Oculomotor behavior of blind patients seeing with a subretinal visual implant.

Electronic implants are able to restore some visual function in blind patients with hereditary retinal degenerations. Subretinal visual implants, such as the CE-approved Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany), sense light through the eye's optics and subsequently stimulate retinal bipolar cells via ∼1500 independent pixels to project visual signals to the brain. Because these devices are directly implanted beneath the fovea, they potentially harness the full benefit of eye movements to scan scenes and fixate objects. However, so far, the oculomotor behavior of patients using subretinal implants has not been characterized. Here, we tracked eye movements in two blind patients seeing with a subretinal implant, and we compared them to those of three healthy controls. We presented bright geometric shapes on a dark background, and we asked the patients to report seeing them or not. We found that once the patients visually localized the shapes, they fixated well and exhibited classic oculomotor fixational patterns, including the generation of microsaccades and ocular drifts. Further, we found that a reduced frequency of saccades and microsaccades was correlated with loss of visibility. Last, but not least, gaze location corresponded to the location of the stimulus, and shape and size aspects of the viewed stimulus were reflected by the direction and size of saccades. Our results pave the way for future use of eye tracking in subretinal implant patients, not only to understand their oculomotor behavior, but also to design oculomotor training strategies that can help improve their quality of life.

Safety evaluation of "retina implant alpha IMS"--a prospective clinical trial.

BACKGROUND: To restore vision in patients with retinitis pigmentosa, several types of electronic devices have been developed to stimulate neurons at different levels along the visual pathway. Subretinal stimulation of the retina with the Retina Implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) has been demonstrated to provide useful vision in daily life. Here we evaluated the safety of this device. METHODS: An interventional, prospective, multi-center, single-arm study was conducted in patients with retinitis pigmentosa with the Retina Implant Alpha IMS. The results from the first nine patients of a single center regarding safety of the device are reported. Any untoward medical occurrence related or unrelated to the tested device was documented and evaluated. RESULTS: Nine adult subjects were included in the study at the Tübingen site. Seventy-five adverse events occurred in total, and 53 affected the eye and its adnexa. Thirty-one ocular adverse events had a relationship to the implant that was classified as "certain" while 19 had a probable or possible relationship; three had no relationship to the implant. Thirty-nine ocular adverse events resolved without sequelae, two resolved with sequelae, 11 remained unresolved, and in one the status was unknown. The intensity of ocular adverse events was mild in the majority of cases (n = 45), while six were of moderate and two of severe intensity. There was no non-ocular adverse event with certain relationship to the device. One subject lost light perception (without light localization) in her study eye. CONCLUSIONS: In conclusion, this prospective study, "Safety and Efficacy of Subretinal Implants for Partial Restoration of Vision in Blind Patients," shows that the Retina Implant Alpha IMS is an option for restoring vision using a subretinal stimulation device with a clinically acceptable safety profile.

Rate and timing of spontaneous resolution in a vitreomacular traction group: should the role of watchful waiting be re-evaluated as an alternative to ocriplasmin therapy?

INTRODUCTION: The incidence of spontaneous resolution of vitreomacular traction (VMT) is low in studies of Ocriplasmin that have had a limited follow-up. Previous studies did not look for morphological parameters in the natural history using spectral-domain ocular coherence tomography (SD-OCT) imaging. The purpose of this study was to investigate how often and when spontaneous VMT resolution occurs in candidates for Ocriplasmin therapy. METHODS: The study is a retrospective chart review of patients who would have high chances of a benefit by an Ocriplasmin injection, without epiretinal membrane or vitreomacular adhesion of 1500 µm or more on SD-OCT. Main outcome measures were the frequency of complete VMT resolution and the best corrected visual acuity seen in the natural history. RESULTS: Out of the 46 patients that were included after screening 889 SD-OCT images, 20 were found to exhibit spontaneous resolution during the follow-up period (median: 594 days, 95% CI 567 to 719 days), the majority after 6-12 months of observation (95% CI 266 to 617 days). The group with spontaneous VMT resolution and a mean improvement of one line in best corrected visual acuity included a few patients losing vision by macular hole formation. In the absence of resolution, patients lost on average one early treatment diabetic retinopathy study letter per year. Younger age was found to increase the chance of spontaneous resolution. CONCLUSIONS: A shorter follow-up might underestimate the incidence of spontaneous VMT resolution as the functional outcome of watchful waiting. The likelihood of resolution does not seem to decrease after 12 months.

