Macular Degeneration: Zrenner E

Zrenner E. · No affiliation provided · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15138767 No free full text.

This publication has no abstract.

Gekeler F, Zrenner E. · Augenklinik der Universität, Tübingen. · Ophthalmologe. · Pubmed #16151772 No free full text.

Abstract: The development of a subretinal prosthesis has come to a stage where human trials are forthcoming. Subretinal prostheses are designed to replace degenerated photoreceptors in diseases such as retinitis pigmentosa or age-related macular degeneration. Microphotodiode arrays are implanted between retinal pigment epithelium and retina. Our group has collected convincing evidence for the principle feasibility of a subretinal prosthesis. Animal experiments have shown that subretinal electrical stimulation can successfully elicit spatially ordered responses in the visual cortex; visual acuity is estimated to reach 0.25 degrees of visual angle. Histological long-term examinations have demonstrated that the retina tolerates a subretinal implant well and also that the implant itself sustains the ocular environments. Surgical procedures have been successfully developed to implant complex subretinal devices.

Besch D, Jägle H, Scholl HP, Seeliger MW, Zrenner E. · University Eye Hospital, Schleichstr. 12-16, D-72076 Tübingen, Germany. · Vision Res. · Pubmed #14611947 No free full text.

Abstract: Alterations of retinoid cycle genes are known to cause retinal diseases characterized by focal white dot fundus lesions. Fundus appearances reveal circumscribed RPE-changes, although generalized metabolic defects and global functional abnormalities are present. As a possible explanation, topographic inhomogeneities of the human photoreceptor mosaic and the role of a cone specific visual cycle will be discussed. Due to particular characteristics of photoreceptor subtypes as well as different pathways for photopigment regeneration the metabolic demand of individual RPE cells might differ. In "flecked retina diseases" heterogeneity of metabolic demand in individual RPE cells could therefore be responsible for their multifocal appearance.

Wissinger B, Dangel S, Jägle H, Hansen L, Baumann B, Rudolph G, Wolf C, Bonin M, Koeppen K, Ladewig T, Kohl S, Zrenner E, Rosenberg T. · Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University Clinics Tübingen, Germany. · Invest Ophthalmol Vis Sci. · Pubmed #18235024 links to  free full text

Abstract: PURPOSE: Cone dystrophy with supernormal rod response (CDSRR) is a retinal disorder characterized by reduced visual acuity, color vision defects, and specific alterations of ERG responses that feature elevated scotopic b-wave amplitudes at high luminance intensities. Mutations in PDE6H and in KCNV2 have been described in CDSRR. A combined clinical and genetic study was conducted in a cohort of patients with CDSRR, to substantiate these prior RESULTS: METHODS: Seventeen patients from 13 families underwent a detailed ophthalmic examination including color vision testing, Goldmann visual fields, fundus photography, Ganzfeld and multifocal ERGs, and optical coherence tomography. The coding sequences and flanking intron/UTR sequences of PDE6C and KCNV2 were screened for mutations by means of DHPLC and direct DNA sequencing of PCR-amplified genomic DNA. results. Whereas no mutations were detected in the PDE6H gene, mutations in KCNV2 were identified in all patients, in either the homozygous or compound heterozygous state. Ten of the 11 identified mutations were novel, including three missense and six truncating mutations and one gross deletion. The mutations concordantly segregate in all available families according a recessive mode of inheritance. The CDSRR phenotype was associated with reduced visual acuity of variable degree and color vision defects. Macular defects ranging from mild pigmentary changes to distinct foveal atrophy were present in nine patients. Progression of the disease was observed in only three of seven patients with follow-up data. CONCLUSIONS: The phenotype of cone dystrophy with supernormal rod response is tightly linked with mutations in KCNV2.

Ziemssen F, Lüke M, Messias A, Beutel J, Tatar O, Zrenner E, Bartz-Schmidt KU, Anonymous00341. · Department for Ophthalmology, Eberhard-Karls University Tuebingen, Tuebingen, Germany. · Int Ophthalmol. · Pubmed #17634860 No free full text.

Abstract: BACKGROUND: Bevacizumab (Avastin) has been used as off-label treatment for the specific inhibition of the vascular endothelial growth factor (VEGF). Although only intravenous administration of the drug is approved in combination therapy of colorectal carcinoma, promising short-term results have been reported about its intravitreal administration. However, VEGF is also known to exhibit neurotrophic capabilities. Therefore, blockage of all VEGF isoforms by bevacizumab could induce toxic effects. Missing randomized controlled studies and unclear long-term risks require further evaluation. METHODS: Intensified monitoring of bevacizumab treatment was performed in consecutive patients. In ten patients, the functional field score was calculated after obtaining Goldmann visual fields at baseline and 1 year after injection. The other subgroup was examined by means of EOG, ERG and colour testing at baseline and 4 months following treatment. Naka-Rushton plots were calculated to enable statements about retinal function. Lanthony desaturated D15 test was used for repeated colour testing. RESULTS: Baseline parameters already disclosed predominant cone dysfunction. Drug-related effects caused a significant improvement of visual acuity. There was no sign of clinically relevant retinal toxicity following the bevacizumab injection. No progression of visual field defects was seen within the follow-up of 1 year. Performance in EOG testing was affected by restricted fixation stability, but no parameter indicated deterioration within the 4-month-period. CONCLUSIONS: Short-term results underline that intraocular bevacizumab injection promises to be not only a cost-effective, but safe treatment option. Assessed functional parameters as error scores (e.g., Lanthony) corresponded to the impaired retinal function which was presumed to be disease-related. Further long-term results have to confirm the good tolerability in repeated treatment.

