Combined Transcranial Direct Current Stimulation and Vision Restoration Training in Subacute Stroke Rehabilitation: A Pilot Study.

BACKGROUND: Visual field defects after posterior cerebral artery stroke can be improved by vision restoration training (VRT), but when combined with transcranial direct current stimulation (tDCS), which alters brain excitability, vision recovery can be potentiated in the chronic stage. To date, the combination of VRT and tDCS has not been evaluated in postacute stroke rehabilitation. OBJECTIVES: To determine whether combined tDCS and VRT can be effectively implemented in the early recovery phase following stroke, and to explore the feasibility, safety and efficacy of an early intervention. DESIGN: Open-label pilot study including a case series of 7 tDCS/VRT versus a convenience sample of 7 control patients (ClinicalTrials.gov ID: NCT02935413). SETTING: Rehabilitation center. SUBJECTS: Patients with homonymous visual field defects following a posterior cerebral artery stroke. METHODS: Seven homonymous hemianopia patients were prospectively treated with 10 sessions of combined tDCS (2.mA, 10 daily sessions of 20 minutes) and VRT at 66 (±50) days on average poststroke. Visual field recovery was compared with the retrospective data of 7 controls, whose defect sizes and age of lesions were matched to those of the experimental subjects and who had received standard rehabilitation with compensatory eye movement and exploration training. RESULTS: All 7 patients in the treatment group completed the treatment protocol. The safety and acceptance were excellent, and patients reported occasional skin itching beneath the electrodes as the only minor side effect. Irrespective of their treatment, both groups (treatment and control) showed improved visual fields as documented by an increased mean sensitivity threshold in decibels in standard static perimetry. Recovery was significantly greater (P < .05) in the tDCS/VRT patients (36.73% ± 37.0%) than in the controls (10.74% ± 8.86%). CONCLUSION: In this open-label pilot study, tDCS/VRT in subacute stroke was demonstrated to be safe, with excellent applicability and acceptance of the treatment. Preliminary effectiveness calculations show that tDCS/VRT may be superior to standard vision training procedures. A confirmatory, larger-sample, controlled, randomized, and double-blind trial is now underway to compare real-tDCS- versus sham-tDCS-supported visual field training in the early vision rehabilitation phase. LEVEL OF EVIDENCE: IV.

Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial.

BACKGROUND: Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. METHODS: We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. RESULTS: The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. CONCLUSION: rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280877.

Effects of alternating current stimulation on the healthy and diseased brain.

Cognitive and neurological dysfunctions can severely impact a patient's daily activities. In addition to medical treatment, non-invasive transcranial alternating current stimulation (tACS) has been proposed as a therapeutic technique to improve the functional state of the brain. Although during the last years tACS was applied in numerous studies to improve motor, somatosensory, visual and higher order cognitive functions, our knowledge is still limited regarding the mechanisms as to which type of ACS can affect cortical functions and altered neuronal oscillations seem to be the key mechanism. Because alternating current send pulses to the brain at predetermined frequencies, the online- and after-effects of ACS strongly depend on the stimulation parameters so that "optimal" ACS paradigms could be achieved. This is of interest not only for neuroscience research but also for clinical practice. In this study, we summarize recent findings on ACS-effects under both normal conditions and in brain diseases.

Visual rehabilitation: visual scanning, multisensory stimulation and vision restoration trainings.

Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: "compensation" and "restoration". Existing methods can be classified into three groups: Visual Scanning Training (VST), Audio-Visual Scanning Training (AViST) and Vision Restoration Training (VRT). VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local "within-system" interactions (i.e., relying on plasticity within peri-lesional spared tissue) and changes in more global "between-system" networks (i.e., recruiting alternative visual pathways) contribute to both vision restoration and compensatory rehabilitation, which ultimately have implications for the rehabilitation of cognitive functions.

Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke.

Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain.

Disturbed temporal dynamics of brain synchronization in vision loss.

Damage along the visual pathway prevents bottom-up visual input from reaching further processing stages and consequently leads to loss of vision. But perception is not a simple bottom-up process - rather it emerges from activity of widespread cortical networks which coordinate visual processing in space and time. Here we set out to study how vision loss affects activity of brain visual networks and how networks' activity is related to perception. Specifically, we focused on studying temporal patterns of brain activity. To this end, resting-state eyes-closed EEG was recorded from partially blind patients suffering from chronic retina and/or optic-nerve damage (n = 19) and healthy controls (n = 13). Amplitude (power) of oscillatory activity and phase locking value (PLV) were used as measures of local and distant synchronization, respectively. Synchronization time series were created for the low- (7-9 Hz) and high-alpha band (11-13 Hz) and analyzed with three measures of temporal patterns: (i) length of synchronized-/desynchronized-periods, (ii) Higuchi Fractal Dimension (HFD), and (iii) Detrended Fluctuation Analysis (DFA). We revealed that patients exhibit less complex, more random and noise-like temporal dynamics of high-alpha band activity. More random temporal patterns were associated with worse performance in static (r = -.54, p = .017) and kinetic perimetry (r = .47, p = .041). We conclude that disturbed temporal patterns of neural synchronization in vision loss patients indicate disrupted communication within brain visual networks caused by prolonged deafferentation. We propose that because the state of brain networks is essential for normal perception, impaired brain synchronization in patients with vision loss might aggravate the functional consequences of reduced visual input.

