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Biomedical subjects

Florian Gekeler

Publications and source records attributed to Florian Gekeler.

13 recordsLinked to original sources
PubMed2007

Compound subretinal prostheses with extra-ocular parts designed for human trials: successful long-term implantation in pigs.

BACKGROUND: Subretinal implants aim to replace photoreceptor function in patients suffering from degenerative retinal disease like retinitis pigmentosa by topically applying electrical stimuli in the subretinal space. This study-as a last step before upcoming human trials-explored a newly developed surgical technique for permanent implantation of complex subretinal implants with extra-ocular parts. METHODS: The implant consisted of a microphoto-diode array (MPDA) with 1550 electrodes and a 4x4 array of gold electrodes for direct electrical stimulation; both were mounted onto a polyimide foil for transscleral placement into the subretinal space. The foil carried connection lanes to a silicone cable that was implanted under the skin and led to a stimulator box in the animal's neck. Surgery was performed in 11 domestic pigs. Improved vitreo-retinal surgical technique consisted of a 180 degrees peripheral retinotomy and use of diathermy to penetrate the choroid in order to avoid choroidal haemorrhage. Subretinal forceps were used to place the implant safely onto the retinal pigment epithelium before the retina was flattened, peripheral laser photocoagulation was applied and the eye was filled with silicon oil. The implant was stabilized by a scleral fixation patch, use of a metal clamp with bone screws on the animal's skull and a tissue ring under the animal's skin in the neck. Behaviour was observed in the freely moving animals after direct subretinal electrical stimulation and funduscopy, optical coherence tomography, fluorescein angiography and histology were performed. RESULTS: All implants were successfully placed subretinally. In three animals a proliferative vitreo-retinopathy was observed after approximately 2 weeks. Otherwise, funduscopy and OCT demonstrated complete retinal attachment and FA showed no retinal vascular abnormalities over and around the implant. The animals showed clear behavioural reactions to electrical stimulation over the whole examination period. Histological examination failed to show any voltage-induced alteration in the cellular architecture of the retina overlying the stimulation electrodes. CONCLUSIONS: This study demonstrates the feasibility of a new surgical procedure for highly safe and controlled implantation of complex subretinal devices with extra-ocular parts. The new implant design proved to be safely implantable in free-moving pigs for an observation period of 4 weeks.

Animals↗
PubMed2007

Investigation of thermal effects of infrared lasers on the rabbit retina: a study in the course of development of an active subretinal prosthesis.

BACKGROUND: Retinal implants are intended to replace photoreceptors in patients suffering from degenerative retinal diseases such as retinitis pigmentosa. Data show that photodiodes in subretinal implants are not powerful enough to stimulate overlying retinal tissue by simply transforming light energy into electrical energy. Therefore, infrared (IR) irradiation has been envisioned to supply additional energy. While epiretinal implants mostly use induction coils for wireless energy transfer, IR irradiation seems to be an additional option. This study investigated the feasibility of an IR energy supply for an active subretinal implant by assessing thermal effects of IR irradiation onto the rabbit retina. METHODS: Polyimide foil strips carrying an optical sensor as well as a thermal sensor were implanted into the subretinal space of the eyes of nine rabbits using a transchoroidal surgical approach. The area of the thermal sensor was irradiated by an IR laser (830 nm) focused on the device. The sensor provided simultaneous real-time measurements of absolute temperature and irradiation density, allowing direct correlation of the temperature increase to different intensities of IR irradiation. Possible IR-related damage to the retina was examined in histological sections. Temperature changes in living and dead animals were evaluated as a function of IR irradiation power of between 0.1 mW and 40 mW (0.03 mW/mm2-12.7 mW/mm2). RESULTS: We found an exponential relationship between IR irradiation power and temperature increase over the whole range (up to 12.7 mW/mm2) in the living animal. The maximum temperature increase caused by IR irradiation of 40 mW (12.7 mW/mm2) was 4.5 degrees C. The ratio of temperature increase to IR irradiation density postmortem (i.e., without ocular blood flow) was linear over the whole range, with 1.15 degrees C per 1 mW/mm2. Thus, the cooling effect of ocular blood flow varied depending on IR irradiance density. In histological sections, no IR-induced damage to the retina was detected. CONCLUSIONS: A temperature increase of 3.2 degrees C in the living rabbit eye is to be expected when powering a subretinal implant with 15 mW (4.8 mW/mm2) IR power, the wattage used in an external power supply for an active implant with 1,500 electrodes. This appears to be a tolerable increase for ocular tissue.

