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Biomedical subjects

F G Holz

Publications and source records attributed to F G Holz.

At least 37 records · Page 2Linked to original sources
PubMed2005

Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration.

AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. RESULTS: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.

Aged↗
PubMed2005

Lower limits of fluorescein and indocyanine green dye for digital cSLO fluorescence angiography.

BACKGROUND: With the advent of digital confocal scanning laser ophthalmoscopy it is possible to detect low levels of fluorescence. Here we used a novel confocal scanning laser ophthalmoscope (cSLO) to determine lower limits of dye required for fluorescein (FL) and indocyanine green (ICG) angiography. METHODS: A cSLO (Heidelberg retina angiograph 2, Heidelberg Engineering, Dossenheim, Germany) with an optically pumped solid state laser (488 nm) for FL and a diode laser (790 nm) for ICG angiography (FL/ICG-A) was used. 62 FL-As were performed in 53 patients and 45 ICG-As were performed in 39 patients with neovascular age related macular degeneration. The volume and overall dye content of bolus injections was gradually tapered (FL: 500 mg, 250 mg, 200 mg, 166 mg, 100 mg; ICG: 25 mg, 20 mg, 15 mg, 10 mg, 5 mg, 2.5 mg), while dye concentrations were kept constant at 100 mg/ml for FL and at 5 mg/ml for ICG. Images were obtained 1, 5, 15, and 30 minutes after dye injection. Image quality was evaluated by two independent readers using standardised criteria. RESULTS: For amounts down to 166 mg for FL and to 5 mg for ICG, sufficient image quality was achieved during all phases following injection. Only late phase images showed less contrast compared to typically used dye amounts, which was irrelevant for interpretation and clinical management. CONCLUSIONS: With the increased sensitivity of this novel cSLO system, amounts of injected dye during FL-A can be reduced to one third for FL and to one fifth for ICG without relevant loss of image quality or information compared to conventionally used dye levels. These amounts can be used for routine angiography and allow relevant savings for units performing FL-A.

Aged↗
PubMed2004

Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2-E may contribute to the pathogenesis of age-related macular degeneration.

Lipofuscin accumulation in the retinal pigment epithelium (RPE) is associated with various blinding retinal diseases, including age-related macular degeneration (AMD). The major lipofuscin fluorophor A2-E is thought to play an important pathogenetic role. In previous studies A2-E was shown to severely impair lysosomal function of RPE cells. However, the underlying molecular mechanism remained obscure. Using purified lysosomes from RPE cells we now demonstrate that A2-E is a potent inhibitor of the ATP-driven proton pump located in the lysosomal membrane. Such inhibition of proton transport to the lysosomal lumen results in an increase of the lysosomal pH with subsequent inhibition of lysosomal hydrolases. An essential task of the lysosomal apparatus of postmitotic RPE for normal photoreceptor function is phagocytosis and degradation of membranous discs shed from photoreceptor outer segments (POS) and of biomolecules from autophagy. When the lysosomes of cultured RPE cells were experimentally loaded with A2-E, we observed intracellular accumulation of exogenously added POS with subsequent congestion of the phagocytic process. Moreover, the autophagic sequestration of cytoplasmic material was also markedly reduced after A2-E loading. These data support the hypothesis that A2-E-induced lysosomal dysfunction contributes to the pathogenesis of AMD and other retinal diseases associated with excessive lipofuscin accumulation.

Adenine↗
PubMed2004

[OCT in age-related macular degeneration. Findings, usage in clinical routine, and assessment of treatment outcome].

Optical coherence tomography (OCT) represents a fast and noninvasive examination technique that generates two-dimensional sections of the posterior pole in vivo. Although this method is now widely applied in the diagnosis of various heterogeneous macular diseases, its role in patients with age-related macular degeneration (AMD) is less well established. OCT allows for quantitative as well as qualitative assessment of various AMD phenotypes. Qualitative assessment comprises the evaluation of intra- or subretinal fluid, intraretinal cystoid spaces, and retinal pigment epithelial detachments. However, together with the clinical findings and fluorescence angiography, it can provide useful additional information including monitoring of treatment effects.

Aging↗
PubMed2004

[Transplantation of retinal pigment pithelium (RPE) following CNV removal in patients with AMD. Techniques, results, outlook].

