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Pathophysiology, Screening and Treatment of ROP: a Multi-Disciplinary Perspective

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Pathophysiology, Screening and Treatment of ROP: a Multi-Disciplinary Perspective Accepted Manuscript Pathophysiology, screening and treatment of ROP: A multi-disciplinary perspective Tailoi Chan-Ling, Glen A. Gole, Graham E. Quinn, Samuel J. Adamson, Brian A. Darlow PII: S1350-9462(16)30077-5 DOI: 10.1016/j.preteyeres.2017.09.002 Reference: JPRR 685 To appear in: Progress in Retinal and Eye Research Received Date: 3 February 2017 Revised Date: 18 September 2017 Accepted Date: 20 September 2017 Please cite this article as: Chan-Ling, T., Gole, G.A., Quinn, G.E., Adamson, S.J., Darlow, B.A., Pathophysiology, screening and treatment of ROP: A multi-disciplinary perspective, Progress in Retinal and Eye Research (2017), doi: 10.1016/j.preteyeres.2017.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Pathophysiology, Screening and Treatment of ROP: a multi-disciplinary perspective Tailoi Chan-Ling 1 Glen A. Gole 2 Graham E. Quinn 3 Samuel J. Adamson 1 Brian A. Darlow 4 Affiliations: 1 Department of Anatomy, School of Medical Sciences and Bosch Institute, University of Sydney, NSW 2006, Australia [email protected] 2 Discipline of Paediatrics and Child Health, University of Queensland, Qld Children’s Hospital, Sth Brisbane, Qld 4101, Australia [email protected] 3. Division of Ophthalmology, The Children’s Hospital of Philadelphia and Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA [email protected] 4. Department of Paediatrics, University of Otago, Christchurch, New Zealand. [email protected]. MANUSCRIPT * TC-L, GAG, GEQ and BAD contributed equally to this review. Corresponding author : Tailoi Chan-Ling Department of Anatomy School of Medical Sciences and Bosch Institute University of Sydney, NSW 2006 Australia [email protected] T: +61 2 9351 2596ACCEPTED F: +61 2 9351 6556 Acknowledgement: This work has been supported by: the National Health and Medical Research Council of Australia (#571100, #1005730), the Brian M Kirby Foundation - Gift of Sight Initiative, the Bonnie Babes Foundation (Lucy Turnbull AO and The Hon. Prime Minister of Australia Malcolm Turnbull), the Baxter Charitable Foundation, the Sydney Medical School Foundation, the Alma Hazel Eddy Trust, The Rebecca L Cooper Medical Research Foundation and the Geoffrey Arnott Foundation to TC-L, the NWG Macintosh Memorial Fund to SJA and Cure Kids New Zealand to BAD. 1 Table of Contents ACCEPTED MANUSCRIPT 2 Abstract ........................................................................................................................................................3 3 List of Abbreviations ...................................................................................................................................4 4 Introduction - Epidemiology of ROP .........................................................................................................7 5 Purpose .........................................................................................................................................................7 6 Cellular and Molecular Mechanisms of Human Retinal Vascularization .............................................8 7 Development of the human retinal vasculature ...................................................................................................8 8 ‘Physiological hypoxia’ model of formation of human retinal vasculature ....................................................10 9 Cellular & molecular mechanisms of formation of the foveal avascular zone (FAZ) ....................................11 10 Glial, vascular and neuronal interactions in the formation of the foveal vasculature ...................................11 11 Neurosensory Retina in ROP ..............................................................................................................................13 12 Effects of premature birth on retinal development and function: Impact on extremely premature infants 13 ................................................................................................................................................................................14 14 Choroidal involution as a component of ROP ...................................................................................................15 15 Optical Coherence Tomography (OCT) and ROP ............................................................................................16 16 Unique susceptibility of posterior ROP: Basis in vasculogenic origin of posterior vessels............................16 17 ROP develops in two phases ................................................................................................................................18 18 Initiating event in pathogenesis of ROP - delayed vascularisation relative to neuronal maturation (Phase 1 19 ROP) ......................................................................................................................................................................19 20 Phase 2 ROP: Hypoxia-induced pathological neovascularization ...................................................................19 21 Limitations of current management strategies for ROP, including anti-VEGF: ...........................................20 22 The Rationale for Dark-Rearing (DR), a non-invasive therapy for the treatment of ROP ...........................20 23 Scientific rationale for distinct pathogenetic mechanisms underlying zone 1 & zone 2 ROP .......................22 24 VEGF165 subserves multiple functions: angiogenic growth factor, vascular permeability factor and 25 neuronal survival factor. ...........................................................................................................................23 26 Background ...........................................................................................................................................................23 27 VEGF Biology .........................................................................................MANUSCRIPT...................................................24 28 Control and expression of VEGF and associated genes via HIF-1 ..................................................................24 29 VEGF Signaling ....................................................................................................................................................25 30 VEGF and pathogenesis of ROP .........................................................................................................................26 31 VEGF and neuroprotection in the retina ...........................................................................................................26 32 Role of VEGF in maintaining vessel stability in early postnatal period..........................................................27 33 Role of VEGF in vascular permeability .............................................................................................................28 34 Screening for ROP .....................................................................................................................................28 35 Telemedicine and ROP screening .......................................................................................................................30 36 Fluorescein angiography before and after treatment for ROP ........................................................................34 37 Treatment of ROP .....................................................................................................................................36 38 CRYO-ROP Study ...............................................................................................................................................37 39 Laser versus Cryotherapy ...................................................................................................................................37 40 Laser for ROP.......................................................................................................................................................38 41 Timing of intervention for severe ROP ..............................................................................................................40 42 Side effects of laser .............................ACCEPTED..................................................................................................................40 43 Long term outcomes of laser treatment .............................................................................................................41 44 Recommendations for long term follow up. .......................................................................................................42 45 Outcomes after laser for AP-ROP ......................................................................................................................42 46 Anti-VEGF therapy in ROP: The pros and cons ..............................................................................................43 47 VEGF-based therapeutic options ........................................................................................................................43
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