Matthias Feucht

A method and technical equipment for an acute human trial to evaluate retinal implant technology

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 microm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

The IMI Retinal Implant System

Ralf Hornig, Thomas Zehnder, Michaela Velikay-Parel, Thomas Laube, Matthias Feucht and Gisbert Richard 1IMI Intelligent Medical Implants GmbH, Bonn, Germany 2IMI Intelligent Medical Implants AG, Zug, Switzerland 3Division of Ophthalmology, University Hospital Graz 4Division of Ophthalmology, University Hospital Essen, Essen, Germany 5Division of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Acute electrical stimulation of the human retina with an epiretinal electrode array

Purpose:  To determine the threshold charges needed for eliciting visual perceptions through acute electrical stimulation of the human retina in patients suffering from retinitis pigmentosa, using an epiretinal microelectrode array.

Development of an epiretinal prosthesis for stimulation of the human retina

Degenerations of the outer retina in retinal diseases such as retinitis pigmentosa lead to blindness due to photoreceptor loss. A therapeutic option for visual rehabilitation is presently not available. Over the last few years, a retinal prosthesis has been developed and its use has been tested in animal experiments as well as in humans. With the epiretinal implant images of the environment are taken by a camera, these data are transmitted to an intraocular encoder, and the retina is electrically stimulated by a retinal stimulator placed epiretinally. The stimulation electrodes are placed as flexible microcontact electrodes by pars plana vitrectomy in an epimacular position. The threshold is determined by stimulations of increasing amplitudes. Initial results of acute epiretinal stimulation using an epiretinal implant in legally blind patients demonstrate that acute epiretinal stimulation of the human retina is feasible and safe.ZusammenfassungDegenerationen der äußeren Retina bei Erkrankungen wie Retinitis pigmentosa können über den Verlust der Photorezeptoren zu Erblindung führen. Eine Therapieoption zur visuellen Rehabilitierung besteht derzeit nicht.In den letzten Jahren wurde eine Retinaprothese entwickelt und die Möglichkeit des Einsatzes in Tierexperimenten und auch beim Menschen getestet.Beim epiretinalen Implantat werden Bilder der Umwelt von einer Kamera aufgenommen, diese Informationen an einen intraokularen Retinaencoder weitergeleitet und über elektrische Stimulation eines epiretinal platzierten Retinastimulators die Netzhaut gereizt.Mittels Pars-plana-Vitrektomie werden die Stimulationselektroden als flexible Mikrokontaktfolien epiretinal platziert. Der Schwellwert der Stimulation wird durch Stimulationsereignisse von steigender Amplitude bestimmt. Ferner werden die visuellen Wahrnehmungen des Probanden festgehalten.Erste Ergebnisse der akuten elektrischen Stimulation mit einem epiretinalen Implantat bei (im Sinne des Gesetzes) blinden Patienten zeigen, dass eine akute epiretinale Stimulation der menschlichen Netzhaut möglich und sicher ist.AbstractDegenerations of the outer retina in retinal diseases such as retinitis pigmentosa lead to blindness due to photoreceptor loss. A therapeutic option for visual rehabilitation is presently not available.Over the last few years, a retinal prosthesis has been developed and its use has been tested in animal experiments as well as in humans.With the epiretinal implant images of the environment are taken by a camera, these data are transmitted to an intraocular encoder, and the retina is electrically stimulated by a retinal stimulator placed epiretinally.The stimulation electrodes are placed as flexible microcontact electrodes by pars plana vitrectomy in an epimacular position. The threshold is determined by stimulations of increasing amplitudes.Initial results of acute epiretinal stimulation using an epiretinal implant in legally blind patients demonstrate that acute epiretinal stimulation of the human retina is feasible and safe.

