Ординатура / Офтальмология / Английские материалы / Ocular Periphery and Disorders_Dartt, Bex, Amore_2011
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x Contributors
C Dorronsoro
Consejo Superior de Investigaciones Cientı´ficas, Madrid, Spain
Y Du
University of Pittsburgh, Pittsburgh, PA, USA
M C Edman
University of Southern California School of Pharmacy,
Los Angeles, CA, USA
C Evinger
SUNY Stony Brook, Stony Brook, NY, USA
P Fagerholm
Linko¨ping University Hospital, Linko¨ping, Sweden
B H Feldman
Philadelphia Eye Associates, Philadelphia, PA, USA
M E Fini
University of Southern California, Los Angeles, CA, USA
T H Flynn
Moorfields Eye Hospital, London, UK
G Frank
University of Pittsburgh School of Medicine, Pittsburgh,
PA, USA
T A Fuchsluger
Schepens Eye Research Institute, Boston, MA, USA
J L Funderburgh
University of Pittsburgh, Pittsburgh, PA, USA
M Fung
University of Minnesota, Minneapolis, MN, USA
P D R Gamlin
University of Alabama at Birmingham, Birmingham,
AL, USA
S Garg
University of California, Irvine, Irvine, CA, USA
K Gentil
University of Bonn, Bonn, Germany
M Ghannoum
Case Western Reserve University, Cleveland, OH, USA
A Ghosh
University of Missouri–Columbia, Columbia, MO, USA
G M Gordon
University of Southern California, Los Angeles,
CA, USA
M S Gregory
Schepens Eye Research Institute, Harvard Medical
School, Boston, MA, USA
M Griffith
University of Ottawa Eye Institute, Ottawa, ON, Canada
J M Hackett
University of Ottawa, Ottawa, ON, Canada
S F Hamm-Alvarez
University of Southern California School of Pharmacy,
Los Angeles, CA, USA
P Hamrah
Harvard Medical School, Boston, MA, USA
E Harb
New England College of Optometry, Boston,
MA, USA
S Hariharan
University of Missouri–Kansas City, Kansas City,
MO, USA
S Hastings-Cowden
University of Athens, Athens, GA, USA
L D Hazlett
Wayne State University School of Medicine, Detroit,
MI, USA
R Hendricks
University of Pittsburgh School of Medicine, Pittsburgh,
PA, USA
R R Hodges
Schepens Eye Research Institute, Boston, MA, USA
Y Imamura
Case Western Reserve University, Cleveland, OH, USA
U V Jurkunas
Schepens Eye Research Institute, Boston, MA, USA
W W-Y Kao
University of Cincinnati, Cincinnati, OH, USA
P K Karla
University of Missouri–Kansas City, Kansas City,
MO, USA
S C Kaufman
University of Minnesota, Minneapolis, MN, USA
S Khanal
University of Western Sydney, NSW, Australia
S Kinoshita
Kyoto Prefectural University of Medicine, Kyoto,
Japan
J Knicklebein
University of Pittsburgh School of Medicine, Pittsburgh,
PA, USA
E Knop
Charite´ – Universita¨tsmedizin Berlin, Berlin, Germany
N Knop
Hannover Medical School, Hannover, Germany
N Koizumi
Kyoto Prefectural University of Medicine, Kyoto, Japan
N Kramarevsky
University of Minnesota, Minneapolis, MN, USA
Contributors xi
D F P Larkin
Moorfields Eye Hospital, London, UK
S Leal
Case Western Reserve University, Cleveland,
OH, USA
R J Leigh
Case Western University, Cleveland, OH, USA
D M Levi
University of California, Berkeley, Berkeley, CA, USA
C-Y Liu
University of Cincinnati, Cincinnati, OH, USA
H Liu
University of Cincinnati, Cincinnati, OH, USA
L Llorente
Consejo Superior de Investigaciones Cientı´ficas, Madrid, Spain
Q Lu
Schepens Eye Research Institute, Boston, MA, USA
R R Marchelletta
University of Southern California School of Pharmacy,
Los Angeles, CA, USA
S Marcos
Consejo Superior de Investigaciones Cientı´ficas, Madrid, Spain
C F Marfurt
Indiana University School of Medicine – Northwest, Gary,
IN, USA
L McCann
Glasgow Caledonian University, Glasgow, UK
A M McDermott
University of Houston, Houston, TX, USA
D H McDougal
University of Alabama at Birmingham, Birmingham,
AL, USA
K C McKenna
University of Pittsburgh, Pittsburgh, PA, USA
L K McLoon
University of Minnesota, Minneapolis, MN, USA
J Merayo-Lloves
Consejo Superior de Investigaciones Cientı´ficas, Madrid, Spain
T J Millar
University of Western Sydney, NSW, Australia
A K Mircheff
University of Southern California, Los Angeles,
