Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

When I was invited to write the Foreword for this sixth edition of Yano and Fine’s Ocular Pathology, by Myron Yano and

Joseph W. Sassani, I felt honored considering that those who have authored the Foreword for the prior editions were amongst the “masters”of academic ophthalmology and ophthalmic pathology, namely Drs. Morton E. Smith, J. Donald M. Gass, Frederick A. Jakobiec, Paul Henkind, Harold G. Scheie, and Lorenz E.

Zimmerman.

This textbook is one of the few in my 35 years of practice of ophthalmology and ophthalmic pathology that I have obtained from the immediate availability of each edition, since it first was published in 1975, both for my clinical o ce and for my ophthalmic pathology research laboratory that is inhabited by my fellows,residents,and medical students.Furthermore,the authors, originally Myron Yano and Ben Fine, and now including Joe Sassani, have been both career-long colleagues and very close friends of mine, mainly as a result of the frequent crossing of our paths at multiple annual academic meetings; these events almost always include our spouses, giving us a feeling of family with the elite in our field.

As expressed by the writers of the Foreword of the previous editions, Ocular Pathology is without a doubt the best current ophthalmic pathology textbook, being a combination of a well organized review text presented in point-like fashion and an atlas with an extensive number of color photographs of most of the described ophthalmic conditions. Furthermore, it is one of the few textbooks on this important subject that is consistently being updated with the latest clinical and pathologic information including more recent “avant-garde” disciplines associated with ophthalmic pathology such as the corresponding advances in molecular genetics.

The names, “Yano ” and “Fine” as co-authors of major textbooks in academic ophthalmology are indicative of a fruitful “marriage” of two of the most outstanding contributors to our knowledge of ophthalmic pathology during the past four decades. These two individuals have shared their extensive experience involving two di erent approaches to this discipline, namely histopathology and electron microscopy respectively, in a continuous, composite fashion almost unmatched in academic

ophthalmology.

Dedicating this sixth edition of Ocular Pathology as a tribute to the late Ben S. Fine is most appropriate. Ben, a fellow Canadian, was a pioneer of the electron microscopic examination of ocular tissues. It was my good fortune that Ben’s academic o ce was directly across from my cubicle during my fellowship at the Armed Forces Institute of Pathology (AFIP) during the early 1970’s. From Ben I learned not only the basics of electron microscopy, which I still practice today, but also his approach to ocular diseases utilizing uniquely clear thought processes. Ben was always available to share his expertise and gave the premier course on the

ultrastructure of normal ocular tissues for several decades in addition to his publications on the electron microscopic findings of numerous pathologic ocular disease processes.

Myron Yano has demonstrated amazing energy, dedication and proficiency in the development of this text while serving both as director of ophthalmic pathology and as a most successful chair of the Department of Ophthalmology, currently at

Drexel University in Philadelphia. During the past 4 decades,

Myron has been a full professor of both ophthalmology and pathology; his distinguished career was culminated by his being the recipient of the American Academy of Ophthalmology’s

Zimmerman Gold Medal just prior to the onset of the 21st century. I take my hat o to his continuous productivity and to his seeing to it that this “jewel” in academic ophthalmology is being perpetuated.

The addition of Dr. Joe Sassani as a co-author is a masterful step forward to ensure the continuity of this most important textbook in ophthalmic pathology. Joe is a disciple of Myron

Yano who has evolved to be one of the leaders in the field of ophthalmic pathology including having served as president of the

American Association of Ophthalmic Pathologists. Joe is director of ophthalmic pathology and professor of ophthalmology and pathology at the Milton Hershey Medical Center in Hershey

Pennsylvania. He also provides additional perspective in his fields of clinical expertise including glaucoma. Having this relatively youthful star participate in the authorship should ensure the continuation of this invaluable resource especially since Joe has broad academic shoulders with a strong reputation of responsibil-

ity and commitment.

Ocular Pathology is most highly recommended for all residents in ophthalmology and fellows in ophthalmic pathology and is an excellent resource for medical students, general pathologists who review ocular specimens, and ophthalmologists who desire to fulfill their academic curiosity. It provides very succinctly the basics of ophthalmic pathology and includes the key information on almost every described ophthalmological disease process with an extensive reference list to enable more elaborate further studies. I would like to express “Bravo” to the authors for providing this update of their masterpiece from which so many will benefit.

