Macular Degeneration: Ziemssen F

Ziemssen F, Grisanti S, Bartz-Schmidt KU, Spitzer MS. · University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Tuebingen, Germany. · Drugs Aging. · Pubmed #19476398 No free full text.

Abstract: There is an active and controversial debate about the role of intravitreal bevacizumab versus approved drugs in the treatment of neovascular age-related macular degeneration (AMD). Because bevacizumab was available prior to the launch of ranibizumab, off-label use of the former became widespread and the cancer drug bevacizumab is the most commonly used medication in ophthalmology nowadays. This review considers every publication identified in MEDLINE using the keywords 'bevacizumab' and 'Avastin' between 1 June 2005 and 31 July 2008. The search identified 511 papers that were evaluated. In 33 studies, there was consistent and clear evidence for the efficacy of bevacizumab in neovascular AMD. However, the highest grade studies (three prospective, randomized, controlled trials) did not attain better than grade 2b level of evidence, and objective evaluation of the benefit of bevacizumab relative to representative controls was therefore not possible. Certainly, the available evidence is inferior to that obtained from the approval studies of ranibizumab and this should influence treatment selection and guidance of patients. These considerations indicate that important quality criteria need to be included in future studies to ensure more meaningful conclusions can be drawn. These include clearly defined inclusion criteria, information about the recruitment procedure (including data on withdrawals, excluded patients, concealed treatment allocation, use of intention-to-treat analyses and blinded assessment procedures). Although preclinical studies have almost exclusively found bevacizumab to be safe, the design utilized in clinical case series cannot rule out a possible increase in adverse events, which already show a high spontaneous incidence in elderly AMD patients. The superior evidence level for ranibizumab and the limited safety data for bevacizumab must be taken into consideration when evaluating the costs that a healthcare system is willing to spend. However, the superior grade of evidence for ranibizumab should not be confused with the (still missing) evidence for superior efficacy. The results of ongoing randomized, controlled, comparative trials will provide further data on the efficacy and cost effectiveness of bevacizumab and ranibizumab in the treatment of AMD. In the meantime, patients should be informed about the alternatives, the price differences and the restricted liability issue when off-label use of bevacizumab is offered.

Ziemssen F, Gelisken F. · Department für Augenheilkunde, Eberhard-Karls-Universität Tübingen. · Klin Monatsbl Augenheilkd. · Pubmed #19173161 No free full text.

Abstract: Since anti-VEGF treatment has been proven to achieve a significant improvement of visual acuity in a cohort of patients with neovascular age-related macular degeneration (AMD), macular surgery and particularly the macular translocation with 360 degrees retinotomy (FMT: full macular translocation) have lost their former popularity. However, the approach of macular surgery still remains a promising therapy in selected cases. A prospective randomised study, comparing FMT and photodynamic therapy in subfoveal classic choroidal neovascularisation (CNV), recently showed the superiority of FMT in terms of visual gain. In spite of the postoperative complications and the disturbed binocular vision, the reading acuity and the life quality of many patients improved. Therefore, it is justified to discuss the chances and advantages of the FMT at least in selected cases. After all, case selection was an important determinant also in the phase III studies of ranibizumab; many patients seen during the routine consulting hours were excluded as a consequence of the study criteria. Most of them were suspected to achieve a less favourable outcome of the anti-VEGF regimen. Thus, patients who did not meet the inclusion criteria of recent studies or showed no response to the anti-VEGF therapy, as well as patients with extensive submacular bleeding or ruptures of the pigment epithelium can also be considered as candidates of FMT. Generally, in the presence of highly effective anti-VEGF drugs, FMT can be discussed for second-line treatment, if the fellow eye has poor function and no additional risk factors of the affected eye are known (e. g., hyperopia, large lesion size, etc). Detailed information relating to the potential adverse events have to be mentioned. Although the indication is restricted, surgeons should have the continuing ability to perform the challenging surgical procedure.

