Neuro-ophthalmology

Neuro-ophthalmology publications

Burstein R, Noseda R, Fulton AB. Neurobiology of Photophobia. J Neuroophthalmol 2019;39(1):94-102.Abstract
BACKGROUND: Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light. PURPOSE: The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine. RECENT FINDINGS: Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex. SUMMARY: The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.
Ing EB, Wang DN, Kirubarajan A, Benard-Seguin E, Ma J, Farmer JP, Belliveau MJ, Sholohov G, Torun N. Systematic Review of the Yield of Temporal Artery Biopsy for Suspected Giant Cell Arteritis. Neuroophthalmology 2019;43(1):18-25.Abstract
PURPOSE: To determine the positive yield (utility rate) of temporal artery biopsy (TAB) in patients with suspected giant cell arteritis (GCA). STUDY DESIGN: Systematic review (CRD42017078508) and meta-regression. MATERIALS AND METHODS: All articles concerning TAB for suspected GCA with English language abstracts from 1998 to 2017 were retrieved. Articles were excluded if they exclusively reported positive TAB, or only cases of known GCA. Where available, the pre-specified predictors of age, sex, vision symptoms, jaw claudication, duration of steroid treatment prior to TAB, specimen length, bilateral TAB, and use of ultrasound/MRI (imaging) were recorded for meta-regression. RESULTS: One hundred and thirteen articles met eligibility criteria. The was 92%, and with such high heterogeneity, meta-analysis is unsuitable. The median yield of TAB was 0.25 (95% confidence interval 0.21 to 0.27), with interquartile range 0.17 to 0.34. On univariate meta-regression age (coefficient 0.012,  = 0.025) was the only statistically significant patient factor associated with TAB yield. CONCLUSIONS: Systematic review revealed high heterogeneity in the yield of TAB. The median utility rate of 25% and its interquartile range provides a benchmark for decisions regarding the under/overutilization of TAB and aids in the evaluation of non-invasive alternatives for the investigation of GCA.
Zhao B, Torun N, Elsayed M, Cheng A-D, Brook A, Chang Y-M, Bhadelia RA. Diagnostic Utility of Optic Nerve Measurements with MRI in Patients with Optic Nerve Atrophy. AJNR Am J Neuroradiol 2019;40(3):558-561.Abstract
BACKGROUND AND PURPOSE: No MR imaging measurement criteria are available for the diagnosis of optic nerve atrophy. We determined a threshold optic nerve area on MR imaging that predicts a clinical diagnosis of optic nerve atrophy and assessed the relationship between optic nerve area and retinal nerve fiber layer thickness measured by optical coherence tomography, an ancillary test used to evaluate optic nerve disorders. MATERIALS AND METHODS: We evaluated 26 patients with suspected optic nerve atrophy (8 with unilateral, 13 with bilateral and 5 with suspected but not demonstrable optic nerve atrophy) who had both orbital MR imaging and optical coherence tomography examinations. Forty-five patients without optic nerve atrophy served as controls. Coronal inversion recovery images were used to measure optic nerve area on MR imaging. Retinal nerve fiber layer thickness was determined by optical coherence tomography. Individual eyes were treated separately; however, bootstrapping was used to account for clustering when appropriate. Correlation coefficients were used to evaluate relationships; receiver operating characteristic curves, to investigate predictive accuracy. RESULTS: There was a significant difference in optic nerve area between patients' affected eyes with optic nerve atrophy (mean, 3.09 ± 1.09 mm), patients' unaffected eyes (mean, 5.27 ± 1.39 mm; = .008), and control eyes (mean, 6.27 ± 2.64 mm; < .001). Optic nerve area ≤ 4.0 mm had a sensitivity of 0.85 and a specificity of 0.83 in predicting the diagnosis of optic nerve atrophy. A significant relationship was found between optic nerve area and retinal nerve fiber layer thickness ( = 0.68, < .001). CONCLUSIONS: MR imaging-measured optic nerve area ≤ 4.0 mm has moderately high sensitivity and specificity for predicting optic nerve atrophy, making it a potential diagnostic tool for radiologists.
Schoemaker D, Quiroz YT, Torrico-Teave H, Arboleda-Velasquez JF. Clinical and research applications of magnetic resonance imaging in the study of CADASIL. Neurosci Lett 2019;698:173-179.Abstract
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited small vessel disease that leads to early cerebrovascular events and functional disability. It is the most common single-gene disorder leading to stroke. Magnetic resonance imaging (MRI) is a central component of the diagnosis and monitoring of CADASIL. Here we provide a descriptive review of the literature on three important aspects pertaining to the use of MRI in CADASIL. First, we review past research exploring MRI markers for this disease. Secondly, we describe results from studies investigating associations between neuroimaging abnormalities and neuropathology in CADASIL. Finally, we discuss previous findings relating MRI markers to clinical symptoms. This review thus provides a summary of the current state of knowledge regarding the use of MRI in CADASIL as well as suggestions for future research.
