Macular Degeneration: Schmidt-Erfurth U

Schmidt-Erfurth U, Kiss C, Sacu S. · Department of Ophthalmology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. · Prog Retin Eye Res. · Pubmed #19272333 No free full text.

Abstract: The clinical benefits of verteporfin therapy have been documented in a wide variety of patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), and there is encouraging evidence of improved outcomes when this angioocclusive modality is combined with antiangiogenic agents. Although the clinical benefits of verteporfin mono- and combination therapy are well established, there has been concern that treatment with verteporfin results in hypoperfusion in the treated area and that concomitant use of antiangiogenic agents could prolong this effect. However, despite well-documented occurrences of hypoperfusion on fluorescein and indocyanine green angiography, there is little evidence of associations with functional impairment or other adverse effects. It has also been suggested that hypoperfusion might actually help to reduce recanalization of CNV and permit neuronal recovery by decreasing exposure to oxygen and oxidative radicals. The reduced need for frequent retreatments clearly has a major appeal due to the lower costs associated with fewer interventions and reduced burden of clinical monitoring and diagnostic reevaluations. Ongoing evaluation in randomized clinical trials will provide further clarification on the effect of verteporfin plus ranibizumab compared with ranibizumab monotherapy in terms of visual acuity, anatomical outcomes, treatment frequency, and health economics. The results of these large-scale clinical trials will provide a strong basis for determining the benefits and risks of combination therapy.

Augustin AJ, Schmidt-Erfurth U. · Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany. · Eur J Ophthalmol. · Pubmed #17191188 No free full text.

Abstract: PURPOSE: Choroidal neovascularization associated with age-related macular degeneration is the primary cause of blindness in the elderly in developed countries, due to a number of pathogenic effects, including angiogenesis, cell-mediated inflammation, leukocyte adhesion and extravasation, and matrix remodeling. METHODS: By producing photochemical effects at the site of target tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood flow stasis, leading to occlusion of vascularization and lesion leakage. RESULTS: PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective in reducing the risk of vision loss in patients with classic containing subfoveal CNV and occult with no classic CNV. However, in predominantly occult CNV, the treatment may be most effective in smaller lesions, and less in larger lesions. Most important, visual acuity rarely is improved. CONCLUSIONS: Pilot studies and large case series suggest that a combination of PDT and intravitreal triamcinolone acetonide has the potential to improve visual outcomes and reduce the need for additional treatments. Randomized, prospective clinical trials are underway to confirm the efficacy and safety of this novel treatment modality.

Michels S, Schmidt-Erfurth U, Rosenfeld PJ. · Klinik für Augenheilkunde und Optometrie, Medizinische Universität Wien, Währinger Gürtel 18-20, Allgemeines Krankenhaus 8i, 1090 Wien/Vienna, Austria. · Expert Opin Investig Drugs. · Pubmed #16787141 No free full text.

Abstract: Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD.

Schmidt-Erfurth U, Michels S, Augustin A. · Department of Ophthalmology, University of Vienna, Vienna, Austria. · Arch Ophthalmol. · Pubmed #16606885 No free full text.

This publication has no abstract.

Schmidt-Erfurth U. · Universitätsklinik der Augenheilkunde und Optometrie, Vienna, Austria. · Dev Ophthalmol. · Pubmed #15604621 No free full text.

Abstract: The impact of nutrition on manifestation and progression of retinal diseases has become an important, controversial topic within recent years. The awareness of this topic in the general population has increased partially due strong commercial advertisements of supplements and diets. However, many potentially beneficial nutritional effects on retinal diseases have not been proven in prospective clinical trials. It is only for a few relatively rare diseases, such as retinitis pigmentosa or gyrate atrophy, that adjustments in nutrition have been proven effective and widely accepted. However, for the majority of patients with retinal diseases the impact of nutritional factors is still insufficiently understood. Theoretically, supplementation of antioxidants could have a beneficial impact on a wide variety of retinal diseases or as a preventive measure by limiting the degree of oxidative damage. The only prospective, controlled, clinical trial providing proven benefit of antioxidant supplementation for a retinal disease is the Age-Related Eye Disease Study (AREDS). Patients with at least intermediate age-related macular degeneration (AMD) were shown to have a significant benefit with regard to disease progression by supplementing with high-dose antioxidants and zinc. It is however unclear whether other antioxidants, such as lutein or zeaxanthin, may be better and whether a preventive supplementation is useful. Especially studies on patients with diabetic retinopathy have implicated an impact of higher cholesterol levels on the progression of the disease. High-fat diets have been overall associated to a number of retinal diseases. With the current knowledge it seems prudent to advise everyone a balanced, low-fat diet as well as vitamin supplementation within the recommended daily allowance. Smoking is an essential factor for oxidative stress, and its cessation should be recommended to everybody in order to prevent or slow down progression of retinal disease. High-dose antioxidant supplementation according to the AREDS trial should currently only be recommended to non-smokers with at least intermediate AMD. Based on results from experimental studies, further prospective clinical studies are warranted on the prevention and inhibition of disease progression in the most common retinal diseases by nutritional means.

