National Board of Examiners in Optometry (NBEO) Part One (Applied Science) - KMK Board Review Guide (2014), Vol. 1 (Etc.)

Part One
Applied
~ Science
Review Gui e
Volume One
1
K M K Part I Applied Science Review

Guide
Tth Edition, Volume 1
K yle M . C h eath am , O .D ., F .A .A .O .
M elissa A. C heatham , M P A S , PA -C
K evin B. W ood, P h .D .
Copyright 2014 by KMK Educational Services, LLC

11
N O T IC E
Optometry and vision science are dynamic fields, each subject to the rapid
modification brought about by the continuing progress in medical and biolog
ical science. Because of the breadth and ever-changing nature of these fields,
the authors, publishers, and all parties involved with the production and prepa
ration of this text cannot be held responsible for possible omissions or errors
throughout the book. While we have gone to painstaking lengths to ensure
the information is correct and complete to the best of our knowledge, we en
courage the reader to consult other sources in both designing a study plan for
board exams and, of course, when gathering information for an accurate clinical
decision.
The National Board of Examiners in Optometry (NBEO) is a registered trade

mark. NBEO does not endorse this guide.
The following is copyrighted material. It is unlawful to distribute without

express written consent from the copyright holder.
Copyright 2014 by K M K Educational Services, LLC.

I ll
C o n trib u to rs
K y le M . C h eath am , O .D ., F .A .A .O . graduated from Centre College with

a B.S. in Biology and completed optometry school at Indiana University School
of Optometry before accepting a residency at the Kansas City VA Hospital. Dr.
Cheatham practices at Heartland Eye Consultants, a secondary eyecare center
in Omaha, Nebraska, where he specializes in ocular disease and low vision.
He serves as an adjunct faculty member o f six colleges of optometry teaching
optometric interns at Heartland Eye Consultants. Dr. Cheatham also provides
consultative care within the ophthalmology department at Creighton University
Medical Center and is a diplomate of the American Board of Optometry (ABO).
M elissa A . C h eath am , M P A S , P A -C graduated from the University of

Nebraska, Lincoln, with a Bachelor of Science degree in Communication Studies
before receiving her Master’s in Physician’s Assistant Studies from University
of Nebraska Medical Center. She has clinical experience in family practice
and obstetrics and gynecology and now practices as a board certified physician
assistant in cardiology with the Bryan Heart Institute in Lincoln, NE.
K e v in B . W o o d , P h .D . graduated Magna Cum Laude from Centre College

(KY) with a B.S. in Chemical Physics before completing an M.S. in Biology, a
double Ph.D. in Theoretical Physics and Physical Chemistry at the University
of California, San Diego (UCSD), and a postdoctoral research fellowship in the
Department of Molecular and Cellular Biology at Harvard University. Kevin
is currently an Assistant Professor of Biophysics and Physics at the University
of Michigan, where he leverages theoretical tools from statistical physics to
study population dynamics and the evolution of drug resistance in microbial
infections and human cancers.
Sarah D o u g h e rty W o o d , O .D ., M .S ., F .A .A .O . graduated Magna Cum

Laude from University of Evansville with a dual major in Biology/Chemistry
and graduated with honors from IU School of Optometry. She completed a
residency at the Kansas City VA Hospital, where later she served as director
of the low vision program, VICTORS, for 3 years. Sarah completed a two
year research fellowship at the Boston VAMC in 2009 where her research was
published in Journal of Glaucoma. Dr. Wood received a Master?s degree in
Vision Science from The New England College of Optometry in 2010. She is a
member of the Optometric Glaucoma Society and serves as chair of the AAO
Glaucoma SIG. She currently practices at the Kellogg Eye Center in Ann Arbor
and is a clinical instructor of ophthalmology and vision science at University
of Michigan.

IV
A d d ition a l con tribu tors:
The authors would like to thank C had R ea d e, M .D ., C hris W olfe, O .D .,

and R ya n Fenska, O .D ., all of whom provided excellent suggestions and
insights which have improved several sections of the text.

V
C hief M edical E d ito r

______________________________________________
K e n d ra R . D a lto n , O .D . graduated from Emory University in Atlanta, GA

with a B.S. in Biology and graduated summa cum laude from Southern College
of Optometry. She completed a residency in ocular disease and low vision re
habilitation at the Kansas City VA Medical Center. She is currently practicing
at the Philadelphia VA Medical Center, where she serves as the Externship
Program Director and provides direct patient care. She is an adjunct faculty
member of New England College of Optometry and Pennsylvania College of
Optometry at Salus University

r
c
c
c
c
c
c
(
(
<
(
(
(
c
(
(
(
(
(
(
c
(
(
c
(
(
(
V ll
Special T hanks to:
Larry Alexander, O.D.

Paula Campbell
Rowan Candy, O.D.
Ryan Fenska, O.D.
Timothy Harkins, O.D.
Chad Reade, M.D.
Thoroughbred Printing, Lexington, KY
Christopher Wolfe, O.D.
The UPS Store (Georgetown, KY)
Matthew Wood
Laura Ruwe

(
(
(
(
c
(
(
(
(
(
(
(
(
(
(
(
(
c
(
(

(
(
(
(
IX
Forew ord
Passage of the National Boards has always been a source of angst for a physician
in training. One’s future in their chosen profession hinges on successful passage
of the series of examinations. The National Boards in Optometry now even take
on more importance, as all states as well as the District of Columbia and Puerto
Rico require passage of the National Boards Parts 1 and 2 for consideration of
licensure. All states likewise require graduation from an accredited school or
college of optometry to sit for the state board. Forty-seven (47) states as well
as District of Columbia and Puerto Rico require passage of Parts 1, 2 and 3
for licensure. The National Boards in Optometry also represent a considerable
investment for the future doctors. The fees for the National Board Examination
exceed $3000 assuming that the tests are passed the first time taken. While
stressful to the optometry student, there is a reason for requiring passage of
the National Boards; the profession of optometry wants to assure the general
population a basic level of competency for optometric physicians.
The pressure to commit to a full-time-job curriculum (often over 32 hours
of classroom time per week) in the schools and colleges of optometry while
attempting to review all necessary materials for the National Boards in Op
tometry has become a daunting task. Schools and colleges of optometry have
excellent curricula and superb instructors and the subject matter is very rel
evant to the requirements of the practice of optometry. Unfortunately, the
amount o f information covered, classroom time, and required study time leave
little time to organize all information into a format that would be applicable
to an effective review strategy for National Boards. While schools and colleges
of optometry often organize National Boards review courses and student orga.-
nizations like the AOSA make refresher courses available at various meetings,
the majority of students are not readily afforded the benefits of these review
courses. The National Boards review course for Part 1 presented herein has
been constructed under the direction of KMK. This course will not only impact
positively on the knowledge base of optometry students and future practition
ers but will likewise facilitate their passage of the National Boards. The course
simply organizes volumes of information in an integrative fashion. The pieces
of the puzzle are put together to bring a sense of organization to the learning
process. The need for a methodology to attack the integration problem has
never before been satisfied within the constructs of the National Boards in Op
tometry. The format chosen by KMK makes learning pleasant and deepens the
knowledge base through integration of previously presented course material.
Very difficult principles are simplified, restructured and reassembled to bring a
sense of organization to the learning process.
While the text herein serves as an excellent study guide, a full face-to-face
course is also an option available to interested students. These courses will
be offered at different schools and colleges of optometry on a rotational basis.

X
Without doubt, the live course will offer a more complete learning situation,
but the study guide will provide more than has ever been accessible to the
optometry student in the past. The KMK organization, comprised of a prac
ticing optometrist, a physician’s assistant and a physicist brings a fascinating
dimension to the production of a study guide for basic science in optometry.
The result is exquisite in both its depth and its simplicity. This text, as well
as the supplementary face-to face course, is also being constantly updated by
the authors to provide cutting edge information.
The pride that I have for the three individuals who developed this concept is
indescribable. I have always been an optometry student advocate. I believe
that the optometry students are my future colleagues and they are the future
of optometry. Why would we all not want to make their learning process both
more pleasant and effective? This National Boards Part 1 study course is big.
It represents movement in a positive direction and will help to modify and im
prove the delivery of information to doctors both pre and post graduation. My
congratulations go to the authors for a significant contribution to the profession
of Optometry and in the art of education.
Larry J. Alexander, O.D.

Private Practice
Jeffersonville Indiana/Louisville Kentucky

XI
We are happy to introduce our seventh edition study guide, which features
a substantial number o f corrections, revisions, and additions. Many of the
improvements in this edition are attributable to our new Chief Medical Editor,
Dr. Kendra Dalton, who brings to the job a great deal of academic expertise
and has shepherded many chapters of the book to their current forms. We are
indebted to Dr. Dalton for her outstanding work, and we’re excited to welcome
her to the KMK team.
P reface to th e Seventh E dition
Overall, we have attempted to incorporate new clinical ideas and further refine
the presentation of all the material. We hope this book will serve as a useful
reference and a beneficial starting point for board exam preparation. As always,
we encourage students to approach the exam with optimism and focus. We’ve
found that when students view the board exams as an opportunity to improve
their clinical skills and increase their knowledge base, the experience can be
rewarding on both a professional and personal level.
We wish you all the best as you begin your studies.
K M K Educational Services, LLC

July 2014

(
(
(
(
(
(
r
(
(
(
(
(
(
(
(
c
(
(
(
(
(
(
(
(
(
c
(
Contents
Contents xiii
1 Histology 1
1.1 The C e l l ......................................................................................... 3
1.2 Tissue T y p e s ................................................................................ 10
1.3 Organ S y s t e m s ............................................................................. 26
2 Neuroscience 43
2.1 Cellular Neuroscience and Electrophysiology............................ 45
2.2 Neuroanatomy ............................................................................. 48
2.3 Divisions of the Central Nervous S y stem .................................. 50
2.4 Blood Supply to the B ra in .......................................................... 54
2.5 Neuro-Ophthalmic Disorders: Optic N e rv e ............................... 55
2.6 Neuro-Ophthalmic Disorders: The P u p i l .................................. 62
2.7 Neuro-Ophthalmic Disorders: Ocular Motor Palsies and Ocular Myasthenia 66
3 Ocular Anatomy 71
3.1 E y e l i d ............................................................................................ 73
3.2 E y e b r o w s ...................................................................................... 80
3.3 Lacrimal S y s t e m .......................................................................... 81
3.4 O r b it................................................................................................ 84
3.5 Blood S u p p ly ................................................................................ 93
3.6 C o rn ea ............................................................................................ 104
3.7 C on ju n ctiva .............................................. Ill
3.8 L e n s ................................................................................................ 113
3.9 S c l e r a ........................... 116
3.10 Anterior Chamber and A n g l e .................................................... 118
3.11 I r i s ................................................................................................... 122
3.12 Posterior Chamber .................. 126
3.13 Ciliary Body ................................................................................ 126
3.14 Choroid ................................................. 130
3.15 Vitreous Chamber ....................................................................... 134
3.16 R e t in a ............................................................................................ 136
3.17 Ocular and Orbital N erves.......................................... 151
3.18 Optic N e r v e .................................... 164
xiii
X IV CONTENTS
3.19 Visual P athw ay............................................................................... 167
4 O cular E m b ry olog y 179
5 P sy ch o lo g y 189
5.1 Vision Development .................................................................... 191
5.2 Effects of Early Environmental Restrictions on Vision . . . . 198
5.3 Child Developm ent....................................................................... 202
5.4 Anomalies of Visual Perceptual D ev elop m en t......................... 209
5.5 The Aging A d u l t .......................................................................... 212
6 B ioch em istry 217

6.1 The C e l l ......................................................................................... 219
6.2 P r o te in s......................................................................................... 223
6.3 Carbohydrates ............................................................................. 235
6.4 L i p i d s ................................................................... 242
6.5 Nutrition ...................................................................................... 248
6.6 Vitamins and M inerals................................................................. 249
6.7 Molecular Biology - DNA, RNA,Techniques............................. 256
7 M icr o b io lo g y 271
7.1 Bacteriology................................................................................... 273
7.2 V ir o lo g y ......................................................................................... 287
7.3 M y c o lo g y .................................................... 292
7.4 Parasitology................................................................................... 296
8 Im m u n olog y 305
8.1 A ntigens......................................................................................... 307
8.2 Antibodies...................................................................................... 307
8.3 Nonspecific Immunity ................................................................. 309
8.4 Specific Immunity.......................................................................... 312
8.5 Primary and Secondary Immune R e s p o n s e s ............................ 317
8.6 Tissue Transplantation / Graft Rejection.................................. 318
8.7 Autoimmunity ............................................................................. 318
8.8 Tumor Immunology............ ■........................................................ 318
8.9 Immunological T e s t s .................................................................... 319
9 System ic D isease 321

9.1 Inflammation and Repair.............................. 323
9.2 Cellular Disease............................................................................. 325
9.3 Immunopathology.......................................................................... 326
9.4 Rheumatologic Disorders.............................................................. 328
9.5 Diseases of Immunodeficiency..................................................... 333
9.6 Integumentary S y s te m ................................................................. 334
9.7 Genetic Principles and D is o rd e rs .............................................. 339
9.8 Hematopoietic and Lymphoid System ........................ 343

CONTENTS xv
9.9 Cardiovascular Hemodynamic D iso rd e rs.................................. 347

9.10 Pathology of the H e a rt................................................................. 351
9.11 Nervous System and Neuromuscular D isease............................ 356
9.12 Pathology of the Endocrine S ystem ........................................... 365
9.13 Renal S y s t e m ................................................................................ 369
9.14 Diseases of the Reproductive S y s te m ........................................ 370
9.15 Congenital and Neonatal Anomalies ........................................ 374
9.16 Gastrointestinal S y s t e m .............................................................. 376
9.17 Head and Neck Disorders .......................................................... 381
9.18 Respiratory System . .................................................................... 382
9.19 N e o p la s ia ...................................................................................... 385
9.20 Nutritional D isorders.................................................................... 387
9.21 Mental Illness and Behavioral D iso rd e rs.................................. 388
10 Ocular Disease 395

10.1 Slit Lamp Techniques.................................................................... 397
10.2 T r a u m a ......................................................................................... 398
10.3 Ocular Adnexa/Orbit/External Disease .................................. 404
10.4 Lids/Lashes/Lacrimal S y stem .................................................... 414
10.5 C on ju n ctiva................................................................................... 423
10.6 Episclera/Sclera/Anterior and Posterior U v e a ......................... 440
10.7 Cornea/Refractive Surgery.......................................................... 450
10.8 Lens/Cataract/IOL Pre-and Post-operative care ................... 488
10.9 Fundoscopy Utilizing Auxiliary L e n s e s ..................................... 496
10.10 V itr e o u s ......................................................................................... 498
10.11 R etin a /C h oroid ................................................................... 500
10.12 Neuro-Ophthalmic Disorders: G la u com a .................................. 530
Index 547

f( '
((. :
(
(' i
(
(
(
{(
(
(
(
(
(
(
(
(
(
(
(
((
(
(l
((
l.
c
(
ci
(_
(
((.
Chapter
Histology
Kyle Cheatham O .D ., F .A .A .O .
1
c
(
(
(
c
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
t

(
c
(
(
CHAPTER 1. HISTOLOGY 3
C o m m e n t o n sou rces: The following is a compilation of facts that are well-

documented throughout many sources. If facts noted are rare or are specific to
an author’s expertise, they are cited. The most helpful text used in preparation
for this section was Barbara Young’s Wheater’s Functional Histology: A Text
and Colour Atlas, 4th edition. Please see the reference section for a complete
list of sources and recommended readings.
H isto lo g y is the study of the various tissues in the body. There are four
major types of tissue: epithelial, nervous, muscle, and connective tissue.
The general organization of the body is as follows: Cells Tissues

—> Organs —y Organ Systems.
SECTION 1.1
T he Cell
The cell is the fundamental unit of life and is a sum of its parts:
Defines the cell boundary. It is 7-10 nm thick with a complex structure com
posed of lipids, proteins, and carbohydrates. It is best described by the fluid
m osaic m od el. The PM functions in protection, cell-cell recognition, and
signaling pathways.
There are three types of lipids prevalent in the PM:
1. Phospholipids: These amphipathic molecules have hydrophilic heads (po

lar phosphates) that face the outer surface of the cell, and hypdrophobic
tails (hydrocarbon chains) that face the inner surface of the cell.
2. Glycolipids: Lipids attached to a sugar side chain,
3. Cholesterol: Found only in eukaryotic cells. Plays a critical role in

maintaining cell membrane fluidity and integrity (see biochemistry sec
tion for further information on cholesterol).

4 1.1. THE CELL
Normal cholesterol values:
• T ota l ch olesterol less than 200.
• T riglycerides less than 150.
• LD L less than 130.
• H D L 40 or higher.
Proteins are classified according to their position in the PM:
Integral proteins span the plasma membrane and serve the following roles:
• Structural: Interacts with cholesterol to maintain membrane struc

ture.
• R ecep tors: Bind to small molecules, proteins, or enzymes for cell
cell communication. May serve as enzymes themselves.
• Channels: Act as passive transporters or active pumps that move

ions down or against their concentration gradients, respectively.
P eriph eral proteins attach to the outer surface of the PM and serve as
hormone receptors and cell surface markers (i.e. antigens). ■
Carbohydrates are covalently attached to other structures (e.g. lipids and

proteins) embedded within the PM. Glycolipids and glycoproteins are generally
located on the outer surface of the PM.
The g ly co ca ly x refers to all the sugar components (glycolipids

and glycoproteins) on the external surface of the cell. These sugar
moieties aid in protection, adhesion, and absorption.

Houses genetic information of the cell (DNA in the form of chromosomes). The
nucleus proper serves as the location for D N A replication and m R N A and
t R N A tran scription .
All forms of RNA must come from transcription of a DNA template

(see biochemistry chapter for further details).
C on ten ts o f th e N u cleu s
N u cleolu s: Although commonly mistaken for a separate compartment, this

is simply a region within the nucleus that contains dense chromatin and
protein machinery necessary for the p ro d u ctio n o f r R N A (the central
component of ribosomes).
R N A : 3 types of RNA (tRNA, mRNA, and rRNA) are transcribed from DNA
within the nucleus.
• rRNA is produced in the nucleolus and combines with proteins to

form ribosomes. Structural ribosomal proteins are produced in the
cell cytosol and then enter the nucleus via nuclear pores. Once the
ribosome is assembled, it is transported back into the cytosol to aid
in protein translation.
• tRNA is responsible for transferring amino acids to a growing pep
tide chain during translation.
• mRNA serves as a template for an amino acid sequence of a unique
protein.
• Transcription — DNA to mRNA
• Translation — mRNA to protein
N u m b er o f N u clei
Most cells have one nucleus.

6 1.1. THE CELL
• Hepatocytes, cardiac muscle, and epithelial cells of the urinary tract are
binuclear.
• Osteoclasts and skeletal muscle cells are raultinuclear.
• R B C s are the on ly anuclear cells in th e b o d y .
Made up o f a fluid component called the cytosol and solid components called
organelles. Organelles are living, often membrane bound structures produced
by the cell that serve a particular function necessary for cell survival.
R ib o so m e s
Composed of rRNA (65%) and protein (35%) without a lipid bilayer (non
membrane bound). Ribosomes are essential for translation. Eukaryotic cells
have 100S ribosomes, composed of a small (40S) and large (60S) subunit.
Prokaroytic cells have 70S ribosomes consisting of 30S and 50S subunits.
• Ribosomes produce a phenomenon known as cy top la sm ic basophilia.

As the number of ribosomes increases during cell growth, the cytoplasm
becomes more acidic and binds better to basic stains (e.g. hematoxylin),
causing the cytoplasm to appear more blue/purple. In neurons, cytoplas
mic basophilia in the rough ER are called N issl substance.
Antibiotics often target ribosomal subunits to inhibit protein pro

duction in bacteria. Aminoglycosides and tetracyclines act on the
30S subunit. Macrolides act on the 50S subunit.
Ribosomes are found within the cell in two forms:
1. Free floating ribosomes are located in the cytosol and are unattached
to other organelles. They aid in the translation of proteins necessary for
cell growth, cell structure, mitosis, etc.
A p oly som e is formed when multiple ribosomes attach to a single

mRNA molecule in order to maximize efficiency of protein transla
tion.

2. B o u n d ribosomes are attached to the endoplasmic reticulum (forming

rough ER) and produce proteins that will be released outside the cell via
exocytosis. These ribosomes may cause cytoplasmic basophilia due to the
increased number of ribosomes necessary for the production of proteins
that will aid in export o f proteins outside the cell.
R ough E R
Flat pancake membranes with ribosomes bound to the outer surface. Surrounds
the nuclear envelope and is connected via its lumen (cistern) with the perin
uclear space of the nucleus. T his rib osom e bou n d organelle is always
in volved in th e p r o d u c t io n o f p rotein s that will b e e x p o rte d ou t o f
th e cell. The rER is also responsible for the initial glycosylation of proteins
(non-ordered addition of sugars to proteins).
S m o o th E R
This tubular organelle has NO bound ribosomes and is continuous with the
rER. The adrenal cortex, liver cells, and muscle cells contain sER with specific
modified functions:
• Adrenal cortex: Steroid production.
• Hepatocytes: Storage and breakdown of glycogen and d etox ifica tion o f

lip id solu b le drugs.
• Muscle cells: sER (aim sarcoplasmic reticulum) sequesters and controls

the release o f Ca2+ necessary for muscle contractions.
G olgi apparatus
Membrane bound organelle that w orks w ith the rE R to modify proteins

that are to be exported out of the cell. Proteins that move through the Golgi
apparatus form either a secretory granule or a lysosome.
L ysosom es
Membrane bound vesicles that pinch off the Golgi. P rim ary lysosom es pinch
off the Golgi and are filled with digestive enzymes (e.g. collagenases and acids).
Lysosomes aid in the digestion of two important substances:
1. Old worn out organelles within the cell.
2. Particles that enter the cell via phagocytosis.

8 1.1. THE CELL
Materials that are phagocytized by the cell form a phagocytic vacuole. The
fusion of a phagocytic vacuole and a primary lysosome forms a secon d ary
lysosom e.
• Secondary lysosomes are either exocytosed out of the cell or undergo

partial degradation, forming a residual b o d y within the cell.
• Residual bodies are partially destroyed, inactive enzymes. Over time,

residual bodies may gain pigment known as lipofuscin.
Tay-Sachs disease is an autosomal recessive disorder character

ized by the accumulation of residual bodies. It typically presents
in the first year of life and usually leads to death by the age of two.
A ch erry red m acula is characteristic of the disease and is found
in 90% of cases (5).
M it o ch on dria
Known as the ‘‘powerhouse” of the cell, this organelle is elliptical in shape and
is enclosed by a double lipid bilayer similar to the nucleus. Mitochondria are
thought to have evolved as separate prokaryotic organisms that developed a
symbiotic relationship within cells. The endosymbiotic theory is supported
by the presence of a separate genome within mitochondria. M itoch on d ria l
D N A is tran sm itted through m aternal inheritance.
L e b e r’ s hereditary o p tic n europathy (L H O N ) is a rare optic

nerve disease that is the result of maternal mitochondrial DNA
mutations (5).
Made up of microfilaments, microtubules, and intermediate filaments.
M icrofilam en ts (A ctin ): Component of muscles that forms the core of m i

crovilli.
• M icrov illi are fingerlike projections that increase the cell surface
area for absorption and diffusion. These projections give the PCT
cells of the kidneys a “brushed border” appearance.
Copyright 2014 by KM K Educational Services, LLC

M icro tu b u le s (T u b u lin ) r Tubulin is the protein at the core of microtubules,

flagella, and cilia. Microtubules form the spindle apparatus that pulls
chromosomes away from each other during cell division. Cilia and flagella
aid in cell motility.
In term ed ia te filam ents: Connect the nuclear membrane to the plasma mem
brane, providing a transport system for organelles within the cytoplasm
and providing resistance against external pressure on the cell.
G a p Ju n ction s
Connect the cytoplasm of neighboring cells through channels known as con-

nexons, allowing for rapid electrical communication via ion flow between cells.
Gap junctions play an important role in conduction in cardiac and nervous
tissue.
T igh t J u n ction s (Z on u la O cclu d en s)
Zonula occludens act as a belt that wraps around the cell. These junctions
serve as an excellent barrier because all particles must pass THROUGH rather
Cell Junctional Complex

Apical Surface
Junctional Complex
Basal Surface
Figure 1.1: Cell Junction Complex

10 1.2. TISSUE TYPES
than around the cell. Tight junctions form the blood-aqueous and blood-retinal
barriers in the eyes.
A d h eren s Junctions
These juctions are composed of fibers (tonofilaments within a mucoprotein

substance) that interweave one cell to another, providing structural support.
1. Zonula adherens: A belt like junction that is similar to zonula occludens

but with a narrow space between cells composed of tonofilaments and
mucoproteins that pulls cells close together.
2. Macular adherens (i.e. desmosomes): Functions like a “spot weld,” pro

viding concentrated support in ONE location.
H em idesm osom e
Hemidesmosomes connect basal cell layers to the underlying basement mem

brane. They are the only type of cell junction that does NOT connect cell to
cell and therefore does NOT provide structural support.
R ecu rren t corneal erosions often result from poor adhesion be
tween epithelial cells and the underlying basement membrane due
to damaged hemidesmosomes (9).
SECTION 1.2
Tissue Types
An avascular tissue that is mitotically active and utilizes significant energy,

requiring it to be closely associated with underlying vascular tissue. The base
ment membrane, composed of the basal lamina (from'the epithelial tissue)
and the pars reticularis (from connective tissue), helps to maintain the close
proximity of the epithelium to the blood vessels.
SIM PLE EPITH ELIU M
There are 3 types of simple epithelium, each with specific functions:

• Sim ple Squam ous: Single layer of thin cells that are in close contact
with the underlying BM and are specialized for diffusion of gas and other
substances through the cell. An example includes the inner lining of
blood vessels.
• Sim ple C u b o id a l: Single layer of slightly thicker, box-like cells that are
specialized for secretion. An example includes the thyroid gland.
• Sim ple C olu m n a r: Single layer of cells that are thicker and longer,
allowing for protection. These cells are specialized for absorption and are
found in the GI tract (excluding the esophagus). Microvilli at the apical
border of columnar cells increases the surface area for absorption.
— P seu d ostra tified colu m n ar epithelium : A type of simple colum

nar epithelium where nuclei are present at different levels within
cells, resulting in a stratified appearance. Pound in the respira
to r y tract.
The three types of simple epithelium are specialized for different

roles. Remember S A D :
• Secretion (cuboidal)
• Absorption (columnar)
• Diffusion (squamous)
S T R A T IF IE D E P IT H E L IU M
Stratified Squam ous N o n -K e ra tin ized E pithelium : A thick protective

tissue that prevents antigens from entering the cell. Increased thickness results
in poor O 2 diffusion. Found in four primary locations: Cornea, con ju n ctiva,
esophagus, and vagina.
• The corneal epithelium is composed of five to six layers of simple squa

mous epithelium. The innermost layer is the basal cell layer that is re
sponsible for secreting the epithelial basement membrane that attaches
to the underlying Bowman’s layer. Basal cells are cuboidal or columnar
in shape. They become flatter and wider (i.e. squamous shaped) as they
move towards the surface of the epithelium.

Stratified Squam ous K eratinized E pithelium : Keratin functions as a

strong outer covering that protects against dehydration and mechanical stress.
Shortly after the cells produce keratin, the nucleus ruptures and the cell dies.
An example includes the thick skin on the palm of the hand.
Stratified C u boidal: Composed of 2 layers of cuboidal epithelium. Found

in larger ducts (e.g. sweat glands), where it functions as a conduit.
Stratified C olu m nar: Composed of 2 layers of columnar epithelium that

aids in protection. Found in the largest ducts (e.g. anus).
Transitional epithelium : Three to seven layers of stratified epithelium lo

cated in the bladder. Specialized for distension, collapse, and protection
against urine.
S E C R E T O R Y E P IT H E L IU M
Secretory epithelium is formed by the invagination of lining epithelium to form a

gland. E x ocrin e and en d ocrin e glands are examples of secretory epithelium.
E x o crin e glands are classified according to several different characteristics,

including cell number (unicellular vs multicellular), the shape of the duct (sim
ple vs compound), and the mechanism of product secretion (holocrine, apoc
rine, and merocrine). The following are key points about these characteristics:
• Unicellular exocrine glands contain one cell that serves as the duct for
secretion. G ob let cells are an example.
• Exocrine glands may have ducts that are straight (simple) or branched
(compound). The m ain lacrim al gland is an example of a compound
tubuloacinar gland.
• Exocrine gland secretion may occur through one of three methods:
1. H olocrin e: The entire cell (the “whole cell”) that contains the prod
uct is shed into the lumen of the duct. M eib o m ia n glands are an
example.
2. A p o crin e: Products are secreted into a membrane bound vesicle at
the apex of the cell that is then pinched off into the lumen. Examples
include g ob let cells and glands o f M oll.
3. M erocrin e: Most common form of exocrine secretion where prod
ucts are simply exocytosed out of the cell. The m ain lacrim al
gland is an example.

• Salivary glands are a type of compound tubuloacinar exocrine gland.

Secretions into the ducts are either serous or m ucous.
— Sublingual glands: Mostly mucous secretions; located below the

tongue and deeply embedded within the connective tissue of the
oral cavity.
— Submandibular glands: Serous AND mucous secretions in equal
amounts. Located under the mandible (NOT in the oral cavity).
— Parotid glands: Mostly serous secretions. The parotid gland is the
largest of the salivary glands and is located the furthest away from
the oral cavity, in front of the ears. Its duct, known as Stenon’s
duct, empties serous fluid into the mouth opposite the upper second
molar.
S jo g re n ’s sy n d rom e is an autoimmune disease that damages the

salivary glands, leading to dry eyes and a dry mouth. Remember
to ask your patients with dry eye if they have a dry mouth as well.
Remember, the pancreas contains both endocrine and exocrine

units, allowing it to have important roles in both the digestive
and e n d o crin e system s,
• The e x o crin e pancreas produces the main digestive en

zymes utilized for carbohydrate, protein, and lipid digestion
in the small intestine; these enzymes are transported to the
duodenum via the pancreatic duct.
• The e n d o crin e pancreas produces insulin, glucagon, and

somatostatin by a cluster of cells called the Islets o f Langer-
hans. The islets do not contain ducts, but instead utilize
fenestrated capillaries for direct entry of substances into the
bloodstream.
E n d ocrin e glands also evolve by invagination of an epithelial surface, but

unlike exocrine glands, the invagination is complete and the surface reforms.
Because endocrine glands do not have ducts, nearby connective tissue forms a
network of blood vessels around the secretory unit. Endocrine glands release

their hormones into the extracellular space, where they are absorbed by the
surrounding capillaries and delivered to the target tissue via the bloodstream.
Unlike exocrine glands, endocrine glands are ductless. D iabetes

m ellitus and G raves5 disease are endocrine gland diseases that
have ocular manifestations.
E n d ocrin e S ystem
Produces hormones that are absorbed into fenestrated capillaries (NOT ducts)
for direct delivery to target tissues via the bloodstream.
T h y ro id G lan d: Butterfly-shaped gland located anterior to the trachea that

contains two types of cells:
• Follicular cells: Simple cuboidal cells that line the follicles of the thy
roid gland and produce inactive thyroid hormone (i.e. colloid). W h e n
p ro m p te d by T S H , the colloid is m od ified t o m ature h orm on es
(T 3 and T 4 ).
• Parafollicular cells: Oval cells located between the follicles. Produce

calciton in , which decreases blood Ca2-t- by inhibiting osteoclast activity.
Signs of h yperth yroid ism include nervousness, heart palpita

tions, heat intolerance, weight loss (despite increased appetite),
and hair loss (including loss o f eyelashes).
P a ra th yroid gland: 4 glands located on the posterior (back) surface of the

thyroid gland.
• Chief cells within the parathyroid gland produce parathyroid hormone

(PTH), which increases blood calcium by stimulating osteoclast activity.

A d ren a l gland : Paired glands that sit on top of each kidney with a sur
rounding connective tissue capsule. The adrenal glands consist of an inner
medulla and outer cortex.
• The inner medulla contains chrom affin granules that produce epinephrine
(85%) and n orep in ep h rin e (15%), neurotransmitters utilized by the
sympathetic nervous system in response to fight or flight conditions (2).
• The cortex conatins three zones:
1. Zonula Glomerulosa: Produces aldosteron e (mineralocorticoid).

2. Zonula Fasciculata: Produces cortisol (glucocorticoid).
3. Zonula Reticularis: Produces androgen.
Prom outer zone to inner zone: salt (mineralocorticoids), sugar

(glucocorticoids), and sex (androgen).
P itu ita ry gland (H y p o p h y sis): Located within the sella tu rcica in the
body of the sphenoid bone. This gland has an anterior and posterior lobe that
are completely separate from one another - they do not share embryo logic,
histologic, or anatomical characteristics.
1. A n terior p itu ita ry: Formed from tissue in the r o o f o f the m ou th

(Rathke’s pouch) that pinches off and fuses with the hypothalamus. The
pars distalis is the largest region of the anterior pituitary, making up
almost the entire anterior lobe. The anterior pituitary contains two types
o f cells:
a) A cid o p h ile s (alpha cells): Stain pink/red due to eosin.

• Somatotrophs: Produce grow th h orm on e during puberty.
• Mamotrophs: Produce prolactin, which produces breast milk.
Prolactin works with oxytocin, which causes milk secretion.
b) B asop h ils (beta cells): Stain blue/purple due to hemotoxylin.
• Gonadotrophs: Produce F SH and LH.
• Thyrotrophs: Produce T S H .
• Corticotrophs: Produce A C T H .

Acidophil tumors cause excessive growth hormone secretion, which

results in gigantism in kids and a crom eg a ly in adults. Basophil
tumors cause excessive ACTH secretion, which results in C ush
in g’ s disease.
Recall from physiology that the hypothalamus releases hormones

that control the production of hormones produced in the anterior
pituitary (growth hormone, prolactin, FSH, LH, TSH, and ACTH).
2. P osterior P itu itary: Develops from neural tissue that originates in

the floor of the diencephalon and remains attached to the hypothalamus.
T his region d oes N O T p ro d u ce any horm on es, but is responsible
for their storage and release.
• The hypothalamus contains paraventricular and supraoptic nuclei

that produce A D H and o x y to cin . These hormones are transported
through the infundibular stem into the pars nervosa of the posterior
pituitary.
• The pars nervosa is the posterior (back) portion of the posterior
pituitary that stores hormones in vesicles known as Herring bodies.
Hormones are released into the bloodstream when the pars nervosa
receives a signal from the hypothalamus.
wsmsmsmMmmMiim mi
Connective tissue includes connective tissue proper and specialized connective
tissue.
* Connective tissue proper is utilized for structure and support and is

packed around every major organ in the body.
• Specialized connective tissue includes blood, bones, and cartilage.
Connective tissue proper and specialized connective tissue are derived from
m esenchym e, a subtype of mesoderm.

C o n n e ctiv e T issu e P r o p e r
Connective tissue (CT) is the most predominant tissue in the body. It is

classified by density and the types of cells and fibers. CT has a prominent
extracellular matrix that includes fibers and glycosaminoglycans (GAGs).
• Dense C T is characterized by lots of fibers with few cells.
• Loose C T is characterized by fewer fibers and more cells (although not

as prominent as epithelial tissue).
Remember, C T has m ore fibers and less cells than epithelial

tissue.
C ells o f C o n n e ctiv e T issu e
• F ib rob la sts: Signature cell of CT that is responsible for producing and

maintaining fibers and ground substance within CT proper.
• P lasm a cells: Mature B lymphocytes that produce antibodies.
• M a st cells: Contain granules with heparin and histamine that, when

released, lead to vascular vasodilation and smooth muscle constriction.
• M a crop h a g es: Aid in phagocytosis and act as antigen presenting cells.

Macrophages have different names depending on their location within
tissues:
— Brain: Microglia
— Liver: Kupffer cells
— Blood: Monocytes until cells leave the blood, then called a macrophage.
H istam in e release during anaphylactic shock results in a clinical

picture that can include itching, redness, wheezing, and hypoten
sion (non-exhaustive list).
• P ericytes: Undifferentiated CT cells that attach to capillaries and can

replace CT in times o f need. They play an important stabilizing role
in maintaining blood flow through capillary walls. P ericyte dam age
con trib u tes to d ia b e tic retinopathy.

F ibers o f C T : C ollagen, Elastin, R eticu la r fibers
1. C ollagen: The predominant fiber in CT and the most predominant pro

tein in the body. There are 8 different types of collagen, depending on
the location within the body.
C ollagen structure includes the sequence (Gly-X-Y)n, with glycine

always comprising 1/3 of the collagen (1).
2. Elastic fibers: Composed of the protein elastin and located within the der
mis o f the skin where they provide recoil when tissue is pulled. Elastin is
also located within the aorta and higher pressured blood vessels. Damage
to elastin by hyaluronic acid and ultraviolet light is the major cause of
wrinkles.
3. Reticular fibers: Immature CT that forms the framework of lymphoid

and myeloid tissues and encompasses much of the interstitial tissue of
organs.
G lycosa m in og lycan s (G A G s) are long, negatively charged polysaccha

rides that contain a core of disaccharide repeating units. GAGs are rigid
(allowing compression), and are attracted to water, characteristics that are
important for maintaining structural integrity in cells. Types of GAGs include
the following:
• Hyaluronic acid: Repeating disaccharide composed of glucuronic acid and

N-acetylglucosamine. Hyaluronic acid is unique because it does NOT
contain any sulfate and is not bound to a protein as a proteoglycan (as
with most GAGs).
H yalu ronic acid (H A ) is found in high concentrations in the

vitreous. Each HA molecule is very large, providing an ideal make
up for shock absorption in the vitreous. Hyaluronic acid is the
dominant substance in the primary vitreous, forming a scaffolding
for collagen fibrils. With age, a breakdown of the blood-retinal
barrier leads to an accumulation of soluble proteins in the vitreous
and subsequent liquefication of the HA/collagen structure (6).

• Chondroitin sulfate: Makes up 33% of GAGs within the cornea. Also

found in cartilage, bone, and heart valves.
• Keratin sulfate: Makes up 66% of GAGs within the cornea. Also found
in bone and cartilage.
• Heparin: Found within granules in mast cells. Aids in anticoagulation by

inhibiting blooding clot formation.
Remember, p ro te o g ly ca n s are comprised of a sulfated GAG

bound to a protein.
We will now introduce the types of specialized connective tissue: blood, bone,
cartilage, and fat.
Blood
Comprised of plasma (55%), RBCs (45%), WBCs and platelets (< 1%) (2).
P lasm a: The non-cellular portion of the blood that consists of 80% water, 18%
protein, and 2% fats and other molecules. A lb u m in is the most abundant
protein in plasma and maintains blood osmolarity. Other plasma proteins
(aka globulins) include the following:
• Beta - Used in the complement pathway of the immune system.

• Alpha - Produced in the liver and aids in blood clotting.
• Gamma - Includes the different classes of antibodies (IgG, IgM, IgA,
etc.) produced by plasma cells.
C om p lem en t p rotein s within blood plasma are activated by

antigen/antibody complexes that occur with IgG, IgM, and IgA
antibodies.
R B C s (45% of total blood): Transports 0% to tissues and removes waste

products (C O 2 via exhalation in the lungs). Key features of RBCs include
the following:

* RBCs are very small (7-8 um) anuclear cells and are the most abun
dant cell within the blood.
• RBCs have a biconcave disk structure that allows for a greater sur
face area for the transport of O 2 to tissues.
* RBCs contain hemoglobin, which consists of Fe (5%) surrounded by
4 globulins (95%). Fe2+ binds 02, CO 2 , and CO (carbon monox
ide).
• RBCs have a life span of approximately 120 days and are recycled in
the spleen. Iron is reused by the spleen and the globulins are trans
ported to the gall bladder as pigment that is used in the formation
of bile. This pigment eventually gives feces its color.
W B C s (< 1% of total blood): All WBCs (i.e. leukocytes) originate from

primitive cells in the bone marrow. They are classified as granular
or agranular based on the appearance of their cytoplasms with light
microscopy (4).
1. G ran u locytes: Include basophils, eosinophils, and neutrophils, all

cells with polymorphonuclear or segmented nuclei.
2. A gra n u locytes: Include lymphocytes and monocytes (monocular
cells).
Remember the most to least common WBCs: Neutrophils (Most

common), Lymphocytes, Monocytes, Eosinophils, Basophils (least
common) - Never Let Monkeys Eat Bananas.
P latelets: Comprise < 1% of blood cells. Platelets produce the enzyme

th rom b opla stin , which converts prothrombin to th rom bin ; thrombin then
acts as an enzyme by converting fibrinogen to fibrin. Fibrinogen is in our
bloodstream at all times. Tissue injury activates platelets to produce throm
boplastin, initiating the cascade for the production of fibrin, which ultimately
forms a blood clot.
L ym ph ocytes are the

chief im mune cells
involved in fig h tin g ..
L ym p h ocytes Lym phocytes are broken into tw o v ir a l infections.
m ajor categories: B and T T h ey also help to fight
lym phocytes. Each o f these chronic bacterial infections
functions are explained below. when P M N s are worn out.

Hemopoietic Stem Cell

(Hemocytoblast)
Proerythroblast / I \ Monoblast
Erythrocyte Myeloblast Mega- ™ ^

j/ karyoblast Lymphoblast Monocyte
Progranulocyte
| II |
r
I
Megakaryocyte
N
Lymphocyte
Neutrophil ^ Basophil
Eosinophil ___| j I N ,
Granulocytes ^ Y T CCell
Thrombocyte B Cell
Agrann locytes
Figure 1.2: All blood cells are produced from a single stem cell in the bone
marrow in a process called h em op oiesis. The stem cell is called a hemocyto
blast and can differentiate into a RBC or WBC. In particular, look closely at
the myeloblast lineage (which leads to granulocyte formation) and the lym
phoblast lineage (which leads to B and T cell formation). In the systemic
disease chapter, you will learn about myelocytic leukemias (AML, CML) and
lym phocytic leukemias (ALL, CLL); this diagram should help in your un
derstanding of the conditions (e.g. in chronic myelocytic leukemia (CML),
increased basophils, eosinophils and neutrophils are expected).
T L y m p h ocytes M ediate the cellular immune

Originate in the bon e marrow, response by regulating B cells
m ature in the Thym us and m acrophages. These differentiate
into helper T cells, cy totoxic T cells
and suppressor T cells.
B L y m p h ocytes M ediate humoral immune response.
O riginate A N D m ature C an potentially becom e plasm a cells
in the bone marrow. and produce A bs.
Copyright 2014 by KMI< Educational Services, LLC

Granulocytes in G reater Detail

WBC (Leukocyte) Contents of Granules Clinical Importance
Basophils Anaphylaxis:
1 % of all WBCs. Bilobar Heparin (anticoagulant) Type 1 Sensitivity Rxn
nucleus with dense basophilic in 10% of the population,
stained granules. Histamine (vasodilator, factors cause excessive
Purpose: Increase vascular bronchoconstrictor). IgE release and
permeability, chemotaxis for other subsequent degranulation
WBCs. Commonly assoc with SRA (slow reacting of mast cells and basophils.
inflammation from allergic anaphylaxis factor). This results in
etiology. bronchospasms.
Eosinophils Histaminase and arylsulphatase
1 - 6% of WBCs. (inhibitors of SRA). An increase in eosinophils
2nd most common granulocyte, is commonly seen
bilobed nucleus, and eosinophilic in allergic reactions
stained granules. Mast cell Histamine initiates and in association
deregulation attracts eosinophils. inflammation, and eosinophils with parasites.
Phagocytic: when Ag/Ab stop it. Excess histamine
complexes form, eosinophils and SRAs signal
attach to the Ab and for eosinophils.
eat the Ag. Major Basic Protein:
used by eosinophils
to destroy parasites.
N eutrophils
40 - 75% of WBCs. Myeloperoxidase
Multilobed nucleus,
neutrally stained granules.
Phagocytic cells, elevated Lysozymes L or R shift;
in acute bacterial If a blood differential
infections or tissue damage. is ordered, and a L shift
Puss produced, indicating the Lactoferrin of neutrophils is seen,
breakdown of Ags, the body is producing many .
Macrophages engulf an antigen PMNs to fight the infection.
and use chemokines to tell Hydrolytic Enzymes A R shift means
neutrophils to leave the blood the fight is over,
and help with the antigen. or the body is
too worn-out to
fight anymore.

M ononuclear W B C s in Greater Detail

WBC (Leukocyte) Function Clinical Importance
M on ocytes Phagocytic cells Tuberculosis
2 - 10% of all
leukocytes. 3rd most
common WBC. Large, Some may also
kidney shaped nucleus. act as antigen In cases like Tb,
Largest of all blood presenting cells macrophages can wall-off
cells. Once these cells (APCs). In this case, the invader, leading to
enter tissues from blood, the macrophage granuloma formation within
they become macrophages displays Ags from the lungs.
of all sorts: a digested cell,
(Liver — KupfFer cells, If these Ags are
CNS = microglia, different than those
Lung = alveolar cells, inherently displayed,
Intestine = mesentery cells) T cells will recognize
this, and hunt down
any other foreign
cells with this marker.
B on e
A type of vascular C T (unlike cartilage) with many unique cells and functions
including:
• Storage site for calcium, phosphate, and other minerals.
• Attachment point for tendons, ligaments, and muscle.
• Protection of internal organs (brain, heart, lungs, etc).
• Provides a structural framework and an ability to resist mechanical stress.
• Produces blood cells within bone marrow.
ECM is calcified in bone (unlike cartilage) and does not allow nutrients to
diffuse through. ECM is produced, matures, and degrades before being renewed
again at a steady rate.
• O ste o cy te s are mature bone cells that surround the central artery. They
are responsible for m ain tenance of the matrix.
• O steob la sts p r o d u ce the matrix, called lamellae, in a concentric ring

around the central artery. Osteoblasts also remove Ca2-(- from the blood
and deposit it in the bone. Once the matrix begins to surround and trap
the osteoblasts, they become osteocytes.
• O steocla sts are large, phagocytic cells responsible for breaking dow n
and re m o d e lin g the matrix.

C a 2 + H om eostasis
• C a lciton in decreases blood Ca2+ levels by in h ibitin g osteoclasts.

Calcitonin also inhibits tubular reabsorption of Ca2+ and phosphorous
in the kidney, causing increased CA2+ loss in the urine.
• P arath yroid h orm on e increases blood Ca2+ levels by stim ulating

osteoclasts,
C artilage
Avascular C T composed of primarily type II collagen and chondroitin sulfate

(primary GAG). Cartilage is very hydrophilic and well-hydrated, allowing sig
nificant flexibility. Cartilage growth occurs via the following:
• Appositional growth: Chondrogenic cells (contribute to the perichon

drium covering cartilage) differentiate into chondroblasts, which then se
crete osteoid, causing cartilage tissue to increase in width from the outside
surface.
• Interstitial growth: Chondrocytes undergo mitosis, causing increased tis

sue growth from within (similar to blowing up a balloon).
M uscle
Developed from m esenchym e of m esod erm origin. Remember, all muscles
cells contain nuclei. Tendons connect muscles to bone and are composed of
fibroblast cells.
SKELETAL M U SCLE
Voluntary, striated muscle with mulitnucleated cells (4-6 nuclei pushed to the
periphery of the cell). Striations are a result of alternating A and I bands.
Skeletal muscle is found in E O M s and the tongue, and is responsible for vol
untary movements of the skeleton.
C A R D IA C M U SCLE
Involuntary striated muscle with mostly binucleated (central location) cells.

Muscle contractions are controlled by the ANS.
SM O O T H M USCLE
Involuntary, non-striated muscle with spindle shaped cells with centrally lo
cated nuclei. Smooth muscle is present in the digestive tract, blood vessels,

bronchioles, and in the ducts o f the urinary and reproductive systems. Cir
cular arrangements of smooth muscle in these locations allows for constriction
and narrowing of the lumen. Longitudinal arrangements of smooth muscle in
the digestive tract also assist in peristalsis. Examples of smooth muscle in the
eye include the iris sp h in cter and dilator muscles.
N eurons
Functional unit o f nervous tissue. There are three common types of neurons
that are classified according to the number of processes that extend from the
cell body:
• Unipolar: Found in the dorsal root ganglion,
• Bipolar: Found in the retina and olfactory mucosa; has one axon and one
dendrite that extend from the cell body.
• Multipolar: Most common type. Has several dendrites and one axon
extending from the cell body; motor neurons are a good example.
The a x on h illock is the portion o f the cell body where action po
tentials are generated. As the number of ribosomes increases during
cell growth, Nissl bodies (indicating rER) are found in the cyto
plasm (mainly) and within dendrites. No Nissl bodies are found in
the axon hillock.
P rop a g a tion o f N erve Im pulses
Propagation is typically unidirectional from dendrite to cell body to axon.

Axon transport can occur bidirectionally:
• Orthograde (i.e. anterograde): Impulse is propagated from cell body to

axon.
• Retrograde: Impulse travels from axon to cell body.

26 1.3. ORGAN SYSTEMS
O rth o grade degeneration can occur from panretinal photoco

agulation (PRP) of the retina. PRP initially causes ganglion cell
body death, which then leads to death of the axons entering the
optic nerve. Optic disc pallor can occur as a result of significant
axon damage. Remember, orthograde degeneration starts with cell
body death, followed by axon death.
M yelin
Increases the speed of conduction of action potentials through neurons. Because

the myelin sheath prevents the inward Na+ current necessary for the production
o f action potentials, action potentials can only be produced at gaps in the
myelin sheath known as the N od es o f R anvier. Action potentials “jump”
from one node to the next in a process called saltatory con d u ction .
• O lig o d e n d rocy tes produce the myelin sheath in the C N S; cytoplasmic

processes (arms) extend to wrap around multiple axons.
• Schwann cells produce the myelin sheath in the P N S ; these cells can
only provide myelin for one axon.
• Microglia: Support cells in the CNS by phagocytizing pathogens and

removing cellular debris.
• Astrocytes: Provide support for capillaries within the brain and con
tribute to the b lo o d /b r a in barrier. They are found only in the CNS.
Schwann cells are encased in a glycoprotein basement membrane

called the neurilem m a, which has been credited for allowing P N S
neurons to regenerate. Oligodendrocytes are NOT covered by
this BM and nerve regeneration does NOT occur in the CNS.
r - SECTION 1.3
O rgan System s
Jn t^lim erit
Includes the epidermis, dermis, and hypodermis.

C H A P T E R !. HISTOLOGY 27
Stratum Cornell m
itratum Luddum
Epidermis
Stratum Granulosum
Stratum Spl nosum
Stratum Basale
Papillary Layer
Reticular Layer
Dermis
Sebaceous Gland
Root Hair Plexus
Layers of the Integument
Figure 1.3: Layers of the Integument
E P ID E R M IS : Consists of an outer layer comprised of stratified squamous

keratinized epithelium that is avascular and thus relies on underlying CT for
blood supply. The epidermis also contains papillae that project into the un
derlying dermis to increase surface area and provide support to avoid shearing.
The epidermis consists of the following layers (see Figure 1.3):
Stratum corn eu m : Mature keratin that contains desmosomes and zonula oc-
cludens junctions for protection.
Stratum lu cid u m : Anuclear cells present in thick skin (NOT thin).
Stratum granulosum : Non-functional, non-mitotic cells with a granular ap

pearance due to immature keratin (keratohyaline).
Stratum spin osu m : Initial site of keratohyaline production. Contains deso-

mosomes but NO zonulae occludens. Mutations in mitotic cells (layers
closest to the stratum basale) can cause squam ous cell carcinom as.
Stratum basal: A single layer of cuboidal cells that forms the basement mem
brane for the epithelium. This is the ONLY mitotic layer in the epidermis.
On average, it takes 2 weeks for basal cells to reach the stratum corneum,
where they eventually slough off. UV exposure to basal cells may cause
a basal cell ca rcin om a .

• Melanocytes are interspersed within the basal cuboidal cells and

contain m elanin wrapped within melanosomes. The melanin within
melanocytes absorb UV light to protect the epidermis. Tanning
causes an inrease in the number of melanosomes, NOT an increase
in the number of melanocytes!
M alignant m elanom a occurs secondary to an increase in the

number of melanocytes. This is the most common intraocular can
cer in the eye. A primary malignant melanoma (starts in eye),
will metastasize most commonly to the liver first (5). The most
common etiology for a systemic metastatic tumor in the eye is
breast cancer (in women) and lung cancer (in men) (5). Seba
ceou s gland carcin om a is a rare, aggressive tumor (10% mortal
ity rate) of the meibomian glands that can mimic the appearance
of a chalazion (5).
O cular albinism (only eyes affected) and ocu lo cu ta n e o u s albinism (eyes

and skin affected) are a result of a deficiency in the enzyme tyrosinase that
converts tyrosine to melanin (5). These conditions are characterized by retinal
hypopigmentation, foveal hypoplasia (with reduced VA from 20/40-20/200),
iris transillumination with secondary photophobia, and nystagmus (see ocular
disease chapter for further details).
D E R M IS : The dermis contains sensory nerve endings that are important

for detecting touch, pressure, temperature, and pain.
O p en en d ed nerve endings
• Ruffini endings/Merkel discs: Mediate touch sensations.
• Nocireceptors: Mediate pain.
The pain caused by a corneal abrasion is the result of the open

ended nerve endings of n ocirecep tors (6).

E n capsu lated nerve en din gs
• Mediate touch and pressure sensations.
• Pacinian corpuscles are located in the dermis and mediate pressure. They
are encapsulated within approximately 30 layers of CT, which aids in the
absorption and localization of the sensation and allows for a much quicker
response to the stimulus.
The dermis is highly vascularized in two areas:
• Cutaneous plexus: Located between dermis and hypodermis.
• Subpapillary plexus: Located under the pars papillaris, the region of the
dermis that is closest to the epidermis.
H Y P O D E R M IS : Adipose tissue that underlies the dermis and serves as an

insulator to keep the core temperature constant. The hypodermis contains hair
follicles, sweat glands, and sebaceous glands:
• Sweat glands cool the body through the evaporation of sweat and produce
odorants that serve as sexual attractants.
• Sebaceous glands secrete oil onto hair follicles for transportation to the
surface of the skin in order to provide nourishment.
Layers o f th e H eart
• Endocardium: Inner lining of the heart chambers (tunica intima equiva

lent in blood vessels).
• Myocardia: Heart muscle (tunica media equivalent).
• Epicardium: Simple squamous epithelium over CT that contains auto

nomic nerves (tunica adventitia equivalent).
Recall from the general physiology chapter that the pu lm on ary

artery is the only artery that carries deoxygenated blood. The
p u lm on a ry vein is the only vein that carries oxygenated blood.

G en eral H istology o f B lo o d Vessels
E n doth eliu m : Almost all blood vessels in the body are lined with simple
squamous epithelium EXCEPT for the blood vessels in the lymph nodes,
which are lined with cuboidal cells.
T u n ica intim a: Composed of an inner wall (blood vessel endothelium) and

an outer wall (the internal elastic membrane) that contains arteries and
veins. The internal elastic membrane is more prominent in arteries.
T u n ica m edia: The middle layer consisting of SM in a circular arrangement,

type III collagen, and elastic fibers. This layer is the thickest layer in
arteries, is thin in veins, and is non-existent in capillaries.
E xtern al elastic lamina: Thin sheet of elastin that lies between the tunica
media and adventitia.
T u n ica adventitia: Outer layer consisting of loose CT that wraps the vessels
and fuses with surrounding CT that lies between the blood vessels.
* Vasa vasorum: Network of blood vessels in the adventitia that sup

ply the outer vessel layers. These vessels are usually affected first in
d iabetes.
C apillaries
A single layer o f simple squamous endothelium. They have no tunica media

and a thin tunica adventitia that connects to neighboring connective tissue.
There are three main types of capillaries:
N on -F en estrated: Most common type of capillary with a lining of endothe

lial cells joined with zonula occludens junctions. Found in the iris and
retina.
F enestrated capillaries: Endothelial cells line the entire lumen but are NOT
joined by tight junctions, creating pores within and between cells that
allow molecules and fluid to leak out of the vessels. Found in the ciliary
b o d y and ch oroid .
D iscon tin u ou s capillaries (aka sinusoidal capillaries): Endothelial cells are

not joined together (i.e. no tight junctions or diaphragms), allowing large
substances (e.g. RBCs) to leave the capillaries. Found in the spleen, bone
marrow, and liver.
C om p a rison o f A rteries and Veins
• Arterial walls are thicker than the lumen. The lumen of veins is in semilu
nar folds and is larger than the walls.

• The tunica media is the most prominent layer in arteries; the tunica
adventitia is the most prominent in veins.
F orm ation o f lym ph : As blood plasma passes through capillaries, hydro

static pressure within the blood pushes some of the fluid out of the plasma arfd
capillary walls and into nearby tissue space. Some of that fluid empties into
lym p h a tic vessels embedded within CT surrounding the capillaries. Once
fluid enters the lymphatic vessels, it is called lymph fluid.
• Lymphatic vessels are open-ended tubes that lead nowhere. They take
the lymph to lymph ducts, which contain smooth muscle and move the
lymph through peristaltic contractions to the left and right subclavian
veins. Before the lymph is returned to the venous circulation, it is filtered
through lymph nodes.
Lym ph N odes
Encapsulated lymph tissue with a kidney bean shaped structure. There are
500-600 lymph nodes located in the body; they are most prominent in the
armpits and at flexor joints (2).
Functions o f L y m p h N o d e s
• Production of lymphocytes and antibodies.
• Filtration of lymph and removal of dead bacteria.
• Transportation of tissue fluid, limiting exudates and edema.
The medial lymphatics in the orbit drain into the submandibular

lymph nodes. The lateral lymphatics of the orbit drain into the
parotid (preauricular) lymph nodes.
A ssocia ted L y m p h Stru ctu res
• Diffuse lymphatics: Scattered areas of accumulated T and B cells in areas

of lamina propria and areolar CT that filters tissue fluid.

• Nodule: Non-encapsulated accumulation of B-blast and plasma cells within

a diffuse lymphatic area. All of the Abs produced in this area are specific
for one antigen.
• MALT (Mucous associated lymphatic tissue): Diffuse lymphatic tissue

under moist membranes that is not encapsulated. Shares similar functions
with lymph nodes and helps to protect tissues from materials that have
crossed cell membranes. MALT is composed of B and T lymphocytes
and areolar CT fibers.
— Peyer’s patches are large patches of MALT (non-encapsulated nod

ules) within the small intestine.
L y m p h o id O rgans
Lymphoid organs all contain germinal centers and produce lymphocytes. Ex
amples include the tonsils, thymus, and spleen.
T onsil: Diffuse lymphatic tissue that is closely associated with an epithelial

surface; Infections within this tissue may lead to swelling, resulting in the
formation of a nodule or a tonsil (very large nodule).
T h ym u s: Located in the mediastinum behind the sternum. T h e size and

fu n ction o f th e thym us decreases after puberty. The thymus is divided
into a right and left lobe that are further separated into septa by thin strands
of C T extending from the CT capsule. Each lobe is divided into a darker
peripheral zone (the cortex) and a lighter central zone (the medulla). Blood
vessels enter and leave the thymus via the septa. The thymus has the following
functions:
• T h y m ic edu ca tion - location of maturation of T cells.
• Initiates the immune response.
• Aids in hematopoiesis in the fetus.
Cells in the thymus include:
• Reticular cells: Cells with an eosinophilic cytoplasm that provide support

to the lobules and secrete substances that allow for the “education” of T
lymphocytes in the cortex. These cells form H assall’s corp u scles as
they degenerate.
• Lymphocytes: Present in the medulla and, to a lesser extent, in the

cortex.
• Macrophages: Present in the cortex and the medulla.

Spleen: Located behind the stomach and below the diaphragm in the upper
left quadrant of the abdomen. The red pulp portion of the spleen has sinusoids
that filter unwanted materials from the blood, including old, worn out RBCs.
The white pulp portion of the spleen contains T and B lymphocytes and other
immunological cells that initiate an immune response to antigens found in the
blood.
The respiratory system consists of the upper and lower respiratory cavities. The
u pp er resp ira tory system includes the nasal cavity, pharynx, and larynx;
the low er resp ira tory system extends from the trachea down to the lungs
(see Figure 1.5).
U p p er R e sp ira to ry S y stem
The nasal cavity contains SSKE and olfactory epithelium. Paranasal si
nuses are air-filled continuations of the respiratory cavity; their names
are derived from the bones they are located within (see Figure 1.4).
The pharynx connects the nasal cavity to the larynx, It is lined with pseu-
dostratified epithelium or stratified squamous epithelium. The posterior
wall of the pharynx is visible when the patient says “Ahhh.”
The larynx contains vocal folds which control airflow and allow for the pro
duction of sound. The larynx is supported by a mix of hyaline and elastic
cartilage.
PARANASAL SINUSES
Sphenoid Sinuses
Figure 1.4: Paranasal Sinuses and Nose

Figure 1.5:
Low er R e sp ira to ry System
Extends from the trachea down to the lungs. The trachea is a 10-12 cm tube
that lies anterior to the esophagus and is lined with pseudostratxfied columnar
epithelium that is loaded with cilia. It contains C-shaped rings comprised of
hyaline cartilage, with the opening of the C facing posteriorly and in front of
the esophagus. The trachealis muscle, a smooth muscle that spans this opening,
constricts during expiration to aid in moving air out. The trachea extends to
the second costal cartilage (2nd rib behind the sternum) before dividing into
R and L primary bronchi.
P rim a ry bron ch i: A primary bronchus enters each lung.
S econ d a ry b ron chi: Intrapulmonary bronchi divide inside the lung. Sec
ondary bronchi are called lobar because each serves a lobe of the lung.
Recall that there are 3 lobes in the right lung and 2 lobes in the left
lung. The right primary intrapulmonary bronchus contains 3 secondary
bronchi and the left primary intrapulmonary bronchus contains 2 sec
ondary bronchi.
T ertiary b ron ch i: Each secondary bronchus divides into tertiary bronchi.

The right lung has 10 tertiary (i.e. segmental) bronchi and the left lung
has 8 segmental bronchi.
B ron ch op u lm on a ry segm ent: Each tertiary bronchus serves a bronchopul

monary segment, which is the smallest independent unit of the lung.

B ron ch ioles: The tertiary bronchi continue to divide into bronchioles. There
is NO hyaline cartialge in bronchioles (only in bronchi). Positive pressure
helps to open up bronchiole walls. Bronchioles divide further into pre-terminal
bronchioles => terminal bronchioles =4- respiratory bronchioles.
* R e sp ira to ry b ron ch ioles: First location of gaseous exchange. Respi

ratory bronchioles branch into alveolar ducts and sacs, both lined with
simple squamous epithelium. Approximately 300 million alveoli branch
off the ducts, sacs, and respiratory bronchioles (2).
The c o n d u ctio n p o r tio n of the respiratory tract extends from the

nasal cavity to the terminal bronchioles. The resp iratory p o rtio n
starts at the respiratory bronchioles and extends throughout the
individual units of the lung.
A lveoli
Type II pneumocytes are flat simple squamous-like cells that are responsible for
gas exchange and for producing surfactant (phospholipids and protein mixture)
to lower the surface tension of the alveoli to prevent the lungs from collaps
ing. Type I pneumocytes CANNOT regenerate if damaged. Instead, type II
pneumocytes will divide and replace Type 1 pneumocytes.
Recall that the sympathetic system causes bronchodilation of the

airways, while the parasympathetic system causes bronchoconstric-
tion.
mmmmsm
The GI tract consists of a muscular tube that extends from the mouth to the
anus. Movement along the tract is initially voluntary to the superior half of
the esophagus, and then becomes autonomically (PNS and SNS) controlled
through the remainder of the tract.
• The vagus nerve of the parasympathetic system stimulates secretions and

motility in the GI tract.
• The sympathetic fibers that innervate the GI tract cause a decrease in

peristalsis and secretions when stimulated.

Each portion of the GI tract is composed of the same layers, although subtle
changes in the layers help to determine location. The four concentric layers of
the lumen of the tract include m ucosa, subm ucosa, m uscularis externa,
and adventitia.
M u co sa : Composed of epithelium, lamina propria, and muscularis mucosa.

Innervated by the PNS that aids in control of villi and microvilli.
S u bm u cosa: Mixture of loose and dense irregular CT that contains the large
muscular arteries and veins of the GI tract. Also contains Meissner’s plexus,
a parasympathetic ganglion that innervates Brunner’s glands, which release
secretions that neutralize HC1. Damage to Meissner’s plexus results in paral
ysis of the muscularis mucosa and lack of secretions from Brunner’s and other
submucosal glands.
M u scu la r externa: Composed of inner circular and outer longitudinal mus

cle layers that move food down the GI tract via peristalsis.
• A u e rb a ch ’ s plexus is located between the two muscle layers and re

ceives parasympathetic and sympathetic innervation to control peristal
sis.
Hirschsprung’s disease is due to a lack of development of Auerbach’s

plexus, resulting in damage to the GI tract.
A d v en titia (Serosa): Outer layer consisting of loose CT that wraps around

the lumen of the GI tract and fuses with the surrounding CT.
O ral C a vity
M o u th and P h arynx: Lined with stratified squamous epithelium that be

comes keratinized on the dorsal side of the tongue and on the upper palate.
Serves as the site of initial fragmentation of food. Salivary glands release se
cretions that break down food into a bolus.
E sophagus: Transports the bolus from the pharynx to the stomach. The
upper 1/3 is composed of skeletal muscle, the mid 1/3 is composed of skeletal
and SM, and the lower 1/3 is composed of SM.

