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Abstract In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision. [ABSTRACT FROM AUTHOR]

Background: Imaging assessment of the anterior visual pathway structures, particularly the optic nerves (ON), requires knowledge of normal dimensions. Several studies suggesting techniques and normal ranges have been performed, but most suffer from various methodological flaws. This study is the first to be performed in a South African population. Objectives: The aim of this study was to establish normal measurements of the ON, optic nerve sheath (ONS) and optic chiasm (OC) on magnetic resonance imaging (MRI). Method: Eighty normal adults between ages of 12 and 65 years were included in this prospective, quantitative, observational, descriptive study to establish normal measurement of the ON, ONS and OC using a T2W 3D MRI sequence. Measurements (width and height) were undertaken by two observers independently. Results: A total of 80 participants with a mean age of 35 years were studied: 49 females (61.25%) and 31 males (38.75%). There were no statistical differences in the measurements between gender and age correlation. Interobserver agreement was best for larger structures, that is, OC width and intracranial ON width, respectively. The overall mean of OC width was 13.63 mm (range: 11.13 mm–16.92 mm, standard deviation [s.d.] 1.21); intraorbital ON height at 5 mm behind the globe 2.29 mm (range: 1.63 mm–3.33 mm, s.d. 0.43), and intracranial ON width 4.27 mm (range: 2.46 mm–5.19 mm, s.d. 0.53). Conclusion: Normal measurements of the anterior visual pathway structures on MRI are best reflected in the larger structures. Interobserver variability was poor for the orbital ON, ONS, intracranial ON height and OC height. We recommend that measurements be obtained for the OC width and intracranial ON width. The overall mean for the OC width is 13.63 mm and intracranial ON width 4.27 mm. [ABSTRACT FROM AUTHOR]

We investigated the diagnostic ability of a new criterion (simple temporal depression) for compressive lesions of the optic chiasm. The subjects were 124 eyes with compressive lesions of the optic chiasm. The controls were 84 eyes. The Humphrey (Carl Zeiss) visual field test was used for visual field testing. The simple temporal depression index was calculated as the ratio of the sums of the thresholds for one line on the nasal side and temporal side of the vertical meridian. The result of new index was 87% sensitivity and 99% specificity. This result suggested that our new criterion will assist the diagnosis in the future. [ABSTRACT FROM AUTHOR]

Highlights • p75NTR was detected in retinal ganglion cells and their axons during the time of axon growth in the optic chiasm. • Lingo-1 was observed in RGC but not on axons at the optic disk, and was localized on axons along the optic pathway. • Lingo-1 also showed a glial localization at the optic disc and a neuronal localization in chiasmatic neurons. Abstract Our previous studies showed interaction of Nogo at the midline with its receptor (NgR) on optic axons plays a role in axon divergence at the mouse optic chiasm. Since NgR lacks a cytoplasmic domain, it needs transmembrane receptor partners for signal transduction. In this study, we examined whether the co-receptors of NgR, low-affinity neurotrophic receptor (p75NTR) and Lingo-1, are localized on axons in the mouse optic pathway. In the retina, p75NTR and Lingo-1 were observed on neuroepithelial cells at E13 and later on the retinal ganglion cells at E14 and E15. At the optic disc, p75NTR was observed on the retinal axons, whereas Lingo-1 was found on glial processes surrounding the axon fascicles. Both p75NTR and Lingo-1 were found on axons in the optic stalk, optic chiasm and optic tract. Furthermore, a transient expression of Lingo-1 was observed on the SSEA-1 positive chiasmatic neurons at E13, but not at later developmental stages. The presence of p75NTR and Lingo-1 on optic axons provides further supports to the contribution of Nogo/NgR signaling in axon divergence at the mouse optic chiasm. [ABSTRACT FROM AUTHOR]

