Macular Degeneration: Kirchhof B

Joussen AM, Kirchhof B. · No affiliation provided · Ophthalmologe. · Pubmed #12723577 No free full text.

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Kirchhof B. · No affiliation provided · Ophthalmologe. · Pubmed #11917792 No free full text.

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Holz FG, Kirchhof B. · No affiliation provided · Ophthalmologe. · Pubmed #11450471 No free full text.

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Joussen AM, Lehmacher W, Hilgers RD, Kirchhof B. · Department of Ophthalmology, University of Düsseldorf, Düsseldorf, Germany. · Surv Ophthalmol. · Pubmed #17472802 No free full text.

Abstract: A large variety of new treatment options for different forms of age-related macular degeneration (ARMD) are becoming available. Not all new therapies may meet the expectations of patients and ophthalmologists. Despite the given statistical significant priority of treatment investigations, the endpoints may not be relevant to the patient's requirements. Therefore, questions inevitably arise regarding patient's benefit and the validity of the randomized controlled trials. The randomized controlled trial is regarded as the "gold standard" in terms of evaluating the effectiveness of interventions. The external validity of randomized controlled trials may be compromised, if, for example, patients assigned to the study group are unrepresentative of the reference population. This review aims to analyze problems with external validity in the randomized controlled trials on ARMD and surveys the endpoints of clinical studies with respect to the patient benefit.

Joussen AM, Llacer H, Mazciewicz J, Kirchhof B. · Abteilung für Netzhaut- und Glaskörperchirurgie, Zentrum für Augenheilkunde, Universität zu Köln. · Ophthalmologe. · Pubmed #15592847 No free full text.

Abstract: Surgical therapy of diabetic retinopathy has been refined since the Early Treatment Diabetic Retinopathy Study (ETDRS). ETDRS did not perform panretinal photocoagulation at the time of surgery, which is currently considered a major part of vitrectomy, e.g., in vitreous hemorrhage. Despite improved surgical techniques, patient expectations and surgical outcome still differ considerably in severe cases of proliferative diabetic retinopathy. In this review of the literature we discuss the current surgical options and indications in diabetic retinopathy and maculopathy.

Fauser S, Krohne TU, Kirchhof B, Joussen AM. · Abteilung für Netzhaut- und Glaskörperchirurgie des Zentrums für Augenheilkunde und Zentrum für Molekulare Medizin, Universität zu Köln. · Klin Monatsbl Augenheilkd. · Pubmed #12953154 No free full text.

Abstract: The current clinical classification into focal, diffuse, and ischaemic maculopathy is useful with respect to pathomechanism and therapy. This review discusses the value of standard therapeutical options as well as the recent surgical and pharmacological approaches.

Krohne TU, Fauser S, Kirchhof B, Joussen AM. · Abteilung für Netzhaut- und Glaskörperchirurgie des Zentrums für Augenheilkunde und Zentrum für Molekulare Medizin, Universität zu Köln, Germany. · Klin Monatsbl Augenheilkd. · Pubmed #12953153 No free full text.

Abstract: Hyperglycaemia causes breakdown of the blood retina barrier leading to formation of macular oedema and consecutive visual loss. Three major mechanisms are involved in barrier breakdown: increased paracellular permeability of vascular endothelium due to disruption of cell junctions, loss of endothelial cell layer integrity due to cell destruction, and increased transcellular transport through the endothelium. This review focuses on the molecular basis of these mechanisms and discusses the role of cytokines and cellular interactions in blood retina barrier breakdown.

Fauser S, Engelmann K, Krohne TU, Lappas A, Kirchhof B, Joussen AM. · Abteilung für Netzhaut- und Glaskörperchirurgie und Zentrum für Molekulare Medizin, Universität zu Köln, Cologne. · Ophthalmologe. · Pubmed #12682762 No free full text.

Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world but the pathogenesis remains poorly understood.Malfunction of the retinal pigment epithelium (RPE) plays a central role in the disease and leads to either choriodal atrophy or proliferation.This article reviews the current concepts of the development of choriodal atrophy and neovascularisation. Furthermore, available animal models and potential therapeutical targets are discussed.

Joussen AM, Lemmen KD, Kirchhof B. · Zentrum für Augenheilkunde, Universität zu Köln, Abt. für Netzhaut- und Glaskörperchirurgie, Joseph Stelzmann Strasse 9, 50931 Köln. · Ophthalmologe. · Pubmed #11594237 No free full text.

