20 TH EDITION
`
`Remington: The
`Science and
`Practice
`of Pharmacy
`
`ALFONSO R GENNARO
`Chairman of the Editorial Board
`and Editor
`
`SENJU EXHIBIT 2008
`MYLAN v. SENJU
`IPR2016-00626
`
`Page 1 of 21
`
`

`
`Editor: D aniel Limmer
`Managing Editor: Matthew J. Hauber
`Marketing Manager: Anne Smith
`
`Lippincott Williams & Wilkins
`
`351 West Camden Street
`Baltimore, Maryland 21201-2436 USA
`
`227 E ast Wa~:;hington Square
`Philadelphia, PA 19106
`
`All rights reserved. This book is protected by copyright. No part of this book may
`be reproduced in any form or by any means, including photocopying, or utilized
`by any information storage and retrieval system without written permission
`from the copyright owner.
`
`The publisher is not responsible (as a matter of product liability, negligence or
`otherwise) for any injury resu lting from any material contained herein. This
`publication contains information relating to general principles of medical care
`which should not be construed as specific instructions for individual patients.
`Manufacturers' product information and package inserts should be reviewed for
`current information, including contraindications, dosages and precautions.
`
`Printed in the United States of America
`
`Entered according to Act of Con gress, in the year 1885 by Joseph P Remington,
`in the Office of the Librarian of Congress, at Washington DC
`
`Copyright 1889, 1894, 1905, 1907, 1917, by Joseph P Remington
`
`Copyright 1926, 1936, by the Joseph P Remington Estate
`
`Copyright 1948, 1951, by the Philadelphia College of Pharmacy and Science
`
`Copyright 1956, 1960, 1965, 1970, 1975, 1980, 1985, 1990, 1995, by the Phila(cid:173)
`delphia College of Pharmacy and Science
`
`Copyright 2000, by the University of the Sciences in Philadelphia
`
`All Rights Reserved
`Library of Congress Catalog Card Information is available
`ISBN 0-683-3064 72
`
`The publishers have made every effort to trace the copyright holders for borrowed
`material. If they have inadvertently overlooked any, they will be pleased to make
`the necessary arrangements at the first opportunity.
`
`The use of structural formulas from USAN and the USP Dictionary of Drug
`Names is by permission of The USP Convention. The Convention is not respon(cid:173)
`sible for any inaccuracy contained herein.
`Notice- This text is not intended to represent, nor shall it be interpreted to be, the
`equivalent of or a substitute for the official United States Pharmacopeia (USP)
`and/or the National Formulary (NF). In the event of any difference or discrep(cid:173)
`ancy between the current official USP or NF standards of strength, quality,
`purity, packaging and labeling for drugs and representations of them herein, the
`context and effect of the official compendia shall prevail.
`
`To purchase additional copies of this book call our customer service department
`at (800) 638-3030 or fax orders to (301) 824-7390. International customers
`should call (301) 714-2324.
`
`02 03 04
`2 3 4 56 7 8 9 10
`
`Page 2 of 21
`
`

`
`Remington: The Science and Practice of Pharmacy . . . A treatise on the theory
`and practice of rhe pharmaceutical sciences, with essential
`information about pharmaceutical and medicinal agents; also, a
`guide to the professional responsibilities of the pharmacist as the
`drug information specialist of the health ream . . . A texrbool~ and
`reference work for pharmacists, physicians, and other practitioners of
`the pharmaceutical and medico/ sciences.
`
`EDITORS
`
`Alfonso P. Gennaro, Choir
`
`Nicholas G Popovich
`
`Ara H Der Marderosian
`
`Glen P. Hanson
`
`Thomas Medwicl~
`
`P.oger L Schnaore
`
`Joseph [5 Schwartz
`
`H Steve White
`
`AUTHORS
`
`The 119 chapters of this edition of Remington were written by the
`
`editors, by members of the Editorial r5oord, and by the authors
`
`listed on pages viii to x.
`
`Managing Editor
`
`John E Hoover, GSc (Phorm)
`
`Editorial Assistant
`
`r5onnie Grighom Pad~er, P.NC, GA
`
`Director
`
`Philip P Gerbino 1995-2000
`
`Twentieth Edition- 2000
`
`Published in the 180th year of the
`PHILADELPHIA COLLEGE OF PHARMACY AND SCIENCE
`
`Page 3 of 21
`
`

`
`Preface to the First Edition
`
`The rapid and substantial progress made in Phaxmacy within
`the la<;t decade has created a necessity for a work treating of the
`imp,·ovcd apparatus, the revised processes, and the recently
`introduced preparations of the age.
