Macular Degeneration: Szurman P

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.

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.

Tatar O, Adam A, Shinoda K, Kaiserling E, Boeyden V, Claes C, Eckardt C, Eckert T, Pertile G, Scharioth GB, Yoeruek E, Szurman P, Bartz-Schmidt KU, Grisanti S. · University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany. · Arch Ophthalmol. · Pubmed #19273790 No free full text.

Abstract: OBJECTIVE: To evaluate the early effects of triamcinolone acetonide (TA) on inflammation, proliferation, and vascular endothelial growth factor (VEGF) in human choroidal neovascularization (CNV). METHODS: Retrospective review of an interventional case series of 29 patients who underwent macular translocation. Fourteen CNV membranes without previous therapy (control CNV group) and 4 CNV membranes excised 3 days after photodynamic therapy (PDT CNV group) comprised the control groups. Eleven patients were treated with intravitreal TA (TA CNV group; n = 5) or PDT and TA combined (PDT+TA CNV group; n = 6) 3 to 9 days preoperatively. The CNV membranes were stained for cytokeratin 18, CD34, VEGF, intercellular adhesion molecule-1 (ICAM-1), E-selectin, CD68, CD45, Ki-67, and Thy-1. RESULTS: Treatment with TA and PDT+TA resulted in increased immunostaining of ICAM-1 in endothelial cells and the stroma and a higher percentage of Thy-1 expression than controls. The density of macrophages was significantly increased in PDT+TA CNV membranes. Leukocyte density and proliferative activity were lower in TA and PDT+TA CNV membranes. The total VEGF score was significantly increased in TA and PDT+TA CNV membranes compared with the control CNV membranes. Evidence of VEGF in the retinal pigment epithelium of PDT+TA CNV membranes was stronger than in control CNV membranes. CONCLUSIONS: Triamcinolone acetonide has no inhibitory effect on macrophage infiltration or ICAM-1, Thy-1, or VEGF expression in CNV membranes in the early term. The clinical benefits of TA are probably not based on pure antiinflammatory or VEGF-suppressing mechanisms.

Tatar O, Shinoda K, Kaiserling E, Claes C, Eckardt C, Eckert T, Pertile G, Boeyden V, Scharioth GB, Yoeruek E, Szurman P, Bartz-Schmidt KU, Anonymous00069, Grisanti S. · University Eye Clinic at the Centre for Ophthalmology, Eberhard-Karls-University, Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #18838410 No free full text.

Abstract: AIM: To evaluate the implications of intravitreal bevacizumab on proangiogenic vascular endothelial growth factor (VEGF) with regard to the endogenous angiogenesis inhibitor endostatin in human choroidal neovascularisation (CNV) secondary to age-related macular degeneration. METHODS: Retrospective review of an interventional case series of 48 patients who underwent full macular translocation surgery with removal of CNV. Twenty-five patients were treated with intravitreal bevacizumab injection 1 to 154 days prior to surgery (bevacizumab CNV). Twenty-three CNV without any kind of previous treatment were used as controls (control CNV). CNV were stained for CD34, cytokeratin18, VEGF, endostatin and E-selectin. A "predominance score of VEGF over endostatin" (PS) was defined by the difference between VEGF and endostatin staining scores. RESULTS: Bevacizumab CNV revealed a weaker VEGF expression in endothelial cells (p = 0.0245) but significantly more intense endostatin in retina pigment epithelium (RPE) (p = 0.0001) and stroma (p<0.0001). Consequently, PS was significantly lower in RPE (p = 0.02), vessels (p = 0.03) and stroma (p = 0.0004) in bevacizumab CNV. The intensity of E-selectin expression in bevacizumab CNV was comparable with that in control CNV. CONCLUSIONS: A shift within the angiogenic balance in terms of decreased VEGF predominance over endostatin is detected in human CNV treated with bevacizumab.

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.

