Macular Degeneration: Joussen AM

Joussen AM. · No affiliation provided · Graefes Arch Clin Exp Ophthalmol. · Pubmed #14745559 No free full text.

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Joussen AM. · No affiliation provided · Klin Monatsbl Augenheilkd. · Pubmed #12953152 No free full text.

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

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Joussen AM. · Augenklinik der Universität Düsseldorf, Germany. · Dtsch Med Wochenschr. · Pubmed #17541869 No free full text.

Abstract: Retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the most common blinding disease in the western world during childhood, in adults, and in the elderly patient. All three diseases have a vascular damage in common that leads to a pathological angiogenesis. The basic mechanisms include complex interactions between endothelial cells, pericytes, and matrix molecules. We know the "vocabulary" and try to understand the regulation of physiological and pathological angiogenesis. Building upon this knowledge, we are now, with the advent of clinically available vascular endothelial growth factors, for the first time able to therapeutically modulate angiogenesis.

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, Joeres S. · Department of Ophthalmology, University of Duesseldorf, Duesseldorf, Germany. · Dev Ophthalmol. · Pubmed #17245079 No free full text.

Abstract: Surgical therapy for diabetic retinopathy has been refined since the 1960s (Early Treatment Diabetic Retinopathy Study). While the Early Treatment Diabetic Retinopathy Study abstained from panretinal photocoagulation at the time of surgery, today, endophotocoagulation is the most important singular reason for vitrectomy, e.g., in vitreous hemorrhage. Despite improved techniques, the surgical prognosis is lagging behind patient expectations, especially in cases of advanced proliferative stages. The following review addresses current surgical options and indications of diabetic retinopathy/maculopathy.

Joussen AM, Smyth N, Niessen C. · Department of Ophthalmology, University of Duesseldorf, Duesseldorf, Germany. · Dev Ophthalmol. · Pubmed #17245075 No free full text.

Abstract: Diabetic maculopathy is the leading cause of visual loss in diabetic patients. The pathogenesis is not fully understood and a satisfactory therapy is currently not available. Malfunction of the blood-retinal barrier plays a central role in the disease and leads to retinal edema and secondary photoreceptor dysfunction. Diabetic vascular leakage and macular edema are regulated by a distinct combination of direct paracellular transport, alterations in endothelial intercellular junctions and endothelial cell death. The distribution and relevance of these three factors to diabetic maculopathy varies over the course of the disease. Cumulative endothelial cell death will become more relevant after prolonged diabetic conditions. This article reviews the current knowledge on the pathogenic mechanisms of diabetic macular edema.

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.

Miller DW, Joussen AM, Holz FG. · Universitäts-Augenklinik Heidelberg. · Ophthalmologe. · Pubmed #12589451 No free full text.

Abstract: Age-related macular degeneration is the leading cause of irreversible vision loss in industrialized countries. While early forms of this disease with drusen and focal pigment alterations generally do not lead to relevant functional limitations, later forms of the disease, either through atrophy or choroidal neovascularization, are associated with significant visual impairment. A significant increase in knowledge about the molecular mechanisms of new vessel formation from the choriocapillaries has occurred over the past few years. This has already allowed for the clinical testing of pharmacological agents which inhibit the formation of new vessels in AMD. This article describes current research in the pathophysiology of choroidal neovascularization secondary to age-related macular degeneration.

Joussen AM. · Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #11820705 No free full text.

Abstract: Most of the blinding diseases, such as diabetic retinopathy, age-related macular degeneration, neovascular glaucoma or trachoma, are related to an aberrant angiogenic response. Common pathological features are ischaemia and increased vascular permeability, in turn leading to neovascularization or atrophy. Recent effort has led to the identification of several factors, such as the angiopoietin-Tie system, which are operative in the control of vasculogenesis and angiogenesis. The aim of this commentary is to summarize briefly the current knowledge about molecular mechanisms involved in the regulation of vascular integrity with special emphasis on the angiopoietins.

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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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.

