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• W2074801102 abstract "Objective: Retinal capillary haemangioma complications are characterized by progressive exudation with consecutive intraretinal and subretinal leakage. A successful therapy without side-effects has not been found. We report a case of retinal juxtapapillary capillary haemangioma causing consecutive leakage with macular involvement. The tumour was treated with a combination of anti-vascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) and was followed for 1 year. Methods: A 44-year-old woman with retinal juxtapapillary capillary haemangioma in the right eye experienced a decrease of visual acuity from 20/20 to 20/60 because of a severe leakage from the tumour involving the macula with lipid depositions. Two sessions of PDT (sparing the part of the haemangioma located within the optic disc) and five injections of bevacizumab were applied in a period of 5 months. Visual acuity, visual field testing, retinal thickness measurements, fundus photography and fluorescein angiography were performed to evaluate the treatment effect. Results: One year after the last injection, visual acuity increased to 20/40. All lipid exudates at the posterior pole resolved. Retinal thickness decreased from 490 to 150 μm with the restoration of normal central macular architecture. Leakage in fluorescence angiography reduced significantly, but hyperfluorescence of the tumour was still evident. Visual field testing and angiography did not show any treatment-related vaso-occlusive side-effects. Conclusion: In this single case, the combination of anti-VEGF and PDT appeared to be an effective strategy for the treatment of retinal juxtapapillary capillary haemangioma without side-effects. Further studies with a greater number of eyes and adequate follow-up are necessary to support these first clinical results. Retinal capillary haemangioma may occur sporadically (in 54% of cases) or as a manifestation of von Hippel–Lindau (VHL) disease (in 46% of cases) (Singh et al. 2001). Age at presentation, degree of visual impairment, morphology and anatomical location of sporadic tumours are similar to those seen in VHL disease (Webster et al. 1999; Singh et al. 2001). The spontaneous course of the disease is usually progressive and the visual prognosis is unfavourable (McCabe et al. 2000). The lesions are characterized by progressive exudation with consecutive intraretinal and subretinal leakage, leading to visual loss caused by accumulation of macular exudates and/or serous retinal detachment (Gass & Braunstein 1980). Multiple therapeutic approaches have been described, including laser coagulation, cryotherapy, radiation therapy, transpupillary thermotherapy, photodynamic therapy (PDT) and vitreoretinal surgery (Garcia-Arumí et al. 2000; Singh et al. 2002). In recent years, several studies have presented vascular endothelial growth factor (VEGF)-A inhibitors as a promising strategy to treat choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) (Algvere et al. 2008; Pedersen et al. 2007). Recently, the therapeutic effect of intravitreal bevacizumab (Avastin®, Roche Pharma AG, Grenzach-Wyhlen, Germany), a humanized monoclonal antibody against VEGF, was reported in neovascular AMD (Rosenfeld et al. 2005; Avery et al. 2006). Avastin was effective in decreasing retinal thickness and angiographic leakage and, perhaps more significantly, in improving vision. We present the successful treatment of a symptomatic retinal juxtapapillary capillary haemangioma by intravitreal anti-VEGF injections combined with PDT. A 44-year-old woman experienced a decrease of visual acuity (VA) and metamorphopsia in the right eye (OD) within 3 months. VA deteriorated from 20/20 to 20/60 because of fluid and lipid accumulation at the macula originating from a juxtapapillary capillary haemangioma at the superotemporal side of the disc (Fig. 1). The tumour size increased over a short period of time and the lipid accumulation reached both the supero- and the inferotemporal vascular arcades. OCT demonstrated a substantial intraretinal accumulation of fluid with an increased retinal thickness of 490 μm (Fig. 1). A consultation 10 years previously had disclosed a tumour of one disc diameter in size without visual impairment. No systemic disease, VHL disease in particular, could be identified. The patient was informed about the natural course of the disease and possible treatment strategies. Based on positive results of PDT in retinal papillary capillary haemangiomas as well as anti-VEGF on CNV (Schmidt-Erfurth