High Resolution Perimetry Research Articles

Glaucoma Rehabilitation Using ElectricAI Transcranial Stimulation (GREAT)-Optimizing Stimulation Protocol for Vision Enhancement Using an RCT.

We compared the effect of three different transcranial electrical stimulation (tES) protocols delivered to the occipital lobe on peripheral vision in patients with glaucoma. A double-masked, placebo-controlled study was conducted with 35 patients with glaucoma. We compared three different tES protocols: anodal transcranial direct current stimulation (a-tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) against sham stimulation. Each patient attended four stimulation sessions (a-tDCS, tACS, tRNS, and sham) in a random order with at least 48hours between visits. Stimulation involved placing an anodal electrode over the occipital lobe (Oz) and cathodal electrode on the cheek for 20minutes. High-resolution perimetry (HRP) and multifocal visual evoked potential (mfVEP) measurements were made before and immediately after stimulation. Changes in HRP detection accuracy/reaction time and mfVEP signal-to-noise ratio (SNR)/latency were analyzed using linear mixed models. Compared to sham, HRP detection accuracy was significantly improved after a-tDCS in both the central 20-degree (b = 0.032, P = 0.018) and peripheral analysis (b = 0.051, P = 0.002). Additionally,mfVEP SNR was significantly increased (b = 0.016, P = 0.017) and the latency was shortened (b = -1.405, P = 0.04) by the a-tDCS in the central 20-degree analysis. In the peripheral analysis, there was a trend toward an enhancement of SNR after a-tDCS stimulation (b = 0.014, P = 0.052), but it did not reach statistical significance; latency was increased after tACS (b = 1.623, P = 0.041). No significant effects were found in comparison to other active tES protocols. A single session of a-tDCS enhances perceptual and electrophysiologic measures of vision in patients with glaucoma. However, the small magnitude of changes observed in HRP (3.2% for accuracy in central and 5.1% in peripheral) did not exceed previous test variability and may not be clinically meaningful. a-tDCS holds promise as a potential treatment for enhancing visual function. However, future studies are needed to evaluate the long-term effects and clinical relevance of this intervention using validated measures of perimetric changes in the visual field.

Computational Methods for Continuous Eye-Tracking Perimetry Based on Spatio-Temporal Integration and a Deep Recurrent Neural Network.

The measurement of retinal sensitivity at different visual field locations–perimetry–is a fundamental procedure in ophthalmology. The most common technique for this scope, the Standard Automated Perimetry, suffers from several issues that make it less suitable to test specific clinical populations: it can be tedious, it requires motor manual feedback, and requires from the patient high levels of compliance. Previous studies attempted to create user-friendlier alternatives to Standard Automated Perimetry by employing eye movements reaction times as a substitute for manual responses while keeping the fixed-grid stimuli presentation typical of Standard Automated Perimetry. This approach, however, does not take advantage of the high spatial and temporal resolution enabled by the use of eye-tracking. In this study, we introduce a novel eye-tracking method to perform high-resolution perimetry. This method is based on the continuous gaze-tracking of a stimulus moving along a pseudo-random walk interleaved with saccadic jumps. We then propose two computational methods to obtain visual field maps from the continuous gaze-tracking data: the first is based on the spatio-temporal integration of ocular positional deviations using the threshold free cluster enhancement (TFCE) algorithm; the second is based on using simulated visual field defects to train a deep recurrent neural network (RNN). These two methods have complementary qualities: the TFCE is neurophysiologically plausible and its output significantly correlates with Standard Automated Perimetry performed with the Humphrey Field Analyzer, while the RNN accuracy significantly outperformed the TFCE in reconstructing the simulated scotomas but did not translate as well to the clinical data from glaucoma patients. While both of these methods require further optimization, they show the potential for a more patient-friendly alternative to Standard Automated Perimetry.

Exploring Test-Retest Variability Using High-Resolution Perimetry.

