Visual System Damage Research Articles

Trim9 regulates the directional differentiation of retinal Müller cells to retinal ganglion cells.

Glaucoma is a leading cause of irreversible blindness, and effective therapies to reverse the visual system damage caused by glaucoma are still lacking. Recently, the stem cell therapy enable the repair and regeneration of the damaged retinal neurons, but challenges regarding the source of stem cells remain. This study aims to investigate a protocol that allows the dedifferentiation of Müller cells into retinal stem cells, following by directed differentiation into retinal ganglion cells with high efficiency, and to provide a new method of cellular acquisition for retinal stem cells. Epidermal cell growth factor and fibroblast growth factor 2 were used to induce the dedifferentiation of rat retinal Müller cells into retinal neural stem cells. Retinal stem cells derived from Müller cells were infected with a Trim9 overexpression lentiviral vector (PGC-FU-Trim9-GFP), and the efficiency of viral infection was assessed by fluorescence microscopy and flow cytometry. Retinoic acid and brain-derived neurotrophic factor treatments were used to induce the differentiation of the retinal stem cells into neurons and glial cells with or without the overexpression of Trim9. The expressions of each cellular marker (GLAST, GS, rhodopsin, PKC, HPC-1, Calbindin, Thy1.1, Brn-3b, Nestin, Pax6) were detected by immunofluorescence, PCR/real-time RT-PCR or Western blotting. Rat retinal Müller cells expressed neural stem cells markers (Nestin and Pax6) with the treatment of epidermal cell growth factor and fibroblast growth factor 2. The Thy1.1 positive cell rate of retinal stem cells overexpressing Trim9 was significantly increased, indicating their directional differentiation into retinal ganglion cells after treatment with retinoic acid and brain-derived neurotrophic factor. In this study, rat retinal Müller cells are dedifferentiated into retinal stem cells successfully, and Trim9 promotes the directional differentiation from retinal stem cells to retinal ganglion cells effectively.

Serum glial fibrillary acidic protein correlates with retinal structural damage in aquaporin-4 antibody positive neuromyelitis optica spectrum disorder

BackgroundAquaporin-4 immunoglobulin-G positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy associated with optic neuritis (ON). Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an oligodendrocytopathy with a similar phenotype. Serum glial fibrillary acidic protein (sGFAP), an astrocyte-derived protein, is associated with disease severity in AQP4-IgG+ NMOSD. Serum neurofilament light (sNfL) indicates neuroaxonal damage. The objective was to investigate the association of sGFAP and sNfL with subclinical afferent visual system damage in clinically stable AQP4-IgG+ NMOSD and MOGAD patients. MethodsIn this cross-sectional study, clinically stable patients with AQP4-IgG+ NMOSD (N = 33) and MOGAD (N = 16), as diseased controls, underwent sGFAP and sNfL measurements by single molecule array, retinal optical coherence tomography and visually evoked potentials. ResultsHigher sGFAP concentrations were associated with thinner ganglion cell-inner plexiform layer (β (95% confidence interval (CI)) = −0.75 (−1.23 to −0.27), p = 0.007) and shallower fovea (average pit depth: β (95%CI) = −0.59 (−0.63 to −0.55), p = 0.020) in NMOSD non-ON eyes. Participants with pathological P100 latency had higher sGFAP (median [interquartile range]: 131.32 [81.10–179.34] vs. 89.50 [53.46–121.91] pg/ml, p = 0.024). In MOGAD, sGFAP was not associated with retinal structural or visual functional measures. ConclusionsThe association of sGFAP with structural and functional markers of afferent visual system damage in absence of ON suggests that sGFAP may be a sensitive biomarker for chronic disease severity in clinically stable AQP4-IgG+ NMOSD.

Multiple Sclerosis: What Methods are Available for the Assessment of Subclinical Visual System Damage?