Michels S, Schmidt-Erfurth U. · University Eye Hospital, Lübeck, Germany. · Semin Ophthalmol. · Pubmed #15513441 No free full text.

Abstract: Photodynamic therapy (PDT) with verteporfin is a new treatment modality in ophthalmology that has previously shown its effectiveness in treatment of a variety of neoplastic pathologies. In this therapeutic approach, the photosensitizer verteporfin is activated by non-thermal laser light to obtain closure of neovascular structures. Preclinical and clinical studies have indicated that PDT is a safe, selective, and effective treatment for choroidal neovascularization in age-related macular degeneration. No significant damage to the neurosensory retina was found, which explains why PDT does not cause loss of visual acuity and may be used in a larger population than laser photocoagulation. This review summarizes the mechanisms of action of PDT, and the results of preclinical and clinical studies in ophthalmology.

Augustin AJ, Dick HB, Offermann I, Schmidt-Erfurth U. · Augenklinik, Klinikum Karlsruhe, Germany. · Klin Monatsbl Augenheilkd. · Pubmed #12410462 No free full text.

Abstract: The eye is at high risk to be damaged by oxidative mechanisms. One major reason is the exposure to light throughout life. Anterior segment structures are mostly exposed to UV light. Visible blue light is believed to be a significant damaging mechanism for the retina. The biochemical composition of the posterior segment structures (unsaturated fatty acids) is an important factor making the eye more susceptible than other organs. Damaging mechanisms such as xanthin oxidase mechanisms are responsible for damage occurring in ischaemic diseases. These mechanisms are well known from diseases of other organs. Ischaemic processes are no longer believed to be the primary damaging mechanisms in diabetic retinopathy. Here, advanced glycation end products (AGE's) and related products may induce oxidative reactions and the expression of growth factors. In age-related macular degeneration photodynamic processes occurring already in childhood are believed to be a major factor contributing to the pathogenesis of the disease process. In addition, the expression of growth factors and new vessel growth can be initiated via inflammatory reactions or oxidative metabolites. In this manuscript we give an overview on oxidative mechanisms involved in the pathogenesis of retinal diseases. Different therapeutical and preventive approaches such as the results of the ARED-Study and possible side effects are discussed.

Schmidt-Erfurth U, Laqua H. · Klinik für Augenheilkunde des Universitätsklinikums Lübeck, Ratzeburger Allee 160, 23538 Lübeck. · Ophthalmologe. · Pubmed #11263053 No free full text.

This publication has no abstract.

Schmidt-Erfurth U, Hasan T. · University Eye Hospital, Lübeck, Germany. · Surv Ophthalmol. · Pubmed #11094244 No free full text.

Abstract: Age-related macular degeneration, especially the neovascular form of the disease, is the leading cause of blindness in elderly people in developed countries. Thermal photocoagulation is still the preferred treatment for choroidal neovascularization that does not involve the fovea, but it is suitable for only a small number of patients and it can lead to immediate loss of visual acuity. Photodynamic therapy with use of photochemical light activation of verteporfin as a photosensitizer (verteporfin therapy) has been shown to be effective in treating vascularized tumors, and its potential to treat other conditions involving neovascularization has also been suggested. Preclinical and clinical studies have indicated that verteporfin therapy can be used to treat choroidal neovascularization secondary to age-related macular degeneration effectively and safely. Selective occlusion of choroidal neovasculature by this therapy causes minimal damage to the neurosensory retina and, therefore, does not induce loss of visual acuity. This benefit allows verteporfin therapy to be used in the large proportion of patients who are not eligible for treatment by laser photocoagulation. The mechanistic aspects of the mode of action of light-activated verteporfin are described in this review.