PurposeTest–retest variability (TRV) of visual field (VF) data seriously degrades our capacity to recognize true VF progression. We conducted repeated high-resolution perimetry with a test interval of 0.5° to investigate the sources of TRV. In particular, we examined whether the spatial variance of the observed sensitivity changes or if their absolute magnitude was of more importance.MethodsSixteen eyes of 16 glaucoma patients were each tested three times at 61 VF locations along the superior-temporal 45° meridian using a modified protocol of the Octopus 900 perimeter. TRV was quantified as the standard deviation of the repeats at each point (retest-SD). We also computed the mean sensitivity at each point (retest-MS) and the running spatial-SD along the tested meridian. Multiple regression models investigated whether any of those variables (and also age, sex, and VF eccentricity) were significant independent determinants of TRV.ResultsThe main independent determinants of TRV were the retest-MS at −0.04 dB TRV/dB loss (P < 0.0001, t-statistic 5.05), and the retest-SD at 0.47 dB spatial variance/dB loss (P < 0.0001, t-statistic 12.5).ConclusionsThe larger effect for the spatial-SD suggested that it was perhaps a stronger determinant of TRV than scotoma depth per se. This might support the hypothesis that interactions between small perimetric stimuli, rapidly varying sensitivity across the field, and normal fixational jitter are strong determinants of TRV.Translational RelevanceOur study indicates that methods that might reduce the effects of jagged sensitivity changes, such as increasing stimulus size or better gaze tracking, could reduce TRV.

Detectability of Visual Field Defects in Glaucoma With High-resolution Perimetry.

To extrapolate the optimal test point resolution for assessment of glaucomatous visual field (VF) defects including subtle functional defects, we performed high-resolution perimetry with the 0.5 degrees test point resolution. Subjects were 11 eyes of 11 normal volunteers and 16 eyes of 16 glaucomatous patients. Octopus 900 custom test was used to measure 61 points with the test point resolution of 0.5 degrees on the temporal meridian of 45 degrees within the eccentricity of 30 degrees. In the glaucoma cases, VF profiles were extracted in 17 patterns of the test point resolutions that ranged from 0.5 to 8.5 degrees and the mean defect (MD), square root of loss variance (sLV), and maximum sensitivity loss (Max loss) were calculated. The influence of the test point resolution on MD, sLV, and Max loss was examined. In addition, the test range from the fixation point to the eccentricity of 30 degrees was divided into 3 zones. Similarly, each zone was investigated if the test point resolution exerted influence on the MD, sLV, and Max loss. Our glaucoma cases did not show any significant differences in MD and sLV regardless of the resolution. Max loss showed significant difference at resolution ≥1.0 degree. MD and sLV did not show significant differences by the change of resolution in each zone. Max loss showed significant differences at resolution ≥1.5 degrees within the central 10 degrees. To detect subtle VF defects within the eccentricity of 10 degrees, high-resolution perimetry with the test point resolution of <1.5 degrees is necessary.

Bernhard Sabel and 'Residual Vision Activation Theory': a History Spanning Three Decades.

This review has the purpose of retracing the work of Professor Bernard Sabel and his group over the last 2-3 decades, in order to understand how they achieved formulation of the 'Residual Vision Activation Theory'. The methodology proposed is described, from the first studies in 1995 with High Resolution Perimetry requiring a six-months training period, to the new technologies, such as repetitive transorbital Alternating Current Stimulation, that require ten days of training. Vision restoration therapy has shown improvement in visual responses irrespective of age at the training, lesion aetiology and site of lesion. The hypothesis that visual training may induce network plasticity, improving neuronal networks in cortical and subcortical areas of both hemispheres, appears to be confirmed by recent studies including observation of the cerebral activity by fMRI and EEG. However, the results are quite variable and the mechanisms that influence cerebral activity are still unclear. The residual vision activation theory has been much criticized, both for its methodology and analysis of the results, but it gave a new impulse to the research in this area, stimulating more studies on induced cerebral plasticity.