ABSTRACT We aimed to assess the visual fields and optical coherence tomography (OCT) measurements in patients with multiple sclerosis (MS) to detect subclinical visual system disease. The study included 15 MS patients with previous optic neuritis (Group I), 17 MS patients without previous optic neuritis (Group II), and 14 healthy controls (Group III). Each subject underwent standard automated perimetry (SAP), frequency doubling technology perimetry (FDTP), and OCT. The mean deviation of SAP in Group I was lower than those in Groups II (p = .018) and III (p = .001). The pattern standard deviation of SAP in Group I was higher than those in Group III (p < .0001). The mean deviation of FDTP in Groups I and II was lower than those in Group III (p = .0001 and p = .016, respectively). The temporal quadrant of the retinal nerve fibre layer in Group I was thinner than those in Groups II and III (p = .005 and p = .003, respectively). The mean macular volume in Group I was thinner than those in Groups II and III (p = .004 and p = .002, respectively). A single method is inadequate for establishing early and/or mild visual impairment in MS. All conventional and non-conventional techniques are complementary in demonstrating subclinical visual damage in MS.

Study on mining of signals of adverse drug reactions of entecavir and tenofovir disoproxil based on the US FAERS database

Objective: To mine the signals of adverse drug reaction (ADR) of entecavir and tenofovir by using the US FDA Adverse Event Reporting System (FAERS) database, so as to provide reference for the safe clinical use of these two drugs. Methods: Reporting odds ratio (ROR) and proportion of report ratio (PRR) method were used to conduct data mining on the 26 quarterly reports of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database between the fourth quarter of 2012 to the first quarter of 2019. The ADR descriptive terminology in the report were standardized by using the World Health Organization Adverse Reaction Terminology (System-Organ Class). ROR and PRR methods common signals were screened. Results: 104 and 187 signals of ADR of entecavir and tenofovir dipivoxil were obtained by ROR and PRR methods. The main screened system-organ classes affected by signals of ADR of entecavir were systemic damage, hepatobiliary system damage, and urinary system damage. The main screened system-organ classes affected by signals of ADR of tenofovir were urinary system damage, skeletal and musculoskeletal system damage, and metabolic and nutritional disorders. Conclusion: The mining signals of adverse drug reaction of entecavir and tenofovir dipivoxil indicate that these two drugs can cause female reproductive system damage, fetal abnormalities, neonatal and infant abnormalities, and male reproductive system damage. However, in addition to the above-mentioned ADR, the ADR instruction manual excludes entecavir and tenofovir dipivoxil primarily for respiratory and visual system damage, and the tenofovir disoproxil primarily for skin and appendage damage, and hearing and vestibular function damage. Therefore, in clinical medication management, it is suggested to pay close attention to the choice of drugs for special population infected with HBV, monitor possible ADR during medication course, and provide pharmacological monitoring to achieve personalized medication.

Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage.

Apoptosis, a key mechanism of programmed cell death, is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage. We developed a novel, non-viral gene therapy to block caspase-3 gene expression using small interfering RNA (siRNA) delivered by polybutylcyanoacrylate nanoparticles (CaspNPs). In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells, and when injected intraocularly in vivo, CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9% in rats with optic nerve crush. Longitudinal, repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1% versus 63.4% in lesioned controls. Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons, siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders. The animal study procedures were approved by the German National Act on the use of experimental animals (Ethic Committee Referat Verbraucherschutz, Veterinärangelegenheiten; Landesverwaltungsamt Sachsen-Anhalt, Halle, Germany, # IMP/G/01-1150/12 and # IMP/G/01-1469/17).

Visual system damage and network maladaptation are associated with cognitive performance in neuromyelitis optica spectrum disorders.