`The vast advances made in theoretical and applied chemistry
`and p hysics have much to do with the development of pharma(cid:173)
`ceutical science, and these have been reflected in all the revised
`editions of the Phannacopoeias which have been recently pub(cid:173)
`lishe·d.When the author was elected in 1874 to the chair of
`Theory and Practice of Pharmacy in the Philadelphia College of
`Phannacy, the outlines of study which had been so carefully
`prepared for the classes by his eminent predecessors, Professor
`William Proctor, Jr, and Professor Edward Parrish, were found
`to be not strictly in accord, either in their arrangement of the
`subjects or in their method of treatment. Desiring to preserve the
`distinctive characterisi..ics of each, an effort was at once made to
`frame a system which should embody their valuable features,
`eml)l·ace new subjects, and still retain that harmony of plan and
`proper sequence which are absolutely essential to the success of
`any system.
`The strictly alphabetical classi.fication of subjects which is
`now universally adopted by phannacopocias and dispensato1ies,
`although admirable in works of reference, presents an effectual
`stumbling block to the acquisition of pharmaceutical knowledge
`through systematic study; the vast accumulation of facts col(cid:173)
`lected under each head arranged lexically, they necessarily have
`no connection with one another, and thus the saving of labor
`effected by considering similar groups together, and the value of
`the association of kindred subjects, are lost to the student.In the
`method of grouping the subjects which is herein adopted, the
`constant aim has been to arrange the latter in such a manner that
`the reader shall be gradually led from the consideration of ele(cid:173)
`ment.ary subjects to those which involve more advanced knowl(cid:173)
`edge, whilst the groups themselves are so placed a..'> to follow one
`another in a natural sequence.
`The work is divided into six parts. Part I is devoted to detailed
`descriptiom of apparatus and definitions and comments on gen(cid:173)
`eral phannaceulical processes.
`The Official Preparations alone are considered in Part II.
`Due weight and prominence are thus given to the Pharma(cid:173)
`copoeia, the National authority, which is now so thoroughly
`recognized.
`In order to suit the convenience ofpham1acists who prefer to
`weigh solids and measu1·e liq~tids, the official formulas are
`expressed, in addition to parts by weight, in avoir·dupois weight
`and apoth.ecari,es' mea.sm·e.These equivalents are printed in bold
`
`type near the margin, and ananged so as to fit them for quick and
`accurate reference.
`Part ID treats of Inorganic Chemical Substances.Precedence is
`of course given to official preparation in these.The descliptions,
`solubilities, and tests for identity and impw-ities of each s ubstance
`are systematically tabulated under its proper title.lt is confidently
`believed that by this method of arrangement the valuable desclip(cid:173)
`tivc features of the Pharmacopoeia will be more prominently de(cid:173)
`veloped, ready reference facilitated, and close study of the details
`rendered easy. Each chemical operation is accompanied by equa(cid:173)
`tions, whilst the reaction is, in addition, explained in words.
`The Carbon Compounds, or Organic Chemical Substances,
`are considered in Part IV.These are naturally grouped according
`to the physical and medical properties of their principal constit(cid:173)
`uenl<;, l>eg•nning ..,vith simple bodies like cellulin, gum, etc, and
`progressing to the most highly organized alkaloids, etc.
`Pa1t V is devoted to Extemporaneous Phannacy.Care ha<;
`been taken to treat. of the practice which would be best adapted
`for the needs of the many phannacists who conduct operations
`upon a moderate scale, rather than for those of the few who
`manage very large establishments.ln this, as well as in other
`parts of the work, operations are illustrated which are conducted
`by manufacturing pharmacists.
`Part VI contains a formulary of Pharmaceutical Preparations
`which have not heen recognized by the Pharn1acopoeia.The rec(cid:173)
`ipes selected are d1iefly those which have been heretofore rather
`difficult of access to most pharmacists, yet such as are likely to
`be in request. Many private formulas are embraced in the collec(cid:173)
`tion; and such of the preparations of the old Pharmacopoeias as
`have not been inducted in the new edition, but are still in use,
`have been inserted.
`In conclusion, tthe author ventures to express the hope that
`the work will prove an efficient help to the pharmaceutical
`student as well as to the pharmacist and the physician.