Meyer CH, Ziemssen F, Heimann H. · Augenklinik, Universitätsklinikum Bonn, Ernst-Abbe-Strasse 2, 53127, Bonn, Germany. · Ophthalmologe. · Pubmed #18256842 No free full text.

Abstract: Intravitreal injection is generally regarded as safe. Many of the potential complications caused by this procedure are extremely rare and can be avoided by careful inspection beforehand and proper performance of the injection. In rare cases, however, the administered drugs may cause various pharmacological side effects. This article summarizes the safety profiles of Macugen and Lucentis from the drug approval studies and describes initial findings on possible or observed side effects after intravitreal administration of Avastin. In addition, important points to observe in order to avoid intra- and postoperative complications are provided.

Völcker M, Peters S, Inhoffen W, Ziemssen F. · Augenklinik, Eberhard-Karls-Universität, Schleichstrasse 12, 72076 Tübingen. · Ophthalmologe. · Pubmed #16763864 No free full text.

Abstract: VEGF is more potent than histamine by a factor of 50,000 for inducing increased vessel permeability. Already in the first few minutes, hydraulic conductivity and diffusive permeability are significantly increased, followed by a longer-lasting, marked leakage over 20 h. Specific inhibition of the angiogenic, vasoactive, and permeability-inducing protein VEGF is now possible by new drugs, one of which is the first available (off-label) treatment in Germany for routine clinical use (Avastin). Retinal edema is composed of increased outflow of water and low molecular substances in the interstitial environment and is an important determinate of functional development in different ocular diseases. First experiences with the anti-hyperpermeability effect show early response and high potential in pathologic leakage. Future examinations have to assess when a permanent benefit can be achieved in respect to the other antiproliferative capabilities of the drug.

Jaissle GB, Ziemssen F, Petermeier K, Szurman P, Ladewig M, Gelisken F, Völker M, Holz FG, Bartz-Schmidt KU. · Abt. I, Universitätsaugenklinik Tübingen, Schleichstrasse 12, 72076 Tübingen. · Ophthalmologe. · Pubmed #16763863 No free full text.

Abstract: 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.

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.

Jaissle GB, Leitritz M, Gelisken F, Ziemssen F, Bartz-Schmidt KU, Szurman P. · University Eye Clinic, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstr. 12, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18696094 No free full text.

Abstract: BACKGROUND: To investigate the long-term effectiveness of intravitreal bevacizumab treatment in eyes with perfused macular edema due to branch retinal vein occlusion (BRVO). METHODS: In this prospective interventional case series, 23 consecutive, previously untreated eyes with perfused macular edema were treated with intravitreal bevacizumab (1.25 mg) injections and followed for 1 year. The main outcome measures were visual acuity (VA) and central retinal thickness (CRT). In addition, VA data were adapted to the non-logarithmic VA charts used in the previously published grid laser photocoagulation BRVO Study. RESULTS: The median VA gained 3.0 lines from baseline at 48 weeks. This was accompanied by a significant decrease of 39% of the median CRT. The mean number of re-injections was 1.6 during the first 6 months of follow-up and only 0.8 during the subsequent 6 months. In 65% of the cases, adapted VA data showed a gain of 1 or more lines and no eye lost more than 1 line. CONCLUSIONS: Repetitive intravitreal bevacizumab injections result in a significant long-term improvement of VA and CRT. The number of re-injections necessary to maintain this effect declined over time. However, the treatment seems to be only slightly better than grid laser photocoagulation.

Spitzer MS, Ziemssen F, Yoeruek E, Petermeier K, Aisenbrey S, Szurman P. · University Eye Clinic Tuebingen, Centre of Ophthalmology, Eberhard-Karls University, Tuebingen, Germany. · J Cataract Refract Surg. · Pubmed #18165084 No free full text.