Animals↗
PubMed2006

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.

Action Potentials↗
PubMed2006

Phosphenes electrically evoked with DTL electrodes: a study in patients with retinitis pigmentosa, glaucoma, and homonymous visual field loss and normal subjects.

PURPOSE: To develop an improved, easy, and safe method for reliably eliciting electrical phosphenes and to compare reported perceptions and values of chronaxie and rheobase in healthy individuals and patients with distinct ophthalmic diseases. METHODS: DTL electrodes were used with a four-alternative, forced-choice method to determine psychophysically the strength-duration curves by using the Weiss model of electrical tissue stimulation in 47 subjects: healthy individuals (n = 17; n = 6 under light- and dark-adapted conditions), patients with open-angle glaucoma (n = 9), retinitis pigmentosa (RP; n = 14), amblyopia (n = 3), or homonymous visual field loss (n = 4). RESULTS: In all subjects, thresholds were safely determined without side effects. Subjects reported a homogenous, central, white, steady phosphene. The rheobase was higher in glaucoma and patients with RP than in healthy subjects (0.1129 +/- 0.0314 and 0.6868 +/- 0.1054 vs. 0.0383 +/- 0.0057 mA; P = 0.05 and <0.00001, respectively), and it increased with age (r = 0.51; P = 0.038). The rheobase was lower in light- than in dark-adapted conditions (difference 0.015 mA; P = 0.016). In patients with RP, no correlation was found between rheobase or chronaxie and retinal thickness (in OCT) or number of years after reading loss, but there was a correlation between rheobase and visual acuity (P = 0.014). In patients with RP or glaucoma, no inhomogeneity of phosphenes was reported, but all patients with homonymous visual field loss reported lateralization of the phosphene into the area of visual loss. CONCLUSIONS: Use of DTL electrodes to elicit electrical phosphenes is safe, fast, and reliable. It bears significant advantages over corneal electrodes and provides a valuable tool to elucidate ophthalmologic disease processes and to screen candidates for retinal prostheses.

Adult↗
PubMed2005

Scotopic threshold responses to infrared irradiation in cats.

Infrared (IR) irradiation is frequently used in ophthalmological diagnosis and treatment. It has been used to selectively stimulate photodiode-based retinal prostheses to prove their function. Data concerning the natural IR-sensitivity of the retina are contradictory. In our experiments in dark-adapted cats an IR-laser (826 nm) and IR emitting diodes (875 nm) elicited clear scotopic threshold responses. Comparison of the two lasers (IR and a visible laser at 670 nm) using Lambs template and our experimental data revealed very similar differences in retinal sensitivity (4.28 and 3.94+/-0.29 log units, respectively). The fact that the cat retina is sensitive to IR-irradiation under certain conditions has important implications in interpreting the results from retinal prostheses and rewards further attention in its use in many ophthalmological applications.

Animals↗
PubMed2005

Intraconal grease-gun injury: a therapeutic dilemma.

The case of a 31-year-old man with an accidental grease-gun injury to his left orbital region is presented. CT and MRI showed a well-delineated intraconal cyst in the superior aspect of the left orbit surrounded by a significant inflammatory response. The patient was followed for 11 months. Diplopia was not reported at any time, and visual acuity, visual fields, and all other examinations remained normal. Uneventful surgical removal was performed at the patient's request. Histopathologic examination demonstrated a typical picture of lipogranulomatous inflammation. In a review of the accessible literature, only four cases of intraorbital grease-gun injuries were detected; all of them submitted to early surgical removal. We conclude, however, that an intraconal oil/grease cyst can be carefully monitored and--in the absence of symptoms--must not necessarily be removed.