Background Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune disease leading to disability from optic neuritis, myelitis and more rarely brain stem attacks and encephalitis. Patients with NMOSD also exhibit cognitive deficits, the cause of which remains unclear. Recent evidence highlights sensory-cognitive parallel processing converging on the primary visual cortex. The objective of this study was to investigate the effect of the primary visual network disruption from damage caused by optic neuritis on cognition in NMOSD.Methods Twenty-nine aquaporin-4 antibody seropositive patients with NMOSD and 22 healthy controls (HC) completed the brief repeatable battery of neuropsychological tests (BRB-N) and underwent 3 Tesla MRI. Primary visual network functional connectivity (FC) at resting state was analyzed and correlated with performance on BRB-N. These correlations were compared between the groups.Results Patients performed significantly worse than HC on the BRB-N Index score (t = 2.366, p = 0.02). Among HC, visual network FC decreased significantly as cognitive performance on the BRB-N Index score increased (rho(17)=-0.507, p = 0.02). Among patients, this association was absent (rho(23)=0.197, p = 0.18), and the difference in correlation direction and strength to HC was significant (z=-2.175, p = 0.01). Visual network FC was able to explain 19% of the variance in cognitive performance in HC, but none in patients.Conclusions A physiological association of the primary visual network FC and cognitive performance appears absent in patients with NMOSD, suggesting a partial explanation for cognitive deficits. Our findings extend neuroscientific concepts on sensory-cognitive parallel processing neural networks to a clearly defined pathological state, and may be relevant for other diseases with visual system damage.

Vision and Vision-Related Measures in Progressive Multiple Sclerosis.

Background: Over the last few years there has been growing interest in use of visual measures as useful tools for multiple sclerosis (MS) prognosis and tracking. Optic neuritis (ON) being a prevalent and often-presenting symptom of the disease, as well as the high occurrence rate of posterior visual system damage independent of ON (optic radiation lesions), make the visual system a prime candidate for such endeavors. However, while the visual system makes for a convenient model in early stages of MS, processes which may be true in those stages may drastically change as the disease progresses, due to accumulated disease load. Here, we examine whether vision-related tools reflect demyelinative and axonal damage of the visual pathways and may be used for assessment in the clinical setup in progressive multiple sclerosis (MS) patients, in whom disease load may alter the early stage picture.Methods: Forty-eight progressive MS patients, with and without prior optic neuritis (ON), underwent a battery of behavioral tests, visual evoked potential (VEP) tests, optical coherence tomography (OCT), and structural MRI scans, at two time-points. Data were analyzed for stability between visits and for correlation between behavioral and electrophysiological data.Results: All measures were stable between visits. Significant differences were found in all measures between the affected and fellow eyes of ON patients and in VEP latencies between the affected and non-ON eyes. Motion perception differentially correlated with latencies of both ON eyes and with the non-ON eyes. Retinal nerve fiber layer thickness correlated with the latencies of non-ON eyes but not of either ON eye. No difference in lesion load was found between the ON and non-ON patients.Conclusions: ON still leaves its mark in the patient's visual system over time, with all visual measures of the affected eyes notably reduced compared to fellow eyes. Motion perception, reflecting myelination level along the visual pathway, shows its usefulness also in progressive MS. In the non-ON eyes, axonal loss appears to explain prolonged latencies, unlike in ON eyes, where demyelination appears to be the main mechanism. Lastly, the visual measures assessed herein are applicable as valid assessment tools in therapeutic studies.

Temporal visual resolution and disease severity in MS.

ObjectiveTo examine temporal visual resolution assessed as critical flicker frequency (CFF) in patients with MS and to investigate associations with visual system damage and general disability and cognitive function.MethodsThirty-nine patients with MS and 31 healthy controls (HCs) were enrolled in this cross-sectional study and underwent CFF testing, high- and low-contrast visual acuity, alertness and information processing speed using the paced auditory serial addition task (PASAT), and retinal optical coherence tomography (OCT). In patients with MS, visual evoked potentials (VEPs) and Expanded Disability Status Scale (EDSS) scores were assessed.ResultsCFF in patients with MS (mean ± SD: 40.9 ± 4.4 Hz) was lower than in HCs (44.8 ± 4.4 Hz, p < 0.001). There was no significant CFF difference between eyes with and without previous optic neuritis (ON). CFF was not associated with visual acuity, VEP latency, the peripapillary retinal nerve fiber layer thickness, and the combined ganglion cell and inner plexiform layer volume. Instead, reduced CFF was associated with worse EDSS scores (r2 = 0.26, p < 0.001) and alertness (r2 = 0.42, p = 0.00042) but not with PASAT (p = 0.33).ConclusionCFF reduction in MS occurs independently of ON and structural visual system damage. Its association with the EDSS score and alertness suggests that CFF reflects global disease processes and higher cortical processing rather than focal optic nerve or retinal damage.

