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      Changes in neurophysiologic markers of visual processing following beneficial anti-VEGF treatment in macular degeneration

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          Abstract

          Purpose

          Antivascular endothelial growth factor (VEGF) agents have been shown to improve visual acuity and prevent vision loss in exudative age-related macular degeneration. As the vision improves relatively quickly in response to intravitreal injections, we wanted to know whether this improvement is reflected in electrophysiological markers of visual cortical processing.

          Patients and methods

          Our interventional case series included six elderly patients who underwent injection treatment to the affected eye. Their visual acuity, tomographic images of retinal thickness, and visual evoked potentials (VEP) were assessed before treatment and six weeks after the last injection.

          Results

          All patients showed improved visual acuity and reduced retinal fluid after the treatment. All but one patient showed increased VEP P100 component amplitudes and/or shortened latencies in the treated eye. These VEP changes were consistent with improved vision while the untreated eyes showed no changes.

          Conclusions

          Our results indicate that antivascular endothelial growth factor injections improved visual function of the treated eyes both in the level of the retina and in the level of visual cortical processing.

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          Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

          Daniel Martin, Maureen Maguire, Gui-shuang Ying … (2011)
          Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).
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            Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial.

            Usha Chakravarthy, Simon Harding, Chris A Rogers … (2012)
            To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). People >50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart. We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001). The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety. Proprietary or commercial disclosures may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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              Endoplasmic reticulum stress in age-related macular degeneration: trigger for neovascularization.

              Antero Salminen, Anu Kauppinen, Juha MT Hyttinen … (2015)
              Age-related macular degeneration (AMD) can be classified into two main categories: the atrophic, dry form and the exudative, wet form. The crucial difference between dry and wet AMD is the development of choroidal neovascularization in wet AMD. One fundamental cause of the neovascularization is the increased expression of VEGF (vascular endothelial growth factor) in retinal pigment epithelial cells. Progression of AMD is linked to augmentation of cellular stress, for example, oxidative stress, proteotoxic stress, inflammation and hypoxia. All these conditions can trigger stress in endoplasmic reticulum (ER), which maintains protein quality control in cells. ER stress induces the unfolded protein response (UPR) via IRE1 (inositol-requiring protein-1), PERK (protein kinase RNA-like ER kinase) and ATF6 (activating transcription factor-6) transducers. UPR signaling is a double-edged sword, that is, it can restore cellular homeostasis as far as possible, but ultimately may lead to chronic, overwhelming stress that can cause apoptotic cell death. Interestingly, ER stress is a well-known inducer of angiogenesis in cancer. Moreover, stress conditions associated with the progress of AMD can induce the expression of VEGF. We discuss the role of ER stress in the regulation of neovascularization and the conversion of dry AMD to its wet, detrimental counterpart.
              Article 0 comments Cited 44 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Ophthalmol
                Journal ID (iso-abbrev): Clin Ophthalmol
                Journal ID (publisher-id): Clinical Ophthalmology
                Title: Clinical Ophthalmology (Auckland, N.Z.)
                Publisher: Dove Medical Press
                ISSN (Print): 1177-5467
                ISSN (Electronic): 1177-5483
                Publication date Collection: 2013
                Publication date (Print): 2013
                Publication date (Electronic): 27 February 2013
                Volume: 7
                Pages: 437-442
                Affiliations
                [1 ]Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland
                [2 ]Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
                [3 ]Department of Clinical Neurophysiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
                [4 ]Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
                Author notes
                Correspondence: Kai Kaarniranta, Department of Ophthalmology, Kuopio University Hospital, PO Box 1777, 70211 Kuopio, Finland, Tel +35 817 172 485, Fax +35 817 172 485, Email kai.kaarniranta@ 123456uef.fi
                Article
                Publisher ID: opth-7-437
                DOI: 10.2147/OPTH.S40427
                PMC ID: 3589120
                PubMed ID: 23467427
                SO-VID: 3af186f2-4c28-4a27-a462-0f1724255443
                Copyright © © 2013 Vottonen et al, publisher and licensee Dove Medical Press Ltd.
                License:

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: age-related eye diseases,exudative age-related macular degeneration,visual evoked potentials,scalp-recorded eeg,visual acuity
                Data availability:
                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: age-related eye diseases, exudative age-related macular degeneration, visual evoked potentials, scalp-recorded eeg, visual acuity

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