Joussen AM, Bornfeld N. · Augenklinik der Universität Düsseldorf, Düsseldorf. · Dtsch Arztebl Int. · Pubmed #19547647 links to  free full text

Abstract: BACKGROUND: Age-related macular degeneration (AMD) is a progressive disease affecting the macula, the area of the retina that has the highest visual acuity. It can progress to geographic atrophy or choroidal neovascularization. METHOD: Selective literature review. RESULTS: The authors discuss the results of therapeutic trials and the treatment recommendations of the ophthalmological societies. Mechanism-targeted treatments and improved modes of administration offer the potential for improved therapy. CONCLUSIONS: With the advent of the antivascular endothelial growth factor (anti-VEGF) therapy, the prognosis of choroidal neovascularization has changed dramatically. Visual acuity can actually be improved, but, in most cases, the improvement can only be sustained with repeated intravitreal injections.

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.

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.

Joussen AM, Weiss C, Bauer D, Hilgers RD, Anonymous00282. · Department of Ophthalmology, University Hospital Duesseldorf, University of Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17653751 No free full text.

Abstract: AIM: Treatment options for persistent diabetic macular edema remain disappointing. ILM peeling and intravitreal triamcinolone have been successfully used in several case series; however, there is no evidence that one of these options is superior for specific groups of patients. The triamcinolone versus ILM peeling in diabetic macular edema study (TIME-study) is designed to investigate the efficacy of these two treatments in patients with persistent diabetic macular edema. METHODS: Patients with persistent diabetic macular edema are randomised to either the control group (no treatment), ppV + ILM peeling, or triamcinolone (4 mg) injection. One hundred thirty-five patients are to be recruited per group and followed-up for one year. The main endpoints are defined as change in visual acuity (VA) at 12 months compared to baseline and the change in retinal thickness after 3 months follow-up. Secondary endpoints include differences in the functional success and anatomical success and the effect of the treatment on the patient's quality of life. Twelve institutions (28 surgeons) in 3 European countries agreed to contribute to the study. RESULTS: The design issues and implications of the study are described. CONCLUSIONS: The TIME study is the first randomised prospective clinical trial to investigate the effectiveness of the two treatment methods. The results of this study should enable physicians to improve therapy and to select cases according to the most promising treatment option.

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.

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.

Shi X, Semkova I, Müther PS, Dell S, Kociok N, Joussen AM. · Department of Vitreoretinal Surgery, Center of Ophthalmology, Germany. · Exp Eye Res. · Pubmed #16959248 No free full text.

Abstract: To investigate the role of the TNF-alpha in the development of laser-induced choroidal neovascularization (CNV) in a mouse model. Four separate laser burns were applied to induce ruptures of Bruch's membrane and subsequent choroidal neovascularization in C57BL/6J mice. TNF-alpha protein expression was semiquantitatively assessed by Western blot analysis of the choroidal and RPE layer from mice with or without laser treatment. To investigate the effect of TNF-alpha inhibition on CNV formation, animals were treated for 7 days via intraperitonealy implanted osmotic pumps either 3 days before or after laser injury with recombinant TNF receptor P75 (etanercept), a chimeric monoclonal antibody (infliximab), or a purified rat anti-mouse/rat TNF monoclonal antibody (TNF-mAb), respectively. Fluorescein angiography, flat-mount preparations, and histopathology were performed at day 7, 10, or 14 after laser treatment. Western blotting demonstrated that TNF-alpha expression was 4.57-fold higher in the choroid and RPE one week after laser injury compared to control mice without laser. When evaluated one and two weeks after laser injury, etanercept and infliximab given from the 3rd day before laser-damage significantly reduced CNV size and pathological fluorescein leakage compared to the control group after laser treatment only. The inhibitory effect of the monoclonal TNF-alpha antibody on CNV formation was evident two weeks after photocoagulation but not after one week. Only etanercept administered 3 days after laser injury still reduced significantly the development of CNV lesions. Histopathology confirmed that CNV lesions in treated mice were smaller in size compared to the control animals without TNF inhibitor treatment. In conclusion, anti-TNF-alpha treatment with different inhibitors reduces both the size and the 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.

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.