CA, USA
A K Mitra
University of Missouri–Kansas City, Kansas City,
MO, USA
R R Mohan
University of Missouri–Columbia, Columbia, MO, USA
M Momany
University of Athens, Athens, GA, USA
P Mudgil
University of Western Sydney, NSW, Australia
P Mukherjee
Case Western Reserve University, Cleveland, OH, USA
J Y Niederkorn
University of Texas Southwestern Medical Center,
Dallas, TX, USA
T Nishida
Yamaguchi University Graduate School of Medicine,
Yamaguchi, Japan
D M Noden
Cornell University, Ithaca, NY, USA
R M M A Nuijts
University Hospital Maastricht, Maastricht, The
Netherlands
F P Paulsen
Martin Luther University Halle-Wittenberg, Halle,
Germany
E Pearlman
Case Western Reserve University, Cleveland, OH, USA
S C Pflugfelder
Baylor College of Medicine, Houston, TX, USA
M A Rafat
University of Ottawa Eye Institute, Ottawa, ON, Canada
D Raja
University of Minnesota, Minneapolis, MN, USA
B Regenfuss
Friedrich-Alexander University Erlangen-Nuernberg,
Erlangen, Germany
P S Reinach
The State University of New York, New York, NY, USA
J E Schechter
University of Southern California, Los Angeles, CA, USA
A Serra
University of Sassari, Sassari, Italy
A Sharma
University of Missouri–Columbia, Columbia, MO, USA
C Siddappa
University of Missouri–Columbia, Columbia, MO, USA
S P Srinivas
Indiana University, Bloomington, IN, USA
F Stapleton
University of New South Wales, Sydney, NSW,
Australia
xii Contributors
R F Steinert
University of California, Irvine, Irvine, CA, USA
M A Stepp
The George Washington University Medical Center,
Washington, DC, USA
M E Stern
Allergan Inc, Irvine, CA, USA
Y Sun
Case Western Reserve University, Cleveland, OH, USA
L Szczotka-Flynn
Case Western Reserve University, Cleveland, OH, USA
Elizabeth A Szliter-Berger
Wayne State University School of Medicine, Detroit,
MI, USA
N G Tahzib
University Hospital Maastricht, Maastricht, The
Netherlands
R S Talluri
University of Missouri–Kansas City, Kansas City,
MO, USA
A Tarabishy
Case Western Reserve University, Cleveland,
OH, USA
A W Taylor
Schepens Eye Research Institute, Boston, MA, USA
A Tomlinson
Glasgow Caledonian University, Glasgow, UK
F A Vera-Diaz
Schepens Eye Research Institute, Harvard Medical
School, Boston, MA, USA
R D Vicetti Miguel
University of Pittsburgh, Pittsburgh, PA, USA
D W Warren
University of Southern California, Los Angeles, CA, USA
D R Whikehart
The University of Alabama at Birmingham, Birmingham,
AL, USA
T Wojno
The Emory Clinic, Atlanta, GA, USA
Y Wu
Institute for Eye Research, Sydney, NSW, Australia
F Zhang
The State University of New York, New York, NY, USA
D Zoukhri
Tufts University, Boston, MA, USA
INTRODUCTION
Protection of the entire eye from the external environment and maintenance of a clear optical pathway through the aqueous humor, lens, and vitreous to the retina are the functions of the ocular periphery. The outermost portion of the periphery is the eyelids that protect the eye through blinking and preserve visual acuity through the movement of the eye by the exceedingly specialized extraocular muscles. The next layer of protection is the tear film, secreted by the ocular adnexa, and the epithelia of the ocular surface, composed of the cornea and conjunctiva. The tears and ocular surface epithelia protect the eye through numerous coordinating layers of structural and functional mechanisms. The tears and cornea also must retain their transparency and maintain a smooth optical surface. Dysfunction and dysregulation of the ocular periphery in disease can compromise the entire visual system and lead to loss of visual acuity, inflammation, and infection, thus jeopardizing the function of the entire eye and, in severe cases, cause loss of vision. This book focuses on both the normal functioning of the tissues of the ocular periphery and their pathophysiology in disease. This volume provides a unique collection of chapters on the multiple, diverse tissues that comprise the ocular periphery and function to protect vision.