Mental distress in patients with cerebral visual injury assessed with the german brief symptom inventory.

BACKGROUND: While there are reports on vision-related quality of life in patients with vision impairment caused by both ophthalmic and brain diseases, little is known about mental distress. In fact, mental distress after cerebral visual injury has been widely ignored. METHODS: Mental health symptoms were assessed in 122 participants with visual field defects after brain damage (72 male, mean age 58.1 ± 15.6 years), who completed the German Brief Symptom Inventory (BSI) at their homes after they had been asked by phone for their participation. RESULTS: Clinically relevant mental distress was present in 25.4% of participants with cerebral visual injury. In case of multisensory impairment, an increased amount and intensity of mental distress symptoms was observed compared to the subsample with only visual impairment. CONCLUSION: Assessment of comorbid mental health symptoms appears to be clinically meaningful in brain-damaged patients with visual sensory impairment. In case of clinically relevant mental distress, psychological supportive therapies are advisable especially in subjects with cerebral visual injury and comorbidities affecting other sensory modalities as well.

Brain functional connectivity network breakdown and restoration in blindness.

OBJECTIVE: To characterize brain functional connectivity in subjects with prechiasmatic visual system damage and relate functional connectivity features to extent of vision loss. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

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.

"Sightblind": perceptual deficits in the "intact" visual field.

Unilateral visual cortex lesions caused by stroke or trauma lead to blindness in contralateral visual field - a condition called homonymous hemianopia. Although the visual field area processed by the uninjured hemisphere is thought to be "intact," it also exhibits marked perceptual deficits in contrast sensitivity, processing speed, and contour integration. Such patients are "sightblind" - their blindness reaches far beyond the primary scotoma. Studies showing perceptual deficits in patients' intact fields are reviewed and implications of these findings are discussed. It is concluded that consequences of partial blindness are greater than previously thought, since perceptual deficits in the "intact" field likely contribute to subjective vision loss in patients with visual field defect. This has important implications for vision diagnosis and rehabilitation.

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 "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. 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 "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. CONCLUSIONS: Processing 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.

Progressive enhancement of alpha activity and visual function in patients with optic neuropathy: a two-week repeated session alternating current stimulation study.

INTRODUCTION: Repetitive transorbital alternating current stimulation (rtACS) can improve visual deficits in patients with optic nerve damage. Recent retrospective results suggest that rtACS enhances oscillatory brain activity. The exact mechanisms of rtACS are unclear and little is known about possibly frequency-specific neural-plastic mechanisms. An association between bandwidth-confined neural-entrainment and vision recovery maximization could offer a novel therapeutic option for patients with optic neuropathy. OBJECTIVES: The goal of this prospective open-label study was to investigate if the enhancement of rhythmic brain activity over 10 days of consecutive rtACS stimulation is associated with visual field recovery. The secondary goal was to investigate neurophysiological mechanisms related to frequency dependent adaptive plasticity. METHODS: 18 Patients with visual field impairments resulting from pre-chiasmatic partial optic nerve damage received rtACS on 10 consecutive days. Daily, subject-specific treatment parameters (<500 µA, 9-37 Hz, 25-40 min/day) were defined and EEG-spectra collected prior to and after rtACS. Visual field data was collected at day 1 and 10. The change of spectral-power in classic bandwidths were investigated and correlated with visual field deficit recovery. RESULTS: After 10 days of rtACS alpha-power over bilateral occipital electrodes was significantly larger than at baseline (F(Time x alpha-power)p < 0.01). This effect was progressive over subsequent days of stimulation (cubic-fit, R(2) 0.70, RMSE 0.008). Perimetric results improved significantly, but they were not associated with changes in alpha-synchronization. DISCUSSION: rtACS can induce cumulative bandwidth-confined changes in brain rhythms over multiple sessions. These findings are in line with the notion of brain-state dependent [1] and bandwidth-confined entrainment [2] as well as rtACS facilitated visual recovery [3].

Reading performance after vision rehabilitation of subjects with homonymous visual field defects.

OBJECTIVE: To examine whether increased visual functioning after vision-restoration training (VRT) coincides with improved reading abilities. DESIGN: Prospective noncontrolled open-label trial. SETTING: Controlled laboratory setting for all diagnostic procedures that were conducted before and after 6 months of home-based VRT with telemedicine support. PATIENTS: Eleven subjects who had experienced a posterior-parietal stroke and have homonymous visual field defects. INTERVENTIONS: Six months of VRT (1 hour daily repeated light stimulation in the partially damaged visual field). MAIN OUTCOME MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Contralesional cross-over in chronic neglect: visual search patterns reveal neglect of the ipsilesional hemispace.