Vision Restoration Training for Glaucoma

IMPORTANCE Visual field loss due to retinal damage is considered irreversible, and methods are needed to achieve vision restoration. Behavioral vision training, shown to improve visual fields in hemianopia and optic nerve damage, might comprise such a method. OBJECTIVE To determine if behavioral activation of areas of residual vision using daily 1-hour vision restoration training for glaucoma for 3 months improves detection accuracy compared with placebo. DESIGN AND SETTING Prospective, double-blind, randomized, placebo-controlled clinical trial in an ambulatory care and home training setting. PARTICIPANTS Volunteer sample of patients with glaucoma (mean age, 61.7 years; age range, 39-79 years) with stable visual fields and well-controlled intraocular pressure. After randomization, 4 patients withdrew from the trial because of mild headaches (n = 2) or lack of time to complete the schedule (n = 2). INTERVENTIONS Computer-based vision restoration training for glaucoma (n = 15) or visual discrimination placebo training in the intact visual field (n = 15). MAIN OUTCOMES AND MEASURES The primary end point was change in detection accuracy in high-resolution perimetry. Secondary end points were 30° white-on-white and 30° blue-on-yellow near-threshold perimetry, as well as reaction time, eye movements, and vision-related and health-related quality of life. RESULTS Vision restoration training for glaucoma led to significant detection accuracy gains in high-resolution perimetry (P = .007), which were not found with white-on-white or blue-on-yellow perimetry. Furthermore, the pre-post differences after vision restoration training for glaucoma were greater compared with placebo in all perimetry tests (P = .02 for high-resolution perimetry, P = .04 for white on white, and P = .04 for blue on yellow), and these results were independent of eye movements. Vision restoration training for glaucoma (but not placebo) also led to faster reaction time (P = .009). Vision-related quality of life was unaffected, but the health-related quality-of-life mental health domain increased in both groups. CONCLUSIONS AND RELEVANCE Visual field defects caused by glaucoma can be improved by repetitively activating residual vision through training the visual field borders and areas of residual vision, thereby increasing their detection sensitivity. Our randomized clinical trial revealed evidence that visual field loss is in part reversible by behavioral, computer-based, online controlled vision training, comprising a new rehabilitation treatment option in glaucoma. Neuroplasticity of the visual cortex or higher cortical areas is the proposed mechanism of action. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01799707.

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 228. Repetitive transorbital alternating current stimulation (rtACS) alpha activity enhancement in patients with visual field deficits: a prospective, randomized, blinded, controlled, multicenter study

Retrospective studies suggested that rtACS simulates neuronal activity and results in neuroplasticity ( Fedorov et al., 2011 ). Prospective, randomized, controlled studies in patients with pre-chiasmatic optic nerve damage showed that rtACS reduces visual field deficits, enhances vision-related Quality of Life ( Gall et al., 2011 ) and entrains rhythmic brain activity (Schmidt et al., 2012). This is understood to reflect periodic enforcing ( Zaehle et al., 2010 ) associated with the activation of residual vision resulting in restoration of visual field deficits ( Sabel et al., 2011 ). The objective of the present prospective multicenter study is to provide evidence that alpha power gain over occipital electrodes is a bio-marker that can predict visual field size improvement. 80 patients with pre-chiasmatic partial optic nerve damage were randomized prior to inclusion in the sham-stimulation controlled rtACS trial ( RCT ). The stimulation group (n = 44) received rtACS for 20–40 min/day on 10 consecutive days. Treatment parameters were defined daily (1) by subject specific amperage when patients have an obvious perception of phosphenes, (2) the strongest alpha frequency over occipital electrodes (lower cut-off) and (3) the flicker-fusion frequency (upper cut-off). The control group ( n = 36) received subliminal stimulation. Electroencephalographic (EEG) power spectra were assessed on each of the 10 days over the occipital cortex. The size of visual fields was measured before and after treatment with high resolution perimetry (HRP). Data analysis was non-parametric regression to account for the heterogeneous patient-population. The EEG data shows a systematic enhancement of alpha-power after stimulation ( p < .05). This effect is stronger in the treatment group as compared with the placebo group ( p < .05). Enhanced alpha-power was associated with reduced visual field deficits ( p < <.05). Clinical results are reported in a complementary abstract. The results confirm that rtACS entrains alpha-oscillatory brain activity and show that changes in brain-rhythms is associated with changes in the visual field size. Thus, EEG alpha-oscillations seem to provide a bio-marker that can predict adaptive processes in a visual system with a pre-chiasmatic lesion. Future studies should continue to address the optimization of rtACS as well as the stratification by etiology prior to clinical application in individuals or small populations. The study was co-funded by the EBS Technologies GmbH.