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Verma L, Das T, Binder S, Heriot WJ, Kirchhof B, Venkatesh P, Krebs I, Stolba U, Jahn C, Feichtinger H, Kellner L, Krugluger H, Pawelka I, Frohner U, Kruger A, Li W, Tewari HK. · R.P Centre for Ophthalmic Sciences, AIIMS, New Delhi, India. · Indian J Ophthalmol. · Pubmed #11340884 links to  free full text

Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population. The prevalence is reported to be 1.2-1.4% in several population-based epidemiological studies. Currently 25-30 million people worldwide are blind due to AMD. With the aging world population it is bound to increase significantly, and could become a significant public health problem in next two decades, with serious socio-economic implications. Several strategies are today available to treat the wet form of AMD, which is responsible for significant visual loss. These were until recently confined to laser photocoagulation, and subretinal surgery, but today two other modalities, namely, radiation and photodynamic therapy, are available. These treatment modalities however, are aimed at preservation of vision only, and not at reversing the process of the disease. Further research on antiangiogenic drugs and gene therapy could significantly help AMD patients.

Maaijwee K, Joussen AM, Kirchhof B, van Meurs JC. · The Rotterdam Eye Hospital, Schiedamse Vest 180, 3011 BH Rotterdam, The Netherlands. · Br J Ophthalmol. · Pubmed #18369068 No free full text.

Abstract: AIM: To investigate whether retinal pigment epithelium (RPE)-choroid translocation would be a suitable treatment for RPE tears, which have a poor prognosis and are encountered more often since the introduction of anti-(vascular endothelial growth factor (VEGF)) therapy for exudative age-related macular degeneration (AMD). METHODS: Prospective interventional case series of six eyes of six patients with AMD with an RPE tear treated with an RPE-choroid translocation. The RPE tear occurred in a vascularised pigment epithelium detachment in four patients and after treatment in the other two. Preoperative and postoperative evaluation included ETDRS visual acuity (VA) and fixation testing. The follow-up period ranged from 6 months to 2 years. RESULTS: The mean preoperative VA was 20/160 (range 20/400-20/80). The mean VA at the last examination after surgery was 20/80 (range 1/60-20/50). One of the six patients had a preoperative VA of >/=20/80, and four had a VA of 20/80 or better at their last examination. Foveal fixation on the graft was present in five of the six eyes up to the last examination. CONCLUSION: These preliminary data show that an RPE-choroid translocation may be a treatment option for patients with an RPE tear.

Lappas A, Foerster AM, Weinberger AW, Coburger S, Schrage NF, Kirchhof B. · Department of Ophthalmology, University of Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15300442 No free full text.

Abstract: PURPOSE: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (ARMD) over 1 year. METHODS: The consecutive interventional case series included 56 patients with exudative ARMD. During vitrectomy the submacular neovascular membrane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, were injected into the submacular space. Included were patients with subfoveal occult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigment epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome measures were visual acuity, foveal fixation, size of CNV and rate of recurrence based on fluorescence angiographic imaging. RESULTS: All patients underwent successful surgical removal of the CNV with consecutive subretinal IPE injection. Visual acuity was better than 20/100 in 19 patients preoperatively and in 18 patients postoperatively. A visual acuity of 20/100 or less was found in 37 patients preoperatively and in 38 patients postoperatively. Mean preoperative visual acuity (1.0+/-0.3 logMAR units) did not change significantly after 1 year (1.0+/-0.3 logMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgically denuded area could be demonstrated in 25 eyes (45%). CONCLUSIONS: Autologous IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasible with a low rate of complications. Continued research seems justified to improve functional outcome.

Lappas A, Weinberger AW, Foerster AM, Kube T, Rezai KA, Kirchhof B. · Augenklinik, Universitätsklinikum der RWTH Aachen, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #11011682 No free full text.