Schmidt-Erfurth U. · University Eye Hospital Luebeck, Medical University, Luebeck, Germany. · Semin Ophthalmol. · Pubmed #10790573 No free full text.

Abstract: Photodynamic therapy (PDT) is currently being evaluated in clinical trials for the treatment of choroidal neovascularization (CNV). Preliminary results indicate that PDT achieves immediate absence of leakage from CNV while maintaining visual acuity. Indocyanine green angiography reveals a reduction in CNV size and a persistent decrease in leakage activity after PDT. PDT appears to be characteristically accompanied by choroidal perfusion changes that regularly resolve within 3 months. Microperimetry shows an improvement of the central visual field with a decrease in scotoma size and intensity. Repeated PDT applications do not cause additional damage to the treated area, but might further enhance the recovery of macular function. A placebo-controlled, multi-center trial (TAP trial) evaluating the benefit of repeated PDT treatments in 3-month intervals is currently underway.

Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C, Anonymous00098. · Department of Ophthalmology, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria. · Ophthalmology. · Pubmed #19410950 No free full text.

Abstract: PURPOSE: To analyze hyperreflective foci typically seen in diabetic macular edema (DME) in optical coherence tomography (OCT). DESIGN: Prospective clinical trial. PARTICIPANTS: Twelve consecutive patients with treatment-naïve, clinically significant DME. METHODS: During a same-day examination, a standardized visual acuity assessment (Early Treatment of Diabetic Retinopathy Study protocol), infrared fundus imaging, color fundus photography, and biomicroscopy were performed. Additionally, all patients were scanned using Stratus, Cirrus, and Spectralis OCT and results correlated. MAIN OUTCOME MEASURES: Morphologic changes secondary to DME. RESULTS: In all eyes with DME, distinct hyperreflective foci distributed throughout all retinal layers were found in the OCT scans of all 3 OCT devices. These deposits could not be identified by infrared imaging, fundus photography, or biomicroscopy as long as they were not confluent. Accumulations of such foci at the border of the outer nuclear and in the outer plexiform layer were recognizable clinically as hard exudates showing the same hyperreflective features in OCT. The hyperreflectivity of these foci did not correspond with intraretinal hemorrhage, nor did the lesions cause the characteristic OCT laser beam scattering phenomena typically seen secondary to intraretinal bleedings or microaneurysms. Further, they were detected within the walls of intraretinal microaneurysms. CONCLUSIONS: Well-demarcated, hyperreflective foci were identified in the retina of patients with DME. The deposits were located within walls of intraretinal microaneurysms and scattered throughout all retinal layers, forming confluent plaques in the outer plexiform layer. It is suggested that the foci represent extravasated lipoproteins and/or proteins being a very early subclinical barrier breakdown sign in DME.

Prager F, Michels S, Kriechbaum K, Georgopoulos M, Funk M, Geitzenauer W, Polak K, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Waehringer Guertel 18-20, 1190 Wien, Austria. · Br J Ophthalmol. · Pubmed #19074916 No free full text.

Abstract: AIMS: The aim of the study was to evaluate functional and anatomical changes after intravitreal bevacizumab (Avastin) in eyes with persistent macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). METHODS: Twenty-nine consecutive eyes with macular oedema secondary to BRVO (21 eyes) or CRVO (eight eyes) were included in a prospective clinical trial. Eyes were treated with three initial intravitreal bevacizumab injections of 1 mg at a monthly interval. Retreatment was based on central retinal thickness (CRT) based on optical coherence tomography. If continuous injections were indicated up to month 6, the dose was increased to 2.5 mg. RESULTS: After 12 months of follow-up, mean visual acuity increased from 50 letters (20/100) at baseline to 66 letters (20/50(+1); +16 letters; p<0.001) at month 12 and CRT decreased from 558 mum at baseline to 309 mum at month 12 (-249 mum; p<0.001). Patients received a mean of eight out of 13 possible injections. No drug-related systemic or ocular side effects following intravitreal bevacizumab treatment were observed. Fluorescein angiography revealed no progression of avascular areas. CONCLUSIONS: Intravitreal therapy using bevacizumab appears to be a safe and effective treatment in patients with macular oedema secondary to retinal vein occlusion. However, the main limitations of this treatment modality are its short-term effectiveness and high recurrence rate.

