E Zrenner

University of Tuebingen, Tübingen, Baden-Württemberg, Germany

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Publications (469)1337.23 Total impact

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    ABSTRACT: Hereditary retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different forms of RD can be caused by mutations in >100 genes, including >1600 exons. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. So far, NGS is not routinely used in gene diagnostics. We developed a diagnostic NGS pipeline to identify mutations in 170 genetically and clinically unselected RD patients. NGS was applied to 105 RD-associated genes. Underrepresented regions were examined by Sanger sequencing. The NGS approach was successfully established using cases with known sequence alterations. Depending on the initial clinical diagnosis, we identified likely causative mutations in 55% of retinitis pigmentosa and 80% of Bardet-Biedl or Usher syndrome cases. Seventy-one novel mutations in 40 genes were newly associated with RD. The genes USH2A, EYS, ABCA4, and RHO were more frequently affected than others. Occasionally, cases carried mutations in more than one RD-associated gene. In addition, we found possible dominant de-novo mutations in cases with sporadic RD, which implies consequences for counseling of patients and families. NGS-based mutation analyses are reliable and cost-efficient approaches in gene diagnostics of genetically heterogeneous diseases like RD.European Journal of Human Genetics advance online publication, 17 April 2013; doi:10.1038/ejhg.2013.72.
    European journal of human genetics: EJHG 04/2013; · 3.56 Impact Factor
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    ABSTRACT: Purpose: To investigate the presence and distribution of l-kynurenine aminotransferases immunoreactivity in human and animal lenses during cataract formation. Methods: Immunohistochemistry was conducted using polyclonal antibodies against KAT I, KAT II and KAT III on sections of 26 anterior capsules from patients undergoing surgical treatment of anterior subcapsular cataract (ASC) and 22 cataractous lenses from human eyes enucleated because of choroidal malignant melanoma. Additionally, the eyes of 11-month-old DBA/2J mice (6 eyes) were investigated (with KAT I and II). Ten clear human lenses and four BL6 mice lenses were used as controls. Spatial immunoreactivity patterns of enzymes were compared with Periodic Acid - Schiff (PAS)-stained sections. Results: Immunohistochemical analysis revealed presence of KAT I, KAT II and KAT III in extracellular structures of all studied types of cataract in human eyes showing specific pattern of the stain. In cortical cataract, immunoreactivity was observed on cortical lens fibres. In nuclear cataract, KAT II revealed stronger and diffused staining than KAT I. Additionally, both KAT showed more pronounced staining at the edge of small clefts. In normal human lenses, KAT I, II and III, immunoreactivity was not observed. Presence of KAT I and KAT II in the intercellular substance of DBA/2J mice cataract was observed. In BL6 mice lenses without cataract, only weak KAT I and KAT II staining was observed. Conclusions: Presence of l-kynurenine aminotransferases in extracellular matrix (ECM) during human cataract formation suggests that products of l-kynurenine pathway might be involved in mechanisms of cataractogenesis.
    Acta ophthalmologica 04/2013; · 2.44 Impact Factor
  • Wilderness and Environmental Medicine 03/2013; 24(1):82–83. · 1.49 Impact Factor
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    ABSTRACT: Abstract Purpose: One approach for restoring vision in end-stage hereditary retinal diseases is implantation of a subretinal microphotodiode array. We analyzed retinal fluorescein angiography findings of the implant area. Methods: In this pilot study, patients (n = 11; 10 men, one woman; ages 45.2 ± 8.7 years), with visual acuity of light perception or worse resulting from a hereditary retinal degenerative disease, received active electronic subretinal visual implants. Implants were removed after 4 weeks (n = 7 subjects) or 4 months (n = 4 subjects). Following implantation, regular fluorescein angiography was performed. Regions of retinal capillary loss, microaneurysms, capillary alterations, neovascularization and leakage over the implant were scored at time points T1 (days 1-14), T2 (days 15-28) and T3 (months 3-4). Occurrence and changes of fluorescein angiographic phenomena are reported. Results: In terms of the number of patients in whom retinal alterations were observed (compared to available images) the occurences of the angiographic phenomena (for time points T1, T2 and T3, respectively) were as follows: regions of capillary loss (five of seven, 10 of 11 and five of five patients), microaneurysms (0 of seven, two of 11 and three of five patients), calibre alterations of the capillaries (three of seven, eight of 11 and five of five patients), retinal neovascularization (one of seven, one of 11 and 0 of five) and leakage (three of seven, seven of 11 and four of five). The Friedman test revealed no significant changes in capillary loss, calibre alteration of the capillaries, neovascularization or leakage. Microaneurysms increased significantly (p = 0.037). Conclusions: Subretinal visual implants lead to increased capillary microaneurysms, a possible compensatory mechanism following recovery of inner retinal activity. There were no significant changes in capillary loss, calibre alteration of the capillaries, retinal neovascularization and leakage at 4 months. Further study will determine whether and to what degree long-term vascular changes are affected by the surgical procedure, the implant itself and/or recovery of retinal neuronal activity.
