Table Of ContentBernard Puech
Jean-Jacques De Laey
Graham E. Holder
Editors
Inherited
Chorioretinal
Dystrophies
A Textbook and Atlas
123
Inherited Chorioretinal Dystrophies
B ernard P uech (cid:129) J ean-Jacques D e Laey
G raham E. H older
Editors
Inherited Chorioretinal
Dystrophies
A Textbook and Atlas
Editors
Bernard Puech Graham E. Holder
Service d’Exploration de la Vision et Department of Electrophysiology
Neuro-ophtalmologie Moorfi elds Eye Hospital, City Road
Centre Hospitalier Universitaire de Lille London
Hôpital Roger Salengro UK
Lille Cedex
France UCL Institute of Ophthalmology
London
Jean-Jacques De Laey UK
Department of Ophthalmology
Ghent University Hospital
Ghent University
Ghent
Belgium
ISBN 978-3-540-69464-9 ISBN 978-3-540-69466-3 (eBook)
DOI 10.1007/978-3-540-69466-3
Springer Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014942263
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Foreword
O ver the last three decades, there have been major advances in the understanding of genetically
determined outer retinal diseases, and there is now a prospect of therapy. One hundred years
ago, it was understood that retinitis pigmentosa could be transmitted as autosomal dominant or
recessive inheritance traits. X-chromosome-linked inheritance was described some time later,
and it is now evident that X-linked retinitis pigmentosa is common, representing up to 50 % of
severe disease. In addition, individual disorders such as Stargardt disease, Best disease and
choroideremia had been identifi ed, but the complexity of retinitis pigmentosa was not appreci-
ated until genetic research pointed to the multiplicity of nosological entities within retinal
dystrophies.
T here is a strong tradition in ophthalmology of phenotyping of retinal diseases. This was
achieved by paintings of retinal appearances followed by photography. Subsequently, ocular
coherence tomography and autofl uorescence imaging provided additional information on the
morphological characteristics of the disease. Phenotyping also included psychophysical and
electrophysiological measures of functional defi cit. It became progressively more evident that
there was a wide variation between morphological changes and functional loss between cases.
Over the last 20 years, the mutations responsible for many constituent disorders have been
discovered, thus enabling a precise diagnosis and identifi cation of the tissue in which the dis-
ease initiated. Correlation of the characteristics of disease and the causative gene allowed
accurate description of many of the individual disorders comprising retina dystrophies. These
advances were made by co-operative research between clinicians and scientists. It demanded
securing large clinical cohorts of well-characterised patients and their pedigrees in specialised
clinical centres and generating registers that contained the genetic information as it became
available.
This radical change in the understanding of inherited retinal diseases has placed a major
responsibility on ophthalmologists in their care of patients. It is now possible to give accurate
counselling concerning genetic risks and visual expectations. This requires a good knowledge
of genetics and the availability of genetic testing. For example, it is particularly important to
assess the risk of patients giving birth to affected offspring at a time when the presence of the
mutant gene cannot be deduced by clinical examination, a situation common in women of
child-bearing age in families with X-linked retinitis pigmentosa or in potential parents in fami-
lies with Sorsby fundus dystrophy. Functional studies allow a prediction of the course of dis-
ease and more accurate visual prognosis than has been possible in the past. Patients can expect
all this information when planning their lives and seeking rehabilitation.
In addition to giving accurate counselling, giving an account of current research and poten-
tial future therapy would be benefi cial to patients and their families. For life-long disorders,
most of which are inexorably progressive, this information represents a potential encouraging
element to the consultation. Although current trials of therapy whereby the course of the dis-
order is modifi ed are in the early stages, such treatments may become commonplace during the
life of many current patients. In addition, certain therapeutic measures such as light restriction,
carbonic anhydrase inhibitors and cataract extraction may help.
I t is the purpose of this book to provide the information in a single source rather than dis-
seminating it into the scientifi c literature alone, which may be diffi cult to access in a short
v
vi Foreword
time. It is written by some of the leading experts in Europe who have worked together for
several years. It was decided that the book should be well illustrated as imaging has been
important to ophthalmic diagnosis since the invention of the ophthalmoscope. The principles
of both functional and genetic testing are described in separate chapters before moving on to
the many disorders or groups of disorders. Finally the prospects of treatment are described. It
is hoped that this single volume will act as source of essential information and a reference.