IS 5. Clinical efficacy of non-invasive transorbital alternating current stimulation in optic neuropathy: A double-blind, randomized, sham-controlled multi-center study

Non-invasive brain current stimulation enhances neuronal plasticity in the visual system both in normal subjects and in patients with visual field loss ( Antal et al., 2012 , Sabel et al., 2011 ). In order to improve visual functions in patients with optic nerve damage we have now validated the efficacy of repetitive transorbital alternating current stimulation (rtACS) for the treatment of optic nerve damage in a randomized, multi-center clinical trial. A total of 98 patients were randomized in rtACS and sham group using stratified block randomisation considering the study center (3 levels) and the defect depth of visual fields at baseline (2 levels) as a potential prognostic factor. Patients were stimulated with 4 stimulation electrodes positioned near the closed eyes on 2 × 5 consecutive weekdays for 25–40 min daily with square pulse rtACS at 125% of individual phosphene threshold based on a preceding parameter optimization study (reported in an accompanying abstract). The sham group received a “minimal dose” of short-lasting single pulse phosphenes once per minute. Diagnostic sessions assessing visual field parameters, reaction times, visual acuity, and EEG were conducted 2 days before and after stimulation and at a 2-months follow-up. Eighty-two patients were finally included in the analyses. The primary analysis was directed to the comparison of percentage changes in detection rates in visual field diagnostics using the high resolution perimetry method (HRP) between the two treatment arms (rtACS vs. sham) with a significant difference in favor of rtACS ( p = 0.011; one-sided Mann–Whitney U ). RtACS-treated patients showed significant improvements after treatment (Hodges–Lehmann estimator for median increase 6.4%, 95%–CI (2.9%, 11.6%); p < 0.001 (Wilcoxon signed rank test one-sided). No significant change was seen in the sham-group (median change 1.1%, 95%–CI (−2.0%; 4.3%); p = 0.256. Due to a higher number of responders in the rtACS-group the mean improvement of visual fields was larger for visual field parameters after rtACS (23.96%) compared to sham (2.53%). RtACS-induced visual field changes were stable at a 2-months follow-up. Secondary perimetry measures confirmed this result, the most pronounced visual field changes being located in the central 5°. Covariance analysis for the logarithms of visual field change parameters did not reveal any significant differences between the study centers, neither as main factor nor as interaction with the treatment arm. EEG findings are reported in an accompanying abstract. RtACS treatment led to visual field improvement in patients with optic neuropathy suggesting that it is a viable clinical tool to improve visual fields in patients with long-lasting visual field loss. Together with the changes in EEG power spectra this finding supports the notion that visual system plasticity can be altered by non-invasive alternating current stimulation. The study was funded by EBS Technologies GmbH (Kleinmachnow, Germany) and the University of Magdeburg.