The goal of this book is to provide a comprehensive and contemporary review of the structure and function of the ocular periphery in health and disease. The book is organized into four sections including I. Extraocular and Eyelid Muscles: Structure, Function, and Pathophysiology, II. Structure and Function of the Tear Film, Ocular Adnexa, Cornea, and Conjunctiva in Health and Pathogenesis in Disease, III. Immune Regulation of the Cornea and Conjunctiva and Its Dysregulation in Disease, and IV. Visual Acuity Related to the Cornea and Its Disorders.
Section I is devoted to the extraocular muscles and the eye lids, the muscles that move the eye and the lids. Chapters include several chapters on the anatomy, function, metabolism, and pathophysiology of the specialized extraocular muscles, along with a chapter on eyelid function and pathophysiology. Final chapters discuss diseases of the extraocular muscles and the clinical diagnosis of the dysfunction of these muscles. The authors have particularly highlighted the special features of the extraorbital muscles that allow them to function without fatiguing, unlike other skeletal muscles as well as specific diseases that preferentially spare or involve these muscles critical for binocular vision.
Section II focuses on two major areas: first, the tear film and the tissues that secrete it and second, the epithelia (cornea and conjunctiva) that form the anterior surface of the eye. Initial chapters in this section focus on the multiple components of the complex tear film and the mechanisms by which they are secreted by the meibomian gland, lacrimal gland, and conjunctiva. The next chapters discuss the structure and function of the conjunctiva and the three layers of the cornea, each of these layers with its specialized functions to maintain the clarity of the cornea while protecting the eye from mechanical, thermal, chemical, and pathogenic challenges of the external environment. Additional chapters in this section focus on corneal disease as well as new modalities for understanding ocular surface dysfunction and repairing this dysfunction.
Section III highlights the unique mechanisms that the cornea uses to respond to immune and infectious challenges. Multiple chapters focus on different aspects of the immune and angiogenic privilege of the cornea that is unique to this tissue, and compare it with the more ‘‘normal’’ response of the conjunctiva. The many facets of the complex immune response of the cornea are presented. In addition, the multiple mechanisms that are responsible for the avascularity of the cornea are discussed. Another theme of this section is inflammation and its involvement with dry eye disease and infectious diseases of the ocular surface.
All together, sections I, II, and III present the multiple layers of structure and diverse overlapping mechanisms that are in place to prevent breach of the interior of the eye by mechanical, thermal, chemical, and pathogenic threats from the external environment and the diseases that result when these defenses are overwhelmed.
Section IV is devoted to the cornea, but in this section, the visual acuity of the cornea is highlighted. Chapters discuss normal visual optics and the conditions that result from changes in corneal shape that disrupt the visual axis and lead to decreased vision.
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xiv Introduction
Each chapter contains text readable to a scientist outside the field of the article, multiple multimedia and color figures to illustrate the most important points of the chapter, and a list of references to provide more in-depth information. Chapters are primarily directed at scientists looking for an entry point into a field tangential to their specialty as well as at graduate students and postdoctoral fellows in eye research. The chapters will be especially useful to scientists designing introductory or generalized courses that cover diverse fields of eye research. Scientists writing review articles or chapters will also find the book’s chapters especially useful as a starting point. The many introductory chapters are written at the level to be understood by undergraduates at university and public libraries, but include enough information to satisfy the more advanced needs of graduate students and postdoctoral fellows. The in-depth chapters on more focused research areas are ideal for postdoctoral fellows and experienced scientists. The plentiful illustrations will be especially helpful in understanding the more complicated points as well as illustrating basic processes and anatomy.
Finally, I thank the other editors of this book who chose the chapters to be included in this book as well as the chapter authors who devoted considerable time to proof-reading these articles. I also thank all the authors for their excellent contributions and Robin R. Hodges for her excellent managerial assistance.
Darlene A. Dartt, Ph.D. Boston, MA USA October 24, 2010
I. EXTRAOCULAR AND EYELID MUSCLES: STRUCTURE, FUNCTION, AND PATHOPHYSIOLOGY
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Eyelid Anatomy and the Pathophysiology of Blinking
C Evinger, SUNY Stony Brook, Stony Brook, NY, USA
ã 2010 Elsevier Ltd. All rights reserved.
Glossary
Blepharospasm – A dystonic muscle contraction disorder characterized by forceful, bilateral, and uncontrolled closure of the eyelids.
Hemifacial spasm – A muscle contraction disorder characterized by forceful uncontrolled contraction of the facial muscles on one side of the face.
