparative physiological approach to aid the further development of this technique by identifying the spatial and temporal factors characteristic of hybrid stimulation that may contribute to experimental variability and/or a lack of reproducibility. Using transient pulses of infrared light delivered simultaneously with a bipolar electrical stimulus in either the marine mollusk Aplysia californica buccal nerve or the rat sciatic nerve, we determined the existence of a finite region of excitability with size altered by the strength of the optical stimulus and recruitment dictated by the polarity of the electrical stimulus. Hybrid stimulation radiant exposures yielding 50% probability of firing (RE50) were shown to be negatively correlated with the underlying changes in electrical stimulation threshold over time. In Aplysia, but not in the rat sciatic nerve, increasing optical radiant exposures (J cm-2) beyond the RE50 ultimately resulted in inhibition of evoked potentials. Accounting for the sources of variability identified in this study increased the reproducibility of stimulation from 35% to 93% in Aplysia and 23% to 76% in the rat with reduced variability.

Biomarkers in primary open angle glaucoma.

PubMed

Kokotas, Haris; Kroupis, Christos; Chiras, Dimitrios; Grigoriadou, Maria; Lamnissou, Klea; Petersen, Michael B; Kitsos, George

2012-12-01

Glaucoma, a leading cause of blindness worldwide, is currently defined as a disturbance of the structural or functional integrity of the optic nerve that causes characteristic atrophic changes in the optic nerve, which may lead to specific visual field defects over time. This disturbance usually can be arrested or diminished by adequate lowering of intraocular pressure (IOP). Glaucoma can be divided roughly into two main categories, ‘ open angle ’ and ‘ closed angle ’ glaucoma.Open angle, chronic glaucoma tends to progress at a slower rate and patients may not notice loss of vision until the disease has progressed significantly. Primary open angle glaucoma(POAG) is described distinctly as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibers. Such loss develops in the presence of open anterior chamber angles, characteristic visual field abnormalities, and IOP that is too high for the healthy eye. It manifests by cupping and atrophy of the optic disc, in the absence of other known causes of glaucomatous disease. Several biological markers have been implicated with the disease. The purpose of this study was to summarize the current knowledge regarding the non-genetic molecular markers which have been predicted to have an association with POAG but have not yet been validated.

Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis

PubMed Central

Khan, Reas S.; Geisler, John G.

2017-01-01

The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria's physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis. PMID:28680531

Optical stimulation of the prostate nerves: A potential diagnostic technique

NASA Astrophysics Data System (ADS)

Tozburun, Serhat

There is wide variability in sexual potency rates (9--86%) after nerve-sparing prostate cancer surgery due to limited knowledge of the location of the cavernous nerves (CN's) on the prostate surface, which are responsible for erectile function. Thus, preservation of the CN's is critical in preserving a man's ability to have spontaneous erections following surgery. Nerve-mapping devices, utilizing conventional Electrical Nerve Stimulation (ENS) techniques, have been used as intra-operative diagnostic tools to assist in preservation of the CN. However, these technologies have proven inconsistent and unreliable in identifying the CN's due to the need for physical contact, the lack of spatial selectivity, and the presence of electrical artifacts in measurements. Optical Nerve Stimulation (ONS), using pulsed infrared laser radiation, is studied as an alternative to ENS. The objective of this study is sevenfold: (1) to develop a laparoscopic laser probe for ONS of the CN's in a rat model, in vivo; (2) to demonstrate faster ONS using continuous-wave infrared laser radiation; (3) to describe and characterize the mechanism of successful ONS using alternative laser wavelengths; (4) to test a compact, inexpensive all-single-mode fiber configuration for optical stimulation of the rat CN studies; (5) to implement fiber optic beam shaping methods for comparison of Gaussian and flat-top spatial beam profiles during ONS; (6) to demonstrate successful ONS of CN's through a thin layer of fascia placed over the nerve and prostate gland; and (7) to verify the experimentally determined therapeutic window for safe and reliable ONS without thermal damage to the CN's by comparison with a computational model for thermal damage. A 5.5-Watt Thulium fiber laser operated at 1870 nm and two pigtailed, single mode, near-IR diode lasers (150-mW, 1455-nm laser and 500-mW, 1550-nm laser) were used for non-contact stimulation of the rat CN's. Successful laser stimulation, as measured by an intracavernous pressure (ICP) response in the penis, was achieved with the laser operating in CW mode. CW optical nerve stimulation provides a significantly faster ICP response time using a lower laser power laser than conventional pulsed stimulation. An all-single-mode fiber design was successfully tested in a rat model. The CN reached a threshold temperature of ˜ 42 °C, with response times as short as 3 s, and ICP responses in the rat penis of up to 50 mmHg compared to a baseline of 5--10 mmHg. Chemical etching of the distal single-mode-fiber tip produced a concave shape and transformed the Gaussian to a flat-top spatial beam profile, resulting in simplified alignment of the laser beam with the nerve. This novel, all-single-mode-fiber laser nerve stimulation system introduces several advantages including: (1) a less expensive and more compact ONS configuration; (2) elimination of alignment and cleaning bulk optical components; and (3) improved spatial beam profile for simplified alignment. For the fascia layers over the CN's (240--600 microm), the 1550 nm laser with an optical penetration depth of ˜ 930 microm in water was substituted for the 1455 nm laser. Successful ONS was achieved, for the first time, in fascia layers up to 450 microm thick which is critical for future clinical translation of this method for intra-operative identification and preservation of CN's during prostate cancer surgery. In order to define the upper limit of the therapeutic window for ONS of CN in a rat model, in vivo, identification of the thermal damage threshold for the CN after laser irradiation was investigated by direct comparison of the visible thermal damage data with a theoretical thermal damage calculation utilizing a standard Arrhenius integral model.

OCT for glaucoma diagnosis, screening and detection of glaucoma progression.