Reshef ER, Schiff ND, Brown EN. A Neurologic Examination for Anesthesiologists: Assessing Arousal Level during Induction, Maintenance, and Emergence. Anesthesiology 2019;130(3):462-471.Abstract
Anesthetics have profound effects on the brain and central nervous system. Vital signs, along with the electroencephalogram and electroencephalogram-based indices, are commonly used to assess the brain states of patients receiving general anesthesia and sedation. Important information about the patient's arousal state during general anesthesia can also be obtained through use of the neurologic examination. This article reviews the main components of the neurologic examination focusing primarily on the brainstem examination. It details the components of the brainstem examination that are most relevant for patient management during induction, maintenance, and emergence from general anesthesia. The examination is easy to apply and provides important complementary information about the patient's arousal level that cannot be discerned from vital signs and electroencephalogram measures.
MacIntosh PW, Fay AM. Update on the ophthalmic management of facial paralysis. Surv Ophthalmol 2019;64(1):79-89.Abstract
Bell's palsy is the most common neurologic condition affecting the cranial nerves. Lagophthalmos, exposure keratopathy, and corneal ulceration are potential complications. In this review, we evaluate various causes of facial paralysis as well as the level 1 evidence supporting the use of a short course of oral steroids for idiopathic Bell's palsy to improve functional outcomes. Various surgical and nonsurgical techniques are also discussed for the management of residual facial dysfunction.
Madhavan R, Bansal AK, Madsen JR, Golby AJ, Tierney TS, Eskandar EN, Anderson WS, Kreiman G. Neural Interactions Underlying Visuomotor Associations in the Human Brain. Cereb Cortex 2018;Abstract
Rapid and flexible learning during behavioral choices is critical to our daily endeavors and constitutes a hallmark of dynamic reasoning. An important paradigm to examine flexible behavior involves learning new arbitrary associations mapping visual inputs to motor outputs. We conjectured that visuomotor rules are instantiated by translating visual signals into actions through dynamic interactions between visual, frontal and motor cortex. We evaluated the neural representation of such visuomotor rules by performing intracranial field potential recordings in epilepsy subjects during a rule-learning delayed match-to-behavior task. Learning new visuomotor mappings led to the emergence of specific responses associating visual signals with motor outputs in 3 anatomical clusters in frontal, anteroventral temporal and posterior parietal cortex. After learning, mapping selective signals during the delay period showed interactions with visual and motor signals. These observations provide initial steps towards elucidating the dynamic circuits underlying flexible behavior and how communication between subregions of frontal, temporal, and parietal cortex leads to rapid learning of task-relevant choices.
Chi Z-L, Adini A, Birsner AE, Bazinet L, Akula JD, D'Amato RJ. PR1P ameliorates neurodegeneration through activation of VEGF signaling pathway and remodeling of the extracellular environment. Neuropharmacology 2018;Abstract
Neurodegenerative diseases affect millions of people worldwide. Optic neuropathies are the most commonly occurring neurodegenerative diseases, characterized by progressive retinal ganglion cell (RGC) degeneration. We recently reported that Prominin-1, a protein found on the surface of stem cells, interacts with VEGF and enhances its activity. VEGF is known to have various protective roles in the nervous system. Subsequently, we have developed a 12-mer peptide derived from Prominin-1, named PR1P, and investigated its effects on neuronal survival of damaged RGCs in a rat model of optic nerve crush (ONC). PR1P prevented RGC apoptosis resulting in improvement of retinal function in the rat ONC model. PR1P treatment significantly increased phosphorylation of ERK and AKT and expression its downstream proteins c-fos and Egr-1 in the retina. Additionally, PR1P beneficially increased the MMP-9/TIMP-1 ratio and promoted glial activation in the retina of ONC rats. Thus, PR1P displayed neuroprotective effects through enhanced VEGF-driven neuronal survival and reconstruction of the extracellular environment in ONC model. Our data indicate that PR1P may be a promising new clinical candidate for the treatment of neurodegenerative diseases.
