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Biomedical subjects

F G Holz

Publications and source records attributed to F G Holz.

At least 19 recordsLinked to original sources

[Modern pharmacotherapy of age-related macular degeneration].

Age-related macular degeneration (AMD) is now the most common cause for blind registration in all developed countries. Epidemiologic data indicate that there are 4.5 millions affected in Germany with constant increase in incidence and prevalence with subsequent considerable health economic implications. Late manifestations of the disease result in the inability to read and to perform daily tasks. Therefore, there is an urgent need for efficacious prophylactic and therapeutic measures to prevent irreversible loss of central vision. Based on a better understanding of the underlying molecular mechanisms new therapeutic approaches have been brought forward and expand previous approaches such as thermal laser surgery or photodynamic therapy. Repeated intravitreal injection of anti-VEGF (vascular endothelial growth factor) agents as well as corticosteroids have a beneficial effect on growth and permeability of neovascular membranes. The risk for progression from early to late stages of AMD can be reduced with certain antioxidative preparations (AREDS medication) in presence of defined funduscopic signs. Early diagnosis is key for all currently available interventions since a beneficial effect can only be achieved in early stages of the disease process.

Adrenal Cortex Hormones↗

[Establishing ophthalmology in the research framework programs of the European Union].

The framework programmes (FP) of the European Commission have substantially contributed to the funding of research within the European countries. The contribution of the funding provided by the EU relative to the funding available on the national level has steadily increased. European ophthalmology and vision research has benefited from this support provided by the EU. This review introduces the European funding policies and the European Research Area (ERA) and provides a list of all projects in ophthalmology and vision research that have been funded within FP1 to FP6. As an example for new instruments within FP6, Integrated Projects, the EVI-GENORET project is introduced. Finally an outlook for FP7 is provided.

Biomedical Research↗

[Intravitreal bevacizumab for neovascular age-related macular degeneration].

The efficacy and safety of the therapeutic anti-VEGF concept has already been demonstrated for pegaptanib and ranibizumab. Bevacizumab acts as an antibody against all VEGF-A isoforms and has been developed for oncological indications with intravenous application. Initial reports on intravitreal administration in patients with neovascular age-related macular disease (AMD) have shown beneficial morphological and functional effects. In the meantime, bevacizumab has been used off-label in thousands of patients with AMD. However, data from prospective, controlled, randomized trials on both safety and efficacy are lacking. Herein recent experiences with bevacizumab are summarized and discussed. Furthermore, a web-based platform for online data registration and pooled analyses is presented.

Angiogenesis Inhibitors↗

[Pseudoxanthoma elasticum].

Pseudoxanthoma elasticum (PXE) is an inherited disorder that is associated with accumulation of mineralized and fragmented elastic fibers in the skin, vessel walls, and Bruch's membrane. Clinically, patients exhibit characteristic lesions of the skin (soft, ivory-colored papules in a reticular pattern that predominantly affect the neck), the posterior segment of the eye (peau d'orange, angioid streaks, choroidal neovascularizations), and the cardiovascular system (peripheral arterial occlusive disease, coronary occlusion, gastrointestinal bleeding). There is no causal therapy. Recent studies suggest that PXE is inherited almost exclusively as an autosomal recessive trait. Its prevalence has been estimated to be 1:25,000-100,000. The ABCC6 gene on chromosome 16p13.1 is associated with the disease. Mutations within the ABCC6 gene cause reduced or absent transmembraneous transport that leads to accumulation of substrate and calcification of elastic fibers. Although based on clinical features the diagnosis appears readily possible, variability in phenotypic expressions and the low prevalence may be responsible that the disease is underdiagnosed. This review covers current knowledge of PXE and presents therapeutic approaches.

Choroidal Neovascularization↗

[Bevacizumab for treatment of macular edema secondary to retinal vein occlusion].

Application of VEGF inhibitors represents a treatment option for macular edema secondary to retinal vein occlusion that targets the disease at the causal molecular level. First reports on intravitreal injections of bevacizumab show promising morphological and functional effects and demonstrate that bevacizumab is a potent antiedematous agent in this context. A significant reduction of the central retinal thickness followed by a rapid improvement of visual acuity may be achieved within days. In a pilot study with a review period of 3 months, we found a significant improvement of one or more lines in 93% and four or more lines in 27% of eyes. This was associated with a concomitant significant reduction in central retinal thickness, which, however, was not sustained by a single injection (64% reduction after 1 month and 28% after 3 months). No relevant adverse events were noted. The duration of action after intravitreal bevacizumab administration is currently unknown. Reinjections will be necessary to maintain a lasting beneficial effect. Prospective, controlled long-term studies are mandatory to develop standardized treatment protocols that allow a safe and effective application of this off-label therapy.

Angiogenesis Inhibitors↗

[Ocular manifestations and surgical results in patients with Marfan syndrome].