Abstract: BACKGROUND: This prospective, non-controlled pilot study investigates the practicability of IPE translocation and functional outcome in ARMD patients. Removal of submacular choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) is usually associated with RPE damage and poor visual prognosis. Homologous RPE transplants fail to preserve macular function, possibly due to immune rejection. Instead of homologous RPE, we suggest translocating autologous iris pigment epithelium (IPE), building on earlier evidence from animal and in vitro investigations that IPE can substitute RPE functions in the experimental animal. Immunological cell rejection is avoided. METHODS: Four eyes with well-defined and eight eyes with ill-defined subfoveal CNV were submitted to operation and followed up for a minimum of 6 months. IPE cells were harvested from a peripheral iridectomy. A vitrectomy was performed. Submacular membranes were removed, and isolated IPE cells were injected into the subretinal space. Examinations included ETDRS visual acuity, fluorescein angiography, and SLO microperimetry. RESULTS: All patients underwent successful surgical removal of CNV and subretinal IPE injection. Compared to preoperative visual acuity (20/400-20/100) no significant change was observed after 6 months (20/320-16/80). A change of more than two ETDRS chart lines was defined as significant. One eye with preoperative ill-defined CNV developed a recurrence, leading to reduced visual acuity. In all patients, postoperative fluorescence angiography revealed early hyperfluorescence (window defect) in the surgically denuded area. Central fixation was demonstrated in 50% of eyes. CONCLUSIONS: Preliminary data suggests that IPE translocation in submacular surgery for ARMD can preserve but not improve preoperative visual acuity over 6 months. Functional results are promising compared to submacular membrane extraction alone and RPE transplantation. Continued research on improvement of IPE translocation seems justified.

Shi X, Semkova I, Kociok N, Gavranic C, Becker M, Joussen AM, Kirchhof B. · Department of Ophthalmology, People's Hospital, Peking University, Beijing 100044, China. · Zhonghua Yan Ke Za Zhi. · Pubmed #18785541 No free full text.

Abstract: OBJECTIVE: To investigate the role of TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in the mouse. METHODS: Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice by making four separate choroidal bums in each eye. Animals were treated 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept, 5 microg/h, group 1, n = 12), chimeric monoclonal antibody (infliximab, 5 microg/h, group 2, n = 12) for 7 days by intraperitonealy implanted osmotic pumps. PBS was used as control (group 3, n = 12). The left eyes were removed for histopathologic examination and the right eyes were removed for flatmounts immunohistochemistry immediately after fluorescien angiography. In mice treated with medications 3 days before laser injury, left eyes were collected at 1 or 2 weeks after laser injury. In mice treated with medications 3 days after laser injury, left eyes were collected at 10 days after laser injury. CNV responses were compared by flatmount analysis of CNV-related fluorescence area and by determination of fluorescein angiographic leakage. The level of protein expression of TNF-alpha was semiquantitatively evaluated by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment. RESULTS: Western blotting demonstrated that TNF-alpha was highly expressed in choroidal and RPE cells of wild type mice 1 week after laser treatment as compared to the control mice without laser treatment. Etanercept and infliximab administrated 3 days before laser-damage significantly reduced CNV size and pathological fluorescein leakage in comparison to the control group one and two weeks after laser injury. Only etanercept administered 3 days after laser injury still significantly reduced the development of CNV lesions. Histopathological examination confirmed that CNV lesions in treated mice had smaller diameter and thinner center as compared to the control animals. CONCLUSIONS: Anti-TNF-alpha treatment reduces the size and leakage of laser-induced CNV. These results suggest the involvement of TNF-alpha in the development of laser-induced CNV and its potential use as a therapeutic agent in the age related macular degeneration.

Heussen FM, Fawzy NF, Joeres S, Lux A, Maaijwee K, Meurs JC, Kirchhof B, Joussen AM. · Department of Vitreoretinal Surgery, Center of Ophthalmology, University of Cologne, Cologne, Germany. · Eye. · Pubmed #17641681 No free full text.

Abstract: AIM: To evaluate the long-term (1 year) functional and anatomical outcome of autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 30 patients with age-related macular degeneration (AMD). METHODS: After the extraction of the neovascular complex, an autologous peripheral full-thickness graft of RPE and choroid was positioned under the macula. Functional tests included ETDRS vision, reading (Radner test), and microperimetry (scanning laser ophthalmoscope). Fluorescein, indocyanine green angiography, and autofluorescence were monitored. RESULTS: Preoperative visual acuity ranged from 20/40 to 20/800 (0.3-1.6 log MAR). Vision ranged from 20/25 to LP (0.1-2.1 log MAR) 1 year after surgery, with stabilization in six eyes, an increase in five eyes, and a decrease in 19 eyes. Deterioration mostly occurred within the first 3 months after surgery. In patients who demonstrated vascularization of the graft after 3 months, this persisted up to 12 months as did fixation when initially stable. Autofluorescence decreased significantly from 6 to 12 months postoperatively. Eleven cases showed a recurrence of choroidal neovascularization (CNV) within this period. CONCLUSION: Patch translocation results in a viable graft. There is no evidence of graft failure within a 1-year follow-up. Nevertheless, there is risk for late CNV formation originating from the edges of the excision side of the CNV and growing peripheral to the graft.