PubMed

Bussel, Igor I; Wollstein, Gadi; Schuman, Joel S

2014-07-01

Optical coherence tomography (OCT) is a commonly used imaging modality in the evaluation of glaucomatous damage. The commercially available spectral domain (SD)-OCT offers benefits in glaucoma assessment over the earlier generation of time domain-OCT due to increased axial resolution, faster scanning speeds and has been reported to have improved reproducibility but similar diagnostic accuracy. The capabilities of SD-OCT are rapidly advancing with 3D imaging, reproducible registration, and advanced segmentation algorithms of macular and optic nerve head regions. A review of the evidence to date suggests that retinal nerve fibre layer remains the dominant parameter for glaucoma diagnosis and detection of progression while initial studies of macular and optic nerve head parameters have shown promising results. SD-OCT still currently lacks the diagnostic performance for glaucoma screening. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Functional Peptidomics: Stimulus- and Time-of-Day-Specific Peptide Release in the Mammalian Circadian Clock.

PubMed

Atkins, Norman; Ren, Shifang; Hatcher, Nathan; Burgoon, Penny W; Mitchell, Jennifer W; Sweedler, Jonathan V; Gillette, Martha U

2018-06-20

Daily oscillations of brain and body states are under complex temporal modulation by environmental light and the hypothalamic suprachiasmatic nucleus (SCN), the master circadian clock. To better understand mediators of differential temporal modulation, we characterize neuropeptide releasate profiles by nonselective capture of secreted neuropeptides in an optic nerve horizontal SCN brain slice model. Releasates are collected following electrophysiological stimulation of the optic nerve/retinohypothalamic tract under conditions that alter the phase of the SCN activity state. Secreted neuropeptides are identified by intact mass via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found time-of-day-specific suites of peptides released downstream of optic nerve stimulation. Peptide release was modified differentially with respect to time-of-day by stimulus parameters and by inhibitors of glutamatergic or PACAPergic neurotransmission. The results suggest that SCN physiology is modulated by differential peptide release of both known and unexpected peptides that communicate time-of-day-specific photic signals via previously unreported neuropeptide signatures.

Optic nerve head biomechanics in aging and disease.

PubMed

Downs, J Crawford

2015-04-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects.

PubMed

Jóhannesson, Gauti; Eklund, Anders; Lindén, Christina

2018-04-12

A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD. For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory. Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

The Central Bright Spot Sign: A Potential New MR Imaging Sign for the Early Diagnosis of Anterior Ischemic Optic Neuropathy due to Giant Cell Arteritis.

PubMed

Remond, P; Attyé, A; Lecler, A; Lamalle, L; Boudiaf, N; Aptel, F; Krainik, A; Chiquet, C

2017-07-01

A rapid identification of the etiology of anterior ischemic optic neuropathy is crucial because it determines therapeutic management. Our aim was to assess MR imaging to study the optic nerve head in patients referred with anterior ischemic optic neuropathy, due to either giant cell arteritis or the nonarteritic form of the disease, compared with healthy subjects. Fifteen patients with giant cell arteritis-related anterior ischemic optic neuropathy and 15 patients with nonarteritic anterior ischemic optic neuropathy from 2 medical centers were prospectively included in our study between August 2015 and May 2016. Fifteen healthy subjects and patients had undergone contrast-enhanced, flow-compensated, 3D T1-weighted MR imaging. The bright spot sign was defined as optic nerve head enhancement with a 3-grade ranking system. Two radiologists and 1 ophthalmologist independently performed blinded evaluations of MR imaging sequences with this scale. Statistical analysis included interobserver agreement. MR imaging scores were significantly higher in patients with giant cell arteritis-related anterior ischemic optic neuropathy than in patients with nonarteritic anterior ischemic optic neuropathy ( P ≤ .05). All patients with giant cell arteritis-related anterior ischemic optic neuropathy (15/15) and 7/15 patients with nonarteritic anterior ischemic optic neuropathy presented with the bright spot sign. No healthy subjects exhibited enhancement of the anterior part of the optic nerve. There was a significant relationship between the side of the bright spot and the side of the anterior ischemic optic neuropathy ( P ≤ .001). Interreader agreement was good for observers (κ = 0.815). Here, we provide evidence of a new MR imaging sign that identifies the acute stage of giant cell arteritis-related anterior ischemic optic neuropathy; patients without this central bright spot sign always had a nonarteritic pathophysiology and therefore did not require emergency corticosteroid therapy. © 2017 by American Journal of Neuroradiology.

Measuring in-vivo and in-situ ex-vivo the 3D deformation of the lamina cribrosa microstructure under elevated intraocular pressure

NASA Astrophysics Data System (ADS)

Wei, Junchao; Yang, Bin; Voorhees, Andrew P.; Tran, Huong; Brazile, Bryn; Wang, Bo; Schuman, Joel; Smith, Matthew A.; Wollstein, Gadi; Sigal, Ian A.

2018-02-01

Elevated intraocular pressure (IOP) deforms the lamina cribrosa (LC), a structure within the optic nerve head (ONH) in the back of the eye. Evidence suggests that these deformations trigger events that eventually cause irreversible blindness, and have therefore been studied in-vivo using optical coherence tomography (OCT), and ex-vivo using OCT and a diversity of techniques. To the best of our knowledge, there have been no in-situ ex-vivo studies of LC mechanics. Our goal was two-fold: to introduce a technique for measuring 3D LC deformations from OCT, and to determine whether deformations of the LC induced by elevated IOP differ between in-vivo and in-situ ex-vivo conditions. A healthy adult rhesus macaque monkey was anesthetized and IOP was controlled by inserting a 27- gauge needle into the anterior chamber of the eye. Spectral domain OCT was used to obtain volumetric scans of the ONH at normal and elevated IOPs. To improve the visibility of the LC microstructure the scans were first processed using a novel denoising technique. Zero-normalized cross-correlation was used to find paired corresponding locations between images. For each location pair, the components of the 3D strain tensor were determined using non-rigid image registration. A mild IOP elevation from 10 to 15mmHg caused LC effective strains as large as 3%, and about 50% larger in-vivo than in-situ ex-vivo. The deformations were highly heterogeneous, with substantial 3D components, suggesting that accurate measurement of LC microstructure deformation requires high-resolution volumes. This technique will help improve understanding of LC biomechanics and how IOP contributes to glaucoma.