Entwicklung einer epiretinalen Prothese zur Stimulation der humanen Netzhaut

Degenerations of the outer retina in retinal diseases such as retinitis pigmentosa lead to blindness due to photoreceptor loss. A therapeutic option for visual rehabilitation is presently not available. Over the last few years, a retinal prosthesis has been developed and its use has been tested in animal experiments as well as in humans. With the epiretinal implant images of the environment are taken by a camera, these data are transmitted to an intraocular encoder, and the retina is electrically stimulated by a retinal stimulator placed epiretinally. The stimulation electrodes are placed as flexible microcontact electrodes by pars plana vitrectomy in an epimacular position. The threshold is determined by stimulations of increasing amplitudes. Initial results of acute epiretinal stimulation using an epiretinal implant in legally blind patients demonstrate that acute epiretinal stimulation of the human retina is feasible and safe.ZusammenfassungDegenerationen der äußeren Retina bei Erkrankungen wie Retinitis pigmentosa können über den Verlust der Photorezeptoren zu Erblindung führen. Eine Therapieoption zur visuellen Rehabilitierung besteht derzeit nicht.In den letzten Jahren wurde eine Retinaprothese entwickelt und die Möglichkeit des Einsatzes in Tierexperimenten und auch beim Menschen getestet.Beim epiretinalen Implantat werden Bilder der Umwelt von einer Kamera aufgenommen, diese Informationen an einen intraokularen Retinaencoder weitergeleitet und über elektrische Stimulation eines epiretinal platzierten Retinastimulators die Netzhaut gereizt.Mittels Pars-plana-Vitrektomie werden die Stimulationselektroden als flexible Mikrokontaktfolien epiretinal platziert. Der Schwellwert der Stimulation wird durch Stimulationsereignisse von steigender Amplitude bestimmt. Ferner werden die visuellen Wahrnehmungen des Probanden festgehalten.Erste Ergebnisse der akuten elektrischen Stimulation mit einem epiretinalen Implantat bei (im Sinne des Gesetzes) blinden Patienten zeigen, dass eine akute epiretinale Stimulation der menschlichen Netzhaut möglich und sicher ist.AbstractDegenerations of the outer retina in retinal diseases such as retinitis pigmentosa lead to blindness due to photoreceptor loss. A therapeutic option for visual rehabilitation is presently not available.Over the last few years, a retinal prosthesis has been developed and its use has been tested in animal experiments as well as in humans.With the epiretinal implant images of the environment are taken by a camera, these data are transmitted to an intraocular encoder, and the retina is electrically stimulated by a retinal stimulator placed epiretinally.The stimulation electrodes are placed as flexible microcontact electrodes by pars plana vitrectomy in an epimacular position. The threshold is determined by stimulations of increasing amplitudes.Initial results of acute epiretinal stimulation using an epiretinal implant in legally blind patients demonstrate that acute epiretinal stimulation of the human retina is feasible and safe.

Neurofibromatosis 2 leads to higher incidence of strabismological and neuro-ophthalmological disorders.

Purpose:  Ophthalmic features of neurofibromatosis 2 (NF2) include juvenile cataract, retinal hamartomas and tumours of the cranial nerves. We hypothesize that these tumours lead to strabismological and neuro‐ophthalmological symptoms, including palsies of cranial nerves III, IV and VI, nystagmus and gaze palsies.

Radial Optic Neurotomy in Central Retinal Vein Occlusion Does Not Influence Ocular Hemodynamics

Purpose: Radial optic neurotomy (RON) is used for the treatment of central retinal vein occlusion. Its effects on visual acuity differ substantially between patients. Our study aims to evaluate if RON has an impact on ocular microcirculation and if analysis of ocular microcirculation might serve as a predictor for surgical success. Procedures: A complete ophthalmologic examination including color Doppler imaging of the retrobulbar vessels was performed before and 2–4 months after RON in 12 patients. Results: Mean visual acuity was 0.09 ± 0.03 prior to and 0.24 ± 0.12 after RON. Visual acuity improved in 7 (+3.5 ± 0.9 lines), was stable in 3 (±0 lines) and worsened in 2 cases (–6 and –2 lines). Doppler parameters were not affected by RON, and no correlations between visual acuity and perfusion parameters were found. Conclusions: Our data indicate that RON does not influence ocular microcirculation. None of the assessed hemodynamic parameters appears to be a predictor for surgical success.

Correlation of Nonsense and Frameshift Mutations With Severity of Retinal Abnormalities in Neurofibromatosis 2

BACKGROUND Neurofibromatosis 2 (NF2) is an autosomal dominant disease that is characterized by nervous system tumors and ocular abnormalities. OBJECTIVE To investigate genotype-phenotype correlations demonstrated for NF2-associated nervous system tumors, cataracts, and retinal lesions. METHODS Forty-eight patients with NF2 from a tertiary neurological referral center underwent screening for constitutional NF2 mutations with multiple screening methods. Each patient underwent a complete ophthalmic examination, including fluorescein angiography to detect retinal vascular lesions. RESULTS Retinal abnormalities (epiretinal membranes or retinal microaneurysms) were present in 25 of the 48 patients (52%). The occurrence of epiretinal membranes and retinal microaneurysms was highly correlated, but retinal abnormalities were not significantly correlated with cataracts (present in 39 of 47 patients [83%]). Logistic regression with full constitutional nonsense or frameshift mutations as the reference group demonstrated that somatic mosaicism was associated with a significantly lower likelihood of retinal abnormalities (odds ratio, 0.05; 95% confidence interval, 0.01-0.49). CONCLUSIONS To our knowledge, this is the first genetic, clinical, and angiographic characterization of retinal abnormalities in NF2. Severe mutations are correlated with a more severe retinal involvement. Clinical Relevance Retinal abnormalities, which can be revealed by means of fluorescein angiography, are more common in patients with NF2 who have nonsense or frameshift mutations.