Joeres S, Llacer H, Heussen FM, Weiss C, Kirchhof B, Joussen AM. · Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne, Cologne, Germany. · Eye. · Pubmed #17332766 No free full text.

Abstract: PURPOSE: To analyse structural changes after autologous translocation of choroid and retinal pigment epithelium (RPE) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT). METHODS: We performed a prospective nonrandomised study in 29 consecutive patients, who underwent submacular surgery with translocation of an autologous full-thickness graft of RPE, Bruch's membrane, and choroid. All patients had recent loss of reading vision due to AMD. OCT was performed before surgery and at 3- and 6- month follow-up to analyse the morphological appearance of the graft and the overlying retina. RESULTS: Maximum retinal thickness decreased from mean 408 microm (standard deviation (SD) 127 microm) preoperative to mean 373 microm (SD 104 microm) at 6-month follow-up (P=0.094). In 11 cases (40%), a nearly physiological shape of the retina was seen at this time point. A macular hole persisted in two eyes after silicone oil removal. In most eyes, the highly reflective band of the graft presumably corresponding to RPE was continuous with the surrounding RPE band in all six OCT scans. Eyes with flat appearance of the graft at 6-month follow-up (<300 microm) showed a significantly better functional outcome than eyes with more prominent grafts. Interestingly, most patients did not complain about metamorphopsia, even though the graft was prominent or wrinkled in some cases. CONCLUSION: OCT is a useful tool in monitoring intra- and subretinal changes after subretinal surgery with graft translocation. We demonstrated that graft translocation may lead to a normalisation of retinal thickness and stabilisation of visual acuity.

Joussen AM, Joeres S, Fawzy N, Heussen FM, Llacer H, van Meurs JC, Kirchhof B. · Department of Ophthalmology, University of Duesseldorf, Duesseldorf, Germany. · Ophthalmology. · Pubmed #17324697 No free full text.

Abstract: PURPOSE: To evaluate the functional and anatomical outcomes of autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in patients with geographic atrophy. DESIGN: Prospective nonrandomized study. PARTICIPANTS: Twelve consecutive patients with geographic atrophy secondary to age-related macular degeneration presenting with recent loss of reading vision. METHODS: An autologous peripheral full-thickness graft of RPE, Bruch's membrane, and choroid was positioned under the macula in patients with geographic atrophy. MAIN OUTCOME MEASURES: Functional tests included Early Treatment Diabetic Retinopathy Study distant vision, reading (Radner Test, measured as logarithm of the reading acuity determination [logRAD]), threshold static perimetry, and determination of the point of fixation. Fluorescein and indocyanine green angiography, autofluorescence, and optical coherence tomography served to evaluate the anatomical outcome in a 6-month follow-up (12 months in 7 patients). RESULTS: Preoperative visual acuity (VA) ranged from 20/800 to 20/40 (mean, 0.6+/-0.4 logarithm of the minimum angle of resolution), and reading vision from 1.1 to 0.5 logRAD (mean, 0.8+/-0.2). Three patients were unable to read. Six months after surgery, VA ranged from hand movements to 20/32, with an increase of > or =5 letters in 2 eyes. Two patients without reading ability preoperatively were able to read after surgery. Reading was possible in a total of 8 patients after 6 months (1.3-0.4 logRAD). In 7 patients who were observed for 1 year, VA remained stable (+/-1 line) in 5 eyes and decreased in 2 eyes between 6 months' and 1 year's follow-up. In all eyes but 2, revascularization was visible on indocyanine green angiography as early as 3 weeks after surgery. Autofluorescence of the RPE was independent of revascularization of the graft and persisted throughout follow-up. Four eyes had unstable fixation and/or extrafoveal fixation before surgery. Two of these eyes stabilized during follow-up. Areas overlying atrophic areas demonstrated low threshold sensitivities that persisted after translocation of a free graft with only limited recovery. Revisional surgery due to proliferative vitreoretinopathy was required in 5 eyes. CONCLUSIONS: The translocation of a full-thickness graft usually results in a vascularized and functioning graft in patients with geographic atrophy, although is associated with a high risk of complications and visual loss. Longer follow-up is necessary to learn about the long-term survival and functionality of the graft.