Vision problems

MedlinePlus

... shade or curtain hanging across part of your visual field. Optic neuritis : inflammation of the optic nerve ... to ask your doctor Images Crossed eyes Eye Visual acuity test Slit-lamp exam Visual field test ...

Automatic segmentation of the optic nerve head for deformation measurements in video rate optical coherence tomography

NASA Astrophysics Data System (ADS)

Hidalgo-Aguirre, Maribel; Gitelman, Julian; Lesk, Mark Richard; Costantino, Santiago

2015-11-01

Optical coherence tomography (OCT) imaging has become a standard diagnostic tool in ophthalmology, providing essential information associated with various eye diseases. In order to investigate the dynamics of the ocular fundus, we present a simple and accurate automated algorithm to segment the inner limiting membrane in video-rate optic nerve head spectral domain (SD) OCT images. The method is based on morphological operations including a two-step contrast enhancement technique, proving to be very robust when dealing with low signal-to-noise ratio images and pathological eyes. An analysis algorithm was also developed to measure neuroretinal tissue deformation from the segmented retinal profiles. The performance of the algorithm is demonstrated, and deformation results are presented for healthy and glaucomatous eyes.

Two cases of bilateral amiodarone-associated optic neuropathy.

PubMed

Chassang, B; Bonnin, N; Moisset, X; Citron, B; Clavelou, P; Chiambaretta, F

2014-03-01

The widespread use of amiodarone is limited by its toxicity, notably to the optic nerve. We report two cases of bilateral optic nerve neuropathy due to amiodarone, and provide a detailed description of the disease. The first case was a 59-year-old man complaining from insidious monocular loss of vision within ten months of initiating amiodarone. Funduscopy and optical coherence tomography showed bilateral optic disc edema. The second case was a 72-year-old man presenting with a decrease in visual acuity in his left eye for a month. Funduscopy showed a left optic nerve edema, and fluorescein angiography showed bilateral papillitis. In both cases, the clinical presentation was not suggestive of ischemic neuropathy, because of the preservation of visual acuity and the insidious onset. In addition, both cardiovascular and inflammatory work-up were normal. An amiodarone-associated neuropathy was suspected, and amiodarone was discontinued with the approval of the cardiologist, with complete regression of the papilledema and a stabilization of visual symptoms. Differentiating between amiodarone-associated optic neuropathy and anterior ischemic optic neuropathy may be complicated by the cardiovascular background of such patients. The major criterion is the absence of a severe decrease in visual acuity; other criteria are the normality of cardiovascular and inflammatory work-up, and the improvement or the absence of worsening of symptoms after discontinuation of amiodarone. Amiodarone-associated neuropathy remains a diagnosis of exclusion, and requires amiodarone discontinuation, which can only be done with the approval of a cardiologist, and sometimes requires replacement therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Evaluation of retinal nerve fiber layer thickness profile in thyroid ophthalmopathy without optic nerve dysfunction

PubMed Central

Mugdha, Kumari; Kaur, Apjit; Sinha, Neha; Saxena, Sandeep

2016-01-01

AIM To evaluate retinal nerve fiber layer (RNFL) thickness profile in patients of thyroid ophthalmopathy with no clinical signs of optic nerve dysfunction. METHODS A prospective, case-control, observational study conducted at a tertiary care centre. Inclusion criteria consisted of patients with eyelid retraction in association with any one of: biochemical thyroid dysfunction, exophthalmos, or extraocular muscle involvement; or thyroid dysfunction in association with either exophthalmos or extra-ocular muscle involvement; or a clinical activity score (CAS)>3/7. Two measurements of RNFL thickness were done for each eye, by Cirrus HD-optical coherence tomography 6mo apart. RESULTS Mean age of the sample was 38.75y (range 13-70y) with 18 males and 22 females. Average RNFL thickness at first visit was 92.06±12.44 µm, significantly lower than control group (101.28±6.64 µm) (P=0.0001). Thickness of inferior quadrant decreased from 118.2±21.27 µm to 115.0±22.27 µm after 6mo (P=0.02). There was no correlation between the change in CAS and RNFL thickness. CONCLUSION Decreased RNFL thickness is an important feature of thyroid orbitopathy, which is an inherent outcome of compressive optic neuropathy of any etiology. Subclinical RNFL damage continues in the absence of clinical activity of the disease. RNFL evaluation is essential in Grave's disease and active intervention may be warranted in the presence of significant damage. PMID:27990368

Viral vector-mediated downregulation of RhoA increases survival and axonal regeneration of retinal ganglion cells

PubMed Central

Koch, Jan Christoph; Tönges, Lars; Michel, Uwe; Bähr, Mathias; Lingor, Paul

2014-01-01

The Rho/ROCK pathway is a promising therapeutic target in neurodegenerative and neurotraumatic diseases. Pharmacological inhibition of various pathway members has been shown to promote neuronal regeneration and survival. However, because pharmacological inhibitors are inherently limited in their specificity, shRNA-mediated approaches can add more information on the function of each single kinase involved. Thus, we generated adeno-associated viral vectors (AAV) to specifically downregulate Ras homologous member A (RhoA) via shRNA. We found that specific knockdown of RhoA promoted neurite outgrowth of retinal ganglion cells (RGC) grown on the inhibitory substrate chondroitin sulfate proteoglycan (CSPG) as well as neurite regeneration of primary midbrain neurons (PMN) after scratch lesion. In the rat optic nerve crush (ONC) model in vivo, downregulation of RhoA significantly enhanced axonal regeneration compared to control. Moreover, survival of RGC transduced with AAV expressing RhoA-shRNA was substantially increased at 2 weeks after optic nerve axotomy. Compared to previous data using pharmacological inhibitors to target RhoA, its upstream regulator Nogo or its main downstream target ROCK, the specific effects of RhoA downregulation shown here were most pronounced in regard to promoting RGC survival but neurite outgrowth and axonal regeneration were also increased significantly. Taken together, we show here that specific knockdown of RhoA substantially increases neuronal survival after optic nerve axotomy and modestly increases neurite outgrowth in vitro and axonal regeneration after optic nerve crush. PMID:25249936

'Green mice' display limitations in enhanced green fluorescent protein expression in retina and optic nerve cells.