Levator palpebrae superioris muscle – A skeletal muscle innervated by cranial motor nerve 3 whose primary function is elevation of the upper eyelid. Mu¨ller’s muscle – A smooth muscle that runs from the inferior surface of the tendon of the levator palpebrae superioris to insert into the tarsal plate. It receives sympathetic nervous system innervation.
Omnipause neurons – Part of the brainstem neural circuit that controls saccades. These neurons fire during fixation and cease firing before and during saccadic movements. Stimulation of omnipause neurons interrupts saccades.
Orbicularis oculi muscle – A circumferential muscle of facial expression innervated by the facial nerve that lies just deep to the skin within both eyelids as well as the surrounding bones of the orbital margin. Its main function is closure of the eyelid.
Paresis – Partial paralysis of a skeletal muscle resulting in muscle weakness.
Retractor bulbi muscle – Skeletal muscles innervated by cranial nerve 6 whose function is to retract the eyeball into the orbit causing movement of the nictitating membrane over the surface of the eye.
Saccades – Rapid eye movements that redirect the line of sight so that the image of interest falls on the fovea of the retina.
Vergence – The coordinated movements of both eyes in opposite directions in order to maintain binocular vision.
Organization of the Eyelid System
To understand the neural control of eyelids, the basis of neurological diseases affecting eyelid control, and how the
eyelids protect the eye, think about the evolutionary origins of eyelids. For fish, a class of vertebrates without eyelids, eye protection primarily requires avoiding objects hitting and damaging the cornea. To avoid objects hitting the eyeball, fish retract their eyes into the orbit by co-contracting their extraocular muscles. Thus, cornea protection was initially linked to neural circuits whose primary goal was to move the eye. When vertebrates moved onto the land, the development of eyelids was a critical step in reducing the dehydrating effects of air on the cornea. Although goblet cells, lacrimal and meibomian glands produce the fluids to coat the corneal surface, it is blinking of the eyelid that spreads the tears to restore the tear film, which maintains corneal hydration. In addition, blinking removes small objects from the surface of the eye and provides some protection from objects getting into the eye. Although blinking is essential for maintaining the cornea, lid closure has the undesirable side effect of blocking vision. Thus, an eyelid control system must generate blinks that minimally disrupt vision while adequately protecting the cornea. The nervous system deals with this constraint by developing fast eyelid closure and opening without carefully controlling absolute eyelid position. The other restriction on the nervous system’s management of the eyelids is that they must move synchronously with vertical eye movements to avoid blocking vision. Overcoming this problem requires the nervous system to control eyelid position accurately. The eyelid control system accomplishes this feat by linking itself to the eye movement system. The melding of the eyelid system with the eye movement system reveals itself first in the anatomical organization of the eyelids.
Only four forces act on the upper eyelid (Figures 1(a) and 2). (1) The phasically active orbicularis oculi (OO) muscle actively closes the eyelid. The ipsilateral facial (VII) nucleus innervates the OO muscle. (2) The tonically active levator palpebrae superioris (LP) muscle actively elevates the upper eyelid. LP innervation arises from the oculomotor (III) nucleus. (3) Raising the eyelid stretches the superior transverse (Whitnall’s) ligament and the lateral and medial canthal tendons to create a passive downward force. Thus, the lowest energy state for the eyelid is closed. (4) Mu¨ller’s smooth muscle (Figure 2), which bridges the belly and the tendon of the LP, raises the eyelid approximately 1.5 mm with sympathetic activation. Post-ganglionic nerves from the superior cervical ganglion innervate Mu¨ller’s muscle. The interaction between the first three forces (OO, LP, and passive downward forces) enables
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4 Extraocular and Eyelid Muscles: Structure, Function, and Pathophysiology
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Figure 1 Forces acting on the eyelid and mammalian blinking. (a) Opening the eye stretches the levator palpebrae (LP) aponeurosis (APO), the superior transverse ligament (Whitnall’s ligament, WL), and the medial and lateral canthal tendons (CT) to create passive downward forces. The lowest energy state for the eyelid system is closed. (b) Lid (Pos) lowering during a blink results from a transient relaxation of the LP followed by a phasic activation of the orbicularis oculi (OO) muscle. Raising the eyelid occurs as the LP resumes its tonic activity following the completion of OO activity. Gray indicates LP activity and black indicates OO activity. (c, d) Individual examples of a reflex blink evoked by stimulation of the supraorbital branch of the trigeminal nerve (SO ▲) for a human (c) and a guinea pig (d). R1 is the short latency response and R2 is the long latency response seen after nerve stimulation. Abbreviations: OOemg, orbicularis oculi EMG; Pos, upper eyelid position.
the eyelids to blink rapidly yet accurately match the vertical position of the eyeball.