Evaluation of two treatment outcome prediction models for restoration of visual fields in patients with postchiasmatic visual pathway lesions

Visual functions of patients with visual field defects after acquired brain injury affecting the primary visual pathway can be improved by means of vision restoration training. Since the extent of the restored visual field varies between patients, the prediction of treatment outcome and its visualization may help patients to decide for or against participating in therapies aimed at vision restoration. For this purpose, two treatment outcome prediction models were established based on either self-organizing maps (SOMs) or categorical regression (CR) to predict visual field change after intervention by several features that were hypothesized to be associated with vision restoration. Prediction was calculated for visual field changes recorded with High Resolution Perimetry (HRP). Both models revealed a similar predictive quality with the CR model being slightly more beneficial. Predictive quality of the SOM model improved when using only a small number of features that exhibited a higher association with treatment outcome than the remaining features, i.e. neighborhood activity and homogeneity within the surrounding 5° visual field of a given position, together with its residual function and distance to the scotoma border. Although both models serve their purpose, these were not able to outperform a primitive prediction rule that attests the importance of areas of residual vision, i.e. regions with partial visual field function, for vision restoration.

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.

Remaining Visual Field and Preserved Subjective Visual Functioning Prevent Mental Distress in Patients with Visual Field Defects

Background: Patients with visual field defects after visual pathway lesion may experience reduced vision-related quality of life (vrQoL). It has not been clarified how vrQoL impairments contribute to vision-related mental distress.Methods: One hundred and eight subjects with visual field defects caused by optic neuropathies (age M = 57.6; SD = 13.7 years) answered the National Eye Institute Visual-Functioning Questionnaire 39 (NEI-VFQ) for vrQoL and the SF-12 Short Form Health Survey for health-related quality of life. A 10 item composite of NEI-VFQ “visual functioning” and 5 items of “mental-health symptoms due to vision problems” were subjected to Rasch analysis. The test battery comprised static and High Resolution Perimetry (HRP). Regression and path analysis were used to investigate associations between QoL, mental distress, and perimetry results.Results: A higher level of “visual functioning” was associated with monocular impairment and a larger remaining visual field compared to binocular impairment. Subjective “visual functioning” but not visual field parameters predicted “mental-health symptoms due to vision problems” which was the only variable associated with the SF-12 mental component score. The SF-12 physical component score was less strongly associated with “mental-health symptoms due to vision problems.” Here, reaction time in HRP and mean threshold in perimetry were additional significant variables. Path analysis revealed a significant path from remaining visual field via visual functioning on mental health.Conclusion: Subjective consequences of visual impairments in everyday life impact mental health rather than “objective” visual function loss as measured by perimetry. Since a higher extent of vrQoL was related to lower levels of mental distress, the maintenance of vrQoL could reduce and prevent mental distress due to vision problems. Patients with persisting visual field defects may benefit from neuropsychological rehabilitation and supportive therapies.

Local topographic influences on vision restoration hot spots after brain damage

Vision restoration training (VRT) in hemianopia patients leads to visual field enlargements, but the mechanisms of this vision restoration are not known. To investigate the role of residual vision in recovery, we studied topographic features of visual field charts and determined residual functions in local regions and their immediate surround. We analyzed High Resolution Perimetry visual field charts of hemianopic stroke patients (n = 23) before and after 6 months of VRT and identified all local visual field regions with ("hot spots", n = 688) or without restoration ("cold spots", n = 3426). Topographic features of these spots at baseline where then related to (i) their respective local residual function, (ii) residual activity in their spatial neighbourhood, and (iii) their distance to the scotoma border estimated in cortical coordinates following magnification factor transformation. Visual field areas had a greater probability of becoming vision restoration hot spots if they had more residual activity in both local areas and in a spatially limited surround of 5° of visual angle. Hot spots were typically also located closer than 4 mm from the scotoma border in cortical coordinates. Thus, restoration depended on residual activity in both the local region and its immediate surround. Our findings confirm the special role of residual structures in visual field restoration which is likely mediated by partially surviving neuronal elements. Because the immediate but not distant surround influenced outcome of individual spots, we propose that lateral interactions, known to play a role in perceptual learning and receptive field plasticity, also play a major role in vision restoration.

