Macular Degeneration: Helb HM

Meyer CH, Helb HM, Eter N. · Augenklinik, Universitätsklinikum Bonn, Ernst-Abbe-Strasse 2, 53127, Bonn, Germany. · Ophthalmologe. · Pubmed #18256841 No free full text.

Abstract: Age-related macular degeneration (AMD) is one of the most common causes of blindness in western industrialised nations. Most AMD patients suffer from the dry early form of AMD; however, wet AMD with choroidal neovascularization (CNV) is the main cause of blindness in all AMD patients. New prospects have been developed in AMD treatment using pharmacological methods available for treating all subtypes of exudative AMD. A number of inhibiting and inducing growth factors, such as vascular endothelial growth factor (VEGF), are particularly important in the pathophysiology of wet AMD. The secreted VEGF appears to play a crucial role in the pathogenesis of CNV and macular edemas as a result of its angiogenetic and permeability-enhancing effect. This recognition led to the treatment approach now used, i.e., competitive VEGF blocking through intravitreal adminsitration of anti-VEGF drugs. The anti-VEGF durgs lead to a rapid decrease in retinal thickness. Optical coherence tomography (OCT) is a valuable monitoring tool, but may only be used to assist in decision-making. Clinical follow-up of patients and further treatment recommendations must always be guided by the overall clinical picture. Visual acuity is regarded as the decisive criterion for repeat treatment.

Ladewig MS, Ziemssen F, Jaissle G, Helb HM, Scholl HP, Eter N, Bartz-Schmidt KU, Holz FG. · Augenklinik, Universität, Ernst-Abbe-Strasse 2, 53127 Bonn. · Ophthalmologe. · Pubmed #16763862 No free full text.

Abstract: 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.

Holz FG, Helb HM, Bindewald-Wittich A, Scholl HP. · Universitäts-Augenklinik, Bonn. · Internist (Berl). · Pubmed #16341677 No free full text.

Abstract: 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.

Fleckenstein M, Charbel Issa P, Helb HM, Schmitz-Valckenberg S, Scholl HP, Holz FG. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Arch Ophthalmol. · Pubmed #18852430 No free full text.

This publication has no abstract.

Fleckenstein M, Charbel Issa P, Helb HM, Schmitz-Valckenberg S, Finger RP, Scholl HP, Loeffler KU, Holz FG. · Department of Ophthalmology, University of Bonn, Bonn, Germany. · Invest Ophthalmol Vis Sci. · Pubmed #18487363 No free full text.

Abstract: PURPOSE: To describe morphologic variations in outer retinal layers in eyes with atrophic age-related macular degeneration (AMD) using high-resolution, spectral-domain optical coherence tomography (SD-OCT). METHODS: SD-OCT scans were obtained with a combined confocal scanning laser ophthalmoscope (cSLO) and SD-OCT for simultaneous tomographic and topographic in vivo imaging. A total of 81 eyes of 56 patients (mean age, 77.8 +/- 7.4 years) with geographic atrophy (GA) were examined. Morphologic alterations were analyzed and classified in the perilesional zone, at the junction between GA and nonatrophic retina, and in the atrophic area itself. RESULTS: In the perilesional zone, distinct morphologic alterations included elevations of the outer retinal layers, thickening, and spikes of the outer hyperreflective band as well as clumps at different neurosensory retinal levels. At the junction, highly variable transitions of the outer retinal layers were present with different degrees of loss of the normal hyperreflective bands. Within the actual GA, hyperreflective clumps at different retinal levels, segmented plaques of the outer band and elevations with variable reflectivity were visualized. CONCLUSIONS: SD-OCT imaging in eyes with GA revealed a wide spectrum of morphologic alterations, both in the surrounding retinal tissue and in the atrophic area. These alterations may reflect different disease stages or, alternatively, heterogeneity on a cellular and molecular level. Longitudinal studies using in vivo SD-OCT imaging may allow evaluation of the relevance of these phenotypic changes as potential predictive markers for the progression of disease (i.e., enlargement rates of GA over time) and may be used for monitoring of future therapeutic interventions.

