Search

Purpose: After promising results of an exploratory study, this study was designed to assess the safety and efficacy of transcorneal electrical stimulation (TES) over 1 year in patients with retinitis pigmentosa (RP)., Methods: We included 52 RP patients in this prospective, randomized, partially-masked study which was done in accordance with rules of good clinical practice. Transcorneal electrical stimulation by Okustim was applied monocularly for 30 minutes per week for 52 consecutive weeks. Patients were assigned randomly to the groups: sham, 150%, or 200% of individual electrical phosphene threshold (EPT). Visual acuity (retroilluminated Snellen charts), visual field (VF; Octopus 900), electroretinography (ERG), rod and cone full-field stimulus threshold, EPTs and IOP were assessed. Primary outcome measures were VF area; secondary outcome measures were development of ERG parameters., Results: The application of TES was tolerated well. Dry eye symptoms (31 of 52 patients) were registered as the main adverse event. Throughout the study period, the VF area showed only a trend for prevention of VF loss in the 200% group (P = 0.24). A significant improvement of light-adapted single flash b-wave was noted for the 200% (P < 0.0001) and 150% (P = 0.006) groups compared to the sham group. Tendencies of improved function were observed for scotopic b-wave amplitude for the 200% group (P = 0.097). Other examination methods did not reach statistical significance., Conclusions: The safety and acceptable tolerability of weekly TES self-administered by patients at home was confirmed over the course of 1 year. Objectively measured improvements in retinal function with ERG provide support for the potential benefits of TES for RP patients.

Purpose: This study aimed to quantify the impact of high altitude on choroidal thickness and relate changes of altered choroidal blood flow to clinical parameters and acute mountain sickness (AMS). This work is related to the Tübingen High Altitude Ophthalmology (THAO) study., Methods: Enhanced depth imaging spectral-domain optical coherence tomography was used to quantify macular choroidal layer thickness. Peripheral oxygen saturation, heart rate, and AMS scores were assessed in eight healthy subjects at baseline (altitude, 341 m) and at altitude (4559 m) for respective correlations., Results: Longitudinal analysis revealed a significant (P = 0.011, ANOVA) increase in central choroidal thickness (CCT) during altitude exposure (CCT baseline = 271 ± 9 μm; CCT altitude = 288 ± 9 μm) due to an increased choroidal blood flow. Incidence of AMS at altitude was 50%, peripheral oxygen saturation decreased by 25%, and heart rate increased by 39%. All changes were completely reversible after descent to low altitudes., Conclusions: A small but significant increase in choroidal thickness was observed upon acute altitude exposure to 4559 m. This increase in choroidal blood flow was not related to AMS and was fully reversible after return to low altitude.

Purpose: This study aimed to quantify the impact of exposure to high altitude on individual layers of the cornea in regard to central corneal thickness (CCT) and the geometry of the anterior chamber angle (ACA). This work is related to the Tübingen High Altitude Ophthalmology study., Methods: Anterior segment spectral domain optical coherence tomography was used to quantify changes in individual corneal layers and to study ACA and angle opening distance (AOD). Peripheral oxygen saturation, heart rate, and scores of acute mountain sickness (AMS) were assessed in 14 healthy subjects at baseline (341 m) and altitude (4559 m) for respective correlations., Results: Longitudinal analysis revealed a significant (P < 0.05) increase of CCT during altitude exposure (CCT(baseline) = 539.27 ± 32.30 μm; CCT(day1) = 558.87 ± 29.39 μm; CCT(day3) = 567.17 ± 33.40 μm; mean ± SD) due to stromal edema. This change was completely reversible upon descent. Geometric measures of aqueous outflow structures remained consistent with no significant changes in AOD or ACA. Incidence of AMS on day 1 was 64% followed by a decrease in AMS scores over time spent at high altitude; while AMS correlated significantly with stromal edema formation just after arrival (r = 0.71; P = 0.01), no correlation was found on day 3 (r = 0.05; P = 0.87); no correlations were found for vital parameters., Conclusions: Significant stromal edema was found during exposure to high altitude in healthy subjects. This seems to occur due to decreased atmospheric pressure under hypoxia but independent of systemic acclimatization. Other measures of anterior chamber geometry remained stable during the challenge to hypoxic conditions at high altitude.