et al. 2002; Rosenfeld et al. 2005; Aggio et al. 2006; Avery et al. 2006), the patient gave her informed consent to a combined treatment with bevacizumab and PDT (Mennel et al. 2007a, 2007b). Analogue to the (monthly injections) regimen of anti-VEGF application in exudative AMD, five monthly injections of 1.25 mg bevacizumab (0.05 ml) were planned in our patient. The option of a second PDT was discussed in case of persistent leakage after 3 months. To avoid vaso-occlusive effects at the optic disc, the laser treatment spot was directed to the superotemporal part of the lesion by sparing the part of the tumour located within the optic disc (Fig. 2). PDT followed the standard protocol (Mennel et al. 2007a, 2007b). The first PDT session was performed 8 days after the intravitreal application of bevacizumab. The patient experienced a moderate improvement in VA. Following the first PDT session, 8 days after the intravitreal application of bevacizumab, the patient experienced a moderate improvement in VA. Two weeks later, macular retinal thickness was reduced from a preoperative level of 490 μm to 190 μm. A second bevacizumab injection was performed 1 month later. Because of persistent leakage, a second PDT followed 2 months later combined with a bevacizumab injection 8 days after PDT. The patient experienced a visual deterioration immediately after the PDT, which was associated with an extensive elevation of the neurosensory retina. Central retinal thickness increased to 970 μm while VA decreased to 20/400 8 days after PDT. After the third bevacizumab injection, VA increased to 20/200 and retinal thickness flattened to 120 μm. Two more injections were performed in the following two months. The patient was followed for 12 months after the last intravitreal application. VA increased to 20/40 and intra- and subretinal fluid, as well as lipid exudates, resolved completely (Fig. 3). Fluorescein angiography demonstrated hyperfluorescence in the area of the tumour, but no leakage towards the macula was detectable. At diagnosis, we assessed an absolute scotoma in the nasal inferior quadrant of the visual field OD corresponding to the tumour; this did not increase postoperatively. Visual field testing in the left eye (OS) was unremarkable. Complications of any kind did not occur during treatment or in the following 12 months. Fundus image (A), optical coherence tomography (OCT) (B), early (C) and late (D) fluorescein angiography (FA) prior to therapy. The fundus image presents a white lesion of one disc diameter at the superior border of the disc surrounded by the subretinal accumulation of fluid. The green arrow indicates the direction, length and location of the corresponding OCT scan. The OCT image includes the central macula as well as the tumour. The macula is elevated to 490 μm because of intra- and subretinal fluid accumulation. The venous phase FA image (4 min after dye injection) on the left side demonstrates the size and early leakage of the tumour, whereas the extensive hyperfluorescence in the late phase image (28 min after dye injection) is caused by the leakage of the tumour. Schematic drawing: the black circle represents the border of the optic disc, the red-filled area represents the tumour and the green circle the laser spot size and location during treatment. Fundus image (A), optical coherence tomography (OCT) (B), early (C) and late (D) fluorescein angiography (FA) 12 months after the second round of photodynamic therapy. The white lesion at the superior border of the disc did not change in size or colour. The whitish discolouration around the tumour was diminished. All lipid exudates at the posterior fundus disappeared completely. The green arrow indicates the direction, length and location of the corresponding OCT scan. The OCT image includes the central macula as well as the tumour. The macula appears with normal physiological architecture and central retinal thickness of 150 μm. No fluid can be detected intra- or subretinally. Early venous phase FA image (20 seconds after dye injection) demonstrates the size and location of the tumour, whereas the late phase image (5 min after dye injection) displays an enlarged area of hyperfluorescence corresponding to the subretinal fluid. The spontaneous course of retinal juxtapapillary capillary haemangioma is, in most cases, unfavourable. In a large series of 72 eyes with juxtapapillary haemangioma, VA was less than 20/40 in 39% of eyes at initial presentation and further declined below this level in 65% of eyes after a mean follow-up of 5.4 years (McCabe et al. 