Lüke C, Lüke M, Aisenbrey S, Dietlein TS, Bartz-Schmidt KU, Kirchhof B, Walter P. · Zentrum für Augenheilkunde der Universität Köln, ERG-Labor Joseph-Stelzmann-Strasse 9, 50924 Köln. · Klin Monatsbl Augenheilkd. · Pubmed #17309008 No free full text.

Abstract: BACKGROUND: The aim of the present study was to evaluate potential electrophysiological changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age-related macular degeneration. METHODS: A consecutive series of 32 patients suffering from subfoveal choroidal neovascularisation secondary to age-related macular degeneration underwent 360 degrees retinotomy and macular translocation. The scotopic triple-flash ERG (TERG) served as the main parameter of the study and was recorded one day prior to the translocation surgery and no earlier than 4 weeks after the silicone oil removal. RESULTS: The TERG amplitudes were significantly reduced after translocation surgery. Depending on the applied flash luminance the mean amplitude reduction of the first b-wave varied between 67 % (0.2 cds/m (2)) and 74 % (0.03 cds/m (2)). The latency of the second b-wave of the preoperative TERG proved to have predictive power with reference to the postoperative visual acuity. A statistically significant correlation between the latency of the second b-wave for a flash intensity of 0.03 and 0.1 cds/m (2) and the postoperative visual acuity was shown (p = 0,016 and p = 0,049). CONCLUSIONS: In accordance with previous studies the present study indicates that a significant electrophysiological decrease is caused by surgical procedures associated with macular translocation. In future, due to predictive parameters of the TERG the preoperative selection of patients could be improved.

Maaijwee KJ, van Meurs JC, Kirchhof B, Mooij CM, Fischer JH, Mackiewicz J, Kobuch K, Joussen AM. · Department of Vitreoretinal Surgery, Center of Ophthalmology, University of Cologne, Germany. · Br J Ophthalmol. · Pubmed #16987900 No free full text.

Abstract: BACKGROUND: Translocation of a free autologous graft consisting of retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in patients with exudative age-related macular degeneration is currently being evaluated in clinical practice. Angiographic studies in these patients suggest that their grafts become revascularised. AIM: To investigate the histological evidence of revascularisation of the graft in a porcine model. METHODS: In 11 pigs (11 eyes), an RPE-choroid graft was translocated from the mid-periphery to an intact or an intentionally damaged RPE and Bruch's membrane at the recipient site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections were evaluated using immunohistochemistry. RESULTS: Bridging vessels between recipient layer and graft were identified from 1 week to 3 months after surgery. This reconnection occurred regardless of whether the Bruch's membrane of the recipient site was left intact or intentionally damaged at the time of transplantation. The vasculature of the graft appeared open and perfused. Vessels with transcapillary pillars and conglomerates of small new vessels were present in the graft. CONCLUSIONS: This study showed histological evidence for revascularisation by angiogenesis of a free autologous RPE-choroid graft.

Joussen AM, Heussen FM, Joeres S, Llacer H, Prinz B, Rohrschneider K, Maaijwee KJ, van Meurs J, Kirchhof B. · Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne, Cologne, Germany. · Am J Ophthalmol. · Pubmed #16815247 No free full text.

Abstract: PURPOSE: To evaluate the autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n = 2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage, n = 3 geographic atrophy). After extraction of the neovascular complex, an autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid was translocated from the midperiphery to the macula. RESULTS: Preoperative distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4 logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32 Snellen equivalent). Revision surgery was required in 22 eyes as a result of proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or vitreous hemorrhage. In eight patients, the patch was renewed. At six months, distant visual acuity ranged from light perception to 20/50 (increase of 15 letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual outcome was unrelated to the type of AMD. Vascularization of the transplant was visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most patients, autofluorescence of the pigment epithelium was coincident with revascularization of the graft. Fixation on the patch was positively related to visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness transplant of choroid and RPE usually results in a vascularized and functioning graft. Vascularization was even achieved in patients with geographic atrophy. Fixation stability and microperimetry before the patch translocation may be helpful in selecting patients who will profit from surgery.