Funk M, Kriechbaum K, Prager F, Benesch T, Georgopoulos M, Zlabinger GJ, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. · Invest Ophthalmol Vis Sci. · Pubmed #19060280 No free full text.

Abstract: PURPOSE: To investigate concentrations of growth factors and inflammatory cytokines in eyes with central (CRVO) and branch (BRVO) retinal vein occlusion before and during therapy with bevacizumab and to identify associations with disease activity. METHODS: In a prospective clinical trial, 13 eyes of patients with CRVO (n = 5) or BRVO (n = 8) were included. Bevacizumab was administered intravitreously at baseline and months 1 and 2. Retreatments were given at monthly visits if OCT showed edema or when vision loss occurred. Aqueous humor samples were taken each time injections were performed. Follow-up was 15 months. Samples from patients with cataract served as the control. Multiplex bead assays were used for measurement of 28 growth factors and cytokines. RESULTS: During therapy with bevacizumab, VEGF levels were reduced to below detection in the first 2 months. Whenever criteria for retreatment were met, VEGF was measurable again. The decrease in VEGF was associated with a decrease in central retinal thickness (CRT) and improvement in visual acuity (VA). Significantly increased concentrations of VEGF, IL-6, IL-8, IP-10, MCP-1, and PDGF-AA were observed in aqueous humor samples of patients with CRVO compared with the control samples. CONCLUSIONS: VEGF levels were significantly elevated in patients with CRVO compared with control subjects. Intravitreal injections of bevacizumab resulted in a substantial decrease of VEGF under physiologic levels and remained low under the loading dose of three consecutive monthly retreatments. Macular edema was related to VEGF levels in the aqueous humor.

Geitzenauer W, Michels S, Prager F, Rosenfeld PJ, Kornek G, Vormittag L, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Austria. · Retina. · Pubmed #18784625 No free full text.

Abstract: BACKGROUND: To compare safety, visual acuity (VA), and anatomic outcomes of 2.5 mg/kg and 5 mg/kg intravenous bevacizumab in patients with neovascular age-related macular degeneration. METHODS: In an institutional cohort study, 16 patients (2 cohorts, 27 eyes) with neovascular age-related macular degeneration were treated with 5 mg/kg intravenous bevacizumab and 2.5 mg/kg, respectively. All patients received 3 initial intravenous infusions at 2-week intervals. The main outcome measures were VA, optical coherence tomography, and fluorescein angiography. RESULTS: No serious systemic or ocular adverse events were identified. By Day 7, mean VA increased from 56 letters (20/80(+1)) at baseline to 60 letters (20/63) in the 5 mg/kg group and mean central retinal thickness decreased by 83 microm. In the 2.5 mg/kg group, mean VA increased from 55 letters (20/80) to 66 letters (20/50(+1)) and mean central retinal thickness decreased by 93 microm. By Month 3, VA improved by 10 letters compared to baseline in the 5 mg/kg group and by 9 letters in the 2.5 mg/kg group. Central retinal thickness was reduced by 128 microm in the 5 mg/kg group and by 127 microm in the 2.5 mg/kg group. These benefits were sustained through 6 months. No statistically significant difference was found between both treatment groups regarding safety, VA, and anatomic outcomes. CONCLUSION: Similar VA, optical coherence tomography, and angiographic improvements were observed in both treatment groups up to 6 months. Further follow-up is required to evaluate the long-term durability and safety of both treatment regimens.

Schmidt-Erfurth U, Wolf S, Anonymous00033. · Department of Ophthalmology, Universitätsklinik fur Augenheilkunde und Optometrie, University of Vienna, AKH Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. · Br J Ophthalmol. · Pubmed #18772178 No free full text.