PubMed

Caminos, Elena; Vaquero, Cecilia F; García-Olmo, Dolores C

2014-12-01

Characterization of retinal cells, cell transplants and gene therapies may be helped by pre-labeled retinal cells, such as those transfected with vectors for green fluorescent protein expression. The aim of this study was to analyze retinal cells and optic nerve components from transgenic green mice (GM) with the 'enhanced' green fluorescent protein (EGFP) gene under the control of the CAG promoter (a chicken β-actin promoter and a cytomegalovirus enhancer). The structural analysis and electroretinography recordings showed a normal, healthy retina. Surprisingly, EGFP expression was not ubiquitously located in the retina and optic nerve. Epithelial cells, photoreceptors and bipolar cells presented high green fluorescence levels. In contrast, horizontal cells, specific amacrine cells and ganglion cells exhibited a null EGFP expression level. The synaptic terminals of rod bipolar cells displayed a high green fluorescence level when animals were kept in the dark. Immature retinas exhibited different EGFP expression patterns to those noted in adults. Axons and glial cells in the optic nerve revealed a specific regional EGFP expression pattern, which correlated with the presence of myelin. These results suggest that EGFP expression might be related to the activity of both the CAG promoter and β-actin in mature retinal neurons and oligodendrocytes. Moreover, EGFP expression might be regulated by light in both immature and adult animals. Since GM are used in numerous retina bioassays, it is essential to know the differential EGFP expression in order to select cells of interest for each study.

Influence of corneal power on circumpapillary retinal nerve fiber layer and optic nerve head measurements by spectral-domain optical coherence tomography.

PubMed

Hirasawa, Kazunori; Shoji, Nobuyuki

2017-01-01

To evaluate the influence of corneal power on circumpapillary retinal nerve fiber layer (cpRNFL) and optic nerve head (ONH) measurements by spectral-domain optical coherence tomography (SD-OCT). Twenty-five eyes of 25 healthy participants (mean age 23.6±3.6y) were imaged by SD-OCT using horizontal raster scans. Disposable soft contact lenses of different powers (from -11 to +5 diopters including 0 diopter) were worn to induce 2-diopter changes in corneal power. Differences in the cpRNFL and ONH measurements per diopter of change in corneal power were analyzed. As corneal power increased by 1 diopter, total and quadrant cpRNFL thicknesses, except for the nasal sector, decreased by --0.19 to -0.32 µm ( P <0.01). Furthermore, the disc, cup, and rim areas decreased by -0.017, -0.007, and -0.015 mm 2 , respectively ( P <0.001); the cup and rim volumes decreased by -0.0013 and -0.006 mm 3 , respectively ( P <0.01); and the vertical and horizontal disc diameters decreased by -0.006 and -0.007 mm, respectively ( P <0.001). For more precise OCT imaging, the ocular magnification should be corrected by considering both the axial length and corneal power. However, the effect of corneal power changes on cpRNFL thickness and ONH topography are small when compare with those of the axial length.

Adenosine receptor distribution in Rhesus monkey ocular tissue.

PubMed

Beach, Krista M; Hung, Li-Fang; Arumugam, Baskar; Smith, Earl L; Ostrin, Lisa A

2018-05-21

Adenosine receptor (ADOR) antagonists, such as 7-methylxanthine (7-MX), have been shown to slow myopia progression in humans and animal models. Adenosine receptors are found throughout the body, and regulate the release of neurotransmitters such as dopamine and glutamate. However, the role of adenosine in eye growth is unclear. Evidence suggests that 7-MX increases scleral collagen fibril diameter, hence preventing axial elongation. This study used immunohistochemistry (IHC) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) to examine the distribution of the four ADORs in the normal monkey eye to help elucidate potential mechanisms of action. Eyes were enucleated from six Rhesus monkeys. Anterior segments and eyecups were separated into components and flash-frozen for RNA extraction or fixed in 4% paraformaldehyde and processed for immunohistochemistry against ADORA1, ADORA2a, ADORA2b, and ADORA3. RNA was reverse-transcribed, and qPCR was performed using custom primers. Relative gene expression was calculated using the ΔΔCt method normalizing to liver expression, and statistical analysis was performed using Relative Expression Software Tool. ADORA1 immunostaining was highest in the iris sphincter muscle, trabecular meshwork, ciliary epithelium, and retinal nerve fiber layer. ADORA2a immunostaining was highest in the corneal epithelium, trabecular meshwork, ciliary epithelium, retinal nerve fiber layer, and scleral fibroblasts. ADORA2b immunostaining was highest in corneal basal epithelium, limbal stem cells, iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells and scattered scleral fibroblasts. ADORA3 immunostaining was highest in the iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells, and scleral fibroblasts. Compared to liver mRNA, ADORA1 mRNA was significantly higher in the brain, retina and choroid, and significantly lower in the iris/ciliary body. ADORA2a expression was higher in brain and retina, ADORA2b expression was higher in retina, and ADORA3 was higher in the choroid. In conclusion, immunohistochemistry and RT-qPCR indicated differential patterns of expression of the four adenosine receptors in the ocular tissues of the normal non-human primate. The presence of ADORs in scleral fibroblasts and the choroid may support mechanisms by which ADOR antagonists prevent myopia. The potential effects of ADOR inhibition on both anterior and posterior ocular structures warrant investigation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Glioma

MedlinePlus

... cells are called mixed gliomas. Tumors such as “optic nerve glioma” and “brain stem glioma” are named ... Oligodendroglioma: Click here to learn more about oligodendroglioma. Optic Glioma: These tumors may involve any part of ...