`Although the labor ha<; been mainly performed amidst the ha(cid:173)
`rassing cares of active professional duties, and perfection is
`known to be unattainable, no pains have been spared to discover
`and correct errors and omissions in the text. The author's wann(cid:173)
`est acknowledgments, are tendered to Mr A B Taylor, Mr Joseph
`McCreery, and Mr George M Smith for their valuable assistance
`in revising the proof sheets, and to the latter especially for his
`work on the index.The outline illustrations, by i.\1r John Collins,
`were drawn eithe1· from the actual objects or from photographs
`taken by the author.
`
`Philadelphia, October, 1885
`
`JPR.
`
`xiii
`
`Page 4 of 21
`
`

`
`Table of Contents
`
`Port 1 Orientation
`
`1 Scope of Pharmacy ... . ...... . .. .
`2 Evolution of Pharmacy . . ..... . . ... . ... . .
`J Ethics and Professionalism . . ....... .. ... . .
`4 The Practice of Community Pharmacy . . . ....... .
`5 Pharmacists in Industry . .
`6 Pharmacists in Government
`7 Pharmacists and Public Health .... . . .
`8 Information Resources in Pharmacy and rhe
`Pharmaceurical Sciences. . . .
`. . . . . . . ... .... .
`9 Clinical Drug Literature . . .
`1 0 Research.
`
`Port 2 Pharmaceutics
`
`11 Pharmaceurical Calculations .. . . . ..... .
`12 Statistics. . . .
`. . . . . . . . . . . . . . .
`1 J Molecular Structure, Properties, and Stores of Motter. .
`14 Complex FormaTion . ..... . . ..... . . ... ... . . .
`15 Thermodynamics . .
`. . ..... . . .. . ..... . .. .
`16 Solutions and Phose Equilibria .. . ............ . .
`17 Ionic Solutions and Electrolytic Equilibria ..... . .. . .
`18 Tonicity. Osmoticity. Osmola lity, and Osmolarity ... .
`19 Chem ical Kinetics . . . . . . .
`. .. . .. . .... .
`20 Interfacial Phenomena.
`_ . . . . _ . . . . . .... . . _
`21 Colloidal DispersiOns ... . .. .. .. . . . . . . ....... .
`22 Coarse Dispersions ..... ......... .... . .. . .. .
`2.3 Rheology ... . . . ... . ... .... ........ . .
`
`Port 3 Phormaceuticol Chemistry
`
`24 Inorganic Pharmaceutical Chemistry . . . _ .. .
`25 Organic Pharmaceutical Chemistry
`_ . .... . . .. .
`26 Natural Products ... . . . . . ....... . ... . .
`27 Drug Nomenclature-United States Adopted
`Names .... . . .
`.... . . . ........... .
`28 Strucrure-Acrivity Relationship and Drug Design .. .. .
`29 Fundamentals of Rodionuclides
`. ... . . . . .
`
`Part 4 Pharmaceutical Testing, Analysis and Control
`
`JO Analysis of Medicinals . . ...... . ... . ... .
`J1 Oiologica l Testing
`. ..... ... ... .. . ... . . .. . . .
`J2 Clinical Analysis . .. . ... . . . ... . . .. • . . .
`JJ Chromatography .... ... . ... ....... . ..... . .
`J4 Instrumenta l Methods of Ana lysis . . . . . . .. . .... . .
`J5 Dissolutio n .
`. . . . . . . . . . .
`. _ . . . . . . . . . .
`
`Part 5 Pharmaceutical Manufacturing
`
`_ . _ . _ . . .
`J6 Seporarion .. _ . . . _ . . . . .
`J7 Powders ...... . ........... . . . . . . . .
`J8 ?reformulation .. ... . .. _ . . ... . . . . ... .
`J9 Solutions. Emulsions. Suspensions. and Extracts ... . .
`40 Sterilization . . . . . . . . . . . .
`. .... .... .
`41 Parenteral Preparations ... ...... .. . ...... .. .
`42 Intravenous Admixtures
`. _ .. __ .. . .
`4J Ophthalmic Preparations . . . _
`_ _ . .. . . .. .
`44 Medicated Topicols . . . . . . . .
`. ... . ... ... . .
`45 Oral Solid Dosoge Forms . . . . . . ... . . . . . ..... .