Abstract: PURPOSE: To describe the efficacy of intravitreal bevacizumab (Avastin) in patients with cystoid macular edema (CME) after cataract surgery (Irvine-Gass syndrome). METHODS: This retrospective case series comprised 16 eyes of 16 patients with CME after cataract surgery refractory to current standard treatment who received an injection of 1.25 mg intravitreal Avastin. The main outcome measures were visual acuity, retinal thickness on optical coherence tomography (OCT), and complications related to treatment. RESULTS: The median duration of CME before treatment with intravitreal Avastin was 14 weeks (range 3 to 84 weeks). Although the mean retinal thickness decreased slightly after intravitreal Avastin, the mean visual acuity remained unchanged. Visual acuity improved by 2 Early Treatment Diabetic Retinopathy Study lines in 1 patient, remained unchanged in 12 patients, and decreased by 2 lines in 2 patients. Repeated Avastin injections did not result in a better outcome. Other than mild ocular irritation, there were no adverse effects of the intravitreal injections. CONCLUSIONS: Intravitreal injection of Avastin, although safe, did not result in improved visual function in patients with postoperative CME. In contrast to findings in a previous case report, the beneficial effect of vascular endothelial growth factor inhibition in Irvine-Gass syndrome was not observed.

Lüke M, Ziemssen F, Völker M, Altpeter E, Beutel J, Besch D, Bartz-Schmidt KU, Gelisken F. · University Eye Hospital, University of Lübeck, Lübeck, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #19214552 No free full text.

Abstract: BACKGROUND: To report the outcome of best-corrected visual acuity (BCVA), near visual acuity (NVA), contrast sensitivity (CS) and vision-related quality of life (VRQOL) in patients 2 years after undergoing photodynamic therapy (PDT) or full macular translocation (FMT) for the treatment of neovascular age-related macular degeneration (AMD). METHODS: Fifty patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. BCVA was determined according a standardized protocol with ETDRS charts. NVA were calculated after testing with SNAB (Swiss National Association of and for the Blind) visual acuity cards. CS was measured with Pelli-Robson charts. The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25 plus supplement) was performed. Primary end points were the changes of BCVA, NVA, CS and VRQOL at 24-month examination. RESULTS: A stabilisation of BCVA (+0.3 letters) was found in the FMT group, whereas a decrease of more than 12 letters (-12.6 letters) was found in the PDT group (p = 0.052). Mean NVA improved by 7.0 letters in the FMT group and was superior to the PDT group (-9.6 letters, p = 0.036), while mean CS showed a time-dependent decrease in both treatment groups (FMT: -3.3 letters, PDT: -3.8 letters, p = 0.726). Considering the results of the VRQOL scores, the improvement of the subscales scores for general vision (p = 0.015), mental health (p = 0.028) and near activity (p = 0.020) were significantly higher in the FMT group. CONCLUSIONS: FMT can stabilise BCVA and improve NVA over a period of 2 years in patients with subfoveal classic CNV secondary to neovascular AMD, whereas a decrease of BCVA and NVA was found in the PDT group. CS did not differ between FMT and PDT. A significant increase of VRQOL scores was only found in the FMT group and not in the PDT group. FMT seems to be a therapeutic approach that can increase visual function resulting in an improvement of patient's VRQOL, but exhibits a higher number of severe complications compared to PDT.

Zhu Q, Ziemssen F, Henke-Fahle S, Tatar O, Szurman P, Aisenbrey S, Schneiderhan-Marra N, Xu X, Anonymous00470, Grisanti S. · Centre for Ophthalmology, Eberhard-Karls University, University Eye Hospital, Tübingen, Germany. · Ophthalmology. · Pubmed #18708261 No free full text.