Accidents, Occupational↗
PubMed2004

Subretinal implantation and testing of polyimide film electrodes in cats.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. One concept under investigation is an electronic subretinal prosthesis to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: In the subretinal prosthesis design concept, an array of stimulation electrodes is placed in the subretinal space. To test the feasibility of the concept and to determine basic stimulation parameters, wire-bound stimulation devices were used in acute trials for up to 12 h in three eyes in anaesthetised cats. These wire-bound stimulation elements were based on strips of polyimide film. The film strips were introduced through a sclerostomy into the vitreous cavity and via a retinotomy into the subretinal space during a modification of the standard three-port vitrectomy procedure. On entry through the retinotomy, the film was advanced mechanically to the desired position in the area centralis. Perfluorocarbon liquid (PFCL) was used to establish close contact between the electrode array and the outer retina. Stimulation was performed with computer-generated sequences of current waveforms in acute trials immediately after surgical implantation of the stimulation film. Cortical recordings in the primary visual cortex were performed with electrodes placed in locations corresponding to the retinal stimulus site. RESULTS: All three implantations were carried out successfully with the stimulation array implanted beneath the outer retina of the area centralis of the operated eye. The retina was attached over the stimulation array in all cases. No cortical responses were recorded in one of the stimulation sessions. The results from another session revealed clear intracortical responses to subretinal stimulation with polyimide films. Following single-site retina stimulation, the estimates of spatial cortical resolution and temporal resolution were approximately 1 mm and 20-50 ms, respectively. DISCUSSION: Our results indicate that focal subretinal stimulation evokes localised spatio-temporal distribution of cortical responses. These findings offer hope that coarse restoration of vision may be feasible by subretinal electrical stimulation.

Animals↗
PubMed2004

Subretinal electrical stimulation of the rabbit retina with acutely implanted electrode arrays.

BACKGROUND: Subretinal implants intend to replace photoreceptor function in patients suffering from degenerative retinal disease by topically applying electrical stimuli from the subretinal space. This study intended to prove the feasibility of a newly developed transchoroidal surgery and, furthermore, of a subretinal electrode array, which closely resembles envisioned human implants to electrically stimulate the visual system in rabbits. METHODS: Five rabbits (ten eyes) were implanted with a 4x2-electrode array via a transchoroidal access to the subretinal space. The electrodes were connected to an arbitrary stimulus generator to apply voltage pulses. Retinae were accessed by light microscopy after stimulation with various intensities. RESULTS: The stimulating foil could be introduced into the subretinal space in all eyes. In seven of ten eyes electrically evoked cortical potentials following subretinal electrical stimulation could be elicited. Threshold voltages ranged from less than 0.1 to 2.38 V with a corresponding threshold charge of approximately 1.0 nC per electrode or 10 micro C/cm(2). Histology revealed localized retinal damage over some of the electrodes succeeding stimulation strengths of 2 V and consistent damage over all electrodes succeeding voltages of 3 V. CONCLUSIONS: The study demonstrates the feasibility of the transchoroidal surgical access to place subretinal implants in rabbit eyes and provides proof of successful cortical activation following subretinal electrical stimulation by an electrode array envisioned for human implantations.

Animals↗
PubMed2004

In vivo assessment of subretinally implanted microphotodiode arrays in cats by optical coherence tomography and fluorescein angiography.