Reading Performance After Vision Rehabilitation of Subjects With Homonymous Visual Field Defects

To examine whether increased visual functioning after vision-restoration training (VRT) coincides with improved reading abilities. Prospective noncontrolled open-label trial. Controlled laboratory setting for all diagnostic procedures that were conducted before and after 6 months of home-based VRT with telemedicine support. Eleven subjects who had experienced a posterior-parietal stroke and have homonymous visual field defects. Six months of VRT (1 hour daily repeated light stimulation in the partially damaged visual field). VRT outcome measures were the number of detected light stimuli in eye-tracker controlled high-resolution perimetry and the spared visual field within the affected hemifield up to the relative and absolute defect visual field border (square degrees). Enlargements of spared visual field within the affected hemifield were correlated with changes of reading speed after VRT. After VRT, the number of detected light stimuli increased by 5.02 ± 4.31% (mean ± SD; P = .03). The spared visual field up to the relative defect visual field border increased from 18.09 ± 32.35 square degrees before to 137.40 ± 53.32 after VRT (P = .006), as well as for the absolute defect visual field border from 36.95 ± 33.77 square degrees before VRT to 152.02 ± 49.70 after VRT (P = .005). Reading speed increased from 108.95 ± 33.95 words per minute before VRT to 122.26 ± 30.35 after VRT (P = .017), which significantly correlated with increased spared visual field up to the relative defect visual field border (r = 0.73, P = .016). Measures of eye movement variability did not correlate with VRT outcome. VRT improved visual fields in parafoveal areas, which are most relevant for reading. This finding cannot be explained by changes in eye movement behavior. Because of a significant association between improvements of parafoveal vision and reading speed, we propose that patients with homonymous visual field defects who have reading deficits may benefit from visual stimulation by training.

Efficacy of vision restoration therapy after optic neuritis (VISION study): study protocol for a randomized controlled trial

BackgroundOptic neuritis is a frequent manifestation of multiple sclerosis. Visual deficits range from a minor impairment of visual functions through to complete loss of vision. Although many patients recover almost completely, roughly 35% of patients remain visually impaired for years, and therapeutic options for those patients hardly exist. Vision restoration therapy is a software-based visual training program that has been shown to improve visual deficits after pre- and postchiasmatic injury. The aim of this pilot study is to evaluate whether residual visual deficits after past or recent optic neuritis can be reduced by means of vision restoration therapy.Methods/designA randomized, controlled, patient- and observer-blinded clinical pilot study (VISION study) was designed to evaluate the efficacy of vision restoration therapy in optic neuritis patients. Eighty patients with a residual visual deficit after optic neuritis (visual acuity ≤0.7 and/or scotoma) will be stratified according to the time of optic neuritis onset (manifestation more than 12 months ago (40 patients, fixed deficit) versus manifestation 2 to 6 months ago (40 patients, recent optic neuritis)), and randomized into vision restoration therapy arm or saccadic training arm (control intervention). Patients will be instructed to complete a computer-based visual training for approximately 30 minutes each day for a period of 6 months. Patients and evaluators remain blinded to the treatment allocation throughout the study. All endpoints will be analyzed and P-values < 0.05 will be considered statistically significant. The primary outcome parameter will be the expansion of the visual field after 3 and 6 months of treatment as determined by static visual field perimetry and high resolution perimetry. Secondary outcome variables will include visual acuity at both low and high contrast, glare contrast sensitivity, visually evoked potentials, optical coherence tomography and other functional tests of the visual system, alertness, health-related quality of life, fatigue, and depression.DiscussionIf vision restoration therapy is shown to improve visual function after optic neuritis, this method might be a first therapeutic option for patients with incomplete recovery from optic neuritis.Trial registrationNCT01274702

Noninvasive transorbital alternating current stimulation improves subjective visual functioning and vision-related quality of life in optic neuropathy