Abstract: PURPOSE: To investigate the vitreous levels of bevacizumab and vascular endothelial growth factor-A (VEGF-A) after intravitreal injection of the drug in patients with choroidal neovascularization (CNV). DESIGN: Interventional case series. PARTICIPANTS: Eleven eyes of 11 patients with submacular hemorrhage and CNV due to age-related macular degeneration (n = 10) or angioid streaks (n = 1). METHODS: All patients were treatment naïve except for a single dose of intravitreal injection of bevacizumab (1.25 mg/50 muL dose) and subsequent vitrectomy after various intervals (1-101 days) because of active and progressive lesion. Intravitreal free bevacizumab and VEGF-A levels were measured using enzyme-linked immunosorbent assay and microsphere-based immunoassay, respectively. Vitreous VEGF-A isoforms were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. MAIN OUTCOME MEASURES: Intravitreal bevacizumab and VEGF-A levels were measured and pharmacokinetic parameters were calculated. RESULTS: Pharmacokinetics of intravitreal bevacizumab followed a 2-compartment model with initial and terminal half-lives of 0.5 and 6.7 days, respectively. Bevacizumab could be detected in all cases, ranging from 2.63 ng/ml to 165 microg/ml. The peak concentration was observed on the second day after intravitreal bevacizumab injection. Vitreous free VEGF-A levels ranged from 0.2 to 33.9 pg/ml and showed a negative correlation with the bevacizumab concentration (P<0.001; r = -0.955) and a positive correlation with time (P<0.001; r = 0.964). However, the percentage expression of VEGF-A(165) exhibited a positive correlation with the bevacizumab concentration (P = 0.032, r = 0.645) and a negative correlation with time (P = 0.007, r = -0.755). A time-dependent increase was found for the percentage expression of VEGF-A(189) (P = 0.023, r = 0.673). Neither bevacizumab- nor time-related alterations were found for VEGF-A(121). CONCLUSIONS: Based on pharmacokinetics, the interval of 6-7 weeks would be appropriate for efficacy, although clinical trials should guide dosing recommendations. Vitreous levels of free VEGF-A showed a negative correlation with the bevacizumab concentration, which confirmed the in vivo binding affinity of bevacizumab to VEGF-A. The analysis of the VEGF-A isoforms suggests differences of interaction between bevacizumab and individual VEGF-A isoforms.

Leitritz M, Gelisken F, Inhoffen W, Voelker M, Ziemssen F. · Department of Ophthalmology, University Eye Hospital, Tuebingen, Germany. · Eye. · Pubmed #18535608 No free full text.

Abstract: BACKGROUND: Retinal pigment epithelium (RPE) tears after bevacizumab treatment for neovascular age-related macular degeneration accompanied by a pigment epithelial detachment (PED) might be caused by stretching forces on the already weakened RPE. The purpose of this study was to evaluate whether simple measurements of optical coherence tomography (OCT) can predict the individual risk of an RPE tear in preoperative candidates. METHODS: A retrospective chart review study of 393 consecutive patients with neovascular age-related macular degeneration evaluated OCT images (Stratus-OCT Zeiss, Jena, Germany). The height of the PED, the central retinal thickness, and the maximum retinal thickness were determined by two independent observers and retrospectively analysed. RESULTS: Fifteen patients with an RPE tear had a significant higher PED than the remaining study population. In contrast, no correlation was seen with the central retinal thickness. In a linear regression model, the probability of an RPE tear exponentially increased in dependence of the extent of PED. CONCLUSION: The risk of an RPE tear can be estimated by simple measurement of the height of the PED on OCT.

Gelisken F, Ziemssen F, Voelker M, Bartz-Schmidt KU, Inhoffen W. · Center for Ophthalmology, University of Tuebingen, Tuebingen, BW, Germany. · Eye. · Pubmed #18239678 No free full text.