A composite measure to explore visual disability in primary progressive multiple sclerosis.

BackgroundOptical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS).ObjectivesThe objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS).MethodsTwenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores.ResultsPCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R2 0.328, p = 0.00004; adjusted R2 0.187, p = 0.002 and adjusted R2 0.180, p = 0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R2 value 0.361, p = 0.00001) and LCVA 2.50% (adjusted R2 value 0.323, p = 0.00003).ConclusionA multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS.

Severe structural and functional visual system damage leads to profound loss of vision-related quality of life in patients with neuromyelitis optica spectrum disorders

BackgroundNeuromyelitis optica spectrum disorders (NMOSD) are characterized by devastating optic neuritis attacks causing more structural damage and visual impairment than in multiple sclerosis (MS). The objective of this study was to compare vision-related quality of life in NMOSD and MS patients and correlate it to structural retinal damage and visual function. MethodsThirty-one NMOSD and 31 matched MS patients were included. Vision-related quality of life was assessed with the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). All patients underwent retinal optical coherence tomography and visual acuity and contrast sensitivity measurements. ResultsVision-related quality of life was reduced in NMOSD compared to MS patients. This difference was driven by a higher incidence of bilateral and more severe optic neuritis in the NMOSD group. Retinal thinning and visual impairment were significantly greater in the NMOSD cohort. Lower vision-related quality of life was associated with more retinal damage and reduced visual function as assessed by visual acuity and contrast sensitivity. ConclusionNMOSD-related bilateral ON-attacks cause severe structural damage and visual impairment that lead to severe loss of vision-related quality of life. The NEI-VFQ is a helpful tool to monitor vision-related quality of life in NMOSD patients.

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients.

BackgroundAntibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in the retina of MOG-IgG-positive patients in comparison with AQP4-IgG-positive NMOSD patients.MethodsAfferent visual system damage following ON was bilaterally assessed in 16 MOG-IgG-positive patients with a history of ON and compared with that in 16 AQP4-IgG-positive NMOSD patients. In addition, 16 healthy controls matched for age, sex, and disease duration were analyzed. Study data included ON history, retinal optical coherence tomography, visual acuity, and visual evoked potentials.ResultsEight MOG-IgG-positive patients had a previous diagnosis of AQP4-IgG-negative NMOSD with ON and myelitis, and eight of (mainly recurrent) ON. Twenty-nine of the 32 eyes of the MOG-IgG-positive patients had been affected by at least one episode of ON. Peripapillary retinal nerve fiber layer thickness (pRNFL) and ganglion cell and inner plexiform layer volume (GCIP) were significantly reduced in ON eyes of MOG-IgG-positive patients (pRNFL = 59 ± 23 μm; GCIP = 1.50 ± 0.34 mm3) compared with healthy controls (pRNFL = 99 ± 6 μm, p < 0.001; GCIP = 1.97 ± 0.11 mm3, p < 0.001). Visual acuity was impaired in eyes after ON in MOG-IgG-positive patients (0.35 ± 0.88 logMAR). There were no significant differences in any structural or functional visual parameters between MOG-IgG-positive and AQP4-IgG-positive patients (pRNFL: 59 ± 21 μm; GCIP: 1.41 ± 0.27 mm3; Visual acuity = 0.72 ± 1.09 logMAR). Importantly, MOG-IgG-positive patients had a significantly higher annual ON relapse rate than AQP4-IgG-positive patients (median 0.69 vs. 0.29 attacks/year, p = 0.004), meaning that on average a single ON episode caused less damage in MOG-IgG-positive than in AQP4-IgG-positive patients. pRNFL and GCIP loss correlated with the number of ON episodes in MOG-IgG-positive patients (p < 0.001), but not in AQP4-IgG-positive patients.ConclusionsRetinal neuro-axonal damage and visual impairment after ON in MOG-IgG-positive patients are as severe as in AQP4-IgG-positive NMOSD patients. In MOG-IgG-positive patients, damage accrual may be driven by higher relapse rates, whereas AQP4-IgG-positive patients showed fewer but more severe episodes of ON. Given the marked damage in some of our MOG-IgG-positive patients, early diagnosis and timely initiation and close monitoring of immunosuppressive therapy are important.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0720-6) contains supplementary material, which is available to authorized users.