Transcorneal electrical stimulation shows neuroprotective effects in retinas of light-exposed rats.

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.

Comparing the effects of two different irrigation solutions on an isolated perfused vertebrate retina.

PURPOSE: To compare the effect of a taurine-containing intraocular irrigation solution (PuriProtect TM) to a standard irrigation solution (BSS TM) we evaluated the retinal function using an electroretinogram (ERG) and analyzed the survival of retinal ganglion cells on isolated whole mount retinas. MATERIALS AND METHODS: During ERG recordings, each irrigation solution was superfused for 45 min with the relevant irrigation solution. To investigate the effects on photoreceptor function, 1 m M asparate was added to obtain a-waves.The recovery of the a- and b-wave was monitored after superfusing the retinas with standard medium again. To evaluate the percentage of dead ganglion cells, retinas were stored for 24 h at 4°C in darkness and after staining the retinas with ethidium homodimer-1 the retinas were analyzed using fluorescence microscopy. RESULTS: The application of standard medium supplemented with 2 m M taurine resulted in a significant increase of the b-wave amplitude compared to standard medium alone. The a-wave amplitudes showed no significant changes under taurine supplementation. Compared to standard medium BSS showed no significant decrease in b-wave amplitudes, but a significant decrease ina-wave amplitudes. In contrast to BSS there were no significant changes in the a- or b-wave amplitudes detectable after the application of PuriProtect. At the end of the washout period no significant changes in a- or b-wave amplitudes were recorded for any tested irrigation solution. Retinas stored for 24 h in PuriProtect or in standard medium with taurine had a statistically significant smaller amount of dead cells than retinas stored in standard medium without taurine supplementation. CONCLUSIONS: BSS does not seem to be an ideal irrigation solution, because it compromises the a-wave in the ERG. In contrast to BSS, PuriProtect showed no significant impact on the ERG and showed a better long-term effect on ganglion cell survival. Taurine supplementation,therefore, seems to be neuroprotective and its supplementation to an intraocular irrigation solution favorable for the retina.

Transcorneal electrical stimulation for patients with retinitis pigmentosa: a prospective, randomized, sham-controlled exploratory study.

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.).

Visualisation of active subretinal implants with external connections by high-resolution CT.

Two patients carrying an active subretinal implant with extra-ocular parts were examined by high-resolution CT. Cranial scans were acquired in the primary position and in eight additional directions of gaze with eyes open and closed to demonstrate the mobility of the eyeball and the implant within the orbital cavity. Three-dimensional images were constructed to visualise the path of the implant from the retro-auricular space around the lateral orbital rim through the orbit and within the subretinal space up to the device's final para-foveal position. Images were obtainable in high quality, resulting in three-dimensional models illustrating all parts of the implant including the micro-photodiode array at the tip in the subretinal space. The implant followed eye movements in all directions of gaze; eye movements were only minimally restricted as described in previous publications. Since all, except intra-ocular, parts of the implant evade direct examination, CT can be useful to assess the technical integrity and the biocompatibility and biostability of retinal implants.

Non-arteritic anterior ischemic optic neuropathy (NA-AION) after intravitreal injection of bevacizumab (Avastin) for treatment of angoid streaks in pseudoxanthoma elasticum.

BACKGROUND: To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin). METHODS: Interventional case report with an 18-month follow-up. RESULTS: A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors. DISCUSSION: Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin) in the treatment of retinal vascular diseases.