Purpose: To evaluate electrically evoked phosphene thresholds (EPTs) in healthy subjects and in patients with retinal disease and to assess repeatability and possible correlations with common ophthalmologic tests., Methods: In all, 117 individuals participated: healthy subjects (n = 20) and patients with retinitis pigmentosa (RP, n = 30), Stargardt's disease (STG, n = 14), retinal artery occlusion (RAO, n = 20), nonarteritic anterior ischemic optic neuropathy (NAION, n = 16), and primary open-angle glaucoma (POAG, n = 17). EPTs were determined at 3, 6, 9, 20, 40, 60, and 80 Hz with 5 + 5-ms biphasic current pulses using DTL electrodes. Subjects were examined twice (test-retest range: 1-6 weeks). An empirical model was developed to describe the current-frequency relationship of EPTs. Visual acuity, visual field (kinetic + static), electrophysiology (RP, RAO, STG: Ganzfeld-electroretinography [ERG]/multifocal-ERG; POAG: pattern-ERG; NAION: VEP), slit-lamp biomicroscopy, fundus examination, and tonometry were assessed., Results: EPTS varied between disease groups (20 HZ: healthy subjects: 0.062 ± 0.038 mA; STG: 0.102 ± 0.097 mA; POAG: 0.127 ± 0.09 mA; NAION: 0.244 ± 0.126 mA; RP: 0.371 ± 0.223 mA; RAO: 0.988 ± 1.142 mA). In all groups EPTs were lowest at 20 Hz. In patients with retinal diseases and across all frequencies EPTs were significantly higher than those in healthy subjects, except in STG at 20 Hz (P = 0.09) and 40 Hz (P = 0.17). Test-retest difference at 20 Hz was 0.006 mA in the healthy group and 0.003-0.04 mA in disease groups., Conclusions: Considering the fast, safe, and reliable practicability of EPT testing, this test might be used more often under clinical circumstances. Determination of EPTs could be potentially useful in elucidation of the progress of ophthalmologic diseases, either in addition to standard clinical assessment or under conditions in which these standard tests cannot be used meaningfully. (ClinicalTrials.gov number, NCT00804102.).

Purpose: To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats., Methods: Thirty-three Sprague Dawley albino rats were divided into three groups: STIM (n = 15) received 60 minutes of TES, whereas SHAM (n = 15) received identical sham stimulation 2 hours before exposure to bright light with 16,000 lux; healthy animals (n = 3) served as controls for histology. At baseline and weekly for 3 consecutive weeks, dark- and light-adapted electroretinography was used to assess retinal function. Analysis of the response versus luminance function retrieved the parameters Vmax (saturation amplitude) and k (luminance to reach ½Vmax). Retinal morphology was assessed by histology (hematoxylin-eosin [HE] staining; TUNEL assay) and immunohistochemistry (rhodopsin staining)., Results: Vmax was higher in the STIM group compared with SHAM 1 week after light damage (mean intra-individual difference between groups 116.06 μV; P = 0.046). The b-wave implicit time for the rod response (0.01 cd.s/m²) was lower in the STIM group compared with the SHAM group 2 weeks after light damage (mean intra-individual difference between groups 5.78 ms; P = 0.023); no other significant differences were found. Histological analyses showed photoreceptor cell death (TUNEL and HE) in SHAM, most pronounced in the superior hemiretina. STIM showed complete outer nuclear layer thickness preservation, reduced photoreceptor cell death, and preserved outer segment length compared with SHAM (HE and rhodopsin)., Conclusions: This sham-controlled study shows that TES can protect retinal cells against mild light-induced degeneration in Sprague Dawley rats. These findings could help to establish TES as a treatment in human forms of retinal degenerative disease.

Purpose: Transcorneal electrical stimulation (TES) has been beneficial in several neurodegenerative ocular diseases, but the exact mechanisms remain to be elucidated. This study was conducted to investigate the effects of TES on the retinas of wild-type Brown Norway (BN) rats by gene expression profiling and to assess its effects on retinal function and morphology., Methods: TES was applied to BN wild-type rat retinas in vivo for 1 hour (1-ms biphasic pulses at 20 Hz; 200 μA). RNA was isolated and processed for microarray-based profiling 4 hours after TES; differentially expressed genes from TES compared with those from sham-treated animals were validated by quantitative real-time polymerase chain reaction. Furthermore, the effect of TES was assessed at the structural and functional levels using electroretinography, confocal scanning laser ophthalmoscopy, optical coherence tomography, and immunohistochemistry., Results: Transcriptome changes associated with TES versus sham-stimulated BN wild-type retina were identified. Four hundred ninety genes were differentially expressed in TES and included potentially neuroprotective genes such as Bax or members of the tumor necrosis factor family (Tnfrsf11b, Tnrsf12a, Tnfsf13b, Tnfsf13). ERG recordings showed physiological retinal function after TES, and structural in vivo and ex vivo studies revealed intact retinal anatomy., Conclusions: These results demonstrate that TES applied to the retina of the wild-type BN rats induces distinct transcriptome level changes and may help in the understanding of the mechanisms underlying TES. In addition, TES treatment indicates no negative effect on structure and function of the wild-type BN retina up to 35 hours after application.

Purpose: To assess the safety of transcorneal electrical stimulation (TES) and explore its efficacy in various subjective and objective parameters of visual function in patients with retinitis pigmentosa (RP)., Methods: Twenty-four patients in this prospective, randomized, partially blinded, good-clinical-practice study underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks. The patients were randomly assigned to one of three groups: sham, 66%, or 150% of individual electrical phosphene threshold (EPT). Visual acuity (VA), visual field (VF; kinetic, static), electroretinography (Ganzfeld, multifocal), dark-adaptation (DA), color discrimination, and EPTs were assessed at all visits or four times, according to the study plan., Results: TES using DTL electrodes was tolerated well; all patients finished the study. Two adverse (foreign body sensation), but no serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and scotopic b-wave amplitude reached statistical significance (P < 0.027 and P < 0.001, respectively). Only desaturated color discrimination and VF mean sensitivity decreased. There was no obvious trend in the 66% group., Conclusions: TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.).