Ординатура / Офтальмология / Английские материалы / Advances in Understanding Mechanisms and Treatment of Infantile Forms of Nystagmus_Leigh, Devereaux_2008

Since the contributions of Hubel and Wiesel, substantial advances have been made in understanding the developmental biology of the visual system, leading to therapies for amblyopia. However, disorders of eye movements that arise early in life remain a major challenge for ophthalmologists, pediatricians, and neurologists. Recently, basic studies of infantile nystagmus have provided new approaches, including psychophysical techniques, development of animal models, genetic linkage studies, and trials of gene therapy.

Over the past 40 years, Louis F. Dell’Osso has made major contributions to our understanding of nystagmus that begins in infancy. Starting with an engineering approach to the control of eye movements, he applied principles of linear control systems to a range of ocular oscillations, including congenital nystagmus (now termed infantile nystagmus syndrome) and latent nystagmus (now termed fusional maldevelopment nystagmus syndrome). Dr. Dell’Osso’s first efforts defined these ocular oscillations with reliable measurements and classified the forms of nystagmus on the basis of their waveforms. He then applied this knowledge to better understand how such nystagmus disturbs a clear view of the world and how reliable measurements of nystagmus can be used to predict each individual’s visual potential.

Throughout his career, Dr. Dell’Osso’s engineering background has led to development of mathematical models to account for the underlying pathophysiology of disturbed gaze control. More recently, he has been involved with animal models of infantile nystagmus due to specific genetic disorders, which hold the promise of human gene therapy. Equally significant

have been his contributions to developing treatments of infantile forms of nystagmus, especially in suggesting and evaluating new surgical procedures. Beyond his scientific contributions, Dr. Dell’Osso brings a personal understanding to those individuals who are visually disabled by congenital forms of nystagmus; this empathy is appreciated by the numerous patients that he has evaluated over four decades.

This volume is the result of a meeting held May 3– 4, 2007, under the auspices of Case Western Reserve University, to celebrate Dr. Dell’Osso’s contributions and the opening of the Daroff-Dell’Osso Laboratory at the Louis Stokes Cleveland Department of Veterans Affairs Medical Center. The meeting was made possible through generous support from the Mt. Sinai Health Care Foundation and the Garson Fund of Cleveland, Ohio. The goal of the meeting was to apply basic information about eye movements in order to better understand the pathophysiology of infantile forms of nystagmus and develop new therapies.

The first section of this book, “Basic Concepts of Stable Vision and Gaze,” comprises five chapters that address psychophysical aspects of vision in normal subjects and individuals with nystagmus and the relative contributions of afference (extraocular proprioception) versus efference (internal copies of the ocular motor commands). The influence of extraocular proprioception on the control of gaze has been considered minor compared with “efference copy” or “corollary discharge” of the ocular motor commands. However, anatomical studies by Jean Büttner-Ennever and colleagues have identified a possible mechanism

for proprioception located near the insertion of nontwitch extraocular muscles in the eyeball. Recent studies by Michael E. Goldberg et al. have established that extraocular proprioception projects to the frontal eye fields, where it may influence the programming and consequences of gaze shifts.

In Part 1, Dr. Steinbach, an abiding proponent of extraocular proprioception, reports that in normal subjects the Jendrassik maneuver (voluntary, forceful contraction of arm muscle groups) affects the registered vergence eye position, possibly by changing activity in the non-twitch muscle fibers–proprioceptive loop. Dr. Bedell summarizes a series of studies of the mechanisms for lack of oscillopsia in infantile nystagmus syndrome and provides evidence for reduced perceptual responses when the eyes are in motion. An accessible and useful review of current notions of spatial and temporal visual functions and spatial constancy in infantile nystagmus syndrome and latent nystagmus is provided by Dr. Abadi. Dr. Abel supplements this information by highlighting the effect of psychological factors on infantile nystagmus. Finally, Dr. Proudlock presents evidence that perceptual fading in normal subjects is influenced by efference commands for eye movements