Neovascular age-related macular degeneration (AMD) has become the leading cause for severe visual loss in all industrialized nations. Surgical excision of choroidal neovascularizations (CNV) is technically feasible but invariably associated with inadvertent removal of corresponding retinal pigment epithelium (RPE) and subsequent atrophy of the choriocapillaris, with the latter two layers being a prerequisite for normal photoreceptor function. To cover the RPE defect both heterologous and homologous RPE cell suspensions have been injected into the subretinal space. The lack of functional improvement has been attributed to various factors including RPE cell dedifferentiation, failure of adherence to Bruch's membrane as well as development of a regular RPE cell monolayer. Therefore, techniques for translocating intact autologous RPE cell sheets have been sought and preservation of foveal neurosensory functions has recently been successfully demonstrated. Besides translocation of a full-thickness RPE/Bruch's membrane/choroid patch outside the macular area, superfluous choroidal tissue may be ablated intraocularly using an excimer laser prior to translocation. Besides recent pharmacological approaches including anti-VEGF agents, these surgical developments open new perspectives for patients with neovascular AMD.

Aged↗
PubMed2004

Lipids and lipid peroxidation products in the pathogenesis of age-related macular degeneration.

In people over 50, age-related macular degeneration (ARMD) has become the most common cause for severe visual loss and legal blindness in all industrialized nations. Currently, there is no effective treatment for the majority of patients. To develop new and effective modes of therapy, understanding of the molecular basis of the disease in mandatory. However, the pathogenesis of ARMD is still poorly understood. Several lines of evidence suggest that aging changes of the retinal pigment epithelium (RPE), in particular the accumulation of autofluorescent lipofuscin granules in the lysosomal compartment of postmitotic RPE cells, play a key role in the pathogenesis of the disease. Recent studies indicate that lipidic compounds of lipofuscin, represented by the retinoid A2-E, and protein damage by lipid peroxidation products, in particular malondialdehyde and 4-hydroxynonenal, induce lysosomal dysfunction and lipofuscinogenesis in the RPE. The possible mechanisms underlying this lysosomal dysfunction and the resulting adverse effects on overall RPE function are discussed.

Age Factors↗
PubMed2003

[Pigmented retinopathy as a presenting sign of mitochondrial encephalomyopathy without external ophthalmoplegia].

BACKGROUND: Mitochondrial encephalomyopathies result from deletions in the nuclear or mitochondrial (mt) DNA. Deletions in the mtDNA are often sporadic. Mitochondriopathies are commonly associated with chronic progessive external ophthalmoplegia (CPEO). Here we describe a patient with a structural mtDNA aberration whose presenting sign was impaired visual acuity in the presence of a pigmented retinopathy but lack of impaired ocular motility. PATIENT: A 7-year-old girl presented with impaired visual acuity (0.4 OD and 0.5 OS), coarse hyperpigmentation of the posterior pole and diffuse hyperpigmentation with irregular depigmentation in the periphery. Scotopic and photopic as well as multifocal ERG were abnormal. Further symptoms included an incomplete inner ear deafness, ataxia, lapses of coordination and an intention tremor. Compared with her twin sister, the patient's speech was less modulated and slower. MRI scanning disclosed symmetric changes of density in the basal ganglia and nucleus dentatus as well as in the brainstem. ECG yielded no evidence of an AV-node block. Molecular biological analysis showed a structural rearrangement of the mtDNA. CONCLUSIONS: Mitochondrial encephalomyopathies in early ages may present with pronounced retinal changes in the absence of external ophthalmoplegia.Therefore, it appears prudent to include a neuropediatric evaluation as well as a mutation screening of the mtDNA in the evaluation of pediatric patients with diffuse non-specific pigmented retinopathies.

Blotting, Southern↗
PubMed2003

[The molecular mechanisms of neovascular age-related macular degeneration].

Age-related macular degeneration is the leading cause of irreversible vision loss in industrialized countries. While early forms of this disease with drusen and focal pigment alterations generally do not lead to relevant functional limitations, later forms of the disease, either through atrophy or choroidal neovascularization, are associated with significant visual impairment. A significant increase in knowledge about the molecular mechanisms of new vessel formation from the choriocapillaries has occurred over the past few years. This has already allowed for the clinical testing of pharmacological agents which inhibit the formation of new vessels in AMD. This article describes current research in the pathophysiology of choroidal neovascularization secondary to age-related macular degeneration.

Aged↗
PubMed2003

[Pharmacological therapy for age-related macular degeneration. Current developments and perspectives].

Current therapeutic options for age-related macular degeneration are very limited and are, at best, only capable of slowing visual loss. Because of this an intensive search for prophylactic agents capable of inhibiting the progression of this disease from early into late forms, as well as for new therapeutic approaches has been undertaken. While neuroprotective substances are hoped to prevent cellular death in this disease process, multiple substances capable of inhibiting neovascularization, such as VEGF inhibitors, are in clinical trials. Inhibitors of matrix-metalloproteinases (MMP) and chemotherapeutic agents are also being clinically tested as novel therapies for AMD. Other targets include the inhibition of toxic compound formation in lipofuscin granules such as AZ-E. What follows is an overview of different substances and their stages of development in clinical trials.