`46 Coating o f Pharmaceutical Dosage Forms . . ... . . .
`47 Contro lled-Release Drug -Delivery Systems _
`48 The Introduction of New Drugs
`... . . . . .
`
`J
`7
`19
`28
`JJ
`J8
`47
`
`60
`70
`81
`
`9 1
`124
`159
`18J
`198
`208
`227
`246
`26J
`275
`288
`J16
`JJ5
`
`J59
`J85
`409
`
`44 1
`458
`469
`
`485
`540
`552
`587
`61 4
`654
`
`669
`681
`700
`721
`75J
`780
`807
`821
`8J6
`858
`894
`90J
`9JO
`
`4 9 Oiorechno logy and Drugs . ... ... . .. . .. .. . ... .
`50 Aerosols . . .......... . . .......... • .. . . . . .
`51 Q ua lity Assurance and Control
`. . ... . .... .
`52 Stability of Pharmaceutical Products . . . .. .. _ . . . . _
`5J Dioavailability a nd Oioequivolency Testing .... . .. .
`54 Plasric Pocl1oging Materials . ...... .... _ ..... . .
`55 Pharmaceutical Necessities ....... . . . . . . .
`
`Port 6 Pharmacodynamics
`
`56 Diseases Manifestations and Pathophysiology
`57 Drug Absorption. Action. and Disposition
`58 Oosic Pharmocol~inetics .... . . . ..... . . . .. .. . . .
`59 Clinical Pharmacollinetics . ....... . . ... . ... . . .
`60 Principles of Immunology .
`. • .. . .. . . . . . . .
`6 1 Adverse Drug Reactions ... . . . . ....... . ... . . .
`62 Pharmacogenetics .
`. . ....... . . .
`6J Pharmacologica l Aspecrs of Subsra nce Abuse .
`
`Port 7 Pharmaceutical and Medicinal Agents
`
`64 Diagnostic Drugs and Reagents.
`65 Topical Drugs . . .
`_ ..... .
`66 Gastrointestinal and Liver Drugs.
`67 1!31ood. Fluids. Elecrrolyres. and Hemorolog:col Drugs .. .
`68 Cordiovosculor Drugs . . .
`. ..... . _ .. . ... .
`69 Respiratory Drugs . . . . . . _ _ . .. _ . ... ...... . .. .
`70 Symporhomimetic Drvgs . . . , .......... , , ... ,
`71 Cholinomimetic Drugs . .
`_ . . ........ . _
`72 Adrenergic and Adrenergic Neuron Olocl1ing Drugs . .
`7J Antim uscorinic and Antispasmodic Drugs . .
`74 Sl~eletal Muscle Relaxants . ..
`7 5 Diureric Drugs . . . _ . . . . . . . _ . . _ . . . . .
`76 Urenne ond Antim igraine Drugs . . . . ... . . . . . .. .
`77 Hormones and Hormone Anragonists
`7 8 General Anesthetics . . . _ . . . _
`79 Local Anesthetics . . .
`. .
`80 Sedative and Hypnotic Drugs .. . .
`81 Antiepileptic Drugs . . . . . . . . . . . ... . . .. . ..... .
`82 PsychophormocologiC Agenrs.
`8J Analgesic. Antipyretic, and Anti-Inflammatory
`Drugs . _ . . . . . . . .
`84 Histamine and Ami histaminic Drugs _ ..... . ..... .
`85 Centra l NeNous System Stimulants. .
`. . . . . . . . .
`86 A ntineoplasric ond lmmunoacrive Drugs . . . ... .. .
`87 Anri-lnfecrives .. ... . . . .... . . . . .... . ... ... .
`88 Parosiricides . .
`89 Immunizing Agents and Allergenic Exrracts
`
`944
`96J
`980
`986
`995
`1005
`1015
`
`105J
`1098
`1127
`1145
`1 156
`1165
`1169
`1175
`
`1185
`1200
`1219
`124J
`1274
`1297
`1J05
`1J14
`1J22
`1J28
`1JJJ
`1J44
`1J54
`1J58
`1J95
`1400
`1407
`1421
`1429
`
`1444
`1464
`1471
`1477
`1507
`1562
`1567
`
`Port 8 Pharmacy Practice
`
`Port 8A Pharmacy Administration
`
`90 l ows Governing Pharmacy
`. . . _ ... . . . _
`91 Pharmocoeconomics .
`. .. . .. ...... .