• Meissner’s plexus: Begins at the inferior portion of the esophagus. The

layer containing the plexus has very thick, stratified squamous non-keratinized
epithelium with submucosal mucus glands.
• Cardiac sphincter: Location of esophagus insertion into the stomach.

Reflex of stomach contents back into the esophagus through the sphincter
leads to heart burn.
Stom a ch
Location where food fragmentation continues and mixes with gastric secretions
to form chyme. The stomach is also the initial site of digestion for alcohol, some
water, and drugs. The stomach has four regions in the following order: cardiac,
fundus, body, and pyloric regions. The cardiac/pyloric regions (branched tubu
lar glands) and the fundus/body regions (straight tubular glands) are known
for their similar histology. The following cells and secretions occur throughout
the stomach (2):
• Goblet cells secrete mucous.
• Parietal cells secrete HC1 and intrinsic factor.
Intrinsic factor is necessary for vitamin B12 absorption. Damage to

parietal cells can lead to low levels of intrinsic factor and subsequent
p ern iciou s anem ia.
• Chief/Peptic cells secrete pepsinogen, an inactive enzyme that is cleaved

into pepsin (the active form) in the presence of HC1.
• Enterochromaffin cells secrete histamine and serotonin,
• G cells secrete gastrin, a key chemical that stimulates parietal cells and
chief cells to secrete HC1 and pepsinogen, respectively.
• D cells secrete somatostatin.
Excessive gastric secretions can cause an erosion of the mucous

membrane of the stomach, leading to gastric ulcers and gastric
reflex. N S A ID use exacerbates this process because they decrease
the production of prostaglandins in the stomach, which aid in the
protection of the mucosal lining.

Sm all Intestine
The mucosa of the small intestine consists of an outer surface of cells that
contain microvilli, resulting in a “brush border” appearance that increases the
surface area for absorp tion (a main key function of this organ). The cell
membrane of microvilli contain enzymes necessary for d ig estion (the 2nd key
function of the SI). The small intestine is composed of three regions: the duo
denum, jejunum, and ileum.
Recall that the pancreas releases enzymes utilized in the small

intestine (along with brush border enzymes) for digestion. The
sphincter of Oddi is the main sphincter of the pancreas. The pres
ence of CCK enzyme in the stomach and small intestine causes
this sphincter to open. B ile and pancreatic en zym es are then
released into the duodenum .
A b s o r p tio n F unctions
• The duodenum and jejunum are the sites of absorption for most carbo
hydrates, lipids, amino acids, calcium, and iron.
• The ileum absorbs most of the bile salts, vitamin B12, water, and elec
trolytes.
Su m m a ry o f D igestion
• Although protein digestion begins in the stomach (via pepsin), the duo
denum and jejunum are the main sites of protein digestion.
• Carbohydrate digestion into monosaccharides begins in the mouth (via

salivary amylase) and is completed in the duodenum (via pancreatic
amlyase). The stomach has no role in carbohydrate digestion.
• Lipid digestion begins in the duodenum via pancreatic lipase.
Large Intestine
The large intestine is responsible for water a b sorp tion and lu b rica tion o f
th e feces. This region has no villi but does contain numerous goblet cells.
The large intestine is composed of 3 regions: the cecum (appendix), colon, and
rectum,
• The outer longitudinal layer o f the large intestine has a unique arrange
ment of 3 separate sheets called tenia coli. The cecum and colon contain
tenia coli. The rectum does not.

C ou rse: Begins in the lower right quadrant at the ileocecal junction and then
ascends upward (ascending colon), travels horizontally to the other side of
the body (transverse colon), then travels down (descending colon) before
forming an S shape (sigmoid colon) and joining the rectum.
Liver
The liver is the largest gland in the body. It sits on the right side of the midline
under the diaphragm and is protected by the rib cage. The liver is divided into
right and left lobes.
• Falciform ligament: Connects the R and L lobes together and attaches

to the anterior wall of the abdomen.
* Coronary ligament: Attaches the liver to the inferior surface overlying

the diaphragm.
The liver is further divided into smaller segments called liver lobules, which are
hexagonal structures surrounded by connective tissue. The hepatocytes within
the liver lobules are large, eosinophilic, binuclear cells that are very active and
contain an abundance of rER, sER, Golgi apparatus, etc.
B lo o d flow th rou g h th e liver comes from two sources...
1. H ep a tic artery: A branch of the descending aorta (O2 rich blood)

that enters the liver and forms numerous smaller branches (each
lobule contains a branch at each corner).
2. P o rta l vein : Carries blood from the GI tract to the liver. The blood
in the portal vein is low in 0% but rich in nutrients (atypical for
veins). The portal vein is the largest structure in the corner of a
liver lobule.
• Each corner of a liver lobule contains a p orta l triad consisting
of a branch of the hepatic artery, portal vein, and bile duct.
- Bile canaliculi are channels formed between the hepatocytes
that receive bile produced by the liver. The canaliculi drain
into the bile ducts of the portal triad, then into the R /L
hepatic ducts (drain R /L sides of the liver), before draining
into the common hepatic duct. The cystic duct branches
from the common hepatic duct and carries bile into the gall
bladder.
C entral vein: The branches of the hepatic artery and portal vein that bring
blood into the liver are lined with sinusoid capillaries that are highly
fenestrated. Blood from each vessel easily leaks into the surrounding
tissue before combining to drain out of the liver through the central vein.

PORTAL SYSTEM
Figure 1.6: T h e P orta l System o f the Liver
• Hepatocytes line the sinusoidal capillaries in the liver and allow for
bidirectional movement of nutrients. They can absorb proteins from
the blood into the liver, or transport proteins, glucose, and other
substances produced in the liver into the blood stream.
• Kupffer cels are macrophages that surround the lumen and phago-
cytose antigens; they are only found in the liver.
The liver has several functions:
• Removes and stores fat-soluble vitamins (A,D,E,K) and vitamin B12.
• Lipid metabolism: Removes lipid molecules from the body.
• Detoxification of blood: Removes nitrogen (from protein metabolism)

from the blood and makes urea that is excreted by the kidneys.
• R eg u la tion o f glucose levels: If blood glucose levels increase, the liver

removes glucose and stores it as glycogen. If blood glucose levels decrease,
the liver breaks down glycogen and transports glucose molecules back into
the bloodstream.
• Produces bile: Hepatocytes produce the enzyme bile that is then stored
in the gall bladder.
— When a RBC dies, bilirubin (bile pigment) is recycled and is trans

ported to the liver, where it combines with bile salts, cholesterol,
and lecithin to form bile.

- Bile salts emulsify fat in the duodenum, creating an increased surface

area for lipases (from the pancreas) to aid in lipid digestion. Bile
pigments have NO function. They simply provide color to feces.
• Protein synthesis: Produces album in, fibrinogen, plasminogen, alpha

globulin (necessary for blood clotting), and beta globulins (function in
the complement system).
Low levels of albu m in in the bloodstream are indicative of mal

nutrition.
R eferences
[1] Bhushan V, Le T. Amin, Chirag. First Aid for USMLE Step 1. New York: McGraw-Hill,
2003.
[2] Fox, Stuart. Human Physiology, 6th ed. Boston: McGraw-Hill, 1999.
[3] Gartner L, Hiatt J. Color Atlas of Histology, 3rd ed. Philadelphia: Lippincott Williams and
Wilkins, 2000.
[4] Junqueira, L., Carneiro, J. Basic Histology, Text and Atlas, 7th ed. New York: McGraw-Hill,
2005.
[5] Kansld, Jack. Clinical Ophthalmology, A Systematic Approach, 4th ed. Oxford: Butterworth-
Heinemann, 1999.
[6] Kaufman P, Aim A, Adler’s Physiology of the Bye, 10th ed. St. Louis: Mosby, 2003
[7] Primo S. “Infectious and Inflammatory Diseases.” Optometry Clinics Vol. 3, Number 4, Sys
temic Disease and the Eye, Norwalk: Appleton and Lange, 1994
[8] Rapuano C, J. Ileng W. Color Atlas and Synopsis of Clinical Ophthalmology. Wills Eye
Hospital. Singapore: McGraw-Hill, 2003.
[9] Remington, Lee Ann. Clinical Anatomy of the Visual System. Boston: Butterworth-
Heinemann, 1988.
[10] Weissman B. “An Introduction to Ocular Immunology.” Optometry Clinics Vol. 3, Number
4, Systemic Disease and the Eye. Norwalk: Appleton and Lange, 1994.
[11] Young, Barbara. Wheater’s Functional Histology: A Test and Colour Atlas. 4th edition.
Cambridge: Churchill Livingston, 2000.

c
f
(
(
(
(
c·
(
(
(
(
(
(
(
( I
l
( .1
((
(
(
((
cc
cc
(c
(( ./
(_
(
(( .
((
((
Chapter 2
Neuroscience
Sarah D ou g h erty W o o d , O .D ., F .A .A .O .
K y le M . C h eath am , O .D ., F .A .A .O .,
43
r
(
(
(
(
(
(
c
c
(
c
(
c
c
{
\
(
(
(
c
c
c
(
c
c
(
c
(
CHAPTER 2. NEUROSCIENCE 45
- SECTION 2.1 ----------------------------------------------------- -----------------------------------
C ellular N euroscience and E lectrophysiology
Nerve cells communicate primarily through intercellular electrical signaling

that is mediated, in many cases, by short range chemical messengers. It is im
portant to understand the basic cellular mechanisms giving rise to the complex
multicellular behavior in the nervous system. We now cover some fundamentals
of cellular neuroscience (16, ch. 2-6) (9, ch. 4-16) (8, ch, 2).
R e stin g P oten tial: Neurons have a resting membrane potential of approxi

mately -60 to -70 mV, meaning that the internal cellular environment is more
negatively charged than its exterior counterpart. Such a potential is main
tained by the balance o f an electrochemical gradient and the active transport
of ions (most importantly Na+ and K + ) across the cell membrane.
C on d u cta n ce: For our purposes, conductance serves as a measure of the

ability of ions to flow across the cellular membrane. For example, a high K +
conductance indicates that potassium ions readily traverse the cellular mem
brane.
R estin g state: When a neuron is in its resting state, K + conductance is

high; thus, K+ ions are the dominant force in determining the resting potential
of the cell. The Na+ / K+ Pump, which exports Na+ and imports I<+ , also
plays a role in setting this resting potential. The table below lists some typical
(approximate) ion concentrations in mammalian neurons (16, pp. 50). Note
that different sources provide slightly different values.
Ion Extracellular Intracellular

Concentration (mM) Concentration (mM)
K+ 5 140
Na+ 145 10
Cl“ 110 4-30
Ca2+ 1-2 10~4
The inside of the cell is negatively charged relative to the exterior

environment. In addition, K + is more abundant inside the cell.

46 2.1. CELLULAR NEUROSCIENCE AND ELECTROPHYSIOLOGY
A c tio n P oten tial: Action potentials, often referred to as neural spikes, re
sult from an active process which generates a traveling electrical impulse. The
process is often termed an “all or none” process, meaning that if the membrane
potential crosses some threshold, there will be an action potential. For poten
tials below threshold, no spike will occur. With some notable exceptions, many
cells in the nervous system communicate primarily via action potentials.
Stages o f a N eu ron A ctio n P otential:
1. Na+ conductance increases in response to a local depolarization of the

membrane, leading to an inward current of Na+ .
2. The membrane potential rises steeply, resulting in a self-reinforcing cas

cade whereby more Na+ channels open.
3. Vm, the membrane potential, peaks at approximately 40 mV (though

this varies across cell types).
4. At this stage, K + conductance increases, meaning that K + readily exits

the cell. This results in the inactivation of Na+ channels.
5. Membrane potential now falls quickly and briefly overshoots the original.
That is, the membrane becomes more negative than at its resting state;
this is known as hyperpolarization.
Sum m ary: The ion channels in the cellular membrane open and close as
a result of various stimuli (another neuron, a physical stimulus, etc). As a
result, ions flow in/out of the cell according to the electrochemical driving
force. This active process leads to a propagating wave of electrical activity
along the neuron, an event known as an action potential or voltage spike.
Synapses are the physical meeting points between cells that facilitate multi
neuron communication. Synapses fall into two main categories:
1. Chemical synapse: Communication across a chemical synapse occurs via

a chemical messenger known as a neurotransmitter. The transmission is
limited by factors including the diffusion rate of the neurotransmitter and
the binding of the neurotransmitter to the subsequent cell membrane.
Sim plified idea: A simplified cascade occurs roughly as follows:
* An action potential occurs in cell A.

• Ca2+ permeability of the membrane increases and calcium enters
into cell A.

• Cell A releases small vesicles filled with neurotransmitter.

• The neurotransmitter diffuses across the syn aptic cleft, which is
the space between cells.
• The neurotransmitter binds to receptors on the surface of cell B.
• This binding results in a post synaptic current (called an E P S P or
IP S P , respectively, depending on whether the current is excitatory
or inhibitory) in cell B. Such a current will lead to a change in V m
in cell B.
• Multiple PSPs falling within small time periods and over small areas
are combined. That is, the effects from many PSPs at different
locations and times are added together into an aggregate response
in cell B.
• As a result, a new local membrane potential is reached.
• If this new V m exceeds a certain threshold, an action potential will
then be generated in cell B. Hence the signal can be passed on to
another cell, and the process begins anew.
Im p orta n t N eu rotra n sm itters: There are several important neuro

transmitters to know. We review some of the major players (16, pp. 127,
ch. 6):
G A B A : GABA is the most widely distributed inhibitory transmitter.

G lycin e: Glycine is an inhibitory neurotransmitter found in the brain
stem, spinal cord, and retina.
C h olin ergic: There are two receptor types for cholinergic neurotrans
mitters:
a) Nicotinic: Found in skeletal muscle and blocked by curare.
b) Muscarinic: Found in smooth muscle (e.g. cardiac muscle).
A d ren erg ic: Adrenergic neurotransmitters are often found in the sym
pathetic nervous system. Important examples are epinephrine and
serotonin (in the brainstem).
Acetylcholine is the neurotransmitter found at the neuromuscular

junction and in the parasympathetic nervous system. Note that
nicotinic Ach receptors are targeted by a - bungarotoxin (snake
venom).

48 2.2. NEUROANATOMY
R e-u p ta k e: The action of a neurotransmitter is often terminated by

the re-uptake of the chemical messenger at nerve terminals.
Neurotransmitter re-uptake is the basis for SSRJs and other drugs,

which manipulate the rate of this uptake.
2. Electrical synapse: At an electrical synapse, communication occurs via

direct electrical contact between cells. This contact is known as a gap
ju n ctio n . The transmission is much faster compared to the transmission
through a chemical synapse.
- SECTION 2,2 ----------------------------------------------------- -------------------------------------------------
N euroanatom y
Neuroanatomy is a diverse and complex field. We give only a brief summary of

some elementary fundamentals (16, ch, 1) (9, ch. 1,17) (21, ch. 5,6,7) (please
see ocular physiology for further details regarding motor and sensory nervous
system pathways).
IPeripheral N ervous System '

The PNS is organized into a sensory portion and a motor portion (16, pp. 11-
12) (21, ch. 6,7). The sensory portion includes a host of sensory neurons and
structures, while the motor portion is further divided into somatic and auto
nomic divisions. The PNS cellular structures are organized into ganglia and
nerves.
G anglia: Ganglia are local collections of nerve cell bodies (soma). An exam
ple is the dorsal root ganglia.
N erves: Nerves are collections of bundled axons.
S en sory D ivision : Ganglia with a sensory function lie near the spinal cord
(dorsal root ganglia) or the brainstem (cranial nerve ganglia).
S om a tic M o to r D ivision: The somatic motor division includes neurons

which innervate skeletal muscles. This division is responsible for most voluntary
motor behavior.

A u to n o m ic M o to r D ivision : The autonomic motor division includes neu

rons which innervate cardiac and smooth muscles and glands. Peripheral motor
neurons in the a u ton om ic ganglia, which receive input from visceral motor
neurons in the brainstem and spinal cord, extend to a wide array of smooth
muscle, glandular, and cardiac targets, thereby controlling a large portion of
involuntary behavior. The autonomic motor division is further subdivided into
the sy m p a th etic and p a ra sym p a th etic divisions. The former includes gan
glia near the vertebral column whose axons extend to a host of peripheral
sites. The latter ganglia are found specifically in the organs with which they
are associated.
The CNS is organized into several main divisions (16, ch. 1) (21, ch. 5) (see
also Figure 2.1). The cellular structures are organized into nuclei and cortex.
N u clei: Nuclei are collections of neurons with similar structure and function.
These are the CNS analog o f ganglia.
C ortex : Cortex refers to sheet-like layers of cells. Cortical cells typically

underlie high level cognitive, sensory, and motor processing. The cortex can
be divided into the following lobes:
• Frontal L o b e - contains the premotor cortex for motor activity (plan

ning and execution of motor tasks). The frontal lobe also contributes
significantly to the general personality of the patient (reasoning, plan
ning). For example, a patient with a frontal lobe tumor can suddenly
Figure 2.1: Brain and brainstem: Note in particular the location of the occipital
lobe. As the location of V I, this region serves a very important role in visual
processing. Drawing modified from SA Kinkel original.

50 2.3. DIVISIONS OF THE CENTRAL NERVOUS SYSTEM
start making comments not at all characteristic of past behavior. The

frontal lobe contains B ro ca ’ s area, which is responsible for speech pro
duction (recall that the frontal lobe is responsible for motor actions).
A lesion in Broca’s area is very frustrating to the patient because they
can not produce the words they want to say (termed aphasia) - B r o c a ’ s
lesions cause “ broken sp eech .”
• P arietal L ob e - responsible for sensory activity and recognition. For

example, a patient with a parietal lobe lesion would be able to tell you
that a pen is used for writing, but they would be unable to call the object
a pen.
• O ccip ita l L o b e - responsible for visual processing.
• T em p ora l L ob e - responsible for perception and sensory recognition

(auditory stimuli, speech) and memory. This also houses the h ip p o ca m
pus, which is responsible for short term memory and spatial orienta
tion. The hippocampus allows association of smell to past memories.
The temporal lobe contains W ernick e’s area, which is responsible for
speech recognition (not production). A patient with a lesion in Wernicke’s
area has perfect-sounding speech (because Broca’s area is normal), but
the words do not make any sense - W ern ick e’s lesions cause “ w ord y
s p e e ch .”
- SECTION 2.3 ------------------------------------------------- ---------------------------------
Divisions of th e C entral N ervous System
1. Spina.1 cord
2. Medulla
3. Pons
4. Midbrain
5. Diencephalon
6. Cerebral Hemispheres
7. Cerebellum
The spinal cord consists of gray matter and white matter.

• Gray matter makes up the butterfly shaped region of the spinal cord (as
seen in slices). It consists of cell bodies and unmyelinated axons. There
are both dorsal root neurons (sensory) and ventral root neurons (motor).
• White matter consists of bundles of myelinated axons (called fasciculi

or tr a c ts ). The white matter is sectioned into three fiber divisions:
1. Posterior funiculus
2. Lateral funiculus
3. Anterior funiculus
These tracts contain a host o f both ascending and descending pathways,

a few of which we will discuss below.
• Ascending Pathways: Ascending pathways (e.g. the spinocerebellar path

way) carry sensory information from the periphery of the body to the
brain. The generic ascending pathway consists of three neurons:
1. 1st order neuron: Soma located in the DRG.

2. 2nd order neuron: Connects 1st and 3rd order neurons.
3. 3rd order neuron: Cell body in the thalamus; projects to the cortex.
• Descending Pathways: Descending pathways (e.g. the pyramidal tracts)

carry motor impulses from the brain to the muscles.
• Spinal Nerves: There are 31 pairs of spinal nerves that innervate most
of the body. Some of these nerves are sensory, while others have motor
function.
Region Nerves Innervation

Cervical C1-C8 1-4: neck, 5-8: upper extremities
Thoracic T1-T12 Tl-12: upper extremities
Lumbar L1-L5 1-4: thigh, 4-5: thigh, leg, foot
Sacral S1-S5 1-3: thigh, leg, foot, 2-4: pelvis
Coccygeal 1 Coccygeal nerve
The brain stem consists of the m edulla, pon s, and the m id
brain. The medulla controls autonomic functions (e.g. heart rate,
digestion, breathing), the pons coordinates movement-related in
formation transfer between the cerebral hemisphere and the cere
bellum, and the midbrain controls an array of sensory and motor
functions, including the c o o rd in a tio n o f eye m ovem ent and
visual reflexes.

52 2.3. DIVISIONS OF THE CENTRAL NERVOUS SYSTEM
U p p e r m edu lla contains the pyramids (ventral and descending) and the
medial lemniscus (ascending dorsal tracts). The latter is made up of gracilus
and cuneate fasciculi (or tracts), which carry information about lower body and
trunk, respectively. Finally, the m edial longitudinal fasciculus (M L F )
relays vestibular information to exterior eye muscles and coord in a tes the
V O R . At this level, the fourth ventricle becomes apparent.
L ow er/ m id d le m edulla denotes the location of the vestibular nuclei as well

as the olivary nuclei, which are associated with learning and memory in cere
bellar function. Finally, we again see the large motor tracts of the pyramids.'
jPbris
The pons relays information between the midbrain and the medulla. It is the
location of the pontine nuclei, which serve as relay stations for motion-related
information transferred between the cortex and the cerebellum. The pons is
also involved in the control of respiration and sleep, and is the location of the
nuclei for cranial nerves V-VIII,
M idbrain ;A'\.
, The u p p er m idbrain is the location of the superior colliculus (colliculus =

small mound), which contains motor neurons controlling orientation of the
head/eyes. In addition, the upper midbrain contains the red nucleus, which
controls movement of the arms and the oculomotor nuclei. The Edxnger-
W estp h a l (III) nuclei contribute to the parasympathetic innervation of the
iris.
A lesion to the oculomotor or E.W. nuclei results in a loss of in

nervation to all extraocular muscles except for the superior oblique
(CN 4) and the lateral rectus (CN 6).
The low er m idb rain contains the inferior colliculus, which is responsible for
reflex response of the head/neck to auditory stimuli, as well as the cranial nerve
IV nucleus, which provides innervation to the contralateral superior oblique
muscle. In addition, at this location we start to make out the cerebellar pe
duncles, which are tracts leading to the cerebellum.

Recall that the neural tube consists o f three general areas: the fore
brain, midbrain, and hindbrain. The forebrain differentiates into
two additional regions, the telencephalon and diencephalon, which
are separated by the optic chiasm in the adult brain. The telen
cephalon gives rise to the cerebral hemispheres. T hus, it cou ld
b e said th at th e foreb ra in gives rise to th e dien ceph alon
and th e cereb ra l hem ispheres.
D ien cep h a lon
The diencephalon consists o f the epithalamus, thalamus, subthalamus, and

hypothalamus.
Epithalam us: The epithalamus contains the pineal gland, which secretes
melatonin.
T halam us: The thalamus relays sensory input to the cortex and includes
nuclei for voluntary motor movements.
Subthalam us: The subthalamus communicates with the basal ganglia to

help control muscle movement.
H ypoth alam u s: The hypothalamus regulates body temperature, eating,

and sleeping behavior.
The cerebral hemispheres are responsible for high level processing related to
sensory interpretation, motor control, intelligence, and emotion. The dominant
hemisphere is more in control of understanding and processing language, inter
mediate and long term memory, word retrieval, and emotional stability. The
non-dominant hemisphere is more responsible for recognizing facial expression
and vocal intonation, and for music and visual learning.
The cerebellum is involved in fine motor movements, posture, and balance.

While the architecture is well organized and therefore largely understood, the
number of cells malting up the cerebellum is positively immense.

54 2Jh BLOOD SUPPLY TO THE BRAIN
CIRCLE OF WILLIS
Anterior Cerebral
Figure 2.2: C ircle o f W illis
— SECTION 2.4 -------------------------------------------------------------------
Blood Supply to th e B rain
The blood supplying architecture in the brain is quite complex; we review only
the basic concepts (16, ch. 1) (25, ch. 21). Blood is supplied to the brain
primarily through two sets of arteries (left and right): the internal carotids
and the v erteb ral arteries. The 4 arteries meet near the pituitary gland.
V ertebrals: The vertebrals. arise from the subclavian arteries and (in concert
with the medullary arteries from the aorta) provide blood to the spinal cord.
The right and left vertebrals join together to form the basilar artery (which
supplies the pons) at the brainstem. The basilar artery then joins the internal
carotids at the C ircle o f W illis.
Internal ca rotids: The internal carotids arise from the common carotid ar
teries in the neck. The left common carotid artery branches off the aortic arch,
while the right common carotid artery branches off the brachiocephalic trunk.

Left Common Carotid Artery
Subclavian Artery
Figure 2.3: A o r tic A rch B ranches
They branch into the anterior and middle cerebral arteries and supply blood
to the forebrain.
C ircle o f W illis: The Circle of Willis is the meeting loop for the basilar
artery the internal carotids, and the anterior and posterior com m u n icatin g
arteries, which are small arteries bridging the basilar and internal carotids.
The Circle of Willis forms an arterial circle beneath the brain and distributes
blood to many parts of the brain.
- SECTION 2.5 -------------------- -----------------------------------------------------------------
N euro-O phthalm ic D isorders: O ptic N erve
A healthy optic nerve head will have distinct disc margins and healthy rim
tissue (both in coloration and structure), and will lack hemorrhages and nerve
fiber layer elevation. It is important to be able to recognize the variations that
represent abnormalities.

56 2.5. NEURO-OPHTHALMIC DISORDERS: OPTIC NERVE
The brightness comparison and red-cap desaturation tests are used

to determine if optic nerve damage is present. Recall that the
photostress test is used to evaluate for macular damage.
life 1
1. The ways an unhealthy optic nerve can manifest:
a) Edematous
b) Atrophic
i. Excavated
ii. Pallid
• Not previously edematous (primary optic atrophy)
* Previously edematous (secondary optic atrophy)
c) Normal (e.g. retrobulbar optic neuritis, posterior ischemic optic
neuropathy)
2. Disc Edema - Unilateral Edematous Optic Nerve
a) Possible signs: decreased acuity, APD, visual field defect, blurred

disc margins and nerve fiber elevation, and hemorrhages.
b) Pathogenesis: Pre-chiasmal disruption of the axoplasmic flow.
c) Most common causes (not exhaustive);
i. Anterior Ischemic Optic Neuropathy
• Arteritic - AAION (Giant Cell)
• Non-arteritic - NAION
ii. Diabetic Papillopathy
iii. CRVO (Central Retinal Vein Occlusion)
iv. Hypotony
v. Optic Neuritis
• Two forms depending on location: Papillitis (anterior) and
retrobulbar (the posterior 2/3 of the nerve).
• Possible causes: multiple sclerosis, viral, toxoplasmosis,
sarcoid, syphilis, tuberculosis, non-infectious uveitis, idio
pathic.
vi. Papillophlebitis
vii. Compressive lesion of the optic nerve
• Meningioma, thyroid disease, lymphoma, hemangioma

3. Papilledema - Bilateral edematous nerves secondary to increased in

tracranial pressure.
a) Possible signs: blurred disc margins, elevated and opaque nerve liber
layer, splinter hemorrhages, Paton’s folds (circumferential retinal
folds), absence of a spontaneous venous pulsation, hyperemia of the
disc, exudates, cotton wool spots, and venous distention. Visual
acuity is normal in the early stages.
b) Pathogenesis: Axoplasmic stasis as a result of elevated cerebrospinal
fluid pressure in the subarachnoid space of the intraorbital portion
of the optic nerve (13).
c) Most common causes (not exhaustive):
i. Malignant HTN
ii. Post-chiasmal tumor (space occupying lesion)
iii. Inflammatory
• Infectious (e.g. meningitis)
• Non-infectious (e.g. sarcoidosis)
iv. Pseudotumor cerebri (Idiopathic Intracranial Hypertension)
v. Compromised or obstructed venous outflow (intrar and extracra-
nially) (13)
4. Atrophic Optic Nerve (unilateral or bilateral)
a) Pathogenesis: destruction or degeneration of the optic nerve axons.

b) Types of optic nerve atrophy:
i. Excavated - loss of neuroretinal rim (see glaucoma section).
ii. Pallid - flat and whitish in color.
c) Causes of pallor of the rim:
i. Primary optic atrophy (not previously edematous)
• Trauma
• Toxic/Nutritional
• Retrograde degeneration (away from the brain towards the
eye, descending) - damage to the retrobulbar optic nerve
eventually causes pallor visible at the optic nerve head (e.g.
pituitary tumor).
• Orthograde degeneration (from the eye towards the brain,
ascending) - sufficient damage to the retinal ganglion cells
leads to nerve pallor (e.g. PRP, CRAO, HP, extensive geo
graphic atrophy).
• Hereditary (e.g. Leber’s Optic Neuropathy and Dominant
Optic Atrophy)
ii. Previously edematous - Secondary optic atrophy (see above list
of edematous causes)

58 2.5. NEUR.0 - OPHTHALMIC DISOB.DERS: OPTIC NERVE
Clinical note: At acute presentation, if a patient has two swollen

nerves, how can you distinguish papilledema from bilateral disc
edema? In general, if it is papilledema, the acuity will be normal.
With disc edema, the acuity will be decreased.
A r te ritic A n te rior Ischem ic O p tic N eu ropath y (A A I O N ) - Occlusion

o f the short posterior ciliary arteries, resulting in infarction of the anterior
optic disc; the most common cause is G iant C ell A rteritis (G C A ), which
is a systemic vasculitis of the medium and large blood vessels.
• Who: >55 years of age (13).
• Symptoms: Sudden vision loss in one eye with associated systemic symp
toms that may include temporal headache, tenderness or nodular tempo
ral artery, malaise, anorexia, scalp tenderness, neck pain, and jaw clau
dication.
• Testing: Elevated erythrocyte sedimentation rate (Westergren ESR), ele

vated C-reactive protein (CRP), and elevated platelets. Temporal artery
biopsies are performed as needed for confirmation of the diagnosis (al
though skip lesions can result in false negatives).
• T h is is an ocu la r em ergency! V ision loss in on e eye can quickly

spread t o the oth er eye!
Elevated ESR for men: >age/2, for women: >(age+ 10)/2
N o n a rteritic A n terior Ischem ic O p tic N eu rop ath y (N A IO N ) - Is

chemia to the anterior portion of the optic disc from an unknown etiology.
• Who: >50 years of age (13), no gender predilection.
• Risk factors: HTN, DM, hypercholesterolemia, disc at risk (small disc,

resulting in crowding of the axons as they pass through the scleral canal).
• Symptoms: Sudden, painless, irreversible, typically non-progressive vi

sion loss in one eye that most often occurs soon after awakening. Visual
field loss is variable (an inferior altitudinal defect is the most common
but is not the majority).

• Findings: Will have a normal sedimentation rate, C-reactive protein,

and platelet count and no systemic symptoms. It is VERY important to
distinguish NAION from AAION1
D ia b e tic pap illopath y - A form of NAION w ith ou t vision loss in a pa

tient with diabetes.
O p tic N euritis - Primary inflammation of the optic nerve (see above list for
possible causes).
• Who: Generally occurs between the ages of 20-45 (23); female predilec
tion (13),
• Symptoms: Unilateral sudden vision loss (VA may range from 20/20 to
NLP), variable visual field defects, and pain on eye m ovem ent (90%).
• Signs: May or may not have a swollen nerve (depending on the location on
inflammation); 1/3 o f cases present as papillitis with disc edema, and 2/3
of cases present as retrobulbar optic neuritis with a norm al appearing
o p tic nerve. In either case, patients will have an APD.
• In general, after the acute episode, vision returns to near normal, al
though patients will likely have decreased contrast sensitivity and optic
nerve pallor.
• Associated with m u ltip le sclerosis; the risk of developing MS after 10

years from the initial optic neuritis episode is 56% for patients with one
or more brain lesions on MRI, and 22% for patients with 0 lesions on
MRI (from the Optic Neuritis Treatment Trial).
MS patients can have INO, a lesion of the MLF (medial longitudinal

fasciculus) that results in no adduction on the ipsilateral side, with
nystagmus on the contralateral side. INO can be bilateral, and
convergence may or may not be intact.
N eu roretin itis - Anterior optic neuritis with a stellate macular star (ex
udates); the star is a result o f optic disc vasculopathy and leakage into the
macula (23). Neuroretinitis is infectious and immune-mediated; causes include
cat scratch fever, histoplasmosis, and toxoplasmosis.
P ap illoph lebitis - Occurs in young, healthy individuals, and is characterized

by retinal venous stasis. Patients retain good vision and have no associated
systemic diseases.

60 2.5. NEURO-OPHTHALMIC DISORDERS: OPTIC NERVE
T h y ro id -R e la te d O phthalm opathy (G raves’ O ph th alm op ath y) - An

autoimmune disorder characterized by edema of the EOMs and orbital adipose
tissue, resulting in optic nerve compression.
• Signs: Disc edema, APD, upper eyelid retraction , decreased acuity

and color vision, visual field defects, exophthalm os, and muscle restric
tions. An orbital CT scan is necessary to confirm the diagnosis. Please
see Ocular Disease for further details.
The in ferior and m edial recti are usually affected first in

thyroid-related ophthalmopathy.
M align an t (severe) H T N - Papilledema that occurs as a result of dan

gerously high blood pressure (>220/>120). T his is an em ergen cy! T h e
patient sh ou ld b e hospitalized im m ediately!
A lw ays check b lo o d pressure on patients who present with pa

pilledema!
F oster K e n n e d y syn drom e - Rare condition caused by a frontal lo b e

tu m o r that causes disc edema in one eye and disc pallor with decreased vision
in the fellow eye.
P se u d o tu m o r cerebri
• Who: Typically an overweight female of child-bearing age.
• Signs/symptoms: Papilledema, transient visual obscurations, enlarged

b lin d sp o t on visual fields, CN 6 palsy, and headaches.
• Diagnosis o f exclusion: Patients will have a normal MRI and CSF content
with a high opening pressure on lumbar puncture (>200 mm water).
• Possible causes/contributors: C A N T (Contraceptives, vitamin A , Naladixic

acid, Tetracyclines).
T o x ic /N u tr itio n a l O p tic N eu ropath y - Classic tem p ora l pallor of the

optic nerves. Characterized by bilateral, painless, progressive vision loss and
central o r ce n troceca l visual field loss; caused by alcoholism, malnutrition,
tobacco abuse, and toxicity from medications.

L e b e r ’s H ereditary O p tic N eu rop a th y - Occurs from mutations in mito

chondrial DNA that are inherited from the mother. 85% of those affected are
males, with an onset in the late teens or early 20s. Characterized by a sudden
onset of decreased central vision (20/200 to CF) (18). Early signs include disc
hyperemia; late signs include optic disc atrophy. The condition spontaneously
improves in 35% of cases (23).
D om in an t O p tic A tro p h y - The most common hereditary optic atrophy. It

develops in early childhood and is characterized by an insidious onset of mild to
moderate visual loss (20/30-20/70) (23), with temporal pallor and excavation
of the optic nerves.
O p tic nerve p it - Unilateral depression of the optic disc that is usually

located inferior/temporal. May develop a serous retinal detachment extending
from the optic pit to the macula. Patients are asymptomatic unless the macula
is involved.
M orn in g g lory sy n d rom e - Unilateral condition characterized by an en

larged, funnel-shaped, excavated optic nerve with resulting poor visual acuity.
O p tic nerve h ypoplasia - Incomplete development of the optic nerve that

may be unilateral or bilateral. Characterized by a hypoplastic disc surrounded
by a ring of sclera and a ring of hyper pigmentation (dou ble ring sign), with
resulting mild to severe vision loss. Patients may have additional systemic
defects. The condition is associated with fetal alcohol syndrome and maternal
drug use.
O p tic nerve c o lo b o m a - Due to incomplete closure of the embryonic fissure,

resulting in a large abnormally shaped disc. Colobomas are usually located
inferior/nasal (corresponding to the location of the embryonic fissure). Patients
can also have systemic defects.
O p tic nerve head drusen - Present in 3.4-24 per 1000 people (13). Char
acterized by hyaline b o d ie s in the optic disc that become more evident with
age and may cause visual field defects. Drusen will appear hyper-reflective on
a B -scan, even at reduced gain levels.

62 2.6. NEUR 0 - OPHTHALMIC DISORDERS: THE PUPIL
m nerve tu m o r
M e la n o c y to m a - Benign, darkly pigmented tumor lying adjacent to or on
top of the optic nerve. More common in African Americans. Has no effect on
vision.
O p tic nerve sheath m eningiom a - Generally benign, unilateral tumor

found in young to middle-aged women. The optic nerve is initially edematous,
followed by secondary optic atrophy and progressive vision loss.
O p tic nerve g liom a - The condition is benign if it presents during childhood

(typically detected in the 1st decade); it is malignant if it presents in adulthood.
Can be associated with neurofibromatosis.
- SECTION 2.6 -------------------------------------- ---------------------------------------------------------------
N euro-O phthalm ic Disorders: T he P u p il
We start by looking at the functions of the pupil size (1, ch. 8) (22, ch. 1).
• Pupil movement optimizes retinal illumination: pupil size can be adjusted

depending on light levels to enhance visual performance.
• Depth of focus: near work induces miosis and allows for an increased
depth of focus.
• Reduces optical aberrations: smaller pupils decrease chromatic and spher

ical aberrations. The amount of spherical aberration scales with the
square of the diameter of the entrance pupil.
The sw inging flash light test (aka Marcus Gunn testing, relative afferent-
pupillary testing) allows for comparison of the afferent pathway between the
two eyes. If one eye has damage or asymmetric bilateral damage, then an APD
should be present.
Causes o f an A P D include extensive retinal damage, a dense vit

reous hemorrhage, and optic nerve or optic tract damage (anterior
to the chiasm).

Testing for an A P D : After confirmation of the direct response in both eyes,

the light is shown in one eye for approximately three seconds and then is moved
as quickly as p ossib le to the other eye, where again there is a three second
pause to observe the pupil response. Then, as quickly as possible, the light is
moved back to the initial eye to observe the pupil response. T his test allows
com p a rison o f th e d irect an d consensual response o f the sam e eye.
These responses should be equal, and therefore n o m ovem ent o f the pupil
sh ou ld o ccu r with the swinging flashlight test. In an abnormal response, the
pupil will dilate in the eye with the unhealthy optic nerve (positive APD).
R everse A P D : The pupil of the “good eye” will constrict on the swinging
flash light test when the fellow eye has an APD. This is helpful to note when the
pupil movement cannot be observed in the “bad eye” (from a corneal opacity,
traumatic pupil, etc.).
We now summarize factors that cause anisocoria (1, ch. 8) (22, ch. 1). In 20%
of cases, an isocoria is physiologic, and therefore should be of no concern (IT).
This can be determined simply by measuring the pupil size in light and dark
conditions; if the difference remains constant between the two eyes, and both
.are equally reactive to light, then it is physiologic anisocoria.
Remember that CN 2 is responsible for afferent innervation, and

CN 3 is responsible for the efferent response (i.e. pupil size); thus,
an isocoria w ill always b e caused b y an efferent issue (never
an afferent (CN 2) issue)!
O verview o f A n isocoria :
• If the abn orm al p u p il is m io tic (there is a larger difference in pupil

size between the two eyes in the dark), consider the following differentials:
H o rn e r’ s syn drom e, uveitis (with posterior synechiae), and an Argyll
Robertson pupil (tertiary syphilis).
• If the abn orm al pu p il is fixed and dilated (there is a larger difference

in pupil size between the two eyes in the light), consider the following
differentials: Adie’s Tonic pupil, C N 3 palsy (may also have ptosis and.
diplopia), pharmacologic dilation, and iris sphincter trauma (usually a
result of intraocular surgery).
It is important to understand the following:
Copyright 2014 by I<MK Educational Services, LLC

64 2.6. NEURO-OPHTHALMIC DISORDERS: THE PUPIL
• If the pupil constricts with 0.125% pilocarpine, the patient has Adie’s
tonic pupil. If there is no response with 0.125%, then proceed to 1%.
• If 1% pilocarpine causes constriction, then the patient most likely has a

3rd nerve palsy. If 1% fails to constrict the pupil, than the pupil is dilated
secondary to trauma or a pharmacological agent (e.g. scopolamine patch,
overuse of Visine, mydriatics/cycloplegics) (1).
A d ie ’s T on ic P u p il
• Acute, dilated pupil caused by a lesion in the ciliary ganglion or ciliary

nerves from an unknown etiology. Commonly affects young (20-40 years
old) females (30% to 70% of cases) (1).
• Aide’s tonic pupil is typically unilateral (80%), although it becomes bi

lateral at a rate of 4% /yr (1).
• The iris will have a verm iform m ovem ent when viewed with the slit
lamp. The pupil with have slow and minimal to no constriction in re
sponse to light, but will slowly constrict in response to a near object.
0.125% pilocarpine will cause pupil constriction due to hypersensitivity
o f the cholinergic receptors on the iris sphincter muscle.
Remember A D ie’s Pupil.... Acute Dilated pupil caused by a CG

lesion.
A rg y ll R o b e r ts o n P u pil
• Miotic pupil associated with neurosyphilis, diabetes, and alcoholism (22).
• Results from a lesion of the tectoteg m en tal tract, which carries in
formation from both pretectal nuclei to their respective ipsilateral and
contralateral Edinger-Westphal nuclei (17).
• The condition is initially unilateral, but becomes bilateral with time (18).
• Characterized by light-near dissociation - the pupil does not react

or constricts poorly to light, but will constrict normally in response to
convergence/accommodation. Remember, pupil constriction in response
to a near object is mediated by fibers from the frontal eye fields that
provide input to the Edinger-Westphal nuclei (NOT the tectotegmental
tract) (11).

Remember, Argyll Robertson Pupil.... Accomodative Response

Present.
H o rn e r’ s S yn drom e
• Miotic pupil that is most notable in dim illumination.
• Due to a lesion of the sympathetic pathway, most notably from a Pan

coast’s tumor at the apex of the lung.
• Patients present with a triad of miosis, anhydrosis (no sweating), and

ptosis on the affected side.
• Pharmacologic testing can be used to confirm a Horner’s pupil:
- Remember that cocaine typically dilates normal eyes by blocking

the re-uptake of norepinephrine, allowing prolonged action of the
neurotransmitter on the radial muscle. In Horner’s syndrome, co
caine DOES NOT cause dilation. Cocaine will not help to determine
whether Horner’s syndrome is due to a pre or postganglionic lesion,
requiring a second step to confirm the diagnosis with pharmacologic
testing.
- Hydroxyamphetamine dilates normal eyes by stimulating the release
of norepinephrine from healthy postganglionic neurons. If 1% hy
droxyamphetamine fails to dilate a Horner’s pupil, then a p o s t
gan glion ic lesion is suspected (1).
Note that cocaine and hydroxyamphetamine are difficult to obtain

in most private practices. Instead, 1% apraclonidine may be
used to confirm a Horner’s pupil; in normal eyes, apraclonidine
has no effect on pupil size. However, apraclonidine will result in
pu p il dilation in a Horner’s pupil due to hypersensitivity of the
adrenergic receptors on the iris dilator muscle.
C om a P upils
H u tch in son ’s P u p il
• Unilateral dilated pupil in a comatose patient,
• Commonly a result of an ipsilateral tumor or subdural hematoma that is

compressing on the pupillary fibers located on the surface of CN 3 (1).

2.7. NEURO-OPHTHALMIC DISORDERS: OCULAR MOTOR PALSIES
66 AND OCULAR MYASTHENIA
Miosis
• The early stages of coma induce miosis because the inhibitory cortical
input to the EW nucleus is absent (1), The pupils will retain their re
sponsiveness to light.
- SECTION 2.7 -----------------------------------------------------------------------------------------------------
N euro-O phthalm ic Disorders: O cular M o to r Palsies

an d O cular M yasthenia
jCranial N erve III: O culom otor nerye ; C attc ;p,.y ^

The oculomotor nerve is composed of two divisions (24):
S u p erior division : Innervates the levator and the superior rectus.

In ferior division : Innervates the inferior rectus, medial rectus, and the
inferior oblique. The parasympathetic fibers that innervate the cil
iary muscle and the iris sphincter muscle also travel in the inferior
division.
A CN 3 palsy is considered complete if all 4 EOMs and the levator are involved.
An incomplete CN 3 palsy is involvement of anything less than a complete
CN 3 palsy. If the CN 3 palsy is complete, the patient will present with
his/her eye deviated down and out, with a significant ipsilateral ptosis.
S y m p tom s: Patients may or may not complain of diplopia, depending on the

extent of the ptosis.
E tio lo g y : The most common causes for a CN 3 palsy include a microvascular

infarct, trauma, and an aneurysm.
P u p il in volvem ent: A compressive lesion (tumor or aneurysm) will almost

always involve the pupil (fixed and dilated) due to the superficial location
of the pupil fibers along CN 3. An ischemic palsy likely will NOT have
pupil involvement.
Any pupil-involving or incomplete CN 3 palsy warrants im m ediate im aging

with an MRI/CT and MRA to rule out a compressive tumor or aneursym
(most commonly involving the posterior communicating artery).
pram
Innervates the superior oblique. A CN 4 palsy will present with a hyper devi
ation that will likely have a torsional component as well.

S ym ptom s: Vertical diplopia. Acquired CN 4 palsies also lead to torsional

diplopia. Patients may present with a head tilt away from th e side
o f th e lesion in order to minimize diplopia.
E tio lo g y : Trauma or congenital in nature. Remember that CN 4 is the most

susceptible to trauma because it has the longest course in the body of all
the cranial nerves.
Separating congenital from acquired: Congenital will have large vertical ver-
gence ranges.
D iagn osis: Park’s three step (see ocular motility chapter); a double Maddox
rod can be used to look for a torsional component. Versions may reveal
an over-action of the ipsilateral inferior oblique.
Innervates the lateral rectus. A CN 6 palsy is the most common o f the three
cranial nerve palsies affecting the EOMs.
S y m p tom : Horizontal diplopia.
E tiolog y : Microvascular infarction, Pseudotumor cerebri (due to stretching

of the nerve secondary to brainstem displacement), trauma, tumor, and
Horner’s syndrome (caused by a tumor involving the cavernous sinus or
brainstem).
D ifferential diagnosis: Duane’s syndrome (see ocular motility chapter) and

infantile or accommodative esotropia (see binocular vision chapter).
Immediate imaging (M R I/C T ) is warranted in the following cases:
• Young patients (< 50)
• Other neurological symptoms are present (headache or pain)
• Multiple cranial nerves are involved
• History of cancer
• Incomplete or pupil-involving CN 3 palsy
T h y ro id eye disease and m yasthenia gravis should be consid

ered as differentials for all ocular motor nerve palsies.
Copyright 2014 by K M K Educational Services, LLC

2.7, NEURO-OPHTHALMIC DISORDERS: OCULAR MOTOR PALSIES
68 AND OCULAR MYASTHENIA
Manifestation of myasthenia gravis (MG) that involves the muscles of the

eye; 90% of patients with systemic MG will have ocular manifestations
at some point in time. In 70% of cases, the ocular findings will be the
initial sign of MG (15).
In MG, acetylcholine (Ach) receptors are blocked or altered at the neuromus

cular junction, resulting in weakness of skeletal muscles.
S y m p tom s: The levator and EOMs are susceptible to a deficiency in inner

vation, resulting in ptosis and diplopia. These signs will be variable and
are worse at the end of the day or when the patient is tired.
D iagn osis: Tensilon test or high serum levels of Ach receptor antibodies.
T en silon test - a short-acting acetylcholinesterase inhibitor (Edro

phonium) is injected intravenously, inhibiting the breakdown of
Ach in the synaptic cleft and prolonging its duration of action.
Edrophonium will cause a temporary improvement in ptosis and / or
ocular misalignment in patients with MG.
References
[1] Bajandas, Frank J. Neuro-Ophthalmology Review Manual, 3rd ed. Slack Incorp. 1988.
[2] Gasser L, Fingeret M, Woodcome H, (1997). A tla s o f P r i m a r y E y e c a r e P ro c e d u re s , Second

edition. Appleton and Lange.
[3] Friedman, Pineda, Kaiser, (1998). T h e M a s s a c h u s e tts B y e a nd E a r I n fir m a r y Illu s tr a ted

M a n u a l o f O p h th a lm o lo g y , W.B. Saunders Company.
[4] Gilbert, S (2000). D e v e lo p m e n ta l B io lo g y , 6th Ed. Sinauer Associates, Inc,
[5] Grossman, Ashley (1998). C lin ica l E n d o cr in o lo g y , 2nd edition, Blackwell Science.
[6] Gurwood, Much nick (1997). T h e O p tic N e r v e in C lin ica l P r a c tic e , Butterworth-Heinemann.
[7] Harkins, Timothy. Clinical Geriatric Eyecare. Ch. 6: Geriatric Ocular Disease. Aston, Sheree
J. Maino, Joseph H. Boston: Butterworth-Heinemann, 1993.
[8] Johnston, D., Miao, S., Wu, S. (1995). F o u n d a tio n s o f C ellu la r N e u r o p h y s io lo g y . M IT Press,
[9] Kandell, E., Schwartz, J., Jessel, T. (2000). P r in c ip le s o f N eu ra l S c i e n c e , 4 th E d. McGraw-

Hill.
[10] Kanald, Jack. Clinical Ophthalmology, 4th edition. Oxford: Butterworth-Heinemann, 1999.
Copyright 2014 by KMK Educational Services, LLG

[11] Kaufman, P.> Aim, A.. Adler’ s Physiology of the Eye, 10th ed. St. Louis: Mosby, 2003
[12] Kline, Bajandas, (2004). N e u r o -o p h th a lm o lo g y r e v ie w m a n u a l, 5th edition, Slack.
[13] Kline, Foroozan, (2007). O p tic N e r v e D is o r d e r s , 2nd edition, Oxford.
[14] Lemmela, Foreman, Sistonen, Eriksson, Forsius, Jarvela, Genome-Wide Scan of Exfoliation
Syndrome, IOVS; Sept. 2007, Vol. 48, No. 9: 4136-4142.
[15] Miller NR, Newman NJ, Biousse V, Kerrison JB, (2008). W a lsh and I-Io y t’s C lin ica l N e u r o
op h th a lm o lo g y : T h e E s s e n tia ls , Second edition. Lippincott, Williams, and Wilkins.
[16] Purves, D., Augustine, G., Fitzpatrick, D., Katz, L., LaMantia, A., McNamara, J, Williams,
S. (2001). N e u r o s c ie n c e , 2 n d E d . Sinauer Associates, Inc.
I-Ieinemann, 1988-
[18] Rhee, Pyfer, (1999). W i ll’s E y e M a n u a l , 3rd edition, Lippincott, Williams, and Wilkins.
[19] Ritch R, Schlotzer-Schrehardt, Konstas, Why is glaucoma associated with exfoliation syn
drome? Progress in Retinal and Eye Research 22 (2003) 253-275.
[20] Schwartz, S. (1999). V isu a l P e r c e p t i o n : A C lin ic a l O r ie n ta tio n , 2 n d E d, McGraw-Hill.
[21] Sherwood, L. (1993). .Human P h y s io lo g y , 2 n d E d . West Publishing Company,
[22] Smith, J.L. The Pupil. The J. Lawton Smith lecture series. University of Miami, 1974.
[23] Spoor, T, (1992). Atlas o f O p tic N e r v e D is o r d e r s , Raven Press.
[24] Third, F ou rth , a nd S ixth N e r v e P a ls ie s , F o ca l P o in t s (1996), Module 8, American Academy

of Ophthalmology,1-14
[25] Tortora, G. and Grabowski, S. (1996). P r i n c ip le s o f A n a to m y and P h y s io lo g y , 8 th Ed.

Harper Collins College Publishers,

((
(
(
((
(
(
(
(
(
( '
(
(
(
(
((
((
(
(
((
((
(
(
(
\
((
((
((
((
((
((
((
((
((
((
(_t
((
Chapter
Ocular Anatomy
b y K y le M . C heatham , O .D ., F .A .A .O .
71
c
(
(
(
r
(
(
c
c
(
(
(
(
(
(
\
(
(
(
(
(
c
c
c
c
(
(
(
CHAPTER 3. OCULAR ANATOM Y 73
Author’s note: Lee Ann Remington’s C linical A n a tom y and

P h y siolog y o f th e V isu al S ystem (36) is currently the stan
dard optometric text for ocular anatomy. Without question, it has
served as a cornerstone of my personal education on the subject,
as it offers a complete and thorough treatment of clinical anatomy
relevant for optometry. Her text, along with the other references
listed at the end of the chapter, have made the following possible.
- SECTION 3.1 ---------------------------------------------
E yelid
We start our review of this subject by summarizing the layers of the eyelid (36,
ch. 9) (47, ch. 3).
Telecanthus is an abnormally increased distance between the me

dial canthi of the eyelids. P oliosis is whitening of the eyelashes.
M adarosis is a loss of eyelashes. Trichiasis is a turning inward
of eyelashes, often secondary to entropion. P hthiriasis p alp e
braru m is an infection of the eyelashes caused by Phthirus pubis.
1. S K IN L A Y E R
Thin layer of skin that contains fine hairs, sweat glands, and sebaceous glands.
The skin layer of the eyelid is unique because it is the thinnest in the b o d y
and contains no fat (43).
2. S U B C U T A N E O U S A R E O L A R L A Y E R
Thin layer of loose connective tissue that lies between the outer skin and the
underlying orbicularis. The upper lid subcutaneous areolar layer contains the
levator aponeruosis as it travels to its insertion within the skin and upper tarsal
plate.
3. O R B IC U L A R IS L A Y E R
Contains the palpebral portion of the orbicularis oculi, one of the muscles of
facial expression innervated by C N V II. Paralysis of the orbicularis will cause

74 S.i. EYELID
O rb ital Portion
o fO rb ic u la ris O c u ii
Lateral
Palpebral Portion of
Palpebral O rb icu la ris O cu ll
Raphe
M edial Palpebral
R aphe
C ilia ry Portion o f
O rb icu la ris O cu ll
Figure 3.1: Orbicularis Oculi
the lower eyelid to droop away from the globe, resulting in a condition known
as e ctro p io n . The orbicularis oculi has two portions:
O rb ita l p o r tio n Attaches to the orbital margins and extends outward. Used
for force d closu re o f the eyelids.
P a lp eb ra l p o r tio n Used for spontaneous and reflex blinking. Contains

two specialized areas:
1. M u scle o f R iolan : Also referred to as the pars ciliaris.

• The most superficial portion of the orbicularis oculi (i.e. sub-
tarsal portion) that keeps th e lid m argin tigh tly app lied to
th e g lo b e during eye movements (36). May contribute to ro
ta tin g th e eyelashes toward the eye during eyelid closure (22).
• The most anterior portion of the muscle of Riolan is the gray
line, a groove located between the eyelash insertions and the
meibomian glands (48). The gray line divides the lid into an
terior and posterior portions and serves as a surgical landmark
during lid repair (36).
2. M u scle o f H orn er: Also referred to as the pars lacrim alls.
• Fibers from the orbicularis (originating from the posterior lacrimal
crest and fascia of the lacrimal sac) that en circle the canali-
culi and help drain tears into the lacrimal sac.

4. S U B M U S C U L A R A R E O L A R L A Y E R
Thin layer of loose connective tissue that lies between the orbicularis and the
orbital septum. The upper lid submuscular areolar layer contains the levator
aponeurosis and the palpebral portion of the main lacrimal gland. The periph
eral and margin arcades are present in this layer within the upper and lower
eyelids.
5, O R B IT A L S E P T U M
Dense irregular connective tissue that serves as a barrier to the orbit in the
upper and lower eyelids. The o rb ita l sep tu m prevents fat from falling down
onto the lid margins and, more importantly, keeps infections localized to the
anterior portion of the eyelid, away from the orbit.
• P e riorb ita loosely covers the orbital bones. It projects anteriorly to

become the orbital septum and posteriorly to fuse with the dura of the
optic nerve.
• The orb ita l sep tu m is continuous with the periorbita and periosteum of
the skull. The orbital septum attaches medially to the posterior lacrimal
crest. The lacrimal sac is anterior to this attachment, meaning the orbital
septum does NOT protect the lacrim al sac from infection.
• The superior orbital septum serves as the insertion site for the levator
aponeurosis.
P resep ta l cellulitis is an infection that occurs anterior to the

orbital septum. O rbital cellu litis is an infection that occurs pos
terior to the orbital septum.
6. P O S T E R I O R M U S C U L A R S Y S T E M
Consists of the superior levator palpebrae muscle and the superior (i.e. Muller’s
muscle) and inferior tarsal muscles.
Superior palp ebral levator m uscle: Originates from the lesser wing of the
sphenoid at the orbital apex and serves as the m ain retractor o f the
u pp er eyelid (15 mm) (43). Whitnall’s ligament (superior transverse
ligament on the zygomatic bone) serves as a fulcrum and changes the
course of the muscle from anterior-posterior.to superior-inferior, allowing
it to perform its function.

76 3.1. EYELID
Figure 3.2: Layers of the Eyelid
• Course: Shortly after reaching Whitnall’s ligament, the levator mus

cle extends into the eyelid as a fan-shaped tendon known as the
levator aponeurosis. The tendon sends fibers anteriorly through
the orbital septum to attach to the skin and anterior surface of the
tarsal plate, forming the superior palp ebral furrow (36).
• The lateral horn of the levator aponeurosis travels across the lacrimal
gland and attaches to Whitnall’s ligament. The medial horn merges
with the medial palpebral ligament.
The su p erior palp ebral furrow is formed by the insertion of the

levator aponeurosis into the skin of the upper eyelid. The inferior
p a lp eb ra l fu rrow is formed by the indirect attachment of the
inferior rectus muscle into the skin of the lower eyelid. The eyelid
furrows separate the tarsal and orbital portions of the eyelid.

M u scle o f M u ller: Smooth muscle (a2 receptors) that is innervated by the

sym pa th etic nervous system (22). Also referred to as the superior tarsal
muscle.
• The superior muscle o f Muller originates on the levator and extends

into the tarsal plate. It widens the palpebral fissure by providing
1-3 mm of upper eyelid lift (m in or retractor).
• The inferior tarsal muscle of the lower eyelid (analogous to Muller’s
muscle) originates from the fascial sheath of the inferior rectus and
extends into the tarsal plate. It is also innervated by the sympathetic
nervous system and provides minor lower lid retraction.
• H o rn e r’ s sy n d rom e can result in m ild u p p er lid ptosis

and a reverse p tosis o f the low er eyelid due to a lack of
sympathetic innervation to the muscle of Muller and inferior
tarsal muscle.
• C N III palsy results in significant u p p er lid ptosis due

to lack of parasympathetic innervation to the levator.
• T h y roid eye disease can result in retra ction o f the mus

cle o f M uller, causing a “stare appearance” that is charac
teristic in these patients.
Recall that the normal interpalpebral fissure distance is 10-12 mm

in adults (22). Also remember that C N III opens the eye and C N
V II closes the eye.
7. T A R S A L P L A T E
Dense irregular connective tissue that provides rigidity to the eyelids. Com
posed of horizontal and vertical collagen fibrils that surround the meibomian
glands (24).
• M e ib o m ia n glands are very large sebaceous glands that are located

posterior to the eyelash follicles within the tarsal plate.
The upper and lower tarsal plates combine medially and laterally to form the
medial and lateral palpebral ligaments, respectively. The medial palpebral
ligament attaches to the maxillary bone, and the lateral palpebral ligament
attaches to Whitnall’s ligament.

78 3.1. EYELID
8. P A L P E B R A L C O N J U N C T IV A
Inner lining of the eyelids that contains two layers:
1, Epithelial layer: Stratified outer protective layer that extends into the
fornices and onto the bulbar conjunctiva- Contains goblet cells that
produce the mucin layer of the tear film. Recall that goblet cells are pre
dominantly found in the inferonasal fornix and on the bulbar conjunctiva
(most concentrated temporally) (22).
2. Stroma: Also referred to as the submucosa or substantia propria. Loose

vascularized CT composed of a superficial lymphoid layer and a deep
fibrous layer (47).
• Superficial lymphoid layer: Very immunologically active layer.

Contains IgA, macrophages, mast cells, PMNs, and eosinophils (36).
• Deep fibrous layer: Connects the conjunctiva to the underlying in
ternal structures.
- Contains the accessory lacrimal glands, nerves and blood
vesvsels of the eyelids (47).
- Becomes continuous with the dense CT of the tarsal plate.
jtSlhiids;:of the Ê^lidanti~

• Meibomian glands: Enormous sebaceous glands within the tarsal plate
that open along the lid margins just posterior to the eyelash follicles.
They produce the anterior lipid layer of the tear film. There are ap
proximately 25 glands in the upper eyelid and 20 glands in the lower
eyelid (24) (22).
• Glands of Zeis: Modified sebaceous glands associated with eyelash fol

licles (usually two Zeis glands per follicle). They lubricate the eyelashes
to prevent them from becoming brittle.
• Glands of M oll: Modified apocrine glands located near the lid margin.
They empty their contents onto eyelash follicles, Zeis glands, and the lid
■ margin (42) (36).
• Glands of Krause: Accessory lacrimal glands that are located in the

fornices of the conjunctiva (36). They are considered merocrine glands
and secrete fluids of the same composition as the main lacrimal gland.
• Glands of Wolfring: Accessory lacrimal glands that are larger and more
numerous than the glands of Krause. They are located predominately in
the tarsal conjunctiva (22).-

1. H olo crin e glands - Meibomian glands and the glands of

Zeis.
2. A p o c r in e glands - Glands o f Moll and goblet cells.
3. M e ro crin e glands - Accessory lacrimal glands.
Remember, during holocrine secretion the whole cell is shed into

the lumen. During apocrine secretion, a portion of the plasma
membrane buds off the cell and enters the lumen for secretion.
During merocrine secretion, cells simply secrete their substances by
exocytosis and therefore remain completely intact after secretion.
• V olu n tary m o to r: Zygomatic branch of the facial nerve; innervates

the orbicularis oculi.
« Involuntary m o to r: Sympathetic nervous system innervates the muscle

of Muller (36) (47).
• Sensory: The upper and lower eyelids are supplied by different branches
of the trigem inal nerve (36; 47):
- U pper eyelid: Innervated by the frontal and lacrimal branches of

V I (ophthalmic nerve).
— Low er eyelid: Innervated by the infraorbital and zygomaticofacial
branches of V 2 (maxillary nerve).
1. Internal C a rotid B ranches: The lateral and medial palpebral arteries

are branches of the ophthalmic artery that supply the deeper eyelid tissue.
• The palp ebral arcades are located in the submucosal areolar layer
of the upper and lower eyelids and are formed by the union of
the m edial p a lp eb ra l artery (ophthalmic artery branch) and the
lateral palp ebral a rtery (lacrimal artery branch). The arcades
supply the deep eyelid structures and are classified into the follow
ing (36):
- M arginal pa lp eb ral arcades are located closest to the eyelid
margin.
Copyright 2014 by KM K Educational Services, LLG

80 3.2. EYEBROWS
— P eriph eral palpebral arcades supply the fornices and the

posterior conjunctiva. They connect with the anterior ciliary
arteries, which supply the anterior region of the conjunctiva.
The an terior ciliary arteries provide circulation to the bulbar

conjunctiva and the ciliary body; this explains why patients with
uveitis can experience circumlimbal injection and decreased aque
ous humor production in the involved eye.
2. E xtern al C a rotid Branches: The facial artery branches off the exter
nal carotid and provides circulation to the superficial areas of the eyelid.
{Veil® ^ f
• The veins of the eyelids parallel the arteries. They drain into the palpe
bral and ophthalmic veins (36).
p o iiju n c ti\^ l L ym phatics ^ u ^ i

Lymphatic vessels are found in the conjunctiva and parallel the veins (43).
• L ateral lym p h atics drain into the parotid (preauricular) lymph nodes.
• M ed ia l lym p h atics drain into the submandibular lymph nodes (19).
- SECTION 3,2 ---------------- --------------------------------------------------------------------------------------
Eyebrows
We now introduce the eyebrows, an important element for p ro te ctio n and fa
cial expression (36, ch. 9). The cilia of the eyebrows and eyelashes are highly
sensitive and are able to elicit a blink reflex when necessary. The following
forehead muscles produce eyebrow movements for facial expression. Each is
innervated by C N V II:
Frontalis: The m ain elevator of the eyebrows and forehead. Fibers run
vertically to raise the eyebrow for a look of surprise or attention.
• Originates high on the scalp and inserts near the superior orbital
rim.
• The frontalis muscle is often use'd to compensate for a ptosis.

CHAPTER 3. OCULAR AN ATOM Y 81
C orru ga tor: M edial dep ressor of the eyebrow. Fibers run obliquely and
move the medial edge of the eyebrow down and inward for a look of
concentration or sorrow.
• Originates at the frontal bone and inserts into the skin above the
medial eyebrows.
• Produces the vertical wrinkles of the forehead as an element of facial
expression.
• Helps to reduce sun glare.
P roceru s: M ed ia l dep ressor of the eyebrow (with the corrugator muscle).

