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Eye And Brain[JOURNAL]

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Curvilinear, symmetrical, and profound pigment deposition on the posterior lens capsule in a patient with bilateral pigmentary dispersion syndrome.

Canestraro J, Sherman J

Eye Brain · 2018 · PMID 30254503 · Full text

INTRODUCTION: The classic presentation of pigmentary dispersion syndrome (PDS) often consists of midperipheral iris transillumination defects, Krukenberg's spindle, and dense homogeneous trabecular pigmentation. Other su... INTRODUCTION: The classic presentation of pigmentary dispersion syndrome (PDS) often consists of midperipheral iris transillumination defects, Krukenberg's spindle, and dense homogeneous trabecular pigmentation. Other subtle, sometimes overlooked features include pigment on the lens zonules, pigment on the anterior lens capsule and pigment along the equator of the posterior lens capsule. CASE: This unique presentation of PDS presented with bilateral, dense, oblique, and symmetrical pigment deposition along the posterior lens capsule that changed in shape, density, and extent over the span of 3 years. DISCUSSION: There have been few reports in the literature that describe a central accumulation of pigment along the posterior lens capsule associated with PDS. There are reported cases of pigment deposition along the central aspect of the posterior lens capsule, some changing over time, although none were bilateral and symmetrical. There are suggestions that perhaps this central pigment deposition is related to a break in the ligament of Weiger, allowing communication between the posterior chamber and posterior lens capsule. This is a case in which curvilinear, symmetrical, and changing pigment deposition on the posterior lens capsule is suggestive of perhaps another key features of PDS.

Effects of tDCS-like electrical stimulation on retinal ganglion cells.

Strang CE, Ray MK, Boggiano MM … +1 more , Amthor FR

Eye Brain · 2018 · PMID 30214335 · Full text

PURPOSE: Transcranial direct current stimulation (tDCS) has been studied in humans for its effects on enhancement of learning, amelioration of psychiatric disorders, and modification of other behaviors for over 50 years.... PURPOSE: Transcranial direct current stimulation (tDCS) has been studied in humans for its effects on enhancement of learning, amelioration of psychiatric disorders, and modification of other behaviors for over 50 years. Typical treatments involve injecting 2 mA current through scalp electrodes for 20 minutes, sometimes repeated weekly for two to five sessions. Little is known about the direct effects of tDCS at the neural circuit or the cellular level. This study assessed the effects of tDCS-like currents on the central nervous system by recording effects on retinal ganglion cell responsiveness using the rabbit retina eyecup preparation. MATERIALS AND METHODS: We examined changes in firing to On and Off light stimuli during and after brief applications of a range of currents and polarity and in different classes of ganglion cells. RESULTS: The responses of Sustained cells were consistently suppressed during the first round of current application, but responses could be enhanced after subsequent rounds of stimulation. The observed first round suppression was independent of current polarity, amplitude, or number of trials. However, the light responses of Transient cells were more likely to be enhanced by negative currents and unaffected or suppressed by first round positive currents. Short-duration currents, that is, minutes, as low as 2.5 µA produced a remarkable persistency of firing changes, for up to 1.5 hours, after cessation of current. CONCLUSION: The results are consistent with postulated tDCS alteration of central nervous system function, which outlast the tDCS session and provide evidence for the isolated retina as a useful model to understand tDCS actions at the neuronal level.

Retinal imaging with optical coherence tomography: a biomarker in multiple sclerosis?