Abstract: OBJECTIVE: To evaluate safety of same-day administration of verteporfin and ranibizumab. METHODS: Prospective, open-label, multicentre study; patients with predominantly classic (n = 13) or occult (n = 19) choroidal neovascularisation secondary to age-related macular degeneration received standard-fluence verteporfin at baseline and months 3, 6 and 9, based on fluorescein angiography (FA). Ranibizumab 0.5 mg was administered at baseline and months 1, 2 and 3. MAIN OUTCOME MEASURE: The incidence of severe vision loss (best-corrected visual acuity (BCVA) loss > or = 30 letters; primary safety assessment). RESULTS: No severe vision loss due to ocular inflammation or uveitis occurred. One patient had moderate vision loss (BCVA loss > or = 15 letters). Three patients had mild/moderate uveitis. Two serious ocular adverse events occurred (retinal pigment epithelial tear and moderate BCVA decrease). No systemic adverse events occurred. At 9 months, all lesions were inactive with no recurrent leakage on FA and optical coherence tomography; macular oedema and subretinal fluid resolved. The mean BCVA measured at 2 m improved by 6.9 letters at 4 months and 2.4 letters at 9 months. CONCLUSIONS/APPLICATION TO CLINICAL PRACTICE: Same-day verteporfin and ranibizumab was safe and not associated with severe vision loss or severe ocular inflammation. Lesions stabilized, with minimal treatment required after month 3.

Kriechbaum K, Michels S, Prager F, Georgopoulos M, Funk M, Geitzenauer W, Schmidt-Erfurth U. · University Eye Hospital Zürich, Frauenklinikstrasse 24, CH-8091 Zurich, Switzerland. · Br J Ophthalmol. · Pubmed #18211942 No free full text.

Abstract: OBJECTIVE: To evaluate efficacy and safety of intravitreal bevacizumab (Avastin) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). METHODS: Twenty-eight consecutive patients (28 patients, 29 eyes, 8 CRVO, 21 BRVO) were enrolled in the study. Three intravitreal injections of 1 mg bevacizumab (0.04 ml) were administered at 4-week intervals; further retreatment was based on optical coherence tomography (OCT) findings. Follow-up examinations were done at days 1, 7 and 28 and at monthly intervals thereafter. RESULTS: Mean baseline central retinal thickness (CRT) in OCT was 558 microm (range 353-928 microm) and mean BCVA was 20/100. One day after the first injection, CRT significantly decreased to 401 microm (p<0.01). Three injections reduced macular oedema to 328 microm CRT (p<0.01) and improved BCVA to 20/50 (p<0.01). At 6 months, CRT was 382 microm (p<0.01), and BCVA was stable at 20/50(-2) (p<0.01), FA showed no evidence of increased avascular zones. CONCLUSION: Intravitreal injections of bevacizumab appear to be a safe and effective therapy in the treatment of macular oedema secondary to retinal vein occlusion.

Schmidt-Erfurth U, Sacu S, Anonymous00230. · Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. · Ophthalmology. · Pubmed #18166408 No free full text.

Abstract: PURPOSE: To compare efficacy and safety of a more intense regimen versus a standard one for retreatment of neovascular age-related macular degeneration (AMD) during the early period of verteporfin therapy (VT). DESIGN: Prospective, randomized, multicenter clinical trial. PARTICIPANTS: Two hundred three patients with predominantly classic choroidal neovascularization (CNV) secondary to AMD. METHODS: During the first 6 months of VT, patients underwent retreatment every 2 (group A) or 3 (group B) months. After 6 months, both groups underwent retreatment every 3 months for as long as CNV activity was documented. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) measured every 6 months, mean number of treatments per patient during 24 months' follow-up, proportions of patients in each group losing at least 3 lines of vision or gaining at least 1 line, greatest linear dimension (GLD) of the lesion as documented by fluorescein angiography every 6 months, and relationship between initial lesion size and BCVA. RESULTS: At all follow-up times, mean BCVAs were similar for groups A and B. Mean numbers of photodynamic therapy treatments were similar for both groups (4.07 vs. 4.36; P = 0.451, paired t test). A lower proportion (51.9% vs. 56.7%) of patients in group A had lost at least 3 lines of vision at 24 months. Groups A and B had similar increases in mean lesion size from baseline to 24 months (2104-3056 microm and 2179-3020 microm). At 24 months, patients in group A with a baseline lesion GLD of < or =2000 microm had significantly less mean loss of vision than patients in group A with a GLD of >2000 microm (P = 0.032); differences also were significant for group A with GLD of < or =2000 microm versus group B with GLD of < or =2000 microm (P = 0.041) or GLD of >2000 microm (P = 0.045); and mean vision losses from baseline were 8, 17, 15, and 14 letters, respectively. CONCLUSIONS: Overall outcomes regarding visual benefit, lesion anatomic features, and number of retreatments after 6 months were similar for patients receiving more intense or standard early therapy. An unplanned retrospective analysis showed that there was significantly less vision loss when the more intense regimen was used to treat smaller lesions.