Pulls the skin between the eyebrows downward for an appearance of men
ace or aggression.
• Originates on the nasal bone (bridge of the nose) and inserts on the
frontalis muscle between the eyebrows on each side of the midline.
• Produces horizontal furrows across the bridge of the nose.
O rbicularis O culi: Primary lateral d ep ressor of the eyebrow.
- SECTION 3.3 — --------------------------------------------------------------------------------------------------
L acrim al System
We now summarize concepts related to the lacrimal system (47, ch. 3) (36).
Lacrim al gland: Located in a fossa on the temporal side of the frontal bone.
The lacrimal gland is divided into an orbital and palpebral portion by the
tendon of the superior levator palpebrae muscle. It is a tubuloalveolar
exocrine gland that releases its products via merocrine secretion.
• The lacrimal gland is supplied by the glandular branches of the

lacrim al artery and is drained by the lacrim al vein. It also
contains the ONLY lymphatic vessels of the orbit (drains into the
parotid lymph nodes).
• The lacrimal gland receives parasympathetic innervation from the
lacrim al nerve of the pterygopalatine ganglion of C N V II; parasym
pathetic stimulation causes secretion o f aqueous humor.
• Some sympathetic nerve fibers also follow the lacrimal artery to
innervate the lacrimal gland.
A c u te dacryoaden itis is an infection and/or inflammation of the

lacrimal gland and can result in acute swelling and discomfort in
the upper lateral eyelid.

82 3.3. LACRIMAL SYSTEM
A cce sso ry lacrim al glands have the same histological makeup as the main
lacrimal gland and include the glands of W olfrin g and the glands of
K rau se, They are located in the subconjunctival tissue from the fornix
up to the tarsal plate (36).
Consists of the lacrimal puncta, canaliculi, lacrimal sac, and the nasolacrimal
duct (see Figure 3.3).
Lacrim al pu n cta: Located within a ring of connective tissue called the lacrimal
papilla. Each puncta in the upper and lower lid drains into a canaliculus.
• The lacrim al papilla is responsible for keeping the puncta open.
C analiculi: 10 mm long tube lined with stratified and pseudostratified epithe

lium that connects each puncta to the lacrimal sac.
• Each tube initially runs vertically 2 mm, then travels medially 8

mm before joining together to form the co m m o n canaliculus that
enters the lacrimal sac. The angle at which the common canaliculus
enters the sac prevents backflow.
• Remember, the m uscle o f H orn er (part of the orbicularis oculi)
surrounds the canaliculi. During eyelid closure, the muscle of Horner
contracts the canaliculi to assist in tear drainage.
L acrim al Sac: Lies within a fossa in the medial orbital wall formed by the
posterior lacrimal crest of the lacrimal bone and the anterior lacrimal
crest of the maxillary bone. The lacrimal sac is 10-12 mm long and is lined
with a double epithelium (superficial columnar and deep basal layers)
Figure 3.3: Lacrimal System

Orbicularis
Ocull
Orbicularis
Ocull
Figure 3.4: Relationship of Lacrimal System to Sinuses
with microvilli and goblet cells. It is continuous with the nasolacrimal

duct.
• The orbital septum is p o s te rio r to the lacrimal sac, malting it more

susceptible to infection. The check ligament of the medial rectus is
also posterior to the lacrimal sac.
• The medial palpebral ligament (from the medial upper and lower
tarsal plates) divides into two sections that attaches in front of and
behind the sac, straddling it.
• The muscle of Horner also surrounds the lacrimal sac, dividing it
into upper and lower sections (24).
D a cry ocy stitis is an infection of the lacrimal sac. It usually oc

curs as a result of nasolacrimal duct obstruction.
N asolacrim al du ct: Travels within the nasolacrimal canal that is formed by

the posterior lacrimal crest of the maxillary bone and the inferior concha
and lies adjacent to the m axillary sinus. The nasolacrimal duct is 15
mm long and is lined with a double epithelium, microvilli, and goblet
cells (similar to the lacrimal sac). The duct terminates in the inferior
meatus of the nasal cavity.

84 3 Jh ORBIT
V alve o f H asner: Located at the end of the nasolacrimal duct. It prevents

back flow of nasal fluids into the lacrimal drainage system (36).
- SECTION 3.4 --------------------------------------------
O rbit
We now summarize concepts related to the orbit (36, ch. 10) (22, ch. 34),
The orbit contains the globe of the eye, the extraocular muscles, the optic nerve
and other smaller nerves, connective tissue, and adipose tissue.
T h y ro id -re la ted oph th alm op ath y is an autoimmune response

against the connective tissue and adipose tissue within the orbit.
It causes swelling and inflammation of the orbital tissues, leading
to proptosis, lid retraction, EOM restrictions, and possible optic
nerve compression (22).
A d ip o s e tissue is separated into two compartments relative to the location

of the EOMs:
* In tracon al adipose tissue is located WITHIN the muscle cone of

the four recti muscles and serves to separate them from the optic
nerve.
• E x tra con a l adipose tissue is located OUTSIDE the muscle cone
between the EOMs and the walls of the orbit.
E x tra ocu la r m uscles are extrinsic muscles of the eye that attach to the
sclera. EOMs have several unique characteristics compared to typical
skeletal muscle fibers (36):
1. B lo o d su p p ly is denser in EOMs.
2. N erve su p ply is denser and more finely tuned in EOMs. '
3. EOM movements are faster and more fatigue resistant due to a
unique combination of white (fast) and red (slow but sustaining)
muscle fibers.

The following provides a summary for the origin and insertion sites for the six
extraocular muscles (see ocular motility chapter for further details on angles of
insertion):
Su p erior rectus: Originates from the co m m o n tendinous ring (aka annu

lus of Zinn) anterior to the superior orbital fissure and inserts 7.7 mm
from the limbus (36).
• The sheath covering the superior rectus is connected to the sheath

of the superior levator palpebrae muscle and the connective tissue
of the superior conjunctival fornix. These connections ensure that
the lid is raised when the eye is in upgaze.
In ferior rectus: Originates from the co m m o n ten din ou s ring at the in
fraoptic tubercule and inserts 6.5 mm from the limbus (36).
• The IR sheath combines with the IO sheath to form the suspensory

ligament of Lockwood. It attaches to the inferior tarsal plate and
extends from the zygomatic bone of the lateral wall to the lacrimal
bone of the medial wall to provide support for the globe.
Lateral rectus: Originates from the C T R at the spina recti lateralis and
inserts 6.9 mm from the limbus. The lateral check ligament anchors the
LR to WhitnalPs tubercule on the zygomatic bone of the orbit (lateral
wall).
Figure 3.5: Extraocular Muscles of the Orbit

86 84- ORBIT
M ed ia l rectus: Originates from the C T R and inserts 5.5 mm from the lim
bus (36). The medial check ligament anchors the MR to the medial orbital
septum, the bone behind the posterior lacrimal crest, the caruncle, and
the plica semilunaris.
ALL recti muscles originate from the C T R . The recti muscle in
sertions on the globe form the Spiral o f Tillaux, with the SR
inserting furthest away and the MR inserting closest to the limbus.
Su p erior o b liq u e: Originates at the lesser w ing o f the sp h en oid b o n e

and the C T R (36) (22). It travels anteriorly before looping through the
trochlea to insert on the superior lateral globe behind the equator.
• The tro ch le a is considered the physiologic origin of the SO because

it changes its direction of action.
In ferior ob liq u e: Originates ANTERIORLY at the maxillary bone posterior

to the medial orbital rim and lateral to the nasolacrimal canal. It inserts
on the inferior lateral globe behind the equator.
'Superior O b liq u e
Medial i H M b - L a t e r a l Rectus
Rectus
Inferior Rectus
Figure 3.6: Anterior Insertions of the EOMs

All EOM tendons pierce Tenon’s capsule, which sends a “sleeve” of

connective tissue with the tendons for a short distance before they
merge with the sclera.
The eyes move in six different primary directions via the following six muscles:
MUSCLE PRIMARY SECONDARY TERTIARY
Lateral Rectus Abduction None None
Medial Rectus Adduction None None
Superior Rectus Elevation Intorsion Adduction
Inferior Rectus Depression Extorsion Adduction
Superior Oblique Intorsion Depression Abduction
Inferior Oblique Extorsion Elevation Abduction
Remember the following (see ocular motility for further details):
1. The prim ary action for the obliq u es is torsion.
2. Superiors always in tort and inferiors always ex tort.
3. O bliques always A B d u c t and s u p e rio r/in fe rio r recti always A D d u ct.
Remember “O ’s (obliques) to the nose:” Because of the angle of

insertion, the superior and inferior obliques are responsible for pure
elevation and depression when the eye is ADducted 51-55 degrees
towards the midline (see ocular motility for further details).
B lo o d S u pply and In n ervation o f E O M s
• The EOMs are predominately supplied by two muscular branches from

the oph th alm ic artery:
1. The superior lateral branch supplies the SR, LR, and SO,
2. The inferior medial branch supplies the M R , IR , and IO,
3. The lacrimal, supraorbital, and infraorbital arteries may provide a
minor blood supply to the EOMs.
• The EOMs are innervated by the following nerves:
— The su perior d ivision o f C N III innervates the S R ,

— The inferior division o f C N III innervates the IR , IO , and M R .
- C N V I innervates the L R ,
- C N IV innervates the SO.

88 34- ORBIT
O rb ita l Fascia
The orbital fascia (aka periorbita or orbital periosteum) is composed of dense

connective tissue that covers the bones of the orbit. It provides support to the
blood vessels within the orbit and serves as a point of attachment for muscles,
tendons, and ligaments. The orbital fascia is continuous with the periosteum
of the skull and bones of the face.
• The orbital fascia within the optic canal is continuous with the dura
mater surrounding the brain and optic nerve and also contributes to the
formation of the CTR.
• A portion o f the orbital fascia covers the lacrimal gland, the lacrimal sac,
and contributes to the lining of the nasolacrimal canal,
• The anterior orbital fascia forms the orb ita l sep tu m within the upper
and lower eyelids and acts as a barrier, preventing prolapse of orbital fat
and orbital infections.
A n atom ic R elationships am ong O rbital 1S tru c tu re s

S p h en oid b o n e
A single bone whose middle portion (the body) forms the base of the cranium.
The optic canal in each eye is located just lateral to the center of the sphenoid
body.
The sella tu rcica is a depression in the body of the sphenoid

bone that houses the pituitary gland. Remember, the optic chiasm
lies superior to the pituitary gland. A pituitary gland tumor can
damage the nasal retinal fibers from each eye that run just superior
to the pituitary gland as they cross in the optic chiasm, causing a
b ite m p o ra l hem ianopsia.
Two wings project from each side of the body of the sphenoid:
Lesser w ing: Projects anteriorly to connect with the frontal bone to form the
r o o f o f th e orb it,
• The o p tic canal is located within the lesser wing and contains the
optic nerve and ophthalmic artery.
G rea ter w ing: Projects laterally to connect with the zygomatic bone to form
the lateral wall of the orbit. The greater wing of the sphenoid contains
three important foramina:

CHAPTER. 3. OCULAR ANATOM Y 89
1. Foramen rotundum: Passage for the maxillary division (V 2 ) of the

trigeminal nerve.
2. Foramen ovale: Passage for the mandibular division (V 3 ) of the
trigeminal nerve and the lesser superficial petrosal nerve.
3. Foramen spinosum: Passage for the middle meningeal artery.
Su p erior O rb ita l Fissure (S O F )
Opening between the greater and lesser wings of the sphenoid bone.
• Located between the posterior lateral wall and the superior wall of the
orbit.
• The cavernous sinus lies just posterior to the SOF within each eye and
travels on the sides of the sphenoid body.
C o m m o n T endinous R in g (C T R )
A circular band of connective tissue that lies just anterior to the superior orbital
fissure (SOF) and serves as the origin o f the recti m uscles (36). The CTR
is also commonly referred to as the annulus o f Zinn.
O rbital C on ten ts and th eir R ela tion sh ip t o the C T R and SO F
The following pass through the SOF AND the CTR:
• Nasociliary nerve (branch of V I), Oculomotor nerve, and Abducens

nerve.
• The sympathetic root of the ciliary ganglion travels with the nasociliary
nerve as it passes through the SOF and CTR.
N O A can fit through the SOF AND the CTR. Recall that the
CTR, serves as the origin for the recti muscles. If a lesion occurs
within this muscle cone, these nerves are most likely to be affected.
The following pass through the SOF and ABOVE the CTR:
• Superior ophthalmic vein, frontal nerve, lacrimal nerve, and the trochlear
nerve.

90 3.4. ORBIT
Superior Orbital Fissure
Levator Palpebrae Superioris
Optic Nerve Superior Oblique

Medial Rectus
Lacrimal Nerve
Frontal Nerve Ophthalmic Artery
Trochlear Nerve Superior Rectus
Oculomotor inferior Rectus

Nerve
Nasociliary Nervi
Inferior Ophthalmic Vein
Lateral Rectus
Abducens Nerve
Figure 3.7: Superior Orbital Fissure
One item passes through the inferior orbital fissure (IOF) and inferior to the
CTR:
• Inferior ophthalmic vein (and occasionally the central retinal vein if it

has not yet joined with the ophthalmic vein).
~ r e n irif
• Optic canal (optic foramen): Optic nerve and ophthalmic artery.
• Carotid canal: Internal carotid artery and the sympathetic plexus.
• Supraorbital foramen: Supraorbital nerve (part of V I) and vessels (supraor

bital artery and vein).
* Infraorbital foramen: Infraorbital nerve (part of V2) and vessels (infraor

bital artery and vein).

• Mandibular foramen: Inferior alveolar nerve and vessel.
* Stylomastoid foramen: Facial nerve.
The orbit consists of 7 bones. The medial walls parallel each other and the
lateral walls extended would make a 90 degree angle (36).
R oof
Comprised of the frontal bone and the lesser wing of the sphenoid bone.
• The anterior portion of the frontal bone serves as the floor of the frontal
sinus.
• The frontal b o n e comprises the majority of the orbital roof.
• The levator muscle lies just below the orbital roof; the superior rectus
lies slightly below the levator muscle.
Remember, the lacrim al gland, lies in the anterolateral portion of

the orbital roof within a fossa of the frontal bone (19).
F lo o r
Comprised of the maxillary, palatine, and zygomatic bones.
• The orbital floor serves as the roof of the maxillary sinus (19),
• The m axillary b o n e comprises the majority of the orbital floor.
• The infraorbital nerve runs along the infraorbital groove of the floor be
fore exiting the orbit through the infraorbital foramen.
Remember the bones that comprise the floor: Maxillary, palatine,

zygomatic “M y pal gets his z ’s on the flo o r.”

92 34■ ORBIT
O rb ita l floor fractures are the most common orbital wall frac
tures because the floor is the weakest wall in the orb it. An
orbital floor fracture can cause the eye to drop down into the max
illary sinus, leading to muscle entrapment and enophthalmos.
M ed ia l W all
Comprised of the ethmoid, lacrimal, and maxilla bones and the body of the
sphenoid. The medial wall is the the thinnest and sm allest wall of the orbit.
The orbital portion of the ethmoid bone is also known as the lam
ina papyracea. An infection in the sinus cavity can often spread
to the orbit through the very thin lamina papyracea, resulting in
o rb ita l cellulitis.
L ateral
Comprised of the greater wing of the sphenoid and the zygomatic bone. The
lateral wall is the stron gest wall in the orbit.
Remember u2-2-3-4 all have sp h en oid except the floor” : De

scribes the number of bones for the roof, lateral wall, floor, and
medial wall, respectively (43).
• R oof bones = Front-Less
• Medial wall bones = E LM S
• Lateral wall bones = G rea t-Z
C avernous hem angiom as are the most common benign orbital

tumors in adults (21). C apillary hem angiom as (aim strawberry
hemangiomas) are the most common benign orbital tumors in chil
dren.

I - SECTION 3.5
B lood Supply
We now summarize blood flow within and around the orbit (36, ch. 11) (22,
ch. 33). The common carotid artery divides into an internal and external
branch. Although the internal and external carotids each have many branches,
this review will focus only on those branches related to the globe and orbit.
E xternal C a rotid A rte ry
Provides blood to the superficial areas of the neck and head and provides
a small portion of the blood supply to the ocular structures. The impor
tant branches of the external carotid artery include the facial artery and the
two terminal branches (the su perficial te m p o ra l artery and the m axillary
artery).
• Facial artery: Branches at the angle of the mandible and travels across
the mandible and cheek towards the medial canthus of the eye.
— The angular a rtery is the terminal branch of the facial artery that
communicates with the dorsal nasal artery (from the ophthalmic
artery) and supplies the m edial canthus.
• M axillary A rte ry : A terminal branch of the external carotid artery

that begins just anterior to the ear in the parotid gland.
— The in fraorbital bran ch of the maxillary artery enters the orbit

through the inferior orbital fissure and supplies the I R and IO .
— It exits the orbit through the infraorbital foramen and supplies the
lower eye lid and the lacrim al sac before joining the angular
artery (from the facial artery of the external carotid) and the dorsal
nasal artery (from the ophthalmic artery).
• Superficial te m p o ra l artery: The second terminal branch of the ex

ternal carotid artery that arises within the parotid gland.
— It has 3 branches that supply the superficial skin, muscles, and soft
tissue around the face and orbit.
— The superficial temporal artery communicates with branches from
the ophthalmic artery.

94 3.5. BLOOD SUPPLY
Supraorbital Artery
Supratrochlear Artery
yi* * ’ Dorsal Nasal Artery
Frental Branch
Superficia I Temporal Superior Medial Palpebral Artery
Artery Angular Artery
Superior Lateral,
Palpebral Artery jj
Inferior La teral”**^
Palpebral Artery
Zygomaticofattal-
Artery
Infraorbital Artery
Figure 3.8: Branches of the External and Internal Carotid Arteries
G iant cell arteritis (aka temporal arteritis) is an inflammation

o f large and medium sized vessels that supply the head. Dam
age to the sh ort p osterior ciliary arteries (circle o f Zinn)
leads to suffocation and irreversible damage of the optic nerve head
(A A IO N ) and results in a significant loss of vision. This inflam
matory process can quickly spread to the fellow eye if not promptly
treated with oral corticosteroids, and is thus considered an ocular
emergency. Please see the neuroscience chapter for further details
regarding AAION and the less serious differential NAION.
Internal C a rotid A r te r y (IC A )
Provides blood to structures within the cranium. Terminal branches of the

op h th a lm ic a rtery (branch of the ICA) assist the external carotid artery
branches in providing circulation to the superficial areas of the face and orbit.
Remember, branches from the internal and external carotid arteries

anastomose to provide for certain ocular structures. For example,
the superficial temporal artery has a connection with the supraor
bital artery (branch of the ophthalmic artery); if the ophthalmic
artery is obstructed and cannot not provide blood flow to the orbit,
this connection can temporarily provide a low level of circulation
to the internal structures of the eye.

C ou rse and branches o f th e IC A
* The ICA enters the skull through the petrous portion of the temporal
bone and travels directly into the cavernous sinus.
* C N V I travels alongside the ICA as it courses through the cavernous

sinus. C N III is lateral and C N II is medial to the ICA just before it
exits the sinus.
* The oph th alm ic a rtery is the first branch of the ICA as it approaches
the orbit.
An internal carotid a rtery aneurysm within the cavernous sinus

will most likely affect C N VI.
jQphthalm ie a rte ry W ';•••’ v A

Enters the orbit within the optic nerve sheath. After leaving the sheath, the
ophthalmic artery travels near the medial wall of the orbit (along with the
nasociliary nerve) between the SO and MR.
B ranches o f th e O ph th alm ic A rte ry
1. C entral R etin al A r te r y (C R A ): The first branch of the ophthalmic

artery. It travels within the optic nerve and supplies the nerve and sur
rounding pia mater via collateral branches. It enters the optic disc slightly
nasal to center and divides into multiple superior and inferior branches.
The CRA supplies the inner 2 /3 o f th e retina.
2. Lacrim al A rte ry : Travels along the lateral wall of the orbit (along
with the lacrimal nerve) and supplies the L R and the lacrim al gland.
It terminates as branches of the lateral pa lp eb ra l artery that supplies
the lateral inferior and superior lids.
* The lateral palpebral arteries anastomose with the medial palpebral

arteries (from the dorsonasal artery) to from the palp ebral arcades
o f the eyelids.
3. M u scu lar artery: Provides blood to the ex tra ocu la r m uscles via two
branches:
• Superior lateral muscular artery supplies the LR, SR, SO, and the
levator muscle.

Doisorasal
Attsjy Supratrochlear
Aitay
Palpebral
A n te rio r.
Meningeal
Muscular
Muscular Branch Branch
Uciimal Artery
Central Retinal Artery
Internal Carotid
Figure 3.9: Right orbit, viewed from above, illustrating oph th alm ic artery
branches.
• Inferior medial muscular artery supplies the MR, IR, and 10.
Branches of the muscular artery that supply the four recti muscles
collectively form the anterior ciliary arteries, a vascular network
that combines with the long posterior ciliary arteries to form the
major arterial circle of the iris.
4. Short P osterior C iliary A rteries: One or two large branches enter the
eye on both sides of the optic nerve before quickly branching 10-20 times
within the choroidal stroma to form the arterial network (the C ircle o f
Zinn) that supplies the superficial optic nerve head (19). The SPCAs
also supply the p oste rio r choroid , including the m acula.
Remember, the C ircle o f Zinn provides blood to the optic disc.

5. L on g P osterior C iliary A rteries: Two arteries enter the eye on each

side of the optic nerve (similar to SPCAs) and travel between the sclera
and the choroid. They join the SPCAs to form a network of blood supply
to the ch oroid.
* LPCAs provide for the anterior ch o ro id before traveling to the

ciliary body to join with the anterior ciliary arteries to form the
M a jo r A rterial C ircle o f th e Iris.
* Overall, the LPCAs supply the iris, ciliary body, and anterior region
of the choroid (19).
The m a jor arterial circle o f th e iris is located within the ciliary

body. It contains fenestrated capillaries that allow plasma to leak
out, which ultimately contributes to aqueous humor formation.
6. Supraorbital artery: Provides blood to structures within the orbit

(SR, SO, and the levator muscle) before exiting the orbit through the
supraorbital notch to supply the superficial scalp and forehead.
7. E th m oid A rtery : Branches supply the sphenoid, frontal and ethmoid

sinuses.
T erm inal B ranches o f th e O ph th alm ic A rte ry
1. Su pratrochlear A rte ry : Supplies the skin of the forehead and scalp,

as well as the muscles of the forehead.
2. D orsal nasal A rtery : Supplies the lacrim al sac and then travels along
the side of the nose to join the angular artery (from the facial branch of
the external carotid artery).
• The dorsal nasal artery branches into the m edial p alp ebral arter
ies that supply the medial superior and inferior eyelids. Remember,
these arteries join with the lateral palpebral arteries to form the
p alp ebral arcades.
O cular ischem ic sy n d rom e is a result o f an occlusion of the

internal carotid or the ophthalmic artery.

Orbital veins are similar to those in the head and neck in that they do not
contain valves. In general, venous drainage of the orbit DOES NOT correspond
to the arterial supply (unlike in other parts of the body) (19).
C entral R e tin a l V ein: Drains blood from the inner 6 layers of the retina
that are supplied by the CRA. It exits the eye through the optic nerve and
then enters the cavernous sinus, either directly or after joining the su p erior
oph th a lm ic vein.
Central and branch retinal vein occlusions (C R V O s and B R -

V O s) are secondary to thrombus formation within the veins. The
major threat to vision in patients with a CRYO is neovascular
g la u com a (“90 day glaucoma”).
A n te rio r C ilia ry Veins: Drain blood from the anterior structures of the
eye including the iris, ciliary body, conjunctiva, and Schlemm’s canal. The
anterior ciliary veins follow the path of the anterior ciliary arteries across the
tendons of the four recti muscles. They drain into the su p erior and inferior
oph th a lm ic veins.
V o r te x V eins: Drain blood from the choroid. Typically each quadrant con
tains at least one vortex vein (although multiple may be present). The vortex
veins drain into the su p erior and inferior oph th alm ic veins.
Su p erior O ph th alm ic V ein: The largest vein in the orbit; it is responsible

for the majority o f venous drainage of the eye, receiving blood from the CRY,
the superior vortex veins, the muscular veins draining the SR and M R (also
receive blood from the anterior ciliary arteries), and the lacrimal vein.
• The superior root of the SOV originates at the superomedial orbital rim
from branches of the supraorbital and supratrochlear veins (drain blood
from the forehead and scalp). The inferior root of the SOV originates
from branches of the angular vein (branch of the facial vein). These two
roots join together to form the SOV just posterior to the trochlea and
medial to the SR insertion.
The SOV exits the orbit through the SOF and drains into the cavernous
sinus.

In ferior O phthalm ic V ein: Originates from a diffuse network of veins along

the anterior medial orbital floor between the globe and the IR. It receives blood
from the muscular veins draining the MR, IR, 10, and LR (which also receive
blood from the anterior ciliary veins), the inferior vortex veins, and small veins
draining the inferior conjunctiva, lower eyelid and the lacrimal sac. The IOV
often forms two branches:
• Inferior branch exits the orbit through the inferior orbital fissure and
drains into the p te ry g o id plexus to communicate with the facial veins.
• Superior branch exits the orbit through the superior orbital fissure and
drains into the cavernous sinus, either directly or after joining with the
superior ophthalmic vein.
Superficial Veins o f th e O rb it and Face
We now briefly describe the superficial veins o f the orbit and face (7):
S u praorbita l V ein: Originates on the forehead and joins the frontal vein
near the medial angle of the orbit to form the angular vein. It sends a branch
through the supraorbital notch that helps form the SOV.
Frontal V ein: Originates from a venous plexus on the forehead. It commu

nicates with the superficial temporal vein before joining the supraorbital vein
at the medial angle of the orbit, forming the angular vein.
A n gu lar Vein: Originates on the side of the nose and the medial angle of the
orbit. It sends a nasofrontal branch into the orbit, which joins the supraorbital
branch to form the SOV. The angular vein eventually becomes the anterior
facial vein at the lower margin of the orbit.
• The anterior facial vein receives blood from a branch of the pterygoid
venous plexus, as well as the superior and inferior palpebral veins.
* It travels from the side of the nose along the masseter until it joins with
the posterior facial vein, forming the common facial vein. The common
facial vein drains into the internal ju g u la r vein.
In fraorbital Vein: Arises from several superficial veins that drain the face.
It enters the orbit via the infraorbital foramen and travels along the floor of the
orbit within the infraorbital groove and canal. The infraorbital vein receives
branches from small veins that drain structures of the inferior orbit before
emptying into the pterygoid venous plexus.

The p te ry g o id ven ou s plexus is located within the infratempo

ral fossa. It communicates with the anterior facial vein and the
cavernous sinus via orbital veins and emissary veins of the cra
nium. The venous plexus eventually forms the m axillary vein.
Superficial T em p ora l V ein: Originates from a venous plexus on the side of

the skull. The frontal branches and parietal branches of the venous plexus join
to form the trunk of the superficial temporal vein. It communicates with the
frontal, supraorbital, posterior auricular1, middle temporal, and occipital veins
before joining the maxillary vein within the parotid gland to form the posterior
facial vein.
• The middle temporal vein receives blood from the orb ita l vein that
originates from lateral palpebral venous branches.
P osterior Facial V ein (aka retromandibular vein): Formed by the union of

the superficial temporal vein and the maxillary vein within the parotid gland.
Divides into an anterior and posterior branch:
• The anterior branch unites with the anterior facial vein to form the com
mon facial vein. The common facial vein drains into the internal ju g u lar
vein.
• The posterior branch joins with the posterior auricular vein (which com
municates with the occipital and superficial temporal veins) to form the
extern al ju g u la r vein.
O ccip ita l V ein : Originates at the posterior vertex of the skull. It may drain
directly to the internal ju gu lar vein or join the posterior auricular to drain
into the extern al ju g u la r vein.
• The extern al ju gu lar vein is formed by the union of the

retromandibular vein and the posterior auricular vein and
drains blood from the superficial face.
• The internal ju g u la r vein is a continuation of the sigmoid

sinus (see below) and drains blood from the common facial,
occipital, lingual, and superior and medial thyroid veins.

iS S B I
Dural sinuses are venous channels located in the dura mater of the brain. They
are lined with an endothelium that is continuous with the endothelium of the
veins and they do NOT contain valves. The dural sinuses are responsible for
draining blood from the head back to the heart (44).
C avernous Sinus: Located between the sphenoid and temporal bones, the
cavernous sinus begins just posterior to the inferior-medial region of the SOF
of each orbit and extends to the petrous portion of the temporal bone (19).
The sphenoid sinus is inferior and the optic chiasm is superior to the cavernous
sinus.
• It receives blood from the su p erior and inferior op h th alm ic veins, as

well as the superficial middle cerebral vein (via the sphenoparietal sinus)
and inferior cerebral veins.
• The cavernous sinus drains into the superior and inferior petrosal sinuses,
which ultimately drain into the internal ju g u la r vein to carry blood to
the heart (36).
• The cavernous sinus may also communicate with the pterygoid plexus
through a network of emissary veins that exit the skull through the fora
men ovale and foramen lacerum.
The area of the face from the corners of the mouth to the bridge
of the nose is sometimes referred to as the “ trian gle o f death.”
Infections in this area can gain access to the brain through the
cavernous sinus because of venous communication between the
facial vein and the ophthalmic veins.
It is important to know the content- and location o f the structures within the
cavernous sinus (see Figure 3.5):
• The cavernous sinus contains CN III, IV, VI, V I, and V2, as well as the
internal carotid artery and postganglionic sympathetic fibers that travel
around the ICA (47).
• Remember that C N V I has a close association with the internal carotid

artery as it traverses through the cavernous sinus, and is thus most likely
to be affected by an ICA aneurysm.

Internal Carotid Artery
Oculom otor Nerve
Trochlear Nerve
Cavernous Sinus
Ophthalm ic Nerve,
Abducens Nerve
Maxillary Nerve
O blique View Through the Cavernous Sinus
• T olosa-H u n t S yn drom e is an inflammation of the SOF

and/or cavernous sinus that often affects CN 3, 4, 5, and
6, resulting in painful external oph th alm op legia and
diplopia.
• C a rotid -cav ern ou s fistula (C C F ) occurs because of an

abnormal communication between the arterial and venous
blood supplies within the cavernous sinus. It is associated
with a painful red eye, orbital bruit, and pulsatile p ro p
tosis (see ocular disease chapter for further details).
S u p erior P etrosal Sinus: Drains blood from the inferior cerebral veins and
some cerebellar veins. It communicates with the cavernous sinus and the trans
verse sinus.
In ferior P etrosal Sinus: Originates from the posterior inferior portion of

the cavernous sinus. It receives blood from the internal auditory veins, as well
as veins from the brainstem and cerebellum. The inferior petrosal sinus exits
the skull through the jugular foramen and drains into the internal jugular vein.

S u p erior Sagittal Sinus: Located within the superior falx cereb ri (strong
folds of dura mater that separate the right and left hemispheres of the brain)
on the upper petrous portion of the temporal bone. The superior sagittal
sinus drains blood horn the superior cerebral veins. It travels posteriorly to
the internal occipital protuberance, where it drains into the right transverse
sinus (44).
In ferior Sagittal Sinus: Travels within the inferior portion of the falx cere
bri between the occipital bone and the petrous portion of the temporal bone.
It receives blood from the inferior cerebral veins. The inferior sagittal sinus
travels posteriorly to join the great cerebral vein to form the straight sinus.
Straight Sinus: Originates at the junction of the falx cerebri and the ten
toriu m (connective tissue separating the brain and the cerebellum). It drains
blood from the superior cerebellar veins before draining into the left transverse
sinus (44).
O ccip ita l Sinus: Originates at the margin of the foramen magnum and trav
els within the falx cerebri along the occipital bone. It receives blood from the
vertebral veins before draining into the left transverse sinus (44).
T ransverse Sinuses: Travels on the surface of the tentorium along the oc
cipital bone and the petrous portion of the temporal bone. The transverse
sinuses receive blood from the superior petrosal sinus, inferior cerebral veins,
and inferior cerebellar veins. It eventually travels interiorly to form the sig
m o id sinus (44).
• The sig m oid sinus receives the inferior petrosal sinus (which commu
nicates with the cavernous sinus). It exits the skull through the jugular
foramen and becomes the internal jugular vein.
The con flu en ce o f th e sinuses is the meeting point for the su
perior sagittal, straight, occipital, and transverse sinuses and is
located on the internal occipital protuberance of the occipital bone.

104 3.6. CORNEA
Imagine the eye as 3 different sections:
1. F ib rou s O u ter Layers: Cornea and Sclera
2. V ascular Inner Layers: Iris, Ciliary body, and Choroid
3. N eu ral Layers: Retina and RPE
The average emmetropic eye has the following dimensions (24):
• Axial length: 24 mm
• Horizontal diameter: 23.5 mm
• Vertical diameter: 23 mm
We now overview the cornea, a thin, transparent, toric structure that consists
of five layers (36, ch. 2) (22, ch. 2) (47, ch. 2). The cornea fits into the anterior
scleral foramen and has a refractive power of approximately 43 D (2/3 the total
refractive power of the eye) (24). The cornea transm its and refracts light
and serves as a barrier against pathogens and edema.
INormal D im ensions . / :-VrVH1,;j

• The air/tear film interface has the largest difference in the index of re
fraction (n) between two layers and thus serves as the main refracting
element, contributing 44 D to the refractive power of the cornea (24).
— Light travels from air (n = 1.00) through the tear film (n — 1.336)
to the cornea (n = 1,376).
— The tear/cornea interface contributes 5 D and the cornea/aqueous
humor interface contributes -6 D to the total refractive power of the
cornea (24).
• The cornea is thicker in the periphery (0.67 mm) than the center (0.55
mm).
• The cornea is a toric structure:
— W ith the R u le (W T R ): The cornea is steeper in the vertical

m eridian.

- A gain st th e R u le (A T R ): The cornea is steeper in the h orizontal

m eridian.
A stig m a tism shifts towards A T R as the crystallin lens ages. A

loss of lid tension may also result in flattening of the vertical merid
ian of the cornea, contributing to an increase in ATR astigmatism.
* The central radius of curvature is 7.8 mm for the anterior corneal surface
and 6.5 mm for the posterior corneal surface.
* The average an terior horizontal diameter is 11,7 mm and the anterior

vertical diameter is 10.6 mm.
* The average p o ste rio r horizontal AND vertical diameter is 11.7 mm,
resulting in the cornea appearing spherical if viewed from behind (43).
CO RN EAL LAYERS
- E p ith eliu m (52 u m ) - Surface, w ing, and basal cells
- B a sem en t m em bran e (B M )
- B o w m a n ’s layer (8 -14 um )
- S trom a (450 u m )
- D e s c e m e t’s m em bran e (5-15 um )
- E n d oth eliu m (5 u m )
Average corneal thickness is approximately 550 um.
E P IT H E L IU M
Consists of stratified squamous non-keratinized epithelium. Contains 5 to 6

cell layers that are approximately 52 um in total thickness. There are four
different layers of the epithelium:

106 3.6. CORNEA
Surface layer: Composed of 2 layers of non-keratinized squamous cells. The

plasma membrane of these cells secretes a glycocalyx and contains mi
crovilli and microplicae to increase the surface area and enhance the sta
bility o f the tear film. As cells age, they are sloughed off into the tear*
film.
• Zonula occludens and desmosomes form a tight barrier between cells

to impede the intercellular movement of particles. This is the ONLY
cell layer within the cornea that contains zonula occludens.
W in g cells: Composed of 2-3 cell layers joined by desmosomes to each other

and to surrounding layers.
Basal layer: The o n ly m ito tic layer in the corneal epithelium; composed
of 1 layer of columnar cells. The basal layer of the epithelium secretes
its own basement membrane (the basal lamina). The BM attaches to the
basal layer via hem idesm osom es. The BM also attaches to the under
lying Bowman’s layer via hemidesmosomes that penetrate Bowman’s and
attach to the extracellular matrix of the corneal stroma (10).
• Reduplication of the BM occurs with age. By 60 years of age, the

BM in normal eyes doubles in thickness (2) (36).
Remember, B M s throughout the body consist of two layers:

• The basal lam ina (secreted by epithelial cells)
* The reticular lam ina (produced by underlying stromal cells)
There are 3 factors that increase the risk of recurrent corneal

erosions (R C E s):
1. Poor hemidesmosome attachments,
2. Epithelial basement membrane dystrophy.
3. Age-related thickening of the BM.
Stem cells: Originate from the P alisades o f V og t, a 0.5 - 1.0 mm band

around the limbus at the same level as the basal layer, allowing for an
easy transition as stem cells migrate circumferentially to become basal
cells. Remember, stem cells b e c o m e basal cells and basal cells
p rod u ce w ing cells that m igrate an teriorly to eventually b e com e
th e surface layer o f th e epith eliu m .

Limbal stem cell deficiency has been shown to contribute to

poor corneal epithelial maintenance in individuals with aniridia,
St ev en s-J oh n son syn drom e, and alkali corneal burns (24).
B O W M A N ’S L A Y E R
An acellular layer composed of random Type 1 collagen fibrils (43), Bowman’s

layer is a tran sition layer from the epithelium into the stroma; it is NOT a
basement membrane.
• Produced prenatally by anterior stromal fibroblasts and is 8-14 um thick (36).
• Tough layer that is resistant to damage or injury; however, if damage

occurs, Bowman’s cannot regenerate, resulting in the formation of a scar.
• Bowman’s may play a role in maintaining the correct curvature of the

cornea (36).
The following are clinical conditions related to Bowman’s layer (see

ocular disease chapter for further details):
1. B an d k eratopath y: Calcium deposits (“swiss-cheese” pat

tern) within Bowman’s layer.
2. P tery g ia : Destroy Bowman’s layer as they progress onto the

cornea.
3. C r o c o d ile Shagreen: Bilateral gray-white polygonal stro

mal opacities that may involve Bowman’s layer.
4. R e is-B u ck le r’s d y strop h y: Rare corneal epithelial dystro

phy that appears early in life and is secondary to damage to
Bowman’s layer.
5. K era to co n u s: Initial damage occurs in Bowman’s layer.

Remember that advanced keratoconus may result in hydrops
due to damage to Descemet’s membrane.
6. R efra ctiv e surgery: The flap created during LASIK con

sists of epithelium AND Bowman’s layer; PRK involves the
application of laser THROUGH Bowman’s layer, resulting in
post-op corneal haze.

108 3.6. CORNEA
STROM A
The stroma (aka substantia propria) is 450 um thick (90% of the cornea). It is
dense, regular connective tissue composed of keratocytes (fibroblasts), collagen
fibrils, ground substance, and water (75-80% of stroma).
• K era tocy tes: Fibroblasts of the cornea that produce collagen fibrils and
the extracellular matrix.
• C ollagen fibrils: The stroma contains about 200-300 layers of uni

form ly spaced 30 nm lamellae (comprised of mainly Type I collagefl
fibrils) that run parallel to the corneal surface (36). Uniform spacing of
collagen lamellae is essential for maintaining corneal transparency.
- The anterior 1 /3 o f the strom a has a higher incidence of cross

linking between collagen fibers compared to the posterior 2/3 of
the stroma, creating more rigidity and helping to maintain corneal
curvature (31) (36).
- The p osterior 2 /3 o f th e strom a is more organized and consists of
very uniformly spaced lamellae that are larger and have less branches
and less cross-linking compared to the anterior 1/3 of the stroma,
factors that result in a higher incidence of corneal edema in the
posterior cornea (36) (12) (31).
• G rou n d substance: Serves as a filler between the collagen fibrils and

keratocytes. Contains GAGs that attract water, contributing to the pre
cise spacing between collagen lamellae that is essential for corneal trans
parency.
- K eratin sulfate is the predominate GAG within the cornea (66%) (22).
D E SC E M E T’S M E M B R A N E
The basement membrane produced by the corneal endothelium (43). It is

composed of Type 4 collagen and is 5-15 um thick in adults (increases in
thickness from birth) (36).
• Descemet’s membrane is very resistant to trauma and damage. Unlike

Bowman’s layer, Descement’s membrane MAY be able to regenerate via
the endothelium if injured (although there is conflicting evidence in the
literature).•
• Descemet’s membrane terminates at the limbus and becomes Schw albe’s

line.

• H y d ro p s occurs in keratoconus as result of ruptures within

Descemet’s membrane.
• H a a b ’s striae are folds in Descemet’s membrane that occur

in congenital glaucoma.
• Hass all-H e nle b o d ie s are small areas of thickened De

scemet’s membrane in the corneal periphery that protude to
wards the anterior chamber. They increase in number with
age and have no visual significance.
E N D O T H E L IU M
Single layer of squamous cells that is approximately 5 um thick. Endothelial

cells contain N a + /K + ATP pumps that help to maintain corneal h y d ra tion
and tra n sp a ren cy by regulating water and ion flow between the aqueous and
corneal stroma (see ocular physiology chapter for further details).
• Endothelial cells are rich in organelles and m itoch on d ria (decrease in

number with age) (43).
• They are linked together at their apical borders (facing the anterior cham
ber) by m aculae occlu d e n s junctions, creating a weak barrier that al
lows amino acids, glucose, and nutrients from the aqueous to enter into
the cornea (22) (36).
• Endothelial cells DO NOT replicate. As they decrease in number with

age, neighboring cells change shape (pleom orphism ) and size (p oly m ega th ism )
to compensate for the decrease in endothelial cell density.
• The loss of endothelial cells results in a decrease in N a + /K + ATP pumps

and may lead to strom a l edem a.
The cornea is AVASCULAR. It obtains nutrients from three outer sources:
1. Diffusion from the aqueous humor.
2. Limbal conjunctival and episcleral capillary networks.
' 3. Palpebral conjunctival networks.

110 3.6. CORNEA
The main source of O 2 for the cornea under OPEN eye conditions is the tear
film that contains O 2 that has diffused from the atmosphere. The p alp ebral
con ju n ctiva l b lo o d vessels serve as the main source of O2 under CLOSED
eye conditions.
C orn eal neovascularization is a defense response to oxygen de

privation. The new vessels arise from endothelial cells of the limbal
capillary network in response to cytokines and growth factors (in
cluding VEGF) (36) (18).
!Gornefd Innervation '

Corneal innervation is responsible for pain sen sation and for p ro p e r w ound
healing (24). V I , the first division of the trigeminal nerve, innervates the
cornea via the long and short posterior ciliary branches from the nasociliary
nerve.
• LPCNs branch directly from the nasociliary nerve. SPCNs are formed af
ter the nasociliary nerve travels through the ciliary ganglion. The LPCNs
and SPCNs form a myelinated network of 60-80 nerves that enter the m id
strom a. •
• After traveling 2-4 mm inside the stroma, the corneal nerves lose their
myelin sheath as they penetrate through Bowman’s layer to enter the
epithelium. These nerves are now highly sensitive “naked” nerves packed
with n o cirecep tors that mediate pain (36).
N e u ro tro p h ic keratitis is characterized by poor corneal sensi

tivity and wound healing and is secondary to damage to V I of
the trigeminal nerve (e.g. herpes simplex, herpes zoster, CVA, di
abetes).
Nerve networks are ultimately formed in three places (47) (36):
1. E pithelium : Referred to as the intraepithelial plexus.
2. A n terior s tro m a /B o w m a n ’ s layer: Referred to as the subepithelial

plexus.
3. M idstrom a : Referred to as the stromal plexus.

There are N O corn ea l nerves in the posterior stroma, Descemet’s

membrane, or corneal endothelium. Remember, the corneal nerves
enter at the level of mid-stroma and travel anterior from there.
r - SECTION 3.7
C onjunctiva •
We now summarize the conjunctiva, a thin, translucent membrane that extends

from the limbus through the fornices and into the eyelids (36, ch. 9) (47, ch. 3).
Recall that the palpebral conjunctiva lines the eyelids, the forniceal conjunc
tiva lines the fornices, and the bulbar conjunctiva lines the globe. The main
functions of the conjunctiva include:
1. Protection of the soft tissues of the eyelid and orbit.
2. Allows extensive movement of the eye without damaging soft tissues.
3. Serves as a source of antimicrobial and other immunological agents.
4. Produces the mucin layer of the tears.
The conjunctiva is composed of two layers (47) (36):
1. Stratified non-keratinized epithelial layer: Composed of cuboidal/columnar

cells in the palpebral conjunctiva that become squamous cells in the bul
bar conjunctiva. The superficial cells contain melanin granules, microvilli,
and goblet cells (number and density decreases closer to the limbus) (36).
2. Submucosa: Loose C T layer that is separated into two layers (36):
* Outer lymphoid layer: Contains Ig A , macrophages, mast cells, lym

phocytes, PMN leukocytes, eosinophils, and Langerhans cells (mi
grate through the conjunctiva),
• Deep fibrous layer: Contains collagen fibrils, fibroblasts, blood ves
sels, lymphatic vessels, nerves, and accessory lacrimal glands. In
general, this layer is loosely attached to underlying structures.
P a lp eb ra l con ju n ctiva : Covers the eyelid margin, tarsal plate, and the for
nices.
• M argin al co n ju n ctiv a lines the eyelid margins and is composed of strat

ified columnar epithelial cells that become continuous with the epithelium
of the skin at the mucocutaneous junction of the lid. The underlying sub
mucosa is very thin with only a deep fibrous layer.

112 3.7. CONJUNCTIVA
• Tarsal con ju n ctiva lines the tarsal plates and is composed of stratified
columnar epithelium. The submucosa is thicker and contains the outer
lymphoid and deep fibrous layer, which contains the accessory lacrimal
glands and is strongly attached to the tarsal plate.
• F orniceal con ju n ctiva lines the fornices. The deep fibrous layer con
tains the accessory lacrimal glands and Muller’s muscle (in the upper
fornix). The EOM fascia attach to the forniceal conjunctiva, moving the
conjunctiva in conjunction with the eye to avoid compression of blood
vessels and nerves within the submucosa.
B u lbar con ju n ctiva: Thin translucent membrane that covers the sclera.
It is composed of stratified squamous cells that become continuous with the
corneal epithelium at the limbus. The submucosa is loosely attached to under
lying Tenon’s capsule until approximately 3 mm from the cornea when it fuses
with the end o f Tenon’s capsule, episclera, and sclera (36).
Lim bus: A 1-2 mm zone that encircles the cornea and serves as the junction
between the conjunctiva, sclera, and cornea.
1. The limbus provides nutrients for neighboring structures.
2. The limbus provides a passageway for aqueous drainage within the eye.
3. The limbus is supplied by blood from the capillary loops of the conjunc
tival and episcleral vessels (36).
Histological and anatomical changes at the limbus include the following:
• The limbal epithelium contains 10 cell layers compared to the 5 cell layers
of the corneal epithelium.
• Bowman’s layer and Descemet’s membrane end at the cornea. Remem

ber that Descemet’s membrane becomes Schwalbe’s line in the anterior
chamber angle.•
• The conjunctival stroma, episclera, and Tenon’s capsule begin at the

limbus.
The Palisades o f V og t are spoke-like projections of limbal con

junctiva that extend 4 mm from the edge of the cornea. The limbal
epithelium is the source of stem cells that migrate to the basal
layer of the cornea (36).

P lic a Sem ilunaris: Composed of stratified squamous bulbar conjunctiva

that folds at the medial canthus, providing slack in the conjunctiva during
lateral eye movements. It also serves as the floor for the lacrimal lake (36).
C aru n cle: A hybrid o f conjunctiva and skin that contains sebaceous glands,
sweat glands, and goblet cells and is located on the medial side o f the plica
semilunaris. Its function is unknown. It is the likely source for the collection of
debris (i.e. “matter”) that is present in the healthy eye upon awakening (36).
C o n ju n ctiva B lo o d Su p ply: Consists o f the following networks:
1. P a lp eb ra l co n ju n ctiv a (including marginal, tarsal, and forniceal con

junctiva) are supplied by the marginal and peripheral palpebral arcades.
2. P o ste rio r bu lb a r co n ju n ctiv a is supplied by the peripheral palpebral

arcades. A n te rio r bulbar conjunctiva is supplied by the anterior ciliary
arteries. The peripheral palpebral arcades combine with the anterior
ciliary arteries at the posterior bulbar conjunctiva.
3. Palpebral and bulbar conjunctiva are drained by the anterior ciliary

veins.
C on ju n ctiva l L ym ph a tics: Lateral lymphatic vessels of the bulbar and

palpebral conjunctiva drain into the p a rotid lymph nodes. Medial lymphatic
vessels drain into the su bm a n d ibu lar lymph nodes.
C o n ju n ctiv a S en sory Innervation: The bulbar conjunctiva is innervated

by the long posterior ciliary nerves (from the nasociliary nerve of V I). The
palpebral conjunctiva is innervated by VI and V2 (lacrimal, infratrochlear,
and supratrochlear nerves).
We now review the lens, an avascular, transparent, biconvex structure located

within the posterior chamber between the vitreous and the iris (36, ch. 5). Its
main function is to assist in the transm ission and focu sin g o f light onto
the retina.•
• The refractive power of the lens is approximately 20 D (1/3 the total

refractive power of the eye).

114 3.8. LENS
• The anterior lens radius of curvature is 8-14 um. The posterior lens radius
of curvature is steeper, measuring 5-8 um (36).
• The pH of the lens is 6.9 and is more acidic compared to the aqueous
humor (pH = 7.6) and the blood plasma (pH = 7.4).
• The lens is aspherical, becoming flatter towards the periphery.
The posterior lens surface is attached to the anterior vitreous face by the ring-
shaped hyaloid capsular ligament. The potential space between the posterior
pole of the lens and the anterior vitreous within this ring is known as the
retrolental space of Berger.
Peripheral flattening and a gradient index of refraction in the lens

help to reduce spherical aberration (11).
{Composition of th e Lens v/.-;;

The lens is composed of 3 parts:
1. Lens capsule: A transparent basement membrane that surrounds the

entire lens and is secreted by the anterior lens epithelium. It is thinnest
at the posterior pole and thickest at the anterior pole of the lens (and is
the thickest BM in the entire body!). It is primarily composed of Type 4
collagen fibers and GAGs.
• The lens capsule serves as a barrier against large molecules (e.g.

albumin, RBCs, WBCs, etc.) entering the lens.
• The lens zonules, which maintain the position of the lens within
the posterior chamber, extend from the non-pigmented ciliary ep
ithelium and insert into the anterior capsule of the lens.
2. Lens epith elium : Composed of a single layer of cuboidal epithelial cells

adjacent to the anterior lens capsule. There is NO posterior lens epithe
lium in the adult lens, as it was used to form the primary lens fibers during
embryological development (see ocular embryology chapter for additional
details). Lens epithelial cells are joined with maculae occludens and gap
junctions. They serve as the main site of lens metabolism.•
• The pre-equatorial region of the lens (just anterior to the lens equa
tor and known as the germ inal zone) contains mitotic epithelial
cells that become secon d ary lens fibers. The production of new
lens fibers is continuous throughout life (see ocular embryology chap
ter for further details).

3. Lens co rte x : Composed of 65 — 70% water, 30 — 35% protein, and 1%

other constituents.
• 80 —90% of lens proteins are water solu ble alpha, beta, and gamma
crystallins that are tightly packed within the cytoplasm of lens fiber
cells (36).
UV exposure and oxidation can cause structural damage to lens

fibers. A lp h a crystallins act as m olecu lar chaperones by help
ing beta and gamma crystallins recover from injuries, thus prevent
ing degradation of lens fibers and loss of lens transparency (22).
• Crystallin concentration varies throughout the lens, creating a gra

dient in d ex o f refra ction that is higher in the nucleus (n = 1.41)
compared to the anterior lens (n — 1.38). Remember that aqueous
and vitreous humor have an index of refraction of 1,336 (36).
• Lens fibers are joined together by multiple interlocking mechanisms

including ball-and-socket and tongue-in-groove junctions, allowing
lens fibers to slide past each other easily during lens movement (i.e.
accommodation).
Lens Zonules
The lens is attached to the ciliary body in the posterior chamber by lens
zonules (aka zonules of Zinn or suspensory ligaments of the lens). Zonules are
produced by the basement membrane of the n on -p ig m en ted ciliary ep ith e
lium in the pars plana and pars plicata.
• Zonules are composed of .microfibrils that contain fibrillin and extracel

lular matrix but NO true elastic fibers (36) (22).
• P rim a ry lens zonules attach directly to the lens capsule in the pre and
post-equatorial regions of the lens. Relatively few primary lens zonules
attach directly at the lens equator.
• S econ d a ry lens zonules connect primary lens zonules to one another or

to the non-pigmented ciliary epithelium of the pars plana.•
• “ T en sion ” zonules connect the primary lens zonules to the valleys be
tween the ciliary processes of the pars plicata.

116 3.9. SCLERA
SECTION 3.9
Sclera
We now summarize concepts relating to the sclera (36, ch. 2) (47, ch. 2) (22,
ch. 4).
ISSliiSK iSliiiiSlIIlB I
• Forms posterior 5/6 of the protective connective tissue coat of the eye (the
cornea forms the remaining 1/6 of the protective CT coat) and helps to
maintain the shape of the globe and to protect intraocular structures (22).
• The sclera serves as a point of attachment for the extraocular muscles.
• The mean radius of curvature is approximately 11.5 mm (22).
• The thickest area of the sclera is 1.0 mm at the posterior pole.
• The thinnest area of the sclera is 0.30 mm under the recti tendon in
sertions; this is clinically relevant during strabismus surgery to avoid
inadvertent globe penetration (43).
• The weakest area of the sclera is the lamina cribrosa (within the optic
nerve).
• The sclera is considered avascular; it receives minimal blood supply from

episcleral vessels, choroidal vessels, and branches of the long posterior
ciliary arteries (22) (36).
• The sclera is minimally innervated by the LPCNs and SPCNs.
1. E pisclera: Loose CT layer that contains a capillary network (from the

anterior ciliary arteries) that surrounds the cornea. Inflammation of the
CB or iris (e.g. iritis) will cause dilation of the anterior ciliary arteries,
leading to the characteristic ciliary flush (i.e. circumlimbal redness) (36).
The anterior ciliary arteries form networks in the anterior con

junctiva and episclera (30).

2. S clera p ro p e r: Thick, dense, avascular CT that is continuous with the

corneal stroma. Composed of irregular collagen bundles that provide
strength but NO transparency. The sclera contains less fibroblasts and
GAGs but similar ground substance compared to the corneal stroma.
The episclera is composed of LOOSE CT and is HIGHLY vascular.

The sclera p ro p e r is composed of DENSE CT and is relatively
AVASCULAR (36).
3. L am ina fusca: The innermost layer of the sclera adjacent to the choroid
that contains elastin fibers and numerous melanocytes (22).
The normal sclera is white in color.
* In infants, the sclera commonly has a blue tint because the

underlying uveal pigmentation is visible through the thinner
sclera. O steogen esis im p erfecta o r E h ler’s D anlos syn
d rom e are also associated with a blue sclera.
* In the elderly, the sclera often becomes yellow as lipids be

come trapped in the dense irregular CT over time. A yellow
sclera may also signify liver disease.
T e n o n ’s capsule (aka fascia bulbi): Thin transparent layer of connective

tissue that covers the episclera. It begins 2 mm posterior to the limbus and
extends posteriorly to encircle the rest of the globe, separating it from the
surrounding orbital adipose tissue (43).
• Tenon’s capsule fuses with the episclera and the conjunctival submucosa
layer.•
• It is perforated posterolaterally by the optic nerve, ciliary vessels and

nerves, and the tendons of the four recti muscles.
Remember the layers of the eye from anterior to posterior: conjunc

tival epithelium, conjunctival stroma, T en on ’s capsule, episclera,
sclera proper, and lamina fusca.

118 3.10. ANTERIOR. CHAMBER AND ANGLE
ri( m
m & am sm m
• A n terior scleral foram en: Area occupied by the cornea (11,7 mm in
diameter) (36).
• P osterior scleral foram en: Area where the optic nerve enters. The
optic nerve is supported by the lam ina crib rosa (i.e. scleral tissue sieve),
which is composed of scleral collagen and elastin fibers that associate with
the axon bundles and astrocytes within the optic nerve.
The lam ina crib rosa is the weakest area of the sclera. The portion
of the optic nerve within the lamina cribrosa is the most likely area
to be damaged with an elevation in IOP.
The sclera contains multiple channels for arteries, veins, and nerves that are
passing through to reach other ocular structures. These em issaria are divided
into 3 sections based on location (22) (36):
1. A n terior em issaria include the following:
• The deep and intrascleral venous plexi travel through the sclera
to connect with the ciliary vein within the ciliary body.
• A n terior ciliary arteries provide blood to most anterior struc
tures of the eye.
• Branches from the episcleral arteries travel through the sclera to
reach the anterior chamber angle.
• A q u eou s veins o f A sch er drain aqueous humor from Schlemm’s
canal.
• LPCNs (forming A x e n fe ld ’s nerve lo o p s) provide innervation to
most anterior structures of the eye.
2. M id d le em issaria (near the equator) include the v o rte x veins that

drain the choroid.
3. P osterior em issaria (near the optic nerve) include channels for the
LPCAs, SPCAs, LPCNs, and SPCNs that travel through the sclera to
reach the suprachoroidal space.
- SECTION 3.10 ---------------------------------------------------------------------------------- -----------------
A n terio r C ham ber an d A ngle
We now introduce concepts related to the anterior chamber and angle (36,
ch. 6) (22, ch. 8).

*Viz< N:.,v.'C^s-2-y. Ei'.Yi A A i L - : A ^ r - t . * z ^
• Approximately 3.6 mm in depth (becomes more shallow in the periphery),

11-12 mm in diameter, and contains 125 uL of fluid (36).
• Average IOP — 15.5 mmHg.
• The boundaries o f the anterior chamber include the corneal endothelium

(anterior boundary), the trabecular meshwork, Schlemm’s canal, ciliary
body, and iris root (peripheral boundaries), and the anterior iris surface
(posterior boundary).
The internal scleral sulcus is located within the eye at the cornea-sclera
junction and contains the site for aqueous filtration. The structures within the
internal scleral sulcus, from posterior to anterior, include:
• Peripheral Iris, Ciliary body, Scleral spur, Trabecular meshwork (TM ),

Schlemm’s canal, and Schwalbe’s Line.
A n g le stru ctu res from posterior to anterior: I Can See The

Stupid Line.
• The B ecker-S h affer grading system is based on the most posterior struc
ture of the angle that is visible:
1. G ra de 4 — Ciliary body
2. G ra d e 3 = Scleral spur
3. G ra d e 2 = 1/2 to 1/3 of the TM
4. G rade 1 ~ Anterior aspect of TM or Schwalbe’s line
5. G ra d e 0 = No structures visible
• The V an Hericlc grading system is based on the width of the chamber

angle compared to the width of the corneal optic section:
1. G ra d e 4 = Width of the chamber interval is 1/2 or greater than

the width of the corneal optic section
2. G ra d e 3 - 1/4-1/2
3. G ra d e 2 = 1/4
4. G ra d e 1 = < 1 /4
5. G rade 0 = No structures visible

120 3.10. ANTERIOR CHAMBER AND ANGLE
Cornea
Ciliary Muscle
Figure 3.10: Structures in the Anterior Chamber
Scleral Spur
Circular’ band of collagen and elastin fibers that extends from the inner aspect
of the sclera. It is the origin site for the longitudinal ciliary muscle fibers
(extend posteriorly) and the TM lamellae (extend anteriorly).
The scleral spur and the lam ina crib rosa are the only areas of
the sclera that contain elastin.
T rabecu lar M eshw ork (T M )
Lines the anterior chamber circumferentially and is the major site for aqueous
h u m or filtration.
• The TM is triangular in shape, with the base of the triangle abutting the
scleral spur and the apex pointing towards the cornea (i.e. Schwalbe’s
line). The juxtacanalicular tissue is the external border of the TM.
• The inferior portion of the angle typically has the greatest amount of
pigment in the TM and is therefore a good starting point when performing
gonioscopy.
The T M has 2 divisions:

1. U veoscleral m esh w ork - The innermost 1-5 layers of the TM that are
located adjacent to the anterior chamber and inward to the scleral spur.
It consists of large pores within a network of cords, which are composed
of an inner core of collagen, elastin, and ground substance surrounded by
a layer of endothelium and basement membrane. The endothelial cells aid
in protein synthesis and contain lysosomes for phagocytosis of melanin
and debris (36).
• Does NOT utilize Schlemm’s canal for outflow; instead, aqueous hu
mor flows between the ciliary muscle fiber bundles, into the supra-
choroidal space, and then through the sclera OR drains through the
anterior ciliary veins, vortex veins, or other routes (36) (5).
• The uveoscleral meshwork is a minor site (i.e. unconventional route)
for aqueous filtration, accounting for 5 — 35% of total aqueous out
flow (33) (25) (1).
Prostaglandins decrease resistance in the uveoscleral meshwork by

relaxing the ciliary muscle and causing changes within the extra
cellular matrix, resulting in an increase in uveoscleral outflow (33).
2. C orn eosclera l m esh w ork - The outer 8-15 layers of the TM that are
located closer to Schlemm’s canal and extend between the scleral spur and
the cornea. It contains smaller pores within a network of sheet-like fibers
similar in composition to the cords of the uveoscleral meshwork. The
pores are even smaller within the portion of the TM closest to Schlemm’s
canal and within the ju xtacan alicu lar tissue (J X T ): •
• The juxtacanalicular tissue is also referred to as the crib riform

layer. It is the outermost portion of the TM and separates the
inner wall of Schlemm’s canal from the TM.
• The JXT is composed of a layer of endothelial cells and extracellular
matrix. It DOES NOT contain pores and therefore is the site o f most
resistance to aqueous outflow.
• In order to penetrate the endothelial tight junctions that line Schlemm’
canal and the endothelial cells that fill the lumen, the aqueous hu
mor must utilize a high to low pressure gradient (i.e. IOP must be
greater than the episcleral venous pressure).
Layers of the TM (from inner division to outer division) = uveoscle

ral meshwork —> corneoscleral meshwork —>juxtacanalicular tissue.

122 3.11. IRIS
Sch lem m ’ s Canal (S C )
Circular venous channel lined by endothelial cells. Serves as the major site of
aqueous humor filtration (up to 90%). The inner border (closest to the anterior
chamber) is located against the scleral spur and TM. The outer border lies
against the sclera near the limbus.
• The inner wall of Schlemm’s canal is lined by endothelial cells that are
in contact with the JXT. The endothelial cells contain multiple giant
vacuoles that transport aqueous humor across the JXT into Schlemm’s
canal.
• The outer wall is lined with normal endothelial cells (i.e. no giant vac
uoles) with a thin outer covering of connective tissue. It also contains
efferent vessels that drain aqueous humor out of the eye.
• Schlemm’s canal often contains multiple channels formed by CT septa

that increase the surface area for aqueous filtration. These channels are
known as internal colle cto r channels (36).
Aqueous humor can drain out of Schlemm’s canal through two major routes:
• Short efferents —^ deep scleral venous plexus -> intrascleral venous plexus
—y episcleral venous plexus.
• External collector channels (aka aqueous veins of Ascher) —» episcleral

ven ou s plexus.
The episcleral venous plexus drains into the anterior ciliary veins —> muscular
veins -T superior/inferior ophthalmic veins.
Schw albe’ s Line
Area of collagenous connective tissue that represents the termination of De-

scemet’s membrane and thus delineates the outer limit of the cornea to the
limbus (36).
P osterior em b ry otoxin represents an anteriorly displaced

Schwalbe’s line.
r - SECTION 3.11
Iris
We now summarize concepts related to the iris (36, ch. 3) (22, ch. 2, 12).

IT*
The iris is a circular structure that divides the space between the cornea and
the lens into anterior and posterior chambers (19).
P u p il: An opening in the iris that is located slightly nasal and inferior to
center. The pupil diameter can range from 1 mm to 8 mm, but under
normal room illumination is an average 3-4 mm.
• The iris at the pupillary margin contains Schw albe’s con tra ction
furrow s that represent variations in the thickness of the posterior
pigmented iris epithelium.
A v era ge w idth : 12 mm
T hickness: Thickest in the colla rette region; thinnest at the iris root (0.5
mm) (36).
C olla rette: A circular ridge approximately 1.5 mm from the pupillary margin
that served as the site of attachment for the fetal pupillary membrane
during embryonic development. The collarette contains remnants of old
fetal vessels in addition to active iris vessels. It divides the iris into
pupillary and ciliary zones.
• Ciliary zone: Contains iris furrows that allow the iris tissue to bunch
towards the periphery during dilation. Also contains radial streaks,
which are often white in color and represent collagen traveling along
the iris vessels.
• Pupillary zone: Radial streaks are still present but are smaller be
cause the iris blood vessels are smaller towards the pupillary margin.
• The crypts of Fuchs span the collarette into the ciliary and pupillary
zones.
A n terior iris strom a l leaf: Located within the ciliary zone of the iris; con
tains the anterior border layer and a small portion of the iris stroma.
P o sterior iris strom a l leaf: Located posterior to the anterior iris stromal
leaf. It contains most of the iris stroma in the ciliary zone and the anterior
border layer and all of the iris stroma in the pupillary zone.
A n irid ia is a rare, bilateral condition that is characterized by the

complete or partial absence of the iris. It has a high association
with glaucoma (75%) due to angle closure from PAS. Patients often
have poor vision due to foveal hypoplasia with a subsequent nys
tagmus. Additional ocular associations include micro cornea, lens
subluxation, and optic nerve hypoplasia.