Costello F, Burton JM

Eye Brain · 2018 · PMID 30104912 · Full text

Multiple sclerosis (MS) is a progressive neurological disorder characterized by both inflammatory and degenerative components that affect genetically susceptible individuals. Currently, the cause of MS remains unclear, a... Multiple sclerosis (MS) is a progressive neurological disorder characterized by both inflammatory and degenerative components that affect genetically susceptible individuals. Currently, the cause of MS remains unclear, and there is no known cure. Commonly used therapies tend to target inflammatory aspects of MS, but may not halt disease progression, which may be governed by the slow, subclinical accumulation of injury to neuroaxonal structures in the central nervous system (CNS). A recognized challenge in the field of MS relates to the need for better methods of detecting, quantifying, and ameliorating the effects of subclinical disease. Simply stated, better biomarkers are required. To this end, optical coherence tomography (OCT) provides highly reliable, reproducible measures of axonal damage and neuronal loss in MS patients. OCT-detected decrements in retinal nerve fiber layer thickness and ganglion-cell layer-inner plexiform layer thickness, which represent markers of axonal damage and neuronal injury, respectively, have been shown to correlate with worse visual outcomes, increased clinical disability, and magnetic resonance imaging-measured burden of disease in MS patients. Recent reports have also suggested that OCT-measured microcystic macular edema and associated thickening of the retinal inner nuclear layer represent markers of active CNS inflammatory activity. Using the visual system as a putative clinical model in MS, OCT measures of neuroaxonal structure can be correlated with functional outcomes to help us elucidate mechanisms of CNS injury and repair. In this review, we evaluate evidence from the published literature and ongoing clinical trials that support the emerging role of OCT in diagnosing, staging, and determining response to therapy in MS patients.

Neurotrophic keratitis: current challenges and future prospects.

Versura P, Giannaccare G, Pellegrini M … +2 more , Sebastiani S, Campos EC

Eye Brain · 2018 · PMID 29988739 · Full text

Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory... Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described.

The development of human visual cortex and clinical implications.

Siu CR, Murphy KM

Eye Brain · 2018 · PMID 29760575 · Full text

The primary visual cortex (V1) is the first cortical area that processes visual information. Normal development of V1 depends on binocular vision during the critical period, and age-related losses of vision are linked wi... The primary visual cortex (V1) is the first cortical area that processes visual information. Normal development of V1 depends on binocular vision during the critical period, and age-related losses of vision are linked with neurobiological changes in V1. Animal studies have provided important details about the neurobiological mechanisms in V1 that support normal vision or are changed by visual diseases. There is very little information, however, about those neurobiological mechanisms in human V1. That lack of information has hampered the translation of biologically inspired treatments from preclinical models to effective clinical treatments. We have studied human V1 to characterize the expression of neurobiological mechanisms that regulate visual perception and neuroplasticity. We have identified five stages of development for human V1 that start in infancy and continue across the life span. Here, we describe these stages, compare them with visual and anatomical milestones, and discuss implications for translating treatments for visual disorders that depend on neuroplasticity of V1 function.

State of the art of robotic surgery related to vision: brain and eye applications of newly available devices.

Nuzzi R, Brusasco L

Eye Brain · 2018 · PMID 29440943 · Full text

BACKGROUND: Robot-assisted surgery has revolutionized many surgical subspecialties, mainly where procedures have to be performed in confined, difficult to visualize spaces. Despite advances in general surgery and neurosu... BACKGROUND: Robot-assisted surgery has revolutionized many surgical subspecialties, mainly where procedures have to be performed in confined, difficult to visualize spaces. Despite advances in general surgery and neurosurgery, in vivo application of robotics to ocular surgery is still in its infancy, owing to the particular complexities of microsurgery. The use of robotic assistance and feedback guidance on surgical maneuvers could improve the technical performance of expert surgeons during the initial phase of the learning curve. EVIDENCE ACQUISITION: We analyzed the advantages and disadvantages of surgical robots, as well as the present applications and future outlook of robotics in neurosurgery in brain areas related to vision and ophthalmology. DISCUSSION: Limitations to robotic assistance remain, that need to be overcome before it can be more widely applied in ocular surgery. CONCLUSION: There is heightened interest in studies documenting computerized systems that filter out hand tremor and optimize speed of movement, control of force, and direction and range of movement. Further research is still needed to validate robot-assisted procedures.

Profile of tocilizumab and its potential in the treatment of giant cell arteritis.