Incorporation of fiber optic beam shaping into a laparoscopic probe for laser stimulation of the cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Lagoda, Gwen A.; Mayeh, Mona; Burnett, Arthur L.; Farahi, Faramarz; Fried, Nathaniel M.

2010-02-01

The cavernous nerves (CN) course along the prostate surface and are responsible for erectile function. Improved identification and preservation of the CN's is critical to maintaining sexual potency after prostate cancer surgery. Noncontact optical nerve stimulation (ONS) of the CN's was recently demonstrated in a rat model, in vivo, as a potential alternative to electrical nerve stimulation (ENS) for identification of the CN's during prostate surgery. However, the therapeutic window for ONS is narrow, so optimal design of the fiber optic delivery system is critical for safe, reproducible stimulation. This study describes modeling, assembly, and testing of an ONS probe for delivering a small, collimated, flat-top laser beam for uniform CN stimulation. A direct comparison of the magnitude and response time of the intracavernosal pressure (ICP) for both Gaussian and flat-top spatial beam profiles was performed. Thulium fiber laser radiation (λ=1870 nm) was delivered through a 200-μm fiber, with distal fiber tip chemically etched to convert a Gaussian to flat-top beam profile. The laser beam was collimated to a 1-mm-diameter spot using an aspheric lens. Computer simulations of light propagation were used to optimize the probe design. The 10-Fr (3.4-mm-OD) laparoscopic probe provided a constant radiant exposure at the nerve surface. The probe was tested in four rats, in vivo. ONS of the CN's was performed with a 1-mm-diameter spot, 5- ms pulse duration, and pulse rate of 20 Hz for a duration of 15-30 s. The flat-top laser beam profile consistently produced a faster and higher ICP response at a lower radiant exposure than the Gaussian beam profile due, in part, to easier alignment of the more uniform beam with nerve. With further development, ONS may be used as a diagnostic tool for identification of the CN's during laparoscopic and robotic nerve-sparing prostate cancer surgery.

Lamina cribrosa position and Bruch's membrane opening differences between anterior ischemic optic neuropathy and open-angle glaucoma.

PubMed

Rebolleda, Gema; Pérez-Sarriegui, Ane; Díez-Álvarez, Laura; De Juan, Victoria; Muñoz-Negrete, Francisco J

2018-06-01

To compare the optic nerve head morphology among primary open-angle glaucoma, non-arteritic anterior ischemic optic neuropathy eyes, their fellow healthy eyes and control eyes, using spectral-domain optical coherence tomography with enhanced depth imaging. Observational cross-sectional study including 88 eyes of 68 patients. In this study, 23 non-arteritic anterior ischemic optic neuropathy eyes, 17 fellow unaffected eyes, 25 primary open-angle glaucoma eyes, and 23 age-matched control eyes were included. Peripapillary retinal nerve fiber layer thickness and optic disk area were evaluated. Bruch's membrane opening diameter, optic cup depth, anterior lamina cribrosa depth, and prelaminar tissue thickness were assessed. Non-arteritic anterior ischemic optic neuropathy and primary open-angle glaucoma eyes had similar visual field mean deviation and peripapillary retinal nerve fiber layer thickness (P = 0.6 and P = 0.56, respectively). Bruch's membrane opening diameter was significantly larger in primary open-angle glaucoma eyes than in control eyes (P = 0.02). Lamina cribrosa and disk cup were deeper in eyes with primary open-angle glaucoma than both control and non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Prelaminar tissue thickness was significantly thinner in primary open-angle glaucoma eyes than in non-arteritic anterior ischemic optic neuropathy eyes (P < 0.001). Lamina cribrosa was shallower in both non-arteritic anterior ischemic optic neuropathy and unaffected fellow eyes compared to healthy eyes (P < 0.001 and P = 0.04, respectively). No differences were found in the optic disk area. A forward lamina cribrosa placement and not a smaller disk could be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. A significantly larger Bruch's membrane opening diameter was found in primary open-angle glaucoma eyes compared with control eyes. This issue has clinical implications because Bruch's membrane opening has been considered a stable reference for disk-related measures.

[Magnetic resonance imaging features in two Chinese family with congenital fibrosis of extraocular muscles].

PubMed

Wu, Li; Zhou, Lian-Hong; Liu, Chang-Sheng; Cha, Yun-Fei; Wang, Jiong; Xing, Yi-Qiao

2009-11-01

The aim of this article was to investigate the structural basis of ocular motility and visual abnormalities in humans with congenital fibrosis of the extraocular muscles (CFEOM). 17 volunteers from 2 CFEOM pedigrees Clinical ophthalmic and motility examed and 18 normal control subjects were correlated with thin-sectioned magnetic resonance imaging (MRI) across the orbit and the brain-stem level. Subjects with CFEOM had severe bilateral blepharoptosis, limited supraduction, and variable ophthalmoplegia. In affected subjects, MRI demonstrated atrophy of the levator palpebrae superioris, all EOMs, and the optic nerves, and small or absent orbital motor nerves. The oculomotor nerve was most severely hypoplastic, but the abducens was also affected. Subjects with CFEOM exhibited subclinical but highly significant reduction from normal in mean optic nerve size (P < 0.05). There are also some difference between the two CFEOM pedigrees. These findings suggest that neuronal disease is primary in CFEOM, with myopathy arising secondary to abnormal innervation and the oculomotor nucleus and trochlear nucleus of the abnormalities defects.

Nerve fibre layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis.

