Dominant Exudative Vitreoretinopathy and other Vascular Developmental Disorders of the Peripheral Retina
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1 Dominant Exudative Vitreoretinopathy and other Vascular Developmental Disorders of the Peripheral Retina
2 Monographs in Ophthalmology 5 Dr W. JUNK PUBLISHERS THE HAGUE/BOSTON/LONDON
3 C.E. van NOUHUYS Dominant Exudative Vitreoretinopathy and other Vascular Developmental Disorders of the Peripheral Retina Dr W. JUNK PUBLISHERS THE HAGUE/ BOSTON/ LONDON
4 Distribu tors: for the United States and Canada Kluwer Boston Inc. 190 Old Derby Street Hingham, MA USA for all other countries Kluwer Academic Publishing Group Distribution Center P.O. Box AH Dordrecht The Netherlands ISBN-13: e-isbn-13: DOl: / Copyright 1982 Dr W. Junk bv Publishers, The Hague, The Netherlands. Softcover reprint of the hardcover 1st edition 1982 All rights reserved. No part of this publication may be reproduced stored in a retrival system, or transmitted in any form or by any means, mechanical, photocopying, recording, or otherwise, without the prior permission of the publishers. Dr W. Junk bv Publishers, P.O. Box 13713, 2501 ES The Hague, The Netherlands.
5 PREFACE Dominant exudative vitreoretinopathy (DEVR) is an eye disease which has only recently received wider attention. In 1969 Criswick and Schepens used the designation "familial exudative vitreoretinopathy" to describe a syndrome they observed in six patients belonging to two families. The condition was characterized by several symptoms involving the vitreous and retina, e.g. "posterior vitreous detachment, organized vitreous membranes, heterotopia of the macula, retinal neovascularizations, subretinal and intraretinal exudates, and localized retinal detachment". The clinical features impressed the authors as strongly reminiscent of retrolental fibroplasia, but none of the patients had a record of premature birth or postnatal oxygen administration. In 1971 Cow and Oliver described the same syndrome in several members of one family. They considered their findings to be compatible with autosomal dominant transmission. Canny and Oliver (I976) were the first to demonstrate the fluorescein-angiographic changes of DEVR in four members of the abovementioned family. The most striking finding was "abrupt cessation of the capillary network in a scaloped edge near the equator". Fluorescein was seen to leak from the retinal vessels localized in this marginal zone, and in some eyes from massive fibrovascular lesions as well. Similar fluoresceinangiographic changes have been described in recent years in other reports on families with DEVR (Nijhuis et ai., 1979; Slusher and Hutton, 1979; Dudgeon, 1979; Ober et a1., 1980; Laqua, 1980). In 1979 I commenced a clinical study of this still little-known condition at the Nijmegen University Institute of Ophthalmology (The Netherlands). This venture was prompted by the fact that two families with DEVR had been known for some time at this institute. The study led to identification of the disease in seven more families. The findings obtained in this total of nine families are presented and discussed in this thesis. Part I briefly reviews the normal development and anatomy of the retinal vasculature, more specifically in the peripheral fundus. Part II discusses the pathology of (peripheral) retinal vascular development. In addition to DEVR there are other eye diseases or general syndromes in which fundus changes are based on disturbed development of the peripheral retinal vasculature, or in which such a pathogenesis is considered not to be improbable. Moreover, other conditions whose primary lesions are not based on disturbed vascular development can be incidentally associated with symp-
6 VI toms suggestive of a disorder in the vasculogenesis of the peripheral retina. The selection of the conditions discussed in part II is based partly on a study of the literature and partly on personal observations, some of which have been presented in previous publications. Apart from DEVR, I have not attempted to discuss all the features of the various other diseases but always accentuated the aspect of disturbed retinal vascular development. Both the literature and the histories of our patients show that DEVR very frequently causes diagnostic confusion. This is why I have given ample attention to differential diagnosis. With regard to diseases in which retinal vascular developmental disorders playa role, the differential diagnosis is discussed in part II. For other diseases this is done in part III. C.E. VAN NOUHUYS Afdeling Oogheelkunde Canisius Wilhelmina Ziekenhuis St.Annastraat GS Nijmegen The Netherlands
7 ACKNOWLEDGEMENTS Several persons have given me the benefit of their assistance in my research and in the preparation of this publication. I am indebted to Mr A.L. Aan de Kerk for his competent help in photographing the peripheral eye fundus in a large number of patients. The ophthalmological study of several members of the A family by Dr F.A. Nijhuis has been of essential importance to me in the early phase of this study. Dr A. Hamburg of the Eye Clinic of the University of Utrecht was kind enough to send me several histological specimens. I thank my colleagues of the Department of Ophthalmology of the Canisius Wilhelmina Hospital, Nijmegen, for their kindness in supplying me with clinical data on their patients. The expert criticism I received from Prof. J.J.de Laey of Ghent (Belgium) and from Prof. S.J. Geerts of Nijmegen proved to be very valuable to me. The photomicrographs and the line drawings were prepared by the audiovisual service of the St. Radboud Hospital and by Mrs Th. Hermans Den Brok, Nijmegen. My wife Jose typed the manuscript in her limited spare time and collated the bibliography. The English translation was made by Mr Th. van Winsen.