Understanding the implications of the diagnosis is essential in rehabilitation and adjusting life
of the individual and their family. In addition, it is important to realise that the expectation of
patients has increased with the formation of various self-help groups which disseminate infor-
mation as it becomes available.
London , UK Alan Bird
Pref ace
O phthalmogenetics and especially hereditary fundus disorders have become increasingly
important not only for ophthalmologists and geneticists but also for other specialities such as
dermatology, neurology, internal medicine, and otorhinolaryngology, and especially for the
patients and their families. Genetics has provided new insights into not only the diagnosis but
also the understanding of disease processes. Recently, the fi rst successful attempts of genetic
treatment of Leber congenital amaurosis have opened new perspectives and new hopes for our
patients. The fi rst condition for proper genetic counselling of hereditary chorioretinal dystro-
phies and for their potential treatment is a correct diagnosis. The more precise the diagnosis,
the better the chances are to detect the gene involved and predict the outcomes of the disease.
Ophthalmologists still rely on pattern recognition to make a diagnosis. The fundus aspect is
however only part of the diagnostic process. It has to be correlated with the data of functional
testing, especially electrophysiology, but also with imaging techniques such as angiography,
autofl uorescence and OCT. Therefore, there is still a need for a richly illustrated textbook. We
were fortunate that various leading opthalmogenetic centres accepted to participate in this
project. This has become a European endeavour from centres in the UK (Moorfi elds London,
Manchester, Cardiff), France (Lille; Quinze-Vingts, Paris; Montpellier), Belgium (Ghent),
Holland (Nijmegen) and Germany (Bonn).
The realisation of this book has been a slow process. This is a major hurdle in a discipline
that changes so rapidly. However, the early chapters were eventually updated and we hope that
we ultimately succeeded in presenting a comprehensive and richly illustrated textbook, which
will be of use to ophthalmologists, geneticists and all those interested in ophthalmogenetics.
We wish to thank Springer Verlag, for this opportunity as well as for their patience; Professor
Alan Bird, who was kind enough to write the foreword; and all the authors whose list reads as
a “who’s who” of European ophthalmogeneticists. We also wish to acknowledge all those who
shared their cases with us as well as our patients and their families.
We would like to dedicate this book to the memory of our mentors who were European
pioneers in ophthalmogenetics: Professor Jules François (Ghent), Professor Pierre François
(Lille) and Dr. Pierre Amalric (Albi).
Because the book was written by so many authors, there may be some lack of consistency
between presentations. Also, despite our best efforts, attentive readers may notice some lacu-
nae. We do apologise for these shortcomings.
Lille Cedex , France Bernard Puech
Ghent , Belgium Jean-Jacques De Laey
vii
Contents
Part I Investigations
1 Introduction to Molecular Genetics and Genetic Testing
for Retinal Dystrophies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Georgina Hall and Graeme Charles M. Black
2 Electrophysiological Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Graham E. Holder
3 Dark Adaptation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Jean Claude Hache
4 Fluorescein Angiography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Jean-Jacques De Laey
5 Indocyanine Green Angiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Jean-Jacques De Laey
6 Fundus Autofl uorescence Imaging in Retinal Dystrophies . . . . . . . . . . . . . . . . . 41
Monika Fleckenstein, Peter Charbel Issa, and Frank G. Holz
7 Spectral-Domain Optical Coherence Tomography in Hereditary
Retinal Dystrophies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Isabelle Meunier, Isabelle Bouvet-Drumare, Xavier Zanlonghi,
Martine Mauget-Faysse, Carl Arndt, Christian Hamel, Aude Affortit,
Sabine Defoort-Dhellemmes, and Bernard Puech
Part II Inherited Retinal Dystrophies
8 Inherited Stationary Disorders of the Retina . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Isabelle Audo, Graham E. Holder, and Anthony T. Moore
9 Retinitis Pigmentosa and Allied Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Bernard Puech and Jean-Jacques De Laey
10 Leber Congenital Amaurosis and Early-Onset Retinal Dystrophy. . . . . . . . . . . 121
Bart P. Leroy
11 Retinitis Punctata Albescens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Christian Hamel, Elodie Dessalces, and Isabelle Meunier
12 Usher Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Bart P. Leroy
13 Cone and Cone–Rod Dystrophies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Michel Michaelides
ix