Abstract: PURPOSE: To analyse retinal pigment epithelial (RPE) tears following single administration of intravitreal bevacizumab for neovascular age-related macular degeneration (AMD) during early follow-up. METHODS: Interventional, retrospective, non-comparative case series included 397 patients (409 eyes) of the 746 consecutive patients that met the eligibility criteria. Standardized visual acuity testing, fluorescein angiography, and optical coherence tomography were performed. Data collected included status of the fellow eye, previous treatment, subtypes of choroidal neovascularization (CNV), size and composition of the lesion. Multiple linear regression modelling was used to explore the effect of baseline parameters on the RPE tears. Primary end point was occurrence of RPE tears within 6 weeks after therapy. RESULTS: Fifteen of the 409 eyes (3.6%) developed RPE tear (95% confidence interval: 2.2-6.0, odds ratio: 26.3). The statistical modelling showed significant association between RPE tear and occult without classic CNV/predominantly haemorrhage vspredominantly/minimal classic CNV (P=0.019), as well as medium or large (>4 disc area) vssmall size of the total lesion (P=0.038). Previous treatment and status of the fellow eye did not statistically influence the risk of RPE tears. CONCLUSIONS: An RPE tear can develop in up to 3.6% of eyes with neovascular AMD following single administration of intravitreal bevacizumab in a short-term follow-up. Medium and large lesion size and occult without classic and predominantly haemorrhagic subtype of CNV were important predictive factors. Preoperative assessment of the lesion characteristics may help in identifying the risk of individual patients with neovascular AMD before intravitreal bevacizumab treatment.

Ziemssen F, Lüke M, Bartz-Schmidt KU, Gelisken F. · Department for Ophthalmology, University Eye Hospital, Eberhard-Karls University, Schleichstr. 12-16, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18071731 No free full text.

Abstract: PURPOSE: To report the change of contrast sensitivity (CS) after photodynamic therapy (PDT) vs full macular translocation (FMT) for neovascular age-related macular degeneration (AMD), and to relate this to other measures of visual function (distance and near acuity). METHODS: Fifty patients (50 eyes) with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomized to PDT or FMT. CS was measured with Pelli-Robson charts. Acuity scores of near visual function (NVS) were calculated after testing with visual acuity cards of the Swiss National Association of and for the Blind (SNAB). Best corrected distance visual acuity (DVA) was determined according to a standardized protocol with EDTRS charts. Primary end point was the change of CS at 12-month examination from baseline. The interaction of the CS with NVS and DVA was analysed. RESULTS: Mean CS showed a decrease in both treatment groups (FMT: -2 letters, PDT: -3 letters, p=0.969) at 12-month examination from baseline. While mean NVS improved by seven letters in the FMT group, a decrease of more than ten letters was seen in the PDT group (p<0.05). We found no agreement between CS and high-contrast acuity (NVS, DVA). In FMT patients, the parameters at baseline (CS, NVS, DVA) correlated poorly with the corresponding 12-month results, therefore providing no informative basis to predict the later functional development. In contrast, PDT patients showed strong baseline-to-outcome coherence with baseline measures also associated with better final values. CONCLUSIONS: Although FMT can initiate recovery of near and distance acuity over the period of 1 year in selected patients with classic CNV, CS did not differ between FMT and PDT. We found no close connection of CS with DVA or NVS, especially after FMT. Knowledge about the unequal variation of visual parameters can provide more comprehensive information when advising patients on different therapeutic options. That also applies in particular to vascular endothelial growth factor inhibitors, which seem to promise an even higher extent of gain in CS and to reach the peak of recovery at an earlier time.

Peters S, Cree IA, Alexander R, Turowski P, Ockrim Z, Patel J, Boyd SR, Joussen AM, Ziemssen F, Hykin PG, Moss SE. · University College of London, Institute of Ophthalmology, Departments of Cell Biology and Pathology, 11-43 Bath Street, London, UK. · Cytokine. · Pubmed #17959386 No free full text.