70%-80% of our sensory input comes from vision. Light hit the retina at the back of our eyes and the visual information is relayed into the dorsal lateral geniculate nuclei (dLGN) and primary visual cortex (V1) thereafter, constituting the image-forming visual circuit. Molecular cues are one of the key factors to guide the wiring and refinement of the image-forming visual circuit during pre- and post-embryonic stages. Distinct molecular cues are involved in different developmental stages and nucleus, suggesting diverse guidance mechanisms. In this review, we summarize molecular guidance cues throughout the image-forming visual circuit, including chiasm determination, eye-specific segregation and refinement in the dLGN, and at last the reciprocal connections between the dLGN and V1. [ABSTRACT FROM AUTHOR]

Abstract In the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC axons in vivo , but the role of extracellular matrix molecules in this process remains poorly understood. Dystroglycan is a laminin-binding transmembrane protein important for formation and maintenance of the extracellular matrix and basement membranes and has previously been implicated in axon guidance in the developing spinal cord. Using two genetic models of functional dystroglycan loss, we show that dystroglycan is necessary for correct sorting of contralateral and ipsilateral RGC axons at the optic chiasm. Mis-sorted axons still target retinorecipient brain regions and persist in adult mice, even after axon pruning is complete. Our results highlight the importance of the extracellular matrix for axon sorting at an intermediate choice point in the developing visual circuit. Highlights • Dystroglycan is required for maintaining the basement membrane in the optic chiasm. • Axons stall and sort inappropriately at the optic chiasm in Dystroglycan mutants. • Retinorecipient areas receive increased innervation from the ipsilateral retina. • Inappropriate ipsilateral innervation persists through adulthood. [ABSTRACT FROM AUTHOR]

Purpose: Intensity modulated radiation therapy (IMRT) is commonly employed for treating head and neck (H&N) cancer with uniform tumor dose and conformal critical organ sparing. Accurate delineation of organs‐at‐risk (OARs) on H&N CT images is thus essential to treatment quality. Manual contouring used in current clinical practice is tedious, time‐consuming, and can produce inconsistent results. Existing automated segmentation methods are challenged by the substantial inter‐patient anatomical variation and low CT soft tissue contrast. To overcome the challenges, we developed a novel automated H&N OARs segmentation method that combines a fully convolutional neural network (FCNN) with a shape representation model (SRM). Methods: Based on manually segmented H&N CT, the SRM and FCNN were trained in two steps: (a) SRM learned the latent shape representation of H&N OARs from the training dataset; (b) the pre‐trained SRM with fixed parameters were used to constrain the FCNN training. The combined segmentation network was then used to delineate nine OARs including the brainstem, optic chiasm, mandible, optical nerves, parotids, and submandibular glands on unseen H&N CT images. Twenty‐two and 10 H&N CT scans provided by the Public Domain Database for Computational Anatomy (PDDCA) were utilized for training and validation, respectively. Dice similarity coefficient (DSC), positive predictive value (PPV), sensitivity (SEN), average surface distance (ASD), and 95% maximum surface distance (95%SD) were calculated to quantitatively evaluate the segmentation accuracy of the proposed method. The proposed method was compared with an active appearance model that won the 2015 MICCAI H&N Segmentation Grand Challenge based on the same dataset, an atlas method and a deep learning method based on different patient datasets. Results: An average DSC = 0.870 (brainstem), DSC = 0.583 (optic chiasm), DSC = 0.937 (mandible), DSC = 0.653 (left optic nerve), DSC = 0.689 (right optic nerve), DSC = 0.835 (left parotid), DSC = 0.832 (right parotid), DSC = 0.755 (left submandibular), and DSC = 0.813 (right submandibular) were achieved. The segmentation results are consistently superior to the results of atlas and statistical shape based methods as well as a patch‐wise convolutional neural network method. Once the networks are trained off‐line, the average time to segment all 9 OARs for an unseen CT scan is 9.5 s. Conclusion: Experiments on clinical datasets of H&N patients demonstrated the effectiveness of the proposed deep neural network segmentation method for multi‐organ segmentation on volumetric CT scans. The accuracy and robustness of the segmentation were further increased by incorporating shape priors using SMR. The proposed method showed competitive performance and took shorter time to segment multiple organs in comparison to state of the art methods. [ABSTRACT FROM AUTHOR]