Part 2, “New Models and Techniques for Studying Gaze Stability,” opens with two chapters concerning animal models of disorders causing nystagmus. Developmental models for strabismus and amblyopia in primates also provide an opportunity to study the nystagmus that often coexists with these conditions. Dr. Das reports the effects of experimentally induced strabismus on programming of voluntary saccades, noting that reaction time (latency) depends on whether viewing is monocular or binocular. Cerebellar lesions in adults induce well-defined disturbances of eye movements that resemble human disease syndromes. Dr. Walker extends this work by demonstrating that cerebellar nodulus lesions also impair the linear (translational) vestibulo-ocular reflex. The final two chapters in this section deal with new technologies. One approach to managing nystagmus has been to attempt to cancel the visual consequences of the ocular oscillations with optical devices. A high-tech version developed by Dr. Stahl incorporates moving prisms that are driven with signals derived from recorded eye movements. Although this device is likely to improve vision in patients with acquired nystagmus, it may not help individuals with infantile nystagmus syndrome. Video displays, including miniaturized portable screens, are now an important part of our lives, especially the lives of our children, who are enchanted by video games. Dr. Tabuchi documents the potential effects of video displays on the response to near viewing by children, of whom 20% show abnormal pupillary responses.

The third section, “New Therapies for Congenital Nystagmus,” applies basic studies to develop a range of new therapies. Dr. Gottlob reports linkage to chromosome Xq26-q27 in patients with idiopathic congenital nystagmus, leading to detection of a novel gene; she also reports that both memantine and gabapentin suppress some forms of infantile nystagmus and support modest improvement of vision. Better identification of genotypes of infantile nystagmus may ultimately enhance our ability to treat individual patients. Dr. Dell’Osso summarizes his singular contributions to several approaches to treating infantile forms of nystag- mus—the importance of reliable measurements, the use of these measurements to predict potential visual acuity, and evaluation of tenotomy and resuture surgical therapies in clinical trials. Dr. Hertle provides the results of a large study of such surgical treatment of those patients with infantile forms of nystagmus that periodically reverse direction. Dr. Tomsak provides a summary of preliminary studies of tenotomy-and-resuture surgical therapies for acquired pendular and downbeat forms of nystagmus, with promising results in three patients. Finally, Dr. Kaminski and colleagues provide a molecular biological approach to the treatment of a disorder that commonly causes double vision—myasthenia gravis—suggesting that complement inhibitor drugs may usher in a new therapeutic approach.

Dr. Dell’Osso’s legacy in training scientists is evident in the final section of this volume, “General Aspects of Normal and Abnormal Gaze Control,” which is a compendium of shorter contributions from some of his former students. These chapters deal with a broad range of aspects of normal gaze control, infantile nystagmus, and acquired disorders of eye movements, including new treatment measures. Further information about the conference and some supplementary material are available at the Daroff-Dell’Osso Ocular Motility Laboratory Web site (http://omlab.org).

We thank the Mt. Sinai Health Care Foundation and the Garson Fund for providing financial support for this conference-symposium. Robert Garson was a longtime member of the Board of Trustees at the Mt. Sinai Medical Center and University Hospitals of Cleveland. The fund was established by his family in his honor, and we thank the Garson family for their generous support. We are grateful to Ann Rutledge, who provided invaluable administrative assistance during the conference and the preparation of this volume. We would also like to take this opportunity to acknowledge support of research at the Daroff-Dell’Osso Laboratory by the U.S. Department of Veterans Affairs, the National Eye Institute, and the Evenor Armington Fund.

R. John Leigh, MD

Michael W. Devereaux, MD

July 2007

Contributors ix

Part I Basic Concepts of Stable Vision

and Gaze

1. Afferent and Efferent Contributions to Knowledge of Eye Position 3

EWA NIECHWIEJ-SZWEDO AND MARTIN J.