2000). Although different strategies have been described, a successful treatment option has not been found. In a small pilot study, pegabtanib was able to decrease retinal thickening minimally and reduce retinal hard exudates in some patients with advanced VHL angiomas, but failed to reduce the size of the tumour (Dahr et al. 2007). The combination of bevacizumab and PDT seems to offer a new therapeutic option for this entity. Possible side-effects caused by PDT monotherapy, such as retinal pigment epithelium alterations in young patients, may be reduced by less retreament (Parodi et al. 2007; Mennel et al. 2006, 2007a, 2007b). Our case demonstrated a successful disappearance of intra- and subretinal fluid as well as lipid exudates. No treatment-related complications occurred. In contrast, photocoagulation may cause damage to the nerve fibre layer, resulting in permanent visual field scotoma (Garcia-Arumí et al. 2000; McCabe et al. 2000). PDT has been presented as successful in reducing tumour size and leakage in papillary capillary haemangioma (Schmidt-Erfurth et al. 2002). In Schmidt-Erfurth et al.’s case series of five patients, the laser parameters were adapted and increased to 100 J/cm2 light at 692 nm. The laser treatment spot included the portion of the haemangioma located in the area of the optic disc. One to three PDT sessions were performed. A decline in VA of 1, 3 and 10 lines, respectively, was documented in three patients over 12 months of follow-up. Complications included transient decompensation of vascular permeability, occlusion of retinal vessels and ischaemia of the optic nerve. The authors concluded that PDT was successful in reducing tumour size and exudative activity and suggested that parameters proven to be safe in CNV may be inappropriate in retinal capillary lesions of the optic nerve. The treatment parameters for our patient were applied according to the TAP (Treatment of Age-related macular degeneration with Photodynamic therapy) study using a light-dose of 50 J/cm2. Because part of the tumour was located within the optic disc, we spared this area by PDT and additional anti-VEGF was applied in combination. These factors may be essential to the fact that no treatment-related vaso-occlusive side-effects occurred. To date, a single treatment combination of PDT and triamcinolone in a case of juxtapapillary capillary haemangioma with exudative oedema involving the macula has been reported without positive effect (von Buelow et al. 2007). In this report, a partial resolution of tumour activity and lipid exudates could be observed only after six cycles of systemic bevacizumab. While the combination of PDT and systemic bevacizumab appears to be better than triamcinolone, the authors recommended the evaluation of intravitreal bevacizumab for this otherwise incurable disease. Recently, a successful approach with a single combined treatment of intravitreal bevacizumab followed 2 weeks later by PDT has been reported (Ziemssen et al. 2007). The laser application time was 166 seconds, in contrast to the 83 seconds used in AMD cases. The authors did not describe the location of PDT laser spot and whether they spared the optic disc. In these circumstances, the risk of a vaso-occlusive event may be higher. While our first PDT session was preceded by anti-VEGF application 8 days previously, the second PDT session was performed 8 days prior to anti-VEGF treatment. Following the first PDT, the patient did not complain about visual disturbances and central retinal thickness decreased from 490 to 190 μm. In contrast, the second PDT caused extensive accumulation of subretinal fluid and central retinal thickness increased to 970 μm with consequent transient visual impairment. Similar findings have been described previously in studies demonstrating that the application of anti-VEGF 5–8 days prior to PDT counteracts early PDT-related pathophysiological alterations (Schmidt-Erfurth et al. 2003; Mennel et al. 2005, 2007a, 2007b). This report presents the combined treatment with anti-VEGF and PDT as an effective option to deal with retinal juxtapapillary capillary haemangioma with low risk for side-effects. Further studies with a greater number of eyes and follow-up beyond 1 year are necessary to assess the efficacy and safety of this treatment strategy." @default.
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• W2074801102 title "Combined intravitreal anti-vascular endothelial growth factor (Avastin®) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma" @default.
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