PubMed

Della Mea, Giovanni; Bacchetti, Sonia; Zeppieri, Marco; Brusini, Paolo; Cutuli, Daniela; Gigli, Gian Luigi

2007-01-01

To evaluate the ability of GDx with variable corneal compensator (VCC) compared to visual-evoked potentials (VEPs) and standard automated perimetry (SAP) in the detection of early optic nerve damage in patients with multiple sclerosis (MS). 46 eyes of 23 MS patients were included. Ten of them had a history of acute retrobulbar optic neuritis. A control group of 20 normal subjects was also included. All subjects underwent a complete ophthalmological examination and testing with SAP, GDx VCC and VEPs. 19 eyes (41.3%) were abnormal with GDx VCC compared to 38 eyes (82.6%) with SAP and 31 (64.4%) with VEPs. In the optic neuritis group, 9 eyes (69.2%) had optic nerve pallor; SAP was abnormal in 8 of these eyes (61.5%) while VEPs and GDx VCC were abnormal in 6 eyes (46.1%). 2/20 eyes (10.0%) in the control group gave a false-positive abnormal result with SAP. GDx VCC and VEP were normal for all the eyes in the control group. GDx VCC is less able to detect early defects in MS patients compared to the currently used standard techniques of SAP and VEPs. Copyright (c) 2007 S. Karger AG, Basel.

Challenges in the management of glaucoma in developing countries.

PubMed

Butt, Nadeem Hafeez; Ayub, Muhammad Hammad; Ali, Muhammad Hassaan

2016-01-01

Glaucoma is the most common optic neuropathy characterized by normal to raised intraocular pressure (IOP), visual field defects, loss of retinal nerve fiber layer, thinning of the neuroretinal rim, and cupping of the optic disc. IOP reduction by medical, laser, or surgical therapies remains the only clinically proven treatment of glaucoma. The challenges in glaucoma management are diverse. They include early detection and diagnosis, setting of appropriate target IOP, choice of treatment, monitoring of quality of life and sight, and compliance with the treatment. Early diagnosis can be made by assessing optic nerve structure using imaging devices and optic nerve function through perimetry. Reducing IOP and controlling its fluctuations are considered to be the most important factors in limiting progression of glaucoma. Selection of the best suitable therapy out of medical, surgical, or laser treatment options is yet another management challenge. Patients suffering from glaucoma experience poor quality of life owing to the diagnosis itself, functional visual loss, inconvenience and cost of treatment, and side effects of treatment. All these factors lead to poor compliance, adherence, and persistence to treatment, and further progression of the disease. It is, therefore, important that ophthalmologists keep all the aforementioned factors in mind when managing patients with glaucoma.

Evaluation of Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Primary Craniopharyngioma by Fourier-Domain Optical Coherence Tomography.

PubMed

Yang, Liu; Qu, Yuanzhen; Lu, Wen; Liu, Fengjun

2016-07-03

BACKGROUND The aim of this study was to compare the differences in macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) in child and adult patients with primary craniopharyngioma by Fourier-domain optical coherence tomography (FD-OCT) and to evaluate their significance in the diagnosis of primary craniopharyngioma. MATERIAL AND METHODS Ninety-six participants were divided into 3 groups: 32 in the child craniopharyngioma group (CCG) and 32 in the adult craniopharyngioma group (ACG) who were treated in Beijing Tiantan Hospital between November 2013 and October 2014, and 32 in the normal group (NG). All subjects were scanned by FD-OCT to map GCC and pRNFL thicknesses. Spearman correlation coefficient was used to assess the correlation between GCC and pRNFL thickness, and pRNFL thickness and optic nerve head (ONH) parameters, including horizontal cup-disc ratio (HCDR), vertical cup-disc ratio (VCDR), optic disc area (ODA), and cup area (CA), respectively. RESULTS The correlation between GCC and pRNFL thickness in the CCG was slightly stronger compared with the ACG. A significant difference in GCC thickness was observed among the CCG, ACG, and NG. Although the pRNFL thickness in both the CCG and ACG was significantly higher than that in NG, no significant difference in pRNFL thickness was detected between the 2 craniopharyngioma groups. The average, superior, and inferior pRNFL thicknesses were negatively correlated with VCDR in the CCG (in double eyes) and ACG (only in left eyes). CONCLUSIONS GCC was more sensitive than pRNFL in detecting optic nerve damage in the eyes of craniopharyngioma patients. A thinner pRNFL was especially correlated with VCDR in child craniopharyngioma patients.

Evaluation of Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Primary Craniopharyngioma by Fourier-Domain Optical Coherence Tomography

PubMed Central

Yang, Liu; Qu, Yuanzhen; Lu, Wen; Liu, Fengjun

2016-01-01

Background The aim of this study was to compare the differences in macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (pRNFL) in child and adult patients with primary craniopharyngioma by Fourier-domain optical coherence tomography (FD-OCT) and to evaluate their significance in the diagnosis of primary craniopharyngioma. Material/Methods Ninety-six participants were divided into 3 groups: 32 in the child craniopharyngioma group (CCG) and 32 in the adult craniopharyngioma group (ACG) who were treated in Beijing Tiantan Hospital between November 2013 and October 2014, and 32 in the normal group (NG). All subjects were scanned by FD-OCT to map GCC and pRNFL thicknesses. Spearman correlation coefficient was used to assess the correlation between GCC and pRNFL thickness, and pRNFL thickness and optic nerve head (ONH) parameters, including horizontal cup-disc ratio (HCDR), vertical cup-disc ratio (VCDR), optic disc area (ODA), and cup area (CA), respectively. Results The correlation between GCC and pRNFL thickness in the CCG was slightly stronger compared with the ACG. A significant difference in GCC thickness was observed among the CCG, ACG, and NG. Although the pRNFL thickness in both the CCG and ACG was significantly higher than that in NG, no significant difference in pRNFL thickness was detected between the 2 craniopharyngioma groups. The average, superior, and inferior pRNFL thicknesses were negatively correlated with VCDR in the CCG (in double eyes) and ACG (only in left eyes). Conclusions GCC was more sensitive than pRNFL in detecting optic nerve damage in the eyes of craniopharyngioma patients. A thinner pRNFL was especially correlated with VCDR in child craniopharyngioma patients. PMID:27372909

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grantham, K; Santanam, L; Goddu, S