Semkova I, Fauser S, Lappas A, Smyth N, Kociok N, Kirchhof B, Paulsson M, Poulaki V, Joussen AM. · Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne, Cologne, Germany. · FASEB J. · Pubmed #16807368 links to  free full text

Abstract: Choroidal neovascularization (CNV) is responsible for the severe visual loss in age-related macular degeneration. CNV formation is considered to be due to an imbalance between pro- and antiangiogenic factors that lead to neovascular growth from the choriocapillaris into the subretinal space. To define whether FasL overexpression in retinal pigment epithelial cells (RPE) can inhibit choroidal neovascularization through Fas-FasL-mediated apoptosis, we examined the role of this pathway in a mouse model of laser-induced choroidal neovascularization. FasL was expressed in the retinal pigment epithelium of transgenic mice. Polymerase chain reaction (PCR), immunoblot, and immunohistochemistry confirmed that the transgene FasL was specifically expressed in RPE. The established laser model was used to induce choroidal neovascularization (CNV) in wild-type (WT) and transgenic mice. CNV formation was compared with respect to fluorescein angiographic leakage (at days 0 and 14 after laser injury) and histological appearance. The lesions were assessed on RPE-choroidal flatmounts after CD31-labeling and with confocal microscopy after perfusion with rhodamine-labeled concanavalin A (Con A). Apoptosis was quantified by TUNEL positivity and caspase activation. FasL mRNA and protein were highly expressed in the RPE of the transgenic mice before and after laser photocoagulation. In contrast, FasL was only weakly expressed in the RPE layer of WT C57BL/6J mice. While ruptures of Bruch's membrane and CNV formation were observed histologically two weeks after laser photocoagulation in transgenic as well as control eyes, the shape and size of CNV lesions were reduced in the transgenic mice. The area of leakage was decreased by 70% in FasL transgenic mice compared with WT mice (P<0.005). The number of TUNEL-positive cells was greater in FasL-overexpressing mice and correlated with the expression of activated caspases. Th expression of other antiangiogenic factors such as PEDF remained unchanged. The specific overexpression of FasL in RPE layer reduced CNV formation in our laser model. Our results strongly point to the FasL-Fas pathway as a potential therapeutic target in controlling pathological choroidal neovascularization.

Thumann G, Hueber A, Dinslage S, Schaefer F, Yasukawa T, Kirchhof B, Yafai Y, Eichler W, Bringmann A, Wiedemann P. · Department of Ophthalmology and IZKF BIOMAT., RHWTH Aachen University, Germany. · Curr Eye Res. · Pubmed #16531281 No free full text.

Abstract: PURPOSE: Transplantation of pigment epithelial cells is a promising treatment modality to repair retinal damage in age-related macular degeneration. For this purpose, it is necessary to establish cell culture techniques that allow acquisition of proper functional and morphological characteristics by the cells to be transplanted. METHODS: Primary retinal pigment epithelial (RPE) and iris pigment epithelial (IPE) cells grown to confluence on collagen membranes were examined for morphology, adhesion, proliferation, apoptosis, as well as viability after ex vivo transplantation. RESULTS: Pigment epithelial cells adhere, proliferate, form monolayers, acquire differentiated properties, and remain viable during transplantation to the subretinal space. CONCLUSIONS: Pigment epithelial cells cultured on collagen membranes acquire differentiated characteristics and are amenable to be transplanted as cell monolayers.

Thumann G, Kirchhof B. · Universitätsklinikum, Köln. · Ophthalmologe. · Pubmed #15300389 No free full text.

Abstract: Transplantation of iris pigment epithelial (IPE) cells to the subretinal space has been attempted as a therapeutic modality for the treatment of age-related macular degeneration (AMD). IPE cells are used because autologous cells are readily available and because IPE and RPE cells share a common embryonic origin, possess the capacity of transdifferentiation into other ocular cells, and share common morphological and functional characteristics. Once the technique of IPE cell transplantation was established in an animal mode, several clinical studies analyzed the behavior of IPE cell suspensions transplanted to the subretinal space of patients with AMD following surgical membrane extraction. In our experience, as well as that of other investigators, transplantation of IPE cells to the subretinal space of AMD patients prevents the recurrence of the subretinal neovascularization and stabilizes but does not improve visual acuity. Since IPE cells transplanted as a cell suspension do not appear to form a cell monolayer in the subretinal space, the transplantation of preformed IPE or RPE cell monolayers is being investigated as the development of an functional cell monolayer is mandatory if functional success, i.e., recovery of vision in AMD patients, is the ultimate goal of IPE cell transplantation.