124 3.11. IRIS
1. A n terior b ord er layer: Extends from the pupil margin to the iris root.
It contains multiple fibroblasts, melanocytes, and collagen fibrils. The
anterior border layer provides definitive color to the iris:
• Iris color is determined by the am ount o f m elanin within iris

melanocytes, NOT the number of melanocytes within the anterior
border layer (and to a minor extent, the iris stroma).
• In the blue iris, the anterior border layer is thin and melanocytes
contain only a small amount of melanin.
• In the brown iris, the anterior border layer is thick and the melanocytes
contain a very large amount of melanin.
• In both light and dark colored irises, the two iris epithelial layers
are heavily pigmented. The only condition characterized by a lack
of pigment within the iris epithelial layers is ocu locu ta n eou s al
binism (47) (36).
• Iris cryp ts are collagenous columns located in the anterior border
layer that serve as passageways for aqueous to enter the iris stroma.
They give the anterior iris surface a rough appearance.
H eteroch rom ia describes a difference in iris color between eyes.

It can be congenital or due to other factors such as topical
prostaglandin use or chronic inflammation (e.g, uveitis).
2. Iris Strom a: Vascularized, loose collagen network with fewer cells than
the anterior border layer. It is continuous with the stroma of the ciliary
body. The iris stroma contains several important elements (47):•
• Cells: Includes fibroblasts, melanocytes, lymphocytes, macrophages,

mast cells, and clump cells (composed of macrophages and detached
epithelial cells that congregate near the iris sphincter muscle).
• N erves: LPCNs and SPCNs. Sensory and sympathetic fibers are
carried within the LPCNs and SPCNs. Parasympathetic fibers are
carried within the SPCNs.
• B lo o d vessels: Iris capillaries are non-fenestrated (with zonula
occludens junctions) and form part of the b lo o d -a q u e o u s barrier
- M a jo r A rterial C ircle o f the Iris: Located in the C B close
to the iris root and extends radially through the iris stroma up
to the pupillary margin. It is formed by anastomoses between
the LPCAs and the anterior ciliary arteries.

CHAPTER 3. OCULAR ANATOMY 125
— M in o r A rteria l C ircle o f the Iris: Located in the iris stroma

near the pupillary margin and inferior to the collarette. It is
formed by anastomoses of the radial arteries that branch from
the major arterial circle of the iris.
— The radial veins of the iris parallel the radial arteries. They
drain blood from the iris into the ciliary body veins —> choroidal
veins —> vortex veins superior/inferior ophthalmic veins.
Remember, the major arterial circle of the iris and its branches (i.e.
radial iris arteries) are non-fenestrated capillaries that form part of
the b lo o d -a q u e o u s barrier.
• S p h in cter m u scle: Circular smooth muscle anchored firmly in the

iris stroma and to the dilator muscle. The sphincter muscle origi
nates from anterior iris epithelial cells that detach and migrate into
the iris stroma and become smooth muscle cells. It is innervated by
CN III parasympathetic fibers traveling with the SPCNs. Parasym
pathetic stimulation results in pupil constriction.
3. A n te rio r E p ith eliu m and D ilator m uscle
• A n terior iris epith eliu m : Lies closest to the iris stroma and ex
tends posteriorly to become the pigmented epithelium of the ciliary
body. The anterior iris epithelium contains pigmented m y oep ith e
lial cells that contain muscular processes at the basal surface that
extend into the iris stroma and attach to the iris sphincter muscle,
forming the d ila tor m uscle.
• D ila to r m uscle: Extends radially from the iris root into the pupil
lary zone and terminates at approximately the midpoint of the iris
sphincter muscle. Sympathetic stimulation of the dilator muscle re
sults in dilation as the pupillary portion of the iris is pulled towards
its origin at the iris root (22).
4. P o ste rio r P ig m en ted Iris E pithelium : Heavily pigmented single

layer of columnar cells attached to the pigmented anterior iris epithe
lium. It extends posteriorly to become the non-pigmented ciliary body
epithelium.•
• The p u p illa ry ru ff is formed by the posterior and anterior iris

epithelial layers curling anteriorly towards the anterior border layer
of the iris.

126 3.12. POSTERIOR CHAMBER
P igm en t dispersion syn drom e is characterized by pigment re

lease from the heavily pigmented iris epithelial layers rubbing
against the lens zonules. Released pigment may accumulate on
the anterior capsule, iris surface, corneal endothelium, or trabecu
lar meshwork and may result in subsequent glaucoma due to poor
aqueous outflow (43).
Remember that the anterior and posterior pigmented iris epithelial

layers are attached apex to apex by desmosomes and microvilli.
Iris cysts can develop if there is a separation between the two
epithelial layers (36).
i - SECTION 3,12
P o sterio r C h am b er
The posterior chamber is located between the iris and the anterior vitreous
and is bound by the posterior surface of the iris, the anterior face of the vit
reous, the equatorial region of the lens, and the ciliary body. It has a total
volume of approximately 0.060 mL (9). The posterior chamber is composed of
3 regions (22) (36):
1. P osterior cham ber p rop er: Bound by the posterior iris epithelium,
the ciliary processes, and the anterior zonules and surface of the lens.
2. C anal o f H annover (aka circumlental space): Located between the

anterior and posterior lens zonules over the equator of the lens. Also
contains the equatorial zonules.
3. Canal o f P etit (aka retrolental space): Located between the most pos
terior lens zonules, the anterior hyaloid membrane, and the posterior
portion of the ciliary body.
- SECTION 3,13 ---------------------------------------------------------------------------- -----------------------
C iliary B ody
We now summarize concepts related to the ciliary body (36, ch. 3). The ciliary
body is a triangular structure with its base located anteriorly at the scleral

spur, iris root, and anterior chamber, and the apex pointing posteriorly at the
ora serrata. It is bound externally by the sclera and internally by the posterior
chamber and vitreous (36). Functions of the ciliary body include:
• A q u e o u s h u m or p ro d u ctio n : The non-pigmented ciliary body epithe

lial cells produce and secrete aqueous humor into the posterior chamber.
• A c c o m m o d a tio n : CN III parasympathetic fibers in the SPCNs from

the ciliary ganglion innervate the ciliary muscle and cause contraction
and subsequent accommodation.
Please see ocular physiology chapter for further details on aqueous

humor formation and accommodation.
Pars Plicata (corona ciliaris): Wide anterior portion that contains 70-80 ciliary
processes that extend into the posterior chamber.
* Valleys of Kuhnt: Heavily pigmented areas located between the cil

iary processes.
• The non-pigmented ciliary body epithelium of the pars plicata is
responsible for the p r o d u ctio n and secretion o f aqueous hum or
into the posterior chamber.
A q u e o u s h u m or flow : Pars plicata —> posterior chamber -p pupil

—> anterior chamber —> trabecular meshwork.
Pars Plana (orbicularis ciliaris): Flatter, more posterior portion that begins at
the pars plicata and extends posteriorly to the ora serrata; it serves as the
anterior border of the retina, located 5 mm anterior to the equator (36).*
* D en ta te p rocesses: Extensions of the peripheral retina (ora ser

rata) onto the ciliary body (pars plana).
• O ral B ays: Posterior extensions of the pars plana that lie between
the dentate processes.
Copyright 2014 by KM K Echicational Services, LLC

128 3.13, CILIARY BODY
Neighboring dentate processes can join together, forming an en

closed oral bay; this can be confused with a retinal hole (36).
• C ou rse o f th e Lens Zonules: Arise within the tertiary vitre

ous from the basement membrane of the NPCE in the pars plana
and from the valleys between the ciliary processes in the pars pli-
cata (17) (36).
— Lens zonules produced by the pars plana extend first to the
valleys of Kuhnt of the pars plicata before inserting into the
lens capsule.
— Ruptured or damaged lens zonules can cause subluxation or
dislocation of the lens.
jLayers of th e C iliary B ody -i ;’ :

Supraciliaris: The outermost layer of the ciliary body that is loosely attached
to the underyling sclera (except at the scleral spur). It is a potential space
filled with loose CT with numerous collagen bands.
• It is continuous with the suprachoroid (the outer layer of the choroid)

at the ora serrata. Blood vessels and nerves travel from the supra
choroid through the supraciliaris to reach the anterior portion of the
eye.
• Fluid can also accumulate in this potential space, causing a ciliary
b o d y detachm ent.
C iliary M u scle: The largest intrinsic muscle of the eye. It is composed of

smooth muscle fibers that are responsible for accommodation. The ciliary
muscle is innervated by CN III parasympathetic fibers and, to a much
smaller extent, sympathetic fibers. It is anchored anteriorly in the scleral
spur and posteriorly in the stroma of the choroid (22). The ciliary muscle
contains 3 types of fibers:
1. L on gitudinal m uscle fibers (o f B ru ck e): Outermost fibers that

comprise the largest proportion of CM fibers (22). The bundles
in the longitudinal muscle form a V-shape, originating at the scle
ral spur and TM, with legs extending into the ch oroid as stellate
shaped terminations (m uscle stars) (36).
2. R a dia l fibers: Also extend in a V-shape from the scleral spur;
radial fibers terminate by inserting into the connective tissue near
the base of the ciliary processes.

3. M u lle r ’s annular m uscle: Circular muscle bundles that comprise

the smallest proportion of CM fibers. They are the most medial
CM fibers and are located near the major arterial circle of the iris.
Muller’s annular muscle originates from the scleral spur and has a
similar action as the iris sphincter muscle when activated (36).
C iliary Strom a: Located between the CM and the epithelial layers. The
ciliary stroma is highly vascularized and contains the m ajor arterial
circle o f th e iris.
• M a jo r A rteria l C ircle o f th e Iris: Located inward from the CM

near the iris root. It contains large, fenestrated capillaries located
near the ciliary epithelium of the pars plicata that are formed by
anastomoses of the LPCAs and the anterior ciliary arteries.
— Although large substances are capable of exiting the blood from
the fenestrated capillaries, the tight zonular junctions of the
non-pigmented ciliary epithelium regulates the release of these
molecules into the anterior chamber.
— As an example, the protein concentration in the blood is 7%
compared to only 2% in the aqueous humor (22),
The remaining blood vessels within the ciliary stroma (outside of the
ciliary processes) are NON-fenestrated capillaries.
A q u e o u s h um or is produce from plasma that escapes the blood

stream via the fenestrated capillaries of the major arterial circle of
the iris.
C iliary epith eliu m : Composed of two layers of epithelium that line the cil
iary body and are joined apex to apex via zonulae occludens to form part
of the b lo o d -a q u e o u s barrier. Both epithelial layers contain highly
active cells.
1. P ig m e n te d ciliary epithelium : The outer cuboidal epithelial

layer that is attached to the ciliary stroma via the basal lamina
(i.e. basement membrane).
• Anteriorly: Continuous with the pigmented anterior iris epithe
lium and its basement membrane.
• Posteriorly: Continuous with the RPE and the inner BM por
tion of Bruch’s membrane.

130 3,11 CHOROID
2. N on -p igm en ted ciliary epith eliu m (N P C E ): The inner cuboidal/columnar

epithelial layer that lines the posterior chamber. Lens zonules arise
from the basal lamina at the pars plana and the valleys of the pars
plicata. Also contains numerous organelles that are necessary for
aqueous secretion.
• Anteriorly: Continuous with the pigmented posterior iris ep
ithelium and its basal lamina.
* Posteriorly: Continuous with the ora serrata, which eventually
becomes neural retina. The basal lamina is continuous with the
internal limiting membrane of the retina.
p51op«!,Suj)i>ly p f Uic OUwry:B<>dy.. // > t ; j

* Branches from the L P C A s and the m a jo r arterial circle o f the iris
supply blood to the ciliary body.
• Veins within the ciliary body eventually drain through the v o rte x veins (36).
Jnriervation of th e C iliary B ody . h V; IT

• CN III parasympathetic nerve fibers travel with SPCNs from the ciliary
ganglion to supply the ciliary muscle for accommodation.
• Sympathetic nerve fibers from the superior cervical ganglion of the sym
pathetic ganglionic chain travel with the LPCNs and SPCNs to innervate
arteries within the ciliary body.
• Sensory nerve fibers from the semilunar ganglion of V 1 travel with LPCNs
to the ciliary body (36).
i - SECTION 3.14
C horoid *•
We now overview concepts related to the choroid (36, ch. 3).
• Located between the sclera and RPE and extends from the ora serrata
to the optic nerve.
• Thickest in the posterior pole (0,2 mm) and thinnest at the ora serrata
(0.1 mm) (38).

Contains 2 central vascularized layers surrounded by 2 non-vascularized mem

branes (4 layers total):
1. S u p ra ch oroid lam ina (lam ina fusca): The potential space located
between the sclera and the choroidal vessels (i.e. above (“supra”) the
choroid). It is loosely packed with collagen fibers, fibroblasts, melanocytes,
and extracellular matrix (36).
• The suprachoroidal space serves as a passage for the LPCAs and

LPCNs that travel from the posterior to the anterior region of the
eye.
L P C N s extend from the mid-equatorial region to the ora serrata

along the 3 and 9 o ’clock meridians.
• The suprachoroid layer contains components of BOTH the choroid

and the sclera (it does NOT belong exclusively to the choroid). If
the choroid and sclera are separated, part of the suprachoroid will
adhere to the choroid and a part will adhere to the sclera (36).
2. C h o ro id a l strom a : Loose CT layer that contains choroidal blood ves

sels, nerves and dense melanin granules.
• The choroidal vessels are innervated by the sym pa th etic nervous

system , which causes vasoconstriction.
• The high density o f blood vessels and melanin granules within the
choroidal stroma creates the potential for the development of choroidal
melanomas.
C h o ro id a l m elan om as are the most common primary intraocular

tumors in adults (21).
T h e S P C A vessels w ith in th e ciliary strom a form tw o separate

layers:•
• Haller’s layer: Posterior layer composed of large vessels that branch

into smaller vessels that form Sattler’s layer, The tributaries of the
vortex veins are also located within Haller’s layer.

132 3.14- CHOROID
• Sattler’s layer: Anterior layer composed of sm aller vessels that

branch to form a capillary bed. The veins that drain blood from the
capillary bed are the large v o rte x veins. Unlike most veins in the
body, vortex veins DO NOT contain valves (36).
3. C h orioca pillaris (aka lamina choroidocapillaris): Composed of a large

bed of fen estrated capillaries that are most concentrated within the
macula. It provides nourishment to the outer layers of the retina.
• Contains few pericytes (aka Rouget cells) that surround the capillary
walls and provide local regulation of blood flow.
Diabetes mellitus can damage the blood vessels and pericytes of

the choroid, preventing proper diffusion of nutrients and O2 to the
macula and resulting in d ia b etic retin opath y.
4. B ru ch ’ s m em brane (basal lam ina): The thin (2 um) innermost layer

of the choroid that extends from the optic nerve to the ciliary body (34).
It represents the fusion of the choriocapillaris and R,PE basement mem
branes. Bruch’s membrane is composed of the following 5 layers:
a) BM of the choriocapillaris.
b) Outer collagenous layer.
c) Elastic layer.
d) Inner collagenous layer. ,
e) BM of the RPE.
The following are noteworthy facts regarding Bruch’s membrane:
• A llow s passage o f nutrients and w astes
— N u trients pass from the choriocapillaris through Bruch’s mem

brane a.nd into the retina.
— W aste p rod u cts pass from the retina through Bruch’s membrane
to the choriocapillaris.
— P h osp h olip id s accumulate on Bruch’s membrane with age, causing
it to become hydrophobic; this impedes water movement, thereby
inhibiting the transport of metabolites (14) (36).

ChorlocapHlails
After)
JBiuch’sMembrane
Figure 3.11: Choroid
D ru sen are deposits of waste material from the retina between

the inner collagenous layer of Bruch’s membrane and the BM of the
RPE. They occur as a result of a decline in nutritional supply to the
retina and are the characteristic finding in age-related m acular
degen eration .
• C h o ro id a l neovascular m em branes (C N V M s ) result from a break

in Bruch’s membrane that can occur in a variety of conditions include ex
udative ARMD, pathological myopia, histoplasmosis, choroidal rupture,
and pseudoxanthoma elasticum (associated with angioid streaks (see
ocular disease chapter for further details)).
A n g io id streaks result from damage to the elastic layer of

Bruch’s membrane. Remember P E P S I for associations with
angioid streaks: Pseudoxanthoma elasticum, Ehlers-Danlos syn
drome, Paget’s disease, Sickle cell disease, and Idiopathic.
B lo o d and N erve S u p p ly t o th e C h oroid
• L P C A s nourish the anterior choroid.
• Branches of the S P C A s form the choriocapillaris and provide blood to

the posterior choroid.

134 3.15. VITREOUS CHAMBER
* V o rte x veins drain the choroid.
• L P C N s /S P C N s carry parasympathetic, sympathetic, and sensory fibers

that innervate the choroid.
— Sympathetic fibers from the superior cervical ganglion cause vaso

constriction of the choroidal vessels.
— CN VII parasympathetic fibers from the pterygopalatine ganglion
cause vasodilation of the choroidal vessels.
— CN III parasympathetic fibers originate from the ciliary ganglion
and have an unknown function within the choroid.
— CN VI provides sensory innervation to the choroid.
- SECTION 3,15 ---------------------------------------------------------------------------------------------------
V itreous Cham ber
We now summarize concepts related to the vitreous chamber (36, ch. 6) (47,
ch. 2).
jGenerai C h aracteristics
• V olu m e: 4 mL (overall volume of eye = 5 mL). Thus it makes up ap
proximately 80% of the globe and is easily the largest single structure of
the eye.
• Shape: Spherical in shape except anteriorly, where it is concave due to

the presence of the lens. This bowl-like depression in the anterior vitreous
is called the patellar fossa.
jCoiitent of th e X H tcpus V ) ^ j
The vitreous is approximately 98.5 — 99.7% HÔ within a matrix of Type II
collagen and hyaluronic acid (HA) (36). The consistency of the vitreous
(i.e. gel or liquid) is determined by the interaction between the collagen fibrils
and HA (39) (43).
• Early in life, the vitreous is almost entirely gel. By age 70-80, the vitreous
is evenly composed of liquid and gel (about 50/50 distribution) (8).
• Most of the changes in the collagen fibril/HA complex occur within the
central vitreous.
H y a locy tes are the predominate cell type in the vitreous and are exclusively
located within the vitreou s cortex . They are responsible for synthesiz
ing HA and may have phagocytic properties (36).

• Hyaluronic acid is a GAG that helps to maintain uniform spacing

between collagen fibrils.
F ib rob la sts are predominately located in the vitreous base and likely syn
thesize collagen fibrils (36).
F loaters occur when the HA/collagen complex is disrupted and

the collagen clumps up in bundles. Over time, liberated collagen
can contract within the vitreous gel, causing the posterior hyaloid
membrane to detach from the retina, resulting in a posterior vitre
ous detachment (P V D ) A W eiss ring is formed when the poste
rior hyaloid completely detaches from the optic disc.
The vitreous has 5 primary attachments to the retina and the lens. This is
clinically relevant because the tigh test attachments have the highest likelihood
of causing a retinal tear as the vitreous shrinks with age.
V itrea l A tta ch m en ts (Strongest —>•Weakest): Vitreous Base —►

Posterior Lens —> Optic Disc —)■ Macula —> Retinal Vessels.
iLcgions o f thfe ^ ik r e o u s • y V-V ;■ " .\j

1. V itre o u s C o r te x
Outer region of the vitreous adjacent to the retina that extends to the ora
serrata. Consists of a high density gel filled with collagen fibrils, cells, proteins,
and a mucopolysaccharide filler substance (47), The vitreous cortex is divided
into anterior and posterior hyaloid regions by the vitreou s base, an area at
the ora serrata that has the strongest attachment to the vitreous.
• A n te rio r H y a loid : Extends from the vitreous base anteriorly to attach

to the lens.
— P atellar fossa: Depression of the anterior vitreous caused by the

posterior lens.
— H yalo ideo capsular ligam ent o f W eiger: Strong circular adhe
sion between the anterior vitreous, posterior zonules, and the pos
terior capsule of lens.

136 3.16. RETINA
— B e rg e r’s space: A potential space between the anterior hyaloid

and the posterior lens capsule that is located in the central area of
non-adhesion within the circular hyaloideocapsular ligament.
• P osterior H yaloid: Begins at the posterior edge of the vitreous base

and extends posteriorly to the optic disc.
2. C lo q u e t’s canal (aka hyaloid channel or retrolental tra ct)
A normal remnant of the primary vitreous that is located in the center of

the vitreous cavity. It is composed of a channel of low density liquid vitreous
surrounded by a wall of high density gel vitreous.
• Cloquet’s canal represents the former site of the hyaloid artery that
was responsible for nourishing the avascular lens during embryological
development.
• After development, the hyaloid artery regresses to the optic disc where it
becomes the central retinal artery.
• The posterior end of Cloquet’s canal near the optic disc is known as the
area of Martegiani.
Remnants of the embryological arterial system are occasionally left

behind and can be detected clinically:
• E picapsular star: Located on the anterior lens capsule; it is

the embryological remnant of the former connection between
the anterior tunica vasculosa lentis and the posterior hyaloid
artery.
• M it t e n d o r f’s d o t: Embryological remnant of the hyaloid

artery on the posterior lens capsule.
• B erg m eister’s papillae: Embryological remnant of the

hyaloid artery on the optic disc.
i— SECTION 3.16
R e tin a
We now summarize concepts related to the retina (36, ch. 4) (47, ch. 2). The
retina is the innermost structure of the eye where light energy is transformed

into chemical energy. It extends from the edge of the optic disc to the ora
serrata.
• The retina is derived from neural ectod erm .
• The retina has 10 layers (including the RPE) and is comprised of several
different types of cells including photoreceptors, horizontal cells, bipolar
cells, amacrine cells and ganglion cells.
IB IS
The RPE is a single layer o f cuboidal pigmented cells. The apical side of the
cells face the retina and the basal side lies adjacent to Bruch’s membrane. The
BM of the RPE strongly adheres to the choroid, forming the innermost portion
of B ru ch ’ s m em bran e,
* The RPE is derived from the outer layer of the optic cup.
* Although the RPE has NO intercellular junctions with the rods and cones,
the apical side of the RPE cells contains microvilli that extend into the
photoreceptor layer to surround the PR outer segments. These microvilli
are responsible for p h a g o cy to sis of the PR outer segments (36).*
* The potential space (i.e. subretinal space) between the RPE microvilli
and P R outer segments is filled with an interphotoreceptor matrix that
has a varied chemical composition around rods compared to cones.
Figure 3.12: Relationship between choroid, RPE, and Photoreceptors

138 3.16. RETINA
The subretinal space between the RPE and neural retina can lead
to the development of retinal detachm ents.
Major functions of the RPE include (22) (36):
1. P h a g o cy tosis o f p h oto re ce p to r ou ter segm ents - RPE cells are

highly active and contain smooth ER, rough ER, Golgi, and lysosomes.
Undigested material from PR outer segments can accumulate within RPE
cells as lipofuscin, which can contribute to RPE cell death (41).
L ysosom es are found within RPE cells and play a significant role
in phagocytosis of the photoreceptor outer segment discs.
2. Transfer o f ions, w ater, and m eta b olites - RPE cells transport sub
stances between the choroid and retina through a complex process that
involves multiple pumps, co-transporters, and channels. Examples in
clude the following:
• Proton-lactate-water cotransporter moves lactate, a biproduct of

anaerobic respiration, from the RPE to the choroid.
• Glucose transporter moves glucose from the choroid to the RPE to
ensure a steady supply to the photoreceptors (26).
3. V ita m in A storage and m etabolism - RPE cells play an important

role in the visual cycle by recycling vitamin A (all-trans retinol) and
retinoids between the photoreceptors and the RPE.
4. B lo o d -re tin a l barrier - RPE cells are tightly linked together by a ter
m inal co m p le x that includes zonulae occludens, zonulae adherens, and
maculae adherens, forming the blood-retinal barrier,
5. A b so rb s light - RPE cells contain pigment granules that absorb stray

light that is not absorbed by the rods and cones.
6. P ro d u ce s g row th factors for tissue m aintenance - RPE cells pro

duce vascular endothelial growth factor (V E G F ), which is essential for
choriocapillaris function, as well as pigment epithelial derived factor (PEDF),
an anti angiogenic factor that counterbalances the effects of VEGF (36).

Figure 3.13: Layers of the Retina
There are 120 million rods and 6-8 million cones per eye. The photoreceptors
are special sensory cells that contain photopigments that absorb photons of
light. Photoreceptors contain an inner and an outer segment:
• Inner S egm ent: Produces p h otop ig m en ts that are transported through

the cilium to the outer segment, where they are incorporated into discs.
— M y o id : The inner layer of the inner segment that contains ER and

Golgi apparatus for p rotein synthesis.
— E llipsoid : The outer layer of the inner segment that is packed with
mitochondria.
— C iliu m : Connects the outer and inner segments of photoreceptors.

140 3.16. RETINA
The myoid region of the inner segment m akes protein. The

elipsoid (en ergy) region of the inner segment has a high concen
tration of mitochondria,
• O u ter Segm ent (O S ): Contains stacks of membranous discs that con

tain photopigments produced by the inner segments.
- The OS produces the discs that surround the photopigment molecules.

There are approximately 600-1000 discs per rod and 1000-1200 discs
per cone (36).
— Disc membranes are continuous with the plasma membrane in cones
but are free-floating (NOT continuous with the plasma membrane)
in rods.
D isc p h otop igm en ts are formed in the inner segment, assembled

into discs at the base of the outer segment, and are continually
shed at the tip of the outer segment for phagocytosis by the RPE.
R ods
Used for sco to p ic vision; rods detect objects under low levels of illumination.
• Rod density is greatest about 5 m m (20 degrees) concentrically from the

fovea in an area known as the r o d ring (37).
• Rod discs contain the photopigment rh od op sin , which absorbs photons

maximally at 507 nm (22); rhodopsin DOES NOT detect color.•
• Rods terminate in spherules (compared to cones, which terminate in pedi

cles).
C on es
Used for p h o to p ic vision. Cones contain 3 different photopigments (iodopsins)

that each contain the same chromophore (11-cis retinal) but differ in their pro
tein (opsin) component.
• Cyanolabe (blue): Maximally absorbs photons at 440 nm.
• Chlorolabe (green): Maximally absorbs photons at 535 rim.

• Erythrolabe (red): Maximally absorbs photos at 565 nm.
The fovea is 5 mm temporal and 0.4 mm inferior to the center of

the optic nerve (superior and nasal to the ONH if viewing with a
78 or 90D condensing lens) and contains ONLY con e p h otore
ce p to rs at the highest concentration in the retina.
Serves as a barrier that is not truly a membrane and does not contain any cells.
The ELM is formed by a band of desmosomal attachments between Muller cells
and the inner segments o f the photoreceptors. It provides structure to the retina
and acts as a barrier against large metabolites.
Contains the cell bodies of ro d s and cones.
Location of the synapse between rod spherules and cone pedicles and the den
drites of bipolar and horizontal cells.
Spherules and p e d icle s are simply the synaptic terminals for rods
and cones, respectively. This is where rods and cones connect with
bipolar and horizontal cells.
R o d spherule: Each rod spherule can synapse with 1 to 4 r o d b ip ola r cell

den drites (the ONLY type of bipolar cell rods synpase to). Horizontal
cell dendrites may also connect to rod spherules (22).
C on e p ed icle: Larger than the rod spherule. Can form a synpatic triad that
consists o f 3 horizontal cell dendrites OR, 2 horizontal cell dendrites on
either side of 1 bipolar cell dendrite within an invagination in the cone
pedicle (36).•
• Cone pedicles may synpase with midget, flat, or diffuse flat bipolar
cells (see below for further description).

142 3.16. RETINA
Note the following regarding the outer plexiform layer (OPL):
• The OPL is the site of the 1st synapse in the visual pathway.
• H en le’s fiber layer describes the OPL within the macula.
• The OPL is the only retinal layer to receive blood supply from the choroid
AND the retina (via the CRA).
Remember, the central retinal artery supplies the inner 2/3 of

the retina including the NFL, GCL, IPL, INL, and a portion of the
OPL.
• R etin osch isis describes a splitting of the OPL.
• H ard exudates are located in the OPL.
;6. IN N E R N U C L R ^ IV l^ Nv; '/L -Vy

Contains the cell bodies of bipolar, horizontal, interplexifbrm, amacrine, and
Muller cells.
B ip o la r cells: Carry signals from photoreceptors to g an glion cells. Bipolar

cells synapse with photoreceptors in the OPL and with ganglion cells in
the IPL. There are four types of bipolar cells:
• R o d b ip ola r cells: ONLY connect with rod photoreceptors.

• M id g et b ip ola r cells: Connect to only one cone and to one gan
glion cell. Midget bipolar cells resolve very fine details and are found
within the fovea.
• Flat b ip ola r cells: Connect with several cone photoreceptors.
• D iffuse flat bipolar cells: Connect with numerous cone photore
ceptors (more than the flat bipolar cells).
H orizon ta l cells: Carry information laterally (i.e. horizontally) within the

retina through synapses with photoreceptors, bipolar cells, and other hor
izontal cells that occur in the O P L . •
• Horizontal cells modify the information that reaches the bipolar cells
by providing lateral inhibition.
• They provide inh ibitory feedback to photoreceptors or in h ibitory
feed-forw ard signals to bipolar cells (22).

• Horizontal cells are joined together through gap junctions.
In terp lex iform cells: Carry information vertically in the retina by relaying
information between the two synaptic layers (OPL and IPL).
A m a crin e cells: Carry information laterally in the retina by connecting with

bipolar cells, interplexiform cells, ganglion cells, and other amacrine cells.
M u ller cells: The most common glial cells of the retina. Muller cells stretch
from the ILM to the ELM and provide structural and nutritional support
(see below for further details).
A m a crin e and h orizon tal cells provide inhibitory feedback that

is necessary to fine-tune the retinal signal.
Location o f the synapse between the 2nd order (bipolar cell) and 3rd order
(ganglion cell) neurons in the visual pathway. A m acrin e cells modify the
synapse between bipolar and ganglion cells by providing temporal input and
increasing signal resolution (22).
• Bipolar cells synapse with one process from an amacrine cell and one
dendrite from a ganglion cell.
• Amacrine cells synapse with bipolar cells, ganglion cells, interplexiform

cells, and other amacrine cells within the IPL.
As a general rule, bipolar and amacrine cells have opposite effects

on ganglion cells (GCs) (37). Bipolar cells increase the stimulation
of GCs, and amacrine cells decrease the stimulation of GCs.
v:--;
. mo-
•VjV-- '--V' Z- -
The location of the ganglion cell bodies. Each ganglion cell has a single axon
that travels within the optic nerve and terminates in the L G N or other areas
of the brain (e.g. superior colliculus or pretectal nucleus).*
* There are NO ganglion cells in the foveala, 4-7 GC layers in the macula,
and 1-2 GC layers in the remaining retina:

144 3.16. RETINA
There are approximately 18 different types of ganglion cells that fall into one
of two broad categories (36) (43):
P -cells: Parvocellular cells have small diameter axons and are sensitive to
c o lo r and fine detail. P-cells are more common than M-cells and
project to the parvocellular layers of the LGN (layers 3, 4, 5, 6). There
are 2 types of P-cells;
• Pi cells are also known as m idget ganglion cells. They are the
most common ganglion cells and contain only one dendrite that
synapses with one midget bipolar cell, which connects with one cone
photoreceptor within the fovea (22, pp. 339) (36).
• P2 cells are larger than Pi cells and contain multiple dendrites that
synapse with multiple bipolar cells.
M -C ells: Magnocellular cells have large diameter axons and are sensitive to
d im changes in illum ination and m otion . M-cells project to the
magnocellular layers of the LGN (layers 1 and 2).
M id g e t ganglion cells are responsible for resolving fine detail

because they carry visual information from a single cone photore
ceptor within the fovea (22, pp. 339) (36).
Composed of the axons of ganglion cells that collectively form the optic nerve.
• The nerve fiber layer (NFL) is thickest at the superior and inferior optic
disc margin where the largest proportion of axons enter the optic nerve.
• The nerve fiber layer is NOT present within the fovea. It begins within
the parafoveal region of the macula and is known as H en le’s fib er layer.
• The papillom acular bundle consists of NFL fibers that extend from
the macula and insert on the temporal margin of the optic disc.
- The superior and inferior temporal fibers arc over the papillomacular
bundle and insert at the superior and inferior margins of the optic
disc.
- The superior and inferior nasal fibers insert directly into the superior
and inferior nasal margins of the1optic disc.

Abnormal findings within the NFL include the following:
• C o tto n w o o l sp o ts (C W S ) (aka soft exudates) are located

within the NFL and are most commonly caused by diabetes.
• Splinter h em orrh ages (aka Drance hemorrhages) are

hemes that occur within the NFL at or near the optic disc,
• F lam e h em orrh ages occur within the NFL and are asso
ciated with retinal vascular pathology (e.g. diabetes, hyper
tension, vein occlusions).
Remember that d o t o r b lo t hem orrhages are associated with

deep retinal vascular pathology and are found within the IN L.
C W S , splinter h em es, and flam e hem es are associated with
superficial retinal vascular pathology and are found within the
N FL.
The innermost boundary of the retina (closest to the vitreous) that is continu
ous with the inner limiting membrane of the ciliary body. The internal limiting
membrane is comprised of the fo otp la tes o f M u ller cells and their basal
lam ina that are bound to vitreous humor collagen fibrils.
• The internal limiting membrane is present over the macula but NOT over
the optic disc. A s tr o c y te s replace the footplates of Muller cells at the
optic disc.•
• E piretinal m em bran es occur on the internal limiting membrane and

are commonly located within the macula.
Copyright 2014 by KM1< Educational Services, LEG

146 3.16. RETINA
N eural M essaging:
• 128 m illion p h otorecep tors —> 35 m illion b ip ola r cells

-> 1 .5 m illion ganglion cells
• The neural message is highly refined from the photoreceptors

to the ganglion cells.
• The optic nerve acts like a “bottleneck” through which all

visual information must pass through (37) (36).
^Neuroglial Cells 'TA
M u ller cells: The most common glial cell that is present exclusively in the
retina (22). Muller cells extend from the E L M to th e IL M . Most Muller
cell bodies are located within the INL.
• Although Muller cells are NOT found within the photoreceptor layer,
microvilli from the apical surface of Muller cells may extend towards
the inner segments of the photoreceptors to form fiber baskets.
Muller cells provide structural and nutritional su p p o rt to the retina in the

following ways:
• Maintain alignment of other neurons within the retina.
• Provide nutrients to the retina and aid in g ly cog en m etabolism .
Remember that the retina is highly metabolically active. Its pri

mary source of energy is glucose that is produced via an aerobic
glycolysis (36), Oxygen and nutrients are transported across the
RPE into the inner segments of the photoreceptors. Excess glucose
is converted to glycogen and stored in M u ller cells to ensure the
photoreceptors have a constant supply of nutrients.
• A c t as a buffer and regulate electrolyte concentration within the ex

tracellular space (particularly K + concentration).•
• A b s o r b and recycle m eta b olic w aste p ro d u cts such as GABA and

glutamate (36).

A stro cy te s: Most concentrated within the inner retinal layers (22). Astro
cytes are fibrous cells that provide structure to nerve fibers and retinal
capillaries.
• Astrocytes help form the ILM at the optic disc (Muller cells form
the ILM throughout the rest of the retina). They perform similar
functions as Muller cells (36) (32).
M icroglia l cells: Phagocytic cells (i.e. modified macrophages) that respond

to inflammation and/or injury. Microglial cells can be found anywhere
in the retina.
N eu roglial cells have NO ROLE in signal processing. They pro

vide protection and structural support to the retina.
[Retinal B lood Siipply ; T

The outer 5 retinal layers receive their blood supply from the choroid ; the
inner retinal layers receive their blood supply from the central retinal artery.
Remember, the OPL is a watershed area that receives blood supply from BOTH
sources.
* The CRA forms two capillary networks: a superficial capillary network

in the N F L and a deep capillary network within the IN L (near the
OPL) (36).•
The cilioretin a l a rtery is a branch from the SPCAs of the chorio-

capillaris that supplies the inner layers of the macula. It is present
in 15 — 20% of the population and allows the macula to be spared
in a C R A O (36).
• The inner retinal layers are drained by the central retinal vein. The
outer retinal layers are drained by the v ortex veins.

148 8.16. RETINA
Retinal arteries and veins share a common adventitia at arteri

ovenous crossings. Because of this close relationship, damage to
the arterial walls results in venous wall compression and throm
bus formation. This explains why almost all branch retinal vein
occlu sion s occur at AV crossings.
We now summarize details regarding the macula (aka macula lutea or area
centralis), the central area within the posterior pole that is bounded by the
superior and inferior arcades (36, ch. 4).
• The macula is 5.5 mm in diameter and subtends an angle of 18 degrees.

It is located approximately 3.5 mm lateral to the edge of the optic disc
and 1 mm inferior to the center of the optic disc (22) (36).
• The macula contains two major xanthophyll pigments (zeaxanthin and

lutein) that are responsible for reducing chromatic aberration and may
provide protection against free radicals. These pigments are mostly found
within the inner segments of the photoreceptors; they contribute to the
more yellow appearance of the macula compared to the surrounding
retina.
• The macula includes the foveala, fovea, parafovea, and perifovea.
Figure 3.14: Layers of the Retina / Macula

Fovea
• D ia m eter: 1.5 mm (approximately 1DD) diameter circle in the center

of the macula. The foveala is located within the central fovea.
The central 0.40-0.50 mm of the fovea is avascular (“foveal avas

cular zone”) in order to minimize light scattering and allow for
resolution of fine details. This area is supplied by the underlying
chorio capillar is via the SPCAs.
Foveala
The foveala (“little fovea”) is approximately 0.35 m m in diam eter and 0.13
m m in thickness. It is the last area of the retina to mature during develop
ment.
• The foveala is the thinnest area o f the retina and contains ONLY con e
p h o to re ce p to rs . The ganglion cells, bipolar cells, and other retinal cells
are laterally displaced in order to minimize light scattering.
Because of the lateral displacement of retinal cells away from

the foveala, the retina is thickest just outside the fovea in the
parafoveal region.
• The foveala has the highest concentration of cones in the retina (199,000
cones/mm2) and is the area of best visual acuity. There are NO blue
cones or rods within the central 1 degree of the foveala.
R e tin a l layers w ith in th e foveala = RPE, photoreceptor layer,

ELM, ONL, Henle’s fiber layer, and ILM.
• H en le’s fiber layer is the term used for the outer plexiform layer within
the macula. This layer contains the axons o f the ph otorecep tors.
Remember that there are NO bipolar cells or ganglion cells within the
fovea or foveala (and thus no INL, IPL, GC layer, or NFL).

150 3.16. RETINA
P arafovea
The parafovea is a 0.5 mm zone that surrounds the fovea (total diameter = 1,0
mm). The clivus (sloping of the retinal layers within the macula) marks the
boundary between the parafovea and the fovea. ALL retinal layers are present
within the parafovea.
• The parafovea is the thickest area of the retina and contains the largest
number of bipolar cells (7-11 layers) and ganglion cells (7-11 layers).
P erifovea
The perifovea is a 1.5 mm zone that surrounds the parafovea (total diameter
= 3.0 mm).
• The boundary between the perifovea and parafovea is the location where
the ganglion cell layer becomes 4 cell layers thick. The boundary
between the perifovea and the periphery is located at the point where
the ganglion cell layer becomes on e cell layer thick.
Remember that the fovea DOES NOT contain rod photoreceptors.

The density of the rods begins to increase 1.2 to 1.7 mm from the
center of the fovea (within the parafovea and perifovea regions).
The rod photoreceptor density peaks 5 mm from the center of the
fovea, forming the r o d ring just outside the perifovea region (22).
^Peripheral R etina •A/• .;-c ;,A ■■H

The peripheral retina terminates approximately 5 mm anterior to the equator
of the eye at the ora serrata (36).
• The ora serrata is a 2 mm band at the anterior-most portion of the retina

and is composed of dentate processes and oral bays.
— Dentate processes are extensions of peripheral retina onto pars plana

of the ciliary body.
- Oral bays are extensions of pars plana into the peripheral retina.
• The RPE becomes the pigmented ciliary epithelium.
• The neural retina significantly thins and transitions into the non-pigmented
ciliary epithelium.

• The vitreou s base, the strongest point of attachment between the vit
reous and the retina, extends over and posterior to the ora serrata
* Retinal vasculature becomes very limited towards the ora serrata. The
peripheral 1.5 mm of anterior retina contains very few, if any, capillar
ies (36).
- SECTION 3.17 ----------------------------------------------------------------------------------------------------
O cular an d O rb ital N erves
NERVE INFO FUNCTION

1-Olfactory Sensory Smell
2-Optic Sensory Vision
3-Oculomotor Motor Eye movement
Accommodation
Pupil constriction
‘4-Trochlear Motor Superior Oblique
5-Trigeminal Both Facial sensation, mastication
6-Abducens Motor Lateral Rectus
7-Facial Both Facial expressions, ant 2/3 taste, lacrimation,
salivation (submaxillary, submandibular glands)
8-Vestibulocochlear Sensory Hearing, balance
9-Glossopharyngeal Both Swallowing, salivation (parotid gland)
post 1/3 taste, monitors carotid sinus
10-Vagus Both Taste, swallowing,
palate elevation, talking,
thoracoabdominal viscera
11-Accessory Motor Head turning, shoulder shrugging
12-Hypoglossal Motor Tongue movement
In a C N X palsy, the u vula deviates away from the side of the

lesion and the palate DOES NOT elevate; the patient will report
a hoarse voice. A C N X I I palsy will result in ton g u e deviation
tow ards the side o f the lesion.
SHIM !
We now introduce the cranial nerves that are involved with ocular struc
tures (36, ch. 12) (47, ch. 6).

152 3.17. OCULAR AND ORBITAL NERVES
O P T IC N E R V E (C N II)
Carries sen sory information only. The optic nerve is composed of the axons of
the ganglion cell bodies within the GCL of the retina. All of the axons converge
at the optic disc, exit the sclera at the lamina cribrosa, and leave the orbit via
the optic foramen, to travel through the optic canal.
• N asal fibers (from GC bodies nasal to the fovea) cross at the optic
chiasm to join the temporal fibers of the other eye within the optic tract.
The optic tract contains nasal fibers from the contralateral eye and
temporal fibers from the ipsilateral eye that carry information from
the sam e side o f the visual field.• *
• CN II fibers travels to one of three final destinations:
1. L G N : Relays visual information to the primary visual cortex (V I).

2. P retecta l nucleus: Involved in pupil innervation.
3. Su p erior colliculus: Involved in control of saccades (36) (47).
O C U L O M O T O R N E R V E (C N III)
CN III has a right and left nucleus located in the m id b ra in at the level
of the superior colliculus. Each nucleus contains sub-nuclei that provide v o l
untary m o to r co n trol to the SR, MR, IR, and 10 muscles, as well as an
E din ger-W estp h al nucleus that provides p arasym path etic innervation
to the ciliary and iris sphincter muscles through the ciliary ganglion (36).
CN III nuclei are connected to the nuclei of CN IV, VI, and VIII
through the medial longitudinal fasciculus (MLF). They also re
ceive information from the superior colliculus and the visual cortex.
• Fibers that leave the sub-nuclei for the medial rectus, inferior rectus, and
inferior oblique project to the ipsilateral m uscles.
• Fibers that leave the sub-nucleus for the su p erior rectu s project to the
contralateral muscle.

The SR fibers are the ONLY fibers from the sub-nuclei that decus
sate (i.e. cross the midline). A lesion of the right SR sub-nucleus
will result in poor control of the left S R muscle.
• The levator palpebrae muscle for each eye is controlled by only one cen
tral subnucleus.
A lesion of the levator p alp ebrae subnucleus will result in a

sudden onset bila teral ptosis.
Fibers from the sub-nuclei join together as they exit the brainstem and then
travel in close proximity to the p o s te rio r com m u n ica tin g artery before
piercing the roof o f the cavern ous sinus. Within the cavernous sinus, CN III
receives sy m p a th etic fibers from the internal carotid artery plexus. CN III
divides into su p erior and in ferior division s just before it enters the orbit
through the su p erior o rb ita l fissure (47).
1. Su p erior division
Innervates the superior rectus and superior levator palpebrae muscle. Sympa
thetic fibers travel with the superior division to innervate Muller’s muscle of
the upper eyelid.
2. In ferior d ivision
Innervates the medial rectus, inferior rectus, inferior oblique, sphincter muscle,
and ciliary muscle.•
• The inferior division contains parasympathetic fibers from the Edinger-

Westphal nucleus that course to the ciliary ganglion; these fibers leave
the ganglion as short posterior ciliary nerves (SPCNs) and innervate the
sphincter (3% of fibers) and the ciliary muscle (97% of fibers) for pu p il
lary co n strictio n and a ccom m od a tion , respectively.

C N III innervates four of the six EOMs (SR, MR, IR, 10) and the
levator palpebrae muscle. It also provides parasympathetic supply
to the ciliary body (accommodation) and the iris sphincter (miosis),
and provides the route for sympathetic supply to Muller’s muscle
of the upper lid, A complete GN III lesion results in a severe
ptosis and the eye looking “ dow n and o u t ” (due to an exotropia
and hypotropia).
The pupillary fibers are located on the ou tsid e of all other fibers within CN
III. Understanding this anatomy is critical for determining whether or not a
CN III lesion should be treated as an emergency.
1. A CN III palsy that is pup il-in volvin g (presents with a fixed and di
lated pupil) should immediately raise suspicion for an aneurysm o f th e
p o ste rio r com m unicating artery. The pupil is involved because the
aneurysm is pushing on the pupillary fibers on the outside of CN III.
* The aneurysm is most likely located at the junction between the

posterior communicating artery and the internal carotid artery.
2. A “pupil sparing” CN III palsy is likely caused by ischem ia of the small

blood vessels that nourish the inner fibers of CN III, most likely as a
result of diabetes or hypertension. Since the pupil is NOT involved, the
likelihood of a compressive lesion (e.g. tumor or aneurysm) pushing on
CN III is quite low.
T R O C H L E A R N ERVE (CN IV )
CN IV is the longest (75 mm) and skinniest cranial nerve. It contains two
nuclei that are located in the m idbrain at the level of the inferior colliculus.
• The CN IV nuclei are connected to the nuclei of CN III, VI, and VIII
through the medial longitudinal fasciculus (M LF). They also connect to
the superior colliculus via the tectobulbar tract, which then connects to
the visual cortex.•
• CN IV is the ONLY cranial nerve that leaves the dorsal side of the
brainstem and decussates to innervate the contralateral superior oblique
muscle.

A patient with a su p erior ob liq u e palsy will try to minimize the

effects by tilting his/her head away from the affected side. Damage
to the right trochlear nucleus will cause a left superior oblique palsy
(because CN IV decussates), and the patient will tilt his/her head
to the right.
• CN IV enters the lateral wall of the cavernous sinus and travels under
neath CN III. It then enters the orbit superior to the annulus of Zinn
through the superior orbital fissure.
• Remember that although the anatomical origin of the su p erior obliq u e

is the lesser wing of the sphenoid bone, the physiologic origin of the
muscle is the troch lea .
T R IG E M IN A L N E R V E (C N V )
Contains two roots, one motor and one sensory, that both originate in the
pons.
• Carries sen sory information from the face and head, including all or
b ita l stru ctu res (36).
• The sensory fibers can be divided into three divisions:
— V I provides sensory information from the head to the tip of the

nose.
— V 2 provides sensory information from the side of the nose to the
mouth.
— V 3 provides sensory information from the head and ear to the
mandible. It also provides m otor information to the m uscles o f
m astication . •
• The sensory fibers travel from the face and head structures, through the
cavernous sinus, and synapse in the trigem inal ganglion (located on the
posterior portion of the cavernous sinus) before traveling to the sensory
nuclei in the pons for relay to the thalamus.
H erpes sim p lex keratitis can affect any or all of the branches
of VI (nasociliary, frontal, and lacrimal branches). Thus, these
patients are much more likely to have involvement of the upper
eyelid and foreh ea d rather than the lower eyelid and forehead.

V I - O ph th alm ic D ivision : Divides into three branches:
N a socilia ry N erve: Garries sensory information from the cornea, iris, and
tip of the nose. It has several branches, including the long ciliary nerves,
short ciliary nerves, inffatrochlear nerve, and the anterior and posterior
ethmoid nerves (36).
• The L P C N s supply sensory fibers to the corn ea, iris, and ciliary
muscle. They also carry sym pathetic fibers to the dilator muscle
of the iris (47).
• The S P C N s also supply sensory fibers to the cornea, iris, and ciliary
muscle.
• The infratrochlear nerve supplies sensory fibers to the medial
angle of the eyelids.
Branches from the nasociliary nerve of V I innervate the cornea

and the tip of the nose. This explains why H u tch in son ’ s sign
(lesions on the tip of the nose) indicates a high likelihood of cornea
involvement in herpes zoster.
Frontal N erve: Branches in the cavernous sinus just before it enters the orbit
through the superior orbital fissure. The frontal nerve divides into two
terminal branches:
1. Su pratrochlear N erve: Passes just superior to the trochlea of the

superior oblique to ultimately provide sensory innervation for the
skin and muscles of the forehead and the m edial p o rtio n of the
upper eyelid and conjunctiva (47).
2. S u praorbital N erve: Provides for the forehead and scalp, the
- central p o rtio n of the upper eyelid, and the conjunctiva (36).
Nerve supply to the upper eyelid (from lateral to medial) =

lacrimal —> supraorbital —> supratrochlear —> infratrochlear nerve.
Su p erior orb ita l rim traum a can cause damage to the supraor
bital and supratrochlear nerves, resulting in hypoesthesia of the
ipsilateral forehead.
L acrim al N erve: Provides sensory feedback for the lacrim al gland.

• Just before it enters the lacrimal gland, the lacrimal nerve receives
pa ra sym pa th etic fibers o f C N V II from the zygomatic branch
of V2; these fibers are responsible for lacrim ation.
• Once it leaves the lacrimal gland, the lacrimal nerve pierces the
orbital septum to supply the lateral conjunctiva and the lateral part
of the upper eyelids (47).
V 2 - M a xilla ry D ivision V2 travels along the inferior lateral portion of the

cavernous sinus before entering the foram en rotu n d u m of the greater wing
of the sphenoid. V2 divides into two terminal branches just before entering the
orbit through the inferior orbital fissure (47):
1. In fraorbital nerve: Enters the maxillary bone through the infraorbital

foramen (4 mm below the inferior orbital rim) to innervate the lower
eyelids, cheek, and the upper lip (36).
2. Z y g om a tic nerve: Courses laterally from the inferior orbital fissure and
divides into two terminal branches that innervate LATERAL structures,
including the lateral aspect of the forehead, the lateral side of the cheek,
and lateral aspect of the lower eyelid. Remember, the zygomatic nerve of
V2 carries parasympathetic fibers from the pterygopalatin e ganglion
o f C N V II to the lacrimal nerve of V I to stimulate lacrimation.
Nerve supply to the low er eyelid (from lateral to medial) = zygo

maticofacial -» infraorbital —> infratrochlear nerve. Note that the
infratrochlear nerve (a branch of the nasociliary nerve) provides
nerve supply to the medial portion of the lower eyelid (majority)
and the upper eyelid (36).
V 3 - M an dibu lar D iv isio n
• Provides sensory innervation to the lower face.
• Provides m o to r in n ervation to the muscles of mastication.
For C N V , immediately think SENSORY, SENSORY, SENSORY

with a minor motor component. The motor component controls
the muscles of mastication through V3.

A B D U C E N S N E R V E (C N V I)
The abducens nucleus is located in the pons. Fibers leave the nucleus betw een
th e p on s and th e m edulla and then make a tight bend over the petrous ridge
o f the temporal bone before entering the cavernous sinus (6).
• An increase in intracranial pressure (e.g. a space occupying

lesion) can compress CN VI against the petrous ridge, result
ing in damage to the nerve and a lateral rectu s palsy (36).
• A C N V I palsy can also result from an internal ca rotid

a rtery aneurysm within the cavernous sinus due to the
close association between the ICA and CN VI as they travel
through the cavernous sinus.
• CN VI enters the orbit through the su p erior orb ita l fissure and passes
through the co m m o n tendinous ring before innervating the lateral
rectus.
- The lacrimal artery and lacrimal nerve course along the superior
edge of the lateral rectus.
— The ciliary ganglion lies medial to the lateral rectus (between the
lateral rectus and the optic nerve).
C N V I palsy will result in an eso deviation. The patient will re

port horizontal diplopia that is most apparent at distance. He/she
may also present with a head turn tow ard the affected side.
F A C IA L N E R V E (C N V II )
Provides motor innervation to the muscles of facial expression and supplies

parasympathetic fibers to the inner ear and facial glands (including the lacrim al
gland). The facial nerve also carries taste sensations (sensory) from the ante
rior 2/3 of the tongue.
T h re e R o o t s o f C N V II: Large motor root and a smaller sensory and parasym

pathetic root.

1. V olu n tary m o to r r o o t: Innervates the facial muscles, including

the orbicu laris o cu li to close the eye.
2. Involuntary m o to r r o o t: Parasympathetic fibers stimulate se
cretion of the facial glands, including lacrim ation of the lacrimal
gland. The involuntary motor root also provides a branch to the
stapedius muscle of the middle ear to dampen sound.
3. Sensory r o o t: Carries taste from the anterior 2/3 of the tongue.
C ou rse o f C N V I I
• CN VII begins in the pre-central motor cortex in the frontal lobe.
• Fibers descend within the corticobulbar tract to the pons, where the
facial motor nucleus and superior salivatory/lacrimal nuclei are located.
• Fibers exit the nuclei of CN VII as a main motor root and the nervus
intermedins root (carries parasympathetic fibers of CN VII). Fibers arch
around the abducens nucleus before exiting the brainstem. They enter
the internal a u d ito ry canal in the petrous portion of the tem p ora l
b o n e and travel through the geniculate ganglion.
Any nuclear lesion of CN VI may also affect CN VII due to the

close association between the two nuclei within the brainstem.
• After leaving the geniculate ganglion, the greater p etrosal nerve and
the ch ord a tym pan i nerve branch off the main root of CN VII. The
remaining fibers exit the temporal bone of the skull through the stylomas
toid foramen. They enter the parotid gland and divide into five branches
to innervate the muscles o f facial expression.
1. G reater P etrosal N erve
• Carries parasympathetic innervation to the lacrim al gland. The greater

p etrosa l nerve joins the deep p etrosa l nerve (contains post-ganglionic
sympathetic fibers) to form the vid ia n nerve.
• The vidian nerve travels to the ptery g op a la tin e (aka sphenopalatine)

ganglion, where parasympathetic fibers synapse.•
• Post-ganglionic parasympathetic fibers leave the pterygopalatine ganglion

and join the zygomatic branch o f V2. The zygomatic branch sends a com
municating branch to the lacrimal nerve of VI to innervate the lacrim al
gland (4).

2. C h ord a tym pani nerve
• Terminal branch of CN VII that carries taste fibers from the anterior 2/3
of the tongue and provides parasympathetic supply to the submandibular
and sublingual glands.
3. Facial expression
The main root of CN VII passes through the stylomastoid foramen and enters
the parotid gland where it divides into five branches (temporal, zygomatic,
buccal, mandibular, and cervical branches) to supply the muscles of facial
expression . The two most superficial branches (temporal and zygomatic)
innervate muscles around the eye:
• The temporal branch innervates the procerus, corrugator, occipital frontalis,

and the orbicularis oculi.
• The zygomatic branch innervates the orbicularis ocu li.
Although the facial nerve branches within the p a ro tid gland, it

DOES NOT innervate the gland. The glossoph aryn geal nerve
(C N I X ) provides innervation to the parotid gland. Removal of
an a cou stic neurom a may result in damage to the nearby parotid
gland and CN VII, causing facial paralysis on the affected side.
For C N V II, immediately think MOTOR, MOTOR, M OTOR

with a minor sensory component. The sensory component carries
taste information from the anterior 2/3 of the tongue.
B e ll’ s P alsy vs. Stroke
Remember that the upper neurons of CN VII in the brainstem receive bilat
eral in pu t from the cerebral cortex. The lower neurons of CN VII receive
contralateral input and provide innervation to ipsilateral facial muscles.
Stroke: A supranuclear lesion results in impaired Innervation to the co n

tralateral m uscles o f the lower face, often resulting in drooping of
the mouth. The contralateral fibers to the upper face that allow eyelid
closure and wrinkling of the forehead are often spared, and patients are
able to firmly close their eyes and wrinkle their forehead.

Bell's Palsy Vs. Stroke
Lower Motor Neuron Lesion Upper Motor Neuron Lesion

Affects Entire Half of Face Affects Only Lower Half
Figure 3.15: Bell’s Palsy vs. Stroke
B e ll’ s P alsy: An id io p a th ic lesion of the lower motor neurons of CN VII

that results in impaired innervation to the u p p er and low er ipsilateral
facial m uscles, causing drooping of the mouth and poor eyelid closure.
Bell’s palsy can result in para ly tic lagophthalm os (the most common
form of lagophthalmos) and secondary ex p osu re keratopathy (4).
Parasympathetic innervation to the eye originates from the midbrain (CN III)
and the pons (CN VII) and performs three major functions:
* O cu lo m o to r nerve (C N II I ): Travels to the iris sphincter and the

ciliary muscle for miosis and accommodation, respectively.
• Facial nerve (C N V I I ): Travels to the lacrimal gland for lacrimation.
1st order pre-gangliionic fibers begin in the hypothalamus and descend to the
C8-T2 region of the spinal cord to synpase in the ciliospinal center o f B udge.

162 S.17. OCULAR AND ORBITAL NERVES
Figure 3.16: O verview o f P arasym pathetic and S y m p a th etic Pathw ays.

Note how CN III enters the ciliary ganglion and leaves as short ciliary nerves to
innervate the ciliary and sphincter muscles. Note how sympathetic fibers from
the hypothalamus synapse in the superior cervical ganglion before traveling
with the long ciliary nerve (a branch of the nasociliary nerve of CN V I) to
innervate the dilator muscle.

2nd order pre-ganglionic fibers leave the ganglion and travel around the clavicle
and across the a p ex o f th e lung before entering the sympathetic chain of
ganglia along the neck. Fibers ascend the chain and synapse in the superior
cervica l ganglion. Post-ganglionic fibers from the superior cervical ganglion
form a plexus around the internal ca rotid artery and enter the skull via the
carotid canal.
A P an coast tu m or of the lung can affect the pre-ganglionic sym

pathetic fibers and result in H o rn e r’s syndrom e.
Once inside the orbit, sympathetic fibers within the ICA plexus may follow
three routes:
1. Follow the superior division of C N III to innervate M u ller’s m uscle of

the upper eyelid.
2. Follow the nasociliary nerve o f C N V l and branch with either the

L P C N s or S P C N s.
* The LPCNs carry sympathetic innervation to the iris dilator and

the ciliary muscle.
* Sympathetic fibers may pass through the ciliary ganglion and exit
with the SPCNs to innervate the choroidal and conjunctival blood
vessels.
Hyperactive sy m p a th etic innervation to the blood vessels of

the choroid is thought to play a role in the development of central
serous ch orioretin op a th y by contributing to localized damage
in Bruch’s membrane.
3. Provide innervation to the blood vessels of the lacrimal gland (causing

vasoconstriction) through the vid ia n nerve (the motor root of the ptery
gopalatine ganglion).

164 3.18, OPTIC NERVE
Sum m ary o f the S P C N s and L P C N s:
• S P C N s originate from the ciliary ganglion and carry post

ganglionic sympathetic and parasympathetic fibers to various
anterior structures of the eye. They also carry sensory in
formation from the eye back to the ciliary ganglion via the
nasociliary nerve.
• L P C N s branch from the n asociliary nerve o f V I as it

crosses the optic nerve. They carry post-ganglionic sympa
thetic fibers to the eye, as well as carry sensory information
from the eye back to the trigeminal ganglion.
• S en sory inform ation carried by both the LPCNs and

SPCNs is eventually taken to the trigem in al ganglion for
analysis.
I— SECTION 3.18
O ptic N erve
We now overview concepts related to the optic nerve (36, ch. 4) (22, ch. 10).
The optic nerve is composed of axons o f ganglion cells that course to one
of three destinations: the midbrain, the LGN, or the superior colliculus.
jGeneral C h aracteristics • . -i
• The optic nerve has little to no regenerative capabilities.
• The intraorbital (post-laminar) portion of the optic nerve is surrounded

by pia, arachnoid, and dura membranes that are continuous with the
meninges of the cranium.
- The subarachnoid space (between the arachnoid and pia sheaths)

of the optic nerve is continuous with the subarachnoid space of the
cranium and contains cerebrospin al fluid.
— The dura and arachnoid meninges fuse together and become con
tinuous with the periorbita and the sclera; they DO NOT continue
with the intracranial portion of the optic nerve (only the pia mater
surrounds the intracranial optic nerve) (36).

CHAPTER S. OCULAR AN ATOM Y 165
P ap illedem a results from an increase in intracranial pressure (e.g.

space occupying lesion, malignant hypertension) that causes CSF
within the subarachnoid space to leak over the superficial optic
disc. The disc margins are blurred in papilledema because the
CSF spreads over the margins into the surrounding RNFL.
• Oligodendrocytes provide myelination to the axons p osterior to the

lam ina crib rosa. Astrocytes provide structural support to the optic
nerve axons.
— Note that Schwann cells are not found within the optic nerve and
therefore DO NOT provide myelination to the optic nerve.
The optic nerve sheath is attached to the sheaths surrounding

the SR and MR muscles. This association explains why approx
imately 90% of patients with o p tic neuritis experience pain on
eye m ovem ent (27).
B lo o d su p ply to th e o p tic nerve:
• R e tin a l N F L : Supplied by the SPCAs and the central retinal artery.

• In traocu lar O N (pre-laminar and laminar layers): Supplied by
the Circle of Zinn (formed by anastomoses of the SPCAs) and other
branches o f the SPCAs.
• In tra orb ita l O N (post-laminar): Supplied by branches from the
central retinal artery and the pial mater arterial plexus.
• In tracranial O N : Supplied by branches of the ophthalmic, anterior
cerebral, anterior communicating, and internal carotid arteries (36).
Remember that the optic nerve is able to autoregulate its blood

supply (like the retina but unlike the choroid).
Copyright 2014 by KMK Educational Services, LEG

166 3.18. OPTIC NERVE
The optic disc is the most anterior part of the optic nerve. It is located in the
nasal retina 15 degrees from fixation (i.e. the fovea) and subtends an angle of
5-7 degrees.
• The disc is slightly larger vertically (1.75 mm) than horizontally (1.50
mm) (43).
• The optic nerve acts as a blind spot in the visual field because it DOES
NOT contain photoreceptors (only contains NFL and ILM).
• Remember, there are NO Muller cells over the optic disc. Instead, as
tro cy te s cover the optic disc and form the IL M o f Elschnig.
The optic nerve is approximately 50-60 mm long and can be divided into the
following four regions: intraocular, infraorbital, intracanalicular, and intracra
nial (36, ch. 14) (22, ch. 25) (47):
1. In traocu lar p o rtio n (1 m m ): Portion of the optic nerve that extends

from the optic disc to the lamina cribrosa. The intraocular portion of the
optic nerve can be divided into two sections:
• P re-lam in ar O N : The optic nerve anterior to the lam ina cribrosa.

Axons are bundled within sheaths of astrocytes for structural sup
port. This portion of the nerve contains NO MYELIN.
— The optic nerve fibers are separated from the surrounding reti
nal tissue by a ring of glial tissue known as the in term ediary
tissue o f K uhnt. This glial tissue continues posteriorly as
the b o rd e r tissue o f Jacoby and separates the optic nerve
fibers from the choroid. Scleral collagen fibers at this level
also surround the glial tissue, forming the b o rd e r tissue o f
E lschnig (36).
— Tight junctions within the glial tissue help to protect the optic
nerve fibers from fluid that leaks from the fenestrated choroidal
vessels.
• Lam inar O N : Section of the optic nerve that exits the globe through
the lam ina cribrosa, a network of collagen .and elastic fibers that
bridge across the posterior scleral foramen and help* support the
optic nerve.
2. In traorbital p o rtio n (30 m m ): Extends posteriorly from the lamina cri-

bosa until it exits the orbit via the optic canal. This portion of the optic
nerve is S-shaped and the axons are separated by connective tissue septa,
allowing for eye movements without damage to the optic nerve.

• The optic nerve axons posterior to the lamina cribrosa become m yeli
nated by oligodendrocytes. The axons are also covered by the
meninges that cover the rest of the brain (36).
3. Intracanalicular (6 -10 m m ): Portion of the optic nerve running through

the optic canal within the cranium.
4, Intracranial (10-16 m m ): Portion of the optic nerve extending from the

optic canal to the optic chiasm.
- SECTION 3 .1 9 ------ ---------------------------------------------------------------------------------------------
V isual P ath w ay
We now summarize concepts related to the visual pathway (36, ch. 14) (3,
ch. 1). Axons of the ganglion cells make a 90 degree turn at the optic disc and
comprise the optic nerve. Fibers within the optic nerve travel to 3 different
locations:
1. 90% of the optic nerve fibers synapse in the L G N before traveling to the
primary visual cortex (V I) (36).
2. Fibers traveling to the su p erior collicu lu s aid in saccadic eye move

ments.
3. Fibers traveling to the p retecta l nucleus aid in pupil movement.
jOrieritation of F ib e rs a t th e O ptic Disc

• P ap illom acu lar b u n dle: Composed of fibers from the macula that
enter the te m p o ra l side of the optic disc. Damage to these fibers can
result in central, centrocecal, and paracentral visual field defects.
A central sc o to m a is often caused by macular disease, but optic

nerve disease that affects the papillom acu lar bundle (i.e. nutri-
tional/toxic optic neuropathy) will also cause reduced visual acuity.
• N asal fibers: Axons from retinal ganglion cells nasal to the fovea enter
the nasal side of the disc.
• Superior and in ferior arcuate fibers: Axons from ganglion cells tem
poral to the fovea that enter the disc and the superior and inferior poles,
respectively.