Purpose: We retrospectively evaluate the dosimetric impact of a 3.5% range uncertainty on CTV coverage and normal organ toxicity for a cohort of brain patients. Methods: Twenty treatment plans involving 20 brain cancer patients treated with Mevions S250 were reviewed. Forty uncertain plans were made by changing the ranges in original plans by ±3.5% while keeping all devices unchanged. Fidelity to the original plans was evaluated with gamma index. Changes in generalized equivalent uniform dose (gEUD) were reported for the following structures: CTV coverage, brainstem, optic chiasm, and optic nerves. Comparisons were made by plotting the relevant endpoints from themore » uncertain plans as a function of the same endpoints from the original clinical plan. Results: Gamma-index analysis resulted in a 50% pass rate of the uncertain plans using a 90% passing rate and 3%/3mm criterion. A 9.5% decrease in the slope of gEUD plot for the CTV was observed for the 3.5% downward range shift. However, the change in slope did not result in a gEUD change greater than 1.1% for the CTV. The slopes of the gEUD plots for normal structures increased by 3.1% 3.9% 2.4% and 0.2% for the chiasm, brainstem, left optic nerve and right optic nerve respectively. The maximum deviation from the gEUD of the clinical plan for normal structures was: 64% in the chiasm, 31% for the brainstem, and 19% for both optic nerves. Conclusion: A retrospective review shows moderate radiobiological impact of range uncertainty in passively scattered proton therapy with sporadic catastrophe. The linear regression analysis on the statistical data indicates a systematic deviation of gEUD from treatment planning in the light of range uncertainty.« less

Characterization of the optic disc in retinal imagery using a probabilistic approach

NASA Astrophysics Data System (ADS)

Tobin, Kenneth W., Jr.; Chaum, Edward; Govindasamy, V. P.; Karnowski, Thomas P.; Sezer, Omer

2006-03-01

The application of computer based image analysis to the diagnosis of retinal disease is rapidly becoming a reality due to the broad-based acceptance of electronic imaging devices throughout the medical community and through the collection and accumulation of large patient histories in picture archiving and communications systems. Advances in the imaging of ocular anatomy and pathology can now provide data to diagnose and quantify specific diseases such as diabetic retinopathy (DR). Visual disability and blindness have a profound socioeconomic impact upon the diabetic population and DR is the leading cause of new blindness in working-age adults in the industrialized world. To reduce the impact of diabetes on vision loss, robust automation is required to achieve productive computer-based screening of large at-risk populations at lower cost. Through this research we are developing automation methods for locating and characterizing important structures in the human retina such as the vascular arcades, optic nerve, macula, and lesions. In this paper we present results for the automatic detection of the optic nerve using digital red-free fundus photography. Our method relies on the accurate segmentation of the vasculature of the retina along with spatial probability distributions describing the luminance across the retina and the density, average thickness, and average orientation of the vasculature in relation to the position of the optic nerve. With these features and other prior knowledge, we predict the location of the optic nerve in the retina using a two-class, Bayesian classifier. We report 81% detection performance on a broad range of red-free fundus images representing a population of over 345 patients with 19 different pathologies associated with DR.

Comparison of peripapillary retinal nerve fiber layer loss and visual outcome in fellow eyes following sequential bilateral non-arteritic anterior ischemic optic neuropathy.

PubMed

Dotan, Gad; Kesler, Anat; Naftaliev, Elvira; Skarf, Barry

2015-05-01

To report on the correlation of structural damage to the axons of the optic nerve and visual outcome following bilateral non-arteritic anterior ischemic optic neuropathy. A retrospective review of the medical records of 25 patients with bilateral sequential non-arteritic anterior ischemic optic neuropathy was performed. Outcome measures were peripapillary retinal nerve fiber layer thickness measured with the Stratus optical coherence tomography scanner, visual acuity and visual field loss. Median peripapillary retinal nerve fiber layer (RNFL) thickness, mean deviation (MD) of visual field, and visual acuity of initially involved NAION eyes (54.00 µm, -17.77 decibels (dB), 0.4, respectively) were comparable to the same parameters measured following development of second NAION event in the other eye (53.70 µm, p = 0.740; -16.83 dB, p = 0.692; 0.4, p = 0.942, respectively). In patients with bilateral NAION, there was a significant correlation of peripapillary RNFL thickness (r = 0.583, p = 0.002) and MD of the visual field (r = 0.457, p = 0.042) for the pairs of affected eyes, whereas a poor correlation was found in visual acuity of these eyes (r = 0.279, p = 0.176). Peripapillary RNFL thickness following NAION was positively correlated with MD of visual field (r = 0.312, p = 0.043) and negatively correlated with logMAR visual acuity (r = -0.365, p = 0.009). In patients who experience bilateral NAION, the magnitude of RNFL loss is similar in each eye. There is a greater similarity in visual field loss than in visual acuity between the two affected eyes with NAION of the same individual.

Melanopsin retinal ganglion cell loss in Alzheimer disease

PubMed Central

Ross‐Cisneros, Fred N.; Koronyo, Yosef; Hannibal, Jens; Gallassi, Roberto; Cantalupo, Gaetano; Sambati, Luisa; Pan, Billy X.; Tozer, Kevin R.; Barboni, Piero; Provini, Federica; Avanzini, Pietro; Carbonelli, Michele; Pelosi, Annalisa; Chui, Helena; Liguori, Rocco; Baruzzi, Agostino; Koronyo‐Hamaoui, Maya; Sadun, Alfredo A.; Carelli, Valerio

2015-01-01

Objective Melanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction. Methods We assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls. Results We demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs. Interpretation We show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109 PMID:26505992

Pathophysiology of blast-induced ocular trauma in rats after repeated exposure to low-level blast overpressure.