In patients with pituitary adenomas (PA) who are unable to undergo complete surgical resection, radiation therapy (RT), specifically stereotactic radiosurgery (SRS), results in excellent local control. However, the utility of radiosurgery may be limited by the proximity of the lesion to the optic chiasm (OC). We evaluate the efficacy of debulking surgery in increasing the PA-OC separation to convert patients into SRS candidates. From 2007 to 2015, 31 patients with PA < 2 mm from the OC underwent debulking surgery followed by RT within 2 years of resection. Coronal and sagittal T1-pre- and post-contrast sequences were used to determine PA-OC separation. Time interval between postoperative and pre-radiotherapy MRI scans and type of radiation therapy were analyzed. Functional tumor status, tumor characteristics [cavernous sinus (CS) or suprasellar (SS) involvement, chiasm/nerve encasement (NE)], and presence of ≥ 2 of these characteristics (multiple factors, MF) was also noted. Surgery converted 9 of 31 patients (29%) to SRS candidates. Median time from surgery to pre-RT planning MRI was 8 months (range 2-20). Of the 31 patients initially ineligible for SRS, 6 became eligible immediately after surgery, and another 3 were deemed eligible on follow-up. Mean PA-OC separation was 0.3 mm preoperative, 1.4 mm postoperative, and 2.1 mm at time of SRS (p = 0.002). Preoperative SS, NE, and MF involvement predicted pre-RT separation < 2 mm. Debulking surgery of unresectable pituitary tumors is a successful strategy for converting select radiosurgery-ineligible patients to radiosurgery candidates. Absence of preoperative SS, NE, and MF predicts for successful conversion. [ABSTRACT FROM AUTHOR]

Although the beneficial effects of quercetin on oligodendrocyte precursor cell (OPCs) population has been evaluated in-vitro, there are few studies about the effects of quercetin on myelin repair in the context of demyelination. The aim of this study was to investigate the effects of querectin on functional recovery and myelin repair of optic chiasm in lysolecithin (LPC)-induced demyelination model. Demyelination was induced by local injection of LPC 1% (2 μl) into rat optic chiasm. Querectin at doses 25 or 50 mg/kg was administrated daily by oral gavage for 7 or 14 days post LPC. Visual evoked potential (VEPs) recordings were used to assess the functional property of the optic pathway. Immunostaining and myelin staining were performed on brain sections 7 or 14 days post lesion. Electrophysiological data indicated that LPC injection increased the latency of VEPs waves and quercetin effectively reduced the delay of visual signals. The level of glial activation was alleviated in animals under treatment of quercetin compared to vehicle group. Furthermore, quercetin treatment decreased the extent of demyelination areas and increased the remyelination process following LPC injection. Overall, our findings indicate that quercetin could remarkably improve the functional recovery of the optic pathway by its protective effects on myelin sheath and attenuation of glial activation. [ABSTRACT FROM AUTHOR]

Background Prolactinomas are typically treated nonsurgically with a dopamine agonist. Once the tumor shrinks, adjacent eloquent structures, such as the optic apparatus, can become skeletonized and herniate into the dilated parasellar space. Case Description A 48-year-old man with a prolactin-secreting macroadenoma treated with cabergoline presented with progressive bitemporal hemianopsia. Magnetic resonance imaging showed no recurrence of disease and a stretched optic chiasm herniating into an empty sella. Elevation of the optic chiasm via a transnasal transsphenoidal approach with ALLODERM graft and septal cartilage strut was performed. The patient was discharged home the next day with significant improvement in vision; magnetic resonance imaging showed interval elevation of the optic chiasm. Conclusions We review secondary empty sella syndrome and discuss surgical strategies for optic chiasmapexy. [ABSTRACT FROM AUTHOR]