Radetzky S, Walter P, Fauser S, Koizumi K, Kirchhof B, Joussen AM. · Department of Vitreoretinal Surgery, Center for Ophthalmology, Joseph Stelzmann-Strasse 9, 50931, Cologne, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #15042375 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of inner limiting membrane (ILM) peeling in persistent macular edema. METHODS: This retrospective review analyzed a series of 23 eyes from 23 patients with persistent macular edema treated by pars plana vitrectomy (PPV) with indocyanine green (ICG)-assisted peeling of the ILM. Thirteen female and 10 male patients with a mean age of 57.2+/-15.6 (24-77) years underwent operation between May 2000 and October 2001. The main diagnoses were uveitis (anterior, intermediate, posterior and panuveitis) ( n=9), central retinal vein occlusion (CRVO) (n=4), diabetic retinopathy (DR) ( n=5), vitreoretinal traction syndrome ( n=2), and Irvine-Gass syndrome ( n=3). Nine eyes had undergone phacoemulsification (PE) previously and two eyes had been subjected to combined PE and ILM peeling. The eyes were tamponaded with gas (3), silicone oil (5) or air (11). In four cases no endotamponade was used. Improvement in visual acuity of 2 lines or more was regarded as significant. RESULTS: Visual acuity improved after 3 months in 9 of the 23 patients. After 6 months and at the follow-up, a significant improvement was found in 6/21 and 7/21 patients. This improvement was predominantly seen in patients with uveitis (5/9), or diabetic maculopathy (3/5); One patient with Irvine-Gass syndrome showed a significant reduction, one with vitreoretinal traction an improvement in visual acuity. The group of patients with CRVO showed no significant change during the follow-up. The choice of endotamponade did not alter the visual acuity outcome. CONCLUSIONS: Different patient groups respond differently to ILM peeling. Although overall significant visual acuity improvement was observed in only one third of all cases 12 months after ILM peeling for persistent macular edema, patients with uveitis and nonproliferative diabetic maculopathy demonstrated a benefit. The lack of long-term improvement in the majority of cases is in accordance with the hypothesis that ILM peeling may reduce the intraretinal edema, but does not affect the underlying mechanism causing macular edema. So far, only diabetics have shown improvement (still unproven) from ILM peeling, and this study provides no justification for extending the treatment to macular edema of other causes. Large-scale investigations are needed to evaluate the efficacy in certain diagnosis groups.

Lüke C, Alteheld N, Aisenbrey S, Lüke M, Bartz-Schmidt KU, Walter P, Kirchhof B. · Center of Ophthalmology, Department of Vitreoretinal Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50924 Cologne, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #12937992 No free full text.

Abstract: PURPOSE: To evaluate potential electro-oculographic changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age-related macular degeneration (AMD) in a randomised comparative (self-controlled) trial. METHODS: A consecutive series of 30 patients suffering from subfoveal choroidal neovascularisation secondary to age-related macular degeneration underwent 360 degrees retinotomy and macular translocation. The EOG served as the main parameter of the study and was recorded 1 day prior to the translocation surgery and no earlier than 21 days after the silicone oil removal. RESULTS: Postoperatively, a statistically significant decrease in mean dark trough by 64% was found for treated eyes (P<0.001). The mean dark trough of the fellow eye remained stable after surgery (P=0.33). The postoperative difference between the treated und untreated eyes proved to be statistically significant (P<0.001). The Arden ratio remained stable in the treated and untreated eyes with mean values of 204% (P=0.81) and 213% (P=0.18), respectively. A significant correlation between the reduction of the dark trough and the visual acuity at the 1-year follow-up was found. CONCLUSIONS: A persistent decrease in the corneofundal potential is associated with 360 degrees retinotomy and macular translocation for exudative AMD. This indicates a substantial postoperative malfunction of retinal pigment epithelial cells and an impaired photoreceptor regeneration. The impeded recovery of the RPE-photoreceptor complex can be interpreted as the result of the surgical trauma on the basis of prediseased RPE. A severe postoperative decrease in dark trough forecasts an incomplete recovery of visual acuity.