Tatar O, Yoeruek E, Szurman P, Bartz-Schmidt KU, Anonymous00212, Adam A, Shinoda K, Eckardt C, Boeyden V, Claes C, Pertile G, Scharioth GB, Grisanti S. · University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University, Tübingen. · Arch Ophthalmol. · Pubmed #18541840 links to  free full text

Abstract: OBJECTIVE: To evaluate the effect of bevacizumab (Avastin; Genentech, Inc, South San Francisco, California) on inflammation and proliferation in human choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: Retrospective review of interventional series of 38 patients who underwent choroidal neaovascular membrane (CNVM) extraction. Twenty-four patients received intravitreal bevacizumab 1 to 154 days preoperatively (bevacizumab CNV group). Fourteen patients received no preoperative therapy (control CNV group). The CNVM were stained for cytokeratin 18, CD68, CD45, intercellular adhesion molecule (ICAM)-1, E-selectin, Ki-67, Thy-1, and endostatin. RESULTS: No significant difference was detected in ICAM-1 and E-selectin expression between groups. The density of leukocytes in the bevacizumab CNV group (median, 271.61 cells/mm(2)) was higher than in the control CNV group (median, 116.87 cells/mm(2); P = .07), but without significance. Density of macrophages (median, 4661.95 cells/mm(2)), proliferative activity (median, 160.19 cells/mm(2)), and percentage of Thy-1-expressing vessels (median, 100%) were significantly higher in the bevacizumab CNV group than in the control CNV group (median, 882.66 cells/mm(2), P < .001; median, 34.34 cells/mm(2), P < .001; and median, 80%, P < .001, respectively). Endostatin immunoreactivity was considerably stronger in the retina pigment epithelium (RPE)-Bruch membrane complex (median, 3; range, 2-3; P < .001), and stroma (median, 3; range, 1-3; P < .001) of the bevacizumab CNV group than control CNV group (median, 1.5; range, 0-3 and median, 1; range, 0-3, respectively). CONCLUSIONS: Unexpectedly, CNVM from patients treated by bevacizumab are characterized by significantly high inflammatory and proliferative activity and enhanced endostatin expression. These characteristics need to be considered when protocols for combination therapies are established.

Tatar O, Shinoda K, Kaiserling E, Pertile G, Eckardt C, Mohr A, Yoeruek E, Szurman P, Bartz-Schmidt KU, Grisanti S. · Centre for Ophthalmology, University Eye Hospital, Eberhard-Karls University, Schleichstrasse 12-15, 72076 Tuebingen, Germany. · Arch Ophthalmol. · Pubmed #18268209 links to  free full text

Abstract: OBJECTIVE: To evaluate the early effects of triamcinolone acetonide as monotherapy or as an adjuvant to ocular verteporfin photodynamic therapy (PDT) on angiogenesis in human choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: Retrospective review of an interventional series of 55 patients who underwent CNV extraction. Eleven patients were treated with intravitreal triamcinolone acetonide (4 mg) monotherapy (triamcinolone-treated CNV group [n = 5]) or with PDT-triamcinolone combination therapy (PDT-triamcinolone-treated CNV group [n = 6]) 3 to 9 days before surgery. Forty patients who underwent CNV extraction without previous therapy (control CNV group) and 4 patients who underwent CNV extraction 3 days after PDT (PDT CNV group) served as control subjects. The CNV samples were stained for CD34, endostatin, cytokeratin 18, and vascular endothelial growth factor (VEGF). RESULTS: Vascular endothelial growth factor expression was stronger in the PDT CNV samples (P < .001), triamcinolone CNV samples (P = .01), and PDT-triamcinolone CNV samples (P = .007) compared with the control CNV samples. There were no statistically significant differences in VEGF expression among the PDT CNV samples, triamcinolone CNV samples, and PDT-triamcinolone CNV samples. Endostatin expression was weaker in the PDT CNV samples than in the control CNV samples (P = .008). Endostatin expression was stronger in the triamcinolone CNV samples and the PDT-triamcinolone CNV samples compared with the control CNV samples (P = .001 and P < .001, respectively) and the PDT CNV samples (P < .001 for both). CONCLUSION: To some extent, triamcinolone monotherapy seems to exert its angiogenesis inhibitory effects on CNV by enhancing endostatin expression rather than by suppressing VEGF expression.

Aisenbrey S, Bartz-Schmidt KU, Walter P, Hilgers RD, Ayertey H, Szurman P, Thumann G. · Department of Ophthalmology, University of Tuebingen, Schleichstrasse 12-16, 72076 Tuebingen, Germany. · Arch Ophthalmol. · Pubmed #17923545 links to  free full text

Abstract: OBJECTIVE: To assess long-term functional and morphological changes after macular translocation in patients with exudative age-related macular degeneration. METHODS: Evaluation of a noncomparative cohort study of 90 patients with a follow-up of 14 to 79 months (mean, 38.2 months). RESULTS: Visual acuity increased by 3 or more lines in 15 patients, remained stable in 35 patients, and deteriorated in 40 patients at final examination. Pigment epithelium atrophy extending to the new fovea was detected in 44 patients; in 25 patients this new atrophy was associated with loss of visual function. CONCLUSIONS: Long-term follow-up of macular translocation with 360 degrees retinotomy showed stabilization or improvement in half of the patients. Progressive atrophy of the pigment epithelium represented one major limiting factor of the beneficial effect of the treatment. Macular translocation may be an option for cases of exudative age-related macular degeneration that are not eligible for or do not respond to alternative treatments.