STEINBACH

2.Perceptual Influences of the Extraretinal Signals for Normal Eye Movements and

Infantile Nystagmus 11

HAROLD E. BEDELL, JIANLIANG TONG, SAUMIL S.

PATEL, AND JANIS M. WHITE

3. Perception with Unstable Fixation 23

RICHARD V. ABADI

4. Internal and External Influences on Foveation and Perception in Infantile

Nystagmus Syndrome 33

LARRY A. ABEL AND LINDA MALESIC

5. Perceptual Fading during Voluntary and Involuntary Eye Movements 42

FRANK A. PROUDLOCK, ASTRID Y. JORGENSEN,

AND IRENE GOTTLOB

Part II New Models and Techniques for Studying Gaze Stability

6.Alternating Saccades in a Primate Model of Strabismus 47

VALLABH E. DAS

7. Effects of Cerebellar Lesions in Monkeys on Gaze Stability 55

MARK F. WALKER, JING TIAN, XIAOYAN SHAN,

RAFAEL J. TAMARGO, HOWARD YING, AND

DAVID S. ZEE

8. Development of Visual Stabilization

Devices with Applications for Acquired and

Infantile Nystagmus 61

JOHN S. STAHL, IGOR S. KOFMAN, AND ZACHARY

C. THUMSER

9.Pupil Abnormalities of the Near Response in Children with Visual Display Terminal Syndrome 70

AKIO TABUCHI, ATSUSHI FUJIWARA, AND

MAHMOODI KHADIJA

Part III New Therapies for Congenital Nystagmus

10.Genetics and Pharmacological Treatment of Nystagmus: A Review of the Literature

and Recent Findings 79

IRENE GOTTLOB

RICHARD W. HERTLE, LEAH REZNICK,

DONGSHENG YANG, AND KIMBERLY ZOWORTY

viii

13.Eye Muscle Surgery for Acquired Forms of Nystagmus 112

ROBERT L. TOMSAK, LOUIS F. DELL’OSSO,

JONATHAN B. JACOBS, ZHONG I. WANG, AND

R. JOHN LEIGH

14.The Complement Hypothesis to Explain Preferential Involvement of Extraocular

Muscle in Myasthenia Gravis 117

HENRY J. KAMINSKI, YUEFANG ZHOU, JINDRICH

SOLTYS, AND LINDA L. KUSNER

CONTENTS

21.Posterior Internuclear Ophthalmoplegia of Lutz Revisited: Report of a Case

JANET C. RUCKER

Part IV General Aspects of Normal and

Abnormal Gaze Control

15. Studies of the Ability to Hold the Eye in Eccentric Gaze: Measurements in Normal Subjects with the Head Erect 129

JEFFREY T. SOMERS, MILLARD F. RESCHKE, ALAN H. FEIVESON, R. JOHN LEIGH, SCOTT J. WOOD, WILLIAM H. PALOSKI AND LUDMILA KORNILOVA

24.Involuntary Version-Vergence Nystagmus Induced by Ground-Plane Optic Flow: Analysis of Dynamic Characteristics of

Nystagmus Quick Phases 170

DONGSHENG YANG, MINGXIA ZHU, AND RICHARD W. HERTLE

25. The Neuro-ophthalmologic Complications

of Chiropractic Manipulation 175

16.Effect of Eye Exercise on Clinical Outcome of Noncompressive Ocular

MICHAEL W. DEVEREAUX

18.Extension of the eXpanded Nystagmus Acuity Function to Vertical and Multiplanar Data 143

JONATHAN B. JACOBS AND LOUIS F. DELL’OSSO

ARI Z. ZIVOTOFSKY, ADI BERCOVICH, JASON FRIEDMAN, EVA KELMAN, ELINOR SHINHERTZ, AND TAMAR FLASH

28.Multifocal Electroretinographic Study

of Patients with Oculocutaneous Albinism

and Infantile Nystagmus Syndrome 189

ELISA BALA, JONATHAN B. JACOBS, AND NEAL S.

PEACHEY

Index 193