Objective: A major cause of readmission after transsphenoidal surgery (TSS) is delayed hyponatraemia. The purpose of this study was to identify predictors of hyponatraemia one week post surgery and predictors of 30-day readmissions for hyponatraemia. Design: A retrospective cohort study including patients who had TSS performed for pituitary lesions. Method: The risk of readmission for hyponatraemia was assessed in consecutive patients between January 2008 and March 2016. The risk of hyponatraemia one week post surgery was assessed in patients admitted for TSS between July 2011 and March 2016. Results: Of all included patients, 56/522 (10.7%) were readmitted within 30 days. Hyponatraemia was found in 14/56 (25%) of 30-day readmissions. We did not identify any predictive variable for hyponatraemia on readmission. The number of patients with hyponatraemia on the seventh post-operative day was 26/314 (8.3%). The risk of hyponatraemia one week post surgery was increased by an odds ratio of 2.40 (95% CI: 1.06-5.40) in patients with a tumour abutting the optic chiasm and by an odds ratio of 1.16 (1.04-1.31) per mmol/L decrease in sodium levels on the first post-operative day. Conclusions: Hyponatraemia occurred in 25% of readmissions; however, we did not identify any predictive variable for readmission with hyponatraemia. One week post surgery, 8.9% had hyponatraemia. Tumours pressing on the optic chiasm as well as a fall in sodium levels on the first post-operative day were associated with an increased risk of hyponatraemia one week post surgery. We suggest that a day 7 serum sodium <130 nmol/L should lead to concern and the provision of patient advice. [ABSTRACT FROM AUTHOR]

Background Glioblastomas in the sellar region are very rare; in most cases, the tumor originates from the optic nerve or optic chiasm. Only 4 cases of sellar glioblastoma with a nonoptic origin have been reported. We present such a case with detailed clinical, imaging, and histopathologic information. We also review similar published cases. Case Description A 42-year-old woman presented with endocrinologic abnormalities, including amenorrhea and lactation, symptoms of diabetes insipidus, and signs of elevated intracranial pressure. Magnetic resonance imaging showed a giant, heterogeneously enhancing lesion involving the intrasellar, parasellar, and suprasellar regions, with hypercellularity and signs of infiltration of adjacent structures. Intraoperative examination revealed the tumor to be independent from the optic pathways, but it showed infiltration of the hypothalamic region. Histopathologic examination demonstrated uniformly packed small cells and negative staining for glial fibrillary acidic protein, which was consistent with a diagnosis of small cell glioblastoma. Conclusions This is the first report of a small cell glioblastoma in the sella turcica region. Glioblastomas in the sellar region with no clear evidence of an optic origin should be viewed as an independent disease entity. The typical characteristics of this tumor indicate it should be considered a rare subtype of glioblastoma. Further accumulation of experience is needed to better differentiate these cases and to offer optimal treatment. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system which has no any known definitive treatment. Studies have shown that thyroid hormones (THs) in addition to their roles in the development of the nervous system and the production of myelin have important roles in the adult's brain function. Since the only way to treat MS is the restoration of myelin, the aim of this study was to evaluate the effects of levothyroxine on visual evoked potential (VEP) impairment following local injections of lysolecithin into the rat optic chiasm. Methods: To induce demyelination, lysolecithin was injected into the optic chiasm of male Wistar rats. VEP recording was used to evaluate demyelination and remyelination before and 10, 17, and 24 days after the lysolecithin injection. The rats received an intraperitoneal injection of levothyroxine with doses 20, 50, and 100 µg/kg in different experimental groups. Results: VEP latency and amplitude showed demyelination at 10 and 17 days after an induced lesion in MS group which was reversed at day 24. Levothyroxine prevented these impairments, especially in high doses. Conclusions: According to the results, lysolecithin-induced demyelination at optic chiasm and VEP impairments can be restored by administration of levothyroxine. Therefore, THs probably have positive effects in demyelinating diseases. [ABSTRACT FROM AUTHOR]