Scholl HP, Schuster AM, Vonthein R, Zrenner E. · Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye Hospital, Schleichstrasse 12-16, 72076 Tübingen, Germany. · Vision Res. · Pubmed #11934455 No free full text.

Abstract: In order to evaluate the function of the retina in Best macular dystrophy (BMD) 18 patients were examined by means of the multifocal electroretinogram (mfERG). The mfERG peak amplitudes of the central and pericentral responses were significantly reduced in the BMD patients (p<0.001). The ERG amplitude decrease of the central response was significantly correlated with visual acuity loss and with the funduscopic staging. The implicit times in more eccentric groups were slightly but significantly increased. The markedly reduced mfERG amplitudes with only slightly increased implicit times may indicate cone photoreceptor cell loss or damage to the cone outer segments.

Kohler K, Hartmann JA, Werts D, Zrenner E. · Forschungsstelle für Experimentelle Ophthalmologie, Universitäts-Augenklinik Tübingen. · Ophthalmologe. · Pubmed #11374277 No free full text.

Abstract: Two basic biological premises determine the success of replacement of degenerated photoreceptors by a technical implant. First, the neuronal network in the residual retina of patients selected for implantation must still be capable of processing technically generated signals. Secondly, the implant itself must be biocompatible with tissue, i.e. it may not itself induce further degeneration. Our studies in animal models with advanced retinal degeneration and with donor retinas of retinitis pigmentosa patients have shown that even after complete destruction of the photoreceptors and long periods of blindness, the inner retina in the macular area remains for the most part histologically intact, and that all neurons are demonstrably still present and capable of successfully transmitting and processing signals. Biocompatibility of subretinal implants was studied in pigs. After 14 months of implantation, histological examination of tissue covering the implant showed that the inner retina was completely intact. There were no signs of histopathologic changes.

Scholl HP, Langrová H, Weber BH, Zrenner E, Apfelstedt-Sylla E. · University Eye Clinic, Schleichstrasse 12-16, 72076 Tübingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #11372548 No free full text.

Abstract: BACKGROUND: The scotopic 15-Hz flicker electroretinogram (ERG) has two limbs (slow and fast ERG rod signals), and these have been attributed to two retinal rod pathways (the ON rod bipolar and AII amacrine pathway and the rodcone gap-junction pathway). The aim of this study was to provide normative values of the scotopic 15-Hz flicker ERG, to estimate the inter-individual variability, and to apply this method to a clinical setting. METHODS: Twenty-two normal subjects, one patient with retinitis pigmentosa (RP), and two patients with Stargardt's mascular dystrophy (SMD) participated in the study. The SMD patients were screened for mutations in the 50 exons of the ABCA4 (formerly ABCR) gene. We measured ERG response amplitudes and phases to flicker intensities ranging from -3.37 to -0.57 log scotopic trolands s at a flicker frequency of 15 Hz. RESULTS: The normal scotopic 15-Hz flicker ERG showed a biphasic amplitude pattern with a minimum at about-1.57 log scotopic trolands s, where there was an abrupt phase shift of about 180 deg. The inter-individual variability in ERG amplitude ranged from 47% to 67% for the slow and from 41% to 64% for the fast rod signal. Both the RP patient and the SMD patients (who were compound heterozygotes for mutations in the ABCA4 gene) showed reduced amplitudes for the two rod ERG pathways. CONCLUSION: The inter-individual variability might be explained by anatomical differences between individual retinae. In the RP patient, the amplitude reductions corresponded well with the standard rod ERG. In the SMD patients, however, the scotopic 15-Hz flicker ERG revealed rod dysfunction, whereas the standard rod ERG was within normal limits. The scotopic 15-Hz flicker method may be more sensitive than the standard rod ERG.

Scholl HP, Kremers J, Apfelstedt-Sylla E, Zrenner E. · University Eye Hospital, Schleichstr. 12-16, 72076, Tübingen, Germany. · Vision Res. · Pubmed #10996618 No free full text.

Abstract: To study the L- and M-cone pathways and their interactions in patients with Best's macular dystrophy (BMD), ERG response thresholds were measured to stimuli which modulated exclusively the L- or the M-cones, or both in various combinations. The ERG threshold data could be described with a vector addition model. Compared with normals, BMD patients showed generally larger amplitudes of the L-cone driven ERGs. However, the M-cone driven ERGs were similar in amplitude but significantly phase advanced. The data confirm our previous observations that L- and M-cone pathways can be affected differently by retinal degeneration, despite their large physiological and biochemical similarities.

Kretschmann U, Stilling R, Rüther K, Zrenner E. · University Eye Hospital, Department for Pathophysiology of Vision and Neuro-Ophthalmology, Tübingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #10333111 No free full text.

Abstract: BACKGROUND: It is difficult to detect receptor dysfunction in patients with marked bilateral visual loss but only mild morphological alterations of the fundus. METHODS: Two patients, father and son, with visual acuity loss to 20/100 were examined. Using the multifocal ERG, 61 local cone ERGs from each eye were derived from the central visual field. The dark-adapted two-color threshold perimetry using stimuli of 500 nm and 656 nm for rod and cone function was investigated along the horizontal meridian of the visual field. RESULTS: In the multifocal ERG of both patients a macular response was absent. From eccentricity at and anterior to 5 degrees, good multifocal cone activity was recorded. Cone thresholds were markedly diminished in the macula. The rod thresholds were borderline in the father and normal in the son. CONCLUSIONS: Multifocal ERG is a novel technique, very well suited to reveal the topography of cone function. Using two-color threshold perimetry affords an opportunity to differentiate between rod and cone functional defects. Both together helped to establish the diagnosis of macular cone dystrophy in the present family.