    Current eye research 02/2013; · 1.51 Impact Factor
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    ABSTRACT: Stargardt's disease is an autosomal recessive inherited juvenile macular degeneration and at present no acknowledged science-based therapy is available for these patients. Recently, reports have been published on the effectiveness of electrical stimulation in experimental animal models and in patients with neurodegenerative ocular disease, particularly retinitis pigmentosa. This study included 12 patients with Stargardt's disease who were randomized into one of three groups (n = 4) with 0% (sham), 66% or 150% of the individual electrically stimulated phosphene threshold. Outcome measures of the study were safety and efficacy of transcorneal electrical stimulation (TES) with DTL electrodes in subjective and objective parameters of visual function under therapy. In general TES was well tolerated and no adverse or serious events were noted. Neither Ganzfeld, multifocal ERG, OCT nor visual field testing showed statistically significant changes in any group.
    Der Ophthalmologe 01/2013; 110(1):68-74. · 0.53 Impact Factor
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    ABSTRACT: 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 mm(2) 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 implant's power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life.
    Proceedings of the Royal Society B: Biological Sciences 01/2013; 280(1757):20130077. · 5.68 Impact Factor
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    ABSTRACT: Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD.For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards.PATIENTS WITH AMD HAD SIGNIFICANTLY HIGHER AQUEOUS HUMOR LEVELS OF CADMIUM (MEDIAN: 0.70 µmol/L, IQR: 0.40-0.84 vs. 0.06 µmol/L; IQR: 0.01-.018; p = 0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62-3.15 vs. 1.17 µmol/L; IQR: 0.95-1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289-329 vs. 129 µmol/L; IQR: 111-145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9-32.6 vs. 5.1 µmol/L; IQR: 4.4-9.4; p = 0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4-31.3 vs. 49.9 µmol/L; IQR: 32.0-.142.0; p = 0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD.Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD.
    PLoS ONE 01/2013; 8(2):e56734. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Participation in first human applications of retinal neuroprosthesis may create psychological stress for blind retinitis pigmentosa patients. The aim of this study was to assess the emotional wellbeing of patients undergoing implantation of a subretinal implant. METHODS: Nine blind patients participating in a pilot trial with subretinal implants were enlisted. The Brief Symptom Inventory (BSI), a short self-report scale of nine primary symptoms, was used to assess reaction to the psychological distress related to study participation. The number and the intensity of symptoms were analysed, and global scores for overall psychological distress (tGSI), severity of reported symptoms (tPDSI), and level number of self-reported symptoms (tPST) were calculated. The questionnaire was administered before implantation, 2-3 times during the trial and before explantation. RESULTS: There were no significant alterations during the trial for the average scores of the nine primary symptoms. One patient, however, showed values higher than the norm, for six subscores before implantation and for eight subscores before explantation. A significant improvement was found in both the overall psychological distress level (tGSI) and the severity of reported symptoms (tPDSI) at the final visit, compared to those at the study start. The number of self-reported symptoms (tPST) was not significantly altered. CONCLUSION: In the first ongoing pilot trial with an active, cable-bound subretinal implant, we found that trial participation and the implant procedure and subsequent testing did not have any adverse effects on the participants' emotional wellbeing. Their distress generally improved during study participation, rather than showing signs of decreased wellbeing.