Bolz M, Michels S, Geitzenauer W, Prager F, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. · Br J Ophthalmol. · Pubmed #17050580 No free full text.

Abstract: BACKGROUND: To evaluate the effect of systemic bevacizumab (Avastin) therapy on pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD) and to identify prognostic factors for PED regression and improvement in best corrected visual acuity (BCVA). Study design: Prospective uncontrolled pilot study. METHODS: Nine patients (nine eyes) received three systemic bevacizumab treatments at 2 week intervals and were examined at baseline, weeks 1, 2, 4, 6 and month 3 by using optical coherence tomography (Stratus OC, Carl Zeiss Meditec, Dublin, California, USA). Changes in maximum PED height and greatest linear diameter (GLD) were planimetrically analysed by using Adobe Photoshop CS and correlated with retinal morphological changes and changes in BCVA. RESULTS: Systemic bevacizumab therapy was well tolerated. Mean maximum PED height decreased significantly by 21% as early as 1 week (-96 microm (SD 48.8), p<0.01). At 3 months follow-up, two PEDs resolved completely, mean maximum PED height decreased significantly by 39% (-179 microm (SD 178), p = 0.02) and mean PED GLD by 24% (-714 microm (SD 1010), p = 0.07). Mean BCVA improved significantly by week 2 (+8.7 letters (SD 5.7), p<0.01) and at 3 months with 12.7 letters (SD 6.4) (p<0.01). CONCLUSION: In the examined nine patients, systemic bevacizumab therapy showed evidence for an effect on PED secondary to neovascular AMD in terms of a decrease in lesion height and diameter. A high PED at baseline was found to be a negative predictive factor for visual outcome.

Michels S, Wachtlin J, Gamulescu MA, Heimann H, Prünte C, Inhoffen W, Krebs I, Schmidt-Erfurth U. · Klinik für Augenheilkunde und Optometrie, Medizinische Universität Wien, Vienna, Austria. · Ophthalmology. · Pubmed #16225928 No free full text.

Abstract: PURPOSE: To compare the efficacy and safety of early retreatment with verteporfin therapy with that of approved standard verteporfin therapy in neovascular age-related macular degeneration. DESIGN: Prospective, randomized, multicenter clinical trial. PARTICIPANTS: Two hundred three patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration. METHODS: Throughout the first 6 months of follow-up, patients received retreatment with verteporfin therapy either every 2 months (group A) or 3 months (group B). From 6 to 12 months, both groups received retreatment at 3-month intervals. MAIN OUTCOME MEASURES: The primary outcome of the study was best-corrected mean visual acuity as measured using the Early Treatment Diabetic Retinopathy Study protocol. The secondary outcomes were percentage of patients losing at least 3 lines of vision, percentage of patients gaining at least 1 line of vision, and lesion size based on the greatest linear dimension (GLD) documented by fluorescein angiography, impact of initial lesion size, and retreatment rate as well as safety. RESULTS: Visual acuity was similar in both groups at baseline with a mean visual acuity of 20/100(-1). During the 12 months of follow-up, mean visual acuity was better in the early retreatment group at all intervals; however, no statistically significant benefit was seen in the overall population at any time (P>0.1). At month 12, mean visual acuity was 20/160(+1) in group A and 20/160(-1) in group B. There was a trend for better outcomes in the early retreatment group with regard to loss of less than 3 lines of vision at 12 months (61% vs. 51.7%). No statistically significant difference was seen with regard to lesion size for either group throughout follow-up with a final GLD of the lesion of 2790 microm (group A) and 2996 microm (group B). However, subgroup analysis indicated a statistically relevant benefit (P< or =0.004) for patients with small lesions (GLD<2000 microm) at baseline receiving early retreatment. CONCLUSIONS: Early retreatment in 2-month intervals did not show a significant overall benefit at 1 year of follow-up compared with the standard regimen. However, smaller lesions seemed to benefit from early retreatment with verteporfin therapy in contrast to larger lesions.