Retinal regeneration mechanisms linked to multiple cancer molecules: A therapeutic conundrum.

Over the last decade, a large number of research articles have been published demonstrating regeneration and/or neuroprotection of retinal ganglion cells following manipulation of specific genetic and molecular targets. Interestingly, of the targets that have been identified to promote repair following visual system damage, many are genes known to be mutated in different types of cancer. This review explores recent literature on the potential for modulating cancer genes as a therapeutic strategy for visual system repair and looks at the potential clinical challenges associated with implementing this type of therapy. We also discuss signalling mechanisms that have been implicated in cancer and consider how similar mechanisms may improve axonal regeneration in the optic nerve.

Neuronal Afferent Visual System Damage in MOG-Antibody Associated Optic Neuritis Is as Severe as in AQP4-Antibody Positive NMOSD (P4.275)

Neuronal Afferent Visual System Damage in MOG-Antibody Associated Optic Neuritis Is as Severe as in AQP4-Antibody Positive NMOSD (P4.275)

Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243.

Traumatic brain injury (TBI) frequently leads to chronic visual dysfunction. The purpose of this study was to investigate the effect of TBI on retinal ganglion cells (RGCs), and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent in vivo functional deficits in the visual system. Blast-mediated TBI was modeled using an enclosed over-pressure blast chamber. The RGC physiology was evaluated using a multielectrode array and pattern electroretinogram (PERG). Histological analysis of RGC dendritic field and cell number were evaluated at the end of the study. Visual outcome measures also were evaluated based on treatment of mice with P7C3-S243 or vehicle control. We show that deficits in neutral position PERG after blast-mediated TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with development of dendritic abnormalities and irreversible death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction. Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic CNS and visual system damage after TBI at an earlier stage when treatments may be more effective in preventing these sequelae. In addition, treatment with the neuroprotective agent P7C3-S243 after TBI protects from visual system dysfunction after TBI.

Brain-state-dependent non-invasive brain stimulation and functional priming: a hypothesis.

Brain-state-dependent non-invasive brain stimulation and functional priming: a hypothesis.

Insulin-like growth factor-1 binding protein 3 (IGFBP-3) promotes recovery from trauma-induced expression of inflammatory and apoptotic factors in retina

Ocular trauma affects 20% of Americans in their lifetime and can cause permanent visual system damage. We have used a mouse model of ocular trauma (exposure to an air blast from a paintball gun) to examine pathways that trigger the resulting retinal damage and to develop treatment strategies that might ameliorate the deleterious effects of trauma on retinal tissue. Our previous studies have shown that ocular blast causes an increase in protein levels of inflammatory mediators and apoptotic factors, including tumor necrosis factor alpha (TNFα) and interleukin-1-beta (IL-1β), as well as the apoptotic markers, Bax, cytochrome C, and cleaved caspase 3. Furthermore, topical treatment by eye drop application of a β-adrenergic receptor agonist, Compound 49b, was shown to decrease these inflammation/apoptosis markers and thus ameliorate the effects of blast trauma. We postulate that the protective effect of Compound 49b may be linked to its demonstrated ability to activate the β-adrenergic receptor and in turn trigger production of insulin-like growth factor binding protein 3 (IGFBP-3). In the current study, we tested this hypothesis using mice with minimal IGFBP-3 activity (IGFBP-3 knockdown mouse) vs. wildtype mice. We found that ocular blast alone did not affect IGFBP-3 levels in retinas of wild type or knockdown mice and surprisingly, the lower levels of IGFBP-3 in knockdown animals did not exacerbate the blast-induced increase in protein levels of inflammation/apoptosis markers. Nevertheless, the levels of IGFBP-3 were significantly increased in knockdown mouse retina by treatment with Compound 49b 24h post-trauma and as expected, the increase in IGFBP-3 was linked to a decrease in inflammation/apoptosis markers. We conclude that while lowered IGFBP-3 may not make the retina more vulnerable to blast injury, an increase in IGFBP-3 post-trauma may play an important role in limiting trauma-induced inflammatory and apoptotic pathways leading to retinal damage. Eye drop application of the β-adrenergic receptor agonist, Compound 49b, provides a promising treatment strategy for increasing IGFBP-3 levels to promote recovery from retinal inflammation and apoptosis after ocular blast.