    Albrecht von Graæes Archiv für Ophthalmologie 11/2012; · 1.93 Impact Factor
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    ABSTRACT: BACKGROUND: Replacing the function of visual pathway neurons by electronic implants is a novel approach presently explored by various groups in basic research and clinical trials. The novelty raises unexplored methodological aspects of clinical trial design that may require adaptation and validation. METHODS: We present procedures of efficacy and safety testing for subretinal visual implants in humans, as developed during our pilot trial 2005 to 2009 and multi-centre clinical trial since 2010. RESULTS: Planning such a trial requires appropriate inclusion and exclusion criteria. For subretinal electronic visual implants, patients with photoreceptor degeneration are the target patient group, whereas presence of additional diseases affecting clear optic media or the visual pathway must be excluded. Because sham surgery is not possible, a masked study design with implant power ON versus OFF is necessary. Prior to the efficacy testing by psychophysical tests, the implant's technical characteristics have to be controlled via electroretinography (ERG). Moreover the testing methods require adaptation to the particular technology. We recommend standardised tasks first to determine the light perception thresholds, light localisation and movement detection, followed by grating acuity and vision acuity test via Landolt C rings. A laboratory setup for assessing essential activities of daily living is presented. Subjective visual experiences with the implant in a natural environment, as well as questionnaires and psychological counselling are further important aspects. CONCLUSIONS: A clinical trial protocol for artificial vision in humans, which leads a patient from blindness to the state of very low vision is a challenge and cannot be defined completely prior to the study. Available tests of visual function may not be sufficiently suited for efficacy testing of artificial vision devices. A protocol based on experience with subretinal visual implants in 22 patients is presented that has been found adequate to monitor safety and efficacy.
    Clinical and Experimental Optometry 11/2012; · 0.92 Impact Factor
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    ABSTRACT: PURPOSE: To compare visual acuities estimated by three methods of visual evoked potential (VEP) recordings to those obtained by two subjective measures [ETDRS and FrACT (Freiburg acuity test)]. METHODS: Ten healthy subjects, aged between 26 and 67 years (mean 43.5), were examined. Best-corrected acuity determined by the ETDRS was between 0.03 and -0.3 logMAR (mean -0.06). Sweep VEPs (sweepVEP), pattern appearance VEPs (pappVEP) and steady-state VEPs (ssVEP) were recorded with two electrode placements (10-20 and Laplace) with best optical correction and with artificially degraded vision using five Bangerter occlusion foils, reducing acuity to about 0.1, 0.22, 0.52, 0.7 and 1.0 logMAR (0.8, 0.6, 0.3, 0.2 and 0.1 decimal scale). Two runs were performed. RESULTS: ETDRS and FrACT acuities showed good agreement, even though ETDRS seemed to underestimate acuity compared with FrACT at higher acuities. Laplace derivation did not improve any of the VEP-estimated acuities over the 10-20. SweepVEP tended to overestimate lower FrACT acuities, but showed good repeatability. PappVEP placed FrACT acuities into correct or neighboring categories in 87 % of cases. Average ssVEP acuity showed little difference to those of FrACT but variance was larger. ROC analysis for typical clinical application showed good performance for all three methods. CONCLUSIONS: The two subjective measurements of acuities are well correlated. Under the conditions of our experiment, sweepVEP results were less variable and had a better repeatability than ssVEP acuities, whose analysis, in contrast to sweepVEP, can be automated. PappVEP estimates, however, offer a viable alternative, that is, quicker but of lower performance regarding the detection of low acuity thresholds. All methods had a good performance regarding minimum acuity detection if an average of two runs is used.
