Florian Gekeler

Subretinal electronic chips allow blind patients to read letters and combine them to words

A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes (‘chip’), each with its own amplifier and local stimulation electrode. At the implants tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron–electrode interface. Visual scenes are projected naturally through the eyes lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals.

Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS

This study aims at substituting the essential functions of photoreceptors in patients who are blind owing to untreatable forms of hereditary retinal degenerations. A microelectronic neuroprosthetic device, powered via transdermal inductive transmission, carrying 1500 independent microphotodiode-amplifier-electrode elements on a 9 mm2 chip, was subretinally implanted in nine blind patients. Light perception (8/9), light localization (7/9), motion detection (5/9, angular speed up to 35 deg s−1), grating acuity measurement (6/9, up to 3.3 cycles per degree) and visual acuity measurement with Landolt C-rings (2/9) up to Snellen visual acuity of 20/546 (corresponding to decimal 0.037 or corresponding to 1.43 logMAR (minimum angle of resolution)) were restored via the subretinal implant. Additionally, the identification, localization and discrimination of objects improved significantly (n = 8; p < 0.05 for each subtest) in repeated tests over a nine-month period. Three subjects were able to read letters spontaneously and one subject was able to read letters after training in an alternative-force choice test. Five subjects reported implant-mediated visual perceptions in daily life within a field of 15° of visual angle. Control tests were performed each time with the implants power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life.

Spatial Resolution and Perception of Patterns Mediated by a Subretinal 16-Electrode Array in Patients Blinded by Hereditary Retinal Dystrophies

PURPOSE The perception of 11 persons blinded by hereditary retinal degeneration elicited by a subretinally implanted 16-electrode array used for light-independent direct stimulation of the retina is described. This device is part of the Tübingen retina implant, which also employs a light-sensitive, multiphotodiode array (MPDA). The ability to reliably recognize complex spatial percepts was investigated. METHODS Eleven blind volunteers received implants and participated in standardized psychophysical tests investigating the size and shape of perceptions elicited by single-electrode activation, multiple-electrode activation, and activation of compound patterns such as simplified letters. RESULTS Visual percepts were elicited reliably in 8 of 11 patients. On single-electrode activation, percepts were generally described as round spots of light of distinguishable localization in the visual field. On activation of a pattern of electrodes, percepts matched that pattern when electrodes were activated sequentially. Patterns such as horizontal or vertical bars were identified reliably; the most recent participant was able to recognize simplified letters presented on the 16-electrode array. The smallest distance between sites of concurrent retinal stimulation still yielding discernible spots of light was assessed to be 280 μm, corresponding to a logMAR of 1.78. CONCLUSIONS Subretinal electric stimulation can yield reliable, predictable percepts. Patterned perception is feasible, enabling blind persons to recognize shapes and discriminate different letters. Stimulation paradigms must be optimized, to further increase spatial resolution, demanding a better understanding of physical and biological effects of single versus repetitive stimulation (ClinicalTrials.gov number, NCT00515814).

Subretinal Visual Implant Alpha IMS – Clinical trial interim report

A subretinal visual implant (Alpha IMS, Retina Implant AG, Reutlingen, Germany) was implanted in 29 blind participants with outer retinal degeneration in an international multicenter clinical trial. Primary efficacy endpoints of the study protocol were a significant improvement of activities of daily living and mobility to be assessed by activities of daily living tasks, recognition tasks, mobility, or a combination thereof. Secondary efficacy endpoints were a significant improvement of visual acuity/light perception and/or object recognition (clinicaltrials.gov, NCT01024803). During up to 12 months observation time twenty-one participants (72%) reached the primary endpoints, of which thirteen participants (45%) reported restoration of visual function which they use in daily life. Additionally, detection, localization, and identification of objects were significantly better with the implant power switched on in the first 3 months. Twenty-five participants (86%) reached the secondary endpoints. Measurable grating acuity was up to 3.3 cycles per degree, visual acuities using standardized Landolt C-rings were 20/2000, 20/2000, 20/606 and 20/546. Maximal correct motion perception ranged from 3 to 35 degrees per second. These results show that subretinal implants can restore very-low-vision or low vision in blind (light perception or less) patients with end-stage hereditary retinal degenerations.

Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients

Background: Due to low energy levels in microphotodiode-based subretinal visual prostheses, an external power supply is mandatory. We report on the surgical feasibility and the functional outcome of the extraocular part of an approach to connect a subretinal prosthesis to an extracorporeal connector in the retro-auricular space via a trans-scleral, transchoroidal cable. Methods: Seven volunteers with retinitis pigmentosa received an active subretinal implant; energy was supplied by gold wires on a trans-sclerally, transchoroidally implanted polyimide foil leading to the lateral orbital rim where it was fixated and connected to a silicone cable. The cable was implanted subperiostally beneath the temporal muscle using a trocar to the retro-auricular space where it penetrated the skin for connection to a stimulator. To avoid subretinal movement of the implant, three tension relief points have been introduced. Results: All implantations were performed as planned without complications, and no serious adverse events occurred in the postoperative period. Fixation of the implants was stable throughout the entire study duration of 4 weeks; permanent skin penetration proved to be uncomplicated. Motility was minimally restricted in downgaze and ab-/adduction. Explantation was uneventful. Conclusion: The above-described procedure provides a method for stable fixation of a subretinal device with a trans-scleral, transchoroidal cable connection to an extracorporeal connector.

Visual resolution with retinal implants estimated from recordings in cat visual cortex.