Tatar O, Adam A, Shinoda K, Yoeruek E, Szurman P, Bopp S, Eckardt C, Bartz-Schmidt KU, Grisanti S. · University Eye Hospital at the Center for Ophthalmology, Eberhard-Karls University Tuebingen, Germany. · Retina. · Pubmed #17621180 No free full text.

Abstract: PURPOSE: To examine the short- and long-term consequences of verteporfin photodynamic therapy (PDT) on inflammation with regard to infiltration of macrophages and leukocytes and expression of thy-1 in human choroidal neovascularization membranes (CNV) secondary to age-related macular degeneration (AMD). METHODS: Retrospective review of an interventional case series of 43 patients who underwent removal of CNV. Twenty patients were treated with PDT 3 to 246 days preoperatively. Twenty-three CNV without previous treatment were used as control. CNV were stained for CD34, CD105, cytokeratin 18, Ki-67, thy-1, an endothelial cell glycoprotein known to be upregulated only by inflammatory cytokines, CD68 (macrophages), and CD45 (common leukocyte antigen). RESULTS: Specimens treated by PDT 3 days previously showed significantly reduced endothelial thy-1 expression (P = 0.008), leukocyte (P=0.04) and macrophage (P=0.0063) infiltration, and proliferative activity (P=0.02) compared to control CNV. Specimens at longer intervals after PDT, in contrast, disclosed a significantly increased expression of thy-1 (P=0.004), infiltration with leukocytes (P=0.044) and macrophages (P=0.01), and proliferative activity (P=0.03) compared to CNV excised 3 days after PDT. CONCLUSIONS: The rebound effect after PDT seems to be based on an inflammatory response that contributes to enhanced proliferation. These data support the need for an anti-inflammatory therapy as adjuvant to PDT.

Lüke M, Januschowski K, Warga M, Beutel J, Leitritz M, Gelisken F, Grisanti S, Schneider T, Lüke C, Bartz-Schmidt KU, Szurman P, Anonymous00138. · Department of Ophthalmology, University of Tuebingen, Schleichstr. 12-16, D-72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #17383998 No free full text.

Abstract: AIM: To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). METHODS: Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 microg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 microg/ml, 60 microg/ml and 200 mug/ml) on the a- and b-wave amplitudes were investigated. The percentages of a- and b-wave reduction during application and at washout were calculated. RESULTS: During application of bevacizumab (0.25 mg/ml) in co-application with 20 microg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 microg/ml and 60 microg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 microg/ml rt-PA did not alter the a-wave amplitude. However, 60 microg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 microg/ml rt-PA, a significant reduction of the a- and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout. CONCLUSION: The present study suggests that a subretinal injection of 20 microg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.

Aisenbrey S, Gelisken F, Szurman P, Bartz-Schmidt KU. · Center of Ophthalmology, University of Tuebingen, Schleichstr. 12, D-72076 Tuebingen, Germany. · Br J Ophthalmol. · Pubmed #17301123 No free full text.

Abstract: OBJECTIVE: To report the functional and morphological outcome of surgical treatment of peripapillary choroidal neovascularisation due to age-related macular degeneration. METHODS: Consecutive interventional case series of eight patients with extensive peripapillary choroidal neovascularisation and accompanying haemorrhage who underwent subretinal surgery including extraction of the neovascular complex. Ophthalmic examination, including visual acuity testing, colour photography and fluorescein angiography, was performed at baseline and at 3, 6, 9 and 12 months, and then yearly. RESULTS: Mean follow-up was 26 months (12-60 months). Preoperative best corrected visual acuity (BCVA) ranged from logMAR (logarithm of minimum angle of acuity) 1.0 (20/200) to logMAR 0.0 (20/20), with a mean of logMAR 0.5 (20/63). Mean postoperative BCVA was logMAR 0.3 (20/40). BCVA improved in six patients, was stable in one patient and deteriorated in one patient. Two years after surgery, one patient developed recurrence of the CNV that was removed surgically. One patient showed retinal detachment 5 years after subretinal surgery. CONCLUSIONS: In this small case series of PPCNV, functional improvement was achieved after surgery in the majority of patients. Surgical extraction of the CNV represents an alternative treatment option in eyes with vision-threatening extensive PPCNV. Randomised controlled studies seem to be justified to evaluate further the beneficial effect and long-term functional outcome of this therapy approach.