8 CONTENTS Preface Acknowledgements v VII Part 1: The normal vasculature of the peripheral retina 1. Development and anatomy of the normal vasculature of the peripheral retina Definitions of anatomical boundaries Development and regression of the hyaloid vessels and the primary vitreous Development of the choroid of the peripheral fundus Development of the retinal vasculature Anatomy of the vasculature of the peripheral retina Structure of the retinal vessels and the vitreoretinal juncture of the peripheral fundus Clinical examination of peripheral retinal blood vessels and circulation Indirect ophthalmoscopy... : Three-mirror contact lens examination a The biomicroscopic features of the normal vasculature of the peripheral retina Photography and fluorescein angiography of the peripheral fundus a The fluorescein angiogram of the normal peripheral fundus Part II: Disturbed development of the peripheral retinal vessels Clinical studies of families with dominant exudative vitreoretinopathy Materials and methods The A family
9 x 3.3 The B family The C family The D family The E family l The F family The G family The H family The I family Results and discussion of the family studies Numbers of affected and probably affected persons in the various families Age and sex distribution of the affected and probably affected persons Visual acuity Refraction Amblyopia Nystagmus Eye position Intraocular pressure Anterior segment Vitreous Fundus a Biomicroscopic changes b Fluorescein-angiographic changes Visual fields l3 Ultrasonography Electroretinography and electro-oculography Dark adaptation Colour vision Histology General physical examination Stages and course Genetic aspects and pathogenesis of dominant exudative vitreoretinopathy 221 Genetic aspects Mode of transmission Gene penetrance Gene expression a Genetic factors b Influence of the "environment" Incidence and distribution of the gene
10 5A.a Ethnic and geographical distribution Genetic counselling Pathogenesis DEVR as a vascular developmental disorder..., Deformation of the foetal network of retinal vessels as direct consequence of disturbed vascular development. A hypothesis Objections to qualification of DEVR as "vitreoretinal dys trophy" Prevention and treatment of complications of dominant exudative vitreoretinopathy Early diagnosis and selection of high risk patients Treatment Congenital retinal fold (ablatio falciformis congenita) The clinical features of congenital retinal fold Conditions which may be associated with congenital retinal fold Congenital retinal fold as a manifestation of DEVR A Congenital retinal fold and microcephaly Pathogenesis of congenital retinal fold a Early versus late hypothesis b Additional pathogenetic mechanisms c Unilateral congenital retinal fold of obscure pathogenesis Retrolental fibroplasia Clinical symptoms l.a Active retrolen tal fibroplasia l.b Cicatricial retrolental fibroplasia Histology The influence of oxygen on the development of the immature retinal vasculature Treatment Differential diagnosis a "Retrolental fibroplasia" without neonatal oxygen administration or prematurity Consequences of oxygen administration to premature neonates with the genotype of DEVR Affections with congenital or neonatal vitreous organizations and retinal detachment Incontinentia pigmenti (Bloch-Sulzberger syndrome) XI
11 XII a Clinical ocular symptoms b Genetic aspects c Histology and pathogenesis d Differential diagnosis e Treatment.... Norrie's disease a Clinical symptoms b Histology c Pathogenesis d Differential diagnosis.... Reese-Blodi-Straatsma syndrome and trisomy a Histology b Pathogenesis c Differential diagnosis.... Congenital encephalo-ophthalmic dysplasia a Clinical symptoms.... Proliferative retinopathy in anencephalia a Pathogenesis.... Familial unilateral proliferative retinopathy.... Observations on Wagner's syndrome, sex-linked juvenile retinoschisis and juvenile rhegmatogenous retinal detachment Wagner's syndrome.... 1O.1.a Clinical symptoms.... 1O.1.b Histology.... 1O.1.c General manifestations: clefting syndromes.... 1O.1.d Fluorescein-angiographic study of the circulation of the equatorial retina and choroid.... 1O.1.e Pathogenesis of the aberrant configuration of retinal vessels in the posterior pole and ectopia of the macula. Sex-linked juvenile retinoschisis.... 1O.2.a Clinical symptoms b Vascular changes.... 1O.2.c Histology and pathogenesis.... Juvenile rhegmatogenous retinal detachment a Personal observations.... Congenital bilateral arterial anastomosis between the choroid and the peripheral retina Coats' disease and retinal angiomatosis Coats' disease a Clinical symptoms b Histology
12 XIII 12 J.c Pathogenesis d Differential diagnosis e Treatment Retinal angiomatosis a Clinical symptoms b Histology and pathogenesis c Differential diagnosis d Treatment Sturge-Weber's syndrome Part III: Additional differential diagnoses from dominant exudative vitreoretinopathy Congenital conditions not associated with retinal vascular developmental disorders Persistent hyperplastic primary vitreous l.a Clinical symptoms J.b Histology I.c Differential diagnosis I.d Posterior PHPV and congenital retinal fold Congenital toxoplasmosis Retinoblastoma Acquired conditions Eales'disease l.a Clinical symptoms b Differential diagnosis from DEVR Sickle cell retinopathy a Differential diagnosis from DEVR Pars planitis a Clinical symptoms b Differential diagnosis from DEVR Toxocariasis a Clinical symptoms b Differential diagnosis Myopia a Perfusion disorders of the peripheral retina in myopia b Ectopia of the macula in high myopia Ectopia of the macula due to a pucker of the peripheral retina. 384 Summary Samenvatting References Curriculum vitae
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