AIM: This retrospective study should examine and judge the surgical indications and the therapeutic possibilities as well as their complications in patients with ocular manifestations of Marfan syndrome (MFS) diagnosed according to the criteria of the Ghent nosology. PATIENTS AND METHODS: The study included 17 patients. Operative indications were increasing subluxation of the lens, retinal detachments and secondary glaucoma. The operative procedure depended on patient age and findings. Eleven MFS patients were operated in both eyes and six MFS patients in one eye. RESULTS: Stabilization or functional improvement of visual acuity could be achieved in all patients in whom no disorders limiting visual acuity or amblyopia were present preoperatively. In six eyes of five patients, lens insertion was accomplished via a pars plana approach. Lens removal without implantation of an intraocular lens was performed in 16 eyes of 10 patients. Pars plana vitrectomy was accomplished in 12 eyes. Complications were well controlled by pars plana vitrectomy. CONCLUSIONS: Difficult preoperative situations and postoperative complications are not rare in MFS patients. However, they can be controlled well by means of modern vitreous surgery.

Adolescent↗

[PresbyLASIK: treatment approaches with the excimer laser].

Presbyopia represents the most common refractive error. There is currently no surgical treatment for presbyopia, which is effective, reliable, and safe. Excimer laser surgery has become a routine procedure for the correction of myopia, hyperopia, and astigmatism for years. Various treatment strategies for presbyopia have been brought forward using the excimer lasers. Besides monovision, creation of a multifocal cornea represents an attractive option. This procedure is also called "PresbyLASIK." Different ablation profiles to form a multifocal cornea are reviewed here and first clinical results are summarized."PresbyLASIK" is a new, interesting treatment strategy, with a huge potential for the future. At the present it should be used in controlled studies only because of some unsolved questions.

Humans↗

Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO).

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) provides an accurate delineation of areas of geographic atrophy (GA). Automated computer-assisted methods for detecting and removing interfering vessels are needed to support the GA quantification process in longitudinal studies and in reading centres. METHODS: A test tool was implemented that uses region-growing techniques to segment GA areas. An algorithm for illuminating shadows can be used to process low-quality images. Agreement between observers and between three different methods was evaluated by two independent readers in a pilot study. Agreement and objectivity were assessed using the Bland-Altman approach. RESULTS: The new method (C) identifies vascular structures that interfere with the delineation of GA. Results are comparable to those of two commonly used procedures (A, B), with a mean difference between C and A of -0.67 mm2 (95% CI [-0.99, -0.36]), between B and A of -0.81 mm2, (95% CI [-1.08, -0.53]), and between C and B of 0.15 mm2 (95% CI [-0.12, 0.41]). Objectivity of a method is quantified by the mean difference between observers: A 0.30 mm2 (95% CI [0.02, 0.57]), B -0.11 mm2 (95% CI [-0.28, 0.10]), and C 0.12 mm2 (95% CI [0.02, 0.22]). CONCLUSION: The novel procedure is comparable with regard to objectivity and inter-reader agreement to established methods of quantifying GA. It considerably speeds up the lengthy measurement process in AF with well defined GA zones.

Algorithms↗

[cSLO digital fundus autofluorescence imaging].

BACKGROUND: Fundus autofluorescence (FAF) originates from age- and disease-dependent accumulation of lipofuscin in the lysosomal compartment of the retinal pigment epithelium (RPE). FAF imaging is a noninvasive method to detect intrinsic RPE fluorescence in vivo. We describe features of a novel confocal scanning laser ophthalmoscope (cSLO) for FAF imaging and compare images to the previous cSLO system. METHODS: FAF images were obtained with a cSLO using an optically pumped solid state laser (OPSL) instead of an argon laser for generation of excitation light at 488 nm. For detection of emitted FAF signals >500 nm a barrier filter was used. RESULTS: The novel cSLO allows FAF imaging with a resolution of up to 5 microm/pixel to delineate normal and pathological features in various retinal pathologies including early-stage and advanced atrophic or neovascular age-related macular degeneration, macular edema, and retinal dystrophies. Further technical improvements include an internal fixation target and an enlarged optical focus adaption range. CONCLUSIONS: Improved image quality using the novel cSLO for FAF imaging is of clinical relevance for diagnosis and precise phenotyping of retinal diseases. This method may also be useful to monitor therapeutic effects targeting RPE lipofuscin accumulation as a common pathogenetic pathway in various degenerative and hereditary retinal diseases.

Aged↗

[The complement system and its possible role in the pathogenesis of age-related macular degeneration (AMD)].

The discovery of the complement factor H (CFH) polymorphism in age-related macular degeneration (AMD) strongly suggests a causative role of the complement system in the pathogenesis of this disease. The complement system is part of the innate immune system and is closely associated with the cellular response and the adaptive immune system. This article provides an overview of the complement system and, taking the new data into account, of possible immunopathogenetic processes in AMD.

Bruch Membrane↗

[Y402H polymorphism in complement factor H and age-related macula degeneration (AMD)].

Age-related macular degeneration is a complex genetic disorder. Recent data suggest that the additive genetic risk for late-stage disease is more than two-thirds. Comprehensive genetic studies (candidate gene approaches, linkage and association studies) have been performed in recent years to identity the genetic risk factors at the molecular lavel. Very recently, a significant risk allele, Y402H, has been discovered in the complement factor H (CFH) gene. The relative risk of developing AMD has been estimated between 2.4-4.6 for heterozygotes and 3.3-7.4 for homozygotes. This polymorphism accounts for approximately 20-50% of the overall risk of developing AMD. In this review the results from molecular genetic studies in AMD are summarized, with a special emphasis on the recent data obtained for the CFH gene.

Aryl Hydrocarbon Hydroxylases↗

[Classification of biomedical research reports as a reference for evidence-based medicine in ophthalmology. A survey considering as example the journal Der Ophthalmologe].

BACKGROUND: Evidence-based medicine requires careful appraisal of published data derived from experimental and clinical studies. Based on classification of biomedical research reports, evidence levels can be determined and recommendations for therapeutic decisions can be made. METHODS: A classification system for clinical studies was developed. It was evaluated in classifying the reports published in Der Ophthalmologe during 2003-2004 (study design: descriptive cross-sectional study, case series). RESULTS: In the 2-year interval, 70 longitudinal and 95 cross-sectional studies were published. The vast majority of the longitudinal studies were interventional cohort studies. Not considering case reports, 73% of the original articles were longitudinal prospective studies, 1% were retrospective (case-control) studies, and 26% were cross-sectional studies. CONCLUSIONS: The study design of all published articles could be classified using the classification system. This classification system proves to be applicable in the context of clinical studies in ophthalmology and may be helpful in the process of critical appraisal of the literature and synthesis of clinical evidence and an evidence-based recommendation.

Bibliometrics↗

[Cataract surgery in cases of age-related macular degeneration].

It has been noted for some time that cataract surgery in the presence of retinal comorbidity such as diabetic macular edema may generate a progression of macular changes and result in a poor visual outcome. Recent findings show that adverse events may also occur in the presence of age-related macular degeneration (AMD). Therefore, when indicating cataract surgery the surgeon needs to consider the risks both for progression of early into late stages of AMD or further deterioration of late manifestations of AMD. Furthermore, in the presence of advanced atrophic or neovascular AMD the question arises whether or not the patient may benefit from cataract surgery in spite of an already existing central visual loss. Here we critically review results from recent studies.

Cataract Extraction↗

[Variations in intraocular pressure (IOP) and necessity for paracentesis following intravitreal triamcinolone injection].

BACKGROUND: Intravitreal triamcinolone injection (IVT) has become a treatment option for macular edema of heterogeneous etiology and neovascular retinal diseases including AMD. Besides the risk for a steroid-induced secondary open-angle glaucoma, the acute rise in intravitreal volume induces IOP elevations immediately after injection. To decrease the intravitreal volume a paracentesis is advocated by many surgeons. The aim of this study was to determine variations in IOP at different time points immediately after IVT in order to assess the necessity for routine paracentesis. METHODS: The IOP was recorded by Goldmann applanation tonometry preoperatively, 10 minutes, 1, 3 and 24 hours after intravitreal injection of 0.1 mL (4 mg) triamcinolone. A consecutive series of 32 eyes of 32 patients with diabetic macular edema, diffuse edema after central vein occlusion or occult subfoveal choroidal neovascularization due to age-related macular degeneration was included. Statistical analysis was performed with ANOVA test and Bonferroni correction. RESULTS: Compared to baseline (15.24 +/- 0.52 mm Hg) IOP was significantly elevated 10 min postoperatively (22.28 +/- 1.4 mmHg; p < 0.05). One hour after injection IOP decreased to 15.58 +/- 0.69 mmHg (p < 0.05). Three and 24 h after injection mean IOP was not significantly different from preoperative baseline levels. Immediately after IVT light perception was tested and retinal perfusion was evaluated by indirect ophthalmoscopy. In none of the patients was a paracentesis necessary. CONCLUSION: Intravitreal injection of 0.1 mL triamcinolone led to a moderate transient rise in IOP. Based on these results, a routinely performed paracentesis immediately before or after IVT is not required. As paracentesis bears an additional risk including endophthalmitis it should only be considered if functional testing following injection indicates a relevant impairment of retinal perfusion.

Aged↗

Modelling the natural history of geographic atrophy in patients with age-related macular degeneration.

PURPOSE: To model the natural course of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS: Data on the natural course of GA were collected in the multi-center, longitudinal, prospective observational FAM study. The size of GA was measured by autofluorescence scanning laser ophthalmoscopy. The natural course of GA is modelled by two different mixed effect models (MEM). Both models are compared with respect to the correctness of the model assumptions, goodness of fit, and predictive behavior. RESULTS: The linear model results in better prediction, the non-linear model is more in agreement with the model assumptions. The non-linear model fits the data for small and large areas of GA better, while the linear model seems to be more adequate for the medial areas. More data will be needed to study the interplay of both models in more detail. CONCLUSIONS: The natural course of GA varies extremely between individuals. However, reliable factors for the explanation of this variability have so far not been established. MEM are useful for describing "inter-individual" as well as "intra-individual" influences without the need for precise knowledge of the influencing factors. Using MEM to evaluate data on the natural history of GA allows one to derive parameter estimates, which could be used to design interventional trials for modes of therapy with a potential to reduce or stop the progression of GA in patients with AMD.

Aged↗