Adrenal Cortex Hormones↗
PubMed2003

[Retinal vein occlusions].

There are still gaps in understanding the etiology and pathogenesis of circulatory disorders of the central retinal vein. Although various new therapeutic approaches have been developed in the past few years, existing therapy forms are subject to controversy and available data are to some extent inconsistent. This discussion in the German-language literature is associated with varied and nonuniform terminology, which should do justice in particular to concepts of pathomechanism and degree of specificity. The general designation, "occlusion" seems to be the most suitable of all available terms since this implies no conclusions on possible etiological factors. Retinal vein occlusions develop at different sites and to varying extents. Depending on t he location of the occlusion, they can be classified into occlusions of the central vein, hemicentral vein, major branch vein, and macular branch vein. This overview provides information on the current knowledge of the pathogenesis and both established approaches and those in ongoing clinical trials for the treatment of central venous and branch vein occlusions.

Diagnosis, Differential↗
PubMed2003

[Incidence and extent of postoperative macular edema following vitreoretinal surgery with and without combined cataract operation].

PURPOSE: In the majority of patients with full-thickness macular hole, closure can be achieved with vitreoretinal surgery techniques. However, postoperative function is variable and the prognostic determinants for visual acuity are incompletely understood. We evaluated the incidence and extent of macular edema after macular foramen surgery with and without combined cataract-surgery. METHODS: Between October 1997 and March 2001 macular foramen surgery was performed in 125 eyes from 116 patients. Fluorescein angiograms with sufficient quality were obtained from 59 eyes using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph, HRA, Heidelberg Engineering, Heidelberg) and were evaluated by two independent observers. RESULTS: Angiographic macular edema was noted on average 4.2 months after the operation in 47 out of 59 (79.7%) eyes. The incidence of macular edema was 87% in eyes after a combined cataract operation compared to 66.7 % in eyes with no simultaneous operation ( p=0.735). Mean postoperative visual acuity was 0.4 (min 0.1-max 1.2) with no significant difference between eyes with (4.1 lines) and without macular edema (3.5 lines) with regard to visual improvement from baseline. CONCLUSIONS: The results indicate a high incidence of macular edema in eyes after macular hole surgery with subsequent anatomical success. Apparently, the presence of macular edema is not associated with short term visual impairment. Furthermore it seems that a combined cataract operation compared to a consecutive procedure is not associated with disadvantages regarding the functional outcome.

Aged↗
PubMed2003

[Diagnostic vitrectomy in uveitis: possibilities of molecular biology].

Recent developments in molecular biology allow novel diagnostic approaches in intraocular inflammation. Genetic markers as well as species-specific sequences are used for the diagnostics of infection or masquerade syndromes. This article provides state-of-the art information about diagnostic vitrectomy.

Biopsy↗
PubMed2003

[Therapeutic vitrectomy in uveitis: current status and recommendations].

With the advent of modern vitreoretinal surgical techniques, the spectrum for surgical intervention in various forms of uveitis has been notably expanded. Removal of optically relevant vitreous opacities, improvement of secondary macular edema, delamination of epiretinal membranes, and release of traction in the presence of abnormal vitreoretinal adhesions represent indications for vitreoretinal procedures in uveitis patients. Furthermore, retinal and choroidal biopsies may be obtained if the precise etiology is unknown. This in turn offers the opportunity to better target pharmacological interventions. Combined cataract surgery or intravitreal implantation of drug devices may also be of therapeutic benefit. So far no prospective, controlled clinical trials have been performed to precisely evaluate the role of pars plana vitrectomy (ppV) as a single or combined surgical procedure in patients with intraocular inflammation. Inconsistent data exist regarding prognostic determinants and the role of perioperative immunosuppression. Here, the current knowledge on the subject is reviewed and critically discussed, and recommendations for patient management are given. Further studies are needed.

Combined Modality Therapy↗
PubMed2003

Multifocal ERG recording with simultaneous fundus monitoring using a confocal scanning laser ophthalmoscope.