Brain functional connectivity network breakdown and restoration in blindness.

To characterize brain functional connectivity in subjects with prechiasmatic visual system damage and relate functional connectivity features to extent of vision loss. In this case-control study, resting-state, eyes-closed EEG activity was recorded in patients with partial optic nerve damage (n = 15) and uninjured controls (n = 13). We analyzed power density and functional connectivity (coherence, Granger causality), the latter as (1) between-areal coupling strength and (2) individually thresholded binary graphs. Functional connectivity was then modulated by noninvasive repetitive transorbital alternating current stimulation (rtACS; 10 days, 40 minutes daily; n = 7; sham, n = 8) to study how this would affect connectivity networks and perception. Patients exhibited lower spectral power (p = 0.005), decreased short- (p = 0.015) and long-range (p = 0.033) coherence, and less densely clustered coherence networks (p = 0.025) in the high-alpha frequency band (11-13 Hz). rtACS strengthened short- (p = 0.003) and long-range (p = 0.032) alpha coherence and this was correlated with improved detection abilities (r = 0.57, p = 0.035) and processing speed (r = 0.56, p = 0.049), respectively. Vision loss in the blind is caused not only by primary tissue damage but also by a breakdown of synchronization in brain networks. Because visual field improvements are associated with resynchronization of alpha band coherence, brain connectivity is a key component in partial blindness and in restoration of vision.

The second face of blindness: Processing speed deficits in the intact visual field after pre- and post-chiasmatic lesions

PURPOSE Damage along the visual pathway results in a visual field defect (scotoma), which retinotopically corresponds to the damaged neural tissue. Other parts of the visual field, processed by the uninjured tissue, are considered to be intact. However, perceptual deficits have been observed in the visual field, but these functional impairments are poorly understood. We now studied temporal processing deficits in the intact visual field of patients with either pre- or post-chiasmatic lesions to better understand the functional consequences of partial blindness. METHODS Patients with pre- (n = 53) or post-chiasmatic lesions (n = 98) were tested with high resolution perimetry--a method used to map visual fields with supra-threshold light stimuli. Reaction time of detections in the intact visual field was then analyzed as an indicator of processing speed and correlated with features of the visual field defect. RESULTS Patients from both groups exhibited processing speed deficits in their presumably field as indicated by comparison to a normative sample. Further, in both groups processing speed was found to be a function of two factors. Firstly, a spatially restricted (retinotopic) influence of the scotoma was seen in longer reaction times when stimuli were presented in intact field sectors close to the defect. Secondly, patients with larger scotomata had on average longer reaction times in their intact field indicating a more general (non-retinotopic) influence of the scotoma. CONCLUSIONS Processing speed deficits in the visual field of patients with visual system damage demonstrate that visual system lesions have more widespread consequences on perception than previously thought. Because dysfunctions of the seeing field are expected to contribute to subjective vision, including visual tests of the presumed field may help to better understand vision loss and to improve methods of vision restoration and rehabilitation.