Gelisken F, Voelker M, Schwabe R, Besch D, Aisenbrey S, Szurman P, Grisanti S, Herzau V, Bartz-Schmidt KU. · Centre for Ophthalmology, University of Tuebingen, Schleichstr. 12, 72076 Tuebingen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17219106 No free full text.

Abstract: BACKGROUND: The purpose of this study was to compare full macular translocation (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related macular degeneration (AMD). METHODS: In a prospective, randomised, non-masked, mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or PDT. Baseline and control examinations in 3-monthly intervals over a 12-month period included standardized protocol refraction, visual acuity testing and fluorescein angiography. Primary outcome measurements were made to establish the change in distant visual acuity from the baseline to the 12-month examination. The statistical analyses were carried out on the intent-to-treat principle. RESULTS: The improvement of one or more ETDRS lines was 56% (14/25) of the eyes in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five patients) were recorded in the FMT group. None of the eyes treated in the FMT group had phtysis. CONCLUSION: This pilot study showed that no statistically significant difference existed between the FMT and PDT in terms of the vision loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of vision improvement was significantly higher for the patients in the FMT group. However, in the era of promising therapy with anti-vascular endothelial growth factor for neovascular AMD, FMT should not be offered as a standard primary procedure for neovascular 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.

Aisenbrey S, Lafaut BA, Szurman P, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU, Thumann G. · Center of Ophthalmology, Department of Vitreoretinal Surgery, Eberhard-Karls University Tuebingen, Tuebingen, Germany. · Arch Ophthalmol. · Pubmed #16476887 links to  free full text

Abstract: OBJECTIVE: To report the functional and anatomical outcome of 20 patients who underwent surgical removal of choroidal neovascularization combined with transplantation of autologous iris pigment epithelial cells to the subretinal space 3 years after treatment. METHODS: Freshly isolated autologous iris pigment epithelial cells were translocated to the subretinal space in 20 patients after membrane extraction. Patients were followed up by funduscopy, angiography, microperimetry, and visual acuity testing. RESULTS: After a follow-up of 3 years, 1 patient showed improved visual acuity, 13 patients retained stable visual acuity, and 3 patients had reduced visual acuity. No macular edema or recurrent choroidal neovascularization was apparent at any time during the follow-up. CONCLUSIONS: Transplanted autologous iris pigment epithelial cells were well tolerated for 3 years and stabilization of visual acuity was achieved in most patients. These results suggest that iris pigment epithelial cells may serve as a substitute for retinal pigment epithelial cells after choroidal neovascularization removal in patients with exudative macular degeneration; however, whether these cells will be of any value for the restoration of vision and possible protection against choroidal neovascularization recurrence awaits further clinical observation and additional research.

Grisanti S, Tatar O, Canbek S, Lafaut BA, Gelisken F, Inhoffen W, Szurman P, Aisenbrey S, Oficjalska-Mlynczak J, Bartz-Schmidt KU. · Department of Ophthalmology I, Division of Vitreoretinal Surgery, Eberhard-Karls University of Tuebingen, Schleichstrasse 12-15, 72076 Tuebingen, Germany. · Am J Ophthalmol. · Pubmed #15126158 No free full text.

Abstract: PURPOSE: To evaluate the vascularization and proliferative activity in choroidal neovascular membranes due to age-related macular degeneration after verteporfin photodynamic therapy and submacular removal. DESIGN: Interventional case series. METHODS: In a retrospective review of seven patients who underwent removal of subfoveal classic choroidal neovascular membranes after treatment with photodynamic therapy 3 to 146 days earlier, membranes were stained for CD 34, CD 105, and Ki-67 and correlated with clinical pictures and fluorescein angiography. RESULTS: Fluorescein angiography performed on the day of surgery disclosed nonperfusion of the treated area 3 days after photodynamic therapy, but perfusion and leakage were seen at greater post-photodynamic therapy intervals. Membranes excised 3 days after photodynamic therapy showed CD34 and CD105 positive, mostly occluded vessels. The endothelial cells appeared damaged. Ki-67 activity was low. In membranes excised 34 to 146 days after photodynamic therapy, all vessels appeared patent and were lined by healthy endothelial cells with strong expression of CD34 and CD105. Ki-67 expression was elevated after 34 days but decreased thereafter. CONCLUSION: Photodynamic therapy did not cause a general or complete occlusion of vessels within the choroidal neovascular membranes, as suggested by fluorescein angiography 3 days postintervention, but the endothelial cells appeared to be severely damaged. Proliferative activity within these specimens was reduced. At longer intervals after photodynamic therapy, the fibrovascular tissue seemed to recover; perfusion, hyperfluorescence, and leakage of the choroidal neovascular membranes could be detected by fluorescein angiography. The clinical appearance showed a correlation with the immunohistologic characteristics of an increased proliferative activity and patent vascularization.