PURPOSE: To assess the general feasibility of recording multifocal electroretinograms (mfERGs) with simultaneous fundus monitoring in a clinical setting. METHODS: An mfERG system (RETIscan) and a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph) were connected to record mfERGs elicited by a pseudorandom binary m-sequence stimulus generated by a 514 nm laser source. Recordings were compared to a conventional mfERG system using monitor stimulation. A total of five subjects (two normal subjects and three patients) were examined. RESULTS: In normal volunteers records obtained by the fundus-monitored mfERG showed highest response densities in the central fundus area and a decrease of response amplitudes towards the periphery paralleling cone receptor density. However, compared to the monitor stimulation, the drop-off of amplitudes as a function of eccentricity was not as clearly defined. The responses obtained from patients with retinal diseases were diminished in the areas of retinal dysfunction. CONCLUSIONS: These preliminary findings indicate that the technique of laser stimulation in principle allows for topographic retinal recording. This method might be useful, for example if the retinal position of the stimulus array is not centred onto the fovea but deviates due to fixation problems. However, further improvement of the technique appears necessary before considering routine clinical application.

Adult↗
PubMed2003

Digital analysis of choroidal neovascularisation in consecutive fluorescein angiograms for use in longitudinal clinical trials.

BACKGROUND/AIMS: To document the natural history and to assess the efficacy of interventional therapies in neovascular age related macular degeneration (AMD), an accurate and reproducible method is required for analysis of consecutive fluorescence angiograms. The development and evaluation of an image analysis software for this purpose is described here. It allows for the quantitative analysis of changes in CNV and/or leakage area over time. METHODS: In digitised angiograms, a mouse driven arrow was used to delineate the CNV border. The ratio of the CNV area to the square of the distance between two vessels was automatically calculated by pixel count to compensate for variation in image sizes at different examination times. These results were directly transferred and stored in a database. To assess reproducibility, CNV areas in 20 patients with occult and 20 patients with classic CNV were determined independently by two readers. RESULTS: There was only marginal variability between observers with this method: the mean deviation was 0.01 pixels for classic CNV (95% CI -0.17 to +0.15, SD 0.35) and 0.55 pixels for occult CNV (95% CI -1.06 to -0.04, SD 1.14). CONCLUSIONS: This practical PC based method allows for quantification of angiographic features such as CNV size in early frames and area of leakage in late frames. Limitations include non-readily defined borders in angiograms of poor image quality or indistinct borders of the hyperfluorescent areas of interest. The software is applicable to future clinical trials where the analysis of neovascular complex changes is required, for example, following therapeutic intervention.

Choroidal Neovascularization↗
PubMed2003

Intraocular microablation of choroidal tissue by a 308 nm AIDA excimer laser for RPE-transplantation in patients with age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the western nations beyond 50 years of age. The most frequent cause for severe visual loss is the growth of neovascular membrances from the choroid into the subretinal space. This usually results in irreversible degeneration of the overlying retina. Surgical removal of the membrane is feasible, however, usually results in functional loss of apposing retinal photoreceptors since retinal pigment epithelial (RPE) cells are removed concurrently due to their tight adherence to the neovascular complex. Therefore, various attempts have been undertaken to fill the resulting RPE cell defect with either heterologous or autologous RPE cell transplants. So far cell survival, function and subsequent visual function has been disappointing. To minimize trauma and resulting dedifferentiation harvesting in the eye and transplantation in whole sheets and without temporary removal from the eyes would be desirable. This may be achieved by isolating grafts consisting of choroid, Bruch's membrance and RPE cells from the peripheral retina and transplantation of this graft under the neurosensory retina after removal of the choroidal neovascularization. However, the choroidal component of such a graft would be expected to interfere with diffusion of metabolites to and from the retina. Therefore, outcome would be expected to be better if the choroidal tissue would be removed before translocation. In preclinical experiments we used a 308 nm UV AIDA excimer laser to microablate choroidal tissue from such a graft in human donor eyes.

Choroid↗
PubMed2002

Proteome analysis of lipofuscin in human retinal pigment epithelial cells.

Excessive accumulation of lipofuscin in postmitotic retinal pigment epithelial cells is a common pathogenetic pathway in various blinding retinal diseases including age-related macular degeneration, which is now the most common cause of registerable blindness in the industrialized nations. To better understand the role of lipofuscin accumulation and to manipulate the pathogenetic mechanisms on both experimental and therapeutic levels we analyzed the proteome of isolated human ocular lipofuscin granules from human RPE cells. After homogenization and fractionation by gradient ultracentrifugation of the RPE/choroid complex from 10 pairs of human donors, protein compounds were separated by 2D gel electrophoresis and analyzed using matrix-assisted laser desorption/ionization mass spectrometry and HPLC-coupled electrospray tandem mass spectrometry. Besides a better understanding of downstream pathways, this approach may provide new targets for therapeutic interventions in a currently untreatable disease.

Chromatography, High Pressure Liquid↗