Table Of ContentYozo Miyake
Electrodiagnosis of Retinal Diseases
Yozo Miyake
Electrodiagnosis of
Retinal Diseases
With 258 Figures,Including 93 in Color
Yozo Miyake
Professor Emeritus,Nagoya University
Head of the National Institute of Sensory Organs
National Hospital Organization Tokyo Medical Center
2-5-1 Higashigaoka,Meguro-ku,Tokyo 152-8902,Japan
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Preface
Soon it will be time for me to retire from my position as professor ofoph-
thalmology in the Department of Ophthalmology, Nagoya University
School of Medicine. I have therefore decided to summarize my experi-
ence of more than 30 years of studies on the clinical electrophysiology of
vision.These studies were performed in our department through the hard
work and good ideas of many co-workers,and the chapters of this book
cover the rationale and results ofour studies.Because excellent textbooks
on clinical electroretinography already exist, my wish is not to write
another textbook;instead,this book is in the form of essays that include
my beliefs and philosophy on the clinical electrophysiology of vision.As
such,this book does not include every clinical disease but only those that
we have identified or studied in detail.
In addition to full-field electroretinography (ERG),we developed the
techniques and instrumentation to record focal macular ERG more than
two decades ago. Using these techniques, we were able to determine
several new physiological properties of the normal macula, many new
pathophysiological mechanisms of known diseases,and some new clini-
cal entities with unique functional properties.
Fortunately,the recent advances of macular surgery and imaging are
such that the macular configuration can easily be determined.During the
process ofsurgery,we have obtained considerable information on the cor-
relation of macular function and macular morphology using focal
macular ERGs and optical coherence tomography (OCT). The develop-
ment of multifocal ERGs followed our focal macular ERGs,and this tech-
nique has allowed the objective examination of macular function
throughout the world.
There has been no similar occasion in the past where the advancement
of technology has allowed us to discover such correlations and, more
importantly,to determine the mechanisms for many retinal diseases.As
one who has dedicated his life to this area, I hope that this book will
inspire young researchers and clinicians to enjoy the pleasure and
fulfillment that can come from studying the retina. Most importantly,
there are many more challenges that have to be taken on and conquered.
Yozo Miyake
Nagoya
March 2005
Acknowledgments
There are many people who have helped make this book a reality;
however, some merit special attention. Dr. Hiroko Terasaki has con-
tributed very much with her skills in the new surgical procedures and in
psychophysical measurements in normal subjects and patients with
retinal diseases who underwent retinal surgery. Dr. Mineo Kondo has
always been with me to analyze the clinical data and to perform the
animal experiments during the past 10 years. Dr. Masayuki Horiguchi
worked with me for a long time before he moved to Fujita Health Uni-
versity as chairman and professor of the Department of Ophthalmology.
He had many unique ideas and contributed greatly to our studies. Dr.
Yoshihiro Hotta opened a new field of molecular genetics in our depart-
ment and Dr. Makoto Nakamura has provided important molecular
genetic data of our patients.It would not have been possible to complete
this book without the invaluable contribution of these investigators.
Special thanks go to Dr.Tatsuo Hirose ofBoston,who was a great inspi-
ration to me and who also pointed out the importance of focal macular
ERGs when I was a young investigator. I learned basic retinal electro-
physiology from Dr.Genyo Mitarai in Nagoya,and he has been an impor-
tant teacher in my life.
Finally, I would like to express my sincere gratitude to Dr. Duco
Hamasaki ofMiami,my close friend,for his kind revision and many valu-
able suggestions regarding the English content of this book.During the
past 10 years,he has made an enormous contribution to Japanese oph-
thalmology by revising many manuscripts written by Japanese investiga-
tors that eventually were published in English journals.On behalf of the
Japanese Society of Ophthalmology,I would like to thank him again.