Neurofibromatosis 2 leads to choroidal hyperfluorescence in fluorescein angiography.

BackgroundFor the diagnosis of NF 2, ocular findings like juvenile cataract, retinal and combined hamartomas of the retinal pigment epithelium and the retina as well as tumours of the optic nerve play an important role. An early diagnosis is essential in order to inhibit deafness from bilateral vestibular schwannoma. But sometimes the Manchester diagnostic criteria for NF2 are not completely fulfilled. Frequently, suspicious macular anatomy is found in neurofibromatosis 2 (NF2) patients. We hypothesise that the underlying retinal pigment epithelium or the retina of the macular region alters in NF2 patients. Therefore, we have tested by fluorescence angiography whether NF2 is associated with chorioretinal changes.Methods and patientsIn a prospective study, 48 patients matching the criteria for NF2 with known genotype underwent a complete ophthalmic examination including funduscopy and fluorescence angiography. The influence of the genotype was statistically analysed by odds ratios and their 95% confidence intervals.ResultsEleven eyes of nine patients showed choroidal hyperfluorescence in the macular region on fluorescence angiography. There was staining spreading from grainy hyperfluorescence to minor variants of a combined hamartoma of the retina and the retinal pigment epithelium. All of these manifestations presented without leakage in the late angiographic phases. These choroidal findings were present in one patient with frameshift mutation, in two patients with nonsense mutations and in six patients with splice site mutations of the NF2 gene. The statistical analysis showed a significant lower risk of choroidal alterations in patients with somatic mosaicism, deletions and unfound mutations.ConclusionUsing fluorescence angiography pathological changes of the macular region can be detected in NF2 patients. The ophthalmic examination, which often is limited to the anterior eye segment, may play a role in finding the diagnosis in incomplete NIH criteria. The presented study shows chorioretinal hyperfluorecences without leakage of the macular region, which might be considered as a forme fruste of a hamartoma. Choroidal hyperfluorescences add to the spectrum of genotype-phenotype correlations in NF2.

Functional and morphological long-term results after arteriovenous crossing sheathotomy.

the means of normal populations, assuming that their unknown variances are equal. The central limit theorem justifies the assumption of normality for mean comparisons, but unknown variances need not be equal. This renders the ANOVA unsuitable for general mean comparisons. As Linnik (1966) has shown that t-statistics for the difference between means based on their sample means and variances do not exist, this problem is not removed by futilely (Kendall & Stuart 1973) testing for the equality of variances or making arbitrary assertions about them. Nor is the problem avoided by avoiding the normality assumption with nonparametric rank tests such as the Wilcoxon test. Being a comparison of distributions, such rank tests say nothing about the means if significant and are biased (Lehmann 1959) to one side in a two-sided test. Tsakok (1978a) has solved this Behrens–Fisher problem of comparing normal population means with unknown variances at exact significance levels and simultaneously shown that the Tsakok solution is more effective in detecting significant mean differences even with unknown equal variances. Its exposition (Tsakok 2002) is available. The software GSP (AD Tsakok Mathematical Centre, London, UK) implements the Tsakok technique. It is now used to compare means at 0.02 significance level (one significant figure) per pair. There are significant mean differences between Tecnis z9003 and Acrysof IQ in their best-corrected visual acuity [BCVA, Table 3 (Lee et al. 2010)] and refractive error of Table 4 (Lee et al. 2010), at 6 months postoperative day (POD). Again for Table 4 (Lee et al. 2010), there are significant mean differences between Tecnis z9003 versus Acrysof IQ and between Acrysof IQ versus Adapt AO in their refractive error at 2 months POD. In Table 5 (Lee et al. 2010), there are significant mean differences between Tecnis z9003 versus Acrysof IQ and between Tecnis z9003 versus Adapt AO in their spherical aberration at 2 months POD. The attention given to the data means they deserve correct analysis. The Tsakok articles on mathematical statistics are reprinted (Tsakok 1987). This includes the article by Tsakok (1978b) on constructing exact uniformly most powerful unbiased tests, which is applicable to the nonparametric two-sample problem, resulting in a test which supersedes the Wilcoxon test.