    Documenta Ophthalmologica 11/2012; · 1.54 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate electrically evoked phosphene thresholds (EPTs) in healthy subjects and patients with retinal disease and assess repeatability and possible correlations with common ophthalmological tests. METHODS: 117 individuals participated: healthy subjects (n=20), 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 80Hz with 5+5ms 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: full-field/multifocal-ERG; POAG: pattern-ERG; NAION: VEP), slit-lamp-biomicroscopy, fundus examination and tonometry were assessed. RESULTS: EPTs were lowest in healthy subjects and highest in RAO (20Hz: healthy: 0.062±0.038mA, STG: 0.102±0.097mA, POAG: 0.127±0.09mA, NAION: 0.244±0.126mA, RP: 0.371±0.223mA, RAO: 0.988±1.142mA). In all groups EPTs were lowest at 20Hz. In patients with retinal diseases and across all frequencies EPTs were significantly higher than in healthy subjects; except in STG at 20Hz (p=0.09) and 40Hz (p=0.17). Test-retest-difference at 20Hz was 0.006mA in healthy and 0.003-0.04mA in disease groups. CONCLUSIONS: Considering the fast, safe and reliable practicability of EPTs 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 where these standard tests cannot be used meaningfully.
    Investigative ophthalmology & visual science 10/2012; · 3.43 Impact Factor
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    ABSTRACT: Purpose Restitution of vision in blind Retinitis Pigmentosa patients by the new wireless implant Alpha-IMS (Retina Implant AG, Tübingen, Germany). Methods Each of the 1500 subfoveal photodiodes within an 11 by 11 deg field controls an amplifier that ejects light evoked currents onto bipolar cells via TiN electrodes (Zrenner et al. Proc. R. Soc. B 2011, 278: 1489ff). Power and control signals are transmitted transdermally via retroauricular inductive coils connected to a subdermal cable to the eye. Results Ten patients received implants since 2010 (average age 46±84). In 8 patients the chip was at the desired subfoveal position; in 2 patients slightly parafoveal. All patients were able to perform the function tests except one due to loss of inner retina function after surgery. Results in all other patients were: light perception 9/9; light localization 8/9; motion recognition 5/9; grating resolution 8/9 (up to 3,3 cycle/degree); Landolt C rings 3/9 (up to 0,036); recognition of geometric objects 8/9; recognition of objects in table setup 8/9; letter reading 4/9; clock hands reading 3/9; grey scale differentiation 6/9; improved outdoor mobility 5/9. Patients` experiences: recognition of unknown objects, facial or clothes’ characteristics, moving objects in nature and traffic, small objects (glasses, telephone, doors, door handles, washing basin, dices). Conclusion The wireless Alpha-IMS implant can restore useful visual abilities in blind RP-patients. Subretinal surgery for positioning chips subfoveally is safe and the multicenter part of the study has been started in Oxford, London and Hongkong. Commercial interest
    Acta ophthalmologica 09/2012; 90(s249). · 2.44 Impact Factor
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    ABSTRACT: To explore the effect of ketamine-xylazine anesthesia on light-induced retinal degeneration in rats. Rats were anesthetized with ketamine and xylazine (100 and 5 mg, respectively) for 1 h, followed by a recovery phase of 2 h before exposure to 16,000 lux of environmental illumination for 2 h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosin staining, TUNEL assay) and immunohistochemistry (GFAP and rhodopsin staining) were performed at baseline (ERG), 36 h, 7 d and 14 d post-treatment. Non-anesthetized animals treated with light damage served as controls. Ketamine-xylazine pre-treatment preserved retinal function and protected against light-induced retinal degeneration. In vivo retinal imaging demonstrated a significant increase of outer nuclear layer (ONL) thickness in the non-anesthetized group at 36 h (p<0.01) and significant reduction one week (p<0.01) after light damage. In contrast, ketamine-xylazine pre-treated animals showed no significant alteration of total retinal or ONL thickness at either time point (p>0.05), indicating a stabilizing and/or protective effect with regard to phototoxicity. Histology confirmed light-induced photoreceptor cell death and Müller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazine treated rats showed reduced photoreceptor cell death (TUNEL staining: p<0.001 after 7 d), thicker ONL and longer IS/OS. Fourteen days after light damage, a reduction of standard flash induced a-wave amplitudes and a-wave slopes (p = 0.01) and significant alterations in parameters of the scotopic sensitivity function (e.g. Vmax of the Naka Rushton fit p = 0.03) were observed in non-treated vs. ketamine-xylazine treated animals. Our results suggest that pre-treatment with ketamine-xylazine anesthesia protects retinas against light damage, reducing photoreceptor cell death. These data support the notion that anesthesia with ketamine-xylazine provides neuroprotective effects in light-induced cell damage.