Noninvasive repetitive transorbital alternating current stimulation (rtACS) can improve visual field size in patients with optic nerve damage, but it is not known if this is of subjective relevance. We now assessed patient reported outcomes to determine the association between visual field changes and vision-related quality of life (QoL). Patients having visual field impairments long after optic nerve damage (mean lesion age 5.5 years) were randomly assigned to a rtACS (n = 24) or sham stimulation group (n = 18). Visual fields and patient reported outcome measures (vision-related QoL: National Eye Institute Visual Function Questionnaire, NEI-VFQ and health-related QoL: Short Form Health Survey, SF-36) were collected before and after a 10-day treatment course with daily sessions of 20 to 40 minutes. The primary outcome measure was the percent change from baseline of detection ability (DA) in defective visual field sectors as defined by computer-based high resolution perimetry (HRP). Secondary outcome parameters included further HRP parameters as well as static and kinetic perimetry results. Changes in QoL measures were correlated with changes in primary and secondary outcome measures in both groups. DA increase in the defective visual field was significantly larger after rtACS (41.1 ± 78.9%, M ± SD) than after sham stimulation (13.6 ± 26.3%), P < 0.05. While there was a significant increase of DA in the whole tested HRP visual field after rtACS (26.8 ± 76.7%, P < 0.05), DA in sham-stimulation patients remained largely unchanged (2.7 ± 20.2%, ns). Results of secondary outcome measures (static and kinetic perimetry) provided further evidence of rtACS efficacy. Improvements in NEI-VFQ subscale "general vision" were observed in both groups but were larger in the rtACS group (11.3 ± 13.5, Z = -3.21, P < 0.001) than in the sham group (4.2 ± 9.4, Z = -1.73, P < 0.05) with a significant difference between groups (Z = -1.71, P < 0.05). DA change and some NEI-VFQ domains were correlated (r = 0.29, P < 0.05), but no significant correlations were observed between DA and SF-36 results. rtACS facilitates vision restoration after unilateral, long-term optic nerve lesion as assessed both by objective DA changes and improvements in some NEI-VFQ subscales. Both were positively but low correlated, which suggests that factors other than visual field size also contribute to improved vision-related QoL.

Combining Visual Rehabilitative Training and Noninvasive Brain Stimulation to Enhance Visual Function in Patients With Hemianopia: A Comparative Case Study

To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT). A comparative case study assessing feasibility and safety. A controlled laboratory setting. Two patients, both with right hemianopia after occipital stroke damage. METHODS AND OUTCOME MEASUREMENTS: Both patients underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2 sham tDCS with VRT was performed. The primary outcome, visual field border, was defined objectively by using high-resolution perimetry. Secondary outcomes included subjective characterization of visual deficit and functional surveys that assessed performance on activities of daily living. For patient 1, the neural correlates of visual recovery were also investigated, by using functional magnetic resonance imaging. Delivery of combined tDCS with VRT was feasible and safe. High-resolution perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient 1 also showed greater recovery of function in activities of daily living. Contrary to the expectation, patient 2 perceived greater subjective improvement in visual field despite objective high-resolution perimetry results that indicated otherwise. In patient 1, visual function recovery was associated with functional magnetic resonance imaging activity in surviving peri-lesional and bilateral higher-order visual areas. Results of preliminary case comparisons suggest that occipital cortical tDCS may enhance recovery of visual function associated with concurrent VRT through visual cortical reorganization. Future studies may benefit from incorporating protocol refinements such as those described here, which include global capture of function, control for potential confounds, and investigation of underlying neural substrates of recovery.