We investigated cortical responses to electrical stimulation of the retina using epi- and sub-retinal electrodes of 20-100 microm diameter. Temporal and spatial resolutions were assessed by recordings from the visual cortex with arrays of microelectrodes and optical imaging. The estimated resolutions were approximately 40 ms and approximately 1 degrees of visual angle. This temporal resolution of 25 frames per second and spatial resolution of about 0.8 cm at about 1m and correspondingly 8 cm at 10 m distance seems sufficient for useful object recognition and visuo-motor behavior in many in- and out-door situations of daily life.

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.).

Intraocular lens power calculation and optimized constants for highly myopic eyes

PURPOSE: To determine the accuracy of intraocular lens (IOL) power calculations in eyes with high myopia and to suggest adjusted constants for these cases. SETTING: Centre for Ophthalmology, Eberhard‐Karls‐University, Tuebingen, Germany. METHODS: Patients with high myopia having phacoemulsification with implantation of an AcrySof MA60MA IOL (power range +5.00 to −5.00 diopters [D]) were evaluated. Optical biometry (IOLMaster) and IOL calculations were performed before and after IOL implantation. Because of different optic principal planes of negative‐diopter and positive‐diopter IOLs, separate constants were calculated for these groups. RESULTS: Fifty eyes (32 patients) were evaluated. Thirty eyes (mean AL 31.15 mm ± 1.69 [SD]) had implantation of a positive‐diopter IOL (mean power +3.10 ± 1.50 D) and 18 eyes (mean AL 33.20 ± 2.25 mm), a negative‐diopter IOL (mean power −3.20 ± 1.70 D). Postoperatively, the mean spherical equivalent was −1.42 ± 1.33 D and −0.41 ± 1.81 D, respectively. The difference in optimized constants between positive‐ and negative‐diopter IOLs was significant for all formulas. Power calculation with the SRK II formula showed a wide range of deviation of postoperative refraction from target refraction. Calculation with the Haigis, SRK/T, Holladay 1, and Hoffer Q formulas showed a mean deviation of 0.00 D with an SD of 0.88, 0.92, 1.03, and 1.15, respectively. CONCLUSIONS: Results indicate that the SRK II formula cannot be recommended for IOL power calculation in highly myopic patients. With optimized constants, the SRK/T, Haigis, Hoffer Q, and Holladay 1 formulas produced small deviation of postoperative refraction from target refraction.

Effect of +3.00 diopter and +4.00 diopter additions in multifocal intraocular lenses on defocus profiles, patient satisfaction, and contrast sensitivity

PURPOSE: To evaluate the advantages and disadvantages of the new low‐addition (add) (+3.00 diopter [D]) ReSTOR multifocal IOL compared with the preceding ReSTOR model with +4.00 D add. SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Comparative case series. METHODS: Patients with a +3.00 D or +4.00 D add multifocal IOL were examined for uncorrected and distance‐corrected visual acuity at distance, intermediate, and near. A defocus profile was assessed, individual reading distance and the distance for lowest intermediate visual acuity were determined. Patient satisfaction was evaluated with a standardized questionnaire. Contrast sensitivity was tested under mesopic and photopic conditions. RESULTS: Uncorrected and distance‐corrected intermediate visual acuities were statistically significantly better in the +3.00 D add group (24 eyes) than in the +4.00 D add group (30 eyes); distance and near visual acuities were not different between groups. The defocus profile significantly varied between groups. The +4.00 D add group had a closer reading distance (33.0 cm) than the +3.00 D add group (43.5 cm), a closer point of lowest intermediate visual acuity (65.8 cm versus 86.9 cm) and worse lowest intermediate visual acuity (20/59 ± 4.5 letters [SD] versus 20/48 ± 5.5 letters). Thus, patients in the +3.00 D add group reported being more satisfied with intermediate visual acuity. The +3.00 D add group reported more glare but less halos than the +4.00 D add group; contrast sensitivity was not different. CONCLUSION: The lower addition resulted in a narrower defocus profile, a farther reading distance, and better intermediate visual acuity and thus increased patient satisfaction. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.

Functional Outcome in Subretinal Electronic Implants Depends on Foveal Eccentricity

PURPOSE An active microelectronic subretinal implant, developed to replace the photoreceptive function in hereditary degenerations of the outer retina, has been applied in a pilot and clinical study in patients with end-stage retinal degeneration. METHODS The study population comprised 20 blind patients, all of whom lost vision as result of a hereditary retinal disease. An active visual implant was placed surgically within the subretinal space of each patient: subfoveal placement in eight patients (group 1) and parafoveal placement in 12 (group 2). Standardized low-vision tests, including light perception, light localization, movement detection, grating acuity, and visual acuity by Landolt C-rings, were used under masked, randomized implant-OFF and implant-ON conditions. For the chip-mediated vision functional results of both subject groups were compared. RESULTS Three of 20 patients were excluded from analysis because of surgical or technical implant issues. Among patients with nonfoveal placement of the implant, 80% could perceive light, 10% recognized location, and 10% correctly distinguished stripe patterns up to a resolution of 0.33 cycles/degree. No nonfoveal placement patient passed the motion or Landolt C-ring tests. When the implant was placed subfoveally, 100% of patients could perceive light and determine light localization, 75% could resolve motion up to 35°/s, 88% correctly distinguished stripe patterns up to a resolution of 3.3 cycles/degree, and 38% passed a Landolt C-ring test with a decimal visual acuity of up to 20/546 (logMAR 1.43). CONCLUSIONS Subfoveal placement of active subretinal visual implants allows superior measurable outcomes compared to para- or nonfoveal placement locations. (ClinicalTrials.gov numbers, NCT01024803, NCT00515814.).