BACKGROUND: Following multiple promising investigations into restoration of vision in degenerative retinal disease by implantation of a sub- or epiretinal prosthesis, the step to clinical use in humans is impending. In this study we intended to establish optical coherence tomography (OCT) and fluorescein angiography (FA) first in research animals for noninvasive assessment of the condition of the posterior pole of eyes after intraocular implant surgery. METHODS: Three adult cats that had undergone subretinal implant surgery were evaluated by OCT and FA between 1 and 470 days postoperatively. Eight adult cats served as control. In addition histology was performed. RESULTS: In all three cats OCT demonstrated stable positioning of the implants in the subretinal space during the complete examination period. Transient retinal edema was found in the early postoperative period but decreased during follow-up. The retina over the implants was well attached at all times in cats 1 and 2; however, in cat 3 localized retinal detachment was demonstrated. FA showed intact retinal vasculature over the subretinal implant in high detail without interference from choroidal background fluorescence. CONCLUSIONS: OCT and FA have been fruitfully applied to cats to assess the morphological and circulatory conditions of the neuroretina and of its interface with the subretinal implant. The techniques may therefore provide a tool for objective, noninvasive in vivo evaluation of eyes that have undergone subretinal implant surgery, both in research animals and in humans.

Animals↗
PubMed2004

Electroretinography as a screening method for mutations causing retinal dysfunction in mice.

PURPOSE: To detect mice with hereditary retinal impairment, a high-throughput electroretinography (ERG) screening system was established. METHOD: Mice from eight different strains without known retinal disorders (102, 129/SvJ, AKR, C57BL/6J, C57BL/6JIco, CBA/CaJ, and DBA/2NCrlBR) and one control strain with retinal degeneration (C3HeB/FeJ) were fixed on a specially constructed sled, ERG electrodes were placed on the cornea, and mice were moved into a Ganzfeld stimulator. From a luminance range of 0.0125 to 500 cd-s/m(2) in a pretest series two levels (5 and 125 cd-s/m(2)) were chosen to shorten examination times. The root mean square (RMS) of the ERG-recording was analyzed to detect animals with abnormal retinal function. ERG responses of the left and right eyes were compared in amplitudes and implicit times of the a- and b-waves. Statistical analysis of the latter parameters was performed in all wild-type animals. Histology was performed on selected mice. RESULTS: ERG recordings of individual animals for the left and right eye revealed good agreement in amplitudes and implicit times of the a- and b-waves (P < 0.05). Comparison of these parameters among the wild-type strains showed several differences. Evaluation of the RMS revealed, in addition to the C3HeB/FeJ mice, a subgroup of mice within the 129/SvJ strain with abnormal retinal function. Molecular analysis of these mice demonstrated the presence of the same retroviral insertion in the Pde6b gene, which is causative of the Pde6b(rd1) allele carried in C3HeB/FeJ mice. Histologic analysis demonstrated good correlation between retinal electrophysiology and morphology. CONCLUSIONS: The present results demonstrate the feasibility of ERG for screening a large number of mice to detect animals with functional retinal impairment.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

An in vivo doxycycline-controlled expression system for functional studies of the retina.

PURPOSE: Transgenic mice were developed that express tetracycline-controlled transactivator 1 (tTA1) specifically in photoreceptor cells. In these mice the transcription of the gene of interest can be easily inactivated in the retina in a short time frame. METHODS: A construct was prepared containing tTA1 under control of the murine rhodopsin regulatory region. This construct was used for the generation of transgenic mice. In situ hybridization was performed to study the distribution of the transactivator in the retina. The activity of the transactivator was analyzed by mating the lines with a luciferase reporter transgenic mouse. tTA1 activity and doxycycline's ability to block it were analyzed by luciferase assay. The effects of tTA1 on the retina were assessed by histology and electrophysiology. RESULTS: Two transgenic lines were developed that specifically express tTA1 in photoreceptor cells. The time course of transgene expression replicated transcription of endogenous rhodopsin. tTA1 was not toxic to the retina. Transactivator activity was blocked readily by doxycycline. CONCLUSIONS: An expression system for photoreceptor cells was generated to drive transcription in a cell-specific and time-controllable manner. This system is suitable for the study of factors involved in retinal biology and of mutant forms of genes involved in retinal diseases.

Animals↗
PubMed2002

Diffusion-weighted magnetic resonance imaging during the aura of pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis.

A typical feature of pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis (PMP) is the long duration of aura symptoms. To determine if these prolonged auras cause early ischemic parenchymal changes, we performed diffusion-weighted magnetic resonance imaging during the aura of a patient with PMP and found no reduction of water diffusion.

Adult↗