`Q2 Marl~eting Pharmaceutical Core SeNices . . . ..... _
`9J Documenting ond Oilling for Phormaceurical Core
`SeNices . ... _.. ... ...
`. . ......
`94 Community Pharmacy Economics and
`Management .
`95 'Producr Recalls and Withdrawals
`
`1595
`1625
`1604
`
`1640
`
`1650
`1666
`
`Port 8D Fundamentals of Pharmacy Practice
`
`96 Drug Education _ . ... . . . . . . ....... . .. ... . . .
`
`1677
`
`xiv
`
`Page 5 of 21
`
`

`
`97
`98
`99
`100
`101
`102
`103
`
`104
`105
`106
`107
`108
`109
`
`The Prescription . . . . . . __ ..... . . .. _ . . .. ... .
`Extemporaneous Prescription Compounding
`Poison Conrrol .. ... __ . _ . _ ... _ . . .
`. . _ .... .
`Nurririon 1n Pharmacy Practice
`. . ... .. ... .. ... .
`Self-Core/Diagnostic Product.s ... . .... . ........ .
`_ . _ . _ .. .
`Drug lnreroctions . _ . _ . _ . _
`Complemenrary and Alternative Medical Health
`Core.
`__ __ _____ ..
`Nuclear Pharmacy Practice _ . ............... .
`Enzymes
`_ ... _ . __ . __ _ _ __ . .. ... .. .. .. . . .
`Vitamins and Other Nutriems
`. .. .. . __ _ . .
`Pesticides . . . _ . . . _
`Surgical Supplies ... . . . _
`Health Accessories _
`
`1687
`1706
`1716
`1725
`1738
`1746
`
`1762
`1781
`1792
`1796
`1825
`1846
`1857
`
`Port 8C Patient Core
`
`11 0 Ambulatory Panenr Core ..........•.........
`11 1 Institutional Potiem Core ..............•. . •..
`112 Long-Term Core Focil1nes ... ... . _ ..•..... _ .. .
`
`189J
`1911
`1932
`
`113
`11 4
`115
`116
`117
`118
`119
`
`The Potienr: Qehoviorol Dererminonrs .
`Patient Communication . _ . .. _ . . _ .
`Patienr Compliance
`.
`. . ... _ .
`Phormocoepidemiology . . . . .
`. . . .. . . .
`lnregrored Healrh-Care Delivery Systems . . . . . ... .
`Home Health Patient Core .. _ . _ . . . . . . _ ... _ . .
`Aseptic Technology for Home-Core
`Pharmaceutica ls . _ . . . . . . . . . . . . . _ . . . _ . . . _
`
`Appendixes
`
`Dose Equivalenrs .
`Periodic Chart ...
`Logarithms __ _
`
`Glossary ond Index
`
`Glossary . . . . .. ..•......
`Index . . . _ . . . _ . . .
`
`1948
`1957
`1966
`1980
`1990
`2012
`
`2020
`
`2033
`2034
`2036
`
`2037
`2039
`
`XV
`
`Page 6 of 21
`
`

`
`Ophthalmic Preparations
`
`C HAP T E R 43
`
`Gerald Hecht, PhD
`Senior Director, Pharmaceutical Sciences
`Alcon Laboratories
`Fort Worth, TX 76101
`
`Ophthalmic preparations are sterile products essentially free
`from foreign particles, suitably compounded and packaged for
`instillation into the eye. Ophthalmic preparations include so(cid:173)
`lutions, suspensions, ointments, and solid dosage forms. The
`solutions and suspensions are, for the most part, aqueous.
`Ophthalmic ointments usually contain a white petrolatum(cid:173)
`mineral oil base.
`Ophthalmic preparations can be grouped broadly into two
`divisions of major significance to the pharmacist. These include
`single or multidose prescription products and the category de(cid:173)
`scribed as OTC or over-the-counter ophthalmic products. The
`latter group has been subjected to a searching review and
`analysis by a body of experts as a part of the Food and Drug
`Administration's (FDA) OTC Drug Review process.
`The single dominant factor characteristic of all ophthalmic
`products is the specification of sterility. Any product intended
`for use in the eye regardless of form, substance, or intent must
`be sterile. This requirement increases the similarity between
`ophthalmic and parenteral products; however the physiology
`of the human eye in many respects imposes more rigid
`formulation requirements. This is considered in the following
`discussion.
