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      Intravitreal ranibizumab injection combined trabeculectomy versus Ahmed valve surgery in the treatment of neovascular glaucoma: assessment of efficacy and complications

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          Abstract

          Background

          Researches have shown anti-vascular endothelial growth factor (VEGF) agent is effective in treating neovascular eye diseases. The purpose of this study is to evaluate the efficacy and safety of intravitreal ranibizumab (IVR) injection combined trabeculectomy in the treatment of neovascular glaucoma (NVG), and compared it with Ahmed valve surgery.

          Methods

          Thirty-six NVG patients (37 eyes) from the First Affiliated Hospital of Zhejiang medical college, between January 1, 2014 and January 31, 2015, were included in this prospective, interventional clinical study. Eighteen NVG eyes were given IVR injection one week before trabeculectomy. Ahmed valve implantation surgery was performed in nineteen eyes. Ocular pain, best corrected visual acuity (BCVA), intraocular pressure (IOP) and surgical complications were evaluated before and after the surgery.

          Results

          IOP was significantly decreased following IVR injection combined trabeculectomy treatment (baseline 57.1 ± 8.9 mmHg; week 1, 15.2 ± 4.3 mmHg p = 0.000; month 1, 16.9 ± 2.1 mmHg p = 0.000; month 3, 20.3 ± 7.7 mmHg p = 0.000; month 6, 19.7 ± 7.3 mmHg p = 0.000). There was a significant, though modest, BCVA improvement in sighted eyes of IVR group (baseline 2.42 ± 0.68, W1 1.80 ± 0.91, P = 0.013; M1 1.77 ± 0.93, p = 0.011). IVR injection combined trabeculectomy had less postoperative complications and lower failure ratio than Ahmed surgery (IVR 5.6 %, Ahmed 31.6 %).

          Conclusions

          The study revealed that IVR injection combined trabeculectomy was an effective and safe treatment for NVG. Compared with Ahmed surgery, IVR injection combined trabeculectomy had less complications and higher success ratio. (Chinese Clinical Registry, TRN ChiCTR-OPN-16008147, 3/24/2016, retrospectively registered)

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          Most cited references22

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          Efficacy and safety of trabeculectomy vs nonpenetrating surgical procedures: a systematic review and meta-analysis.

          To date, only a few studies have directly compared nonpenetrating surgery (NPS) and trabeculectomy (TE). Therefore, there is no strong evidence as to which surgical technique leads to the best results in terms of ocular hypotensive effect and safety. To compare the hypotensive effect and safety of NPS and TE in terms of intraocular pressure (IOP) reduction and incidence of complications. The MEDLINE and EMBASE databases were searched for studies potentially eligible in any language published up to March 31, 2013. Systematic review and meta-analysis of comparative studies of 2 or more surgical techniques (1 of which had to be TE), including patients with open-angle glaucoma. The considered interventions were TE, deep sclerectomy (DS), viscocanalostomy, and canaloplasty. The primary outcome was the mean between-group difference in the reduction in diurnal IOP from baseline to the 6- or 12-month follow-up evaluation. We also considered the incidence of complications, expressed as relative risk. Eighteen articles, accounting for 20 comparisons, were selected for data extraction and analysis. Analysis of the 6-month follow-up data showed that the pooled estimate of the mean between-group difference was -2.15 mm Hg (95% CI, -2.85 to -1.44) in favor of TE. There was no difference between the NPS subgroups. In the subgroup antimetabolite analysis, the addition of mitomycin C to TE and DS decreased the difference in the reduction in IOP (TE and DS without mitomycin C: -2.65 mm Hg [95% CI, -3.90 to -1.39]; TE and DS with mitomycin C: -0.83 mm Hg [95% CI, -2.40 to 0.74]). In the subgroup analysis by implant addition, no significant difference induced by DS with or without drainage devices was detected (test for subgroup differences: χ(2)(1) = 0.24; P = .62). The absolute risk of hypotony, choroidal effusion, cataract, and flat or shallow anterior chamber was higher in the TE group than in the NPS group. Trabeculectomy seems to be the most effective surgical procedure for reducing IOP in patients with open-angle glaucoma. However, as expected, it was associated with a higher incidence of complications when compared with NPS.
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            Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery.

            Filtration failure due to excessive postoperative scarring remains a major problem after glaucoma surgery. The authors have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab, can reduce postoperative scar formation and improve surgical outcome. The levels of VEGF in samples of aqueous humor were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis. VEGF levels were increased significantly in the aqueous humor of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits. VEGF was upregulated in the aqueous humor of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring process after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved surgical outcome.
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              Neovascular glaucoma.

              Neovascular glaucoma (NVG) is a severely blinding, intractable disease. The objective of this review is to provide detailed information on its basic and clinical aspects, to enable us to manage it logically. Therefore, its causes, pathogenesis and pathology, methods of early diagnosis and management are discussed. To prevent or reduce the extent of visual loss caused by NVG, the first essential is to have a high index of suspicion of its development. The most common diseases responsible for development of NVG are ischemic central retinal vein occlusion (CRVO), diabetic retinopathy and ocular ischemic syndrome. In the management strategy, the first priority should be to try to prevent its development by appropriate management of the causative diseases. If NVG develops, early diagnosis is crucial to reduce the extent of visual loss. Management of NVG primarily consists of controlling the high IOP by medical and/or surgical means to minimize the visual loss. Currently, we still do not have a satisfactory means of treating NVG and preventing visual loss in the majority, in spite of multiple modes of medical and surgical options advocated over the years and claims made. This review discusses the pros and cons for the various advocated treatments.
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                Author and article information

                Contributors
                +8657187236791 , +8657187236628 , you2000xiang@sina.cn
                Journal
                BMC Ophthalmol
                BMC Ophthalmol
                BMC Ophthalmology
                BioMed Central (London )
                1471-2415
                26 May 2016
                26 May 2016
                2016
                : 16
                : 65
                Affiliations
                [ ]Department of Ophthalmology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, People’s Republic of China
                [ ]Department of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
                Article
                248
                10.1186/s12886-016-0248-7
                4882850
                27230388
                1c7fd770-c161-40be-bb43-c000feab4910
                © Liu et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 October 2015
                : 21 May 2016
                Funding
                Funded by: Medical and Health Science Project of Zhejiang Province
                Award ID: 2016151091
                Award Recipient :
                Funded by: Education Project of Zhejiang Province Office
                Award ID: Y201328272
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2016

                Ophthalmology & Optometry
                neovascular glaucoma (nvg),ranibizumab,vascular endothelial growth factor (vegf),trabeculectomy,ahmed valve surgery

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