INTRODUCTION: With neuropsychological rehabilitation approaches neglect patients can learn to compensate for the reduced awareness of the contralesional hemispace that is often observed after right brain damage. Here, we report contralesional "cross-over" deviations in line bisection that are hypothesized to be a result of focusing on the contralesional hemispace while the intact hemispace is "neglected". We investigate whether this unexpected pattern of deviation is related to defects in the visual field, motor intention/hypokinesia deficits or deficits in working memory. METHODS: Neglect patients with and without homonymous field defects were screened for contralesional cross-over deviations in line bisection of long lines. During line bisection eye movements were recorded in two conditions with and without requiring hand movements in order to search for directional hypokinesia. Visual fields were tested with near-threshold perimetry and with supra-threshold campimetry. RESULTS: Of 53 chronic neglect patients only 8 showed cross-over in line bisection. Evidence for directional hypokinesia was found in only one patient. Patients with cross-over focused more often to the left than to the right of the objective line midpoint. Patients with and without visual field defects did not differ in the extent of cross-over deviations. Cross-over deviation and inconsistent stimulus detection in left hemispace were correlated irrespective of the presence of a visual field deficit. Larger cross-over deviations were associated with poorer verbal working memory span, and disorganized patterns of eye movement were related to reduced visuo-spatial working memory capacity. CONCLUSION: Increasing awareness of the disorder and the use of compensatory strategies may have led to a cross-over shift of visual search dominance towards the neglected side resulting in an exploration deficit of the ipsilesional side.

Psychological distress is associated with vision-related but not with generic quality of life in patients with visual field defects after cerebral lesions.

Considerably diminished quality of life (QoL) is observed in patients with visual field defects after lesions affecting the visual pathway. But little is known to what extent vision-and health-related QoL impairments are associated with psychological distress. In 24 patients with chronic visual field defects (mean age=56.17±12.36) the National Eye Institute-visual functioning questionnaire (NEI-VFQ) for vision-related QoL, the Short Form Health Survey-36 (SF-36) for generic QoL and the revised Symptom-Checklist (SCL-90-R) were administered. Cases with clinically relevant SCL-90-R symptoms were defined. Demographic, QoL and visual field parameters were correlated with SCL-90-R scales. About 40% of the investigated patients met the criteria for the definition of psychiatric caseness. 8/12 NEI-VFQ scales correlated significantly with SCL-90-R phobic anxiety (r-range -0.41 to -0.64, P<0.05), 5/12 NEI-VFQ scales correlated with SCL-90-R interpersonal sensitivity (-0.43 to -0.50), and 3/12 with SCL-90-R depression (-0.51 to -0.57) and obsessive-compulsiveness (-0.41 to -0.43). In contrast, only 1/8 SF-36 scales correlated significantly with SCL-90-R depression, phobic anxiety and interpersonal sensitivity (-0.41 to -0.54). No substantial correlations were observed between visual field parameters and SCL-90-R scales. Significant correlations of SCL-90-R with NEI-VFQ but not with SF-36 suggest that self-rated psychological distress is the result of diminished vision-related QoL as a consequence of visual field loss. The extent of visual field loss itself did not influence the rating of psychological distress directly, since SCL-90-R symptoms were only reported when diminished vision-related QoL was present. Patients with reduced vision-related QoL due to persisting visual field defects should therefore be offered additional neuropsychological rehabilitation and supportive psychotherapeutic interventions even years after the lesion.

Non-invasive alternating current stimulation improves vision in optic neuropathy.

PURPOSE: Partial blindness after visual system damage is considered irreversible, yet the brain has residual visual capacities and considerable plasticity potential. We now applied non-invasive alternating current stimulation (ACS) to the visual system of patients with optic nerve damage with the aim to induce recovery of visual functions. METHODS: In a prospective, double-blind, randomized, placebo-controlled clinical trial patients with several year old partial optic nerve lesions were treated with ACS (n = 12) or placebo-stimulation (n = 10). ACS was delivered transorbitally for 40 minutes on 10 days. Visual outcome measures and EEG were measured before and after treatment. RESULTS: ACS, but not placebo, led to significant improvement of a visual field detection deficit by 69%, and also significantly improved temporal processing of visual stimuli, detection performance in static perimetry, and visual acuity. These changes were associated with alpha-band changes in the EEG power spectra. Visual improvements were stable for at least 2-months. CONCLUSIONS: ACS can induce vision restoration many years after optic neuropathy. Though the mechanism is still unclear, EEG changes indicate increased synchronization in posterior brain regions. The present study provides Class Ib evidence that non-invasive transorbital ACS is well tolerated and improves visual function in optic neuropathy.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.