    PLoS ONE 08/2012; 7(4):e35687. · 3.53 Impact Factor
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    ABSTRACT: To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats. 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). 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). 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.
    Investigative ophthalmology & visual science 07/2012; 53(9):5552-61. · 3.43 Impact Factor
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    Elena Prokofyeva, Alfred Wegener, Eberhart Zrenner
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    ABSTRACT: This literature review is aimed at the evaluation of the potential for cataract prevention in Europe. It was performed using PubMed with Mesh and free-text terms. Studies included were (i) performed on a population of Caucasian origin at an age range of 40-95 years, (ii) cataract was clinically verified, (iii) drug record of prescriptions, their indication, a record of every diagnosis, dosage and quantity of prescribed medicine were available, (iv) sample size >300 and (v) published between 1990 and 2009. The results of 29 articles were reviewed. Former [3.75 (2.26-6.21)] or current smoking [2.34 (1.07-5.15)], diabetes of duration >10 years [2.72 (1.72-4.28)], asthma or chronic bronchitis [2.04 (1.04-3.81)], and cardiovascular disease [1.96 (1.22-3.14)] increased the risk of cataract. Cataract was more common in patients taking chlorpromazine during ≥90 days with a dosage ≥300 mg [8.8 (3.1-25.1)] and corticosteroids >5 years [3.25 (1.39-7.58)] in a daily dose >1600 mg [1.69 (1.17-2.43)]. Intake of a multivitamin/mineral formulation [2.00 (1.35-2.98)] or corticosteroids [2.12 (1.93-2.33)] also increased the risk of cataract. Corticosteroids applied orally [3.25 (1.39-7.58)], parenteral [1.56 (1.34-1.82)] or inhalational [1.58 (1.46-1.71)] lead to cataract more frequently than those applied topically: nasal [1.33 (1.21-1.45)], ear [1.31 (1.19-1.45)] or skin [1.43 (1.36-1.50)]. Outpatient cataract surgery was negatively associated with total cataract surgery costs, and chlorpromazine, corticosteroids and multivitamin/mineral formation increase the risk of posterior subcapsular cataract dependent on dose, treatment application and duration. This review presented a comprehensive overview of specific and general cataract risk factors and an update on most recent experimental studies and randomized control trials directed at cataract prevention.
    Acta ophthalmologica 06/2012; · 2.44 Impact Factor
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    ABSTRACT: X-linked juvenile retinoschisis (XLRS) is the most common juvenile maculopathy in men and is caused by mutations in the gene encoding retinoschisin (RS1). Evidence in the literature on the therapeutic effect of carboanhydrase inhibitors (CAIs) to treat schisis formation in the retina has remained equivocal. Here, we evaluate the effect of the CAI dorzolamide on the structural and functional disease progression in the mouse model for XLRS (Rs1h(-/y)). Rs1h (-/y) mice were treated unilaterally with dorzolamide eye drops (Trusopt(®) 20 mg/mL) every 12 h for 2 weeks starting on postnatal day 14 (n = 27). Changes of retinal structure were monitored by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography 12 h, 14 days, 4 weeks, 2 months, and 6 months after completion of the treatment. Schisis formation (peak at 3 months) preceded photoreceptor degeneration and hyper-fluorescence (peak at 7 months). Structural pathology was most severe in the superior hemi-retina with previously unreported hyper-fluorescent lesions. Quantitative analysis showed no significant differences regarding the inner or outer retinal thickness of the treated vs. untreated eyes 12 h after the completion of treatment (IRT(12 h) = -1.29 ± 1.89 μm; ORT(12 h) = 0.61 ± 2.08 μm; mean ± 95%CI) or at any later time point. Time line analysis after short-term treatment with CAI failed to show short-, intermediate-, or long-term evidence of structural improvement in Rs1h(-/y) mice. Schisis formation in the inner retina peaked at the age of 3 months and was followed by photoreceptor degeneration predominantly in the superior hemi-retina. Previously unreported hyper-fluorescent lesions co-register with structural retinal pathologies.