168 3.19. VISUAL PATHWAY
The IS N T rule describes the comparative thickness of the rim

tissue, with the inferior rim being thickest and the temporal rim
being thinnest.
Recall that the superior and inferior nasal fibers (carrying information from
the temporal visual field) cross at the o p tic chiasm (see Figure 3.17). It is
important to remember that the superior and inferior nasal fibers take different
paths when crossing through the chiasm:
1. A n terior K n ees o f W ilb ra n d : Inferior nasal fibers that cross through

the optic chiasm and then loop anteriorly into the contralateral optic
nerve before entering the optic tract.
2. P o ste rio r K nees o f W ilb ra n d : S uperior nasal fibers that loop pos
teriorly into the ipsilateral optic tract before crossing through the optic
chiasm.
3. O p tic chiasm : Located within the Circle of Willis. The internal carotid
artery and posterior communicating arteries travel along the lateral edges
o f the optic chiasm. The pituitary gland is located inferior to the optic
chiasm.
; -v,
The optic tract extends from the o p tic chiasm to th e L G N and contains
fibers (crossed and uncrossed) from each eye that provide information from the
same side of the visual field. The optic tract travels along the lateral surface
of the cerebral peduncles parallel to the posterior cerebral artery.
A n E xam ple: T h e R igh t O p tic T ract (see Figure 3.17).
• S u p erior fibers (nasal and temporal) course to the m edial side of the
optic tract. The medial portion of the right optic tract contains right
superior temporal and left superior nasal fibers.
• In ferior fibers course to the lateral side of the optic tract (36). The
lateral portion of the right optic tract contains right inferior temporal
and left inferior nasal fibers.•
• M acu lar fibers travel in tbe m iddle of the optic tract.

Left Optic Nerve Right Optic Nerve
Figure 3.17: Remember, the o p tic tra ct contains the fibers that travel from
the optic chiasm to the LGN. Note how the posterior knee (which contains
the superior fibers) courses to the medial side of the left optic tract, while the
anterior knee (containing inferior fibers) courses to the lateral side of the tract.
Macular fibers are protected in the middle of the tract.

nmammam
Fibers within the optic tract synapse at the lateral gen icu late ganglion
located within the thalamus. Remember that approximately 90% of optic nerve
fibers synapse at the LGN before projecting to the primary visual cortex. The
LGN is composed of six layers that contain three types of cells (36):
1. Magnocellular layers: Layers 1 and 2 (located interiorly) that contain

large magno cells.
2. Parvocellular layers: Layers 3-6 (extend superiorly) that contain medium

parvo cells.
3. Koniocellular layers: Contains small cells located between each layer.
Crossed fibers of the optic tract synapse in LGN layers 1, 4, and

6. Uncrossed fibers of the optic tract synapse in LGN layers 2, 3,
and 5.
The fibers within the optic tract maintain their precise topography as they
synapse within the LGN:
• Superior fibers synapse in the m edial LG N .
• Inferior fibers synapse in the lateral LG N .
• Macular fibers form a w edge of synapses at the dorsal edge of the LGN
and extend throughout its entire thickness.
In addition to serving as the location of the first synapse within

the visual pathway, the LGN also receives fibers from subcortical
areas and the primary visual cortex that help to fine-tune the visual
information that is relayed to the primary visual cortex.
The fibers that leave the LGN and travel to the primary visual cortex (V I) are
called the o p tic radiations.

CHAPTER. 3. OCULAR AN ATOM Y 171
• In ferior radiation s: Composed of the inferior retinal fibers from the

lateral side of the LGN. These fibers travel through the tem p ora l lo b e
and around the tip of the lateral ventricle into the parietal lobe (forming
M e y e r’ s L o o p ) before terminating in V I in the occipital lobe.
• Su perior radiation s: Composed o f the superior retinal fibers from the

medial side of the LGN, These fibers course directly posterior through the
inferior parietal lo b e before terminating in VI in the posterior portion
of the occipital lobe.
P rim a ry V isu al C o r te x and the C alcarine Fissure
The primary visual cortex (aka V 1/Brodmann’s area 17/striate cortex) is lo
cated on the medial surface o f the o ccip ita l lob e. The calcarine fissure
divides the internal posterior portion of the occipital lobe into anterior and
posterior sections:
1. C uneus gyrus: The superior portion of the visual cortex in the occipital
lobe. Su p erior retin al fibers terminate here.
2. Lingual gyrus: The inferior portion of V I in the occipital lobe. Inferior

retinal fibers terminate here.
M acu la
Macular fibers project to the o u ter surface o f th e apex o f the occip ita l
lo b e and make up approximately 50% of the fibers within VI.
• Superior macular fibers project to the cuneus gyrus.
• Inferior macular fibers project to the lingual gyrus.
Sum m ary o f th e In ferior R etin a l F ibers: Lower fibers (in

ferior fibers) course Laterally in the optic tract and form Meyer’s
Loop before ending in the Lingual gyrus (36).
P rim ary V isu al C o r te x ( V I )
The primary visual cortex contains myelinated nerve fiber layers that mainly
project from the LGN, as well as fibers from the superior colliculus and the
frontal eye fields (36). It is organized into six horizontal layers and multiple
vertical columns of neurons.

• Layer 4 is the location of the synapse between the optic radiations and
the neurons of the striate cortex. Fibers from the parvo and magnocel-
lular layers of the LGN synapse in different strata within layer 4. Axons
projecting from the neurons within layer 4 of V I travel to higher cortical
areas (V2-V5) for further visual information processing.
• Layer 5 sends axons to the su p erior colliculus for control of saccadic

eye movements.
• Layer 6 provides feedback information back to the LGN.
• Vertical columns of cells are organized into ocu lar dom in an ce colu m n s
that contain fibers from only one eye. Ocular dominance columns are fur
ther organized into stimulus orientation columns (responds to a stimulus
of a particular orientation in front of a particular eye).
B in o cu la r processin g of visual information begins at the level of

the prim a ry visual cortex.
B lo o d su pply o f the Visual Pathw ay
Please see optic nerve section for blood supply of the optic nerve.
• O p tic chiasm : Supplied by the Circle of Willis and branches of the

internal carotid artery.
• O p tic tracts: Supplied by the anterior choroidal branch of the middle

cerebral artery.
, • L G N : Supplied by the anterior choroidal and posterior cerebral arteries.
• O p tic radiations: Supplied by the anterior choroidal, middle cerebral,

and posterior cerebral arteries.•
• P rim a ry visual cortex : Supplied by the p osterior cerebral artery

and the m iddle cerebral artery.
The posterior cerebral and middle cerebral arteries serve as a dual

b lo o d su p ply to the primary visual cortex. If one arterial blood
supply is blocked (e.g. stroke), vision is often spared because the
2nd arterial blood supply is still able to provide nutrients and Oi
to the visual cortex.

CHAPTER S. OCULAR AN ATOM Y 173
We now discuss how pathology can affect visual function (16, ch. 6) (3, ch. 1).
P ost-C h ia sm a l Lesions
1. P ost-ch iasm al lesions p ro d u ce h om on y m ou s visual field defects.

This means that the sam e side o f the visual field is affected in both eyes.
• Example: A right post-chiasmal lesion will result in loss of the left

visual field in the right AND left eye.
2. T h e m ore p o ste rio r a p ost-ch iasm al lesion is loca ted , the m ore
con gru ou s th e visual field d efects are betw een th e eyes.
C on gru ity refers to the similarity between homonymous defects in each

eye. Remember that fibers from each eye that cany visual inform s
tion about a particular point in the visual field travel closer to
gether as they travel more posterior in the visual pathway. Thus,
these fibers are often damaged together, producing visual field de
fects with a similar size and shape between the two eyes.
O ccip ita l lo b e lesions cause congruous defects because it is the

most posterior location within the visual pathway.
In con gru ou s field defects are homonymous defects that DO NOT have
a similar size and shape between the two eyes. Lesions that are m ore
an terior in the visual pathway cause incongruous field defects.
3. T em pora l lo b e lesions cause su p erior visual field defects. This is

often referred to as a “ pie in th e sk y” defect. Remember that a lesion in
the temporal lobe damages the inferior retinal fibers forming Meyer’s
Loop.
4. P arietal lo b e lesions cause inferior visual field defects. This is often

referred to as a “ pie o n th e flo o r” defect. Remember that a lesion
in the parietal lobe damages the su p erior retinal fibers (and is also
associated with asymmetric OI<N responses).

Remember the phrase P IT S for visual field defects:

• Parietal lobe lesions classically produce Inferior visual field
defects.
• Temporal lobe lesions classically produce Superior visual field
defects.
5. V isu al acu ity is unaffected in post-chiasmal lesions unless bilateral

lesions are present (16). Remember that in order for visual acuity to be
affected, the macular region of the occipital lobe has to lose BOTH of its
blood supplies.
• The macula receives a dual blood supply from the middle cerebral
and the posterior cerebral arteries.
• A m acular involving visual field defect (with reduced visual acu
ity) will only occur if BOTH blood supplies are affected.
• If only one blood supply is affected, vision will remain unaffected
(m acular sparing) because the other blood supply will continue
to provide nutrients to the macular fibers within the occipital lobe.
M a cu la r Sparing H om on ym ou s H em ianopia: Most commonly re

sults from a stroke that has affected either the middle or the pos
terior cerebral artery (but NOT both). It is very rare for a stroke
to affect BOTH blood supplies of the superficial occipital lobe.
M a cu la O N L Y H om on ym ou s H em ianopia: Most commonly occurs
from a tu m or that has compressed BOTH blood supplies to the
macular cortex. Although it can result from multiple strokes that
affect the middle and posterior cerebral arteries, this is extremely
rare.
O p tic C h iasm Lesions
1. A b ite m p o ra l hem ianopsia is classically caused by a p itu itary gland

tu m o r that compresses the nasal fibers from each eye that cross at the
optic chiasm.
2. An optic chiasm lesion that extends towards one of the optic nerves causes
a ju n ctio n a l scotom a (3). A junctional scotoma often appears as cen
tral vision loss in one eye and superior temporal loss in the fellow eye
(due to compression of the inferior nasal fibers) (16) (36).

• The eye with the affected optic nerve will have very poor visual acu
ity. The other eye will have minimal damage (and good visual acu
ity) because the anterior knee of Wilbrand (carrying inferior nasal
fibers) loops into the damaged optic nerve.
Bitemporal defects or a junctional scotoma indicate a lesion at the

optic cliiasm.
1. VP defects that respect the horizon tal m idline result from

lesions an terior to the chiasm and are most commonly due
to glaucoma.
2. VF defects that respect the v ertica l m idline result from

post-ch ia sm a l lesions and are most commonly due to
. strokes.
90% of homonymous hemianopsias are secondary to strokes. The

main exception occurs with m acula o n ly h om on y m ou s hem i
anopsias, which are rarely caused by strokes (think compressive
lesion!) (3).
O ptic N erve Lesions
1. Cause asymmetric visual field loss between the eyes.
2. Defects typically respect the horizontal midline.
3. Defects may be bilateral but they are NOT congruous (3).
4. An APD can occur if asymmetrical damage between the optic nerves is

great enough.
5. Visual field defects will correspond to the location of the lesion within
the retinal nerve fiber layer.

176 3.19. VISUAL PATHW AY
Unilateral defect, binasal step, and/or arcuate scotoma =

Retinal or optic nerve pathology.
Retinal Lesions
1. Causes asymmetric visual field loss between the eyes.
2. Defects DO NOT respect the horizontal or vertical midline.
3. Defects may be bilateral but they are NOT congruous.
References
[1] Aim A, Nilsson SF. Uveoscleral outflow-a review. Exp Eye Res. 2009 Apr;88(4):760-8. Epub
2009 Jan 3.
[2] Alvarado J, Murphy C, Juster R. Age-related changes in the basement membrane of the
human corneal epithelium. Invest Ophthalmol Vis Sci, 1983 Aug;24(8): 1015-28.
[4] Bartlett, Jimmy D,, Jaanus, Siret D. Clinical Ocular Pharmacology, 5th Edition.
Butterworth-IIeinemann, 2008.
[5] Bill A. Some aspects of aqueous humour drainage. Eye (Loud). 1993,‘ 7 (Pt l):14-9.
[6] Doxanas MT, anderson RL. Clinical Orbital Anatomy. Baltimore; Williams and Wilkins,
1984; 131.
[7] Dutton JJ. Atlas of Clinical and Surgical Orbital Anatomy, 2nd ed, Philadelphia; Saunders,
2011.
[8] Eisner G, Clinical Anatomy of the Vitreous, In W Tasman, EA Jaeger (eds), Duane’ s Foun
dations of Clinical Ophthalmology (Vol 1), Philadelphia; Lippincott, 1994; 1,
[9] http:/ / ww w .eopht ha.com / eop ht ha /p df / % 2Gfi1es/ Wall % 2OHan ge r.p df.
[10] Gipson IK, Spurr-Michaud SJ, Tisdale AS. Anchoring fibrils form a complex network in
human and rabbit cornea. Invest Ophthalmol Vis Sci 1987; 23(2):212
[11] Gipson IK, Spurr-Michaud SJ, Tisdale A, et al. Reassembly of the anchoring structures of
the corneal epithelium during wound repair in the rabbit. Invest Ophthalmol Vis Sci 1989;
30:425
[12] Goldman J, Benedek, G, Dohlman C. Structural alterations affecting transparency in swollen

human corneas. Invest. Ophthalmol, Vis. Sci. October 1968 vol. 7 no. 5 501-519.
[13] Guyer DR, Miller NR, Auer CL, Fine SL. The risk of cerebrovascular and cardiovascu
lar disease in patients with anterior ischemic optic neuropathy. Arch Ophthalmol. 1985
Aug; 103(8): 1136-42.
[14] Guymer R, Lutliert P, Bird A.Changes in Bruch’s membrane and related structures with age.
Prog Retin Eye Res. 1999 Jan; 18(1):59-90.
[15] Hanna, G, O ’ Brien JE, Cell production and migration in the epithelial layer of the cornea.
Arch Ophthalmol 1D60;64:536,

[16] Harkins, Timothy. Clinical Geriatric Eyecare. Ch. 6: Geriatric Ocular Disease. Aston, Sheree
J. Maino, Joseph I-I. Boston: Butterworth-Heinemann, 1993.
[17] Hogan MJ, Alvarado JA, Weddell E: Histology of the Human Eye. Philadelphia: W B Saun
ders, 1971,
[18] Holland, E,, Cornea, 2nd edition, volume 1, Fundamentals, Diagnosis and Management
(2005), pp 1335-1340.
[19] Imaging of Orbital and Visual Pathway Pathology, W.S Muller-Forell. Berlin Heidelberg:
Springer, 2002.
[20] Ischemic Optic Neuropathy Decompression Trial. Characteristics of patients witli nonarteritic
anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression
Trial. Arch Ophthalmol. 1996 Nov; 114(11): 1366-74.
[21] Kanski, Jack. Clinical Ophthalmology 4th ed. Woburn; Butterworth and Heinmann, 1999.
[22] Kaufman, Paul. Aim, Albert. Adler’s Physiology of the Eye, 10th ed. St. Louis: Mosby, 2003.
[23] Komai Y, Ushiki T. The three dimensional organization of collagen fibrils in the human
cornea and sclera. Invest Ophthalmol Vis Sci 1991; 32:2244.
[24] Krachmer JH, Mannis MJ, Holland EJ. Cornea. 2nd ed. Philadelphia: Mosby, 2011.
[25] Krohn J, Bertelsen T. Corrosion casts of the suprachoroidal space and nveoscleral drainage
routes in the pig eye. Acta Ophthalmol Scand. 1997 Feb;75(l):28-31.
[26] La Cour, M. and Tezel, T, H. The Retinal Pigment Epithelium. In Fischbarg J, ed. The
biology of the eye, 2006, Elservier, 253-271.
[27] Lepore FE. The origin of pain in optic neuritis. Arch Neurol 1991;48:748-749.
[28] Macular Photocoagulation Study Group: Risk factors for choroidal neovascularization in the
second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary
to age-related macular degeneration. Arch Ophthalmol 115: 741-747, 1997,
[29] Macular Photocoagulation Study Group: Occult choroidal neovascularization. Influence on

visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 114:
400-412, 1996.
[30] Meyer PA, Watson PG. Br J Ophthalmol. 1987 Jan;71(l):2-10. Low dose fluorescein angiog
raphy of the conjunctiva and episclera.
[31] MUller LJ, Pels E, Vrensen GF. The specific architecture of the anterior stroma accounts for
maintenance of corneal curvature. J Ophthalmol. 2001 Apr;85(4);437-43.
[32] Ramirez JM, Trivino A. Ramirez AI, et al: Structural Specializations of Human Retinal Glial
Cells. Vision Res 36(14): 2029t)2036, 1996.
[33] Nilsson SF.The uveoscleral outflow routes. Eye (Lond).1997;ll (Pt 2): 149-64.
[34] Ramrattan,R, et. al. Morphometric Analysis of Bruch’s Membrane, the Choriocapillaris, and
the Choroid in Aging. Investigative Ophthalmology and Visual Science, 1994; 35(6)
[35] Rapuano, Christopher J, Heng, Wee-Jin. Color Atlas and Synopsis of Clinical Ophthalmology,
Wills Eye Hospital. Singapore: McGraw-Hill, 2003.
[36] Remington, Lee Ann. Clinical Anatomy and Physiology o f the Visual System, 3rd Ed. Boston:
Butterworth-Heinemann, 1988.
[37] Rodieck, R.W, The First Steps in Seeing. Sunderland: Sinauer Associates, 1998.
[38] Sameer Trikha, Samantha de Silva, Hemal Mehta and Simon Keightley. MCQS for FR-
COPHTH and ICO Basic Science Examinations. Radclifle Publishing, 2012.
[39] Sebag J. The Vitreous. In W M Hart Jr (ed), Adler’s Physiology of the Eye (9th ed). St.
Louis: Mosby, 1992; 268,

[40] Smetana GW, Shmerling RH, Does this patient have temporal arteritis? JAMA. 2002 Jan
2;287(1):92-101.
[41] Sparrow JR, Nakanishi K, Parish CA. The lipofuscin fluorophore A2E mediates blue light-
induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci. 2000
Jun;41(7);1981-9.
[42] Stoeclrelhuber M, Stoeckelhuber BM, Welsch U, Human glands of Moll; histochemical and
ultrastructural characterization of the glands of Moll in the human eyelid. J Invest Dermatol.
2003 Ju);121(l):28-36.
[43] Tamesis, Richard R. Ophthalmology Board Review., 2nd Edition. McGraw-Hill, 2006.
[44] http; / / www.theodora.com/anatomy/thesinusesoftheduramater.html
[45] US National Eye Institute, Facts About The Cornea and Corneal Disease Keratoconus. A c
cessed 12 Feb 2006.
[46] Wobig JL. The Eyelids. In MJ Reeh, JL Wobig, JD Wirtschafter (eds), Ophthalmic Anatomy,
San Francisco: American Academy of Ophthalmology, 1981; 38.
[47] Wolffe, Eugene. Eugene W olff’s Anatomy of the Eye and Orbit. Warwick, R (ed). Philadel
phia: Saunders, 1976; 160.
[48] Wulc AE, Dryden RM, Kliatcliaturian T. Where is the gray line? Arch Ophthalmol. 1987
Aug;105(8): 1092-8.

Chapter
I 4 T _________
Ocular Embryology
Kyle M . Cheatham, O .D ., F .A .A .O .
179
C
(
c
180
(
c
(
(
(
(
(
(
(
(
<
(
(
(
(
c
(
(
(
(
(
(
(
(
CHAPTER 4 . OCULAR EMBRYOLOGY 181
Recall that the neural tube consists of three general areas: the forebrain, mid
brain, and hindbrain. The forebrain differentiates into two additional regions,
the telencephalon and diencephalon, which are separated by the optic chiasm
in the adult brain. The eye begins to form from the wall of the diencephalon.
Recall that the developing embryo is comprised of three layers:
1. M esod erm : Used for development of the notochord, muscles, and mes
enchyme.
• Mesenchyme gives rise to the dermis, circulatory system (heart,

blood vessels), and connective tissue (CT). Remember, bone, blood,
and cartilage are all specialized CT.
2. E cto d e rm : Consists of surface ectoderm and neural ectoderm, both of

major importance in the development of ocular structures. Overall, used
for the development of the CNS (brain and spinal cord), as well as the
epidermis and associated skin, hair, nails, etc.
3. E n d od erm : Forms the gut, most glands, and the inner lining of the di
gestive and respiratory tubes. N o con trib u tion to ocu lar structures.
. T;"-
:V .
* On approximately the 18th day o f development, two neural folds develop

in the ectoderm and fuse together, forming the neural tube by day 22.
• The formation of the neural tube leads to a realignment of ectoderm into

the surface ectoderm (above the neural tube) and the neural ectoderm
(the lining of the tube).
- Neural crest cells from the neural ectoderm are formed during this
process and lie between surface and neural ectoderm.
- Mesoderm, the middle layer of the embryo, also lies between these
two layers along with the neural crest cells.
• On day 25, neural e c to d e rm on each side of the neural tube begins to

grow outward, forming o p tic vesicles.
- Each optic vesicle invaginates and forms a two-layered optic cup

with an optic stalk (precursor to the optic nerve) that connects to
the neural tube, and a fetal fissure (for the hyaloid artery and vein).
— The em b ryon ic fetal fissure is the last structure to close during
the formation of the optic cup, allowing mesenchyme to migrate to
this region for development of the hyaloid artery plexus.
Copyright 2014 by KMK Educational Services. LLC

182
Wall of Forebrain
Surface Ectoderm
Optic Grove
Figure 4.1: Note how the optic vesicles (of neural ectoderm) bulge outward
and contact surface ectoderm. The vesicles later invaginate forming the neural
retina and RPE. The surface ectoderm becomes the corneal epithelium and
lens.
— The hyaloid plexus within the vitreous cavity eventually disinte

grates, but the posterior hyaloid artery persists as the central retinal
artery.
Failure of the fetal fissure to close properly results in a colob om a .

The choroid, retina, optic nerve, upper/lower eyelid, iris, and cil
iary body can have colobomas. Inferior colo b o m a s are the most
common due to the inferior location of the embryonic fissure.
The inner and outer layers of the cup contribute to the following:

Figure 4.2: D ev elop m en t o f M a jo r O cular Structures. Note how the

invaginating lens placode becomes the optic vesicle. It pinches off the surface
ectoderm and becomes the lens.
IN N E R L A Y E R O F T H E O P T IC C U P
• Becomes the neural retina, non-pigmented ciliary body epithelium (NPCE),

and posterior pigment layer of the iris. The inner layer of the optic cup
differentiates into the following:
1. O u ter n eu rob la stic layer - consists of photoreceptors, bipolar

cells, horizontal cells,
2. Inner n eu rob la stic layer - consists of amacrine cells, Muller cells,

ganglion cells.
The R P E is the first layer of the retina to develop. The cells of

the neural retina develop in the following order: Ganglion (1st) /
Horizontal / Cones / Amacrine / Bipolar / Rods / Muller cells. The
m acula is the first area of the retina to begin cell differentiation,
but it is the LAST to complete development; foveal maturation is
not complete until approximately 4 years of age (4).

184
O U T E R L A Y E R O F T H E O P T IC C U P
• Becomes the RPE, the outer pigmented ciliary body epithelium (PCE),
and the anterior iris epithelium.
R e tin o b la sto m a (Rb) is the most common primary intraocular

malignancy in children. The tumor occurs during retinal devel
op m en t as a result of mutations in the R,b tumor-suppressor gene.
The development of the lens occurs approximately the same time the optic
cups are developing (day 27). While the optic vesicles begin to form (before
invagination), the adjacent surface e ctod erm thickens and forms the lens
p la cod e. The lens placode invaginates, forming a lens pit, before becoming a
lens vesicle as it separates from the surface ectoderm.
Lens epith eliu m : The lens vesicle is a hollow ball of cells that contains an
anterior and posterior lens epithelium.
P osterior lens epithelium : Differentiates into primary lens fibers that elon
gate towards the anterior lens epithelium and fill the lumen of the lens
vesicle. During this process, the primary lens cells produce crystallins.
Primary lens fibers form the em bry on ic nucleus (first nucleus) by 2
months (3).
• Young lens fibers are very uniform in shape and maintain precise
alignment. Only the young outer fibers are nucleated and contain
organelles. With age, they lose their regularity, become less orga
nized, and their nuclei and other organelles disintegrate.
A ll lens grow th after the d evelopm en t o f th e em bry on ic

nucleus can b e attribu ted to secon d ary lens fibers. T h e
p o ste rio r lens epithelium is N O T present in adults.
A n te rio r lens epithelium : Contains the germinative zone located just an
terior to the equator. After formation of the embryonic nucleus from
the posterior lens epithelium, the cuboidal cells of the germinative re
gion become columnar and elongated anteriorly and posteriorly, forming
secondary lens fibers. These fibers contribute to the development of all
remaining nuclei in the following order: fetal nucleus, juvenile nucleus,
adult nucleus, and lens cortex.

CHAPTER l OCULAR EM BRYOLOGY 185
• A d u lt nucleus: Contains lens fibers that are formed from birth to

sexual maturation.
• Lens co rte x : Contains lens fibers formed after sexual maturation.
The p o sterior lens ep ith eliu m becomes primary lens fibers that
form the embryonic nucleus. There are NO sutures within the
embryonic nucleus. The anterior lens epith eliu m becomes sec
ondary fibers that form the fetal nucleus. The inverted Y sutures
seen with a slit lamp are from secondary lens fibers and denote the
boundaries of the fetal nucleus.
In d u ction is a term that refers to how the development of one

tissue influences the development of another tissue; an example
during ocular development is how optic cup formation stimulates
lens development (3).
CORNEAL DEVELOPM ENT
• Corneal Epithelium: As the lens vesicle is being developed, the surface

ectoderm forms the corneal epithelium.
* Rest of the Cornea: N eu ral crest cells contribute to the formation

of the corneal stroma (which produces Bowman’s layer) and the corneal
endothelium (which produces Descemet’s membrane).
N eural crest cells represent a specialized type of neural ectoderm

that play a pivotal role in corneal development. These cells also
contribute to cranial nerve formation.
• Corneal epithelium, conjunctival epithelium, eyelid epithelium.

186
* Lens (recall that all lens fibers are derived from epithelium).
Remember that lens zonular fibers are derived from tertiary vitre
ous (2) (3).
• Meibomian, Zeis, Moll, Krause, and Wolfring glands.
• Lacrimal gland, lacrimal sac, canaliculi, nasolacrimal duct, caruncle.
Remember, surface ectoderm gives rise to “surface” (superficial)

structures. Think epithelium , lens, and glands; most, if not all,
ocular glands are derived from surface ectoderm.
NEURAL ECTODERM
• Neural retina, RPE, and neuroglia.
• Epithelium of CB and iris.
• Sphincter and dilator muscles.
• Optic nerve fibers.
Most muscle tissue develops from mesoderm. The iris m uscles

develop from neural e cto d e rm and are thus exceptions to this
general rule.
• Corneal layers except for the epithelium (the endothelium develops first).
• Trabecular meshwork.
• Iris and CB stroma.
• Sclera and choroid.

• Vitreous.
Irregular iridocorneal adhesions occur as a result of abnorm al

neural crest cell dev elop m en t and are characteristics of Axen-
feld’s anomaly/syndrome and Reiger’s anomaly/syndrome (1).
C on gen ital gla u com a is a rare condition that results from poor development
of the angle architecture, resulting in poor aqueous outflow and increased IOP.
• The increased IOP causes the sclera and cornea to stretch and may lead
to H a a b 's striae (folds in Descemet’s membrane) (1).
• Increased IOP may also lead to corneal edema with resulting corneal haze,
the most frequently noted sign in these patients.
• Optic nerve damage, high myopia, and subluxation of the lens (rare) may
also occur (1).•
Congenital glaucoma is often characterized by buphthalm os, an

enlarged eye prior to age 3 secondary to elevated IOP.
• EOMs
• Endothelium of blood vessels
• Orbicularis oculi
• Levator palpebrae
• Muscle of Muller
Neural crest cells and mesoderm combine to form the connective

tissue of the globe and orbit (3).
Copyright 2014: by KM K Educational Services, LLC

188
References
[1] Kansld, Jack. Clinical Ophthalmology 4tli ed. Woburn: Butterworth and Heinmann, 1999.
[2] Kaufman, P. Aim, A. Adler’s Physiology of the Eye, 10th ed. St, Louis; Mosby, 2003.
[3] Remington, Lee Ann. Clinical Anatomy of the Visual System.. Boston: Butterworth-
Heinemann, 1988.

Chapter 5
Psychology
K y le C h eath am , O .D ., F .A .A .O .
189
c
(
c
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
t
(
(
(
(
(
CHAPTER 5. PSYCHOLOGY 191
I— SECTION 5.1
V ision D evelopm ent
The human visual system is not fully developed at birth. The neurosensory
retina, visual pathway, and striate cortex continue to mature from birth before
reaching adult levels by early childhood. Proper development of the visual
system is essential as clear, comfortable stereoscopic vision allows children to
interact more fully with their environment, setting the stage for successful
learning and further promoting their emotional, social, and gross/fine motor
development.
wmmmmsmmmmmasm,
Visual function can be measured as early as one week in infants using flash vi
sual evoked p oten tia l (VEP) testing. After approximately 1 month, pattern
VEP testing may be used to estimate the level of spatial acuity (aka resolu
tion acuity) in infants. By 6 m onths, infants have been shown to demonstrate
20/20 visual acuity with p a ttern V E P testin g (5).
Although VEPs provide information about the integrity of the

pathway of the visual system, results do not provide information
regarding the infant’s ability to p erceiv e a visual stimulus. Subjec
tive methods of visual acuity that require visual processing by the
infant do not show 20/20 VA levels until 3-4 years of age (5) (16).
The most common subjective method of measuring VA in infants is forced

ch oice preferential look in g (F C P L ). FCPL is based on the knowledge that
infants prefer to look at a patterned stimulus rather than a solid background.
The Teller acuity cards are based on the FCPL method and are widely used
in pediatric clinics for infants up to 12 months of age (5).
• H ow to : The Teller acuity cards have a solid gray background on one

end and a spatial frequency grating on the opposite end with matching
luminance. A small hole is in the center between the two backgrounds.
The examiner holds up a card and watches the infant’s direction of gaze
through the small hole.•
• The examiner will guess which side o f the card has the grating stimulus
based on the direction of gaze of the infant (assuming the infant will
choose to look at the patterned stimulus if he/she can resolve the spatial
grating).

192 5 .1. VISION DE VEL OPMEN T
• The examiner shows cards from low to high spatial frequency gratings
(larger to smaller grating width). The highest spatial frequency grating
the examiner correctly guesses the infant looks at 75% of the time is the
spatial visual acuity.
Additional examples of FCPL acuity tests for infants up to 18 months of age

include:
• Cardiff cards
• Broken wheel cards
Spatial visual acuity using FCPL methods is approximately 20/600-

20/1200 by 1 month of age and 20/50-20/60 by 1 year of age.
Spatial VA does not reach 20/20 until 3-4 years of age (5) (16).
An additional method of estimating acuity levels in infants involves the O K N

drum . The OKN drum is a series of black and white stripes that elicits an
o p to k in e tic nystagm us when rotated slowly and watched by the patient. A
slow eye movement will follow the direction of rotation of the drum, followed
by a fast saccade in the opposite direction to refocus on a stripe (see ocular
motility chapter for more details). Changing the viewing distance will change
the resulting spatial frequency of the stripes on the retina, allowing for an
estimate of the infant’s visual acuity.•
• Recall that infants have an asymmetric OKN until 3-5 years of age due
to incomplete development of the cortex. Temporal to nasal OKN will
be normal (T O N S of movement) while nasal to temporal OKN will be
abnormal.
• A positive OKN when watching the OKN drum indicates the

infant can resolve the stripes.
• A negative response to the OKN drum is inconclusive.

The infant may not be able to resolve the stripes or the infant
is not paying attention to the stripes (OKN requires the infant
attend to and accommodate to the OKN drum) (5).

V ern ier acuity (aka hyperacuity) is the ability to detect a misalignment of

two lines. It develops slowly and is worse than spatial acuity until about
4 months of age, when it rapidly develops and improves beyond spatial
acuity for the remainder of adulthood. Vernier acuity reaches adult levels
by 6-8 years of age (5) (16).
R e co g n itio n acu ity (the ability to detect optotypes) does not develop until
approximately 2-3 years of age (5). Visual acuity using pictures is often
better than VA using letters. Examples of acuity charts for toddlers and
pre-schoolers include:
• Allen pictures
• American Optical pictures
• HO TV chart
• Lea symbols
• Landolt C chart
• Tumbling E chart
The Snellen acuity chart can be used for school-age children, al
though note that many children as young as 2 and older may be
able to respond to the Snellen chart (5).
Visual acuity in the infant is poor until 3-5 years of age for three reasons (5):
• Foveal cone photoreceptors are shorter and wider in infants compared to

photoreceptors in adults. The length and density of the cones does not
reach adult levels until 4 years of age.
Although the retina develops from the center to the periphery until
1 year of age, it takes several months for photoreceptors to migrate
to the fovea and for Henle’s fibers to develop. In addition to poor
visual acuity, infants will NOT have a bright foveal reflex until
about 15 months of age (16).
• Myelination of the visual pathways is incomplete. Although most of the

visual pathway is myelinated by 24 months, the process is not complete
until 2 years of age.•
• The visual cortex is not fully developed in infants. Most cortical visual
systems begin to reach adult levels by 6 months of age, but development
extends well into childhood.

194 5.1. VISION DEVELOPMENT
m s
The average refractive error in full term newborns is + 2 .0 0 D (+/-0.75D ) (4) (5).
The average axial length for full term newborns is 16 m m (90 D) compared
to the adult axial length of 22 mm (60 D) (8).
E m m etrop iza tion describes the processes that occur in the eye
after birth that results in the eye losing 30 D of power to reach a
refractive state of emmetropia (5).
The greatest degree of emmetropization is thought to occur within the first 2

years of life in response to retinal blur and the location of the blur relative to
the retina (anterior or posterior). When the visual cortex receives a blurred
image, it signals the eye to make anatomical adjustments to reduce and/or
eliminate retinal blur (5) (16).
• At 10 weeks of age, the mean refractive error is piano to +4.00D. As em

metropization occurs, the degree of hyperopia decreases, reaching piano
to +3.00D by 20 weeks (9).
• At approximately 1 year of age, the mean refractive error is +0.50D to

-f 1.00D (+1.00D SD) and remains stable until the teen years (5).
• Myopia increases in prevalence during the school years (6% of 6 year olds
are myopic compared to 15% of 15 year olds), although 80 —85% of school
children remain hyperopic (+0.50D to +3.00D) (5).
Emmetropization usually does not occur for extreme newborn re

fractive errors (> +5.00D/-4.50D) (5).
Premature infants (born at < 37 weeks) usually have high myopia, high astig
matism, or anisometropia at birth but often have normal emmetropization with
similar levels of hyperopia and astigmatism by 12 months of age compared to
full term infants (5).
Preterm infants with ROP have high my-

opia/astigmatism/anisometropia that increases until 12 months
of age. Although emmetropization may still occur, it often does
not result in refractive emmetropia (compared to preterm infants
without ROP) (5).

CHAPTER S. PSYCHOLOGY 195
A stig m a tism is present in 50% of newborn infants, with an average of 2.00D

A T R astigmatism at 6 months of age. By 2 years, the amount of astigmatism
has decreased to 0.50D or less (5) (14).
m sm m m m m aim sm m
Cycloplegic studies have shown that infants are capable of accommodation
within a few weeks of birth, although there is a wide range in the response due to
poor ability to sustain accommodation at a given distance. The accommodative
response gradually increases in flexibility from near to far until reaching adult
levels at 3-4 months of age (3) (5).
Infants have a very large depth of focus that allows them to have
an imprecise accommodative response for a given distance without
significantly impairing visual acuity (5).
jVergencb eye m ovem ents : . v" .Vy/v ~'

Although infants can make vergence movements within the first few weeks
after birth, the eye movements are often unstable and inaccurate and cannot
be initiated based on image disparity alone. By 1 month, infants can make
consistent divergence eye movements; consistent convergence movements do
not occur until 2 months of age. Vergence eye movements reach adult levels
and can be initiated based on disparity alone by 6 months of age (5).
Accommodation and convergence become linked after 2 months of

age once the infant is capable of making consistent convergence eye
movements.
F ixa tion : Newborns take longer and have less steady fixation compared to
older children. They often have apparent strabismus for short periods of
time as a result of unsteady fixation.
Saccades: Although infants are capable of making saccades, they often make
a series of small saccades rather than one large saccade to the target of
interest (18). The number of small saccades necessary to reach the target
increases as the target distance increases. By 6 months of age, only

196 5.1. VISION DEVELOPMENT
about 30% of infants make a series of saccades rather than one large
saccade. The initial poor accuracy is thought to be due to immature
cortical systems rather than an immature motor system (5).
P u rsu its: Infants make a series of small saccades rather than smooth pursuits
when following a moving target until 8 weeks of age. Normal pursuit gain
(eye velocity = target velocity) is reached by 4 months of age (5).
By 6 months of age, all eye movements have usually reached adult

levels.
Stereopsis often appears suddenly in infants at 3-5 months of age followed by a

rapid development to adult levels by 4-6 months of age. Nearly 100% of infants
have stereopsis by 7 months of age. By 24 months, stereoacuity reaches adult
levels of 1 minute of arc (16).
Immaturity of the visual cortex is thought to be the initial limiting

factor to sensory fusion and stereopsis before 3 months of age rather
than eye movements that are necessary for bifoveal fixation (5).
Testing for sensory fusion and stereopsis in infants is very important to rule
out developmental anomalies (e.g. strabismus, anisometropia) that may result
in amblyopia. Tests include:
• Prisby test plates (FCPL method for children 13 months or older)
• Lang stereo tests (6 months - 4 years)
• Random dot E (3 years and older)
• Titmus house fly (3 years and older)
• Randot (4 years and older)
• Worth 4 dot (sensory fusion)
• Keystone visual skills cards (sensory fusion for children 4 years and older)
• Vectograms (3 years and older)

:‘ -i. EV>.i' w t i S . ; $ t :v i£ L
S:V- &
Although the peak o f the contrast sensitivity function reaches adult levels by
4 years of age, overall contrast sensitivity does not reach adult levels until 7-9
years of age when infants have similar sensitivity as adults to low contrast,
high spatial frequency gratings. The initial limitations in contrast sensitivity
are due to immature retinal photoreceptors rather than slow development of
the visual cortex (16).
The critical flicker frequency of infants reaches adult levels by 3 months of

age (16).
visiori
Newborns can only discriminate between red and achromatic stimuli until ap
proximately 3 months of age. The ability to discriminate all hues from achro
matic stimuli reaches adult levels by 3-4 months, but continues to develop
well into childhood (5). Photopic sensitivity curves of newborns closely match
adults, but the scotopic sensitivity curve in infants does not reach adult levels
until 4-7 months of age (16).
Color vision testing for infants is very important because color

vision abnormalities may impair the child’s ability to perform
well in school. Color vision testing for infants utilizes the FCPL
method (5).
Copyright 20,14 by KMI< Educational Services, LLC

5.2. EFFECTS OF EARLY ENVIRONMENTAL RESTRICTIONS ON
198 VISION
R e v ie w o f dev elop m en t o f the human visual system (m od ified from

( 16))
Visual Attribute Approximate Age of Maturity (Months)
CFF (temporal vision) 4
Scotopic Luminosity 4
Photopic Luminosity 4
Accommodation 3
Vergences 2
Pursuits/saccades 4-6
Stereopsis 3
Contrast Sensitivity 3-4
Color Vision 3-4
Grating Acuity 36-48 (3-4 yrs)
Vernier Acuity 72-96 (6-8 yrs)
- S E C T IO N 5.2 ----------------------------------------------------------------------------------------------------------------
Effects of E arly E nvironm ental R estrictio n s on V ision
A N o te o n Sou rces: The main points of this section follow the topics given
in Schwartz, Chapter 17. We feel it provides a more logical flow of pertinent
information (as opposed to the boards outline) and will allow more efficient
understanding of the material.
■ Deprivation stu d ies of H ubei and W eisel ?;;\ '/:rV :-f •'' v ■ \
In 1952, Hubei and Weisel performed studies on monkeys and cats that looked
at the neural input from the eyes to the cells within the visual cortex. They
discovered that most cells in the visual cortex receive neural signals from both
the left and right eyes, although the degree of neural input from each eye to
one cortical cell may be unequal. In other words, certain cortical cells may
have more input from the right eye compared to the left eye (and vice versa).
This finding can be represented by an ocu lar d om in an ce histogram .
An ocu la r d om in an ce histogram visually displays the number of cells that

are driven by the left eye only, right eye only, or both eyes along with the
degree of neural input from the right versus left eye for binocular cortical
cells. The ocular dominance histogram is a reflection of one hemisphere
of the brain. Let’s look at Figure 5.1 as an example of an norm ally
d e v e lo p e d ocular dominance histogram of the right hem isphere.
• Column 1 represents cortical cells that are driven by the con tralat
eral eye (in this case, the left eye).

Normal Development
Abnormal Development Ocular Dominance Category

1 = Only driven by contralateral
7 = Only driven by ipsilateral
4 = Equal drive from each eye
# of Cells
Figure 5.1: In the top figure, a normal ODH is shown. The largest number of
cells fall in category 4. The bottom figures shows two abnormal ODHs.
• Column 7 represents cortical cells that are driven by the ipsilateral

eye (in this case, the right eye).
• Columns 2-6 represent binocular cortical cells that receive some de
gree of input from b o th eyes. C olu m n 4 represents cortical cells
that receive equal in pu t from the right and left eyes.
As can be seen from the vertical axis noting the number of cortical cells
in each column, the majority of cells are binocular cells (and the majority
of those cells are driven equally by each eye).
How does the ocular dominance histogram change if one eye is completely
occluded during development? Hubei and Weisel helped to answer this
question by recording ocular dominance histograms in mature kittens
after one eye had been sutured closed at birth. Let’s look at Figure 5.1
as an example, assuming the right eye has been occluded and we are
looking at an ocular dominance histogram of the right hem isphere. •
• Remember the cortical neurons are driven by the neural input of the
two eyes. The more neural signals an eye sends to a cortical neuron,
the stronger the connection between that eye and the visual cortex.

5.2. EFFECTS OF EARLY ENVIRONMENTAL RESTRICTIONS ON
200 VISION
• When one eye is deprived of vision during the developmental years,

that eye will no longer be able to send neural signals to cortical cells.
Over time, the cortical cells become completely driven by the fellow
non-occluded eye that is still able to provide neural input to the
cortex.
• In our specific example (right eye is occluded), the ocular dominance
histogram will show only cortical cells in colum n 1, as all cortical
cells will be driven by the contralateral left eye.
The ocular dominance histogram will only be altered if one eye

is deprived of vision during the critical p eriod of development.
The critical period extends from birth to 7-9 years in humans;
the first 2 years of life are the most sensitive in terms of visual
development (16).
How does the ocular dominance histogram change if the patient has an al
ternating strabismus (either eye used for fixation but never at the same
time)? Let’s look at Figure 5.1 as an example, assuming the ocular dom
inance histogram represents the right hem isphere.
• Column 1 and column 7 have the most cortical cells. Because each
eye is used for fixation, the right eye will send strong neural signals
to one group of cortical cells, and the left eye will send strong neural
signals to a second group of cortical cells.
• There are virtually no binocular cells, represented by the loss of
columns 3, 4, and 5. Although each eye can fixate individually, the
eyes never fixate on an object together and therefore never send
neural signals to the SAME cortical cell.
• Over time, almost all cortical cells become monocularly driven by
one eye or the other and the patient will have abnormal binocular
vision with reduced stereopsis.
Dissimilar retinal images or monocular deprivation that occurs during the crit
ical period results in reduced cortical connections in one eye compared to the
other and causes a decrease in vision known as am blyopia. The EYE itself is
healthy without structural or physiological abnormalities, but vision is reduced
due to a lack of strong connections with the visual cortex. There are 3 main
types o f amblyopia (refer to BV chapter for further details):

1. O cclu sion am blyopia (ala form deprivation amblyopia) occurs when

one eye is deprived of vision during the critical period, preventing the
development of connections with cortical cells. The visual cortex becomes
completely driven by the fellow eye without the occlusion. Congenital
cataracts, ptosis, or corneal opacities may lead to occlusion amblyopia.
2. R efra ctiv e am blyopia occurs when there is an asymmetric or large

uncorrected refractive error in the two eyes, resulting in a blurred retinal
image and decreased neural input to cortical cells from one or both eyes.
There are 3 types of refractive amblyopia:
* A n iso m e tro p ic a m blyopia occurs when there is a large asym

metric refractive error between the eyes. This asymmetry leads to
a clear retinal image in one eye and a blurred retinal image in the
fellow eye. The eye with the blurred retinal image will develop less
cortical connections, leading to amblyopia.
Remember that the risk o f development and severity of amblyopia

is much greater in patients with a n isom etrop ic h y p erop ia com
pared to anisometropic myopia. Please refer to BV chapter for
further explanation.
• Isom etrop ic a m b lyopia occurs when there is a large symmetrical

refractive error in each eye. Because the refractive error is so large,
neither eye will receive a clear retinal image, resulting in reduced
neural input to the visual cortex in each eye and decreased vision.
• M erid ion a l a m b lyopia occurs with large uncorrected amounts of
astigmatism during the critical period.
— Remember that certain cells in the visual cortex response more
to a certain line orientation compared to others.
- Uncorrected astigmatism leads to a near line and a far line on
either side o f the retina. The line closest to the retina will be
clearer than the other line image, resulting in decreased cortical
connections and decreased sensitivity to stimuli with the same
orientation as the line image furthest from the retina.
3. Strabism ic a m b lyopia occurs when there is a constant, unilateral de

viation o f one eye compared to the other. In order to prevent diplopia
and confusion caused by the ocular deviation, the visual cortex begins to
gradually “ignore” the image from the deviated eye, resulting in suppres
sion and amblyopia.

202 5.3. CHILD DEVELOPMENT
Alternating strabismus WILL NOT result in amblyopia as each eye

is used for fixation at some point in time. These patients will have
p o o r stereopsis because the eyes are never used at the same time
when viewing an object.
I - SE C T IO N 5.3
C hild D evelopm ent
D evelopm ental M ilestones ^ A 1

Infant Examination
Newborns require a thorough evaluation to insure proper development; this in

cludes a careful examination of the entire body, including the eyes, mouth, cra
nium, hearing, heart, lungs, gastrointestinal, urinary and musculoskeletal sys
tems. A complete neurologic exam includes the following reflex testing (17) (5):
Survival reflexes (reflexes that ensure the newborn’s survival) include:
• Sucking reflex - When an object is inserted into the mouth, the baby
starts sucking on it. This reflex is necessary for the baby to feed and
is involuntary until 2 months of age.
• Rooting reflex - If you stroke a newborn’s cheek, he/she will turn
his/her head in the same direction as the check and open his/her
mouth.
Non-survival reflexes include:
• Palmar grasp - a newborn will grasp your finger if you apply light
pressure/stroke his/her palm.
• Babinski reflex - Stroking an infant’s foot will cause the toes to fan
outward and towards the infant’s body.
• Plantar grasp - The toes will curl downward if the plantar surface
of the foot is touched.
• Placing - If a baby is held next to a surface, he/she will lift his/her
foot as if stepping onto that surface.
• Stepping - When a baby is held up so that his/her feet are touching
a surface, the baby should mimic walking.
• Fencing - When you turn a baby’s head to one side, the arm and leg
on that side should extend while flexion of the arm and leg occur on
the contralateral side.

Reflexes are controlled by systems within the lower areas of the

brain. They are gradually replaced by voluntary movements (be
ginning 3 months after birth) as the cortex matures and the neural
pathways become myelinated. Any infants who continue to demon
strate primitive reflexes after 1 year should be tested further for
possible developmental delays (5).
A p p ro p ria te G row th
Growth charts are used to track physical dev elop m en t. The child’s weight,
height, and head circumference are measured and charted along a grid and
analyzed against an age-appropriate curve. If the child deviates from the curve,
further testing may be warranted.
G ross and F ine M o t o r D ev elop m en t
Arnold Gesell, one of the best known researchers in development, studied mat
uration of motor skills in children from birth to 10 years of age. Gesell believed
that all children pass through certain stages of motor development in life that
then sets the stage for the development of cognition. There are two areas of
motor control that develop as muscles start to develop: gross motor control and
fine motor control. Because large muscles develop before small muscles, children
naturally learn gross motor skills before they develop fine muscle control. The
following are important milestones in gross and fine motor development (5):
• 5 m onths: Infants can raise their head from a lying position and are
able to roll over onto their back from their stomach.
• 7 m onths: Infants start to creep (drag themselves on their stomach).

They also transition to the pincer grasp (holding objects between their
thumb and forefinger).
• 9-10 m onths: Infants start to crawl (moving on their hands and knees)
and cruise (can walk a few steps if holding on to furniture).
• 12 m onths: Infants are capable of walking with someone holding their

hand. They are refining the pincer grasp and are also learning to properly
release objects.
• 15 m onths: Infants are capable of walking on their own. They are now
able to throw items with a good release, turn pages of a book, hold a
spoon, and build a tower with two blocks.•
• 15 m on th s - 2 years: Toddlers can walk backward, climb up and down

stairs if someone holds their hand, jump, and scribble on paper.

• 2 years: Toddlers are now able to walk up the stairs on their own (always
placing two feet on the same step). They learn to run faster, open doors,
kick a ball, and build a tower with 7 blocks.
• 3 years: Toddlers can manipulate buttons and scissors, walk up the

stairs like an adult (one foot on each step), build a tower with 10 blocks,
and draw a circle.
• 5 years: Children can copy a circle (3 years), a cross (3.5 years), a square
(4 years), and a triangle (5 years).
• By 6 years of age, each child’s motor skills begin to vary. Some children
may develop motor skills for certain sports, while others develop motor
skills necessary to play instruments.
N orm a l C og n itiv e and Social D evelop m en t
Jean Piaget’s “Theory of Cognitive Development” describes the process of cog

nitive maturation in children. Piaget believed cognition develops through a
series o f behavioral adaptations in order to meet new challenges. He described
the following 4 stages of cognition that children pass through in order (exact
timing for each child may vary) (5):
S en sorim otor stage (b irth - 2 years): In the first two years of a child’s
life, his/her cognitive understanding is shaped by his/her im m ed iate e x p e
riences. Piaget divides this stage into 6 sub-categories (5):
• B irth - 1 m onth: The newborn’s actions are limited to primitive re

flexes. The newborn does not learn any behavior and does not see itself
as different from other objects in its immediate environment.
• P rim a ry circular reaction (1-4 m onths): A newborn exhibits a be

havior that causes something to happen by chance; the baby then contin
ues to repeat the behavior. An example given by Piaget is thumb sucking
- as the newborn waves his/her hands, his/her thumb makes contact with
the mouth. The baby then continues to repeat the behavior of bringing
the thumb to the mouth. Primary circular reactions describe a behav
ior that involves the newborn’s own body. This sub-stage lasts from 1-4
months.
• S econ d a ry circu lar reaction (4-10 m on th s): The newborn shows

a behavior that has an effect on an external object. The newborn then
continues to repeat that behavior in order to understand the consequences
of that behavior (e.g. throwing a cup repeatedly on the floor).•
• C o o rd in a tio n o f schem es (10 m onths - 1 year): The infant is able to

anticipate the consequences from a certain behavior and learns to mimic

actions displayed by people around them. The infant displays a certain

behavior in order to accomplish something (i.e. goal-oriented behavior).
• T ertiary circular rea ction s (12-18 m on th s): The infant develops

an understanding of cause and effect relationships. They also actively
explore new objects and experiment with new behaviors.
• B eginnings o f sy m b o lic th ou gh t (18 m onths - 2 years): The child

is able to create memories and can also solve problems cognitively (rather
than physically). The child is also able to mimic an action that has been
seen in the past (i.e. delayed imitation).
At the end of the sensorimotor stage, the child also exhibits o b je c t

p erm a n en cy - the child understands that a toy still exists even if
that toy is no longer in the room.
P re-op era tion a l Stage (2 -7 years): This stage begins after a child un
derstands object permanency. Major developmental milestones include the
following:
• Rapid development of new language.
• The child displays e g ocen trism (i.e. belief that everyone sees and un
derstands as he/she does).
• Development of a sense of time and space.
• The child learns the concept of con serv ation (i.e. the ability to under
stand that quantity does not change if the shape changes).
— Piaget demonstrated the concept of conversation by pouring a short,

wide glass of water into a tall, thin glass. Children at the beginning
of this stage perceived the taller, thinner glass as having more water
simply because the water was higher than in the shorter glass. The
behavior of focusing on only one aspect of an object is known as
centration.
- Once children surpass the milestone of centration, they are able to
understand con servation - each glass holds the same amount of
water even though the glasses are two different shapes.•
• The child develops an understanding of reversibility.

C o n cre te O p era tion s Stage (7-12 years): At this stage, children have a
mature understanding of the concepts of conservation and reversibility. They
are able to understand multiple aspects of an object that they have personal
experience with, although they still do not have the full capability to think in
abstractions. The child becomes less egocentric in thought and starts to see
and understand things from different perspectives.
F orm al O p era tion s Stage (12 years and o ld er): By this stage, children
are capable of using abstract reasoning and are more logical in their thought
processes. They now understand conversation and reversibility in real and
imagined situations.
E m otion a l D ev elop m en t
The emotional development of infants is closely linked to social development.

Infants must first learn to show their own emotions before they can learn to
react and HOW to react to the emotions of others in different situations. De
veloping relationships, first with caregivers and then with other non-family
members (i.e. socialization), furthers the emotional development of infants as
they transition into the toddler years when they learn the rules and values
of society that govern emotions and relationships. The emotional and social
milestones o f development include the following (5):
• 3 m on th s - Infants learn to smile at human faces. They develop imme

diate emotional reactions to current situations (i.e. crying when meeting
a stranger).
• 4-5 m on th s - Infants learn to smile only at faces they recogn ize. They
will not smile at strangers. By this stage, infants have begun to develop a
sense of self, allowing them to develop strong relationships with caregivers
that they now recognize are separate from themselves.
• By 10 m onths, infants have learned how to moderate their emotions

instead o f responding immediately to a certain situation (i.e. not crying
immediately when meeting someone new). By the end of the first year,
infants will also learn how to interact with their caregivers by signaling
or gesturing to them.
• By 2 years of age, toddlers have developed secon d ary em otion s (emo

tions beyond the primary emotions of fear, anger, surprise, and joy).
Toddlers at this stage are capable of feeling shame, although they begin
to show defiance as they start to become more independent from their
caregivers.•
• 5 years - Children are capable of controlling their impulses and have a

sense o f understanding regarding what is and is not appropriate behavior.
Children at this stage will often comply to their parent’s wishes, even if

the parents are not present. Most children at this stage start to do many
activities on their own. They also begin to understand traditional gender
roles.
• By 6-12 years of age, children begin to develop a sense of competence

and feelings of success. Peer interaction is very important at this stage
and almost rivals the importance of family; children begin to act differ
ently around those they view as friends compared to others who are not
seen as friends. Although children at this stage start to judge and reject
one another, they also learn the concepts of cooperation, fairness, and
reciprocity and are capable of developing loyal friendships within their
group of peers.
Language D evelop m en t
The development of language in infants is dependent on the development of two

processes: reception and expression. R e c e p tio n describes the ability to attend
to and recognize certain sounds and is closely tied to hearing. E xpression
refers to the ability to produce and organize those sounds into meaningful
sentences. Although there is no universally accepted theory as to how children
acquire the use of language, it is understood that the development of language
is closely linked to the development of cognition. There are several milestones
of language development (5):
• 4 m on th s - Infants begin to pay attention to sounds that have meaning

to them (e.g. sound of their mother’s voice). The infant will try to
vocalize when interacting with another person face to face and will often
babble or cry loudly if he/she is bothered or is hungry.
• 6 m on th s - Infants learn to make cooing sounds.
• 7 m onths - Infants recognize emotion behind the speech pattern of

adults. They will often babble for long periods of time using different
pitches. Infants may also try to mimic the vocalizations of adults at this
stage.
• X year - The infant recognizes words for common activities and is able
to consistently use a few single words correctly. The infant begins to
recognize his/her own name and the names of family members.
• 2 years - Most toddlers at this stage have a vocabulary of 50 words

and are able to combine 2-3 words into short but meaningful sentences.
Children at this stage can also respond correctly when spoken to.
• 3 years - Children’s vocabulary has increased to 900 words and they

are able to form larger and more complex sentences.•
• 5 years - Children start to narrate long stories. Their vocabulary has

increased to 1500 words.

• 7 years - Children are able to have long conversations and have a solid un
derstanding of spoken directions in a variety of situations (home/ school/ social
situations).
An estimated 5—10% of the pediatric population has a developmental disability.

Multiple developmental screening tests have been developed in the hopes of
identifying and treating developmental delays at an early stage (13).
Infants who are born p rem atu rely (less than 35 weeks) or with a
low b irth w eight (less than 5.5 lbs) are at the greatest risk for
developmental delays (5).
The D en ver II d ev elop m en tal screening test is one of the most widely
used developmental screening tools for children from birth to 6 years of
age. The standardized test includes 125 items that are divided into the
following four sections:
1. Social/Personal - Items assess different aspects of socialization inside

and outside the home.
2. Fine motor function - Items include eye-hand coordination and ma
nipulation of small objects.
3. Gross motor function - Includes sitting, walking, and jumping (among
other movements).
4. Language - Items assess the ability to recognize, understand, pro
duce, and utilize language.
Although the DDST II is one of the most widely used developmental

screening tests with a large, standardized, normative database and an
swers that are based on the objective evaluation of a child’s abilities
(rather than reports from parents), it has a limited sensitivity (56 —83%)
and specificity (43 —80%), leading to concerns of missing children with
mild developmental delays or over-referring children who do not have
developmental issues (19).
The B atelle d evelop m en tal inventory screening test is another common

screening test for children aged 6 months to 8 years. It includes direct ob
servation of the child’s abilities as well as reports from parents regarding
their level of concern for possible developmental delays. The test consists
of 96 items in the areas of personal-social development, adaptation, gross
and fine motor development, communication (receptive and expressive),

and cognition. Research has shown better sensitivity (80%) and speci
ficity (74%) compared to other screening tests. Please see (13) for farther
details on the large variety of available developmental screening tests.
Common developmental milestones are summarized in the following chart on

the next page:
- SECTION 5,4 -----------------------------------------------------------------------------------------------------
A nom alies of V isual P e rc e p tu a l D evelopm ent *•
V isu al in form ation processin g (V I P ) describes the ability to discrimi

nate, recognize, and interpret visual stimuli. Impairments of VIP may result
in learning-related visual disorders that can often be misdiagnosed as devel
opmental disabilities. It is important for optometrists to recognize the signs,
symptoms, and appropriate tests used in the diagnosis of VIP disorders so chil
dren receive appropriate treatment (15). There are 4 diagnostic categories of
VIP:
1. V isu al-spatial skills
Visual-spatial orientation describes the awareness of one’s self in space

related to other objects and the position of objects in space rela
tive to each other. The vestibular system works closely with the
visual system to integrate information from objects in space to head
movements. Visual-spatial skills include the following:
• B ilateral in tegration: Awareness and ability to use both sides
o f the body independently or together.
• L aterality: Understanding one’s own right and left.
• D irection a lity: Ability to distinguish between left and right
of an object in space.
S ig n s/sy m p to m s: Lack of coordination and balance, not knowing
right from left, reversing letters when writing.
Testing:
• B ilateral in tegration tests: Standing test (body control),
chalkboard circles test, standing angels in the snow.
• L aterality: Piaget’s right-left awareness test.
• D irection a lity: Jordan left-right reversal test, reversals fre
quency test, Piaget’s right-left awareness test.
2. V isual-analysis skills (aim visual perception)
Visual-analysis skills involve gathering and evaluating visual information

■ from the environment, allowing us to answer the following questions:

5.4. ANOMALIES OF VISUAL PERCEPTUAL DEVELOPMENT
Age Vision and Hearing and Gross Movements Social

Fine Movements Language and Emotional
3 mos Looks at faces. Started by loud Hands open and Excited by happy
Follows moving objects. sounds, close. Lifts head stimuli (tickles,
smiles at and chest baths, etc.)

familiar voices. when placed
Turns head toward on stomach.
sound.
6 mos Reaches out for small Uses single syllables. Grabs own feet. Takes everything
objects. Palmar grasp. Begins to respond to Rolls from front to mouth. Responds to ■
“NO” and own name. to back. Sits alone. emotion from others.
1 year Pincer grasp between Understands Crawls on belly Cries when mom
forefinger and thumb. several words. and begins to walk. or dad leaves.
Looks for missing toys. Imitates sounds. Pulls self up Shows preferences
to stand. for people, toys, etc.
2 years Scribbles, can draw Points to object Kicks a ball and Bladder control
line, builds tower o f when named. begins to run. during the day-
four or more blocks. Knows several Climbs up and Enjoys other
Starting to use one words by 18 mos. down furniture. children. Begins to
hand over the other. Repeats words. Walks alone. show defiant behavior.
3 years Copies a circle. Knows Knows name, age Can run, jump, Imitates adults and
colors. Cuts with and sex. Asks lots stand on one playmates. Eats with
scissors. of questions. foot. utensils.
Speaks in sentences.
4 years Copies a cross and square. Can Understands the Skips, runs and Co-operates with
draw people. concepts of same plays games. other children.
and different. Knows Understands rules. More
rules of grammar. Tells independent.
stories.
210
CHAPTER. 5. PSYCHOLOGY 211
a) W h a t am I seeing?
b) W h e re is it located?
c) W h y is it important?
Visual analysis describes the ability to use visual memory to identify
objects in the environment when certain characteristics are missing
or when distracting objects are present. Visual analysis skills are
important for letter and number recognition, mathematics, main
taining concentration, and completing tasks efficiently. Visual per
ception is divided into the following sub-categories:
a) V isual discrim in ation : The ability to identify features of an
object (e.g. size, shape, color, direction) that differentiate it
from other objects.
b) V isual closu re: The ability to identify an object when portions
of it are missing.
c) V isu al form con sta n cy : The ability to identify an object
based on its shape even when the size, color, or orientation of
the object changes.
d) V isu al figure grou nd : The ability to identify an object from
a background with distracting stimuli, while still attending to
the interaction between the object and the background.
e) V isual spatial relations: The ability to identify an object
based on its orientation when it is surrounded by other objects
of similar size, shape, and color.
f) V isu al m em ory : The ability to recall visual objects that were
previously present.
Signs/ sym ptom s: Difficulty learning the alphabet or recognizing words,
difficulty writing, poor number recognition, difficulty with math,
poor reading comprehension, and short attention span.
Tests:
• T V P S (Test of Visual Perceptual Skills) - Includes tests for
each sub-category o f visual perception.
• M F V P (Motor Free Vision Perception Test)
• D T V P (Developmental Test o f Visual Perception)
3. V isual atten tion and p rocessin g skills
Visual attention describes the ability to attend to a single object for

sustained periods of time, as well as the ability to shift attention
between multiple objects. Visual attention is closely tied to visual
processing, which describes the ability to perceive and analyze an
object in order to create an image of the object in the mind.
S ig n s/sy m p to m s: Easily distracted, slow reading speed, difficulty
completing written assignments, difficulty attending to homework,
and decreased reading comprehension.

2X2 5.5. THE AGING ADULT
Tests:
• Symbol Digit Modalities Test
• Children’s Color Trails Test
4. V isu al m o to r integration skills
Visual motor integration describes the ability to use visual processing

information to direct fine motor movements (typically hand skills
such as writing or typing). Visual motor integration involves visual
analysis (perceiving the characteristics of an object), visual concep
tualization (reconstructing the image in the mind), and fine motor
control (eye-hand coordination).
S ig n s/sy m p to m s: Difficulty copying from the board during school,
poor spacing of letters/words, significantly rotating the paper when
writing, poor spelling when writing, and difficulty organizing math
ematical columns of numbers (1).
Tests:
• Development of Visual Motor Integration Test
• Wold Sentence Copy Test
• Test of Visual Motor Skills - Revised Test
I— SECTION 5.5
T he Aging A dult
^Clinical C h a rac te ristic s of th e O lder A d u lt ;f .. '.