Bressler NM, Bressler SB, Haynes LA, Hao Y, Kaiser PK, Miller JW, Naor J, Potter MJ, Pournaras CJ, Reaves A, Rosenfeld PJ, Schmidt-Erfurth U, Slakter JS, Strong A, Vannier S. · No affiliation provided · Arch Ophthalmol. · Pubmed #16157822 No free full text.

This publication has no abstract.

Schmidt-Erfurth U, Michels S, Michels R, Aue A. · Department of Ophthalmology, University of Vienna, Vienna - Austria. · Eur J Ophthalmol. · Pubmed #16001382 No free full text.

Abstract: PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated clinically for treatment of exudative age-related macular degeneration (ARMD). A randomized, placebo-controlled, efficacy and safety dose duration study of anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient population was completed in June 2003. As part of this trial, 128 patients with subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and treated for up to 2 years by 18 clinical sites in the United States and European Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic examinations, general physical examinations, assessments of best-corrected logMAR visual acuity, and angiographic evaluations. The Digital Angiography Reading Center (New York City, NY) assessed lesion eligibility while the clinical investigators assessed overall patient eligibility prior to treatment. As part of this study, study medication was delivered as a posterior juxtascleral depot using a specially designed curved cannula at 6-month intervals if in the masked investigator's opinion the patient's lesion could benefit from additional treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was statistically superior to placebo for stabilization of vision (<3 logMAR line change from baseline) and for inhibition of neovascular lesion growth. There were no serious treatment-related safety issues associated with either the study medication or the procedure for administration. CONCLUSIONS: Anecortave acetate 15 mg for depot suspension is clinically efficacious compared to placebo for treatment of subfoveal exudative ARMD lesions when administered at 6-month intervals as a posterior juxtascleral depot.

Ahlswede W, Michels S, Birngruber R, Schmidt-Erfurth U. · Augenklinik, Universitätsklinikum Schleswig-Holstein, Lübeck. · Ophthalmologe. · Pubmed #15309484 No free full text.

Abstract: PURPOSE: Photodynamic therapy (PDT) induces occlusive and regenerative effects in choroidal neovascularization (CNV) and physiological choroid. The process of vascular alteration is documented quantitatively and qualitatively by three-dimensional angiography. METHOD: In a prospective, randomized trial 30 patients with subfoveal CNV due to age-related macular degeneration (AMD) were treated with PDT or placebo. Fluorescence series with 32 tomographic images over a 4-mm depth were analyzed topographically and reproduced in a three-dimensional display. RESULTS: At initial presentation CNV lesions were documented as a well-defined prominence in all patients. In the verteporfin group CNV height continuously decreased with each interval. In the placebo group CNV slightly increased in height during the first 6 months and remained stable at about 90% of the initial prominence at long-term follow-up. After 12 months 44% of the patients in the verteporfin group developed an additional choroidal defect. CONCLUSION: Three-dimensional angiography offers a reliable documentation of CNV progression and regression during PDT. A decrease in CNV size is associated with an increase in choroidal perfusion defects.

Ergun E, Maár N, Radner W, Barbazetto I, Schmidt-Erfurth U, Stur M. · Department of Ophthalmology, University of Vienna Medical School, Vienna, Austria. · Ophthalmology. · Pubmed #12511348 No free full text.

Abstract: PURPOSE: To investigate the correlation between reading speed and scotoma size in patients with subfoveal occult with no classic choroidal neovascularization (CNV) in age-related macular degeneration (AMD) participating at 2 of 28 centers in the Verteporfin in Photodynamic Therapy trial. DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-two eyes of 22 patients with occult with no classic CNV in AMD. METHODS: Patients' reading speed was examined using a German-language reading test (Radner Lesetest). Scotoma size was measured using the microperimetry program 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. MAIN OUTCOME MEASURES: Reading acuity, reading speed, size of absolute (AS) and relative scotoma (RS). RESULTS: There was a significant correlation between the size of AS and reading speed (r = -0.48, P = 0.023), as well as AS and reading acuity (r = 0.52, P = 0.013). No correlation was seen between RS and reading speed or reading capacity. CONCLUSION: The size of absolute scotoma correlated significantly with reading capacity and reading speed and may influence these measures.

Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA, Anonymous00111. · Wilmer Photograph Reading Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2002, USA. · Arch Ophthalmol. · Pubmed #12427056 No free full text.