Grisanti S, Canbek S, Kaiserling E, Adam A, Lafaut B, Gelisken F, Szurman P, Henke-Fahle S, Oficjalska-Mlynczak J, Bartz-Schmidt KU. · Department of Vitreoretinal Surgery, Center of Ophthalmology, Eberhard-Karls University Tuebingen, Schleichstrasse 12-15, FRG 72070 Tuebingen, Germany. · Exp Eye Res. · Pubmed #14729353 No free full text.

Abstract: Endoglin (CD105) is a membrane protein involved in the TGF-beta receptor signalling pathway with predominant expression by proliferating endothelial cells. The aim of this study is to analyze the expression of Endoglin in choroidal neovascularization membranes (CNVM) and to compare it to the overall proliferative status of CNVM. Thirty surgically excised CNVM, secondary to age-related macular degeneration, were investigated using light microscopic immunohistochemistry and confocal immunofluorescence microscopy using verified antibodies directed against the endothelial cell markers Endoglin, von Willebrand factor (vWF) and CD34 and the proliferation marker Ki-67. Donor eyes were used as controls. A selective expression of CD34 and vWF as well as Endoglin was found in endothelial cells. Endoglin expression was elevated in vascular endothelial cells contained within CNVM, but a moderate Endoglin expression could also be visualized in quiescent CD34 and vWF positive ocular vasculature. Ki-67 positive cells were detected in CNVM, but these were rarely endothelial cells. Endoglin expression in endothelial cells of CNVM is increased, but rarely associated with a concomitant expression of the proliferation marker Ki-67. The elevated expression of Endoglin in surgically excised CNVM suggests a persisting post-mitotic activation in an advanced stage of this neovascular tissue.

Aisenbrey S, Lafaut BA, Reynders S, Szurman P, Grisanti S, Vanden Broecke C, Walter P, Bartz-Schmidt KU. · Department of Vitreo-Retinal Surgery, Center of Ophthalmology, University of Cologne, Cologne, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #12719987 No free full text.

Abstract: PURPOSE: To analyze the histopathology of choroidal neovascularization after external beam radiotherapy in age-related macular degeneration. METHODS: A retrospective non-case-matched comparative histopathologic study. The histoarchitecture of nine surgically removed subretinal specimens from nine patients that had undergone external beam radiotherapy for exudative age-related macular degeneration was studied. Seven patients had received 20 Gy in 10 fractions and two 15 Gy in 5 fractions with an average time interval between radiotherapy and surgical extraction of 14 months (range 3-28). A consecutive series of classic, mixed and occult choroidal neovascular membranes served as controls. RESULTS: Clinical findings. Radiation-associated choroidal neovasculopathy was angiographically suspected in four patients: a coarse net of vessels on fluorescein angiography developing at the border of previously irradiated choroidal neovascularization was observed in three patients; blebs at the margin of a plaque on indocyanine green angiography were observed in two patients. Pathological findings. Diffuse drusen as well as intra-Bruch's fibrovascular tissue was found in all irradiated specimens. In four specimens an edematous vascularized layer was seen between diffuse drusen and normal-appearing intra-Bruch's fibrovascular tissue. This lesion was not found in the control specimens. A particular correlation for the bleb lesion was not recognized. CONCLUSION: The appearance of an edematous subretinal pigment epithelial vascularized layer between diffuse drusen and normal-appearing fibrovascular tissue in four of nine irradiated membranes may be secondary to previous irradiation. It may correlate with the unusual exudative manifestations observed after external beam radiotherapy.

Aisenbrey S, Lafaut BA, Szurman P, Grisanti S, Lüke C, Krott R, Thumann G, Fricke J, Neugebauer A, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU. · Department I, University Eye Clinic Tuebingen, Schleichstrasse 12-16, 72076 Tuebingen, Germany. · Arch Ophthalmol. · Pubmed #11934318 No free full text.