Mollan SP, Horsburgh J, Dasgupta B

Eye Brain · 2018 · PMID 29416384 · Full text

Giant cell arteritis (GCA) remains a medical emergency due to the threat of permanent sight loss. High-dose glucocorticoids (GCs) are effective in inducing remission in the majority of patients, however, relapses are com... Giant cell arteritis (GCA) remains a medical emergency due to the threat of permanent sight loss. High-dose glucocorticoids (GCs) are effective in inducing remission in the majority of patients, however, relapses are common which lengthen GC therapy. GC toxicity remains a major morbidity in this group of patients, and conventional steroid-sparing therapies have not yet shown enough of a clinical benefit to change the standard of care. As the understanding of the underlying immunopathophysiology of GCA has increased, positive clinical observations have been made with the use of IL-6 receptor inhibitor therapies, such as tocilizumab (TCZ). This has led to prospective randomized control trials that have highlighted the safety and efficacy of TCZ in both new-onset and relapsing GCA.

Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management.

Berry S, Lin WV, Sadaka A … +1 more , Lee AG

Eye Brain · 2017 · PMID 29033621 · Full text

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic... Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea). The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION.

Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2.

Zarella MD, Ts'o DY

Eye Brain · 2017 · PMID 28761385 · Full text

Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having acce... Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure-ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure-ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure-ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization.

Visual consequences of medications for multiple sclerosis: the good, the bad, the ugly, and the unknown.

Moss HE

Eye Brain · 2017 · PMID 28721111 · Full text

Multiple sclerosis (MS) is associated with vision changes both due to MS effects on visual pathways and due to medication effects on the visual pathways. Distinguishing the causes of vision change are critical to appropr... Multiple sclerosis (MS) is associated with vision changes both due to MS effects on visual pathways and due to medication effects on the visual pathways. Distinguishing the causes of vision change are critical to appropriate diagnosis and management. The incidence, presentation, and treatment of fingolimod-associated macular edema, alemtuzumab-associated thyroid orbitopathy, and progressive multifocal leukoencephalopathy in MS patients are reviewed. Evidence for beneficial effects of acute, chronic, and symptomatic MS medications on vision is presented.

Optic neuritis as an early sign of multiple sclerosis.

Kale N

Eye Brain · 2016 · PMID 28539814 · Full text

Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve. The general characteristics of isolated ON include unilateral, subacute, and painful visual loss without systemic or other neurologi... Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve. The general characteristics of isolated ON include unilateral, subacute, and painful visual loss without systemic or other neurological symptoms. The etiology for ON varies including demyelinating disorders or infections, inflammation, toxic reasons, and genetic disorders. In most cases the responsible etiology may not be known for ON and in this case, it is termed idiopathic ON. When a patient presents with an initial episode of ON, patients should undergo further tests. Assessing the patient with routine blood work, magnetic resonance imaging, cerebrospinal fluid tests, and visual evoked potentials provide further insight. In this review, we aimed to provide a review of ON as an initial symptom of multiple sclerosis and present clinical characteristics, therapy options, and recent literature.

Cue combination encoding via contextual modulation of V1 and V2 neurons.

Zarella MD, Ts'o DY

Eye Brain · 2016 · PMID 28539813 · Full text

Neurons in early visual cortical areas encode the local properties of a stimulus in a number of different feature dimensions such as color, orientation, and motion. It has been shown, however, that stimuli presented well... Neurons in early visual cortical areas encode the local properties of a stimulus in a number of different feature dimensions such as color, orientation, and motion. It has been shown, however, that stimuli presented well beyond the confines of the classical receptive field can augment these responses in a way that emphasizes these local attributes within the greater context of the visual scene. This mechanism imparts global information to cells that are otherwise considered local feature detectors and can potentially serve as an important foundation for surface segmentation, texture representation, and figure-ground segregation. The role of early visual cortex toward these functions remains somewhat of an enigma, as it is unclear how surface segmentation cues are integrated from multiple feature dimensions. We examined the impact of orientation- and motion-defined surface segmentation cues in V1 and V2 neurons using a stimulus in which the two features are completely separable. We find that, although some cells are modulated in a cue-invariant manner, many cells are influenced by only one cue or the other. Furthermore, cells that are modulated by both cues tend to be more strongly affected when both cues are presented together than when presented individually. These results demonstrate two mechanisms by which cue combinations can enhance salience. We find that feature-specific populations are more frequently encountered in V1, while cue additivity is more prominent in V2. These results highlight how two strongly interconnected areas at different stages in the cortical hierarchy can potentially contribute to scene segmentation.

Prosopagnosia: current perspectives.

Corrow SL, Dalrymple KA, Barton JJ

Eye Brain · 2016 · PMID 28539812 · Full text

Prosopagnosia is a selective visual agnosia characterized by the inability to recognize the identity of faces. There are both acquired forms secondary to brain damage and developmental forms without obvious structural le... Prosopagnosia is a selective visual agnosia characterized by the inability to recognize the identity of faces. There are both acquired forms secondary to brain damage and developmental forms without obvious structural lesions. In this review, we first discuss the diagnosis of acquired and developmental prosopagnosia, and the challenges present in the latter case. Second, we discuss the evidence regarding the selectivity of the prosopagnosic defect, particularly in relation to the recognition of other objects, written words (another visual object category requiring high expertise), and voices. Third, we summarize recent findings about the structural and functional basis of prosopagnosia from studies using magnetic resonance imaging, functional magnetic resonance imaging, and event-related potentials. Finally, we discuss recent attempts at rehabilitation of face recognition in prosopagnosia.

Traumatic brain injury and vestibulo-ocular function: current challenges and future prospects.

Wallace B, Lifshitz J

Eye Brain · 2016 · PMID 28539811 · Full text

Normal function of the vestibulo-ocular reflex (VOR) coordinates eye movement with head movement, in order to provide clear vision during motion and maintain balance. VOR is generated within the semicircular canals of th... Normal function of the vestibulo-ocular reflex (VOR) coordinates eye movement with head movement, in order to provide clear vision during motion and maintain balance. VOR is generated within the semicircular canals of the inner ear to elicit compensatory eye movements, which maintain stability of images on the fovea during brief, rapid head motion, otherwise known as gaze stability. Normal VOR function is necessary in carrying out activities of daily living (eg, walking and riding in a car) and is of particular importance in higher demand activities (eg, sports-related activities). Disruption or damage in the VOR can result in symptoms such as movement-related dizziness, blurry vision, difficulty maintaining balance with head movements, and even nausea. Dizziness is one of the most common symptoms following traumatic brain injury (TBI) and is considered a risk factor for a prolonged recovery. Assessment of the vestibular system is of particular importance following TBI, in conjunction with oculomotor control, due to the intrinsic neural circuitry that exists between the ocular and vestibular systems. The purpose of this article is to review the physiology of the VOR and the visual-vestibular symptoms associated with TBI and to discuss assessment and treatment guidelines for TBI. Current challenges and future prospects will also be addressed.

Screening and treatments using telemedicine in retinopathy of prematurity.

Thanos A, Yonekawa Y, Todorich B … +2 more , Moshfeghi DM, Trese MT

Eye Brain · 2016 · PMID 28539810 · Full text

Several studies have validated the role of telemedicine as a new powerful screening and diagnostic tool for retinal disorders, such as diabetic retinopathy and retinopathy of prematurity. With regard to retinopathy of pr... Several studies have validated the role of telemedicine as a new powerful screening and diagnostic tool for retinal disorders, such as diabetic retinopathy and retinopathy of prematurity. With regard to retinopathy of prematurity, bedside examination with binocular indirect ophthalmoscopy has been the gold standard technique for screening, yet with several limitations. Herein, we review the current evidence that supports the role of telemedicine for the screening of infants with retinopathy of prematurity.

Wnt signaling pathway in retinal vascularization.

Drenser KA

Eye Brain · 2016 · PMID 28539809 · Full text

Wnt-signaling, a ubiquitous pathway that directs differentiation, cell polarity, and tissue specificity, has been implicated as an important gene-expression pathway in retinal development. An increasing body of evidence... Wnt-signaling, a ubiquitous pathway that directs differentiation, cell polarity, and tissue specificity, has been implicated as an important gene-expression pathway in retinal development. An increasing body of evidence supports the importance of Wnt-signaling, and specifically, norrin-mediated Wnt-signaling in retinal development and retinal maintenance. Gene mutations affecting the Wnt-signaling pathways result in a variety of inherited vitreoretinopathies. Additionally, there is growing evidence that prematurity and associated retinopathy are associated with alterations in the Wnt-signaling pathways. Further investigations may allow for improved diagnoses, management, and therapies in the future.