Meyer CH, Scholl HP, Eter N, Helb HM, Holz FG. · Department of Ophthalmology, University of Bonn, Germany. · Acta Ophthalmol. · Pubmed #18221499 No free full text.

Abstract: PURPOSE: To assess the effectiveness of consecutive intravitreal injections of recombined tissue plasminogen activator (rtPA), expansile gas and bevacizumab in eyes with acute subretinal haemorrhage (SRH). METHODS: A retrospective, non-randomized consecutive case series included 19 eyes in 19 patients with SRH related to exudative age-related macular degeneration (AMD). The initial size of the subfoveal SRH was 1-3 disc diameters. Each patient received a triple procedure using 0.05 ml rtPA (50 microg), 0.3 ml of sulphur hexafluoride (SF6) gas and 0.05 ml bevacizumab (1.25 mg). Lesion size, location of the SRH and early treatment in diabetic retinopathy study (ETDRS) visual acuity were evaluated pretreatment as well as 1 and 3 months after the procedure. RESULTS: At the initial presentation, the patients' mean age was 77 years (range 63-88 years) and the mean duration of symptoms was 9.3 days (range 4-12 days). The mean visual acuity pretreatment (20/133) improved significantly to 20/86 at 1 month and to 20/74 at 3 months. The mean ETDRS visual acuity improved from baseline by 2.1 lines at 1 month (Wilcoxon ranks test; P < 0.005) and 3.7 lines at 3 months after treatment (Wilcoxon ranks test; P < 0.005). None of our patients had reading visual acuity prior to treatment, with visual acuity below 0.3. One month after the triple procedure, 25% of our patients had reading visual acuity (> or = 0.4); at 3 months, the figure was 35%. A successful inferior displacement of the SRH was achieved in 17/19 eyes. Eyes with elevated intraocular pressure were treated immediately by a corneal paracentesis. CONCLUSION: The intravitreal application of rtPA, gas and bevacizumab appears to be beneficial and well tolerated in the treatment of SRH in the short term. The triple approach seems a logical alternative to the current combined dual approach in limiting the progression of the underlying disease and achieving better visual outcome. Further randomized evaluations are warranted.

Ladewig MS, Karl SE, Hamelmann V, Helb HM, Scholl HP, Holz FG, Eter N. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, 53127, Bonn, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17701197 No free full text.

Abstract: BACKGROUND: Our aim was to evaluate the short-term safety and efficacy of combined photodynamic therapy (PDT) with verteporfin and intravitreal bevacizumab in neovascular age-related macular degeneration (AMD). METHODS: A prospective non-randomized interventional case series of 30 eyes of 30 patients with choroidal neovascularization (CNV) caused by AMD was studied. All patients were treated with PDT followed by an intravitreal injection of bevacizumab (1.5 mg) on the same day. Ophthalmic evaluations included determination of best-corrected visual acuity by using ETDRS charts. CNV lesion characteristics were determined by fluorescein angiography, and retinal morphology by optical coherence tomography. Review examinations were performed 1, 4, and 12 weeks following treatment. RESULTS: The median ETDRS letter scores increased by 3 letters after 4 weeks and 4.3 letters after 12 weeks. Median central retinal thickness decreased from the baseline by 145 microm (week 1), 205 microm (week 4), and 171 microm (week 12), respectively (P < 0.0001, for all comparisons). One patient experienced a transient moderate vision loss after 4 weeks post treatment. Leakage on fluorescein angiography was resolved in all patients at week 12. No significant ocular or systemic side-effects were observed. CONCLUSIONS: Short-term results suggest that a single PDT in combination with intravitreal bevacizumab is safe and associated with stabilization of visual acuity and decrease of intraretinal and subretinal fluid accumulation in the macula. Further evaluation of this treatment strategy for neovascular AMD appears warranted.

Bindewald A, Stuhrmann O, Roth F, Schmitz-Valckenberg S, Helb HM, Wegener A, Eter N, Holz FG. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany. · Br J Ophthalmol. · Pubmed #16299141 links to  free full text

Abstract: 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.