`Preparations intended for the treatment of eye disorders
`can be traced to antiquity. Egyptian papyri writings describe
`eye medications. The Greeks and Romans expanded such uses
`and gave us the term collyria. Collyria refers collectively to
`materials that were dissolved in water, milk, or egg white for
`use as eyedrops. In the Middle Ages collyria included mydriatic
`substances to dilate the pupils of milady's eyes for cosmetic
`purposes, thus the term belladonna, or beautiful lady.
`From the time of belladonna collyria, ophthalmic technology
`progressed at a pharmaceutical snail's pace well into modern
`times. It was not until after World War II that the concept of
`sterility became mandatory for ophthalmic solutions. Prior to
`World War II and continuing into the 1940s very few ophthal(cid:173)
`mic preparations were available commercially or were de(cid:173)
`scribed officially. The USP XIV, official in 1950, included only
`three ophthalmic preparations, and all three were ointments.
`Preparations to be used in the eye, either solutions or oint(cid:173)
`ments, invariably were compounded in the community or hos(cid:173)
`pital pharmacy and were intended for immediate (prescription)
`use. Such preparation and prompt use is reflected in the phar(cid:173)
`maceutical literature of the times. The stability of ophthalmic
`preparations is discussed in terms of days or a few months.
`One of the most important attributes of ophthalmic products
`is the requirement of sterility. Even that, however, is a sur(cid:173)
`prisingly recent event. The USP XV in 1955 was the first
`official compendium to include a sterility requirement for oph(cid:173)
`thalmic solutions . The FDA in 1953 adopted the position that a
`nonsterile ophthalmic solution was adulterated. Sterile oph(cid:173)
`thalmic products were, of course, available prior to the mid-
`1950s; however the legal requirement of sterility dates only
`from 1955.
`
`The sterility requirements for ophthalmic ointments ap(cid:173)
`peared first in the USP XVIII, Third Supplement (1972). Prior
`to that date there was no legal requirement for a sterile oph(cid:173)
`thalmic ointment. This probably was due to the difficulty (at
`that time) of testing for sterility in such nonaqueous systems
`and also the anticipated difficulties in sterilizing and maintain(cid:173)
`ing sterile conditions during the manufacture and filling of
`ointments on a large scale.
`
`ANATOMY AND PHYSIOLOGY OF THE EYE
`
`The human eye is a challenging subject for topical administra(cid:173)
`tion of drugs. The basis of this can be found in the anatomical
`arrangement of the surface tissues and in the permeability of
`the cornea. The protective operation ofthe eyelids and lacrimal
`system is such that there is rapid removal of material instilled
`into the eye, unless the material is suitably small in volume
`and chemically and physiologically compatible with surface
`tissues . Figures 43-1 1 and 43-2 1 include pertinent anatomy of
`the human eye.
`EYELIDS-The eyelids serve two purposes: mechanical
`protection of the globe and creation of an optimum milieu for
`the cornea. The eyelids are lubricated and kept fluid-filled by
`secretions of the lacrimal glands and specialized cells residing
`in the bulbar conjunctiva. The antechamber has the shape of a
`narrow cleft directly over the front of the eyeball, with pocket(cid:173)
`like extensions upward and downward. The pockets are called
`the superior and inferior fornices (vaults), and the entire space,
`the cul-de-sac. The elliptical opening between the eyelids is
`called the palpebral fissure.
`EYEBALL-The wall of the human eyeball (bulbus, globe)
`is composed of three concentric layers.
`1. The outer fibrous layer.
`2. A middle vascular layer-the uvea or uveal tract, consisting of the
`choroid, the ciliary body, and the iris.
`3. A nervous layer-the retina.
`The outer layer is tough, pliable, but only slightly stretchable.
`In its front portion-the portion facing the outside world-the
`fine structure of the outer layer is so regular and the water
`content so carefully adjusted that it acts as a clear, transparent
`window (the cornea). It is devoid of blood vessels. Over the
`remaining two-thirds the fibrous coat is opaque (the white of
`the eye) and is called the sclera. It contains the microcircula(cid:173)
`tion, which nourishes the tissues of this anterior segment, and
`is usually white except when irritated and vessel dilatation
`occurs.