Yozo Miyake
Contents
Preface V
Acknowledgments VII
1
Principles and Methods 1
1.1 Full-Field Electroretinograms 2
1.2 Focal Macular ERGs 20
1.3 Multifocal ERGs 33
1.4 Electrooculography 41
1.5 Optical Coherence Tomography 42
2
Hereditary Retinal and Allied
Diseases 43
2.1 Retinitis Pigmentosa 44
2.2 Crystalline Retinopathy (Bietti) 55
2.3 Batten Disease 58
2.4 Kearns-Sayre Syndrome 61
2.5 Choroideremia 64
2.6 Gyrate Atrophy 66
2.7 Enhanced S-Cone Syndrome 68
2.8 X-Linked Retinoschisis 72
2.9 Nettleship-Falls X-Linked Ocular Albinism 87
2.10 Complete and Incomplete Types of CSNB 90
2.11 Fundus Albipunctatus 114
2.12 Oguchi’s Disease 119
2.13 Cone Dystrophy 123
2.14 Rod Monochromacy 136
X Contents
2.15 Blue Cone Monochromacy 138
2.16 Congenital Tritanopia — Differential Diagnosis of
Dominantly Inherited Juvenile Optic Atrophy 141
2.17 Rod–Cone Dysfunction Syndrome with an Unusual Form
of ERG 144
2.18 Association of Negative ERG with Diseases of Unknown
Etiology 147
2.19 Occult Macular Dystrophy 153
2.20 Stargardt’s Disease (Fundus flavimaculatus) 160
2.21 Best’s Disease 165
3
Acquired Retinal Diseases 169
3.1 Diabetic Retinopathy 170
3.2 Retinal Circulatory Disturbances 180
3.3 Retinal and Choroidal Detachment 183
3.4 Inflammatory Diseases of Retina and Choroid 186
4
Acquired Macular Diseases 199
4.1 Central Serous Chorioretinopathy 200
4.2 Aphakic or Pseudophakic Cystoid Macular Edema 203
4.3 Idiopathic Epimacular Membranes 209
4.4 Foveal Thickness and Focal Macular ERG 213
4.5 Idiopathic Macular Hole 214
4.6 Macular Pseudohole 221
4.7 Age-Related Macular Degeneration 223
Subject Index 233
1
Principles and Methods
The purpose of this chapter is to present the ties and the origin ofERG responses are shown
principles and techniques used to perform for normal subjects to demonstrate the appear-
clinical electroretinography—electroretinograms ance and properties of normal ERGs. These
(ERGs) and electrooculograms (EOGs)—and observations should provide a foundation for
to show how they are incorporated into the the better understanding of abnormal ERGs in
examination of patients. Some special proper- the analysis of clinical cases.
2 1 Principles and Methods
1.1 Full-Field Electroretinograms
The development and advancement of clinical Ganzfeld, stimulator represents such a stimu-
electroretinography (ERG) were the conse- lus.It is composed of a large-diameter (40cm)
quence of a better understanding of the cellu- hemispheric dome (Fig. 1.1), with a xenon
lar origins of the major components of the stroboscopic light bulb placed at the top of the
ERG initially demonstrated by Granit in 1934 dome.This configuration allows presentation of
[1];the progressive improvement ofthe record- diffuse and homogeneous stimuli and back-
ing devices, as shown by introduction of the ground illumination to the entire retina. This
contact lens electrode by several investigators stimulus system has been recommended by the
such as Riggs [2], Karpe [3], and Burian and International Society of Clinical Electrophysi-
Allen [4]; and the development of computers ology for Vision (ISCEV) Standards Committee
for improving the signal-to-noise ratio by aver- for use when obtaining clinical ERG recordings
aging techniques. [10],and the ISCEV protocol is now being used
Many Japanese investigators have con- internationally.The establishment of standard-
tributed significantly to full-field clinical ERG. ized recording conditions for full-field ERGs
Among the representative studies are the was an important accomplishment for the
method for distinguishing cone from rod ISCEV because it allowed us to make reason-
responses pioneered by Motokawa and Mita able comparisons of the ERGs recorded in any
[5], the study of human oscillatory potentials country throughout the world that record ERGs
(OPs) by Yonemura et al.[6],and the study of using ISCEV standards.
photopic ERG by Nagata [7]. In 1968 when I
became an ophthalmologist,I thought that the
major works on clinical ERG had already been
done. However, looking back on the past 37
years,it is now realized that many advances in
clinical ERG have taken place since then that
have contributed greatly not only to the elec-
trophysiology ofthe eye but to the understand-
ing of many ophthalmological diseases.
The human ERG recorded at the cornea and
elicited by a full-field stimulus is a mass
response generated by cells across the entire
retina. To obtain reproducible amplitudes and
implicit times in the responses, the stimulus
and background light should be homogeneous
and cover the entire retina,so all of the recep-
tors are stimulated or adapted in a relatively Fig. 1.1. Ganzfeld (full-field) dome for full-field elec-
troretinography (ERG) recordings
homogeneous manner [8, 9]. The full-field, or