    Veterinary Ophthalmology 06/2012; 15 Suppl 2:123-33. · 0.96 Impact Factor
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    ABSTRACT: To optimize methods for positioning subretinal visual implants, customizing their cable length, guiding them to the predetermined retinal position, and evaluating their performance. Ten eyes of 10 patients (6 male, 4 female, mean age 46.4 years) were investigated before implantation of a subretinal visual implant. The structural characteristics of the retina as well as the ocular dimensions were determined. Topographic images of the prospective implantation site were subdivided into grids of squares. Each square received a weighted score for suitability. The sum of the scores was calculated, and the region with the highest score was chosen for the implant. In each case, the implant's power supply cable length was calculated by means of magnetic resonance imaging. The planned and achieved positions before and after implantation were compared. The mean light sensitivity ratio between the area actually covered by the chip and that of the planned position was 90.8% with an SD of 11.4%. In two cases with almost perfect positioning, the computed ratio was 100%. Measurements showed that to achieve a 95% sensitivity rate the difference between the planned and achieved chip position must be less than 1.7 mm. Preoperative calculations of the intraocular cable length proved accurate in all cases. Preoperative evaluation of retinal structures and eye morphology is useful for guiding a retinal implant to the designated area. It is a meaningful tool for planning and performing retinal chip implantation, and it optimizes personalized implantation. (ClinicalTrials.gov numbers, NCT00515814, NCT01024803.).
    Investigative ophthalmology & visual science 05/2012; 53(7):3748-55. · 3.43 Impact Factor

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8k Citations
1,337.23 Total Impact Points


  • 1994–2014
    • University of Tuebingen
      • • Institute for Ophthalmic Research
      • • Institute of Musicology
      • • Institute of Physical and Theoretical Chemistry
      Tübingen, Baden-Württemberg, Germany
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
    • Universität zu Lübeck
      • Institut für Humangenetik
      Lübeck, Schleswig-Holstein, Germany
  • 2013
    • Universitätsklinikum Erlangen
      • Department of Ophthalmology
      Erlangen, Bavaria, Germany
  • 1970–2013
    • Universitätsklinikum Tübingen
      • Division of Experimental oncology
      Tübingen, Baden-Württemberg, Germany
  • 2009
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2006–2009
    • University of Zurich
      Zürich, Zurich, Switzerland
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 2004–2007
    • Medical University of Lublin
      • Department of Toxicology (Pharmacy)
      Lyublin, Lublin Voivodeship, Poland
    • Forschungszentrum Jülich
      Jülich, North Rhine-Westphalia, Germany
    • Maria Curie-Sklodowska University in Lublin
      • Department of Virology and Immunology
      Lublin, Lublin Voivodeship, Poland
  • 2002
    • Hospital of the University of Pennsylvania
      • Department of Ophthalmology
      Philadelphia, Pennsylvania, United States
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 2001–2002
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2000
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 1999
    • University of Hamburg
      • Department of Human Genetics
      Hamburg, Hamburg, Germany
    • Universität Stuttgart
      • Institute of Physics
      Stuttgart, Baden-Wuerttemberg, Germany
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • Hohenheim University
      • Institute of Biological Chemistry and Nutrition Sciences
      Stuttgart, Baden-Wuerttemberg, Germany
  • 1997–1998
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
    • Otto-von-Guericke-Universität Magdeburg
      • Clinic for Ophthamology
      Magdeburg, Saxony-Anhalt, Germany
  • 1995
    • University Hospital Essen
      Essen, North Rhine-Westphalia, Germany
  • 1993
    • Universitätsmedizin Göttingen
      • Department of Clinical Neurophysiology
      Göttingen, Lower Saxony, Germany
  • 1992
    • Radboud University Medical Centre (Radboudumc)
      • Department of Human Genetics
      Nymegen, Gelderland, Netherlands
  • 1989
    • University of Cambridge
      Cambridge, England, United Kingdom