Seymour Brownstein, MD FRCSC

Les Amis Chair in Vision Science

Professor, Departments of Ophthalmology

and Laboratory Medicine (Pathology)

Director, Ophthalmic Pathology Laboratory

University of Ottawa Eye Institute

T e Ottawa Hospitalh / University of Ottawa

Ottawa Health Research Institute

Ottawa, Ontario, Canada

During the year of the observance of the 100th anniversary (1874–1974) of the University of Pennsylvania’s Department of Ophthalmology, it is exciting to have the publication of a volume whose coauthors have contributed significantly to the strides in ocular pathology taken by the Department in the past several years.

Myron Yano , a highly regarded member of our sta , began a residency in ophthalmology in 1962, upon graduating from the

University’s School of Medicine. The residency continued for the next five years, during the first two of which he also held a residency in the Department of Pathology. His keen interest and ability in ocular pathology were readily apparent, and I encouraged him to apply for a fellowship at the Armed Forces Institute of Pathology (AFIP), Washington, DC. From July, 1964, through June, 1965, he carried out exceptional research at the AFIP in both ophthalmology and pathology. He returned to our Department in July, 1965, where the caliber both of his clinical and research work was of the highest. When he completed his residency in June, 1967, I invited him to join the sta , and he has recently attained the rank of full professor. During the ensuing years he has contributed substantially to the literature, particularly in the fields of ophthalmic and experimental pathology.

He is Board certified in ophthalmology and in pathology.

Ben Fine, noted for his work in electron microscopy at AFIP and at George Washington University, has shared his expertise in the field through lectures presented as part of the curriculum of the annual 16-week Basic Science Course in the Department’s graduate program.

It can be said that 100 years ago ophthalmology was a specialty that had been gradually evolving during the preceding 100 years, dating from the time of the invention of bifocals by Benjamin Franklin in 1785. Few American physicians of that era, however, knew how to treat diseases of the eye, but as medical education became more specialized it was inevitable that ophthalmology would also become a specialty.

With the invention of the ophthalmoscope in 1851, great advances were made in the reaching and practice of ophthalmology. This contributed greatly, of course, to setting the scene for the establishment of the University’s Department of Ophthalmology. It was on February 3, 1874, that Dr. William F. Norris was elected First Clinical Professor of Diseases of the Eye. Similar chairs had been established earlier in only three other institutions. The chair at the University of Pennsylvania later became known as the William F. Norris and George E. de Schweinitz Chair of Ophthalmology.

Both Dr. Norris and Dr. de Schweinitz actively engaged in the study of ocular pathology. Dr. Norris stressed the importance

of the examination of the eye by microscopy and of the correlation of findings from pathology specimens with the clinical signs.

Dr. de Schweinitz was instrumental in having a member of his sta accepted as ophthalmic pathologist with the Department of Pathology.

In the years that followed under succeeding chairmen of the

Department, other aspects of ophthalmology were stressed.Then, in 1947, during the chairmanship of Dr. Francis Heed Adler, Dr. Larry L. Calkins was appointed to a residency. Dr. Calkins, like Dr. Yano , displayed a keen interest in ocular pathology. Accordingly, he was instrumental in its study being revitalized during the three years of his residency. Another resident, Dr. William

C. Frayer, who came to the Department in 1949, joined Dr.

Calkins in his interest in ocular pathology. Dr. Frayer received additional training in the Department of Pathology and then became the ophthalmic pathologist of the department.

The importance of ocular pathology was increasingly evident, but facilities for carrying out the work in the Department of

Ophthalmology were unfortunately limited. Until 1964, the pathology laboratory had been confined to a small room in the outpatient area of the Department. Then we were able to acquire larger quarters in the Pathology Building of the Philadelphia General Hospital located next door to the Hospital of the University of Pennsylvania. Although the building was earmarked for eventual demolition, the space was fairly adequate for research and also for conducting weekly ophthalmic pathology teaching conferences. Despite the physical aspects, we saw to it that Dr.

Yano and his team of workers had a well equipped laboratory.