`The eyeball houses an optical apparatus that causes in(cid:173)
`verted reduced images of the outside world to form on the
`retina, which is a thin translucent membrane. The optical
`apparatus consists, in sequence, of the precorneal film, the
`cornea, the aqueous humor, the pupil, the crystalline lens, the
`
`821
`
`Page 7 of 21
`
`

`
`822
`
`CHAPTER 43
`
`WOLFRING'S
`GU,NDS---':'':--------:-
`
`GLANDS OF
`.If--~-:+--- MANZ
`
`CR YPTS OF
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`
`VITREOUS
`HUMOR
`
`Figure 43-1. The eye: vertical section. 1
`
`vitreous humor, and the retina. The aqueous and vitreous
`humors are layers of clear fluid or gel-like material interposed
`between the solid structures. The pupil, a round centric hole in
`a contractile membranous partition (called the iris), acts as the
`variable aperture of the system. The crystalline lens is a re(cid:173)
`fractive element with variable power controlled and supported
`by a muscle incorporated in the ciliary body. The choroid is the
`metabolic support for the retina.
`The optical function of the eye calls for stability of its di(cid:173)
`mensions, which is provided partly by the fibrous outer coat;
`more effective as a stabilizing factor is the intraocular pres(cid:173)
`sure, which exceeds the pressure prevailing in the surrounding
`tissues. This intraocular pressure is the result of a steady
`production of specific fluid, the aqueous humor, which origi(cid:173)
`nates from the ciliary processes and leaves the eye by an
`intricate system of outflow channels. The resistance encoun(cid:173)
`tered during this passage and the rate of aqueous production
`are the principal factors determining the level of the intraocu(cid:173)
`lar pressure. In addition to this hydromechanical function, the
`aqueous humor acts as a carrier of nutrients, substrates, and
`metabolites for the avascular tissues of the eye.
`The bones of the skull join to form an approximately
`pyramid-shaped housing for the eyeball, called the orbit.
`CONJUNCTIVA-The conjunctival membrane covers the
`outer surface of the white portion of the eye and the inner
`aspect of the eyelids. In most places it is attached loosely and
`thus permits free movement of the eyeball. This makes possible
`subconjunctival injections. Except for the cornea the conjunc(cid:173)
`tiva is the most exposed portion of the eye.
`LACRIMAL SYSTEM-The conjunctival and corneal sur(cid:173)
`faces are covered and lubricated by a film of fluid secreted by
`the conjunctival and lacrimal glands. The secretion of the lac(cid:173)
`rimal gland, the tears, is delivered through a number of fine
`ducts into the conjunctival fornix. The secretion is a clear,
`watery fluid containing numerous salts, glucose, other organic
`
`compounds, approximately 0. 7% protein, and the enzyme ly(cid:173)
`sozyme. Small accessory lacrimal glands are situated in the
`conjunctival fornices. Their secretion suffices for lubrication
`and cleansing under ordinary conditions and for maintaining a
`thin fluid film covering the cornea and conjunctiva (the precor(cid:173)
`neal film). The mucin-protein layer of the film is especially
`important in maintaining the stability of the film. The main
`lacrimal gland is called into play only on special occasions. The
`sebaceous glands of the eyelids secrete an oily fluid that helps
`to prevent overflowing of tears at the lid margin and reduces
`evaporation from the exposed surfaces of the eye by spreading
`over the tear film.
`Spontaneous blinking replenishes the fluid film by pushing
`a thin layer of fluid ahead of the lid margins as they come
`together. The excess fluid is directed into the lacrimal lake-a
`small, triangular area lying in the angle bound by the inner(cid:173)
`most portions of the lids. The skin of the eyelids is the thinnest
`in the body and folds easily, thus permitting rapid opening and
`closing of the palpebral fissures. The movement of the eyelids
`includes a narrowing of the palpebral fissures in a zipper-like
`action from the lateral canthus toward the medial canthus
`(canthi: the corners where the eyelids meet). This aids the
`transport or movement of fluid toward the lacrimal lake.
`Tears are drained from the lacrimal lake by two small
`tubes-the lacrimal canaliculi-which lead into the upper part
`of the nasolacrimal duct, the roomy beginning of which is called
`the lacrimal sac. The drainage of tears into the nose does not
`depend merely on gravity. Fluid enters and passes along the
`lacrimal canaliculi by capillary attraction aided by aspiration
`caused by contraction of muscle embedded in the eyelids. When
`the lids close, as in blinking, contraction of the muscle causes
`dilatation of the upper part of the lacrimal sac and compression
`of its lower portion. Tears are thus aspirated into the sac, and
`any that have collected in its lower part are forced down the
`nasolacrimal duct toward its opening into the nose. As the lids
`open, the muscle relaxes. The upper part of the sac then
`collapses and forces fluid into the lower part, which at the same
`time is released from compression. Thus, the act of blinking
`exerts a suction force-pump action in removing tears from
`the lacrimal lake and emptying them into the nasal cavity.