PubMed

Choi, Jae Hyek; Greene, Whitney A; Johnson, Anthony J; Chavko, Mikulas; Cleland, Jeffery M; McCarron, Richard M; Wang, Heuy-Ching

2015-04-01

The incidence of blast-induced ocular injury has dramatically increased due to advances in weaponry and military tactics. A single exposure to blast overpressure (BOP) has been shown to cause damage to the eye in animal models; however, on the battlefield, military personnel are exposed to BOP multiple times. The effects of repeated exposures to BOP on ocular tissues have not been investigated. The purpose of this study is to characterize the effects of single or repeated exposure on ocular tissues. A compressed air shock tube was used to deliver 70 ± 7 KPa BOP to rats, once (single blast overpressure [SBOP]) or once daily for 5 days (repeated blast overpressure [RBOP]). Immunohistochemistry was performed to characterize the pathophysiology of ocular injuries induced by SBOP and RBOP. Apoptosis was determined by quantification activated caspase 3. Gliosis was examined by detection of glial fibrillary acidic protein (GFAP). Inflammation was examined by detection of CD68. Activated caspase 3 was detected in ocular tissues from all animals subjected to BOP, while those exposed to RBOP had more activated caspase 3 in the optic nerve than those exposed to SBOP. GFAP was detected in the retinas from all animals subjected to BOP. CD68 was detected in optic nerves from all animals exposed to BOP. SBOP and RBOP induced retinal damage. RBOP caused more apoptosis in the optic nerve than SBOP, suggesting that RBOP causes more severe optic neuropathy than SBOP. SBOP and RBOP caused gliosis in the retina and increased inflammation in the optic nerve. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Comparison of Laser Scanning Diagnostic Devices for Early Glaucoma Detection.

PubMed

Schulze, Andreas; Lamparter, Julia; Pfeiffer, Norbert; Berisha, Fatmire; Schmidtmann, Irene; Hoffmann, Esther M

2015-08-01

To compare the diagnostic accuracy and to evaluate the correlation of optic nerve head and retinal nerve fiber layer thickness values between Fourier-Domain optical coherence tomography (FD-OCT), confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) for early glaucoma detection. Ninety-three patients with early open-angle glaucoma, 58 patients with ocular hypertension, and 60 healthy control subjects were included in this observational, cross-sectional study. All study participants underwent FD-OCT (RTVue-100), CSLO (HRT3), and SLP (GDx VCC) imaging of the optic nerve head and the retinal nerve fiber layer. Area under the receiver operating characteristic curves (AUROC) and Bland-Altman analysis were performed. The parameters with the highest diagnostic accuracy were found for FD-OCT cup-to-disc ratio (AUROC=0.841), for SLP NFI (AUROC=0.835), and for CSLO cup-to-disc ratio (AUROC=0.789). Diagnostic accuracy of the best CSLO and SLP parameter was similar (P=0.259). There was a small statistically significant difference between the best CSLO and FD-OCT parameters for differentiating between glaucoma and healthy eyes (P=0.047). FD-OCT and SLP have a similarly good diagnostic ability to distinguish between early glaucoma and healthy subjects. The diagnostic accuracy of CSLO was comparable with SLP and marginally lower compared with FD-OCT.

Cloning and characteristics of fish glial fibrillary acidic protein: implications for optic nerve regeneration.

PubMed

Cohen, I; Shani, Y; Schwartz, M

1993-08-15

Mammalian central nervous system neurons do not regenerate after axonal injury, unlike their counterparts in fish and amphibians. After axonal injury, glial cells in mammals do not support regrowth of axons, while in fish they support the regeneration process. Controversy exists as to whether or not the intact fish optic nerve expresses glial fibrillary acidic protein, a well-known marker for mature astrocytes, and thus whether its astrocytes differ in this respect from those of the brain and spinal cord, as well as from optic nerve astrocytes of other species. In an attempt to resolve this question we cloned fish glial fibrillary acidic protein. Two different complementary DNA clones were isolated from a carp brain complementary DNA library, each encoding a different form of glial fibrillary acidic protein apparently originating from different genes. Monospecific polyclonal antibodies were raised against a peptide synthesized according to the predicted amino acid sequence, and used to identify and localize the fish glial fibrillary acidic protein. Two glial fibrillary acidic proteins (of 49 kDa and 51 kDa) were identified by the antibodies in all tested fish central nervous system tissues. The antibodies were then used to examine glial fibrillary acidic protein immunoreactivity in sections taken from uninjured and injured optic nerves of goldfish. Injury was followed by an elevation in glial fibrillary acidic protein immunoreactivity along the whole length of the nerve, except at the site of the injury, where--as in the case of vimentin--no immunoreactivity was detectable. However, in contrast to vimentin-positive glial cells, which repopulate the site of the injury soon after the optic nerve is injured, glial fibrillary acidic protein-positive glial cells remained outside the injury site for as long as 6 weeks after the injury. Despite the injury-induced changes in glial fibrillary acidic protein immunoreactivity, no change was observed in the level of transcript encoding glial fibrillary acidic protein after injury, while there was an increase in the amount of glial fibrillary acidic protein associated with the cytoskeleton and a reduction in the soluble form. These results suggest that the injury-induced changes in immunoreactivity on sections involve changes not in transcription or translation of glial fibrillary acidic protein, but in glial fibrillary acidic protein compartmentalization.

Expression of Inducible Heat Shock Proteins Hsp27 and Hsp70 in the Visual Pathway of Rats Subjected to Various Models of Retinal Ganglion Cell Injury

PubMed Central

Chidlow, Glyn; Wood, John P. M.; Casson, Robert J.

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and −70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and −70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration. PMID:25535743

Molecular Solutions to Low Vision Resulting from Battlefield Injuries

DTIC Science & Technology

2006-05-01

promote optic nerve regeneration; (5) dry eye bydetermining how to minimize dry eye after LASIK refractive surgery by developing new tests to predict...Nerve Loss in LASIK Surgery, Invest. Ophthalmol. Vis. Sci. 2006 47: E-Abstract 4600. CONCLUSIONS We conclude that in the normal mouse conjunctiva, the...Mimicking Nerve Loss in LASIK Surgery, Invest. Ophthalmol. Vis. Sci. 2006 47: E-Abstract 4600. Services Email this article to a friend Similar articles in