P 125. Transorbital alternating current stimulation strengthens oscillatory activity and functional connectivity in patients with visual system damage: A resting-state EEG study

Introduction Non-invasive brain stimulation is an emerging treatment option for patients suffering from visual system damage and persistent visual field loss. Transorbital alternating current stimulation (tACS) applied daily for 10days was shown to improve patients‘ detection abilities (Sabel et al., 2011) and subjective quality of vision (Gall et al., 2011). Further, 10days tACS treatment progressively increases alpha band power in the resting state EEG of the treated subjects (Schmidt et al., in press). However, immediate neurophysiological after-effects of tACS have not been studied so far. Objective To investigate immediate neurophysiological effects of a single tACS session in patients with visual system damage. Methods Optic neuropathy patients were randomly assigned to either placebo ( n =7) or verum group ( n =7). The stimulation was delivered with electrodes attached below and above each eye. Current parameters were individually adjusted: amplitude was set above the phosphene threshold, and frequencies ranging from 8 to 22Hz were used. Resting state eyes-closed EEG (20 electrodes acc. to 10–20 system) was recorded immediately before and after the tACS. Power density and coherence were calculated. Coherence graphs, representing the same number (40) of strongest connections (Fig. 2), were created for each subject and characterized by graph measures indicating of the small-world structure. Changes in EEG parameters were correlated with the extent of visual system damage as assessed by perimetry. Results One session of tACS: (i) increased power of delta, theta and beta bands at the occipital region; (ii) increased theta and beta bands coherence between occipital electrodes (Fig. 1); (iii) altered the structure of beta band coherence graphs, as indicated by decreased characteristic path length (Fig. 2). Coherence increase was more profound in subjects with less extensive damage ( r =0.94; p =0.016). Conclusions One session of tACS modulates brain activity and connectivity in patients with visual system damage. The neuromodulation includes increase of power (delta, theta, beta bands) and coherence (theta, beta), and results in a modification of coherence network topology (beta) towards more optimal small-world pattern. These neurophysiological effects are stronger in subjects with mild optic nerve damage. Further, tACS induced neuromodulation seems to be non-specific, as power of frequencies not included in the stimulation protocol (delta, theta) also increased. Further studies need to elucidate how long these changes persist and how they relate to perceptual functioning and vision restoration. Funding The study was funded by the Otto-von-Guericke University, Magdeburg (see Figs. 1 and 2).

The Second Face of Blindness: Processing Speed Deficits in the Intact Visual Field after Pre- and Post-Chiasmatic Lesions

PurposeDamage along the visual pathway results in a visual field defect (scotoma), which retinotopically corresponds to the damaged neural tissue. Other parts of the visual field, processed by the uninjured tissue, are considered to be intact. However, perceptual deficits have been observed in the “intact” visual field, but these functional impairments are poorly understood. We now studied temporal processing deficits in the intact visual field of patients with either pre- or post-chiasmatic lesions to better understand the functional consequences of partial blindness.MethodsPatients with pre- (n = 53) or post- chiasmatic lesions (n = 98) were tested with high resolution perimetry – a method used to map visual fields with supra-threshold light stimuli. Reaction time of detections in the intact visual field was then analyzed as an indicator of processing speed and correlated with features of the visual field defect.ResultsPatients from both groups exhibited processing speed deficits in their presumably “intact” field as indicated by comparison to a normative sample. Further, in both groups processing speed was found to be a function of two factors. Firstly, a spatially restricted (retinotopic) influence of the scotoma was seen in longer reaction times when stimuli were presented in intact field sectors close to the defect. Secondly, patients with larger scotomata had on average longer reaction times in their intact field indicating a more general (non-retinotopic) influence of the scotoma.ConclusionsProcessing speed deficits in the “intact” visual field of patients with visual system damage demonstrate that visual system lesions have more widespread consequences on perception than previously thought. Because dysfunctions of the seeing field are expected to contribute to subjective vision, including visual tests of the presumed “intact” field may help to better understand vision loss and to improve methods of vision restoration and rehabilitation.