Abstract: PURPOSE: Vascular permeability is important at many sites, but particularly so in diabetic retinopathy where macular oedema is the major cause of blindness. Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are important factors involved in neovascularization and vascular leakage, but there is little data on their interaction to promote increased vascular permeability. METHODS: Porcine retinal endothelial cells (PREC) were seeded into permeable inserts and cultured in 24-well plates that permit measurement of permeability using fluorescent dextrans. Cell purity was assessed immunohistochemically. At confluency, PREC were treated with increasing concentrations of VEGF (20-100ng/ml) and Ang-2 (15-75ng/ml). The effect on tight junctions was assessed by visualization with an anti-ZO-1 antibody. RESULTS: Immunohistochemistry showed high purity of isolated PREC. Permeability of untreated PREC monolayers was low. The increase in permeability in Ang-2 treated cells (25-30% compared with non-treated cells) was less than that for cells treated with VEGF only (20-100% compared with untreated cells). Highest permeability was seen with a combination of Ang-2 and VEGF (100-400% compared with untreated cells). Permeability increased with time after growth factor application. Preliminary ZO-1 immunohistochemistry appeared to demonstrate the presence of tight junctions between untreated PREC, and loss of tight junctions after treatment with VEGF and Ang-2. CONCLUSIONS: VEGF alone is twice as potent in interrupting tight junctions in an endothelial cell monolayer as Ang-2. However, both growth factors acting together increase permeability three times as much as VEGF alone. Treatments designed to reduce vascular permeability in diabetic macular oedema should consider that crosstalk between growth factors including VEGF and the Ang-2/Tie-2 system can multiply their effects.

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

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

Lüke M, Ziemssen F, Bartz-Schmidt KU, Gelisken F. · University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Schleichstr. 12-16, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17347809 No free full text.

Abstract: PURPOSE: To assess visual function and its effects on vision-targeted, health-related quality of life (QOL) of patients with neovascular age-related macular degeneration (AMD) treated with photodynamic therapy (PDT) or full macular translocation (FMT). METHODS: Fifty patients with predominantly classic subfoveal choroidal neovascularisation (CNV) secondary to AMD were randomised to PDT or FMT. To test the vision-targeted QOL, the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25 plus supplement) was administered prior to and 1 year after therapy. The change of vision-related QOL at 1 year in comparison to baseline was defined as primary end point. RESULTS: The vision-related subscales showed a stabilisation or even higher mean scores at 1 year in both treatment groups. A significant improvement in the quality of the subject's vision-related subscales was only observed after FMT correlating with a more frequent increase in visual acuity. Comparing the results of the QOL scores after 1 year, the improvement of the subscale scores general vision (p = 0.03), mental health (p = 0.02) and dependency (p = 0.03) were significantly higher in the FMT arm. CONCLUSIONS: FMT and PDT can achieve a stabilisation in vision-related QOL, in which FMT was superior to the PDT after 1 year. The discrepancy between the amount of patients with an increased visual acuity after FMT and a moderate improvement in QOL might be caused by the onset of complications related to this surgical procedure. Besides visual acuity, the impact of therapy-related complications has to be taken into consideration when evaluating new therapeutic concepts in exudative AMD.

Aisenbrey S, Ziemssen F, Völker M, Gelisken F, Szurman P, Jaissle G, Grisanti S, Bartz-Schmidt KU. · Center of Ophthalmology, University of Tuebingen, Schleichstrasse 12, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17186262 No free full text.

Abstract: BACKGROUND: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. METHODS: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. RESULTS: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). CONCLUSIONS: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

Petermeier K, Tatar O, Inhoffen W, Völker M, Lafaut BA, Henke-Fahle S, Gelisken F, Ziemssen F, Bopp S, Bartz-Schmidt KU, Grisanti S. · Univerisity Eye Clinic at the Centre for Ophthalmology, Eberhard-Karls University Tuebingen, Schleichstrasse 12-16, 72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #16613924 links to  free full text

Abstract: AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age related macular degeneration. METHODS: Retrospective review of 22 surgically excised CNV. 12 of these patients had been treated with PDT 3-146 days previously. Apoptotic cells were detected with the TUNEL technique and compared to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised both by collapsed and patent vessels. The EC displayed a statistical significant positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001) and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV excised 1-5 months after PDT displayed a patent vascularisation and high proliferative activity. All membranes either treated or untreated disclosed only sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS: Verteporfin PDT leads to selective and effective damage of EC within CNV. Both patent and occluded vessels were lined by apoptotic EC. This finding and the increased expression of proliferation marker at later time points suggest that revascularisation after PDT is caused by angiogenesis rather than recanalisation.