Sabel BA, Flammer J, Merabet LB. Residual vision activation and the brain-eye-vascular triad: Dysregulation, plasticity and restoration in low vision and blindness - a review. Restor Neurol Neurosci 2018;Abstract
Vision loss due to ocular diseases such as glaucoma, optic neuropathy, macular degeneration, or diabetic retinopathy, are generally considered an exclusive affair of the retina and/or optic nerve. However, the brain, through multiple indirect influences, has also a major impact on functional visual impairment. Such indirect influences include intracerebral pressure, eye movements, top-down modulation (attention, cognition), and emotionally triggered stress hormone release affecting blood vessel dysregulation. Therefore, vision loss should be viewed as the result of multiple interactions within a "brain-eye-vascular triad", and several eye diseases may also be considered as brain diseases in disguise. While the brain is part of the problem, it can also be part of the solution. Neuronal networks of the brain can "amplify" residual vision through neuroplasticity changes of local and global functional connectivity by activating, modulating and strengthening residual visual signals. The activation of residual vision can be achieved by different means such as vision restoration training, non-invasive brain stimulation, or blood flow enhancing medications. Modulating brain functional networks and improving vascular regulation may offer new opportunities to recover or restore low vision by increasing visual field size, visual acuity and overall functional vision. Hence, neuroscience offers new insights to better understand vision loss, and modulating brain and vascular function is a promising source for new opportunities to activate residual vision to achieve restoration and recovery to improve quality of live in patients suffering from vision loss.
Chwalisz BK, Stone JH. Neuro-ophthalmic complications of IgG4-related disease. Curr Opin Ophthalmol 2018;29(6):485-494.Abstract
PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is increasingly recognized as a fibroinflammatory disease with a plethora of organ-specific manifestations but a particular predilection for head and neck tissues, including the nervous system. This review discusses general features and organ-specific presentations of IgG4-RD as well as treatment considerations, particularly emphasizing features of neuro-ophthalmic interest. RECENT FINDINGS: IgG4-RD is emerging as a common cause of several fibroinflammatory disorders in the head and neck that were previously considered idiopathic, such as sclerosing orbital pseudotumor, orbital myositis, hypophysitis, and hypertrophic pachymeningitis. New and unusual presentations continue to be described, including a number of vascular manifestations. Substantial progress has been made in elucidating the cell types involved in IgG4-RD, and new pathogenic models are being proposed. Although clinicopathologic correlation remains the cornerstone of diagnosis, ancillary tests such as flow cytometry for circulating plasmablasts and PET-computed tomography have high sensitivity, and certain radiologic features are recognized to be particularly suggestive, such as infraorbital nerve enlargement in IgG4-RD orbitopathy. IgG4-RD often responds to steroids but incomplete responses and relapses are common. Rituximab is emerging as a promising new therapy. SUMMARY: The current review summarizes manifestations of IgG4RD that are of particular relevance to neuro-ophthalmic practice.
Fortin E, Cestari DM, Weinberg DH. Ocular myasthenia gravis: an update on diagnosis and treatment. Curr Opin Ophthalmol 2018;29(6):477-484.Abstract
PURPOSE OF REVIEW: Myasthenia gravis is an autoimmune disease that commonly affects the palpebral and extraocular muscles. Ocular myasthenia gravis (OMG) is a variant of the disease that is confined to the ocular muscles but frequently becomes generalized over time. The diagnosis of OMG is often challenging but both clinical and laboratory findings are helpful in confirming the clinical suspicion. This review provides an update on the diagnostic approach and therapeutic options for OMG. RECENT FINDINGS: Antimuscle-specific tyrosine kinase and LDL-related receptor-related protein 4 are newly available serologic testing for myasthenia gravis that can help in increasing the diagnostic sensitivity of OMG. They should be included to the diagnostic algorithm of OMG in appropriate clinical situations. SUMMARY: OMG remains a primarily clinical diagnosis, but recent advances in laboratory testing can improve the diagnostic accuracy and should be used in appropriate clinical settings. The mainstay of treatment for OMG has not significantly changed over the past years, but the increasing availability of steroid-sparing agents improved the disease control while minimizing steroid-induced complications.