It is important to keep in mind several factors when treating and managing
elderly patients (21):
1. Not all abnormalities that are found require treatment.
2. Diseases that present in the elderly are often multifactorial in nature and
often have an atypical presentation.
3. The interaction of multiple medications may cause adverse effects and

contribute to and/or exacerbate symptoms in the elderly.
C o m m o n A rea s o f D ecreased Function
H earing L oss
Approximately 50% of patients over the age of 85 have hearing loss (21). The
loss of hearing in the elderly is due to multiple factors:

CHAPTER 5, PSYCHOLOGY 213
• Deterioration of hair cells in the Organ of Corti.
• Excess deposition o f bone cells, resulting in fusion of the oval window and
stapes.
• Increased impaction of ear wax in the external canal due to loss of seba
ceous glands.
• Decreased or loss of conduction of sound due to sclerosis and increased

translucency o f the tympanic membrane.
C o o rd in a tio n
Aging causes a decrease in muscle mass and reduced neural control, leading to
a loss of coordination and balance. The elderly will also have a reduction in
bone mass, resulting in kyphosis (back hump), reduced vertebral height, and
increased risk for bone fractures.
C o g n itio n
The risk of dementia doubles every 5 years after the age of 60 (21). The M ini-
M en ta l Status E xam (MMSE) is a screening test for cognitive deficits and
evaluates five areas:
• Orientation
• Attention and recall
• Calculations
• Language
• Figure construction
N orm a l C hanges in V ision w ith A g in g
1. V isu al acuity: High contrast visual acuity remains stable until 65-70
years of age. Acuity levels in low contrast, low illumination settings
decreases from age 50-80 primarily due to lenticular changes and senile
miosis (less commonly retinal changes) (16).
2. R efra ctive error: Expect a shift towards A T R astigmatism due to

changes in the lens. Although an increase in h y p erop ia is also expected
with aging, the development o f nuclear sclerosis (NS) will often result in
a gradual myopic shift in the refractive error.

214 5 .5 . THE AGING ADULT
3. S p ectra l transm ission th rou gh the ocu la r m edia: Spectral trans

mission of light decreases with aging. N uclear sclerosis is the most
significant age-related change that impacts the type and amount of light
reaching the retina. Senile m iosis also contributes to an overall reduc
tion in the amount of illumination reaching the retina (2).
4. C on trast sen sitivity: Remains stable until approximately 65 years of

age. Senile miosis, the development of NS, and less commonly aging of
the neural elements of the retina and central nervous system contribute
to the reduction in contrast sensitivity.
5. G lare: Disability and discomfort glare increases with age due to the
development of cataracts. Visual acuity in elderly patients also takes
longer to recover after exposure to glare (16).
6. C o lo r vision : The development of NS most often causes a yellowing

of the lens, leading to increased absorption of blue light and resulting
b lu e-yellow colo r d efects in the elderly.
7. A c c o m m o d a tio n and con vergen ce: Accommodation decreases with

age due to a decrease in elasticity of the lens and age-related changes
in the zonules and ciliary muscles. The reduction in accommodation is
accompanied by a decrease in accommodative convergence due to the near
reflex triad. Research has shown positive fusional vergence decreases with
age while negative fusional vergence remains unchanged (12).
8. O cu lo m o to r system : Elderly patients use more saccades to maintain

fixation and also have more saccadic intrusions during smooth pursuits.
U pgaze is usually the most difficult movement to make for elderly pa
tients.
9. S tereopsis: Stereopsis and stereoacuity decrease after approximately 50

years of age, likely due to cortical changes in the elderly (16).
10. V isu al fields: The overall sensitivity of the visual field decreases with
age in static and dynamic visual field testing, with a greater rate of decline
in the peripheral field compared to the central field (2). The reduction
in sensitivity is most likely related to neuro-sensory loss (6). Although
the expanse of the visual field does not change significantly with age, the
expanse of the useful field (the extent of the visual field when a patient
is dividing attention between two objects) begins to decline after 50 years
of age (16).
11. Spatial vision: Decreases with age (see visual perception chapter for
detailed explanation).
12. T em p ora l vision : Temporal frequency sensitivities decrease with age

due to senile miosis and the development of cataracts. The ability to
detect peripheral motion also decreases in the elderly, primarily due to
changes in the visual cortex (as evidenced in animal studies) (16) (10).

13. D ark ada ptation : Decreases with age due to a reduction in the forma
tion of rhodopsin in the photoreceptor outer segments. Elderly patients
often express concern about their increased difficulty with seeing and
navigating in poorly illuminated areas,
14. V isu al atten tion : Elderly patients are less resistant to distracting stim
uli in their environment. They experience increased difficulty selectively
attending to one object when there are competing visual stimuli (10).
R eferences
[1] AOA Clinical Practice Guidelines. Learning related vision problems. 2008.
[2] Aston, S. Maino J. Clinical Geriatric Eyecare. Boston; Butterworth-Heineman, 1993.
[3] Banks MS. The development of visual accommodation during early infancy. Child Develop
ment 1980;51:646-66.
[4] Cook RC, Glasscock RE. Refractive and ocular findings in the newborn. Am J Ophthalmol
1951;34:1407-12.
[5] Duckman RH. Visual development, diagnosis, and treatment of the pediatric patient.
Philadelphia: Lippincott, Williams, and Wilkins, 2006.
[6] Haas A, Flammer J, Schneider U. Influence of Age on the visual fields of normal subjects.
Am J Ophthalmol 1986,; 101: 199-203
[7] Kaufman, Paul. Aim, Albert.Adler’s Physiology of the Eye, 10th ed. St. Louis: Mosby, 2003
[8] Larsen JS. The sagittal growth of the eye. IV. Ultrasonic measurement of the axial length of
the eye from birth to puberty. Acta Ophthalmologica 1971;49:873-86.
[9] Mayer DL, Hansen RM, Moore BD, Kim S, Pulton AB. Cycloplegic refractions in healthy
children aged 1 through 48 months. Archives of Ophthalmology 2001;119:1625-8.
[10] Morgan, M,W. “The Ciliary Body in Accomodation and Accomodative Convergence.” Amer
ican Journal of Optometry and Archives of American Academy of Optometry 31 (1954):
219-229.
[11] Remington, Lee Ann, Clinical Anatomy of the Visual System, Boston: Butterworth-
Heinemann, 1988.
[12] Rosenbloom, A. Morgan, Meredith. Vision and Aging. General and Clinical Perspectives.
New York; Fairchild Publications, 1986.
[13] Rydz D, Shevill MI. Developmental screening. J Child Neurol. 2005;20(1):4-21,
[14] Saunders KJ. Early refractive development in humans, Surv Ophthalmol 1995;40:207-16.
[16] Scheiman M and Rouse M, Optometric Management of Learning-Related Vision Problems.

Mosby. 2006, p. 369-413.
[16] Schwartz, Steven. Visual Perception: A Clinical Orientation, 2nd edition, McGraw-Hill, 1999.
[17] Seidel, Henry et al. Mosby’s Guide to Physical Examination. 4th ed. St. Louis: Mosby.
[18] Simons, Kurt. Early visual development: normal and abnormal, Oxford University Press,
1993.

216 5.5. THE AGING ADULT
[19] Tidy C, 2014 Mar 03. Denver Developmental Screening Test. Medscape.
< http://www.patient.co.uk/doctor/denver-developmental-screening-test> , Accessed
2014 May 17.
[20] Yen KG. 2014 Mar 20. Amblyopia treatment and management. Medscape.
< http://eniedicine.niedscape.coin/article/1214603-treatme2rt> . Accessed 20.14 May
10.
[21] Tierney, Lawrence M., McPhee, Stephen, and Maxine A. Papadakis Eds. Current Medical
Diagnosis and Treatment, 46th ed. New York: McGraw-Hill, 2006,
[22] Yuodelis C, and Hendrickson A, A qualitative and quantitative analysis of the human fovea
during development. Vision Res, 1986;26(6):847-55.

Chapter 6
Biochemistry
K y le M . C heatham , O .D ., F .A .A .O .
217
(
(
c
c
c
('
(
(
(
(
c
(
(
(
(
(
(
(
(
(
(
(
(
(
c
t
(
CHAPTER 6 . BIOCHEMISTRY 219
- SECTION 6.1 ---------------------------------------- ------
T he Cell
Eukaryotic cells are composed of multiple internal membranes that form or
ganelles. Organelles are living compartments inside the cell that serve a partic
ular role in maintaining the health and function of the cell. Certain biochemical
processes necessary for cell survival cannot occur in the regular internal envi
ronment of the cell due to denaturation of proteins or competition between var
ious enzymes. The com pa rtm en ta liza tion of biochemical processes within
specific organelles ensures an appropriate environment that will allow these
processes to function properly (2).
|Cedl s^fu ctu ê

We will now provide a brief review of cell structure and the function of or
ganelles (5). Please refer to the histology chapter for more details regarding
the cell.
The cell is separated from the external environment by the plasm a m em

brane composed of phospholipids, proteins, and carbohydrates. The
plasma membrane plays a role in the following functions:
• Cell-cell adhesion
• Cell protection
• C ell com m u n ica tion
The environment outside the plasma membrane is termed the extracellular

environment. The intracellular en viron m en t is composed of fluid (the
cy tosol) and solid living compartments (the org a n elles).•
• G lycolysis, the first step in the breakdown of carbohydrates into

ATP, occurs within the cytosol.
Cell organelles include the following:
• The nucleus contains DNA in the form of chromosomes which serve

as the genetic blueprint of the cell. D N A replication , m R N A
tran scription , and t R N A tra n scrip tion occur in the nucleus.
- The nucleolus is a region within the nucleus that contains
dense chromatin and serves as the site for r R N A tran scrip
tion.
• R ib o so m e s are non-membrane bound structures that are essential
for tran slation of mRNA into proteins.
Copyright 203.4 by KMK Educational Services, LLC

220 6.1. THE CELL
* The rou g h endop lasm ic reticulu m surrounds and is connected

to the perinuclear space of the nucleus and is bound to multiple ri
bosomes. It is involved with the production of extracellular p r o
teins.
* The sm o o th en dop lasm ic reticulum is continuous with the rER
and does NOT contain ribosomes. Functions of the sER include:
- Steroid production in the adrenal cortex
- Storage and breakdown of glycogen and detoxification of lipid
soluble drugs.
- Storage and release of calcium for muscle contractions in muscle
cells.
* The G olg i apparatus helps the rER modify proteins that will be
exported into the extracellular environment.
* L ysosom es contain multiple enzymes responsible for d ig estion of
waste components within the cell.
* M ito ch o n d ria are termed the “powerhouse” of the cell as it serves
as the location for the K rebs cy cle and oxid ative p h osp h ory la
tion , processes necessary for the production of A T P .
Proteins contain specific sequences that serve as a marker for the

final destination of the protein within organelles, the cell cytosol,
or the extracellular matrix (2).
com m unication
Cell-cell communication is essential for cell survival and plays a role in the
regulation of cell metabolism, proliferation, differentiation, and cell movement.
Cell communication includes direct cell-cell signaling or the release o f signal
m olecu les that act on local or distant target cells (5).
D ire ct cell-cell signaling plays an important role in the embryonic develop

ment and differentiation of cells, cellular proliferation, and cell survival. Direct
cell-cell signaling involves the following modes of communication:•
• G a p ju n ctio n s connect the cytoplasm of adjacent cells and serve as a

passageway for small hydrophilic molecules, ions, and metabolites to pass
directly from one cell to another.

Gap junctions are often found in abundance in tissues such as the

heart that require a synchronous and rapid response of multiple
cells to electrical or other types of signals. Gap junctions are also
crucial for the nourishment and survival of cells that are located
far away from blood vessels, including the intraocu lar lens (2).
• Cell surface adhesion molecules such as integrins and cadherins also

serve as signal molecules that bind to surface receptors on adjacent cells
to help regulate cell proliferation, cell differentiation, and maintain the
proper internal cellular environment (5).
Cell signaling through the secretion of signaling molecules can be divided

into three modes of communication:
• E n docrin e signaling involves the release of horm on es that are

carried to distant target cells through the b lood strea m .
— A variety of hormones are secreted from endocrine glands in
cluding the gonads, the pituitary, thyroid, pancreas, and adrenal
glands (see general physiology chapter for further details).
• P aracrine signaling occurs when a signal molecule released from
one cell acts on a local neighboring cell.
— The release of n eu rotran sm itters into the synapse between
neighboring neurons is an example of paracrine signaling (2).
• A u to crin e signaling occurs when a cell responds to its ow n sig
nal m olecu le that it released.
— T-lymphocytes often produce a growth factor that initiates their
own proliferation in response to a foreign antigen (5).
Signal tran sdu ction
Cell communication through the release o f signal molecules involves the initi
ation of signal tran sd u ction cascades within the cell, resulting in the acti
vation of certain enzymes and transcription factors that alter gene expression
within the cell nucleus (5).
• When a signal molecule (aka ligand) binds to a transmembrane protein

receptor, the ligand produces a conformational change in the protein that
is then detected in the cytoplasm.*
* Many protein receptors are coupled to G T P , forming a G protein. The

conformational change in a G protein often leads to the activation of
adenylyl cyclase, an enzyme that produces multiple secondary messengers
known as c A M P molecules.

222 6.1. THE CELL
• Although cAMP molecules may act on a variety of molecules within the

cell, it often activates p rotein kinase A , an enzyme responsible for the
phosphorylation of multiple target proteins that produce a widespread
effect on cellular biochemical processes, including gene expression (2).
• Additional signal transduction pathways include cGMP, PIP2 transmem

brane proteins, MAP ldnsases, and Ras proteins (5).
R h o d o p s in is an example of a transmembrane protein that is stim

ulated by photons to produce a signal transduction cascade within
photoreceptors (2).
Signal transduction cascades result in signal am plification. A single ligand

that binds to a transmembrane protein receptor results in the production of
multiple secondary messengers that then act on an even greater number of
target enzymes, producing a widespread effect throughout the cell.
C h em ical b on d s
There are a variety of chemical bonds that are important for maintaining the
structure of carbohydrates, proteins, lipids, and nucleic acids, the main com
ponents of cell structure and biochemical processes (2).
• C ovalent b o n d s involve the sharing of electrons between two molecules

and are the stron gest of all the chemical bonds.
• Non-covalent bonds (those that do not involve a sharing of electrons)

include:
— E le ctrosta tic interactions occur between negative and positively

charged atoms.
— H y d ro g e n b on d s are relatively weak bonds that form between

two electronegative atoms that share an H atom (H 2 O is the classic
example).
— V an der W aals interactions are momentary bonds between two

oppositely charged atoms. Van der Waals interactions between two
molecules constantly change as the electric charge around the atom/molecule
changes over time.

CHAPTER 6 , BIOCHEMISTRY 223
SECTION 6.2
P ro te in s
We now summarize concepts regarding proteins (10, ch. 5). Proteins are com
prised of amino acids linked covalently by peptide bonds.
A m in o acids (AAs) are comprised of an amino group (N H 2 ), a carboxyl

group (COOH), a hydrogen atom (H), and a functional group (R) attached to
a central carbon atom (C).
• Each amino acid has a unique functional group (P.) that differentiates
proteins from one another.
There are 20 amino acids that can be classified in several different ways:
1. Essential vs nonessential AAs.

• E ssential A A s (9) cannot be synthesized in the body and must
be obtained from the diet. They include histidine, isoleucine,
leucine, lysine, methionine, phenylalanine, threonine, trypto
phan, and valine.
• N onessential A A s (11) are synthesized by cells. They include
alanine, arginine, asparagine, aspartate, cysteine, glycine, glu
tamate, glutamine, proline, serine, and tyrosine.
• Although arginine, cysteine, glutam ine, and tyrosine are
commonly considered nonessential AAs, they may become es
sential under conditions of stress or illness (i.e. con d ition ally
essential or semi-essential AAs) (3) (1).
- For example, tyrosine is synthesized from the essential AA
phenylalanine. Patients with phenylketonuria (PKU) lack
the necessary enzyme to metabolize phenylalanine to tyro
sine. Because tyrosine can no longer be produced, cells are
now dependent on obtaining this A A from the diet (7).
A m in o A cid (AA)
R
I
COOH----- ----- C -------— NHa
Figure 6.1:

224 6.2. PROTEINS
2. Polar (12 AAs) vs nonpolar (8 AAs).

3. Acidic, basic, or neutral.
4. R group.
5. Metabolic end product.
• K e to g e n ic AAs yield A cety l C o A when broken down.
• G lu cog en ic AAs yield pyruvate when broken down.
• Ketogenic and glucogenic.
Multiple amino acids are linked together by a p ep tid e b on d , a covalent

bond between the N H 2 group of one amino acid and the COOH group
of a fellow amino acid. The formation of a peptide bond releases H 2 O.
• D ip e p tid e : 2 AAs bound together.

• T rip e p tid e: 3 AAs bound together.
• P o ly p e p tid e : 4 or more AAs bound together.
The lengths of polypeptides can vary greatly. When the length

of polypeptides becomes very large (involving > 100 AAs), the
structure is termed a protein.
Amino acids have several functions within the body:
• Serve as the building blocks of proteins.

• Serve as substrates for the production of metabolic energy.
• Serve as precursors for the synthesis of heme, coenzymes, melanin,
collagen, etc.
- Glycine is a precursor for porphyrins such as heme.
- Arginine is a precursor for nitric oxide.
- Tryptophan is a precursor for serotonin (a neurotransmitter).
- Tyrosine (derived from phenylalanine) is a precursor for dopamine,
epinephrine, and norepinephrine (catecholamine neurotransmit
ters).
- Glycine, glutamine, and aspartate are precursors for nucleotide
synthesis.

A lbin ism is a group of genetic disorders characterized by muta

tions in the enzyme tyrosinase, which is necessary for the conversion
of tyrosine to m elanin. O cu locu ta n eou s albinism is character
ized by skin and fundus hypopigmentation, iris translucency, and
foveal h ypoplasia with resulting decreased visual acuity and nys
tagmus.
Proteins have four distinct structural levels:
1. P rim a ry: A m in o acid sequ en ce o f the protein. Each protein has a

different primary structure.
2. S econ dary: Refers to local in teraction s between neighboring amino

acids that cause twisting within the protein helix that is stabilized by
hydrogen bonds. Examples of common secondary structures include:
• A lp h a helices: Most common in transmembrane proteins and in

soluble proteins, including rh od op sin .
• B e ta sheets: Commonly found in soluble proteins including crys-
tallin proteins in the lens and cornea. Beta turns connect beta
sheets.
• R a n d o m coils: Connect different secondary structures together.
3. T ertiary: A polypeptide chain bends and folds on itself, creating a three

dimensional protein shape that is often stabilized by covalent di-sulfide
bonds (11). Common tertiary structures include:
• G lob u la r stru ctu re: Water soluble polypeptide chains that fold
tightly on themselves to create a compact, spherical shape. P lasm a
protein s (e.g. albumin), transport proteins, nuclear proteins, and
most enzymes have a globular tertiary structure.
• F ib rou s stru ctu re: Water IN-soluble polypeptide chains that ex
tend along one axis. These proteins are most often involved in pro
tection and maintaining cell/tissue structure and include collagen,
keratin, and elastin.
4. Q uaternary: Multiple polypeptide chains linked together with non-

covalent and covalent di-sulfide bonds to form m ultim ers. Examples
include hemoglobin (4 polypeptide chains) and insulin (2 polypeptide
chains).

226 6.2. PROTEINS
liB S liffiH lS is K liH K M iilii

E nzym es: Proteins that serve as catalysts by lowering the activation en
ergy needed to initiate a reaction. Each enzyme has a unique active site that
is specific for a particular substrate.
A n tib o d ie s: Highly specific Y-shaped proteins produced by plasma cells in

response to an antigen. These proteins function in the im m une response.
Antibodies are either secreted into systemic circulation or they act as antigen
receptors on the surface of B-cells.
Ig M : First antibody made in response to an antigen. Found primarily in the

blood and on the surface of immature B-cells.
Ig G : Most plentiful Ab in circulation. IgG is the only Ab that is able to cross

the placenta to protect the fetus. IgG provides the majority of Ab-based
protection against antigens.
Ig A : Primary antibody in excretions such as mucous, saliva, tears, and breast

milk.
IgD : Acts as an antigen receptor on the surface of mature B-cells.
IgE : Binds to allergens and triggers histamine release from mast cells, leading
to allergy symptoms and ty p e 1 h ypersensitivity reactions. IgE also
provides protection against parasites.
C ollagen : Fibrous protein that provides tensile strength to tissues including

tendons, ligaments, skin, muscles, blood vessels, bone and teeth. Collagen is
the most abundant protein in the body, accounting for 25-35% of the body’s
total protein content.
• P r o colla g en is the initial precursor to collagen and consists of 3 polypep

tide strands stabilized by disulfide bonds and eventually wound into a
triple helix.
• Each polypeptide strand consists of Glycine-X-Y repeats (proline and

lysine are commonly in the X and Y positions). The first essential step
in the production of procollagen to collagen involves the hydroxylation of
lysine and proline residues within the polypeptide strands. V ita m in C is
an essential co fa cto r for the hydroxylase enzymes that are responsible
for these modifications.•
• The Golgi apparatus modifies pro collagen into tr o p o collagen by re

moving the terminal ends of the polypeptide strand. Tropocollagen is
the basic building block of collagen.
Copyright 20X4 by KMK Educational Services, LLC

• Collagen fibrils are formed by covalent bonds between multiple tropocolla-

gen strands. Collagen fibrils are linked together to form collagen fibers (11)
Most collagen found in the body is Type I, type II or type III.
• Type I collagen is found in the cornea, sclera, and B o w m a n ’s m em

brane.
• Type II collagen is found in the vitreous.
• Type IV collagen is found in D e sce m e t’s m em brane.
• Type V collagen is found in the corn ea and helps to maintain a uniform

organization of type I collagen to prevent light scattering and loss of
transparency.
Defects in collagen synthesis lead to multiple systemic diseases:
S cu rvy is caused by V ita m in C deficien cy , resulting in defective colla

gen synthesis and weakened connective tissue. Signs and symptoms in
clude deterioration and bleeding of the gums, skin discoloration, and poor
wound healing.
S ystem ic lupus eryth em atosu s and rh eu m a toid arthritis are autoim

mune disorders that develop when the body attacks healthy collagen
fibers.
O steogen esis im p erfecta results from an autosomal dominant genetic de

fect in the production of type I collagen, causing weak bones and con
nective tissue. Common signs include multiple fractures, poor wound
healing, hearing loss, and blue sclera (11).
E h ler’s D an los syn drom e results from a mutation causing abnormal syn
thesis, structure, and secretion of primarily type I and type III collagen.
Signs include loose and hyperextended joints, hyperelastic skin, aortic
dissection, blue sclera, and corneal th in n in g (II).
O steop orosis is caused by reduced levels of collagen in the skin and bones
with aging.
E lastin: Synthesis of elastin is very similar to the synthesis of collagen.

Fibers are much more elastic than collagen because they do not contain hy-
droxylysine. The elasticity of the fibers allows tissues to resume their original
shape after significant stretching.

228 6.2. PROTEINS
H e m o g lo b in ( H b ): Hemoglobin is a component of red blood cells (RBCs)

and is responsible for transporting O2 to tissues throughout the body. Each
Hb molecule consists of 4 polypeptide chains (2 alpha and 2 beta chains) that
each have an F e 2 containing heme group that binds with oxygen, allowing each
Hb molecule to transport four molecules of O2 (one per heme group). There
are over 280 hemoglobin molecules within one RBC (10). For more details
regarding hemoglobin, please see the general physiology chapter.
M echanism s o f E nzym e Ab tiion

B ioca ta lysis involves the use of enzymes and other natural substances to
increase the speed of chemical reactions. Enzymes are catalysts that low er
th e activa tion en erg y needed to initiate a reaction, resulting in an increase
in the the rate of the reaction WITHOUT changing the equilibrium of the
reaction (11) (10, ch. 14).
M ich a elis-M en ten (M M ) E quation
The M M eq u a tion describes the relationship between substrate concentra

tion ([S]) and the rate of a reaction (Vo).
• When [S] is low, the level of enzyme activity is limited by the con
centration of the substrate. Increases in [S] will result in an increase
in enzyme activity and the rate of the reaction.
• At a certain substrate concentration, the enzyme becomes saturated
and reaches its maximal velocity (Vmax). Any increase in [S] will
NOT increase the rate of the reaction as the enzyme is already func
tioning at Vmax.
K m is the concentration of the substrate when the rate of the reaction is 50%
o f V m a x . In other words, Km is a measure of the enzym e affinity for
the substrate (see Figure 6.2).
• When Km is low, the enzyme has a high affinity for the substrate
and less [S] is required to saturate the enzyme.
• When Km is high, the enzyme has a low affinity for the substrate
and more [S] is required to saturate the enzyme.
Vmax [S]
Vo = ------------—- ( 6. 1)
Km + [S]
• V o= the rate of the reaction
• Vmax — the maximum rate of the reaction
• Km — the [S] when the rate of the reaction is 50% of Vmax

CHAPTER 6. BIOCHEMISTRY 229
• S = the concentration of the substrate
L inew eaver-B urk P lo t
The Lineweaver-Burk plot is a linear graphical representation of the MM equa

tion that is obtained by taking the log of both sides o f the equation, resulting
in an equation with the form y — mx + b, where m is the slope and b is the y-
intercept. This graphical representation allows for easier analysis of MM data
(see Figure 6.3).
* X-intercept =
• Y-intercept = ^
C o m p e titiv e In h ibition : A “look-alike” molecule mimics the substrate and

binds to the active site, preventing the binding of the ligand. In reversible
competitive inhibition, increasing the concentration of the substrate overcomes
the binding of the competitor.
• Km INCREASES due to decreased affinity between the enzyme and the

substrate because the competitor molecule is bound to the active site.
• Vmax STAYS THE SAME.
• The x-intercept (-^^) on the Lineweaver-Burk plot will shift towards the
right.
Figure 6.2: M ich a elis-M en ten P lo t. Remember, Km is a measure of sub

strate concentration. The higher the Km, lower the affinity of the enzyme for
the substrate and the slower the rate of the reaction.

230 Non Competitive 6.2. PROTEINS
Uninhibited
Figure 6.3: Line we ave r-B u r ke P lo t. Note how the competitive and unin
hibited lines cross the y-axis at the same position - Vmax is unchanged in
competitive inhibition. Note how the noncompetitive and uninhibited lines
cross the x-axis at the same position - Km is unchanged with noncompetitive
inhibition.
In irreversible competitive inhibition, an increase in substrate concentration

WILL NOT overcome the binding of the competitor to the enzyme. The cell
must produce new enzymes.
• Aspirin is an example of an irreversible inhibitor of cyclooxygenase, the

enzyme response for producing proinflammatory prostaglandins and leukotrienes.
N o n -C o m p e titiv e In h ibition : The ligand does not resemble the substrate

and binds to an allosteric site rather than the active site. Although the
substrate may still bind to the active site, the inhibitor at the allosteric site
prevents the reaction from occurring.
• Km will be UNCHANGED because there is no competition and therefore

no change in the affinity between the enzyme and the substrate.
• Vmax will DECREASE due to inhibition of the enzyme. Any increase in

[S] will not overcome the presence of the ligand at the other site.•
• The Lineweaver-Burk plot will shift upwards as Vmax decreases.
Competitive inhibitors shift x-intercept ( j ^ ) of the Lineweaver-

Burk plot towards the right. Non-competitive inhibitors shift the
y-intercept ( vmax) Lineweaver-Burk plot upwards.

A llo s te ric ligands bind to an allosteric site away from the active site of the
enzyme that binds the substrate. Allosteric molecules alter the configuration
of the active site and the ability of the substrate to produce an enzymatic
reaction. Allosteric ligands may inhibit or p ro m o te enzyme activity (11).
• P ositive allosteric ligands stabilize the enzyme and increase the affinity
of the enzyme for the substrate. K m decreases resulting in a displace
ment of the Lineweaver-Burk plot towards the left.
• N ega tive allosteric ligands decrease the affinity of the enzyme for the
substrate, resulting in an increase in K m with a resulting shift in the
Lineweaver-Burk plot towards the right.
C o o p e ra tiv ity occurs when the binding of one substrate to the

active site of an enzyme increases the affinity of the active site for
additional identical substrate molecules (11).
E n zym e R eg u la tion
Cells are capable of regulating enzymatic activity through a variety of meth

ods (11) (5) (2):
F eedback regu lation involves the end product of a reaction binding to an

allosteric site on the enzyme to increase or decrease enzyme activity.
• F eedback in h ibition occurs when an adequate concentration of

the end product of a reaction has been produced. The end product
acts as an allosteric inhibitor, decreasing enzyme activity. Several
biochemical pathways, including the hypothalamus - pituitary gland
- thyroid gland axis, are regulated through feedback inhibition.
• P ositive feedback occurs when the end product of a reaction binds
to an allosteric site on the enzyme and increases enzyme activity.
One of the most well understood positive feedback loops occurs dur
ing child birth - the release of the hormone oxytocin increases the in
tensity and number of contractions throughout labor until the baby
is born.
P ro te o ly tic activation occurs when an inactive storage form of an enzyme

(i.e. proenyzme or zymogen) is activated by removing an inhibitory
molecule.•
• Digestive proteases are initially produced as zymogens and are acti

vated by proteins after being released into the stomach and/or small
intestine.

232 6.2. PROTEINS
R eversib le covalent m od ifica tion involves the phosphorylation/dephosphorylation

of enzymes in order to activate/inhibit enzyme activity. A T P is the most
common donor of the phosphate group necessary for enzyme activation,
although GTP may also be used for certain enzymes.
• An en zym e cascade describes the sequential activation of a series

of enzymes in order to amplify a small signal into a large response.
For example, when glucagon binds to a receptor on a liver cell, it
triggers an enzymatic cascade that leads to the release of multiple
glycogen molecules and the production of an even greater number
o f glucose molecules, resulting in a rapid increase in blood glucose
levels.
pio en crg o n ics and E nergy Storage /-; ' 2 ; ; y t
E x ergon ic, E n d erg on ic and C ou p led R eaction s
G ib b s free e n erg y (G) predicts whether a reaction will occur spontaneously

at a given temperature and pressure. Gibbs free energy can be described using
the following equation:
A G = AIT - T A S (6.2)
• E nthalpy (A H ) is the amount of heat given off (ex oth erm ic (—till))
or absorbed (en d oth erm ic (+A/J)) in reactions.
• E n trop y (A S) is a measure of disorder (i.e. randomness). Because

enzymatic reactions favor disorder, the higher the A S the more likely
the reaction is to proceed.
• T = Temperature
E xergon ic reaction s (—SG) release energy and occur spontaneously.
E n d erg on ic reaction s (T<5G) require energy for the reaction to proceed and
DO NOT occur spontaneously.
The reaction is in equ ilibriu m if the 5G is 0.
A reaction will proceed spontaneously if it is an exothermic ( —SH)

reaction that results in a high degree of randomness (large tiS)
resulting in a negative 5G.

C o u p le d reaction s occur when an exergonic reaction provides the energy

necessary to drive an endergonic reaction that it is linked to through a com
mon intermediate product. Because the overall free energy of the pathway is
negative, the coupled reaction will occur spontaneously (2).
Although SG provides information regarding the direction of the

reaction, it DOES NOT provide information regarding the R ATE
of the reaction.
We now introduce concepts related to oxidation-reduction reactions (10, ch. 14).

Oxidation-reduction reactions (aka redox reactions) are very important in bi
ological pathways. In these reactions, electrons (e-) are transferred from a
reducing agent to an oxidizing agent.
• Oxidized substance (aka reducing agent): Lost an electron
• Reduced substance (aka oxidizing agent): Gained an electron
Remember, LEO the lion says G E R !
• Lose electrons = Oxidized.
• Gain electrons — Reduced.
B io lo g ica l M olecu les In volved in R e d o x R ea ction s
• N A D H and F A D H : Both are electron carriers (they act as reducing

agents). When oxidized, they take the forms N AD+ and FAD+. NADH
and FADH play an important role in the Krebs Cycle.
• N A D P H : Another e lectron carrier (acts as reducing agent) that is

often involved in the synthesis o f biological molecules. The oxidized form
of this molecule is NADP.•
• A T P : The m ost co m m o n source o f en erg y in biological reactions.

ATP has three negatively charged phosphate groups that repel one an
other. Energy is given off when one phosphate is released from ATP,
creating ADP. ADP has less energy due to resonance and less phosphate
groups compared to ATP.

234 6 .2 . PROTEINS
— Although ATP is the primary source of energy for most biochemical

reactions, other nucleotide triphosphates equivalent to ATP may be
used to drive certain cell processes (2):
1. G TP is the primary energy source for protein synthesis.
2. CTP serves a feedback inhibitor during nucleotide synthesis.
3. UTP is the energy source for glycogen synthesis.
• A ce ty l C o A : An important metabolite produced from pyruvate that en

ters the Krebs cycle and is oxidized, transferring electrons to the electron
carriers NADH and FADE. Acetyl CoA also plays a role in the synthesis
and oxidation of fatty acids and the metabolism of amino acids.
p u ffers arid p H yAf■-c■.7 ■ Tty

We now introduce concepts related to buffers and pH, including the Henderson-
Hasselbalch equation (10, ch. 4). pH is simply a measure of the concentration
of H+ ions in a solution. The formal definition is pH = - log [ H-|~ ].
• A cid s d o n a te hydrogen ions. Acidic substances have a pH < 7.
• B ases a ccep t hydrogen ions. Basic substances have a pH > 7.
A ssessing S trengths o f A cid s and Bases
Acids and bases are characterized by K a, a measure of the strength of an acid.

Stronger acids have a higher Ka value.
It is often more convenient to describe an acid or base in terms of

p K a , where pKa = -log(Ka). A high pKa is equivalent to a low
Ka (less acidic substance).
B uffers consist of a weak conjugate acid-base pair (weak acid + conjugate

base or vice versa) that is capable of neutralizing small amounts of added
acid or base in order to maintain the pH of a solution. The most impor
tant biological buffer systems in the body include (11):•
• Dihydrogen phosphate buffer system maintains the internal pH of

cells.
• Carbonic acid buffer system maintains the pH of blood and plasma
(see general physiology chapter for further details).
• Protein buffer system helps maintain the pH of blood and intracel
lular solutions.

The ca pa city of the buffer describes the extent of acid/base the buffer can
absorb while still maintaining pH.
H en derson -H asselbalch E quation
The Henderson-Hasselbalch equation is used to determine the pH of a buffer

solution.
pH — pKa -f- log ( [Base] / [Acid] ) (0.3)
Example 6.1: Find the pH o f a solution with 0.3M HAc and 0.2M NaAc. Ka = 10 5 for
acetic acid (HAc) (Ac~ is an abbreviation for the acetate anion, CHaCOO~ ). Solution
6.1: We are dealing with acetic acid and its conjugate base, Ac~. pH = - log (Ka) +
log (2/3) = 5 + (-0.176) = 4.8.
r~ SECTION 6.3
C arb o h y d rates •
We now introduce concepts related to carbohydrates (10, ch. 9).
Carbohydrates are organic compounds with a carbon backbone with a general

structure of CHoQn. They are classified according to the number of carbons
and the types and combinations of H and O bound to the carbon backbone:
M on osacch arides are the simplest carbohydrates with an aldehyde or ketone

backbone and two or more hydroxyl groups. They are the building blocks
for larger carbohydrate molecules.
• Examples include glucose, fructose, and galactose.
D isaccharides are two monosaccharides joined by a covalent O -g ly cosid ic

b on d.
• Maltose = glucose + glucose

• Lactose = glucose + galactose
• Sucrose = glucose + fructose
O ligosaccharides are composed of 3-10 monomers (aka monosaccharides).

Examples include blood group antigens and membrane glycoproteins (11).

236 6.3, CARBOHYDRATES
P olysacch arid es are composed of greater than 10 monomers. Examples

include:
• Starch is composed of thousands of glucose subunits. Starch is the

storage form of glucose in plants.
• G ly co g e n is composed of thousands of glucose subunits in a more
branched pattern compared to starch. Glycogen is the storage form
of glucose in humans and is found primarily in muscle and liver cells.
• G ly cosa m in og ly ca n s (GAGs) are polysaccharides made up of re
peating disaccharide units. GAGs are negatively charged molecules
that are strongly attracted to H 2 O. They are the main component
of the extracellular matrix. Common GAGs include:
— Cliondroitin sulfate: The most prevalent GAG that serves as
the major component of connective tissue in the blood vessels,
bone, cartilage, heart valves, and tendons. Helps to provide
strength, flexibility, and shock absorption in the joints.
— H yalu ron ic acid (aka hyaluronate or hyaluronan): Located in
the v itreou s hum or, synovial fluid, and the ECM of loose con
nective tissue. Contributes to cell proliferation, cell migration,
and wound healing.
— Heparin sulfate: Common GAG found in basement membranes
and cell surface receptors for viruses.
— Heparin: Located in mast cell granules of the lungs, liver, and
skin. May be used as an injectable anticoagulant.
— K eratan sulfate: Present in the cornea, cartilage, and bones,
— Dermatan sulfate: Located in the skin, blood vessels, and heart
valves.
• P ro te o g ly ca n s are composed of one or more GAG chains covalently
linked to proteins. They attract JÔ because of their negative charge
and are found in abundance in the extracellular matrix.
• G ly co p ro te in s are proteins covalently linked to various carbohy
drate groups. Unlike proteoglycans (which have a significant carbo
hydrate component), the carbohydrate groups account for a much
smaller percentage of the overall weight in glycoproteins. Glycopro
teins are an important component of cell membranes and play a role
in cell adhesion and cell signaling. Blood antigen groups (ABO) and
coagulation factors are also important glycoproteins.
We now introduce concepts related to glycolysis (10, ch. 14). Glycolysis is the
first step in the catabolism of glucose molecules to produce energy for cells and
occurs in the cell cytoplasm.

• One molecule of glucose CgHÔe is converted into 2 molecules of pyru

vate C 3 H 4 O 3 . Pliosphofructokinase is the rate limiting enzyme of the
glycolytic pathway.
• Glycolysis is an exergonic process that is coupled to an endergonic re

action involving the addition of a phosphate group to ADP to generate
ATP.
• Glycolysis results in a net gain o f 2 A T P and 2 N A D H per glucose

molecule.
P o st-G ly co ly sis and A n a erob ic R esp ira tion
Pyruvate molecules produced in glycolysis have two possible fates depending

on the amount of available oxygen in the cell.
• If oxygen is available (aerobic respiration), pyruvate is converted to

Acetyl CoA in order to enter the K reb s cycle.
• If oxygen is unavailable (anaerobic respiration), pyruvate is converted

into lactic acid. The cell gains a net total of 2 A T P s per glucose
molecule during anaerobic respiration.
The conversion of pyruvate to Acetyl CoA occurs in the cytoplasm by the en
zyme pyruvate dehydrogenase. This reaction generates 1 NADH per pyruvate,
for a total of 2 N A D H per unit of glucose (see Figure 6.4).
itrib acid cy cle,v

We now introduce the Krebs cycle, the second step o f cellular respiration that
occurs within the mitochondrial matrix (10, ch. 16).
The Krebs cycle produces reducing agents (NADH and FADH) that
will then be used in oxidative phosphorylation to produce energy
in the form of ATP. The Krebs cycle DOES NOT directly produce
ATP.
NAD NADH
Pyruvate Acetyl CoA

Figure 6.4: The production of Acetyl CoA is necessary to enter the T C A Cycle.

238 6.3. CARBOHYDRATES
The first reaction in the Krebs cycle involves the conversion of Acetyl CoA to
citric acid by the enzyme citrate synthase.
• Low levels of citrate synthase may occur during starvation or in

patients with diabetes, resulting in the inability to produce citric
acid from Acetyl CoA.
• In these cases, Acetyl CoA is converted into ketone b od ies that
are used as an alternative source of energy by many organs.
Each TC A cycle produces 3 NADH, 1 F A D H 2 , and 1 ATP per molecule of

Acetyl CoA.
Because two molecules of Acetyl CoA (from 2 pyruvates) enter the

Krebs cycle per one glucose molecule, the net gain is 6 N A D H , 2
F A D H 2 , and 2 A T P .
O X ID A T IV E P H O S P H Q I^L A fF IO N (Q P )
We now introduce oxidative phosphorylation, the last step in cellular respira
tion that occurs in the inner mitochondrial matrix and serves as the m a jo r
sou rce o f A T P in aerobic organisms (10, ch. 19).
Oxidative phosphorylation is the production of ATP coupled to

the donation of electrons by NADH and F A D H 2 to 0 2 through a
series of enzymes that make up the electron tran sp ort chain in
the inner mitchondrial membrane (11).
• The electron transport chain is a series of four large multiprotein com

plexes located in the cristae of the inner mitochondrial membrane. NADH
and F A D H 2 donate their electrons to the ETC.
Oxaloacetate
Citrate
Acetyl CoA
Figure 6.5: The first step of Krebs Cycle,

• As electrons move down the ETC, the protein complexes pump H+ ions
across the mitochondrial inner membrane into the intermembrane space,
creating a strong proton gradient.
• Hydrogen ions eventually diffuse down the concentration gradient through

a proton channel coupled to the enzyme A T P synthase, resulting in the
production of ATP. This is termed p H o r ch em iosm otic coupling.
• The last step in the ETC involves the transfer of electrons and hydrogen
to O 2 to form H 2 O.
Defects in mitochondrial DNA associated with ETC proteins and

ATP synthesis will have a substantial impact on tissues with a
very high oxygen demand. L e b e r’s h ered ita ry o p tic n eu ropa
thy and K earn s-S ayre syn drom e are examples of mitochondrial
diseases with significant visual consequences.
A T P G E N E R A T E D F R O M G L Y C O L Y S IS , K R E B S , A N D O P
Remember the total production of molecules for each step in cellular respira
tion:
Glycolysis produces 2 NADH and 2 ATP.
The conversion of 2 pyruvate to Acetyl CoA produces 2 NADH
Krebs cycle produces 6 NADH, 2 F A D H 2 , and 2 ATP
Oxidative phosphorylation produces 3 A T P per N A D H and 2

A T P per F A D H 2.
Therefore the TOTAL NET ATP per glucose molecule is 36 A T P .
• 10 NADH x 3 ATP = 30
• 2 F A D H 2 x 2 ATP - 4
• 2 ATP = 2

240 6.3. CARBOHYDRATES
We now summarize the pentose phosphate shunt (10, ch. 15).
The pentose phosphate shunt occurs in the cell cytoplasm, particularly in

tissues that are involved in the synthesis of fatty acids and/or cholesterol
(i.e. liver, adipose tissue, adrenal cortex, lactating mammary glands).
The pentose phosphate shunt metabolizes glucose-6 phosphate and plays

a role in the following functions:
• Production of 12 N A D P H per glucose molecule to be used in the

synthesis of fatty acids and steroids.
• Production of rib ose-5 -p h osp h a te used in the synthesis of RNA,
DNA, and nucleotide coenzymes.
• C ell d etox ifica tion by removing harmful O2 radicals through the
reduction of glutathione.
d u c o n e o g e n e sis
We now summarize concepts related to glucose production (10, ch. 20).
G lu con eogen esis describes the production of glucose without the break
down of glycogen. Glucose production occurs primarily in the liver (and oc
casionally the kidneys) and provides the most benefit to tissues with a high
energy demand (i.e. brain and retina).
Lactate, amino acids, and glycerol may all be used to generate glucose. Let’s
look at the production of glucose from lactate:•
• Excess lactic acid that accumulates during exercise can be converted

into pyruvic acid in the liver via the enzyme lactic dehydrogenase.
• The liver will then convert pyruvic acid to glucose in order to gen
erate ATP for the skeletal muscles.
Although most tissues in the body primarily use the aerobic cellu
lar respiration pathway to generate ATP from glucose, tissues with
a very high energy demand (i.e. brain and retina) will ALSO con
vert pyruvate to lactic acid to QUICKLY generate a large amount
of ATP. The simultaneous use of aerobic and anaerobic cellular
respiration pathways is termed the W arburg effect.

We now summarize concepts related to the synthesis of glycogen (10, ch. 20).
* Glycogenesis involves the conversion of glucose into the storage form of

glycogen. This process occurs primarily in the m uscles and liver.
— Cells cannot survive the increase in osmotic pressure that occurs

with the storage of individual glucose subunits. The transformation
of glucose to glycogen allows cells to keep an energy reserve without
the danger of exploding!
• Glycogenesis involves the conversion of glucose into glucose-6-phosphate

==> glucose-1-phosphate => UDP-glucose. UDP-glucose is then added to
a growing glycogen chain by the enzyme glycogen synthase.
We now summarize concepts related to the breakdown of glycogen (10, ch. 15).
• Glycogen is broken down into glucose subunits when there is an increased

tissue demand for energy. Glycogenolysis occurs in the m uscles and
liver,
• Glucose-6-phosphate monomers are released from glycogen via the en

zyme glycogen phosphorylase. Glucose-6-phosphate can then be shuttled
into glycolysis or the pentose phosphate shunt pathway to generate ATP.
• When ATP is no longer needed by the cell, excess glucose-6-phosphate

monomers can be converted back to glycogen.
T h e R o le o f th e Liver
The biochemical pathways described above must be tightly regulated in order

to maintain adequate blood glucose levels, depending on the body’s needs (10,
ch. 23).
• After a large meal with carbohydrates, the liver initiates glycogenesis

and lipogenesis to transform glucose and lipids into the storage forms of
glycogen and triglycerides, respectively.•
• During fasting conditions, the liver initiates glycogenolysis and gluconeo-

genesis to produce glucose that can be carried to various tissues via the
blood stream. Many organs may spare blood glucose during fasting by
using fatty acids, lactic acid, or ketone bodies (produced from Acetyl
CoA) as alternative sources of energy.

242 6.1 LIPIDS
Although the brain almost exclusively uses blood glucose for energy,
it will use k eton e b o d ie s if absolutely necessary to maintain tissue
function.
I - SECTION 6.4
Lipids
We now introduce concepts related to lipids (10, ch. 11).
jStrueture and Function o f Lipids

Although lipids are a large, diverse class of molecules with several different
functions, all lipids are non-polar and are insoluble in water.
• Similar to carbohydrates, lipids contain the organic atoms C, H, and O

and serve as a major source of energy for cells. Carbohydrates and lipids
account for most of the calories consumed in food.
• Because of differences in physical and chemical properties, lipids have

very different functions compared to carbohydrates.
The following are major functions of lipids:
• Serve as one of the main sources of energy for the body.

• Act as building blocks of phospholipids and glycolipids.
• Lipid derivatives function as hormones and intracellular messengers.
• Modify proteins.
Fatty A cid s (F A s): Each fatty acid molecule consists of a hydrocarbon

chain of varied length with a terminal carboxyl group. Fatty acids may be
classified as saturated or unsaturated:
• Saturated FAs: All carbons in the chain are joined by single covalent
bon ds.
• Unsaturated FAs: Two or more carbons in the chain are joined by dou ble
covalent b on d s.

T riglycerid es: Serve as the storage form of fatty acids in adipose tissue or
travel in the bloodstream to provide energy to various tissues.
• Triglycerides are composed of 3 fatty acid (FA) molecules connected by

1 molecule of glycerol. Each FA molecule contains a hydrocarbon chain
of varied length with a terminal carboxyl group.
• Lipases are enzymes that break down triglycerides into fatty acids to be
used for energy.
P h osp h olip id s: Consist of a 3 carbon glycerol molecule attached to 2 fatty

acid “tails” and a phosphate “head” group. The polar phosphate group serves
as a binding site to other molecules. A variety of lipids with different functions
are included in this group.
Phospholipids are the major component of the lipid bilayer in cell

membranes.
S ph ingom yelins: A specific phospholipid that serves as an important struc

tural component of nerve cell membranes and is the major component of the
m yelin sheath.
• Sphingomyelins are composed of a sphingosine backbone (rather than

glycerol) with an attached fatty acid and phosphorylcholine.
Sphingolipidoses are characterized by defective lysosomal enzymes

necessary for the breakdown of sphingolipids. Thy-Sachs disease
is an example of such a condition and is characterized by a ch erry
red sp o t within the macula (11).
Isopren oids: The major class of lipids in plants, animals, and bacteria. Iso-
prenoids are composed of five carbon atoms, with typically four of the carbon
atoms in a linear chain and the fifth carbon attached to the first carbon in the
chain.
Copyright 20,1,4 by KMK Educational Services, LLC

244 6.1 LIPIDS
C h olesterol: Produced from acetyl C o A in the cytoplasm of cells in the

liver and the intestines; NADPH functions as the reducing agent in this series
o f reactions. Cholesterol has two major functions:
• Serves as a precursor for steroid hormones produced in the adrenal cortex

(corticosteroids including glucocorticoids and mineralocorticoids) and the
gonads (estrogen, progesterone, and testosterone) (see general physiology
chapter for further details).
• Acts as a major structural component within lipid membranes that helps

to maintain membrane fluidity.
E icosan oids: Serve as short-range signaling molecules. A rach id on ic acid,

released from phospholipids by the enzyme phospholipase A 2 , serves as the
precursor for eicosanoids that are produced via two pathways (11):
1. The cy clo o x y g en a se pathway produces prostaglandins and thrombox

ane.
• Prostaglandins are pro-inflammatory molecules that produce a var

riety of effects within tissue, including an increase in uveoscleral
ou tflow in the eye.
• Thromboxane promotes arteriole constriction and platelet aggrega
tion.
2. The lip o o x y g en a se pathway produces leukotrienes; these molecules pro

mote inflammation and play a role in allergic reactions.
Lipid D igestion . • • ^ .A. . .. y: rV ^ 0 } ^ yyj

We now introduce concepts related to the breakdown of lipids (10, ch. 17) (11).
• The presence of triglycerides in the duodenum stimulates the release of

bile from the gall bladder. Bile salts emulsify triglycerides, breaking them
down into triglyceride droplets. The droplets have a greater surface area,
promoting further enzymatic breakdown.
• P an creatic lipase, released by the pancreas into the small intestine,

removes two fatty acid molecules from triglyceride, creating free FAs and
a monosaccharide.•
• Bile salts, free FAs, and monosaccharides combine to form “mixed mi
celles” that are absorbed across the brush border into the epithelium of
the small intestine.

• Once within the small intestine epithelial cells, short and medium chain
FAs are directly absorbed into the portal circulation. Triglycerides and
cholesterol molecules are resynthesized and combined with phospholipids,
fat soluble vitamins, and proteins to form ch ylom icrons.
• Chylomicrons are secreted into lymph capillaries within the intestinal villi
and are transported through the lymph system before ultimately reaching
the venous system.
• Once chylomicrons reach the bloodstream, the enzyme lipoprotein lipase

(attached to endothelial cells of blood vessels), breaks down triglycerides,
releasing free FAs that can be used as energy by cells.
• Because cholesterol is hydrophobic and insoluble in blood, cholesterol

molecules from chylomicrons are absorbed by the liver and attached to
carrier proteins before being released into the bloodstream.
— V LD L (very low density lipoprotein): delivers cholesterol to various

organs.
— LDL (low density lipoprotein): VLDL becomes LDL after delivering
cholesterol to various tissues.
— HDL (high density lipoprotein): Excess cholesterol released by or
gans attaches to HDL to be transported back to the liver.
Remember the normative values for cholesterol;
• Total cholesterol < 200
• LDL < 130
• Triglycerides < 1 5 0
• HDL > 40
------------------------------------------------------------------------------------------------------------------------------------------
X an th elasm a are yellow, sharply demarcated cholesterol deposits
within the periorbital skin. They may be associated with high
cholesterol (although are often a result of aging).

246 64- LIPIDS
We now introduce concepts related to the breakdown of fatty acids (10, ch. 17).
B e ta ox id a tion occurs within the mitochondria and involves the conversion

of fatty acids into a ctey l C o A in order to generate NADH and F A D H2. This
process is similar to glycolysis in the production of acetyl CoA, and similar to
the TCA cycle in the production of reducing molecules.
• The first step o f beta oxidation involves the conversion of fatty acid to
fatty acyl CoA. This reaction requires ATP and occurs within the outer
mitochondrial membrane.
• The remaining four steps involve two “dehydrogenation” reactions, one

reaction that produces F A D H 2i and one reaction that yields NADH.
Acetyl CoA will be sent to the Krebs cycle to generate additional reducing
agents that can then be used in oxidative phosphorylation to produce ATP.
Proteins, carbohydrates, and lipids can all be degraded into A cety l

C o A for use in the Krebs cycle.
K e to n e B od ies
• When the liver has produced sufficient amounts of ATP through beta ox
idation, acetyl CoA is shuttled out of the organ in order to prevent nega
tive feedback and subsequent inactivation of the beta oxidation pathway.
• Acetyl CoA is diverted away from the TCA cycle and is used to form
ketone b o d ies, an alternative source of energy used by many organs.
Ketone bodies include acetoacetate, beta-h y d rox yb u tyrate,

and aceton e.
We now introduce concepts related to the production of fatty acids that occurs
in the cell cytosol (10, ch. 21).

• Fatty acid synthesis is a four step process of condensation, reduction,

dehydration, and reduction that is catalyzed by the enzyme fatty acid
synthetase. Each reduction step utilizes N A D P H as the reducing agent.
• The four step process occurs in four cycles and yields a 16 carbon fatty
acid molecule.
We now overview the basics of membrane biochemistry (10, ch. 12). The
molecules discussed above interact to form a dynamic plasma membrane (aka
unit membrane) that serves a “barrier” to the internal cellular environment.
Membranes are selectively perm eable, allowing limited movement of molecules
based on size, charge, and polarity (see histology chapter for further details).
The structure of membranes is based on the fluid m osaic m od el:

proteins are embedded within the phospholipid bilayer through
non-covalent bonds, allowing free lateral movement of proteins
while still maintaining an intact cell “barrier.”
P h osp h olip id s are the major component of cellular membranes. They are
a m p h ip a th ic molecules with hydrophilic (water-loving) phosphate heads and
hydrophobic (water-fearing) fatty acid tails.
• The polar heads form electrostatic and hydrogen bonds with surrounding
water molecules.
* The non-polar tails are hydrophobic and interact with one another through
Van der Waal interactions.
M em b ra n e protein s have multiple functions and often serve as channels,

pumps, and/or components in cell signaling pathways. Membrane proteins are
classified into two groups:
• Integral protein s: Span the entire thickness o f the membrane. The

centers of the proteins are hydrophobic and form hydrophobic bonds with
the tails of the phospholipids. Integral proteins often serve as carrier
proteins and ion and HÔ channels.•
• P eriph eral protein s: Hydrophilic proteins that are attached to the sur
face of the membrane through electrostatic interactions. These proteins
serve as cell surface antigens and hormone receptors.

248 6.5. NUTRITION
I— SECTION 6.5
N u tritio n
Understanding the ocular nutritional benefits of fatty acids is important in

clinical care. Essential fatty acids (must be ingested through the diet) include
two subclasses:
O m ega-3 fatty acids: Include alpha-linolenic acid (ALA), eicosapentaenoic

acid (EPA), and docosahexaenoic acid (DHA). ALA is the precursor to EPA
and DHA (8).
* Omega-3 fatty acids are less prevalent in the diet compared to omega-6
fatty acids. They are found in buffalo, venison, walnuts, and oily fish
such as halibut, herring, and tuna. ALA is found in flaxseed oil, linseed
oil, various vegetable oils, and leafy green vegetables.
* Omega-3 fatty acids are an ti-inflam m atory molecules.
Omega-3 supplementation may improve dry eye syndrome through

the inhibition of inflammatory mediators, possible alteration of
lipid composition within the meibomian glands, and stimulation
of aqueous tear secretion (13).
O m ega-6 fatty acids: Include linoleic acid (LA), gamma-linoleic acid (GLA),
and arachidonic acid (ARA).
• Omega-6 fatty acids are abundant in meat, corn oil, and margarine. They
are p ro-in fla m m a tory m olecu les (in particular ARA).
An ideal omega-6 to omega-3 ratio is between 1:1 and 3:1. The ratio in a typical
Western diet is 10:1 to 20:1 (8).
Protein catabolism yields 4 cal/g, carbohydrate catabolism yields

4 cal/g, and lipid catabolism yields 9 cal/g.

r - SECTION 6.6
V itam ins and M inerals
We now summarize concepts related to vitamins and minerals (12, ch. 11).
Vitamins serve as cofa ctors (aka coenzymes) for enzymatic reac

tions and are therefore essential components of many biochemical
reactions necessary for cell survival.
W a te r-so lu b le vitamins are NOT stored in the body and can therefore be
depleted within a number of days during periods of starvation. These vitamins
include:
1. V ita m in B 1 (Thiamine)
Source: Yeast, pork, whole grain.

Function: Metabolism of carbohydrates and amino acids.
Disorder caused by deficiency:
• B eriberi: Peripheral nerve damage that manifests as severe
muscle weakness and wasting that leads to delirium, memory
loss, o c u lo m o to r paralysis, and heart failure.
• May be associated with malnutrition or alcoholism (aka Wernicke-
Korsakoff syndrome).
Because B1 is not stored in the body, levels may be depleted in

14 days if not replenished through the diet. Patients with beriberi
may rapidly recover (within hours) after a thiamine injection.
2. V ita m in B 2 (Riboflavin)
Source: Liver, yeast, eggs, meat, mushrooms, almonds, fortified milk.

Function: Serves as a component of the cofactors FAD and FMN; also
helps to release energy from food.
• Cracking of skin and corners of mouth (angular cheilitis).

250 6 . 6 . VITAMINS AND MINERALS
• Seborrheic dermatitis,
• Magenta tongue.
• Most common in alcoholics.
Because vitamin B2 is continuously excreted, deficiency is not un

common, but it is always accompanied by other vitamin deficien
cies.
3. V ita m in B 3 (Niacin)
Source: Meat, fish, liver, grains, legumes. May also be synthesized from
tryptophan.
Function: Serves as a component of the cofactors NAD and NADP.
• Pellagra: Chronic niacin deficiency usually seen in conditions
of poverty, malnutrition, and chronic alcoholism. Symptoms
include diarrhea, dermatitis, and dementia.
4. V ita m in B 6 (Pyridoxine)
Source: Liver, fish, nuts, grains, eggs, yeast.

Function: Important coenzyme for transamination (synthesis of amino
acids). Also aids in the formation of RBCs and has been linked to
cancer immunity.
• Most common in alcoh olics but may also be associated with
oral contraceptives.
• Symptoms include fatigue, depression, impaired growth, and
seizures.
5. V ita m in B 12 (Cobalamin)
Source: Muscle and organ meats, eggs, dairy, and fish (strict vegetarians
may have low vitamin B12 levels).
Function: Serves as the building blocks of DNA and RNA and is thus
in high demand in rapidly growing tissues including fetal tissue,
immune cells, and RBCs.
• P ern iciou s anem ia: An autoimmune disorder that destroys
the parietal cells of the stomach, causing a loss of production of
intrinsic factor necessary for vitamin B12 absorption.

• May also lead to neurological disorders and glossitis.
Vitamin B12 deficiency is the most common deficiency seen world-

wide and is often associated with alcoholism .
6. Vitamin C (Ascorbic acid)
Source: Citrus fruit, green vegetables, melons.

Function:
• Serves as a cofactor in collagen synthesis.
• Aids in wound healing, bone formation, and capillary integrity
(non-exhaustive list).
• Acts as an antioxidant.
• Serves as a cofactor in dopamine and norepinephrine synthesis.
• Scurvy: Results in muscle weakness, breakdown of bone, de
layed wound healing, rotting of the teeth and gums, and spon
taneous hemorrhaging.
7. Folic acid (Folate)
Source; Liver, yeast, green vegetables, and certain fruits. Folate can be
stored in the liver.
Function: Aids in the synthesis of purine and pyrimidine nucleotides
necessary for DNA synthesis.
Disorders caused by deficiency (as a result of impaired DNA replication
in dividing cells):
• Spina bifida: Neural tube defects in the developing fetus.
• Anencephaly.
• Megaloblastic anemia.
• Diarrhea.
• Glossitis.
Folate deficiency is the most common vitamin deficiency in the

United States and often affects pregnant women and alcoholics.

252 6 .6 . VITAMINS AND MINERALS
Fat soluble vitam ins (DEAK) are carried in fat and can be stored in the
liver. Excess storage may lead to toxicity (unlike water soluble vitamins that
cannot be stored).
1. V ita m in D (Calciferol)
Source: Egg yolk, saltwater fish, liver, fortified foods. Vitamin D must
be converted into the active form in the liver or the kidneys.
Sunlight converts cholesterol into vitamin D. Vitamin D is essential

only for those people who stay out of the sun.
Function: Increases intestinal absorption of calcium and phosphate.

Disorder caused by DEFICIENCY:
• R ick etts in children and osteom alacia in adults. The body
tries to maintain blood calcium levels by leaching calcium from
the bones, causing them to soften in children or become brittle
in adults.
Disorder caused by EXCESS:
• Hypercalcemia may result in sarcoidosis, with symptoms of
loss of appetite and fatigue.
Vitamin D is the m ost to x ic fat soluble vitamin.
2. V ita m in E (Tocopherol)
Source: Vegetable oils and seeds and leafy green vegetables.

Function: Acts as an antioxidant and protects RBCs from hemolysis.
• Hemolysis
• Neurological dysfunction in premature infants.
Vitamin E is the least to x ic of the fat soluble vitamins.
3. V ita m in A (Retinol)

Source: Meat, liver, eggs, dairy, fish oil, and vegetables.
B eta ca roten e is a major precursor for vitamin E and is found in

carrots and other orange vegetables.
Function:
• Helps to develop and maintain epithelial tissue, thereby helping
to increase resistance to infections.
• Serves as component of rh od op sin and iod op sin , retinal pho-
topigments necessary for night vision and color vision.
• Acts as an antioxidant and protects against cancer.
Disorders caused by DEFICIENCY:
• Slight night blindness.
• Dryness of the skin and eyes (x erop h th alm ia with B ito t’s
sp ots on the conjunctiva).
• K eratom alacia: Blindness secondary to chronic dryness that
leads to necrosis and ulceration of the cornea.
Disorders caused by EXCESS:
• Toxicity may occur with low levels of vitamin E and may lead
to changes in the skin, fatigue, headache, sore throat, and joint
pain.
• May potentially cause diplopia, nystagm us, nerve palsies,
and papilledem a.
4. V ita m in K
Source: Green and yellow vegetables, fruits, and meats. Also synthe
sized by intestinal bacteria.
Function: Required for synthesis of prothrombin and clotting factors II,
VII, IX, and X in the liver.
W arfarin is a vitamin K antagonist.
Disorder caused by deficiency: Clotting disorder with excessive hemor

rhaging.
Vitamin K deficiency is most common in newborns.

254 6 .6 . VITAMINS AND MINERALS
M inerals are inorganic micronutrients required by the body that play impor
tant roles in bone and teeth formation, muscle and nerve function, and water
balance. Important m a jo r m inerals include:
• C alcium : Aids in bone and tooth formation, muscle contraction, nerve

transmission, blood clotting.
Osteopenia and osteoporosis develop secondary to calcium defi

ciency.
• C h lorid e: Major negative ion in extracellular fluid. Helps with mem

brane function, water balance, and digestion.
• M agn esiu m : Important cofactor in protein synthesis.
• P h osp h orou s: Aids in bone and tooth formation, acid-base balance

(phosphate buffer system), and energy storage and release (ADP < ->
ATP).
• P otassium : Major positive ion in intracellular fluid. Aids in membrane

function, acid-base balance, nerve function, muscle relaxation, and water
balance.
• S od iu m : Major positive ion in extracellular fluid. Helps with membrane

function, acid-base balance, nerve function, and water balance.
Important m in or m inerals include:
• C o b a lt: Constituent of vitamin B12. Deficiency results in pernicious

anem ia.
• C o p p e r: Cofactor for enzymes necessary for iron metabolism and nerve

function. Also aids in the maturation of collagen and elastin.
W ils o n ’ s disease (hepatolenticular degeneration) results from

large accumulations of copper. Patients may have a K ayser-
F leischer ring on the cornea and sunflower cataracts.
• Iod in e: Critical for th y roid fu n ction as it serves as a component of

thyroid hormones (T3 and T4). Helps to regulate energy metabolism.•
• Iron : Component of hemoglobin and cofactor for enzymes involved in

energy metabolism.

• Z in c: Required for DNA synthesis, supports a healthy immune system

via cell mediated immunity, supports normal growth and development,
and maintains sense of taste and smell.
O x y g e n to x icity and free radicals
A radical is an atom or molecule with one or more unpaired electrons. Radicals

are normal byproducts of a wide range of normal biochemical reactions. How
ever, because of their high chemical reactivity, excess production or inadequate
control of radicals may lead to major tissue damage (18).
O x y g e n free radicals are the most concerning free radicals in the body.
They are formed in the mitochondria as O 2 is reduced along the electron trans
port chain, but can also be generated as intermediates in various biochemical
reactions. Oxygen free radicals are often produced in excess in the following
situations (18):
• Neutrophils and other WBCs produce O 2 radicals as a defense against

invading pathogens.
• Hypoxic or hyperoxic cells generate excessive 0% radicals.
• Ionizing radiation leads to the production of O 2 radicals, especially in

tissues with a high oxygen demand.
Oxygen free radicals include superoxide, p erox id e, singlet o x y

gen, and h ydroxyl radical.
Oxygen radicals may damage lipids, proteins, and nucleic acids (18).
• Oxygen reactive species often leads to lipid p erox id a tion in cellular

membranes, leading to decreased membrane fluidity and altered mem
brane permeability.
• Oxygen radicals may cause protein-protein crosslinking, leading to de

creased activity of membrane bound enzymes and protein receptors.
A n tioxida n ts are responsible for eliminating free radicals and thus help to
protect cells from oxidative stress. Important antioxidants include (18):
• Glutathione peroxidase and glutathione transferase.
• Vitamin E - protects membranes from oxidative damage.