Voelker M, Gelisken F, Ziemssen F, Wachtlin J, Grisanti S. · Department of Ophthalmology I, University of Tübingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #16010552 No free full text.

Abstract: PURPOSE: To report the results of verteporfin photodynamic therapy (PDT) of extrafoveal predominantly classic choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). METHODS: In this retrospective study 20 consecutive patients (20 eyes) undergoing verteporfin PDT for extrafoveal predominantly classic CNV in AMD were examined. Colour photography of the fundus, fluorescein angiography and complete ophthalmic examination, including visual acuity assessment with ETDRS charts, were performed before treatment and at 3-month intervals thereafter. The primary outcome criterion was the change in visual acuity. The secondary outcome criterion was the extension of the CNV beneath the centre of the fovea during the follow-up period. RESULTS: Mean follow-up time of the patients was 24.2 months (range 12 to 58 months). Visual acuity at baseline varied from 20/200 to 20/20 (mean 20/50+/-2.3 lines). Final visual acuity ranged from 20/1000 to 20/20 (mean 20/200+/-5.1 lines) (P<0.001). In 85% (17/20) of the eyes visual acuity worsened. Visual acuity improved in 15% (3/20) of the eyes. During the course of the follow-up period, subfoveal extension of the CNV was detected in 80% (16/20) of the eyes. CONCLUSION: In 85% of the eyes with extrafoveal predominantly classic CNV secondary to AMD, visual acuity worsened after verteporfin PDT in an average follow-up time of 24 months. Subfoveal CNV was found in 80% of the eyes during follow-up. Even though verteporfin PDT can preserve visual acuity in selected cases, deterioration was seen in the majority of the patients.

Ziemssen F, Warga M, Bartz-Schmidt KU, Wilhelm H. · Abteilung I, Augenklinik, Eberhard-Karls-Universität Tübingen. · Ophthalmologe. · Pubmed #15912318 No free full text.

Abstract: PURPOSE: Since completion of the AREDS study, evidence has accumulated to suggest that some form of dietary supplementation may be of value in special individuals who are at risk of progressive age-related macular degeneration (ARMD). We wanted to find out which of the many supplements available are recommended in practice and which instructions, promises, and purchasing arguments are used by German pharmacies. METHODS: A blinded consultation following a standardized protocol was carried out in 60 pharmacies. RESULTS: In 36 pharmacies specific products for dietary supplementation were recommended, but the dosage never complied with the AREDS study, and in 24 pharmacies, the necessity for a medical examination or consultation with an ophthalmologist was not mentioned. Possible interactions with other drugs or side effects were generally excluded. CONCLUSIONS: Potential risks of supplement intake were underestimated. Medical knowledge of the most frequent cause of blindness in the Western world was insufficient. A clear policy of recommendations according to evidence-based criteria is needed.

Ziemssen F, Heiduschka P, Schraermeyer U, Anonymous00107. · No affiliation provided · Retina. · Pubmed #18040264 No free full text.

This publication has no abstract.

Ziemssen F, Deuter CM, Stuebiger N, Zierhut M. · No affiliation provided · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17219112 No free full text.

This publication has no abstract.

Gelisken F, Ziemssen F, Voelker M, Bartz-Schmidt KU. · No affiliation provided · Acta Ophthalmol Scand. · Pubmed #17083554 No free full text.

This publication has no abstract.

Ziemssen F, Grisanti S, Bartz-Schmidt KU. · No affiliation provided · Br J Ophthalmol. · Pubmed #17057183 No free full text.

This publication has no abstract.

Ziemssen F, Warga M, Neuhann IM, Leitritz M, Biester S, Grisanti S, Bartz-Schmidt KU. · No affiliation provided · Br J Ophthalmol. · Pubmed #16782958 links to  free full text

This publication has no abstract.