Review of effects of anti-VEGF treatment on refractive error.

Mintz-Hittner HA, Geloneck MM

Eye Brain · 2016 · PMID 28539808 · Full text

To examine the effect of anti-vascular endothelial growth factor (anti-VEGF) agents on refractive error in the setting of retinopathy of prematurity (ROP) through a review of the literature, a PubMed search was performed... To examine the effect of anti-vascular endothelial growth factor (anti-VEGF) agents on refractive error in the setting of retinopathy of prematurity (ROP) through a review of the literature, a PubMed search was performed of appropriate search terms, and the results of all relevant studies were extracted and compiled. Eleven relevant articles were identified in the literature, totaling 466 eyes, treated with varied anti-VEGF agents (bevacizumab, ranibizumab, and aflibercept) with mean spherical equivalent refractions ranging from +0.75 D to -3.57 D, with prevalence of high myopia ranging from 0 to 35%. Anti-VEGF monotherapy for ROP leads to low levels of myopia, and there may be a differential effect of specific anti-VEGF agents utilized on refractive outcomes.

Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development.

Rothman AL, Mangalesh S, Chen X … +1 more , Toth CA

Eye Brain · 2016 · PMID 28539807 · Full text

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the ante... Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment.

Promoting vascular repair in the retina: can stem/progenitor cells help?

Trinh TLP, Li Calzi S, Shaw LC … +2 more , Yoder MC, Grant MB

Eye Brain · 2016 · PMID 28539806 · Full text

Since its first epidemic in the 1940s, retinopathy of prematurity (ROP) has been a challenging illness in neonatology. Higher than physiological oxygen levels impede the development of the immature retinal neuropil and v... Since its first epidemic in the 1940s, retinopathy of prematurity (ROP) has been a challenging illness in neonatology. Higher than physiological oxygen levels impede the development of the immature retinal neuropil and vasculature. Current treatment regimens include cryotherapy, laser photocoagulation, and anti-VEGF agents. Unfortunately, none of these approaches can rescue the normal retinal vasculature, and each has significant safety concerns. The limitations of these approaches have led to new efforts to understand the pathological characteristics in each phase of ROP and to find a safer and more effective therapeutic approach. In the era of stem cell biology and with the need for new treatments for ROP, this review discusses the possible future use of unique populations of proangiogenic cells for therapeutic revascularization of the preterm retina.

Retinal, visual, and refractive development in retinopathy of prematurity.

Moskowitz A, Hansen RM, Fulton AB

Eye Brain · 2016 · PMID 28539805 · Full text

The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human R... The pivotal role of the neurosensory retina in retinopathy of prematurity (ROP) disease processes has been amply demonstrated in rat models. We have hypothesized that analogous cellular processes are operative in human ROP and have evaluated these presumptions in a series on non-invasive investigations of the photoreceptor and post-receptor peripheral and central retina in infants and children. Key results are slowed kinetics of phototransduction and deficits in photoreceptor sensitivity that persist years after ROP has completely resolved based on clinical criteria. On the other hand, deficits in post-receptor sensitivity are present in infancy regardless of the severity of the ROP but are not present in older children if the ROP was so mild that it never required treatment and resolved without a clinical trace. Accompanying the persistent deficits in photoreceptor sensitivity, there is increased receptive field size and thickening of the post-receptor retinal laminae in the peripheral retina of ROP subjects. In the late maturing central retina, which mediates visual acuity, attenuation of multifocal electroretinogram activity in the post-receptor retina led us to the discovery of a shallow foveal pit and significant thickening of the post-receptor retinal laminae in the macular region; this is most likely due to failure of the normal centrifugal movement of the post-receptor cells during foveal development. As for refractive development, myopia, at times high, is more common in ROP subjects than in control subjects, in accord with refractive findings in other populations of former preterms. This information about the neurosensory retina enhances understanding of vision in patients with a history of ROP, and taken as a whole, raises the possibility that the neurosensory retina is a target for therapeutic intervention.
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