256 6.7. MOLECULAR B IO L O G Y -D N A , RNA, TECHNIQUES
• Vitamin C - helps recycle vitamin E radicals.
• Flavonoids and carotenoids.
- SECTION 6.7 ------------------------------------- -------------------------------------------------
M olecular Biology - D N A , R N A , Techniques
We now introduce the major concepts of molecular biology (9, ch. II).
D N A contains the genetic information of the cell that serves as a code for the
production of a wide range of proteins necessary for cell survival. This genetic
information is passed through generations through cell mitosis and meiosis.
DNA is composed of n itrogen ou s bases:
• Purines (2 ring structure): Adenine (A) and guanine (G)
• Pyrimidines (1 ring structure): Cytosine (C) and thymine (T)
N itrogen ou s bases are attached to a sugar phosphate b ack bon e com

posed of deoxyribose (5 carbon) molecules. Covalent bonds link the 5** P (phos
phate) group and 3’ OH group of neighboring sugars.
The direction of DNA strands are designated as 5’ and 3’. The 5’

direction starts at the phosphate group (5’ P) and the 3’ direction
starts at the hydroxyl group (3’ OH).
The D N A d ou b le h elix is a three dimensional structure with a major and mi

nor groove and is composed of two anti-parallel strands (5’-3} and 3’~5’ strand)
linked through the following nucleotide base pairs:
• Adenine - Thymine (2 hydrogen bonds)
• Cytosine - Guanine (3 hydrogen bonds - stronger than A -T bonds)
DNA is found in the nucleus of the cell and is usually tightly compacted (11).
• DNA strands wrap around histone proteins to form nucleosomes

(“beads on a string” structure).
• Nucleosomes are then arranged into supercoils to from a compact
30 nm ch rom atin fiber.

CHAPTER 6 , BIOCHEMISTRY 257
• Chromatin fibers further eompact to form ch rom osom es. Hete

rochromatin is highly condensed and inactive. Euchromatin is less
condensed and is active in transcription.
Fluoroquinolone antibiotics inhibit DNA compaction in bacteria

without affecting DNA compaction in human cells.
D N A R E P L IC A T IO N
DNA replication allows cells to pass on their genetic information to subsequent

generations. Prior to mitosis, cells make an identical copy of their DNA that
is then passed on to daughter cells (see cell cycle for further information).
DNA replication is sem i-conservative - each new DNA molecule

in a daughter cell consists of one old DNA strand from the parent
cell and one newly synthesized DNA strand.
DNA replication involves the following enzymes:
H elicase: Unwinds the parent DNA strands in an ATP dependent manner.
P rim ases (R N A p oly m era se): Synthesizes primers, which are short se
quences of RNA on the parent DNA strand that will serve as an initiation
site for DNA polymerase.
D N A polym era se: Extends the new DNA strand from 5’ to 3’ and helps to
proofread base pair's in the newly synthesized strand. DNA polymerase
CANNOT begin de novo - it must have a primer to initiate synthesis of
the new strand.
D N A ligase: Connects DNA fragments on the lagging strand (the strand

where DNA polymerase and helicase work in opposite directions).
Remember that antivirals (e.g. viroptic, acyclovir) inhibit DNA

polymerase in DNA viruses such as herpes sim plex.
The process of DNA replication involves the following steps:

258 6.7. MOLECULAR BIOLOGY - DNA, RNA, TECHNIQUES
1. Helicase unwinds a portion of the parent DNA strand.
2. Primase adds a short strand of RNA primer to each single strand of DNA.
3. DNA polymerase delta begins at the RNA primer and synthesizes a new
complimentary strand of DNA on the parent strand, working in the 5* to
3’ direction.
• The leading strand is the strand where DNA polymerase and he
licase are working in the SAME direction.
• The lagging strand is the strand where DNA polymerase and he
licase work in OPPOSITE directions.
4. DNA polymerase epsilon binds to the lagging strand and synthesizes short
DNA fragments (aka Okazaki fragm ents) in the 5’ to 3’ direction.
5. Okazaki fragments on the lagging strand are joined together by DNA

ligase.
R N A S tru c tu re aiid/F unction -JA -T; t TT-A T; •

RNA is a single strand molecule (although it will occasionally fold on itself
to form double-stranded regions) composed of a sugar-phosphate backbone
(rib ose sugars) linked to the following nitrogenous bases:
• Purines: Adenine and guanine
• Pyrimidines: Cytosine and uracil (replaces thymine found in DNA)
R N A base pairs are cytosine ~ guanine (CG) and adenine-uracil

(AU in contrast to AT DNA base pairs).
Because RNA is a single strand, the number of purines IS NOT necessarily

equal to the number of pyrimidines (in contrast to DNA). RNA is much more
unstable compared to DNA. There are three types of RNA molecules (11):
1. m essenger R N A (mRNA): Coding RNA that serves as the blueprint

for a specific amino acid sequence.
2. transfer R N A (tRNA): Cloverleaf shape RNA that matches the genetic

information from an mRNA strand (i.e. codons) to specific amino acids.
3. rib osom a l R N A (rRNA): Assembles with proteins to form ribosomes

necessary for protein synthesis.
Copyright 2014 by KM K Educational Services, L L C

DNA provides the genetic information necessary for protein synthesis.
M a in Idea: DNA —►RNA -y Protein
• DNA is transcribed to a single strand of complementary mRNA. mRNA

is composed of a series of 3 base sequences known as co d o n s that corre
spond to a particular amino acid. Translation involves the formation of
an amino acid sequence complementary to the mRNA codons.
Although the codons within mRNA dictate the amino acid se
quence, the DNA sequence provides the information necessary to
synthesize an mRNA strand that will lead to the synthesis o f a
desired protein. Thus DNA serves as the gen etic c o d e for protein
synthesis.
• The genetic code is redundant, as there are 64 possible codons that are
associated with only 20 amino acids.
— The initiation codon for every mRNA strand is A U G , which codes

for the amino acid methionine.
— Stop codons do not code for any amino acid but instead signal the
termination of the amino acid chain.
• In tron s are the parts of the DNA strand that DO NOT code for proteins.
E xtron s are the parts of the DNA strand that DO code for proteins and
are intermixed with introns.
Which part is coding? Just think, introns are IN THE WAY (4).
T R A N S C R IP T IO N
Transcription is the process of converting DNA into single strand of mRNA

that can be transported outside the nucleus to be used as template for the
synthesis of proteins. A complimentary mRNA strand is transcribed from a
DNA strand by the following series of steps (9, ch. II):
In itiation: The enzyme RNA polymerase binds to RNA at the p rom oter
region.

E lon gation : RNA polymerase unwinds the DNA and synthesizes a compli
mentary mRNA strand in the 5’ to 3’ direction (i.e. travels in the 3’ to
5Jdirection on the DNA strand).
T erm ination: When RNA polymerase reaches a termination sequence on the

DNA strand, elongation stops and the mRNA strand is released.
Prior to exportation of the mRNA from the cell nucleus, a series of modifica
tions are made to the mRNA strand:
1. Addition of a modified GTP 5’ cap
2. Addition of a 3’ poly-A tail (multiple As)
3. Introns are spliced from the mRNA sequence.
The addition of a 5* GTP cap and 3’ poly-A tail to the mRNA

strand aids in the protection and exportation of mRNA out of the
nucleus into the cell cytoplasm.
T R A N S L A T IO N
After mRNA is exported from the nucleus into the cell cytoplasm, the mRNA
sequence is translated into an amino acid sequence that serves as the primary
structure of a particular protein. The major components of translation include
mRNA, tRNA, and ribosomes.
* R ib o so m e s are composed of two subunits (made of protein and rRNA)

that will bind to mRNA and tRNA molecules to facilitate the translation
of mRNA into an amino acid sequence. Each ribosome has 2 binding
sites (A and P sites) for tRNA and 1 binding site for mRNA.
• t R N A has a clover leaf structure with an acceptor arm that is attached

to a specific amino acid and a 3 base an ticod on that corresponds to a
particular codon within the mRNA strand.
— Aminoacyl tRNA synthetase is the enzyme responsible for binding

a unique amino acid to the acceptor arm of tRNA.
Steps o f T ra n sla tio n /P ro te in Synthesis
Initiation: mRNA and the first tRNA (corresponding to the initiation codon
AUG) bind to the small ribosomal subunit, followed by binding of the
large ribosomal subunit to the mRNA/tRNA/small ribsomal subunit
complex.

CHAPTER 6, BIOCHEMISTRY 261
• Proteins (i.e. initiation factors) and GTP (for energy) facilitate the
assembly of the mRNA, tRNA, and ribosomal subunits.
• The first tRNA occupies the P site of the ribosome. The next tRNA
molecule corresponding to the second codon on the mRNA strand
will bind at the A site adjacent to the P site.
E lon ga tion : The amino acid sequence is extended as new tRNAs bring amino
acids (corresponding to mRNA codons) to the ribosome.
• The mRNA codon is recognized by the ribosome and the tRNA

with the appropriate anticodon and amino acid is transported to
the ribosome complex.
• tRNA binds to mRNA at the A site of the ribosome (requires GTP).
• A peptide bond is formed between tRNA amino acids at the A and
P sites.
• The empty tRNA at the P site dissociates from the ribosome, fol
lowed by translocation of the mRNA sequence in order to vacate the
A site for a new tRNA.
• This process continues until a stop c o d o n is reached.
T erm in a tion : The stop codon serves as a signal for the activation of peptidyl
transferase, an enzyme that cleaves the remaining bond between tRNA
and the peptide chain. A release factor will also bind to the ribosome,
causing disassembly of the ribosomal complex and release of the peptide
chain into the cytoplasm.
Post-translation Protein Modification
Most proteins are chemically inactive after translation. The production of most
membrane, lysosomal, and secreted proteins is completed within the rou gh
E R . Examples of post-translation modifications include (11):•
• Proteolytic cleavage: Occurs with digestive enzymes (trypsinogen to trypsin),

clotting factors (prothrombin to thrombin), and hormones (proinsulin to
insulin).
• Disulfide bond formation.
• Glycosylation (addition of sugars): Occurs with ABO blood group deter

minants and immunoglobulins.
After modification in the rER, proteins are transported to the Golgi apparatus.
• The Golgi apparatus modifies proteins by adding certain groups that

serve as a signal for the final destination of the proteins.

262 6.7. MOLECULAR B IO L O G Y - DNA, RNA, TECHNIQUES
• Proteins are then sorted into different transport vesicles that bud from the
Golgi apparatus and travel along specific secretory pathways to deliver
the proteins to their final intra or extracellular destinations.
Protein modification and secretion is regulated by hormones, neu-

rotransmittcrs, and digestive enzymes (depending on the specific
tissue) (5).
R eg u la tion o f G en e E xpression
Gene expression is dependent on the regulation of DNA transcription. The

control of transcription may occur in two ways:
The physical access of RNA polymerase and transcription factors to DNA

may be limited or enhanced.
• The degree of compaction of chromatin in the region of a gene will

determine the ability of the necessary proteins and enzymes to gain
access to that gene to initiate transcription.
• Remember that heterochromatin is tightly condensed, preventing
transcription, E u ch rom atin is loosely condensed, promoting tran
scription.
The rate o f b in din g of RNA polymerase and transcription factors to the

DNA strand of interest may be increased or decreased.•
• Transcription factors bind to specific DNA sequences (e.g. CAAT

box, TATA box, CG box) and will promote or inhibit the binding
of RNA polymerase to the promoter region.
• E nhancers are DNA sequences that bind to transcription activa
tion factors. Silencers are DNA sequences that bind to transcrip
tion in h ibition factors.
• S teroid h orm on es and grow th factors that bind to intracellular
receptors often function as transcription activators to promote gene
expression.
Tamoxifen, used in the treatment of breast cancer, prevents es

trogen from binding to intracellular receptors and decreases gene
expression in tumor cells within breast tissue (11).

Errors that occur during DNA replication, or alterations in DNA structure

from environmental factors, lead to a change in the DNA sequence and the
production of non-functional proteins. M ism atch repair en zym es detect
distortions in the DNA helix due to mismatched or damaged bases. The repair
enzymes remove the incorrect sequence and synthesize a new DNA fragment.
DNA ligase then seals the new fragment to the rest of the DNA strand. Ex
amples of DNA base alterations include:
• Cytosine may spontaneously deaminate to uracil, changing a GC base

pair to an AU base pair.
• P ry im id in e dim ers (two thymines linked together on the same strand)

are often produced by excessive exposure to UVB light and lead to dis
tortion of the DNA helix.
• G u an in e bases in DNA may become methylated when exposed to alky

lating agents (e.g. antineoplastic drugs).
• Both DNA strands may become damaged if exposed to ionizing radiation

or free radical oxidation.
M u ta tio n s are alterations in the DNA sequence that escape detection by

proofreading and repair enzymes, resulting in permanent changes to the cell
genome that will be passed on to subsequent generations through cell division.
Radiation, UV light, chemicals, and certain viruses can cause ge

netic mutations.
There are several different types of mutations that may or may not alter protein
function:
A p o in t m u tation involves a change in a single nucleotide base. They may be

transition mutations (purine for purine) or transverse mutations (purine
for pyrimidine). Point mutations may have three possible outcomes:•
• Silent m u tation : The new codon specifies the same amino acid as
the original codon.
• M issen se m u tation : The new codon specifies a different amino
acid, leading to an alteration in protein function (e.g, missense
mutations lead to altered hemoglobin in sickle cell disease).
• N on sen se m u tation : The new codon is a stop codon, causing
premature termination of protein synthesis and the production of a
nonfunctional protein.

264 6.7. MOLECULAR B IO L O G Y - DNA, RNA} TECHNIQUES
Fram eshift m u tation s occur when the addition or deletion of nucleotides

causes a shift in the reading frame of codons during translation of mRNA,
resulting in the production of an incorrect amino acid sequence. These
mutations are often nonsense mutations.
T rin u cleotide rep eat m utations are caused by errors in DNA replication
that result in an abnormal number of repeated trinucleotides within a
gene.
Huntington’s disease, fragile X syndrome, and myotonic dystrophy

are examples of trinucleotide repeat disorders. These disorders
tend to increase in severity with each successive generation (i.e.
anticipation) due to lengthening of the trinucleotide repeat.
T ran slocation s involve the movement of part or all of a gene to another lo
cation within the DNA, resulting in inappropriate activation or inhibition
of gene expression.
Mutations may involve a gain o r loss o f an entire chrom osom e. Most

changes in chromosome number occur during meiosis when homologous
chromosomes fail to separate properly, resulting in some gametes having
fewer chromosomes compared to other gametes,
• D o w n ’s sy n d rom e is due to an extra copy of chromosome 21.
D N A M u ta tion s and C an cer
Most cancers are disorders that result from an accumulation of multiple muta
tions within cells over time. The development of cancer is primarily associated
with mutations in the following genes (11):
P r o to on cogen es produce proteins that inhibit cell apoptosis and/or pro

mote cell proliferation. Mutations in protooncogenes convert them into
oncogenes.
• Oncogenes are genes that produce normal proteins in excessive amounts.

Only one copy of an oncogene is necessary to produce an effect (dom
inant inheritance).
T u m or suppressor genes produce proteins that promote cell apoptosis

and/or inhibit cell proliferation. Mutations resulting in loss of function
of tumor suppressor genes promote uninhibited cellular proliferation and
increase the risk for cancer.

• Tumor suppressor genes are recessive alleles. Both copies of the gene
must be mutated in order to have an effect on cell function.
Mutations in tumor suppressor genes have been associated with

breast cancer, o p tic nerve gliom a in neurofibromatosis, and
retin ob la stom a (11).
Defects in D N A repair genes increase the risk of DNA damage and subse
quent development of cancer.
A p o p to sis is a process of programmed cell death, termed “cell

suicide,” and is used to protect the organism by destroying cells
that represent threats.
We now summarize the cell cycle, which includes the following stages (10,
ch. 13):
G l : Period of cell growth and preparation of chromosomes for DNA replica

tion.
S: DNA synthesis and replication occurs.
G 2 : Organelles are duplicated as the cell prepares for mitosis.
M (m ito sis): The process of cell division that occurs in the following 4 stages:
1. P rop h a se: Chromosomes (composed of two identical chromatids

joined by centromeres) condense and the mitotic spindle forms (ma
chinery that pulls chromatids to the periphery).
2. M eta ph a se: Chromosomes line up at the equator of the cell.
3. A n aph ase: Chromatids separate at the centromere and are pulled
to opposite edges of the cell by the mitotic spindle.
4. T elophase: The cell separates into two cells in a process known as
cytokinesis.

Mitosis
Figure 6.6:
Biochem ical T echniques .j V? ^ \ :''N v i ;

G en om ics is the study of the structure and function of the genome, the
complete set of DNA within a single cell in a given organism. It involves DNA
sequencing and the use of recombinant DNA to search for target DNA sequences
of interest. P ro teom ics is tied into genomics and involves the study of the
complete set of proteins (i.e. the proteome) produced by a cell at any given
time. Proteomics involves the separation and identification of proteins and
their particular functions. We will now introduce techniques used in genomics
and proteomics that allow for more effective DNA and protein analysis (9,
ch. 9).
P olym erase C hain R e a ctio n (P C R ): Used to amplify quantities of DNA.

PCR uses a DNA polymerase that is capable of functioning in high temper
atures that are necessary for unwinding the DNA helix. Self-designed RNA
primers are used to amplify the DNA sequence of interest (you must know the
DNA sequence you wish to amplify!). PCR involves the following steps:
• Heat DNA to approximately 100 degrees C to promote natural unwinding

of the double helix.•
• Cool to a temperature that allows the RNA primers to bind to the single
strands of DNA.
• DNA polymerase will synthesize a new DNA strand from the RNA primers.
• The solution is heated once more to repeat the process.

S ou th ern B lo t: This technique is used to detect the presence of a specific

gene (or DNA strand) within a sample of DNA, The process occurs in the
following steps:
• The target DNA sequence is separated from the sample DNA using re
striction en zym es that cleave DNA at specific locations (you must know
the target sequence you are looking for in order to select the appropriate
restriction enzymes!).
• The digested DNA is run on an agarose gel using electrophoresis.
• The DNA is chemically denatured and then transferred to a special blot

ting membrane.
• Complimentary binding strands to the DNA sequence of interest are la

beled (often with a fluorescent tag) and applied to the blotting membrane.
Fluorescent areas on the blotting membrane indicate the target DNA is
present.
W estern B lo t is used to detect specific proteins within a tissue.

N o rth e rn B lo t is used to detect specific RNA sequences.
C h ro m o so m e A nalysis: Also known as a karyotype, this technique involves

an analysis of the number and structure of chromosomes within a sample of
cells to ensure the correct number of chromosomes are present and to detect
any deletions, duplications, or rearrangements of chromosomes. Cells may be
taken from the blood, bone marrow, strand of hair, from a swab applied to
the inside of the mouth, or from the amniotic fluid surrounding a fetus (i.e.
amniocentesis). Chromosome analysis is often recommended for the following
conditions (14):
• Problems with early growth or development in children.
• Stillbirths or neonatal deaths.
• Difficulties with fertility.
• Pregnancy or delivery in women 35 years or older.
• Family history of chromosomal disorders.
Chromosome analysis will not be able to detect small alterations

in chromosome structure or single genetic disorders.

268 6.7; MOLECULAR B IO LO G Y - DNA, RNA} TECHNIQUES
M olecu la r T h erap y
G en e therapy is an experimental technique that involves the introduction

o f a specific gene into cells for three major purposes (15):
• Replace an abnormal gene with a healthy copy of the gene.
• Inactivate a mutated gene that is functioning improperly by inhibiting

transcription or mRNA translation (e.g. anti-sense therapy)
• Provide a new gene that will produce a protein that will fight or prevent
disease.
Because genes that are inserted directly into the cell usually do not function,
genes must be incorporated into various carriers that will deliver the gene to
the cells of interest. The most common carrier used to date are viruses that
have been modified so they cannot cause an infection when injected inside the
body. Although gene therapy and anti-sense therapy are promising treatments
for genetic conditions, the techniques and carriers involved are risky and are
still under study to ensure the treatment is safe and effective for humans. Gene
therapy is currently only being researched for the treatment of diseases that
have no cure.
V itra ven e is the first FDA-approved anti-sense drug for the treat
ment o f C M V retin itis in immunocompromised patients (6).
R eferences
[1] Appleton J. Arginine: Clinical potential of a semi-essential amino acid. Altern Med Rev
2002;7(6):512-522.
[2] Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: WH Freeman, 2002.
[3] Bhagavan NV. Medical Biochemistry. 4th ed. San Diego: Harcourt/Academic Press, 2002.
[4] Bhuslian, Vikas, Le, Tao, Amin, Chirag. First Aid for the USMLE Step 1. New York;
McGraw-Hill, 2003.
[5] Cooper GM. The cell: A molecular approach. 2nd ed. Sunderland (MA): Sinauer Associates,
2000.
[6] Dias N, Stein CA, Antisense oligonucleotides: Basic concepts and mechanisms. Mol Cancer
Ther 2002(1);347.
[7] Insel P, Turner RE, Ross D. Nutrition. 2nd ed. Sudbury: Jones and Bartlett Publishers, Inc.,
2004.
[8] Jones L, Essential fatty acids and dry eye: What do we know? Research Review, Contact
Lens Spectrum; July, 2000,

[9] Lodish H, Berk A, Matsudaira P, Kaiser C> Kreiger M, Scott M, Zipursky S, Darnell J.
Molecular cell biology. 5th Ed. New York: WH Freeman, 2004.
[10] Nelson D, Cox M. Lehninger Principles of Biochemistry. 3rd ed. New York: Worth, 2000.
[11] Pelley JW, Goljan EF. Rapid review biochemistry. 3rd ed. Philadelphia: Mosby, 2011.
[12] Zubay G. Biochemistry. 4th Ed. McGraw-I-Iill, 1998.
[13] http:/ /w w w .eye world .org/article.php?sid=338 5
[14] http://genetics.emory.edu/docs/EmoryHumanGeneticsChromosomeAnalysis.PDF.
[15] http://ghr.nlm.nih.gov/handbook/therapy/genetherapy.
[16] http://www.indstate.edu/thcme/mwking/protein-structure.html.
[17] http://en.W ikipedia,org/wiki/Antibody
[18] http://www.vivo, colosta te. edu/hbooks/pathphys/tnisc_topics/radicals. html.

c
c·
c--
("■
c
('
((
(:
(
((
(( ■
(( .
((
((
(
((
(
(
((
((
((
((
((
((
(( . :
((
cC,
(( ,
(.
(_.
(( ,
c.
(_
Chapter
Microbiology
Melissa A . Cheatham, M P A S, P A-C
271
C
(
(
272
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(.
I
c
CHAPTER 7. MICROBIOLOGY 273
SECTION 7.1
B acteriology
[Eukaryotic vs. iV p . ' 'C.'-..; PY Y y- ■
Distinguishing Differences
EUKARYOTES PROKARYOTES
Include Algae, fungi, protozoa Bacteria
Plants and Animals Archaeobacteria
Nucleus YES NO
Membrane Bound MANY NONE
Organelles
Cell Wall Simple Cell Wall Complex Cell Wall
No Peptidoglycan Layer With Peptidoglycan
Ribosomes 80S (60S and 40S subunits) 70S (30S and 50S subunits)
Mitosis and Meiosis YES NO
Phagocytosis and YES NO
Pinocytosis
GRAM NEG. GRAMPOS.
Lipopolysaccharide
and Protein
Peptidoglycan
Membrane
Figure 7.1:

274 7.1. BACTERIOLOGY
Almost all bacteria, except for m ycoplasm a and archaeobacteria, have strong
cell walls that provide shape and protection. Different characteristics are seen
in gram positive and gram negative cell walls.
G ram (-)-) Cell wall consists of a single (20-80 nm) thick peptidoglycan layer
ou tside the plasm a m em brane. This layer contains techoic acids (polymers
of negatively charged glycerol) that serve the following functions:
• Provide the Gram (+ ) cell wall with its negative charge (14).
• Act as antigens to differentiate between various bacterial strains.
• Aid in bacterial adhesion to target host cells.
Techoic acids are relatively porous to multiple molecules, including antibi

otics (16). Gram (+ ) bacteria will stain pu rp le because of the thick, exposed
peptidoglycan layer.
G ram (-) A more complex cell wall that consists of a single, thin (2-7 nm)
peptidoglycan layer surrounded by a thick (7-8 nm) outer membrane. Gram (-)
bacteria will stain red because the outer membrane prevents dye from staining
the peptidoglycan cell wall. The outer membrane serves as a protective barrier
and contains the following components:
L ip opolysa cch a rides (L P S s): Large complex molecules composed of lipid

and carbohydrates that gives the outer membrane its negative charge.
LPSs consist of lipid A, a core polysaccharide chain, and an O-antigen (14) (7).
Lipid A: A phosphorylated glucosamine disaccharide with multiple fatty

acid chains. Lipid A is attached to the outer membrane and acts as
an en d otox in , causing symptoms associated with many gram (-)
bacterial infections.
Core polysaccharides: A branched polysaccharide that is attached to lipid
A on the outer surface. The structure varies among different bacte
rial species (16).
O side chain (O-antigen): Short polysaccharide chains that extend from
the core polysaccharide on the outermost portion of the LPS. O-
antigens are easily recognized by antibodies. Gram (-) bacteria can
quickly change O-antigen structure, helping them to avoid detection
by the host immune system.
P orin protein s: Form channels located within the outer membrane that al
low small hydrophilic molecules (including some antimicrobials) to pass

through, while limiting entry of large or hydrophobic molecules. The sus

ceptibility of bacteria to certain antibiotics is influenced by the ability of
the antibiotics to pass through porin channels.
The periplasmic space, located between the outer membrane and cytoplasmic
membrane, is filled with digestive enzymes (e.g. beta-lactam ase) and various
transport proteins.
Gram POSITIVE stains PURPLE. Gram NEGATIVE stains

RED.
Because peptidoglycan is critical for maintaining bacterial cell

structure, it serves as a major target for various antibiotics. Bac
itracin, penicillins, cephalosporins, and vancomycin interfere with
cell wall synthesis, leading to bacterial cell lysis and death (16).
jBacter ial G ro w th AV;.; v -

Life cy cle : Most bacteria undergo binary fission, a form of asexual repro
duction that occurs in three stages:
• I (in itia tion ) p e r io d - The bacterial cell elongates.
• C p e r io d - The bacterial chromosome replicates and proteins needed for

cell division are synthesized.
• D (d iv ision ) p e r io d - The plasma membrane pinches inward, pulling

the peptidoglycan cell wall in with it. The cell wall thickens and divides
the original cell into two daughter bacterial cells (14).
P h ases o f B acterial G row th
• Lag phase: Cells are active and grow without dividing.
• L og phase: Cells are growing and divid in g at an exponential pace

during this peak period of activity. Antibiotics are most effective when
used during this stage.
• S ta tion ary phase: Cell number remains constant. This period usually
begins when an essential nutrient for bacterial survival becomes depleted.•
• D ea th phase: Population declines as the dead cells outnumber the living

cells.

A e r o b ic vs. A n a erob ic B a cteria
A e ro b ic organism s require oxygen for growth and survival.
• O bligate aerobes are organisms that are COMPLETELY dependent on

oxygen for survival. Almost all higher organisms fall into this category
as O 2 is the final electron acceptor in the electron transport chain.
A n a erob ic organism s CANNOT survive in the presence of O2 . Fermenta

tion or anaerobic respiration is utilized for energy with an inorganic substance
serving as the final electron acceptor.
• Facultative anaerobes do not require O 2 for growth but will grow

better in its presence (14).
S p ore form ation : G ram (-}-) rod s can form endospores when nutrients are
limited. Endospores have no metabolic activity and provide protection against
excessive heat, UV radiation, chemicals, and dehydration.
Examples of spore forming bacteria include B acillus anthracis

(causing anthrax) and C lostrid iu m botu lin u m (causing bo
tulism) .
G enetic M echanism s of B a cteria - A 'AA
The bacterial cell genome is composed of a single, double-stranded circular

DNA molecule. Some bacteria may also have plasm ids, which are small, cir
cular extrachromosomal segments of DNA that can replicate independently of
the bacterial chromosome and often contain drug resistance or tox in genes.
Although bacteria replicate via asexual binary fission, they are capable of trans
ferring genetic information through several different mechanisms (16):
T ransform ation: A segment of DNA is taken up by the cell and incorporated

into the bacterial chromosome.
T ransduction: A segment of DNA within a phage particle is taken up by

the cell and incorporated into the bacterial chromosome,
C on ju gation : A segment of DNA is directly transferred from a donor cell

(male) to a recipient cell (female). This transfer occurs via a sex pilus
that forms a channel (i.e. “mating bridge”) in between cells. Proteins
necessary for the formation of a sex pilus are encoded by an F plasm id
within the donor cell.

T ra n sp osition : A tra n sp oson (aka “jumping gene”) is a DNA sequence that

can move from one position to another within a bacterial chromosome or
between different molecules of DNA.
* Simple transposons only contain the genes necessary for movement.

* Complex transposons consist of other genes (e.g. drug resistance
genes) in addition to those genes necessary for movement.
* Pathogenicity islands are large transposons that contain all the genes
necessary for initiating a certain pathogenic mechanism of disease.
N o rm a l B o d y F lora
We are essentially covered in bacteria! Non-sterile areas in the body, such as

the GI and urogenital tracts, mouth, pharynx, skin, and eyelids, are home to
normal bacterial flora that allow the body to function properly (e.g. E. coli in
the colon aids in the breakdown of food). When normal body flora is destroyed
by antibiotics or other pathologies, new competing and often drug-resistant
bacteria may begin to grow excessively, resulting in disease (16).
jSpecific B a cteria > '■/ ... . y.- .... c d : ■.7 ,; '- .
G R A M P O S IT IV E C O C C I
S ta p h y lo co ccu s aureus
• Gram (+ ) cocci that grows in clusters.
• C atalase ( + ) and C oagulase (-(-)
— Catalase decreases the risk of bacterial phagocytosis by converting

H20 2 to H20.
— Coagulase helps to isolate an infection by forming a fibrin layer
around an abscess.
• May produce penicillinase (i.e. bet a-lactamase), an enzyme that cleaves

the beta-lactam ring found in penicillins and cephalosporins, providing
resistance against these antibiotics (16).•
• Part of the normal body flora. It is found in much lower concentrations

than Staph epidermidis, but causes more severe ocular infections.
Approximately half of all ocular infections are caused by Staph

aureus (1).

• May contribute to con ju n ctiv itis, blepharitis, bacterial keratitis,

hordeola, abscesses, boils, and acute bacterial endocarditis (an infection
of the heart valves).
• S ta p h y lococca l h ypersen sitivity results from chronic staphylococcal

blepharitis. The excessive growth of Staph aureus on the lid margin
causes a bilateral hypersensitivity reaction with formation of infiltrates
near the corneal limbus (see ocular disease chapter for further details).
T O X IC S H O C K S Y N D R O M E is a rapid infection caused by

Staphlyococcus aureus that leads to high fever, vomiting, and wa
tery diarrhea. The entertoxins released by Staph act as super
antigens, binding directly to T4 lymphocytes to induce an immune
response. This condition is most commonly due to food poisoning
or prolonged female tampon use (16).
S ta p h y lococcu s epiderm idis
• Gram (+ ) cocci that grow in clusters. Staph epidermis is more prevalent

than Staph aureus, but is less pathogenic. These bacteria are found on
the skin and mucous membranes.
• Catalase (+ ) but coagulase negative.
• M o st co m m o n cause o f acute p osto p e ra tiv e endophthalm itis (9).
• May contribute to stitch abscesses or endocarditis and commonly adhere

to vascular catheters, shunts, and prosthetic joints (3) (16).
B acterial con ju n ctivitis (caused primarily by S. aureus, S. epi

dermidis, or S. pneumoniae) is much more common in children. It
is characterized by rapid onset and mucopurulent or purulent dis
charge that commonly causes the eyelids to be stuck together upon
awakening (see ocular disease chapter for further details).

S tr e p to c o c cu s pn eu m on iae
• Gram (+ ) cocci that are falcultative anaerobes, classically grow in pairs,

and are catalase (-) (3).
• Can cause p e d ia tric bacterial con ju n ctivitis and corn eal ulcers.
• Most common cause of bacterial pneumonia, meningitis and otitis me-

dia. (18) (19).
Eyelid infections such as blepharitis and hordeola are caused by

gram p o sitiv e bacteria. Topical ointments (bacitracin, ery
thromycin, and polysporin) and oral agents (dicloxacillin and doxy-
cycline) are common gram positive fighting drugs (see pharmacol
ogy chapter for complete list).
S tr e p to c o c cu s pyogenes
• Gram (+ ) cocci that grow in chains and are catalase (-). Referred to as
G ro u p A Strep.
• Common cause of bacterial pharyngitis (i.e. strep throat). May also

cause scarlet fever, rheumatic fever, impetigo, and toxic shock (16).•
• R a re cause o f ocu la r in fections including conjunctivitis, dacryocys

titis, and central corneal ulcers (among others).
C an you tell th e difference? If you are culturing gram posi

tive bacteria, the main way to separate Staph and Strep is by the
catalase test.
• Staph are catalase positive
• Strep are catalase negative
To differentiate Staph aureus from other forms of Staph, perform

the coagulase test:
• Staph aureus is coagulase (+ )
• All other Staph specise are coagulase (-)

G R A M P O S IT IV E R O D S
Bacillus anthracis
• Large spore forming, aerobic, non-motile bacteria that grow alone or in

short chains.
• Can cause anthrax in humans, especially if handling wools, furs, or hides (16).
Clostridium
• Gram (-J-), motile (except C. perfringens), obligate anaerobe rods that

can produce spores.
• C. perfringens causes gas gangrene.
• C. botulinum causes botulism.
• C; tetani causes tetanus.
Corynebacterium diptheriae
• Curved or club shaped gram positive rods that tare non-motile and aero
bic.
• Causes diphtheria (3).
• Can penetrate an intact corneal epithelium!
Gram(+) rods are NOT common sources for ocular infection (1).
G R A M N E G A T IV E R O D S
P seu d om on as aeruginosa
• Motile, oxidase positive, Gram (-) aerobic rod with 1-3 flagellae.
• Has a grape juice odor and produces blue/green pigment.
• C om m o n w ith corn eal ulcers in con ta ct lens wearers, burn vic

tims, and immunocompromised patients.

P se u d om on a s . A L E R T ! These patients will present with a

painful red eye with thick mucopurulent discharge, often accom
panied by hypopyon. Corneal ulcers are the main concern - treat
with gram negative fighting antibiotics such as fluoroquinolones (9).
Haemophilus influenzae
• Non-motile, gram (-) rod that causes upper respiratory tract infections,
otitis media, sinusitis, pneumonia, and meningitis (1).
• C o m m o n cause o f in fections in children - esp ecially otitis m edia,

w hich is o ften seen con cu rren tly w ith con ju n ctiv itis (1). The
incidence of H. influenza has decreased dramatically since a vaccine was
introduced against H. influenza type b.
• Culture: Chocolate Agar (Thayer Martin Agar).
G R A M N E G A T IV E C O C C I
N eisseria g on orrh ea
• Non-motile, aerobic, Gram (~) diplococci that are sexually transmitted

or passed on to an infant as he/she descends through the birth canal.
• C an cause a severe vision threatening corneal ulcer that m ay

result in corn ea l p erfora tion (11).
• Neonates infected with ocular N. gonorrhea during birth may be treated

with silver nitrate or erythromycin ointment.•
• Culture: Chocolate Agar (Thayer Martin Agar).
G o n o c o c c a l B acterial C on ju n ctivitis is a rare, bilateral con

dition characterized by h yperacu te on set of excessive mucopu
rulent discharge. Gram stain for N. gonorrhea will show gram-
negative intracellular diplococci.

Neisseria meningitidis
• Coffee bean-shaped, aerobic, Gram (-) rods that appear as individual

bacteria, in pairs, or tetrad groupings.
• Causes meningitis.
• Cultured on blood agar (3).
Moraxella catarrhalis
• Coffee bean-shaped, beta lactamase positive, gram (~) cocci.
• Causes pseudogonococcal conjunctivitis and angular blepharoconjunc

tivitis.
• Associated with shared eye makeup.
Bordatella pertussis
• Minute coccobacillus that are slow growing, non-motile, and aerobic.
• Causes the Whooping Cough (19) (13).
G R A M N E G A T IV E E N T E R IC B A C T E R IA
Escherichia coli
• Non-encapsulated gram negative rods that may be motile or non-motile.

They are part of the normal flora of the GI tract.
• Can cause conjunctivitis, corneal ulcers and endophthalmitis (1).
• Causes gastrointestinal (epidemic diarrhea), urinary tract, wound, and

respiratory tract infections.
Klebsiella pneumoniae
• Straight, aerobic, and citrate positive rods.
• Causes pneumonia, sinusitis and pharyngitis (3) (19).
Proteus mirabilis
• Straight, motile, aerobic rods that demonstrate swarming growth when

cultured on Endo agar.•
• Inhabit the GI tract and cause gastritis, diarrhea and urinary tract in
fections (3).

S erratia m arcescens
• Very short, plump, motile, aerobic rods that are found in water, soil, and
milk and grow well on un-enriched media.
• Produce a characteristic red pigm ent (3).
• When pathogenic, patients become critically ill with considerable mor

tality.
O T H E R B A C T E R I A - N O T C L A S S IF IE D B Y G R A M S T A IN
A ctin o m y ce te s
• Non-motile, non acid-fast, anaerobic rod that will Gram stain slightly
positive. Best seen by direct examination on wet mount or on thioglycol-
late broth.
• Present in normal oral flora and can cause oral and facial abscesses with
sulfur granules that can drain through the sinus tracts in the skin. May
also cause severe pulmonary infections.
M y co b a c te r ia
• Aerobic rods that are weakly gram positive and acid-fast organisms.
• Mycobacterium tuberculosis causes tuberculosis (TB), with symptoms

including fever, night sw eats, and w eight loss (19).
• Respiratory transmission through air droplets'causes a granulomatous

reaction that will ultimately wall off the bacteria in the lungs.
• A TB skin test, chest x-ray, and sputum cultures are necessary for diag
nosis.
• Mycobacterium leprae causes leprosy.
Spiral-shaped bacteria with axial filaments; includes Borrelia, Leptospira, and

Treponema (3).
T re p o n e m a pallidu m
• Sexually transmitted disease that can be congenital or acquired.

• RPR (rapid plasma reagent card test) and VDRL (Venereal Disease Re
search Laboratory) testing for active disease (17). Fluorescent trepone
mal antibody absorption (FTA-Abs) test detects antibodies against the
spirochete and is used to determine if a patient has ever been infected
with the disease (15).
• Causes Syphilis - P resents in 3 stages:
1. Primary: Chancre sore at the site of entry of the infection.

2. Secondary: Fever, sore throat, skin rash, hepatitis, and con ju n c
tivitis.
3. Tertiary: Neurological and/or cardiovascular abnormalities. Can
cause the patient to be blind, deaf, and/or insane. C on ju n ctivitis
is also seen in this stage (19) (11) (17).
A r g y ll-R o b e rts o n p u p il and interstitial keratitis are two oc

ular findings in syphilis.
C h lam ydia T rachom atis
• Obligate intracellular parasite (similar to viruses) that causes mucosal in

fections (11). It is very common in 3rd world countries due to unsanitary
conditions.
• Chlamydia is also similar to bacteria in that it contains DNA and RJSfA

and is inhibited by antibiotics (18).
• C hlam ydial In clu sion C on ju n ctiv itis is a chronic, sexually trans

mitted condition (50% have a concomitant genital infection) caused by
Chlamydia trachomatis serotypes D-K (12). It is usually unilateral and
is characterized by the presence of limbal or palpebral follices that are ,
most concentrated in the inferior p alp ebral fornxces.•
• T rachom a C on ju n ctivitis is caused by Chlamydia trachomatis serotypes

A-C. It is most prevalent in countries where hygiene is poor, and is cur
rently the leading cause of preventable blindness in the world (due to
corneal ulceration) (15).

C h la m yd ia is the num ber one bacterial S T D in the United

States (17). Ocular manifestations include a chron ic red eye and
large in ferior palp ebral conju n ctival follicles (19). These
findings warrant a consult with a primary care provider for STD
testing.
O ph th alm ia n eon a toru m is acute con ju n ctivitis in the new

born from any source. The leading cause of this condition in the
United States is C h lam ydia (10).
R ick ettsia
• Non-motile, gram negative, obligate intracellular parasites transmitted

by insect vectors (3), Commonly appears as coccobacillus with rigid cell
walls.
• Causes a classic triad o f sy m p tom s including headache, fever and

rash.
• Causes Rocky Mountain Spotted Fever through tick bites.
• Treatment is doxycycline.
M y co p la sm a
• Non-motile, facultative anaerobes that are pleomorphic in shape. My

coplasma organisms are unable to produce peptidoglycan and DO NOT
CONTAIN CELL WALLS! They are thus resistant to antibiotics that
inhibit cell well synthesis.•
• Mycoplasma pneumoniae causes primary atypical “walking” pneumonia.

Symptoms have an insidious onset and include a non-productive cough
and headache. May be treated with clindamycin, erythromycin, or azithromycin (19) (4).
Remember, if a bacterium has no cell wall, penicillin is not effective

because it is a cell wall synthesis inhibitor! This is why mycoplasma
is resistant to penicillin!

B lS iH S iS S S M M H B S E iE liliS IS i"
Culturing bacteria is based upon the nutritional and environmental require
ments o f different bacterial strains. These requirements include (but are not
limited to) preferred pH, O 2 level, and carbohydrate utilization. Please see the
end of this chapter for gram negative and gram positive flow charts - they will
help you categorize and differentiate the bacteria based on their unique char
acteristics. Several different methods may be used to obtain a pure culture:
1. Streak Plate Method: Using an inoculating loop, the specimen is “streaked”

over an agar plate. The pipette is flamed to sterilize, and an additional
streak is made through the first streak. This process is continued until
you have an isolated colony (3) (14).
2. Spread plate method: The specimen is diluted in solution and then, using
a glass rod, the bacteria are spread across the entire surface of an agar
plate.
3. Pour plate method: Much like the spread plate method, the specimen is
diluted in solution and then poured onto the media.
4. Enrichment Culture: A specific bacterial specimen can be isolated from

a sample by using selective growth agar tailored to the specimen in ques
tion. Examples include Thayer-martin Agar, Endo agar, etc. (3) (14).
p ro c e d u re s for A n tibiotic S usceptibility Testing- . 5

The two most widely used methods for susceptibility testing are the Kirby-
Bauer agar-diffusion and the broth serial-dilution methods (3) (14).
Kirby-Bauer agar diffusion
The specimen is diluted and poured onto an agar plate. Disks of different
antibiotics are then applied to the inoculated agar. After a period of incubation,
the zones of clearing around the disks are measured to see which antibiotics
the bacterium are resistant, intermediate, or susceptible to.
Broth Serial-Diluted Method
A series of tubes are prepared with broth and predetermined amounts of an
tibiotic in descending concentrations. Bacteria is inoculated into each tube
and incubated for a period of time. The lowest concentration of antibiotic in
which the bacteria are unable to grow is the minimal inhibitory concentration
(MIC) (3) (14).

AN710BIOTIC SU5CEPTJBILITYTEST
Figure 7.2: Kirby-Bauer Agar Diffusion
jQuality C o n tro l, S terilization an d D isinfection

• Sterilization is the elimination of all microbes from a given surface.
Sterizilation is absolute - the surface is either sterilized or it is not. Re
moval of spores for sterilization is generally achieved through an au to
clave that is set at 121 C (250 F ) for 15 m inutes.
• D isin fection refers to the reduction in the number of microbes on a given

surface. A disinfectant, which is a chemical agent employed to destroy
microbes, may or may not be able to sterilize a surface.
- SECTION 7 .2 -----------------------------------------------------------------------------------------------------
Virology *•
Viruses are obligate intracellular parasites that can reproduce only within living
cells. They contain either DNA or R,NA (never both) and do not contain any
organelles. Most viruses are too small to be visible with a light microscope and
are therefore viewed with scanning or transmission electron microscopes (14).
V iru s P a rticle C h em istry and M o rp h o lo g y
• Range in size from 10-300 um (smallest is the size of a ribosome, largest

is the size o f a bacterium).

288 7.2. VIROLOGY
• All viruses have a nucleocapsid core -> D N A/RNA within a protein coat
(capsid).
- The capsid protects and aids in the transfer of virus genetic material.
The shape of the capsid influences the overall shape of the virus (14).
'Classification Schem e f^ r V iruses A

D N A vs. R N A V iruses
• D N A en velop ed viruses: HSV (1+2), VZV, CMV, EBV, Hepatitis B,

and smallpox virus.
• D N A n u cleocap sid viruses: Adenovirus, papilloma viruses, and par

vovirus.
• R N A en velop ed viruses: HIV, measles, mumps, rabies and influenza.
• R N A n u cleocap sid viruses: Enteroviruses (poliovirus, coxsackievirus,

echovirus, Hepatitis A, rhinovirus, and rheovirus).
•Genetic M echanism s of V iruses / . p • -j
R ecom b in a tion : Occurs when genes are exchanged between two chromo
somes of very similar base sequences.
R eassort m ent: Very high frequency recombinations that are the cause of
worldwide epidemics. Occurs only in viruses with segmented genomes (they
exchange segments). Segmented viruses are in some RNA viruses, including
the influenza virus.
C om plem en ta tion : If two viruses infect a cell and one has a mutation that
causes it to produce a non-functional protein, the non-mutated virus will com
plement the mutated one by making a protein that provides for both.
P h e n o ty p ic m ixing: Occurs if one virus coats the other with its own surface
proteins. This is important as the outer core determines what cells a virus is
able to infect.
V iral R e p lica tion in H ost cells
DNA viruses replicate in the nucleus (except for poxvirus), RNA viruses repli
cate in the cytoplasm (except for the influenza virus and retroviruses (HIV)).

A D E N O V IR U S
• Polyhedral, non-enveloped, double-stranded DNA virus (40 different types).
• The most noted infections caused by adenovirus include ep id em ic ker

a to co n ju n ctiv itis (E K C ), pneumonia, and viral pharyngitis.
Epidemic keratoconjunctivitis (EKC) results from serotypes 8, 19

and 37 and is well-known for pain and corneal involvem ent
(80% of cases) (12).
H E R P E S V IR U S
H erp es S im p lex V iru s ty p e 1
• Primarily oral, but can occasionally be in the genital area.
• Polyhedral, double-stranded DNA virus that is enveloped.
H erp es S im p lex V iru s ty p e 2
• Primarily genital, but can occasionally be in the oral cavities.
• Sexually transmitted disease (17).
Both IiSV-1 and I-ISV-2 can cause keratoconjunctivitis (much more

commonly H S V -1.
V A R IC E L L A Z O S T E R V IR U S (V Z V )
Virus that causes chickenpox and shingles.
E pstein -B a rr V iru s (E B V )
• Virus that causes infectious mononucleosis.
• Has also been implicated as the cause of certain cancers.

290 7.2. VIROLOGY
C Y T O M E G A L O V IR U S (C M V )
• Can cause life threatening infections in im m u n ocom p rom ised patients.
• The most common ocular infection and the leading cause o f blindness
in A ID S . 10-34% of AIDS patients develop CMV retinitis (11, pp. 135).
CMV can cause uveitis and hemorrhagic retinitis with vascular

sheathing. It is prevalent in AIDS patients with C D 4 counts o f
less than 50.
P O X V IR U S
• Circular, enveloped, double-stranded DNA virus.
• Can cause m ollu scu m contagiosum , a skin condition characterized by

single or multiple umbilicated, waxy, dome-shaped nodules. Can cause
palpebral follicular conjunctivitis if nodules on the lid margin rupture.
• M u ltip le m ollu scu m n odu les should raise suspicion for H IV .
P A P O V A V IR U S
Circular, non-enveloped, double-stranded DNA virus.
H U M A N P A P IL L O V IR U S (H P V )
Causes genital warts and cervical cancer (17). This is the most common viral
STD in the United States, affecting up to 80% of the sexually active popu
lation (17). Physicians screen for this virus when performing a Papanicolaou
(Pap) smear.
H E P A T IT IS
H epatitis A - Spread through fecal-oral transmission. Causes a limited in

fection. A vaccine is available.
H epatitis B - This belongs to the Hepadnavirus family. It is the only Hep

atitis that is a D N A virus. It is primarily transmitted through blood, IV
drugs, and sex. A vaccine is available.

H ep a titis C - Has similar transmission routes and effects as Hepatitis B.

There is NO vaccine available for hepatitis C.
H ep a titis D - Carried only with Hepatitis B as a super-infection and in

creases the morbidity and mortality rate.
H ep a titis E - Transmitted through the fecal-oral route. No vaccine is avail

able.
Viruses cannot be cultured on broth-like media as can bacteria. They must

be reproduced in suitable host animals, embryonated chicken eggs, or grown
in tissue cultures of animals cells in Petri dishes exposed to the virus. The
destruction of the animal cells, or microscopic abnormalities in the host cells,
is referred to as c y to p a th ic effects.
Viruses can be isolated using several virus properties. The four properties are
listed for your reference only (DO NOT memorize this!):
1. Precipitation of viruses: Purified through concentrated ammonium sul

fate.
2. Differential and density gradient centrifugation: The viruses are cen

trifuged and separated into suspensions based on viral particle size.
3. Enzymatic digestion of cell constituents: Removal of cellular proteins and

nucleic acids through enzymatic degradation.
4. Denaturation of contaminants: Change in heat or pH can be used to

purify viruses. Different organic solvents are also used to extract lipids
from the viral preparations (14).
|Virus-like S tru c tu re s ^ t /
V IR O ID S
• Circular single-stranded RNA molecules.
• Transmitted between plants through mechanical means, pollen, and/or

ovules.•
• Viroids are smaller than viruses (only about 250-370 nucleotides long).

292 7.3. MYCOLOGY
P R IO N S (In fectiou s particles m ade o f p rotein s)
• Comprised of hydrophobic membrane proteins that cause disease in live

stock and humans.
• Scrapie is the best understood prion, and causes CNS degeneration in

sheep and goats.
• Unlike viruses and viriods, prions do not contain any nucleic acids (14).
“Mad Cow Disease” is a prion disease that causes progressive brain

degeneration and death (4) (5).
I - SECTION 7.3
M ycology
B IO L O G Y OF F U N G I •' ' ;. ' . ;

Fungi are eukaryotic, spore-bearing organisms with no chlorophyll that repro
duce both asexually and sexually. Fungi grow best in dark, moist environments,
but are found wherever organic material is present. Fungi use glycogen as their
primary fuel source; most use carbohydrates and nitrogenous compounds to
synthesize their own amino acids and proteins. Fungi are usually aerobic, al
though some yeast are facultative anaerobes and can obtain energy by fermen
tation. Fungi have many important functions, including decomposition and
fermentation.
These are eukaryotic, non-photosynthetic, obligate facultative aerobes.
L a b ora tory E xam ination o f Fungi
S a b ou ra u d ’s agar is a culture media used for the growth of fungi. Evaluation

of fungi are performed with the following methods (6):
1. Potassium hydroxide (KOH) solution.
2. Fungal culture.
3. Methenamine Silver stains (more sensitive than KOH testing or fungal

culture).

YEAST
• Unicellular fungus with one nucleus and many typical eukaryotic or
ganelles. Commonly spherical, larger than bacteria, and do not contain
flagella (3).
• Can reproduce sexually (transverse division) or asexually (through spore

formation).
M OLDS
• Multicellular fungus that consists of long, thread-like cell filaments called

hyphae (3). Hyphae are composed of an outer wall and an inner lumen
that contains cytosol and organelles.
• Multiple hyphae form a mass called mycelium. Cross-walls within the

hyphae (i.e. septa) distinguish some groups of fungi from others (3).
D IM O R P H IC F U N G I
• Dimorphic fungi are capable of shifting from a mold (in the external
environment) to a yeast (in the host) in order to cause disease in humans
and animals (14).
lAsexiial aih<i S exu ^ R eprodu ction ; tC :
A S E X U A L R E P R O D U C T IO N
1. Transverse fission: The parent cell can develop a fissure, forming a new
cell wall that splits the cell into two daughter cells.
2. Budding: Yeast often bud and produce new organisms.
3. Spore production: Occurs inside a fungus. Initiation occurs with mitosis,

and then subsequent cell division occurs. This is the most common form
of asexual reproduction utilized by fungi (14).
S E X U A L R E P R O D U C T IO N This process is initiated by the fusion of

hyphae of different mating strands. In some fungi, the nuclei fuse immediately
and form a zygote. In other fungi, the different nuclei remain separate and form
pairs that divide synchronously. In either case, sexual reproduction in fungi
requires fusion of two nuclei to form a zygote. Nuclear fusion yields production
of spores.

294 7.3. MYCOLOGY
F E R T IL IZ A T IO N Two fungi can unite sexually without fusion of nuclei.
Asexual and sexual reproduction produce spores! Asexual spores

are used to disperse the species. Sexual spores are used to aid in
the survival of the species in extreme environmental conditions.
Spores are also essential for differentiating fungal species based on
color, size, and shape (14).
Disease statq s, lYarisrnission, P ath o g en ic j

SUPERFICIAL M Y C O S E S
1. Dermatophyte infections
• Can only invade the stratum corneum of the skin, hair, and nails.
• Common sites of infection include the feet, nails, and hair.
2. Yeast infections (Candida albicans)
• Opportunistic infection that causes thrush and vaginitis.

• Much higher virulence in im m u n ocom p rom ised patients.
• Candida may overgrow after the use of antibiotics that decrease the
body’s normal flora.
• Diagnostic tests include a fungal culture and visualizing hyphae with
potassium hydroxide (6) (17) (19).
Remember from Pharmacology: Treatment of C andida includes

antifungals such as ketoconazole, mycostatin, and fluconazole (6).
C U TA N E O U S M YC O SE S
1. Tinea versicolor
• Caused by Malassezia furfur.

• Usually presents in hot, humid weather and is seen as hypopig-
mented lesions on the skin.
• Treat with topical miconazole or other antifungals (6).

CHAPTER 7 MICROBIOLOGY 295
2. Tinea nigra
• Caused by Cladosporium wernecldi.

• Causes a brownish spot on the outer keratinized layer of the skin.
• Treat with topical salicylic acid.
3. Tinea pedis, corporis, capitas, and cruris
• Caused by dermatophytes.
• Symptoms include pruritic lesions with central clearing (appears as
a ring).
SUBCUTANEOUS M YCOSES
Sporotrichosis (Sporothrix schenckii)
• Dimorphic fungus that lives on vegetation (e.g. thorn bushes, moss,

mulch)
• Causes local ulcers or pustules, as well as nodules on lymphatic vessels.
• Minor systemic involvement.
• Treat with itraconazole or potassium iodide.
S Y S T E M IC M Y C O S E S
Coccidioides immitis
• Causes an endemic infection in the Southwestern U.S. (California).
• The infection can be acute, benign, and non-progressive, or can be chronic

and fatal. The infection involves the skin, lymph nodes, kidneys, brain,
meninges, etc.
H istoplasm a capsu latu m
• Endemic infection in the Mississippi and Ohio River valleys (11).
• Caused by inhalation of spores from moist soil laden with the droppings
of birds, bats, and chickens.
• May present as acute, acute non-progressive, or chronic-progressive:
— Acute: Rarely fatal infection that lasts 1-6 months.

— Acute non-progressive: Usually fatal within 6 weeks and character
ized by a fever and weight loss.

296 7Jh PARASITOLOGY
— Chronic-progressive: May last for years; resembles chronic TB.
CLINICAL NOTE: H istoplasm osis is often seen as a classic triad

of peripapillary atrophy of the optic nerve, punched out peripheral
lesions, and maculopathy (12).
Candida albicans
• Common cause of fungal corneal ulcers.
• Can cause oral thrush in immunocompromised patients (e.g. diabetes,

steroids, AIDS, neonates). May also lead to vagnitis (e.g. diabetes, an
tibiotic use, high vaginal pH) (17).
Aspergillus fumigatus
• Mold that causes allergic bronchopulmonary aspergillus, lung cavity as-

pergilloma, and invasive aspergillosis.
Cryptococcus neoformans
• Heavily encapsulated yeast found in soil and pigeon droppings. Stains

with India ink and is cultured on Sabouraud’s agar.
• Causes cryptococcal meningitis and cryptococcosis.
Mucor and Rhizopus Species
• Molds that cause disease primarily in xmmunosuppressed and diabetic

patients.
• The mold has irregular branching hyphae (greater than 90 degree angles).
• It grows on the walls of the blood vessels and causes tissue infarction (3).
- SECTION 7.4 -----------------------------------------------------------------------------------------------------
P arasito lo g y
PATH O G EN IC M E C H A N IS M S Parasites can cause local necrosis at the

site of entry into the body. They may also enter cells, causing direct cell death

and immune damage. Parasites, such as malaria, can enter blood cells, causing
a change in the shape of the cell that ultimately results in organ dysfunction.
Some parasites, such as worms, may live in the digestive system for years,
absorbing nutrients and causing gastrointestinal discomfort.
C lin ical N o te : To culture a parasite in the eye, you can submit

the following to the lab:
1. A contact lens from the patient.
2. A swab brushed under the eyelid.
3. A corneal scraping.
[Disease S ta te s, Life Cycles, ^ a iis in is s io n , a n d ;S ym ptom s

M E T A Z O A (w orm s)
1. Trematodes (flukes)
• Infection caused by eating undercooked fish, crab meat, and snails.

• Adult worms, eggs, and secretions cause widespread inflammation
and tissue destruction.
2. Cestodes (tapeworms)
• Intestinal parasite transmitted by eating undercooked pork or from

ingestion of eggs from feces.
• Can cause mass lesions in the brain and/or anaphylaxis.
3. Nematodes (roundworms)
• Intestinal parasites that include hookworms and pinworms.

• Found in contaminated food and drinking water, soil, feces, and
mosquitoes (among others). Examples include the following:
- Enterobiasis: A pin worm that causes perianal itching, de
creased appetite, and insomnia.
- Onchocerca volvulus: Transmitted by female black flies; causes
river blindness.
- Loa loa: Causes skin and con ju n ctival sw elling (may see
worms within the conjunctiva).

298 74- PARASITOLOGY
AN TH R O PO ID S
Deraodex folliculitis (M ITES)
• Mites that are located in the hair follicles and sebaceous glands (include
the m eiboiraan glands.
• Will cause itching and a foreign body sensation. Commonly presents

with “sleeves” on the base of the eyelashes. Treatment includes vasoline
to smother the mites (6).
Pediculosis capitis (LICE)
• Common parasites, especially in schools and poverty stricken areas. Trans

mitted through contact with bedding, brushes, or clothing.
• Can be located on any hair shaft on the body. The females lay eggs (nits)
on the hair shafts, which hatch within 6-10 days after they are laid.
• Can cause chronic follicular conjunctivitis, with symptoms of itching

and burning.
• Treat with permethrin lotion (6).
Sarcoptes scabiei (Scabies)
• Very common in children, bedridden patients, and in areas of poverty.
• Scabies lives only on human skin and is transmitted via skin to skin
contact.
• Tunnel into the skin and deposit feces in the tunnels.
• Treat with permethrin lotion (6) (19).
O T H ER C O M M O N P AR ASITES
Plasmodium (Malaria)
• Plasmodium invades young red blood cells called reticulocytes. The

young blood cells then mature into pale, large, heme-deficient red blood
cells that are crescent shaped (sickle cells).•
• The destruction of red blood cells can cause blockage within capillaries,
leading to decreased organ perfusion.
• Patients may be asymptomatic, or complain of fever and chills.
• A blood smear will show Maurer’s dots and basophilic stippling (13).

Sickle cells may obstruct the small capillaries of the retina, leading
to sickle cell retin opath y. Patients are at risk for traction al
retin al deta ch m en ts due to retinal neovascularization (classically
“sea fan” in appearance).
G ia rd ia
• Heart-shaped parasite with flagella and two nuclei with large karyosomes.
• G. lamblia is spread through drinking contaminated water or through

contact with carrier's such as baby goats. It causes diarrhea.
• The parasite is identified by observing the ovum or egg in stool.
T ox op la sm osis g on dii
• Obligate intracellular parasite that is spread by exposure to infected cats

(through cat litter) or by ingesting undercooked meat. It is NOT trans
ferred from human to human.
• Toxoplasmosis causes 3 different syndromes:
— Acquired: The patient is usually asymptomatic.
— Congenital: Occurs as a result of transplacental transmission; causes

hydrocephalus or mental retardation.
— Immunocompromised patients often contract the acquired form of

toxoplasmosis that may come and go; causes pneumonitis and/or
myocarditis (19) (13).
T O X O vs. H IS T O : Toxoplasmosis infections start in the retina

and can spread to the choroid (retinochoroidal lesions). Histoplas
mosis infections start in the choroid and can spread to the retina
(chorioretinal lesions).

(
7.1 PARASITOLOGY
300
(
(
(
(
(
(
(
(
(
(
Enterococcus (
Figure 7.3: (
(
(
(
(
(
(
(
Figure 7.4: C
(
CHAPTER 7. M ICROBIOLOGY 3 01
P n e u m o cy stis jiro v e ci (form erly P n eu m ocy stis carinii)
• Inhaled yeast that causes pneumonia in im m u n ocom p rom ised pa

tients.
• HIV patients with CD4 counts < 200 should receive prophylactic treat
ment.
• Causes pink, frothy alveolar exudates in the lungs.
• Can silver stain the sputum for diagnosis.
A ca n th a m o e b a
• Associated with contact lens over wear and/or inadequate contact lens
hygiene (tap water, homemade saline solution, swimming or hot-tub use
while wearing contact lenses).
• Patients will often present with sy m p tom s that outw eigh clinical
signs,
• Acanthamoeba often progresses to a classic ring ulcer.
• Culture should be performed with a non-nutrient agar with heat-ldlled

E .C o li (20).
T rich om on a s vaginalis
• Trichomonas has pyriform flagellate and is colorless and very motile.
• A sexually transmitted disease that causes vaginitis (17).
• Patients may be asymptomatic, or complain of extreme itching and irri

tation.
• Direct visualization under the microscope on a wet smear is diagnostic

for the condition.
• Treat with metronidazole (17) (19) (13).
jLabm atdry Identification of P a ra s ite s ; ’ A" A A - - :

Most, if not all, parasites are identified by direct examination under the micro
scope. The following are different methods for looking at parasites:•
• Blood parasites such as malaria are submitted to the lab as a thick and
thin blood smear slide. The smears are examined by a medical technician
or pathologist for identification.

302 7 4 - p a r a s it o l o g y
• Parasites that cause intestinal problems (such as Giardia) are sent to the
lab as three stool specimens from different days. The clinicians examine
the stool for ova or eggs of the parasite.
• Pinworms are examined by using the ’’scotch tape test.” This involves
taking a piece of invisible tape and pressing the sticky surface against the
perianal region. The tape is then viewed under a microscope to identify
the parasite.
R eferences
[1] Bartlett, J im m y D,, Jaanus, Siret D. Clinical Ocular Pharmacology. Boston; Butt or worth,
2008.
[2] Blair, Lennette, and Joseph Truant. Manual of Clinical Microbiology. Baltimore; Williams
and Wilkins Company, 1970.
[3] Bottone, Edward Ed. Schneierson’s Atlas o f Diagnostic Microbiology, 8th ed. North Chicago:
Abbott Laboratories, 1982.
[4] Chesebro, Bruce. "BSE and Prions; Uncertainties about the Agents.” Science 2 279 (1 9 8 8 ):
42-43,
[5] DeArmond, SL and SB Prusiner. ’’Prion Protein Transgenes and the Neuropathology in Prion
Diseases.” Brain Pathology 1 (1995): 77-89.
[G] Fitzpatrick, Thomas et. al. Color Atlas and Synopsis of Clinical Dermatology, 4th ed. St.
Louis: McGraw-Hill, 2001,
[7] Fox, Stuart Ira. Human Physiology, 6th ed. Boston: McGraw-Hill, 1999,
[8] Freeman, W R et al, ”A prospective study of ophthalmologic findings in AIDS.” American

Journal of Opthalmology. 97 (1984) 133-42.
[9] Friedman, Neil J. Kaiser, Peter K. The Massachusetts Eye and Ear Infirmary. 3rd Edition.
Elsevier, 2009.
[10] Goldbloom, Richard B. ’’Prophylaxis for Gonococcal and Chlamydial Ophthamia Neonato
rum.” 11 Dec. 2005. < h ttp//w w w .ctfphc..org//u /l 7'ea:t/chl 6full.htm>
[11] Harkins, Timothy, ’’Sexually Transmitted Diseases,” Optometry Clinics Vol. 3, Number 4,
Systemic Disease and the Eye. Eds. John G. Classe and Charles J. Patorgis. Norwalk: Ap
pleton and Lange, 1994.
[12] Kansld, Jack. Clinical Opthalmology A Systemic Approach, 4th ed. Woburn: Butterworth-
Heinemann, 2000.
[13] Noble, John, Ed. Textbook of Primary Care Medicine, 3rd ed. St. Louis; Mosby, 2001.
[14] Prescott, Harley, and Donald Klein. Microbiology, 4th ed. Boston: McGraw-Hill, 1999.
[15] Rapuano, Christopher J. Heng, Wee-Jin. Color Atlas and Synopsis of Clinical Ophthalmology.
Wills Eye Hospital. Singapore; McGraw-Hill, 2003.
[16] Rosenthal I<S, Tan MJ. Rapid review microbiology and immunology. 3rd ed. Philadelphia:
M obby-Elsevier, 2011 .
[17] Stenchever, Morton et al. Comprehensive Gynecology, 4tli ed. St. Louis; Mosby, 2001.
[18] Terry, Jack. Ocular Disease: Detection, Diagnosis and Treatment, Springfield: Charch C.
Thomas, 1984,

[19] Tierney. Lawrence M., McPhee, McPhee, Stephen, and Maxine A. Papadakis Eds. Current
Medical Diagnosis and Treatment, 41st ed. New York: McGraw-Hill, 2002.