Ibrahim AS, Elmasry K, Wan M, Abdulmoneim S, Still A, Khan F, Khalil A, Saul A, Hoda MN, Al-Shabrawey M. A Controlled Impact of Optic Nerve as a New Model of Traumatic Optic Neuropathy in Mouse. Invest Ophthalmol Vis Sci 2018;59(13):5548-5557.Abstract
Purpose: Traumatic optic neuropathy (TON) is the most feared visual consequence of head and ocular trauma in both military and civilian communities, for which standard treatment does not exist. Animal models are critical for the development of novel TON therapies as well as the understanding of TON pathophysiology. However, the models currently used for TON have some limitations regarding consistency and mirroring the exact pathological progression of TON in closed ocular trauma. In this study, we modified the model of controlled cortical impact and adapted it for studying TON. Methods: We defined new standardized procedures to induce TON in mice, wherein the optic nerve is reproducibly exposed to a graded controlled impact of known velocity to produce a graded deficit in retinal ganglion cell (RGC) electrophysiological functions. Results: The key results of validating this newly modified model, "controlled orbital impact (COI)," included (1) the injury parameters (velocity as well as contusion depth and time), which were quantifiable and manageable to generate a wide range of TON severities; (2) a reproducible endpoint of diminished positive scotopic threshold response (pSTR) has been achieved without the interference of surgical variability and destruction of surrounding tissues; (3) the contralateral eyes showed no significant difference to the eyes of naïve mice, allowing them to be used as an internal control to minimize interindividual variability among mice; and (4) the occurrence of injury-associated mortality and/or ocular comorbidity was rare. Conclusions: Taken together, this model overcomes some limitations of prior TON mouse models and provides an innovative platform to identify therapeutic targets for neuroprotection and/or neurorestoration following traumatic ocular injury.
Chun BY, Cestari DM. Myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis. Curr Opin Ophthalmol 2018;29(6):508-513.Abstract
PURPOSE OF REVIEW: Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated optic neuritis has been established as a new entity of optic neuropathy. We will review recent advances in pathophysiology, diagnosis, and clinical manifestations of MOG-IgG-associated optic neuritis to better understand its distinctive characteristics. RECENT FINDINGS: MOG is expressed on the surface of myelin sheaths and oligodendrocytes. MOG is highly immunogenic and is a potential target of inflammatory demyelinating disease. MOG-IgG activate immune responses and cause demyelination without astrocytopathy. MOG-IgG are measured by cell-based assays, which have higher sensitivity and specificity than ELISA. Patients with MOG-IgG-associated optic neuritis present with initially severe vision loss, are more likely to have optic disc edema, but have favorable visual outcomes. Furthermore, patients with MOG-IgG-associated optic neuritis have higher rates of recurrence compared with MOG-IgG seronegative patients. MOG-IgG-associated optic neuritis responds well to steroid treatment, however, close monitoring for signs of relapse and long-term immunosuppression may be necessary. SUMMARY: MOG-IgG associated optic neuritis demonstrates distinctive pathophysiological and clinical characteristics from optic neuritis in aquaporin4-IgG seropositive or multiple sclerosis patients. Measurements of MOG-IgG titers by cell-based assays will be helpful for the diagnosis and treatment of optic neuritis.
Galli J, Ambrosi C, Micheletti S, Merabet LB, Pinardi C, Gasparotti R, Fazzi E. White matter changes associated with cognitive visual dysfunctions in children with cerebral palsy: A diffusion tensor imaging study. J Neurosci Res 2018;96(11):1766-1774.Abstract
Children with cerebral palsy often present with cognitive-visual dysfunctions characterized by visuo-perceptual and/or visuo-spatial deficits associated with a malfunctioning of visual-associative areas. The neurofunctional model of this condition remains poorly understood due to the lack of a clear correlation between cognitive-visual deficit and morphological brain anomalies. The aim of our study was to quantify the pattern of white matter abnormalities within the whole brain in children with cerebral palsy, and to identify white matter tracts sub-serving cognitive-visual functions, in order to better understand the basis of cognitive-visual processing. Nine subjects (three males, mean age 8 years 9 months) with cerebral palsy underwent a visual and cognitive-visual evaluation. Conventional brain MRI and diffusion tensor imaging were performed. The fractional anisotropy maps were calculated for every child and compared with data from 13 (four males, mean age 10 years 7 months) healthy children. Children with cerebral palsy showed decreased fractional anisotropy (a marker of white matter integrity) in corticospinal tract bilaterally, left superior longitudinal fasciculus and bilateral hippocampus. Focusing on the superior longitudinal fasciculus, the mean fractional anisotropy values were significantly lower in children affected by cerebral palsy with cognitive-visual deficits than in those without cognitive-visual deficits. Our findings reveal an association between cognitive-visual profile and the superior longitudinal fasciculus integrity in children with cerebral palsy, supporting the hypothesis that visuo-associative deficits are related to changes in fibers connecting the occipital cortex with the parietal-frontal cortices. Decreased fractional anisotropy within the superior longitudinal fasciculus could be considered a biomarker for cognitive-visual dysfunctions.

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