The characteristic rapid eyelid closure of a blink followed by lid opening at approximately half the speed of lid closure follows directly from the anatomical organization of the eyelid (Figures 1(b)–1(d)). A blink begins with relaxation of the tonically active LP muscle. LP relaxation releases the passive downward forces to initiate lid closure. The phasically active OO muscle discharge combines with the passive downward forces to lower the eyelid rapidly. As the OO muscle relaxes, the LP muscle slowly resumes its tonic discharge. This LP contraction raises the upper eyelid. Eyelid elevation is slower than lid closure because the LP muscle must work against the passive downward forces. The point at which the tonically active LP force matches the passive downward force created by tendon and ligament stretching determines final lid position. This anatomical organization is conserved so that the pattern of blinking is similar among mammals (Figures 1(c) and 1(d)).
In contrast to the interactions between the OO and LP muscles and passive downward forces with blinking, the coordination of eyelid motion with vertical eye movement arises from the antagonistic interactions between the LP muscle and the passive downward forces. The linkage with eye movements occurs because the LP behaves like the superior rectus muscle, which rotates the eye upward. Embryologically, the LP muscle arises from the superior rectus muscle, and LP motor neurons are always adjacent to superior rectus motor neurons in the oculomotor nucleus. LP and superior rectus motor neurons exhibit similar patterns of activity except during a blink. The tonic firing frequency of superior rectus and LP motor neurons correlates with vertical eye position. With an upward saccadic eye movement, superior rectus and LP motor neurons generate a burst of action potentials followed by an increased tonic firing frequency that holds the eye in the new elevated position. A downward saccade results from a cessation of tonic activity followed by a lower frequency tonic discharge to hold the eye in the
Eyelid Anatomy and the Pathophysiology of Blinking |
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Figure 2 Montage of a sagittal section of the eyelid from an adult rabbit stained with hematoxylin and eosin. Courtesy of Dr. Linda K. McLoon.
depressed position. When the LP motor neurons transiently cease discharging during a downward saccadic eye movement, unopposed passive downward forces lower the eyelid. When the LP motor neuron resumes its activity at a lower tonic firing frequency, the new balance point between passive downward forces and active upward LP muscle force establishes the final eyelid position. With an upward eye movement, the increased LP motor neuron firing frequency pulls the eyelid upward until the LP muscle and passive downward forces match. Although it seems counter-intuitive that passive downward forces rather than the OO muscle act as the antagonist to the LP muscle with eye movements, it is clear that the OO does not participate in eyelid movement with vertical saccades. For example, individuals with OO denervation created by seventh nerve palsy exhibit nearly normal saccadic lid movements with vertical saccadic eye movements, but abnormally slow blinks.
Further evidence of the evolutionary linkage of blinking with the oculomotor system is that blinks frequently occur with saccadic eye movements. These gaze-evoked blinks most commonly accompany large saccades to visual targets that do not have a strong behavioral significance. The advantage of combining blinks with saccades is that visual suppression occurs during both blinks and saccades. A gaze-evoked blink refreshes the tear film,
but does not produce more loss of vision than the saccadic eye movement. The evolutionary linkage also appears in the eye movements associated with blinking, blink-evoked eye movements. When looking straight ahead, there is an adducting and downward rotation of the eye with each blink. Nevertheless, the state of the eyelid system determines the trajectory of blink-evoked eye movements. These movements exhibit an upward trajectory in both eyes and are smaller than normal in individuals with a unilateral seventh nerve palsy. Eyeball retraction is also a component of these blink-evoked eye movements. For mammals, the eyeball retraction with blinking results from extraocular muscle co-contraction and contraction of the retractor bulbi muscle. This accessory extraocular muscle is innervated by motor neurons in the accessory abducens nucleus that send their axons to the orbit as part of the VIth nerve. Extraocular muscle co-contraction with blinking in mammals appears to reflect the evolutionary origins of the eyelid control system from eye retraction of fish. Despite blink-evoked eye movements accompanying all blinks, neither gaze-evoked nor reflex blinks occurring with a saccade prevent the eye from achieving its desired endpoint. With a simultaneous blink and saccade, the eyes follow a complex trajectory instead of the nearly straight path of a saccadic eye movement alone. This complex