Visual field expansion after visual restoration therapy

Objective: To determine whether visual field expansion occurs with visual restoration therapy (VRT), using fundus-controlled microperimetry to assess visual fields. Design: This longitudinal cohort analysis assesses patients’ visual fields before and after visual restoration therapy using microperimetry and standard high-resolution perimetry. Subjects: Seven patients with stroke-induced homonymous field cuts were studied. Intervention: Visual restoration therapy is a computerized, home-based treatment aimed at reducing the size of the visual field defect of stroke patients with hemianopia through repetitive stimulation of the visual borderzone adjacent to the blind field. During twice-daily therapy for three months patients maintain central fixation while responding to eccentrically placed stimuli in the visual borderzone. The programme is adjusted monthly to changes in the patient’s visual field. Controversy exists as to whether expansion of visual fields measured at home with high-resolution perimetry is due to inadvertent eye movements and therefore would overrepresent the treatment’s effect. Main measures: Microperimentry uses an infrared camera to track retinal vessels so that any shift or movement between the reference image and the real-time fundus image corrects the stimulus position, thus delivering stimuli to known retinal locations, and allowing accurate assessment of visual fields independent of eye movements. Results: There was an average improvement in stimulus detection rate by microperimetry of 12.5% (range —1.4% to 38.9%, P =0.033). Six of 7 patients had ≥ 3% improvement in stimulus detection by home-based perimetry. Conclusion: Our results demonstrate modest but real expansion in visual fields following visual restoration therapy which is not due to eye movements.

Vision Restoration Through Extrastriate Stimulation in Patients With Visual Field Defects: A Double-Blind and Randomized Experimental Study

Background. Vision restoration therapy (VRT) to treat visual field defects used single-point visual stimulation in areas of residual vision up to now. The question arises if the efficiency of restoration can be increased when the entire region of blindness is trained by a visual stimulus aimed at activating extrastriate pathways (extrastriate VRT). Methods. In this crossover study, 18 patients with visual field defects with prior VRT experience were treated with 2 training paradigms. Group 1 (n = 8) first used extrastriate VRT followed by conventional standard VRT. Group 2 (n = 10) trained in reverse order. Visual field size was assessed with computer-based perimetry and subjective vision with the National Eye Institute Visual Function Questionnaire (NEI-VFQ). Results . In group 1, stimulus detection in high-resolution perimetry (HRP) improved by 5.9% (P < .01) after extrastriate VRT. After the second training period (standard VRT), detection further improved by 1.8% (P = .093). In group 2, detection performance improved after standard VRT by 2.9% (P < .05) and after extrastriate VRT by 2.9% (P < .05). Detection performance increased twice as much after extrastriate VRT (4.2%) than after standard VRT (2.4%; P < .05). All changes in fixation performance were unrelated to detection improvements. NEI-VFQ did not show any significant changes. Conclusion. Greater improvement after extrastriate VRT is interpreted as an activation of extrastriate pathways by massive “spiral-like” stimulation. These pathways bypass the damaged visual cortex, stimulating extrastriate cortical regions, and are thought to be involved in blindsight.

Long-term learning of visual functions in patients after brain damage

Purpose Systematic vision restoration training has been shown to improve the detection performance of brain-damaged patients with visual-field defects. So far, patients have been trained daily up to 6 months. We wished to determine whether intensive long-term training of 12 months further increases visual detection abilities. Methods Retrospective comparison of 17 patients with visual-field defects using vision restoration training for 12 months with a group of patients training for 6 months. Computer-based home training was completed for 6 months (about 195,000 stimuli presentations) or for 12 months (about 390,000 stimuli presentations). Visual fields were measured at baseline with Rodenstock Perimat 206 (monocular) at 90° eccentricity and at 54° eccentricity with high resolution perimetry (HRP) (binocular) after 6 months (post-6) and after 12 months (post-12) of training. Results Near-threshold perimetry revealed minor training effects, beyond 6 months, of 3.5% ( p = 0.099) in the right eye and of 1.5% ( p = 0.57) in the left eye. No effects of long-term training were evident in above threshold testing (0.8% detection improvement, n.s.). Conclusions Learning to detect above-threshold stimuli in patients with post-retinal lesions is completed after 6 months of practice with only marginal improvements thereafter. Near-threshold testing reveals that peripheral areas of the visual-field benefit from long-term training even if they are not trained.