During the next several years as I saw that my dream for an eye institute with facilities for patient care, reaching and research under one roof was to become a reality, I was delighted to be able to include prime space on the research floor for the ever enlarging scope of ocular pathology. In addition to all that Dr. Yano has had to build upon from the past tradition of our Department of Ophthalmology, I would like to think that the new facilities at the Institute have in some measure contributed to the contents of this excellent volume. With grateful appreciation, therefore, I look upon this book as the authors’ birthday present to the Department. From these same facilities, as Dr. Yano and Dr. Fine continue to collaborate, I can hope will come insights and answers for which all of us are ever searching in the battle against eye disease.

Harold G. Scheie, MD

Chairman, Department of Ophthalmology

University of Pennsylvania

Director, Scheie Eye Institute

From their earliest days in ophthalmology Myron Yano and

Ben Fine impressed me as exceptional students. As they have matured and progressed up the academic ladder, they have become equally dedicated and e ective teachers.Their anatomical studies of normal and diseased tissues have always been oriented toward providing meaningful answers to practical as well as esoteric clinical questions. Their ability to draw upon their large personal experience in clinical ophthalmology, ocular pathology, and laboratory investigation for their lectures at the Armed

Forces Institute of Pathology and at the University of Pennsylvania have contributed immeasurably to the success of those courses. Now they have used the same time-tested approach in assembling their material for this book. Beginning with their basic lecture outlines, then expanding these with just enough text to substitute for what would have been said verbally in lecture, adding a remarkable amount of illustrative material for the amount of space consumed, and then providing pertinent references to get the more ambitious student started in the pursuit of a subject, Drs. Yano and Fine have provided us with a sorely needed teaching aid for both the student and the teacher of ocular pathology. It should prove to be especially popular among

medical students and residents in both ophthalmology and ocular pathology. With it one gets good orientation from the wellconceived outlines and fine clinicopathologic correlations from the selection of appropriate illustrations.

It is with considerable pride and admiration that I’ve watched the evolution of the authors’ work and its fruition in the form of this latest book. I am proud that both authors launched their respective careers with periods of intensive study at the Armed

Forces Institute of Pathology and that ever since, they have remained loyal, dedicated, and highly ethical colleagues. I admire their youthful energy, their patient, careful attitude, their friendly cooperative nature, and their ability to get important things accomplished. I’m appreciative of this opportunity to express my gratitude for the work they have been doing. If it is true that “by his pupils, a teacher will be judged,” I could only wish to have had several dozen more like Drs. Yano and Fine.

Lorenz E. Zimmerman, MD

Chief, Ophthalmic Pathology Division

Armed Forces Institute of Pathology

Washington, DC

It has been 33 years since the first edition of OCULAR PATHOLOGY was published in 1975. At that time the book contained the basics of eye pathology, which still are very much current. New entities have appeared and have been incorporated into subsequent editions, as well as into this edition. The enormous recent explosion of information that has expanded our knowledge and understanding of ocular pathology has occurred mainly in the fields of genetics, immunohistochemistry, and molecular biology. Newer imaging techniques such ultrasound biomicroscopy and optical coherence tomography are bringing resolution approaching histopathologic techniques to the clinical setting. We have integrated the pertinent information from these fields into this sixth edition.

Among the numerous entities introduced into this sixth edition are De Barsy Syndrome; autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy, endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT) syndrome; dentatorubropallidoluysian atrophy; microdot stromal degeneration; corneal fibrosis syndrome; toxic anterior segment syndrome; laryngo-onycho-cutaneous (LOC or Shabbir) syndrome; conjunctivochalasis; nevus lipomatosus (pedunculated nevus); Laugier-Hunziker syndrome; melanoma-associated spongiform scleropathy; Knobloch Syndrome; Ma uci’s syndrome, malignant mesenchymoma; mantle cell lymphoma; congenital simple hamartoma of the retinal pigment epithelium; TNM (tumor, node, metastasis) classification; posterior microphthalmos; lymphedema–distichiasis syndrome; solitary spindlecell xanthogranuloma; arteriovenous malformation of the iris; retinal angiomatous proliferation; complications of LASIK surgery; fibrous hamartoma of infancy, and others.

Additionally, numerous existing topics have been updated. They include the classification system for retinoblastoma, genetic features of persistent hyperplastic primary vitreous, pathobiology of Norrie’s disease, multiple new insights into the pathology of incontinentia pigmenti, anatomic and pathologic correlates in the cornea, immunopathology of Herpes keratitis, updated genetics of corneal dystrophies, new features of Schnyder’s corneal crystalline dystrophy (central stromal crystalline corneal dystrophy) and keratoconus, complications of retinal reattachment and glaucoma surgery, pathobiology of corneal abrasion; extensive revision of such topics as the anatomy of the conjunctiva, the pathobiology of vernal keratoconjunctivitis, and of graft-versus-host disease.

Other updated topics include the pathobiology of conjunctival and orbital lymphoma, squamous cell carcinoma of the conjunctiva, the genetics of pseudoexfoliation and uveal melanoma, and the inclusion of specific entities such as Fabry disease.

Particular attention has been directed at the pathobiology of diabetes mellitus. New and modified diabetes-related topics include the international clinical classification of diabetic retinopathy, diabetic, diabetic macular edema severity scales, and the role of VEGF and other factors in the pathobiology of diabetic complications.

Multiple changes and updates in Glaucoma include; syndromes associated with congenital glaucoma such as Hennekam syndrome, nail-patella syndrome, and familial amyloidotic polyneuropathy type I (Met 30).The pathobiology of myocilin/TIGR gene in the development of glaucoma has been revised and new clinical syndromes associated with angle-closure glaucoma have been added. The pathobiology of corticosteroid-induced glaucoma, and of glaucoma-associated damage to ocular tissues have been expanded. Latest features on the pathobiology of central corneal thickness as it relates to the development and diagnosis of glaucoma are discussed.

A unique feature, introduced in this 6th edition of OCULAR PATHOLOGY, is a DVD. It contains the contents of seven histopathology glass slides and the ImageScopeTM software required to view them. The software permits the observation of these virtual microscope slides on the computer video monitor by varying magnification, field of observation, etc. just as could be done with an optical microscope. Also included on the DVD, are all of the images from the book, which are searchable and able to be exported to HTML/PowerPoint slide shows.

Finally, all illustrations have been digitally enhanced and color corrected. New tables and numerous updated references have been added.

This book could not have been completed without the understanding and patience of our wives Karin L. Yano , Ph.D. and Gloria Sassani, M.A. We also wish to acknowledge the help of our assistants, William F. Devers and Sharon Dunkle. Finally, the members of the Elsevier production and editorial team including Russell Gabbedy and Sharon Nash, and also Bryan Potter,

Charles Gray and William Veltre have provided invaluable help and guidance in the production of this 6th edition of OCULAR PATHOLOGY.

The fifth edition of this book was dedicated to the memory of Fruma I. Fine, the wife of Ben S. Fine, the long-time coauthor of this book. Now Ben is no longer with us but his memory, so vivid, lives on as an inspiration to the multitude of people trained by him, and also to those who have been educated by him through his seminal writings. Ben was one of the earliest pioneers in the

field of ocular electron microscopy, first clarifying in exquisite

detail the normal anatomy of the eye, then elucidating the mysteries of numerous ocular pathological entities. His groundbreaking discoveries remain unchallenged as some of the finest work done in the field, and we miss him always. We dedicate this sixth edition to his memory, for his spirit lives on in the pages of this book and in the minds and souls of his peers and students.

INFLAMMATION

Definition*

I.Inflammation is the response of a tissue or tissues to a noxious stimulus.

A.The tissue may be predominantly cellular (e.g., retina), composed mainly of extracellular materials (e.g.,cornea), or a mixture of both (e.g., uvea).

B.The response may be localized or generalized, and the noxious stimulus infectious or noninfectious.

II.In a general way, inflammation is a response to a foreign stimulus that may involve specific (immunologic) or nonspecific reactions. Immune reactions arise in response to specific antigens, but may involve specific components

(e.g., antibodies, T cells) or nonspecific components [e.g., natural killer (NK) cells, lymphokines].

Causes

I.Noninfectious causes.

A.Exogenous causes: originate outside the eye and body, and include local ocular physical injury (e.g., penetrating perforating trauma, radiant energy), chemical injuries (e.g., alkali), or allergic reactions to external antigens (e.g., conjunctivitis secondary to pollen).