`
`·'.
`
`·· ..
`
`NASAL
`SEPTUM
`
`Figure 43-2. Nasolacrimal duct.1
`
`Page 8 of 21
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`

`
`Lacrimation is induced reflexly by stimulation of nerve endings
`of the cornea or conjunctiva. The reflex is abolished by anes(cid:173)
`thetization of the surface of the eye and by disorders affecting
`its nerve components.
`The normal cul-de-sac usually is free of pathogenic organ(cid:173)
`isms and often found sterile. The sterility may be due partly to
`the action of lysozyme in the tears, which normally destroys
`saprophytic organisms but has little action against pathogens.
`More effective in producing sterility may be the fact that the
`secretions, which are normally sterile as they leave the glands,
`constantly wash the bacteria, dust, etc, down in the nose. In
`certain diseases the lacrimal gland, like other glandular struc(cid:173)
`tures in the body, undergoes involution, with the result that
`the lacrimal fluid becomes scanty. Furthermore, changes in the
`conjunctival glands may lead to alteration in the character of
`the secretion so that quality as well as quantity of tears may be
`abnormal. This may lead to symptoms of dryness, burning, and
`general discomfort and may interfere with visual acuity.
`PRE CORNEAL FILM-The cornea must be wet to be an
`optically adequate surface; when dry, it loses both its regular
`gloss and its transparency. The precorneal film, part ofthe tear
`fluid, provides this important moist surface. Its character de(cid:173)
`pends on the condition of the corneal epithelium. The film,
`compatible with both aqueous and lipid ophthalmic prepara(cid:173)
`tions, is composed of a thin outer lipid layer, a thicker middle
`aqueous layer, and a thin inner mucoid layer. It is renewed
`during each blink, and when blinking is suppressed, either by
`drugs or by mechanical means, it dries in patches. It seems to
`be unaffected by the addition of concentrations of up to 2%
`sodium chloride to conjunctival fluid. A pH below 4 or above 9
`causes derangement of the film. The film affects the movement
`of contact lenses and forms more easily on glass than on plastic
`prostheses.
`CORNEA-The cornea, from 0.5 to 1 mm thick, consists
`mainly of the following structures (from the front backward):
`1. Corneal epithelium.
`2. Substantia propria (stroma).
`3. Corneal endothelium.
`
`The cornea is transparent to ordinary diffuse light, largely
`because of a special laminar arrangement of the cells and fibers
`and because of the absence of blood vessels. Cloudiness of the
`cornea may be due to any one of several factors including excess
`pressure in the eyeball as in glaucoma, and scar tissue due to
`injury, infection, or deficiency of oxygen or excess hydration
`such as may occur during the wearing of improperly fitted
`contact lenses. A wound of the cornea usually heals as an
`opaque patch that can be a permanent impairment of vision
`unless it is located in the periphery of the cornea.
`The chief refraction of light for the eye occurs at the outer
`surface of the cornea where the index of refraction changes
`from that of air (1.00) to that of precorneal substance (1.38).
`Any alteration in its shape or transparency interferes with the
`formation of a clear image; therefore, any pathological process,
`however slight, may interfere seriously with the resolving
`power or visual acuity of the eye.
`The normal cornea possesses no blood vessels except at the
`corneoscleral junction. The cornea, therefore, must derive its
`nutrition by diffusion and must have certain permeability char(cid:173)
`acteristics; it also receives nourishment from the fluid circulat(cid:173)
`ing through the chambers of the eye and from the air. The fact
`that the normal cornea is devoid of blood vessels is an impor(cid:173)
`tant feature in surgical grafting. The corneal nerves do not
`supply all forms of sensation to the cornea. Pain and cold are
`well supplied. The pain fibers have a very low threshold, which
`makes the cornea one of the most sensitive areas on the surface
`of the body. It now is agreed generally that the cornea pos(cid:173)
`sesses a true sense of touch; nerve endings supplying the sen(cid:173)
`sation of heat are lacking.
`The corneal epithelium provides an effic