Abstract: BACKGROUND: Macular rotation surgery comprises surgical extraction of choroidal neovascular membranes in age-related macular degeneration (AMD) and translocation of the foveal neural retina over adjacent retinal pigment epithelium. OBJECTIVE: To determine whether macular translocation with 360 degrees retinotomy can stabilize and/or improve visual acuity in patients with subfoveal choroidal neovascularization (CNV) secondary to AMD. DESIGN: This study consisted of a standardized surgical procedure on a series of 90 consecutive patients and follow-up examinations at fixed intervals for 12 months. PARTICIPANTS: All patients in this study had experienced recent visual loss resulting from subfoveal CNV caused by AMD. Twenty-six patients had major macular subretinal hemorrhage, 39 patients had occult subfoveal CNV, and 25 patients had classic subfoveal CNV. METHODS: Macular translocation surgery was performed between 1997 and 1999. The patients were examined preoperatively and at 3, 6, and 12 months postoperatively, including visual acuity, microperimetry, angiography, and orthoptic assessment. RESULTS: Visual acuity increased by 15 or more letters in 24 patients, remained stable in 37 patients, and deteriorated by 15 or more letters in 29 patients at 12 months postoperatively. A secondary procedure was necessary in 17 patients because of severe complications; proliferative vitreoretinopathy was observed in 17 eyes, macular pucker in 5 eyes, and macular hole in 1 patient. CONCLUSION: Macular translocation is a technically demanding surgical procedure. Although the procedure has a high rate of surgical and postoperative complications, the functional and anatomical results appear to be promising for selected patients with subfoveal CNV secondary to AMD.

Aisenbrey S, Lafaut B, Szurman P, Grisanti S, Fricke J, Neugebauer A, Hilgers RD, Esser P, Walter P, Bartz-Schmidt KU. · Zentrum für Augenheilkunde, Universität zu Köln, Joseph-Stelzmann-Strasse 9, 50931 Köln. · Ophthalmologe. · Pubmed #11917797 No free full text.

Abstract: BACKGROUND: During surgical extraction of choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD), the defective foveal retinal pigment epithelium (RPE) is removed. Subsequent translocation of the foveal neural retina to adjacent healthy RPE should result in stabilization and possibly improvement of visual acuity. METHODS: A prospective case series was carried out using controlled surgery and examination protocols with examinations made at fixed intervals. The surgical procedures combine counterrotation of the globe, phacoemulsification and implantation of a posterior chamber lens, complete vitrectomy, induction of a total retinal detachment, 360 degrees anterior retinotomy, removal of the subfoveal neovascular complex, foveal translocation outside the RPE defect, reattachment of the retina using F6H8, peripheral laser retinopexy and temporary silicone oil tamponade. PATIENTS: Macular translocation surgery was performed on 100 patients between December 1997 and December 1999. All patients had experienced recent visual loss due to exudative AMD and of these, 26 patients had major macular subretinal hemorrhage, 39 patients had occult and 25 patients classic subfoveal choroidal neovascularization. The preoperative findings in the remaining patients included tears in the pigment epithelium (n = 4), polypoidal choroidal vasculopathy (n = 1), recurrent subfoveal CNV following laser therapy (n = 2) and deep retinal vascular anomalous complexes (n = 3). RESULTS: A total of 97 patients completed the 12-month examination. Visual acuity increased by 15 or more ETDRS chart letters in 24 patients, remained stable in 42 patients and deteriorated by 15 or more EDTRS chart letters in 34 patients 12 months postoperatively. The silicone oil tamponade was removed in 97 patients, in 10 patients, silicone oil had to be reinjected because of severe complications. A secondary procedure was necessary in 25 patients, primary PVR was observed in 9 eyes, secondary PVR developed in 10 eyes, a macular pucker in 5 eyes and a macular hole in 1 patient. Other postoperative complications included persistent hypotonia, macular edema, IOL dislocation, keratopathy and recurrent CNV (n = 3). CONCLUSIONS: Macular translocation is a technically demanding operation, which requires a considerable learning curve. Although the procedure has a high rate of surgical and postoperative complications, the functional and anatomical results appear to be promising for selected patients with subfoveal CNV secondary to AMD.

Spitzer MS, Szurman P, Bartz-Schmidt KU. · No affiliation provided · J Cataract Refract Surg. · Pubmed #18498977 No free full text.

This publication has no abstract.