Abstract: OBJECTIVE: To explore how baseline lesion composition influenced vision outcomes in patients with age-related macular degeneration (AMD) undergoing photodynamic therapy with verteporfin (Visudyne) for subfoveal choroidal neovascularization (CNV) in the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Investigation. METHODS: Patients with subfoveal lesions secondary to AMD with evidence of classic CNV were categorized into 2 subgroups based on baseline color photographs and fluorescein angiograms assessed by graders at the Wilmer Photograph Reading Center (The Johns Hopkins University School of Medicine) before any outcome analyses as follows: (1) predominantly classic CNV (area of classic CNV >/=50% of the area of the entire lesion) or (2) minimally classic CNV (area of classic CNV <50% but >0% of the area of the entire lesion). Additional exploratory analyses were performed in the predominantly classic subgroup to investigate the effects of visual acuity, lesion size, prior laser photocoagulation, phakic status, micronutrient use, and presence of occult CNV on vision outcomes. MAIN OUTCOME MEASURES: Subgroup analyses of vision and fluorescein angiographic outcomes at 1 and 2 years after study enrollment were examined in an intent-to-treat analysis from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials. RESULTS: Compared with patients who had minimally classic CNV, patients with predominantly classic CNV had a worse initial mean visual acuity and smaller lesions and were more likely to have lesions that included blood or blocked fluorescence. When evaluated by treatment assignment and lesion composition, 84% to 88% completed the month 24 examination. In the subgroup with predominantly classic lesions, visual acuity outcomes were consistently better in verteporfin-treated patients. Outcomes for patients with predominantly classic lesions without occult CNV tended to be better than outcomes for patients with predominantly classic lesions with occult CNV, although the former tended to have smaller lesions and lower levels of visual acuity at baseline. Contrast sensitivity and fluorescein angiographic outcomes (total lesion size, progression of classic CNV, and absence of classic CNV) were better in verteporfin-treated patients than in placebo-treated patients in the predominantly classic and the minimally classic CNV subgroups. In patients with predominantly classic CNV, no interaction of the treatment benefit by phakic status, micronutrient use, or prior laser photocoagulation therapy was noted. CONCLUSIONS: Verteporfin therapy can safely reduce the risk of moderate and severe vision loss in patients with subfoveal lesions that are predominantly classic CNV secondary to AMD. While this benefit seemed to be even greater in the absence of occult CNV, the effect may be related to the smaller lesions and worse visual acuity associated with predominantly classic lesions without occult CNV and not solely to the lesion composition itself. These analyses support initial reports that verteporfin therapy should be used to treat patients with AMD who have predominantly classic CNV, with or without occult CNV, but suggest that further investigations should be performed to determine if lesions with a minimally classic composition might benefit when they are smaller and have lower levels of visual acuity.

Blumenkranz MS, Bressler NM, Bressler SB, Donati G, Fish GE, Haynes LA, Lewis H, Miller JW, Monés JM, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Schachat AP, Schmidt-Erfurth U, Sickenburg M, Singerman LJ, Slakter JS, Strong A, Vannier S, Anonymous00194. · No affiliation provided · Arch Ophthalmol. · Pubmed #12365909 No free full text.

Abstract: OBJECTIVE: To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization (CNV). DESIGN AND SETTING: Open-label extension of selected patients from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials, the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation, at 22 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss. METHODS: Before receiving verteporfin therapy in the extension, eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards. Methods were similar to those described for 1- and 2-year results, with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions, including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment. RESULTS: Of 402 patients in the verteporfin group, 351 (87.3%) completed the month 24 examination; 320 (91.2%) of these enrolled in the extension study. The enrolled participants included 124 (78.0%) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline, of whom 105 (84.7%) completed the month 36 examination. Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study, with or without a month 36 examination, appeared more likely to have a younger age, better level of visual acuity, absence of fluorescein leakage from classic CNV, or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension. For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination, an average of 1.3 treatments were given from the month 24 examination up to, but not including, the month 36 examination. A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 (37.5%) at the month 24 examination compared with 44 (41.9%) of these patients at the month 36 examination. Visual acuity changed little from the month 24 examination (mean, -1.9 lines) to the month 36 examination (mean, -2.0 lines) for these eyes. Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36. Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension. One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension. CONCLUSIONS: Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36, although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination. From these results, the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin. Additional treatment was judged likely to reduce the risk of further vision loss. Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension.