Cover Page
The handle http://hdl.handle.net/1887/65500 holds various files of this Leiden University
dissertation.
Author: Dijk, E.H.C. van
Title: Central serous chorioretinopathy : from pathogenesis to treatment
Issue Date: 2018-09-13
CENTRAL SEROUS
CHORIORETINOPATHY:
FROM PATHOGENESIS TO TREATMENT
Elon Hendrik Cornelis van Dijk by
ISBN
978-94-93019-49-2 Design Cover
Rind Smesseim en Elon van Dijk Design inside
Paula Baggen en Bregje Jaspers, ProefschriftOntwerp.nl, Nijmegen, The Netherlands Print
ProefschriftMaken, Vianen, The Netherlands
The research described in this thesis was financially supported by
Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Landelijke Stichting voor Blinden en Slechtzienden, Retina Nederland Onderzoek Fonds, Stichting Blinden-Penning, and Stichting Macula Fonds (which all contributed through UitZicht), Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting Leids Oogheelkundig Ondersteuningsfonds, and Stichting Ooglijders. Moreover, support was received from a Gisela Thier Fellowship of Leiden University and a VENI grant of the Netherlands Organisation for Scientific Research, which were awarded to prof. dr. C.J.F. Boon to fund this research line.
Financial support for the printing of this thesis was kindly provided by
Bartiméus Sonneheerdt, Landelijke Stichting voor Blinden en Slechtzienden, Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting Leids Oogheelkundig Ondersteuningsfonds, Stichting Oogheelkunde Rijswijk, Stichting voor Ooglijders, Stichting Wetenschappelijk Onderzoek Het Oogziekenhuis Prof. dr. H.J. Flieringa, Bayer, Chiesi Pharmaceuticals BV, ChipSoft, Elvea Low Vision, Fagron, Haags Kunstogen Laboratorium, Horus Benelux, Kuijpers Instruments, Laservision Instruments, Low Vision Totaal, Medical Workshop, Mr. Eyes / CenterVue SpA, Oculenti Contactlenzen, Revoir / Ergra Low Vision, Rockmed BV, Synga Medical, Théa Pharma BV, Tramedico, Ursapharm, Visser Contactlenzen, Vitaminen op Recept, Zeiss
All funding organisations provided unrestricted grants and had no role in the design or conduct of this research.
© Elon Hendrik Cornelis van Dijk (elonvandijk@gmail.com), 2018
No part of this thesis may be reproduced in any form without written permission from the author.
CENTRAL SEROUS
CHORIORETINOPATHY:
FROM PATHOGENESIS TO TREATMENT
Proefschrift ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op donderdag 13 september 2018
klokke 13:45 uur door
Elon Hendrik Cornelis van Dijk
geboren te Rotterdam in 1990
Promotoren:
Prof. dr. C.J.F. Boon Prof. dr. G.P.M. Luyten
Leden promotiecommissie:
Prof. dr. N.E. Schalij-Delfos Prof. dr. ir. S.M. van der Maarel
Prof. dr. L.A. Yannuzzi Columbia University Medical School
Dr. S. Yzer Oogziekenhuis Rotterdam
voor opa Henk voor mijn ouders voor Maxime
ABBREVIATIONS
aCSC acute central serous chorioretinopathy ACTH adrenocorticotropin
AE adverse event
AMD age-related macular degeneration ANA antinuclear antibody
AP50 alternative pathway activity ARA antiretinal antibody
ARFGEF1 adenosine diphosphate ribosylation factor guanine nucleotide exchange factor 1
ARMS2 age-related macular degeneration susceptibility 2
AS Apathy Scale
BCVA best-corrected visual acuity
BM Bruch’s membrane
BMI body mass index
bp base pair
C4B complement factor 4B
cCSC chronic central serous chorioretinopathy CD46 cluster of differentiation 46
CDH5 cadherin 5
CEC choroidal endothelial cell CFH complement factor H
CFHR1/4 complement factor H related 1/4
chr chromosome
CI confidence interval
CM cutaneous melanoma
CNV choroidal neovascularisation CP50 classical pathway activity CRT central retinal thickness
CS Cushing’s syndrome
CSC central serous chorioretinopathy CT choroidal thickness
DAPP-SF Dimensional Assessment of Personality Pathology short form DARA diffuse atrophic retinal pigment epithelium alterations DSMB Data Safety Monitoring Board
EDI enhanced-depth imaging EDTA ethylenediaminetetraacetic acid ELISA enzyme-linked immunosorbent assay ELM external limiting membrane
EOG electro-oculography
EPACTS efficient and parallelizable association container toolbox eQTL expression quantative trait locus
ERG electroretinography
ERM epiretinal membrane
ETDRS Early Treatment of Diabetic Retinopathy Study
EZ ellipsoid zone
FA fluorescein angiography FAF fundus autofluorescence FITC fluorescein isothiocyanate
Freq frequency
GATA5 GATA binding protein 5 GCL ganglion cell layer
GEE generalised estimating equations GR glucocorticoid receptor
GTEx genotype-tissue expression GTP guanosine triphosphate GWAS genome-wide association study
Hg human genome
HPA hypothalamic-pituitary-adrenal HRC haplotype reference consortium
HSML high-density subthreshold micropulse laser ICGA indocyanine green angiography
IIF indirect immunofluorescence ILM internal limiting membrane INL inner nuclear layer
IPL inner plexiform layer IRR infrared reflectance IS Irritability Scale
ISCEV International Society for Clinical Electrophysiology of Vision IZ interdigitation zone
KCNT2 potassium sodium-activated channel subfamily t member 2 LP50 mannose-binding lectin pathway
MAF minor allele frequency
MAGMA multi-marker analysis of genomic annotation MAPK mitogen-activated protein kinase
MEGF6 multiple epidermal growth factor like domains 6 MEK mitogen-activated protein kinase kinase mir-29b-2 micro ribonucleic acid 29b-2
MR mineralocorticoid receptor mSC midnight salivary cortisol
MSigDB molecular signatures database
NA not annotated
nAMD neovascular age-related macular degeneration NBS Nijmegen Biomedical Study
NEI-VFQ25 National Eye Institute Visual Function Questionnaire NR3C2 nuclear receptor subfamily 3 group C member 2
NS not significant
OCT optical coherence tomography ONL outer nuclear layer
OPL outer plexiform layer
OR odds ratio
OS outer segments
PA primary aldosteronism PBS phosphate-buffered saline
PCRD posterior cystoid retinal degeneration PCV polypoidal choroidal vasculopathy PDT photodynamic therapy
PED pigment epithelial detachment
PITPNC1 phosphatidylinositol transfer protein cytoplasmic 1 PPE pachychoroid pigment epitheliopathy
PSS Perceived Stress Scale
RAF rapidly accelerated fibrosarcoma
RAT rat sarcoma
RORA retinoic acid receptor-related orphan receptor alpha RPE retinal pigment epithelium
RVO retinal vein occlusion SAE serious adverse event SBT second band thickness
SD standard deviation
SD-OCT spectral-domain optical coherence tomography
SE standard error
SFCT subfoveal choroidal thickness SNP single nucleotide polymorphism SRF subretinal fluid
TBS tris-buffered saline
TNFRSF10A tumor necrosis factor receptor superfamily member 10a UCS Utrecht Coping Scale
UFC urinary free cortisol
UM uveal melanoma
UTR untranslated region
VEGAS2 versatile gene-based association study 2 VEGF vascular endothelial growth factor
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CONTENTS
1. Introduction
2. Genetics and pathophysiology of central serous chorioretinopathy
2.1 Familial central serous chorioretinopathy.
Retina 2018
2.2 Association of a haplotype in the NR3C2 gene, encoding the mineralocorticoid receptor, with chronic central serous chorioretinopathy.
JAMA Ophthalmol. 2017;135(5):446-51
2.3 Genome-wide assocation study underlines the role of the complement system in chronic central serous chorioretinopathy.
JAMA Ophthalmol. 2018
3. Systemic abnormalities in central serous chorioretinopathy
3.1 Hypothalamic-pituitary-adrenal axis activity in chronic central serous chorioretinopathy.
Frontiers in Endocrinology 2018
3.2 Maladaptive personality traits, psychological morbidity, and coping in chronic central serous chorioretinopathy.
Under review
3.3 Systemic complement activation in central serous chorioretinopathy.
PLoS One 2017;12(7):e0180312
3.4 Antiretinal antibodies in central serous chorioretinopathy: prevalence and clinical implications.
Acta Ophthalmol. 2018;96(1):56-62
4. Steroids and central serous chorioretinopathy
4.1 Central serous chorioretinopathy in primary hyperaldosteronism.
Graefes Arch Clin Exp Ophthalmol. 2016;254(10):2033-42
4.2 Spectrum of retinal abnormalities in renal transplant patients using chronic low-dose steroids.
Graefes Arch Clin Exp Ophthalmol. 2017;255(12):2443-9
4.3 Chronic central serous chorioretinopathy as a presenting symptom of Cushing syndrome.
Eur J Ophthalmol. 2016;26(5):442-8
5. Differential diagnosis of central serous chorioretinopathy
5.1 Serous retinopathy associated with MEK inhibition (binimetinib) for metastatic cutaneous and uveal melanoma.
Ophthalmology 2015;122(9):1907-16
5.2 Loss of MAPK pathway activation in post-mitotic retinal cells as mechanism in MEK inhibition-related retinopathy in cancer patients.
Medicine (Baltimore) 2016;95(18):e3457
5.3 Pimasertib-associated ophthalmological adverse events.
Acta Ophthalmol. 2018
6. Treatment of central serous chorioretinopathy
6.1 Half-dose photodynamic therapy versus high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy: the PLACE trial.
Ophthalmology 2018
6.2 Photodynamic therapy in chronic central serous chorioretinopathy with subretinal fluid outside the fovea.
Graefes Arch Clin Exp Ophthalmol. 2017;255(10):2029-35 7. Summary and general discussion
8. Dutch summary Acknowledgements About the author List of publications
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