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      Hyperreflective Dots: A New Spectral-Domain Optical Coherence Tomography Entity for Follow-Up and Prognosis in Exudative Age-Related Macular Degeneration

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          Abstract

          Purpose: Spectral-domain optical coherence tomography (SD-OCT) enables high-resolution analysis of retinal layers and previously unseen hyperreflective dots (HRD). HRD morphological characteristics, evolution, possible origin and prognostic value are discussed. Methods: We conducted a prospective study of 100 patients with exudative age-related macular degeneration (AMD), who were treated and followed up with monthly imaging examinations. Statistical correlations between visual acuity (VA) and pre-/post- treatment HRD characteristics were evaluated. Results: HRD were present in all cases, mainly in the outer retinal layers but also elsewhere. After treatment, HRD regressed in a few days, 1 month (p < 0.04) and 3 months (p < 0.01). Regression was evident in all VA and morphological subsets. Resolution was associated with better final VA (p < 0.001). Conclusions: Presence of initial/recurrent HRD, rapid treatment response and the growing role that early biological inflammatory reaction plays in AMD suggests HRD are activated microglia cells. The correlation between VA and HRD could make HRD a clinical marker for early decisions about treatment and retreatment.

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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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            Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: role of PKCζ in the Goto Kakizaki rat model.

            Samy Omri, Francine Behar-Cohen, Yvonne de Kozak … (2011)
            Diabetic retinopathy is associated with ocular inflammation, leading to retinal barrier breakdown, macular edema, and visual cell loss. We investigated the molecular mechanisms involved in microglia/macrophages trafficking in the retina and the role of protein kinase Cζ (PKCζ) in this process. Goto Kakizaki (GK) rats, a model for spontaneous type 2 diabetes were studied until 12 months of hyperglycemia. Up to 5 months, sparse microglia/macrophages were detected in the subretinal space, together with numerous pores in retinal pigment epithelial (RPE) cells, allowing inflammatory cell traffic between the retina and choroid. Intercellular adhesion molecule-1 (ICAM-1), caveolin-1 (CAV-1), and PKCζ were identified at the pore border. At 12 months of hyperglycemia, the significant reduction of pores density in RPE cell layer was associated with microglia/macrophages accumulation in the subretinal space together with vacuolization of RPE cells and disorganization of photoreceptors outer segments. The intraocular injection of a PKCζ inhibitor at 12 months reduced iNOS expression in microglia/macrophages and inhibited their migration through the retina, preventing their subretinal accumulation. We show here that a physiological transcellular pathway takes place through RPE cells and contributes to microglia/macrophages retinal trafficking. Chronic hyperglycemia causes alteration of this pathway and subsequent subretinal accumulation of activated microglia/macrophages. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
            Article 0 comments Cited 75 times – based on 0 reviews     Review now
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              Choroidal evaluation using enhanced depth imaging spectral-domain optical coherence tomography in Vogt-Koyanagi-Harada disease.

              Edmund K Li, David Wong, A-C L F W T Fong (2011)
              Current imaging modalities used in the evaluation of Vogt-Koyanagi-Harada (VKH) disease include ultrasound, fluorescein angiogram, indocyanine green angiography, and optical coherence tomography (OCT). However, they all fail to give detailed information on the ultrastructural changes of the choroid. A recent technique using OCT termed "enhanced depth imaging" produces high-resolution cross-sectional images of the whole thickness of the choroid. The purpose of the study was to describe a novel imaging finding in the choroid in cases of VKH uveitis and to assess for interobserver agreement of this new physical sign. This is an age-matched, sex-matched, and spherical equivalent-matched, case-control, cross-sectional study. Six VKH patients in acute and convalescent stages underwent choroidal imaging using enhanced depth imaging spectral-domain OCT imaging. A horizontal enhanced depth imaging spectral-domain OCT scan across the fovea was selected for each eye and was compared with a scan from an age-matched, sex-matched, and spherical equivalent-matched control subject. A loss of focal hyperreflectivity, represented by a decrease in the number of hyperreflective dots in the inner choroid, was observed. This finding was assessed for interobserver agreement using five masked observers. Mean observed agreement and multirater kappa statistics (κ) were calculated. The average choroidal thickness was also calculated and compared among acute-phase VKH patients, convalescent-phase VKH patients, and control subjects. There was a significant loss of focal hyperreflectivity in the inner choroid of VKH patients compared with control subjects in both acute and convalescent stages. Analysis revealed substantial interobserver agreement on this finding. The mean observed agreement was 95%, and the overall kappa coefficient (κ) was 0.80 (P < 0.01). The choroid of acute-phase VKH patients was thicker than that of convalescent-phase patients by 151 μm (P = 0.043) and control subjects by 137 μm (P = 0.001). There was no statistically significant difference in thickness between convalescent eyes and controls. Enhanced depth imaging spectral-domain OCT highlights a loss of focal hyperreflectivity in the inner choroid of eyes with VKH, a feature that is consistently observed by independent masked observers. The presence of this feature in both acute and convalescent phases could represent permanent structural change to small choroidal vessels caused by VKH uveitis.
              Article 0 comments Cited 53 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (publisher-id): OPH
                Journal ID (nlm-ta): Ophthalmologica
                Journal ID (doi): 10.1159/issn.0030-3755
                Title: Ophthalmologica
                Publisher: S. Karger AG
                ISSN (Print): 0030-3755
                ISSN (Electronic): 1423-0267
                Publication date Subscription-year: 2013
                Publication date (Print): December 2012
                Publication date (Electronic): 19 September 2012
                Volume: 229
                Issue: 1
                Pages: 32-37
                Affiliations
                aCentre d’Ophtalmologie and bDepartment of Ophthalmology, University Paris-Est Créteil, Paris XII, France; cDepartment of Ophthalmology, University Vita-Salute, San Raffaele Scientific Institute, Milan, Italy
                Author notes
                *Prof. Gabriel Coscas, Department of Ophthalmology, University Paris-Est Créteil, Centre Hospitalier Intercommunal de Créteil, 40 Avenue de Verdun, FR–94000 Créteil (France), Tel. +33 1 4517 5225, E-Mail gabriel.coscas@gmail.com
                Article
                Publisher ID: 342159 Other ID: Ophthalmologica 2013;229:32–37
                DOI: 10.1159/000342159
                PubMed ID: 23006969
                SO-VID: 91520ac7-4977-4c18-b0be-c0ad5c6d6e07
                Copyright © © 2012 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 20 July 2012
                Date accepted : 20 July 2012
                Page count
                Figures: 2, Tables: 2, Pages: 6
                Categories
                Subject: EURETINA – Original Paper

                ScienceOpen disciplines: Vision sciences,Ophthalmology & Optometry,Pathology
                Keywords: Spectral-domain optical coherence tomography,Anti-vascular endothelial growth factor treatment,Hyperreflective dots,Exudative age-related macular degeneration
                Data availability:
                ScienceOpen disciplines: Vision sciences, Ophthalmology & Optometry, Pathology
                Keywords: Spectral-domain optical coherence tomography, Anti-vascular endothelial growth factor treatment, Hyperreflective dots, Exudative age-related macular degeneration

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