*Inflammation is not synonymous with infection. Inflammation may be caused by an infection (e.g., postoperative staphylococcal endophthalmitis), but it may also be caused by noninfectious agents, such as chemical burns. Conversely, infection is not always accompanied by significant inflammation. For example, in certain diseases of the immune system, widespread infection may be present, but the patient is incapable of mounting an inflammatory response.

B.Endogenous causes: sources originating in the eye and body, such as inflammation secondary to cellular immunity [phacoanaphylactic endophthalmitis (phacoantigenic uveitis)]; spread from continuous structures

(e.g., the sinuses); hematogenous spread (e.g., foreign particles); and conditions of unknown cause (e.g., sarcoidosis).

II.Infectious causes include viral, rickettsial, bacterial, fungal, and parasitic agents.

Phases of Inflammation

I.Acute (immediate or shock) phase (Fig. 1.1).

A.Five cardinal signs: (1) redness (rubor) and (2) heat

(calor)—both caused by increased rate and volume of blood flow; (3) mass (tumor)—caused by exudation of

fluid (edema) and cells; (4) pain (dolor) and (5) loss of function (functio laesa)—both caused by outpouring of fluid and irritating chemicals.

B.The acute phase is related to histamine release from mast cells and factors released from plasma (kinin, complement, and clotting systems).

Without a continuous stimulus the phase is transient, lasting from 3 to 5 hours. Chemical mediators,* whether directly or indirectly, cause smooth-muscle contraction (arteriolar constriction) and a local increase in vascular permeability. The chemical mediators seem to increase vascular permeability by causing the usually “tight” junctions between adjacent ocular vascular endothelial cells (especially in venules) to open, thereby allowing luminal fluid to leak into the surrounding tissue spaces.

*The chemical mediators include, but are not limited to, histamine, serotonin, kinins, plasmin, complement, prostaglandins, and peptide growth factors.

1.Histamine is found in the granules of mast cells, where it is bound to a heparin–protein complex; it is also present in basophils and platelets.

2.The kinins are peptides formed by the enzymatic actin of kallikrein on the α2-globulin kininogen.

Kallikrein is activated by the coagulation factor XII, the Hageman factor, or by plasmin.

3.Plasmin, the proteolytic enzyme responsible for

fibrinolysis, has the capacity to liberate kinins from their precursors and probably to activate kallikrein, which brings about the formation of plasmin from plasminogen.

4.The complement system consists of at least nine discrete protein substances. Complement achieves its e ect through a cascade of the separate components working in special sequences (Fig. 1.2).

At least two pathways exist for the activation of the complement system. The classic pathway is activated by immune complexes of the immunoglobulin M (IgM; macroglobulin) or IgG type. Another pathway is activated by aggregates of IgA, polysaccharides, lipopolysaccharides, or cell-bound IgG. The biologic functions of the complement components include histamine release, facilitation of phagocytosis of foreign protein, generation of anaphylatoxins (which leads to vasodilatation), immune adherence or fixation of an organism to a cell surface, polymorphonuclear leukocyte (PMN) chemotaxis, and lysis of bacteria, red cells, and so forth. Complement, therefore, plays a key role in the inflammatory process.

5.Prostaglandins, which have both inflammatory and anti-inflammatory e ects, are 20-carbon, cyclical, unsaturated fatty acids with a 5-carbon ring and 2 aliphatic side chains.

6.Major histocompatibility complex (MHC), called the human leukocyte antigen (HLA) complex in humans, is critical to the immune response.

a.HLAs are present on most nucleated cells of the body.

The HLA region is on autosomal chromosome 6. In practice, the blood lymphocytes are the cells tested for HLA.

b.The five genetic loci belonging to HLA are designated by letters following HLA. Thus, HLA- A and HLA-B indicate loci A and B, and so forth (HLA-C, HLA-D, and HLA-DR).

c.Individual alleles of each locus (and the corresponding specificities) are designated by numbers following the locus letter; thus HLA-B 35 indicates allele 35 on locus B.

d.A tentatively identified specificity carries the additional letter “W” (workshop) and is inserted between the locus letter and the allele number, e.g., HLA-BW 15.

e.The HLA system is the main human leukocyte isoantigen system and the major human histocompatibility system.