(f
( ·· ..
(
(( .
(( .
((
((
((
((
(I
(
(
((
((
((
((
((_
((
((
((
c.
(
(( ;
((
((
(( . ..
((
((
(( .
((
Chapter 8
Immunology
Kyle Cheatham O .D ., F .A .A .O .
305
f
(
(
c
(■
c
(
(
(
(
(
(
(
(
(
(
(
(
c
(
(
(
(
Copyright 2014 by KMK Educational Services, LL C
(
(
X
(
CHAPTER. 8 . IMMUNOLOGY 307
Im m u n o lo g y is the study of disease resistance.
I— SECTION 8.1
A ntigens
Molecules that stimulate the production of specific antibodies are called anti
gens. Most antigens are large molecules (like proteins, polysaccharides). As
described in this review, antigens (Ag) can also be non-harmful substances lo
cated within the body that, when exposed to the immune system, can fool the
system into thinking that they are foreign.
• A n tigen determ in an t sites: Specific complex areas of the antigen that

are recognized as foreign and result in the production of antibodies. Serve
as the location where antibodies (Abs) bind to the antigen.
jAntdgcn L o catio n s ^n d lmmuriie R esponse

Antigens are primarily found in three locations: blood, connective tissue (CT),
and lymph.
1. B lo o d : Monocytes travel in the bloodstream and act as antigen present

ing cells (APCs).
• K u p ffer cells in the liver and phagocytic cells located in the walls of
blood vessels in the spleen and lymph nodes remove foreign antigens
and “inactivate” them within their cytoplasm.
2. C T : Antigens are hindered from entering tissues by a collection of unen

capsulated T and B cells called diffuse lymphatics that are located in the
lamina propria and pars papillaris, both loose CT layers.
3. L y m p h : The lymph and circulatory systems are very closely related.

Antigens in the blood will circulate through the lymph system, are carried
into lymph nodes, and then are destroyed by waiting B and T cells.
- SECTION 8.2 -----------------------------------------------------------------------------------------------------
A ntibodies
Antibodies are Y-shaped gamma globulin plasma proteins produced by differ

entiated B lymphocytes called plasm a cells. Each Ab is made to fight a very
specific antigen. There are trillions of Abs in each individual, providing the

308 8.2. ANTIBODIES
body with the means to handle almost any sort of antigen that is encountered.
For antibody functions, please see the biochemistry chapter.
Structure
All Abs consist of 4 interconnected polypeptide chains arranged in a Y shape;
two are heavy (H), and two are light (L) chains.
F c p o rtio n
Constant region derived from the stem of the Y.
• This region is the same (constant) for antibodies of the same class.
• The binding of complement proteins to the Fc portion of IgG + IgM

antibodies will initiate the com p lem en t pathw ay (3).
Each class of antibodies (IgG, IgA, etc.) has their own Fc region
that is specific for their class. For example, every IgG antibody has
the same Fc region. The variation in the Fab region among IgG
antibodies allows the antibody to recognize its specific antigen.
Fab p o rtio n
Variable region that is responsible for the variation among antibodies 'within
each subtype, allowing specificity of antibodies for various antigens (7).
CHAPTER 8 . IMMUNOLOGY 309
• The unique Fab region among antibodies allows an antibody to recognize

its specific antigen (4).
• The Fab region is where antibodies bind their antigen.
- SECTION 8.3 -----------------------------------------------------------------------------------------------------
N onspecific Immunity *•
The nonspecific response is the first line o f defense against a pathogen.

When tissue is inflamed and/or infected, chemical mediators are released and
attract leukocytes to the area.
• Neutrophils arrive first (particularly in bacterial infections), followed by

the other granulocytes (basophils and eosinophils) as part of the initial
response.
• The major role of the granulocytes is to release the contents o f their

cytoplasmic granules at the site of infection. Neutrophils also help to
phagocytose the antigen.
• Monocytes arrive later and can be transformed into macrophages for

phagocytosis when necessary.
If the initial immune response does not control the infection, and it starts
to spread within the connective tissue, more neutrophils and monocytes from
the blood come to the rescue. They are able to squeeze through gaps in the
endothelial cells of the blood vessels in a process called diapedesis. Some
general examples of nonspecific immunity include the following:
• Epithelial membranes that cover the surface of the skin. Once bacteria
or other pathogens cross your skin, they run into connective tissue that
is loaded with all of the various leukocytes.
• Strong acidity (pH 1-2) of gastric acid.
Examples of n on sp ecific im m unity in the eye include the blink

ing action of the lids, flushing of the tears, lysozyme and IgA in
the tears, and the shedding of corneal epithelial cells (7).
This review will focus on three prominent examples of nonspecific immunity:

interferons, natural killer cells, and the com plem en t pathway.

310 8.3. NONSPECIFIC IMMUNITY
wmmmMSismmMBSMMMmmMm
When viruses infect cells, polypeptides called interferons are produced to pro
tect neighboring cells. The virus can still penetrate these cells, but is unable
to replicate or produce new virus particles.
• Interferons provide a nonspecific, brief resistance to viral infections.
• There are three types of interferons: alpha, beta, and gamma; alpha and
beta are made by almost all cell types for inhibition of viral replication.
Gamma is only produced by some lymphocytes and natural killer cells
for cessation of tumor growth and cancer.
Treatm ent: Interferon can be used for treatment of various diseases:
• Alpha: Hepatitis C, Hairy-cell leukemia, Kaposi’s sarcoma.

• Beta: Relapsing M u ltip le Sclerosis.
• Gamma: Chronic granulomatous diseases.
2 Natural Killer cells

. ~ . •
Non-specific lymphocytes that can act as a first line of defense (unlike other
lymphocytes) against antigens.
• Unlike T and B lymphocytes, natural killer (NK) cells do not have antigen
recognition sites for a specialized response to an antigen. Thus, they do
NOT require an antigen presenting cell (APC) for activation.
• This allows NK cells to provide a rapid response to virus-infected cells or

tumor cells (4) (3).
3 . A n tig en /A n tib o d y C om plexes and N onspecific Imniu-i

nity
When antibodies bind to an antigen, an antigen/antibody complex is formed
and complement proteins (present in the plasma) are activated.
• If the antibody involved is IgG, IgM, or IgA, the complement protein

can bind to the Fc portion of the antibody and initiate the complement
pathway.•
• It is important to understand that antibodies are unable to destroy anti

gens - they merely highlight the antigen and tell the immune system to
phagocytose it; this process is called opson ization .

CHAPTER 8 . IMMUNOLOGY 3 11
• If the antigen/antibody complex is able to trigger complement proteins,

the com p lem en t pathw ay will destroy the invader via activation of the
following events:
— Direct lysis of bacteria.

— Chemotaxis of neutrophils and macrophages.
— Opsonization.
— Degranulation o f mast cells (causing histamine release and an in
crease in vascular permeability) (3).
E x a m p le: Imagine you were slicing an onion and accidentally cut your finger.
Antigens would attempt to enter the wound and non-specific immune mecha
nisms would be employed to destroy the antigen. Ig G and Ig M an tib od ies
localized within the CT would bind to the antigen and display it for nearby
PMNs and macrophages. Once this non-specific antigen/Ab binding occurs,
proteins from the plasma (complement proteins) are stimulated to help destroy
the antigen.
C o m p le m e n t p rotein s are produced in the eye. C l, for exam

ple, is locally produced in the cornea. IgA in the tears initiates the
alternate pathway. IgG and C l are more concentrated in the pe
ripheral cornea because of the close proximity to the conjunctival
blood vessels (T).
The complement pathway consists of two routes that are activated by different
pathogens.
1. C lassic pathw ay
• Requires Ig G or Ig M for activation. A specific complement protein

(C l) binds to the P c p o r tio n of an IgG or IgM antibody and initiates
the complement process. C l enzymatically cleaves C4 into two fragments,
which then cleaves C2, etc.•
• Eventually, a “membrane attack complex” (M A C ) is formed on the cell

membrane of the antigen. The MAC leads to holes in the membrane,
allowing water to pour into the cell and cause subsequent cell lysis (4) (3).

312 8 .1 SPECIFIC IMMUNITY
2. A ltern ative pathw ay
• Similar to the classic pathway, the alternative pathway results in mem

brane pores and cellular destruction. This pathway differs in that Ig A
and bacterial en d otoxin s initiate the complement process (4) (3).
Remember that in over 60% of uveitis patients, the etiology is un

known. Studies are showing that many of these patients have a
predisposition to excessive complement production in anterior seg
ment structures (1) (6).
SECTION 8.4
Specific Im m u n ity •
This portion of the immune response involves ly m p h o cy te s and the produc

tion of antibodies against specific antigens. In the non-specific immunity exam
ple (onion slicing), we saw how some antibodies are produced in a non-specific
manner; that is, they are not generated in response to a particular antigen but
are instead “pre-made” in mass quantities and placed in areas of high antigen
exposure.
• If non-specific mechanisms are unable to control the antigen, specific

im m unity aids in the response by allowing production of an tibodies
sp ecific for that antigen.
• In the above example, histamine release (from the complement pathway)

would aid in diapedesis, allowing T cells and other leukocytes from the
blood access to the antigen. If the T cell is able to attack the antigen
(see below for details), precise antibodies for that antigen are produced
in the process of specific immunity.
• S pecific im m unity = T cell tells B cell t o p ro d u ce A b .
Both B and T lymphocytes are produced in the bone marrow. T

cells mature in the thymus. B cells mature in the bone marrow.
Copyright 2014 by KMI< Educational Services, LLG

Secrete antibodies into the blood and lymph (both body fluids or humors) -
this allows for hu m oral im m unity.
• B lymphocytes have surface IgM or IgD embedded on their outer mem

brane.
• In most cases when they use these antibodies to bind an antigen, nothing
happens. However, if B cells are activated by IL-2 from helper T cells,
the B cell will undergo blastic transform ation, a process by which B
cells rapidly divide and differentiate into m em ory and plasm a cells.
• Plasma cells are basically factories for Abs, producing over 2,000 per
second (5)!
Do NOT secrete antibodies. They are involved in cellular im m u n ity by

either directly fighting the antigen or by secreting cytokines to mediate the
inflammatory response.
|O verview o f Specific Im nitm ity - y/v •.

When T cells become educated in the thymus, they are made with an antigen
recognition site on their outer surface that is highly specific for a particular
antigen; this site is so specific that only an estimated 1x10s T cells actually
find their target antigens (3)!
• In order for T cell activation to occur, the antigen must first be phago-
cytosed by a macrophage or an antigen presenting cell (A P C ). The
macrophage degrades the antigen with lysosomes, and then exocytoses
remnants of it onto its cell surface.
• As the wandering T helper cell (with a CD4 receptor) approaches the

APC (macrophage) and captured antigen, it looks closely at the receptors
on the APC (MHC 2) and antigen (antigen recognition site).•
• If the antigen recognition site matches the antigen AND the CD/M HC
receptors match (see chart below), specific immunity can begin (5).
If a h elp er T cell passes by an antigen in the bloodstream, it can

not act on the antigen until the invader is inactivated and exposed
by an APC. Even if this occurs, the helper T cell must “recognize”
the antigen for specific immunity to begin.

314 84- SPECIFIC IMMUNITY
M a jo r H isto co m p a tib ility C o m p le x (M H C ): The first step of the immune

response involves recognition of the “foreign” invader.
• It is important that the immune system does not get confused and mis
takenly attack “self’ tissue; therefore, it utilizes a system in which “self1
tissues are marked with proteins on their cell surface.
• All nucleated cells in the body AND antigen presenting cells have these
“markers” on their cell membrane called human leukocyte antigens (HLAs).
They are also called major histocompatibility complex, after the group of
genes on Chromosome 6 that code for them. In either case, the markers
are divided into two categories:
MHC 1
All nucleated cells of the body have Class I MHC receptors. When cells in
the body get infected, the immune system targets their MHC 1 receptors for
removal out of the system.
• T killer cells (with CD 8 receptors) interact with MHC 1 receptors.
When we have a virus, T killer cells are able to destroy sick cells
because their CD 8 receptor is a match for the MHC 1 receptor on
the infected cell’s surface.
MHC 2
Antigen presenting cells (macrophages) have Class II MHC receptors.
• Helper T lymphocytes (with CD 4 receptors) only interact with MHC 2

receptors on APCs (4).
H elper T cells, which have CD 4 receptors, are the primary cell

type attacked in HIV.
R e ce p to r W h o has them W h o Interacts w ith them

MHC 1 All nucleated cells of body T killer cells (with CD8 receptor);
T suppressor cells
MHC 2 Antigen presenting cells Helper T cells (with CD4 receptor)

(APCs, macrophages)

In Summary,..
Antigen
Engulfed by
Macrophage
Becomes
APC
Ag Presenting Cell
Stimulates
V
HelperT cell
Stimulates
/ I \
Stimulates Stimulates
B. Cell MemoryHelper KillerTcell
These Divide and become,...
\ —
Plasma Cells Memory B Cells MemoryT Cells Active KlllerT cells
lf
Secrete Abs
Figure 8.1: Summary of Specific Immunity
M a crop h a g es and T y p e s o f T cells in S pecific Im m unity
There are three major types of A P C s (3):
1. Neutrophils.
2. Organ-specific phagocytes (liver, spleen, lungs, CNS, etc.).
3. Monocytes in the blood and macrophages in CT.
Remember, specific immunity begins by the APC phagocytosing the anti

gen. Once the “match” (described earlier) occurs, the APC is told to release
Interleukin-1 (IL -1), which causes cell division and proliferation of T lym
phocytes into the following (5):
T h elper cells: The “conductor” of the immune system. Called helper T cells
because they secrete cytokines to “help” other T lymphocytes know their
roles (3) (see Figure 8.1.) T helper cells also recruit macrophages by
releasing macrophage stimulating factor (not in chart).

316 84- SPECIFIC IMMUNITY
H elp er T cells assist the immune response by producing lym-

phokines, which promote the proliferation of T cells, B cells, and
macrophages. Suppressor T cells dampen this response. Both of
these groups modulate and fine-tune the production of Abs (2) (5).
T suppressor cells: Decrease the response of B cells and T killer cells. Im
mune system activity depends on the ratio of T suppressor to T helper
cells.
T m em ory cells: These are produced in mass amounts and have a high affin
ity for an antigen upon secondary exposure. This allows the body to
respond quicker upon future invasion by the same pathogen.
T killer cells: T cells that have CD 8 receptors and respond to MHC 1 re
ceptors (all nucleated cells in the body). T killer cells attack cancer cells
and cells that are infected with viruses (as described earlier); they also
respond to general cell damage (3).
T killer cells are responsible for the immune response in tissue

transplant rejections (4) (3). T killer cells secrete perforins, which
are polypeptides that open pores and destroy the cells by allowing
influx of water and cell lysis.
'Cytokines .... ' • -A ' -

Chemical messengers secreted by lymphocytes that include growth factors, in
terleukins, and interferons (discussed earlier in the chapter).
G ro w th Factors: Examples of growth factors include the following;
• MAF (macrophage activating factor): T cell activation produces

lymphokines that will activate local macrophages.
• MIF (migration inhibitory factor): Prevents macrophages from leav
ing the affected area.
Interleukins: Mediators released by helper T cells (mainly) and macrophages

to amplify the immune response. There are several different types, in
cluding IL-1, IL-2, IL-3, etc.

IL -1: Released by macrophages (at T cell request); stimulates T cells, B

cells, neutrophils, and fibroblasts to grow and produce their prod
ucts (4) (5).
IL -2: Released by helper T cells. Stimulates growth of helper and cy
totoxic cells. The helper T cell (Class II MHC) binds to IgM or
IgD receptors on the surface of the antibody. This binding, along
with activation from IL-2, stimulates the production of plasma and
memory cells.
R estasis (cyclosporine 0.05%) inhibits T cell activation by stop

ping the production of interleukin-2.
- SECTION 8.5 ------------------------------------------------- — ------------------------------
P rim a ry an d Secondary Im m une Responses *•
A primary response occurs when a person is first exposed to an antigen. Future

exposure results in a secondary response.
P rim a ry E x p osu re
• Sluggish immune response - it takes the body 5-10 days before measurable
amounts of antibodies appear in the blood.
• IgM antibodies are made first (rather slowly), and the person is likely to
get sick (5).
S econ d E x p o su re
• Fast immune response - it takes the body less than 2 hours to produce
antibodies, and the production is maintained longer than upon primary
exposure. IgG is made first (unlike primary exposure) (5).
• Secondary responses are not completely understood, but the “ clonal se
le ctio n th e o r y ” says that lymphocytes “learn” from their first experience
with the antigen and react by producing clones in the time lapse between
the primary and secondary exposure.
— Each T lymphocyte is genetically formed with the ability to respond

to one particular antigen, and each B lymphocyte with the ability
to produce antibodies specific for that antigen.

318 8 . 6 . TISSUE TRANSPLANTATION / GRAFT REJECTION
— After stimulation by the antigen upon primary exposure, the lym

phocytes specific to that antigen will divide multiple times, forming
clones. Some of these lymphocytes become plasma cells that secrete
antibodies for the primary response; others become memory cells
that can be stimulated to secrete antibodies during the secondary
response (5, pp. 459).
- SECTION 8.6 -----------------------------------------------------------------------------------------------------
Tissue T ran sp lan tatio n / G raft R ejection
As mentioned above, MHC receptors on the leukocytes must be a close match

between the donor and recipient. If not closely enough related, the T lympho
cytes (mainly T killer cells) can reject the tissue through a Type 4 hypersensi
tivity reaction. The following stages of rejection can occur (4):
• H ypera cu te: Occurs within minutes of transplantation and is Ab medi

ated. Occurs because the transplant recipient has preformed Abs against
the donated tissue (4).
• A cu te : Initiated weeks after transplantation and is T cell mediated. T

cells react against foreign MHCs.
• C h ron ic: Occurs months to years after transplantation and is Ab medi

ated and irreversible.
- SECTION 8 .7 ----------- -------------- — -----------------------------------------------------------------
A uto im m u n ity
Autoimmune diseases are not caused by an invading pathogen, but rather a de
fect in the normal functions of the immune system. Essentially, a self-antigen
causes the T cells to overreact and produce large amounts of B cells, and anti
bodies have the potential to produce significant inflammation and organ dam
age. Please see the Systemic Disease chapter for further information regarding
specific autoimmune diseases.
— SECTION 8.8 -----------------------------------------------------------------------------------------------------
T um or Im m unology
B en ign tu m ors: Slow growing and limited to a specific location.
M alignant tum ors: Grow faster than benign tumors and metastasize - tumor
cells spread and new tumors develop in other locations.

CHAPTER 8. IMMUNOLOGY 319
T u m ors: As tumor cells grow and differentiate, surface antigens begin to ap
pear on cells. The immune system recognizes these as foreign and T killer
cells and natural killer cells attack the tumor.
N a tu ra l K iller C ells: Natural killer cells do not require prior exposure to

attack an antigen (they are non-specific cells). Thus, they are often our
first line of defense against tumors.
In terleu kin 2 (IL-2): Made through genetic engineering, this can be used to
fight cancer by stimulating host T killer cells and B lymphocytes to fight
the tumor.
- SECTION 8.9 -----------------------------------------------------------------------------------------------------
Im m unological Tests
C o m p le te B lo o d C ou n t (C B C ): Commonly ordered blood test that indi

cates overall health. Analyzes three different kinds of cells: WBCs, RBCs,
and platelets. CBCs are often ordered to monitor infections (bacterial,
viral, allergic) and for analysis of anemia.
E r y th ro c y te S ed im en ta tion R a te (E S R ): 1 hour n on -sp ecific test o f

in flam m ation in the body. Measures the “sedimentation rate of RBCs”
- how far RBC levels fall in a test tube (in millimeters). ESR is increased
with higher levels of inflammation in the body.
C -re a ctiv e p ro te in te st (C R P ): Another non -sp ecific test o f inflam

m ation. C-reactive protein is a specific protein produced by the liver
that is only present during episodes of acute inflammation.
C B C , E S R , and C R P tests should be ordered in a patient with

suspected temporal arteritis (GCA).
H L A -B 2 7 : Test used to determine if a patient is positive to the gene that

causes ankylosing spondylitis, reactive arthritis, and other diseases that
cause ocular manifestations (1).
H L A -B 5 4 : Test used to determine if a patient is positive to the gene that

causes glaucomatocyclitic crisis (1).
T issu e b io p sy : Analyzes tissue to see if disease is present (e.g. temporal

artery biopsy).

320 8.9. IMMUNOLOGICAL TESTS
A ntinuclear a n tib od y test (A N A ): Evaluates whether autoantibodies are

present in the bloodstream. Antinuclear antibodies are produced when
the immune system attacks the body’s own tissues, thinking they are
foreign.
R eferences
[1] Bardenstein DS, Cheyer GJ, Lee C, Cocuzzi E, Mizuno M, Okada N, Medof ME. Blockage of
complement regulators in the conjunctiva and within the eye leads to massive inflammation
and iritis. Immunology. 2001;3.04: 423-430. doi: 10.1046/j.1365-2567.2001.01316.x.
[2] Beck RW, Optic Neuritis Study Group. The Optic Neuritis Treatment Trial. Arch Ophthalmol
1988; 106:1051-53.
[3] Begley, Carolyn, Giese, Michael J. General Immunology and Inflammation, In Bennett and
Weissman, eds. C lin ica l C o n t a c t L en s P r a c tic e , Lippincott, Philadelphia, PA, 1994.
[4] Bhushan, Vikas, Le, Tao, Amin, Chirag. First Aid for the USMLE Step One, New York:
McGraw-Hill, 2003
[5] Fox, Stuart Ira. Human Physiology, 6th ed. Boston: McGraw-Hill, 1999
[6] Rogoz S, Avramescu C, Silosi I, Drackoulogona O, Badea P, State A. Humoral and cellular
immunity investigation in idiopathic uveitis,. OftaJmologia. 2002;54: 56-60.
[7] Weissman, Barry A. Giese, Michael J. Mondino, Bartly J, An Introduction to Ocular Im
munology. Optometry Clinics Vol. 3, Number 4, Systemic Disease and the Bye. Eds. John G.
Classe and Charles J. Patorgis, Norwalk: Appleton and Lange, 1994,

Chapter 9
Systemic Disease
M elissa C h eath am , P A -C , M P A S
321
r
(
c
c
c
c
(
r
(
(
c
(
c
(
(
(
c
(
(
(
(
(
(
(
c
(
(
CHAPTER 9. SYSTEMIC DISEASE 323
I - SECTION 9.1
Inflam m ation and R ep air
In flam m ation : This is a defense response that eliminates the products of

cellular injuries (e.g, necrotic cells and debris). Inflammation plays a role in
the healing of injured cells by diluting or destroying the agent responsible for
injury. The following are some fundamentals of inflammation and repair (36).
|A.cutc m nam hiation y .: ;:: ; :

Acute inflammation is an immediate response to injury that occurs 1-2 m in
utes post-injury. Leukocytes help clear the injury site of invading bacteria and
degrade necrotic byproducts of the damage. Acute inflammation is determin
istic - it happens the same way every time. There are 3 major components of
acute inflammation:
1. V ascular size changes (dilation) to facilitate increased blood flow.
2. Stru ctu ral changes in the microvasculature (increased permeability)

facilitate the arrival of plasma proteins and leukocytes from the circula
tion,
3. Im m ig ra tion o f n eu trophils (P M N s ) from circulation to the site of

injury.
Clinically, acute inflammation generates R U B O R (redness),

C A L O R (heat), D O L O R (pain), and T U M O R (swelling). Also,
do not forget the presence of WBCs in acute inflammation!
Possible outcomes of acute inflammation are complete resolution, scarring or fi

brosis, abscess formation (pus forming infections), and/or progression to chronic
inflammation.
Prolonged inflammation lasting from weeks to years. Active inflammation,

tissue injury, and healing all progress at the same rate. While acute inflam
mation is marked by changes in vascular structure, edema, and neutrophilic
infiltrates, chronic inflammation is characterized by the following:
1. Infiltration with mononuclear cells (m acrophages, lym p h ocytes, and

plasm a cells).

324 9.1 . INFLAMMATION AND REPAID,
2. Tissue destruction.
3. Repair involving new vessel proliferation (neovascularization) and fibro

sis.
Chronic inflammation will arise in the following situations:
• Persistent infections (e.g. helicobacter pylori).
• Prolonged exposure to potentially toxic agents (e.g. asbestos).
• Autoimmune diseases (e.g. rheumatoid arthritis).
C h ro n ic inflam m ations are not all identical! In fact, the body adjusts
the response according to the type of injury. One type of chronic inflammation
is granulom atous inflam m ation.
G ranulom atous Inflam m ation . t : ^

This type of chronic inflammation is marked by collections of large, activated
m acroph ages with a squamous cell-like appearance. Examples of granuloma
tous inflammation include:
• B acterial: Tuberculosis, Leprosy.
• Fungal: Histoplasmosis, Blastomycosis.
• F oreign B o d y : Suture, vascular graft.
• U nknow n: Sarcoidosis.
tevonts th a t Affect b
• L ocal factors that prolong wound healing include local infection, de
creased blood supply, and the inability to form clots.•
• System ic factors that prolong wound healing include diabetes, im

munocompromised states, decreased peripheral blood flow, systemic in
fection, malnutrition, and increased glucocorticoid production (e.g. stress)

r - SECTION 9.2
C ellular Disease
p e ll In ju ry (reversible and irreversible) p c ..-
R e v e rsib le
• This process is marked by a decrease in blood supply to a cell and a

corresponding decrease in oxygen supply (hypoxia).
• Lack of oxygen will cause two things:
- An increase in glycolysis and anaerobic respiration - the lack of oxy

gen leads to increased lactic acid concentration and a decrease in
tissue pH (36).
- A decrease in ATP production, which disrupts the sodium and potas
sium gradient across the cell; this causes an accumulation of intra
cellular sodium and subsequent cellular edema (36).
• If oxygen is restored to the cell, ATP increases, the sodium-potassium

pump is restored, and anaerobic respiration ceases. Persistent ischemia
will lead to irreversible injury.
Irreversible
• Insufficient ATP results in sodium accumulation and the cell, in turn, be
comes edematous, which disrupts the cell membrane. This causes crucial
cellular components needed for the reconstruction of ATP to leak out, and
thereby further facilitates the depletion of high energy phosphates (36).
• L ack o f ox yg en w ill u ltim a tely increase ischem ia, causing tissue

necrosis. The events leading to this process include:
— Progressive loss of membrane phospholipids.

— Cytoskeletal abnormalities.
— Toxic oxygen radicals, which damage the cell membrane and other
cell components.
— Lipid breakdown products, which accumulate in ischemic cells and
result in phospholipid degradation (36) (48).
jCell In jiiry an d D e a th ^ = '; A- ' ’ P.-. A If' -Ah:: .

N ecrosis: The death of one or more cells as a result of irreversible damage
is called necrosis (52). Two processes occur with necrosis:

326 9.3. IMMUNOPATHOLOGY
1. Enzymatic digestion of the cell.
2. Denaturation of proteins.
Pour T y p es o f N ecrosis
C oagu la tive N ecrosis: The structural boundary of a coagulated cell, tissue,

or vessel is maintained, but integral structural proteins are denatured.
This type of necrosis often occurs following a myocardial infarction (52).
L iquefactfve N ecrosis: A cell with a well-defined boundary remains, but it

consists of dull, gray-white remains. This is seen with fungal infections
and often occurs in the lung.
C aseous N ecrosis: Most often seen in tuberculosis (TB) infections. The term
caseous comes from “cheesy” because the central necrotic tissue appears
white and cheesy.
Fat N ecrosis: This is death to adipose (fat) tissue. Small white lesions are
formed.
A p o p to sis: Well-organized self-destruction of cells; commonly referred to as

programmed cell death. It occurs during embryogenesis, endometrium shedding
during the menstrual cycle, or cell deletion in tumors (36) (48). A p op tosis is
critical in fine-tuning the developin g retina. Over 70% of ganglion cells
die via this process during development (33).
- SECTIO N 9.3 --------------------------------------------------------------------------------------------------------------------
Im m unopathology
H y p e rse n sitiv ity , R eactions . \ .]

A n a p h y la ctic (T y p e I)
• An allergen activates a B-lymphocyte and IgE antibodies are produced

and bind to the surface of mast cells and basophils. A second exposure
to the allergen causes cross-linking of IgE, allowing calcium to enter and
resulting in degranulation of the cell.
• Common causes of anaphylaxis include peanuts, shellfish, drugs (e.g.

penicillins), snake venom, and winged-insect venom (e.g. yellow jackets,
hornets).
• The initial response is evident in 5-30 minutes and resolves in 30-60 min
utes. Late phase response (4-6 hours later) can occur, resulting in tissue
damage (7) (36) (48) (61).

Histamine is the primary mediator released from mast cells and basophils dur
ing a Type 1 allergic reaction. Histamine release can cause a range of clin
ical effects, from benign itching and rhinitis to life-threatening anaphylactic
shock (6).
Type I response is First and Fast!
C y to to x ic (T y p e II)
• Type II hypersensitivity is facilitated by Abs against antigens absorbed

on various tissue components, such as cell surfaces. Ig M and Ig G
antibodies bind an antigen or enemy cell, which leads to its destruc
tion (45) (48) (61).
• One example of this response includes a transfusion reaction, with the

prime example being erythroblastosis fetalis (R h disease) (53), In this
condition, maternal IgG antibodies capable of crossing the placenta at
tack fetal erythrocyte antigens. R h eu m atic fever is also an example of
this type of response (42).
Im m u n e co m p le x -m e d ia te d (T y p e III)
• Mediated by antigen-antibody ( A g /A b ) com p lex es either in the sys

temic circulation, or those formed at the location of antigen deposition.
• These A g / Ab complexes activate the complement response. This triggers

the attack on neutrophils, which then release lysosomal enzymes.
• One example includes sy stem ic lupus erythem atosus (7) (48).
• Serum sickness is also an immune complex disorder in which antibodies

are formed due to the intake of large amounts of foreign proteins (36) (48).
D elayed o r C e ll-M e d ia te d (T y p e IV )
• Sensitized T-Lymphocytes encounter an antigen and release leukokinin,

leading to macrophage activation.•
• Examples include tu b ercu losis skin test, con tact derm atitis, and
corn eal transplant re je ction (36) (48).

328 9.1 RHEUMATOLOGIC DISORDERS
P h lycten u losis occurs as a result of a type 4 delayed-

hypersensitivity reaction, usually from staphylococcal infection sec
ondary to blepharitis.
I— SECTIO N 9.4
R heum atologic D isorders
A utoim rriuhe Diseases /;

System ic Lupus E rythem atosus (SLE )
This autoimmune disease affects multiple systems including the skin, kidneys,
joints, and heart. The female to male SLE affliction ratio is 10 to 1 and often
arises in the second or third decade of life (57). Symptoms include a bu tterfly
rash (m alar rash), discoid lupus, photosensitivity, arthritis, renal disorders,
neurological disorders (e.g. seizures), immunological disorders, and hemolytic
anemia. SLE patients will produce antinuclear antibodies (ANA) and 90% will
have joint pain (57) (58). Ocular findings include:
• D ry eye, recurrent episcleritis, peripheral keratitis, and photophobia.
• Neuro-ophthalmic complications, including disc edema and papilledema (29).
R h e u m a to id A rth ritis (R A )
This common systemic inflammatory disease classically causes symmetric arthri

tis in multiple locations that leads to destruction of articular cartilage. Symp
toms are worse in the morning and can include pain in the hands, wrists, feet,
and small joints (3). Women are affected more commonly than men, with an
age of onset between 40 and 50. These patients will have a positive rheuma
toid factor (RF) test. Approximately 25% of patients with RA will have ocular
manifestations (49). These include:
• Keratoconjunctivitis sicca occurs in 15% to 25% of patients (23) (26).
• Sclerom alacia perforans, peripheral corneal ulceration, and peripheral

keratitis are also common ocular manifestations.
• Choroiditis, retinal vasculitis, episcleral nodules, retinal detachments, and

macular edema are less common ocular associations (23) (26).

Necrotizing scleritis without inflammation occurs in RA patients

and is known as sclerom alacia perforans. Overall, approxi
mately 15% o f all cases of scleritis are caused by rheumatoid arthri
tis (21).
Ju ven ile Id io p a th ic A rth ritis (J IA )
This condition was formerly known as juvenile rheumatoid arthritis (JRA).

JIA has a predilection for young females and can affect multiple joints. These
patients will have a negative RF, but can have a positive ANA. Patients under
the age of 6 with recent onset of the disease and positive ANA are at a higher
risk for ocular manifestations.
• J IA is th e m ost co m m o n cause o f uveitis in children, accounting

for approximately 80% of cases (49).
• The classic clinical picture is a female with asymptomatic, chronic, bilat

eral, non-granulomatous, anterior uveitis.
• These patients will often present with a low-grade fever.
S jog re n ’s sy n d rom e
• Disease marked by the triad of dry m ou th , d ry eyes, and arthritis.

May be associated with rheumatoid arthritis.
• Primarily affects females between the ages of 40 and 60 (58).
Sarcoidosis
Idiopathic condition that classically affects middle-aged African American fe

males. It is characterized by non-caseating granulomas and increased levels
of serum angiotensin converting enzyme (ACE). However, up to 40% of active
cases of sarcoid can have a normal ACE result (20). 90% of patients have
lung involvement - a chest x -ra y is indicated if the disease is suspected (45).
Patients are often asymptomatic, but can have complaints of breathing diffi
culties (after little exertion), dry cough, and unusual rashes. Bell’s palsy is also
associated with the disease.•
• 25% of patients will have ocular manifestations - 75% of these patients

will have anterior gran u lom atous uveitis (45).

330 9Jh RHEUMATOLOGIC DISORDERS
• Posterior segment findings such as vasculitis (candle wax droppings) and

diffuse vitritis can occur. The vitritis is characterized by white, fluffy
opacities in the inferior vitreous (“cotton-ball opacities”) (21).
• 1 — 5% of patients will develop optic nerve disease (45).
• Sarcoidosis may also cause chronic dacryoadenitis.
A n k ylosin g S pondylitis
• Chronic inflammatory disease of the spine and large joints.
• Characterized by a b a m b o o spine, sacroiliitis, uveitis, and aortic

regurgitation.
• Usually affects young males 10-30 years of age.
• 90% of cases will have a positive HLA-B27 gene (42) (57).
C linical N ote: When you suspect a uveitis patient has ankylos

ing sp on dylitis, a sacroiliac x-ray should be ordered. HLA-B27
testing should also be considered.
R ea ctiv e A rth ritis (form erly called R e ite r ’ s S y n d rom e)
• Has a classic triad of urethritis, con ju n ctiv itis a n d /o r anterior

uveitis, and arthritis (51).
• Urinary symptoms will usually appear first. Low-grade fevers, conjunc

tivitis, and arthritis will then develop over the next several weeks.•
• Affects young males more than females and is typically HLA-B27 posi
tive (51).
Remember, Mr. Reiter Can’t See, Can’t Pee, and Can’t Climb a
Tree!

CHAPTER 9. SYSTEMIC DISEASE 3 31
P so ria tic A rth ritis
Characterized by asymmetric, peripheral, small joint pain with accompanying

psoriatic lesions found on the knees, elbows, and scalp. 7% of patients with
psoriatic arthritis may develop anterior uveitis (37). These patients will
have a positive HLA-B27 test. Treatment includes UV-B light exposure and
methotrexate.
Noteworthy positive HLA-B27 conditions include C R A P : Crohn’s

disease, Reactive arthritis, Ankylosing spondylitis, Psoriatic
arthritis.
[Vasculitis D isorders N;;‘t T ® :

T em p ora l A rteritis (G ian t C ell A rteritis)
Systemic vasculitis that affects the medium to large vessels, including the tem
poral artery. These patients are typically older than 55 years of age and present
with complaints of scalp tenderness, temporal headaches, jabbing neck pain,
jaw claudication, and fever. A dilated and nodular temporal artery may also
be present (29). 50% of patients with temporal arteritis may also develop
p oly m ya lg ia rh eu m atica, which is characterized by fatigue and morning
stiffness in the hips and shoulders (58). 90% will have an erythrocyte sedimen
tation rate (ESR) greater than 50 mm/h. C-reactive protein (CRP) testing
is ordered in conjunction with ESR,. A temporal artery biopsy is warranted in
some patients, but can give false negative results due to skip lesions.
• Anterior arteritic ischemic optic neuropathy (AION) occurs secondary to

occlusion of the short posterior ciliary arteries (SPCAs) from the oph
thalmic artery.
• Ischemic optic neuropathy findings may not be present for the first 24-48
hours after the onset of blindness (58).•
• If temporal arteritis is suspected, therapy with prednisone should be ini

tiated immediately. Low dose aspirin (81 mg) should also be considered
to reduce the chance of visual loss or stroke (58).
W e g e n e r’s G ran u lom atosis
Systemic vasculitis involving the upper respiratory tract, lungs, and kidneys.
65% have ocular involvement, including (17):

332 9.4. RHEUMATOLOGIC DISORDERS
• Granulomatous sclerouveitis, retro-orbital mass lesion with proptosis,

conjunctivitis, episcleritis, scleritis, and ciliary vessel vasculitis (17).
• Peripheral sclerokeratitis may also occur and lead to corneal ulceration (42).
S clerod erm a
This is a multisystem disorder causing inflammation and vascular changes of

the skin and internal organs (17). Ocular effects include:
• Dry eye and shrinkage of areas of the skin, including the conjunctiva (1).
O th e r R heum at()logical D isorders ^ b ^7 ■

G out
• Gout is caused by the formation of monosodium urate crystals in joints

in response to increased uric acid levels.
• Occurs most frequently in the metatarsophalangeal (MTP) joint of the

big toe, which is called p od a g ra (57).
• More common in men. Presents with a sudden onset of red, hot joints.
Allopurinol (Zyloprim®) reduces the incidence of gout flare-ups

by inhibiting xanthine oxidase, the enzyme responsible for uric
acid production (39). B and keratopathy can occur secondary to
gout.
The H L A -B 2 7 test can be ordered to help determine uveitis etiology. Most

cases of acute anterior uveitis are idiopathic; however, the three most common
known conditions that cause acute, anterior, non-granulomatous uveitis are
ankylosing spondylitis, inflammatory bowel disease, and reactive arthritis. The
following is the percentage of positive HLA-B27 results for each:
• Ankylosing spondylitis = 90%
• Reactive arthritis = 85 — 95%
• Inflammatory bowel disease = 60% (21).
Since the most common causes of acute, anterior, non-granulomatous uveitis

are commonly HLA-B27 positive, ordering the test fails to differentiate between
the moBt common causes of the condition.

- SECTION 9,5 -----------------------------------------------------------------------
Diseases o f Im m unodeficiency
Diseases of immunodeficiency may develop due to inherited defects in the de

velopment of the immune system, or may be secondary to diseases that affect
the normal immune system. An example of an inherited immunodeficient state
is deficiency of Immunoglobulin A.
• IgA deficiency is the most common of the primary immunodeficiency

diseases.
• IgA is the prominent immunoglobulin in external secretions, including

the tea r film; therefore, it is involved in mucosal defenses.
• A patient with IgA deficiency will show a significant decrease in IgA in

both serum and secretions.
• Patients may be asymptomatic, or may suffer from recurrent respiratory

tract infections, k eratin ization o f the cornea, weight loss, and diar
rhea (36).
Caused by HIV, an RNA virus that uses reverse transcriptase to make vi
ral DNA within infected cells. AIDS is marked by severe immunosuppression
and resulting opportunistic infections. The most common way to acquire HIV
is through sexual contact. The most common symptoms include fever, lym-
phadenopathy, sore throat, rash, myalgia/arthralgia, and headache (31). Pro
longed duration of these vague symptoms with the presence of mucocutaneous
ulcers is suggestive of the disease (31).
In AIDS, a severe loss of C D 4 + T -C ells, combined with impair

ment in the function of surviving Helper T-Cells, leads to a decrease
in immune-related cells. The severity of the disease directly corre
lates with the number of remaining CD4+ T~cells.
• C D 4 cou n t o f 200 means the patient has progressed from HIV to

AIDS (7) (36).•
• E L IS A test (enzyme linked immunosorbent assay) is the screening test

for HIV diagnosis.

334 9.6. INTEGUMENTARY SYSTEM
• W estern b lot is used to confirm the ELISA test.
* Collectively, these tests have a 99.9% specificity rate (58).
The most common ocular infection and the leading cause of blind
ness in AIDS is C ytom egalovirus retinitis; patients with CD4
counts lower than 200 are at risk, and lower than 50 are at high
risk (25).
Common opportunistic infections and neoplasms found in HIV-infected pa

tients include:
• P n e u m o cy stic pn eu m on ia (PCP pneumonia, caused by Pneumocystis

jiroveci)
• Parasitic infections such as toxop lasm osis (discussed in ocular disease

chapter), which can present with papilledema (33%) and cranial nerve
palsies (33%) due to meningoencephalitis.
• Bacterial infections such as pneumonia, meningitis, and M y co b a cte riu m

tu bercu losis.
• Viral infections such as cytomegalovirus and herpes simplex virus. K a

p o s i’s sarcom a is a malignancy caused by the herpes virus HHV-8 (36).
— SECTIO N 9.6 — ------------------------------- -------------------------------------------- —--------------------------------
In teg u m en ta ry System
B enign Skin Lesions 'y;V>;; K-v- k h y V V ■j

S eb orrh eic K eratosis
Crusty, plaque-like, tan lesions that have a classic elevated “stuck-on” appear
ance. These are found most commonly in males over 30. Seborrheic keratosis
is usually not treated; for small lesions, shave excision or curettage is recom
mended; larger lesions require complete surgical excision (21).
K era toa ca n th om a
Isolated dome-shaped nodules usually seen on the face that mimics squa
mous cell carcinoma. It has a spontaneous remission over a period of several
months (42).

P ap illom as
• Common slow-growing squamous epithelial tumors (e.g. viral warts) that

may be caused by human papilloma virus (HPV).
• Characterized by finger-like or cauliflower-like appearance (“skin tag”);

usually elevated and multilob ulated with a central vascular core.
• Treatment for papillomas can range from no intervention to excision or

snipping, chemical cauterization, surgical excision, or cryotherapy (11).
X an th ela sm a
• These are yellow, elevated, plaque-like lesions that are typically bilateral,
symmetric, and located within the medial portion of the eyelids.
• Xanthelasma lesions are associated with older age, female gender, and
high cholesterol, although most patients with xanthelasma have normal
cholesterol (21).
• Treatment for xanthelasma lesions include full-thickness surgical excision,

carbon dioxide laser treatment, and chemical cauterization; recurrences
after treatment are common (21).
M o llu scu m C on ta g iosu m
• Chronic, infectious (spreads by direct contact) skin condition caused by

D N A p o x virus. The condition is common in children and young adults
in communities with poor hygiene.
• Classic presentation is a single or multiple d om e-sh ap ed w axy n odu les

on the eyelid or eyelid margin. Patients are typically asymptomatic, but
nodules can spontaneously open, resulting in a follicular conjunctivitis.
• If multiple molluscum nodules are present, human immunodeficiency virus

(H IV ) should be considered.
• Treatment options include incision and curettage, shaving excision, cau

terization, or cryotherapy (17).
A cn e R o sa ce a
Syndrome of undetermined etiology characterized by vascular abnormalities

and papulopustular lesions on the cheek and forehead. Classic signs include
superficial telangiectasia, rhinophyrna (late-stage finding), and facial flushing.
The latter is associated with triggers such as alcoholic beverages, spicy foods,
caffeine, and increased sun exposure. Ocular findings include:•
• Hordeola, chalazia, phlyctenules, keratitis, and dry eye syndrome.

A llerg ic C on tact D erm atitis
Delayed Type 4 hypersensitivity response of inflammation to any substance

that comes in contact with the skin. Ocular signs include:
• Acute periorbital swelling.
• Conjunctival chemosis, redness, itching, and tearing (see Ocular Disease).
Im p e tig o
Gram (+ ) infection with classic h oney co lo re d cru sted lesions. Very com
mon in children.
H erpes S im plex V irus (H S V )
Two common types: HSV I and HSV II. Both can cause ocular infections, but
type I is significantly more common (98% of cases) (14). Type I HSV usually
causes infections “above the belt” and is transmitted by close personal contact
(e.g. mucous membranes, external skin). Type II HSV usually causes infections
“below the belt” (genital) and is sexually transmitted.
• HSV 1 is most commonly associated with ocular manifestations, but HSV

2 is the most common cause of herpetic keratitis in neonates (75%); trans
mission to newborns occurs through genital secretions during passage
through the birth canal (30) (28).
• 90% of adults with HSV I obtain it from a primary infection as a child (56).
The majority of these cases are asymptomatic; in fact, primary infections
manifest clinically in only 1 — 6% of patients (28).
• After this initial infection, the virus hides within the trigeminal (gasse
rian) ganglion and can reoccur at any time.
• Reactivation of HSV can be triggered by physical and emotional stress,

including sun exposure, hormonal changes, fever, stress, trauma, and
immunosuppression (non-exhaustive list) (21).•
• Noteworthy ocular complications include d en d ritic keratitis, disciform

endotheliitis, uveitis, and blepharoconjunctivitis.
After an initial corneal HSV epithelial infection, there is a 25%

chance of having a recurrence. The risk increases to 40 —45% after
a 2nd episode (56).

H erpes Z oster V iru s (H Z V )
Varicella zoster Virus (VZV) initially presents as chicken pox. After the initial
infection, the virus lays dormant in the nerve roots, Herpes Zoster is the
reactivation of V ZV in the dermatome that was associated with the latent virus.
66% of patients are over the age of 50 (17). Consider a medical evaluation in
patients younger than 40 to determine if they are immunocompromised (30).
In HZV ophthalmicus, consider the following:
• H u tch in so n ’s sign - rash located on the tip of the nose that indicates
a higher risk of ocular involvement.
• Blepharoconjunctivitis (typically with vesicles on the lid margin) and

episcleritis are relatively common.
• Uveitis, keratitis (e.g. pseudodendrite), conjunctivitis, retinitis, propto

sis, and extraocular muscle palsies may also occur (43).
B e h c e t’ s D isease
Inflammatory disease causing multisystem complications. R ecu rren t oral

aph th ou s ulcers and two of the following features are needed for diagnosis:
genital ulcers, eye lesions, or skin lesions (17). Most commonly seen in Asian
and Middle Eastern young adults. Ocular findings include:
• A cu te recu rren t h y p op y on , iritis, posterior and anterior uveitis, reti

nal vasculitis, vitritis, secondary cataracts, glaucoma, and neovascular
lesions (17).
jSkin Gancbrsc
M alignant M e la n o m a
• Most common cancer of young women (58).
• Depth of invasion is the number one prognostic factor (27).
• Bisk factors include age, skin color, family history, and repeated irritation
and sun exposure.
• Characteristics of suspicious skin lesions for malignant melanoma include

ABODE: asymmetry, border irregularity, color differences, large diame
ter, and enlarging.
- S u perficial spreading m elanom a is the most common variant

of melanoma (70% of cases). It lias rapid growth and is classically
found on non-exposed skin (e.g. upper back, anterior tibia) (28).

Basal Cell Carcinoma
• Malignancy of the basal cell layer of the epidermis. Often appears as a

shiny, firm, pearly nodule with superficial telangiectasia. Progression can
lead to central ulceration (“rodent ulcer”) .
• Treatment is with 5-FU or biopsy with surgical removal.
Squamous Cell Carcinoma
• Malignancy of the stratum spinosum layer of the epidermis. Non-healing

ulcer that often appears as an erythematous plaque. It can arise from a
pre-cancerous lesion called actinic keratosis.
jNeurocutancous syndrom es /v : pi
Sturge-Weber syndrome
Rare congenital vascular disorder characterized by a facial capillary malforma

tion known as a port wine stain. These patients may have seizures, focal
neurologic deficits, or mental retardation. Ocular findings include:
• Glaucoma (with corresponding visual field defects).
• Vascular malformations of the conjunctiva, episclera, choroid, and retina (15).
• Iris heterochromia.
Tuberous sclerosis
Multisystem genetic disease that causes benign tumors to grow in the brain
and other organs. About 90% percent of patients with TSC have one of the
characteristic skin lesions (59) which include hypopigmented macules (ash-leaf
spots), shagreen patches (areas of thick leathery skin that are dimpled like an
orange peel, usually found on the lower back or neck), angiofibromas, and a
distinctive brown fibrous plaque on the forehead (59). Ocular findings include:
• Retinal lesions such as astrocytic hamartomas or phakomas, which

appear as a greyish or yellowish-white lesion in the retina. Astrocytic
hamartomas can calcify, and can be seen on a CT scan.•
• Punched-out areas of chorioretinal depigmentation in the mid-periphery

of the retina.
• Coloboma.
• Angiofibromas of the eyelids.
• Papilledema (related to hydrocephalus).

- SECTION 9.7 --------------------------------------------------------------------------
G enetic P rinciples and D isorders
D o w n ’ s sy n d ro m e (T risom y 21)
• Most common chromosomal disorder (affects 1 in 700 children).
• Caused by an extra 21st ch rom osom e.
• Findings include m ental retardation, flat facial profile, p rom in en t

epican th al folds, con g en ita l cataracts, glaucom a, strabism us, a
simian crease oil the palms, congenital heart disease, and early onset of
Alzheimer’s.
• Down’s syndrome patients are at an increased risk for development of

keratocon u s (30).
K lin e fe lte r’s S y n d rom e ( X X Y )
* Most common cause of male primary hypogonadism (32).
• An extra X chromosome (X X Y individual) results in testicular atrophy,

long extremities, gynecomastia, female hair distribution, and hypogo
nadism (53).
T u rn er’s S y n d rom e (XO)
* Due to an absent X ch rom osom e.
• The only sex chromosome aneuploidy with established ocular findings;

common (25% or more) findings include strabismus, amblyopia, reduced
accommodation, and convergence insufficiency (16).
* Affects 1 in 3000 females and is characterized by short stature, dysgenesis,

webbing of the neck, and coarctation of the aorta.•
• Most common cause of primary amenorrhea (no menstrual periods) (53).

340 9.7. GENETIC PRINCIPLES AND DISORDERS
A u tosom a l D om inant
Autosomal dominant disorders result from abnormal structural genes. They

affect many generations and occur equally in males and females. They often
present after p u b erty ; one must consider family history in diagnosis. Exam
ples of autosomal dominant disorders include:
V on H ip p el L indau disease
An inherited, autosomal dominant syndrome manifested by a host of benign

and malignant tumors. Ocular findings include:
• R etin a l angiom as that can hemorrhage if left untreated, leading to

retinal detachment, glaucoma, and loss of vision.
N eu rofib rom a tosis ty p e 1 (V on R eck lin gh au sen ’ s disease)
This disease is characterized by tumor-forming nerve cells; physical problems

arise according to tumor location. It affects 1 in 3000 individuals; 50% of these
patients have new mutations with no prior family history (48). Presents with
the following:
• Classic triad of cafe au lait sp ots, n eu rofibrom as, and Lisch n o d

ules o n th e iris (30).
• O p tic nerve gliom as.
M a rfa n ’s S yn drom e
• Connective tissue disorder characterized by skeletal anomalies (very tall

with long extremities, subluxating joints, and long fingers and toes).
• Causes cardiovascular side effects such as aortic incompetence, dissecting

aortic aneurysm, and floppy mitral valves (48) (57).•
• O cular effects include subluxation o f the crystalline lens and

retinal detachments (30).
H u n tin gton ’s C h orea
• Autosomal dominant disorder that is located on chromosome 4 (58).
• Characterized by a gradual onset and progression of chorea (involuntary

muscle movements) and dementia.

• Clinical onset is between 30-50 years of age, with a 15-20 year survival
rate (58).
• Abnormal eye movements will occur and include a delay in pursuits,

voluntary saccades, and refixation (38).
Familial Adenomatous Polyposis (FAP)
• Deletion on chromosome 5 results in hundreds of polyps on the colon

post-puberty.
• 100% of these patients get colon cancer (42).
- Gardner’s Syndrome is a variant of FAP characterized by multi

focal CHRPEs (4 or more) (30).
Autosomal Recessive
These are usually only seen in 1 generation, as 25% of offspring from 2 carrier
parents are affected. The diseases are often more severe than the dominant
disorders, and will often present in childhood. Examples of autosomal recessive
diseases include:
Sickle Cell Anemia
• Patients have painful crises due to sickle shaped (or crescent shaped)
red blood cells causing blockages within arteriole vessels; this ultimately
results in organ failure.
• The most common form of sickle cell anemia is caused by a single base
pair mutation in the Beta globin gene where valine is substituted for
glutamic acid.
• 1 in 400 African Americans are afflicted (36); 8% of the African-American

population are carriers (32).•
• Sickle cells can occlude retinal arterioles, leading to ischemia and subse
quent retinal neovascularization. The new blood vessels are often called
“sea fan” retinopathy because of their characteristic shape.
P K U (Phenylketonuria)
• PKU is caused by mutations in the enzyme phenylalanine hydrox

ylase; this is used in the amino acid conversion of phenylalanine to tyro
sine. If this disease is not treated, it will result in mental retardation. All
newborns are tested for PKU. If the patient responds as a positive carrier,
then treatment with a diet low in phenylalanine is initiated. Phenylala
nine is found in milk products, aspartame, meat, and chicken.

342 9.7. GENETIC PRINCIPLES AND DISORDERS
• Occurs in 1/10,000 people (36).
Tay-Sachs disease
Tay-Sachs disease is a genetic disorder that most commonly affects eastern

European (Ashkenazi) Jews and results in the progressive destruction of the
nervous system. Ocular findings include;
• Cherry-red spot in the retina.
• Atrophy of the optic nerve.
'X-Linkod genetic disorders A;:ACV;A..A/" ’A*AA, . -

F a b ry ’s D isease
Caused by abnormal lipid deposits in blood vessel walls throughout the body.
Deficiency of the enzyme alpha galactosidase A allows lipids to build up to
harmful levels in the eyes, kidneys, autonomic nervous system, and cardiovas
cular system. It affects adolescent boys and is characterized by excruciating
pains in the extremities and abdomen. Areas of telangiectasias on the umbili
cus, groin, elbows, and knees are diagnostic (36). Ocular findings include:
* Light colored, whorl-shaped corneal opacities (whorl keratopathy).
D u ch en n e M u scular D y strop h y
• Caused by a deletion within the gene encoding dystrop h in .
• 1/3000 male infants are afflicted, with symptoms appearing by age 5.
• Condition is characterized by muscle weakness that begins in the pelvic

girdle and progresses superiorly (36).
jM ultifactorial D isorders
O steogen esis Im p erfecta (B rittle B on e D isease)
Caused by a host of genetic defects giving rise to abnormal collagen synthesis.

Characterized by multiple fractures occurring with minimal trauma. Ocular
findings include:•
• Blue sclera, keratoconus, and megalocornea (54).

These are transmitted only through mothers (m aternal inheritance). All

offspring of affected females may show the disease. An important mitochondrial
disorder with ocular manifestations is Leber’s Hereditary Optic Neuropathy.
L e b e r ’ s H ered ita ry O p tic N eu rop ath y
• Rare recessive disorder that can cause loss of central vision.
• Most commonly seen in men in their late 20s or early 30s (29).
Remember it as M y M o th e r L eber L ost M y Eyes,
- SECTION 9.8 -------------------------------------------------------------------------- —
H em ato p o ietic an d Lym phoid System •
p ^ o r i r N e p p l a ^ t l p ^ ^ i $ p r d § r k ^ ^ ■V: ^v^:t-
A N E M IA S (D ecrea sed h e m og lob in )
Iron D eficien cy A n em ia
• M o st c o m m o n ty p e o f anem ia - m ore than 50% o f anem ias fit

into this ca te g o ry (57).
• In adults, often results from GI blood loss (peptic ulcer disease, colon
cancer, etc.).
• May also occur with malabsorption or increased need with decreased

intake, such as in childhood or pregnancy.
• Iron deficiency impairs cellular functions and can cause brittle hair, nail
spooning, and pica (eating things like dirt or ice).
• Treat with oral iron.
A p la stic A n em ia
• Pancytopenia characterized by severe anemia, neutropenia, and throm

bocytopenia.
• May be caused by infectious agents (viruses), radiation, or drugs (chlo

ramphenicol, a cetazola m id e, chemotherapy drugs).

344 9.8. HEMATOPOIETIC AND LYMPHOID SYSTEM
• Chronically damaged kidneys synthesize inadequate amounts of erythro

poietin (EPO), a hormone that normally stimulates RBC production in
the bone marrow.
Sickle C ell A n em ia
• Review information found in genetic disorders.
C lin ical N ote: Sickle cell anemia can cause proliferative retinopa
thy due to the crescent or sickle-shaped cells occluding retinal ves
sels.
V ita m in B 12 D eficien cy
• Due to inadequate intake or malabsorption of vitamin B12; malabsorption

is often caused by pernicious anemia.
• Pernicious anemia is characterized by autoantibodies against the parietal

cells of the stomach, resulting in decreased production of intrinsic factor.
F olic A c id deficien cy
• Dietary deficiency is the leading cause and is especially common in alco

holics.
• May also be drug-induced (chemotherapy, methotrexate), or from mal

absorption syndromes.
• Folic Acid deficiency in pregnancy increases the risk of neural tube defects
(spina bifida).
jNeoplastic D isorders of P lasm a Cells (7

M u ltip le M y elom a
Proliferation of a malignant clone of plasma cells in the bone marrow. This

often results in extensive skeletal bone destruction, unexplained anemia, hy
percalcemia, and acute renal failure.

jNeoplast ic D isorders o f:W h ite B lopd GclLi (W B C s) .

Leukemia and lymphoma are malignant proliferative diseases involving leuko
cytes. Early cell growth and maturation are inhibited, causing “malignant
clones” of these cells to accumulate. Death results because of substantial loss
of normal cells, and also due to poor organ function owing to the increase in
malignant cells.
L y m p h o m a - L y m p h T u m or
Proliferation of malignant lymphoid cells in solid tissues such as lymph nodes,

spleen, and the GI tract. Initially the tumor is localized, but it may subse
quently spread. There are two types of lymphoma;
1. Hodgkin’s Lymphoma
2. Non-Hodgkin’s Lymphoma
H o d g k in ’s L y m p h o m a (40% o f lym p h om as)
• Two peak age groups: 15-30 and then >50.
• Commonly presents with enlarged lymph nodes, fever, night sweats, and
itching.
• Characterized by R e e d -S te rn b e rg cells (“owl-eyes” nucleus).
• Prognosis is good if diagnosed early.
• 50% o f cases are associated w ith E B V (42) (48) (57).
N o n -H o d g k in ’s L y m p h o m a (60% o f lym p h om as)
• Enlarged lymph nodes and GI tumors (with abdominal pain),
• Heterogeneous group of malignancies with variable prognoses depending

on the type.
• Bone marrow biopsy is performed to determine T or B cell types (42) (48) (57).
A cu te Leukem ia
This disease can affect all ages, but usually occurs in younger patients. The pre
dominate cell type is B last cells: >30% of marrow cells are blasts (immature
cells). There are two major types of Acute Leukemia:
1, A c u te M y e lo b la stic L eukem ia (A M L )

346 9.8. HEMATOPOIETIC AND LYMPHOID SYSTEM
• Occurs in infants and middle aged or older.

• Characterized by a normal W BC count with excessive myeloblasts.
• A u er R o d s may be seen within leukemic cells in the blood (42).
2. A c u te L y m p h oblastic Leukem ia (A L L )
• Peak age is 2-10 years.

• Normal W BC count with excessive lymphoblasts.
• With treatment, 75% of children remain disease free > 5 years (42).
C lin ical N o te ... A retinal hemorrhage with a white spot in the

middle (R o th S p ot) is characteristic of leukemia and endocarditis.
Chronic Leukemia
This disease usually affects older adults. The predominant cells are mature cells
of the bone marrow. Patients are often asymptomatic and may have anemia.
There are two types of chronic leukemia:
1, Chronic Myelocytic Leukemia (CML)
• Age of onset is 25-60 years old. Prognosis is poor, with only a 3 year
survival rate.
• Characterized by a W BC count of 50,000 to 300,000 with increased
granulocytes in all states of maturation.
• 90% of cases have the Philadelphia chromosome (3).
2. Chronic Lymphocytic Leukemia (CLL)
• Age of onset is greater than 50 years old.

• Male/female ratio is 2:1.
• Characterized by a W BC count of 20,000 to 200,000 with a predom
inance of mature small lymphocytes.
• 5 to 10 year survival rate (48).
Non-Neoplastic Disorders of Blood Cells
Leukopenia
• A decrease in the number of white blood cells.
• Due to bone marrow injury, bone marrow inactivation, drugs, or chemical

suppression.

L eu k ocytosis
• Increase in the absolute number of white blood cells.
• Can occur after surgery or result from infections, illness, stress, or preg
nancy.
N eu trop h ilia
• Increase in the absolute number of neutrophils.
• Typically results from stress, exercise, pain, fear, or pathologic infections

(typically bacterial) (non-exhaustive list).
T h r o m b o cy tosis
• Elevated platelet count.
• Causes include inflammation, kidney disease, or spleen removal (58).
P a n cy to p e n ia
• Decrease in the.number of red and white blood cells and platelets.
T h r o m b o c y to p e n ia
• Decrease in platelets.
• Causes include infection, liver failure, and bone marrow disorders (58).
- SECTION 9.9 ----------------------------------------------------------------:-----------------------------------
C ardiovascular H em odynam ic D isorders
' '. ' '•/ • •p / ' •. • -.-TV ' /: - V
Increased interstitial fluid that can be non-inflammatory (yielding protein-

poor transudate) and inflammatory (yielding protein-rich exudate) in etiology.
Edema can be recognized on exam by increased swelling of the legs due sub
cutaneous edema, or shortness of breath due to pulmonary edema. Treatment
includes diuretics and compression stockings.

348 9.9. CAB,DIO VASCULAB HEMOD YNAMIC DISOB,DEBS
N on -in fla m m a tory Causes o f E dem a
• In creased organ pressure - seen in congestive heart failure, liver cir

rhosis, and venous obstruction or compression.
• R e d u ce d plasm a osm otic pressure - protein-losing glomerulo-pathologies

and malnutrition.
• L ym ph a tic ob stru ction - post-surgical or neoplastic.
• S od iu m retention- excessive salt intake with renal insufficiency.
D ia b e tic m acular edem a is caused by microaneurysms and dila

tion of capillary walls. Pericytes, endothelial foot-plates that sur
round the vessels, are damaged, allowing leakage of blood and fluid
with resulting edema (30).
In fla m m a tory causes o f edem a
• Acute and chronic inflammation.
• Angiogenesis.
Leakage of blood due to a vessel injury that may be uncontained or enclosed

within a tissue. Hemorrhages within a tissue are referred to as hematomas. All
are grouped according to size (50).
P etech iae: These are 1-2 mm hemorrhages in the skin.
P u rpu ra: Greater than 3 mm hemorrhages associated with trauma, local vas
cular inflammation, and low platelet counts.
E cch ym oses: Greater than 1-2 cm and include subcutaneous hematomas or

bruises.
H e m o th o r a x /H e m o p e rica rd iu m /H e m o p e rito n e u m : These are large ac

cumulations of blood in body cavities.

I d "Y Y '- e:,,;,bViCo:V iTVC:V T iiy y ;E V ';iTb :'/b;,,■:C V ;yv.j u sC s j
A thrombus results from an inappropriate activation of blood clotting in an

uninjured vein, or an occlusion of a vessel after a relatively minor injury. These
can form anywhere in the circulatory system, may be arterial or venous, and
may be non-occlusive. The most common location of thrombus formation is
the deep venous system in the legs.
V I R C H O W ’ S T R I A D is a major theory delineating the cause

of a venous thromboembolism (VTE). It proposes that VTE occurs
as a result of:
1. Alterations in blood flow (stasis)
2. Vascular endothelial injury
3. Alterations in the constituents of the blood through an in

herited or acquired hypercoagulable state (5).
A cq u ire d causes o f h y p ercoa g u la b le states include: Oral con tra cep

tive (O C P ) use, smoking, vasculitis (e.g. temporal arteritis), and malignan
cies, as well as conditions that cause stasis of blood flow such as immobilization
and pregnancy.
In h erited h y p ercoa g u la b le states include: Factor V Leiden mutation,

prothrombin gene mutation, protein C and S deficiency, and antithrombin III
deficiency.
V enous T h ro m b o sis
Commonly occurs in either the superficial or deep leg veins. Those in the deep
leg veins (typically above the knee) are more likely to embolize to the heart or
lungs.
A rterial T h ro m b o sis
These are commonly formed from atherosclerosis or a myocardial infarction.

They usually travel (embolize) to the brain, kidneys, and spleen.

350 9.9. C.AUDIO VASCULAR HEMOD YNAMJC DISORDERS
C R V O and B R V O ... Systemic hypertension and diabetes are

associated with an increased risk for the development of central
and branch retinal vein occlusions, conditions that most commonly
result from thrombus formation.
A th rom bu s is a clot that remains where it was formed. An em

bolu s is a clot that has dislodged from where it was formed.
Êmbolism ' • '' 'd h V ,

This refers to any intravascular solid, liquid, or gas mass carried by the blood
to a distant site from its point of origin; 99% arise from thrombi (thromboem
bolism). There are six types of emboli (36):
• Fat em b oli are associated with long bone fractures and liposuction.
• A ir em b olism s usually result from gas bubbles after a chest wall injury
or from an obstetric procedure.
• T h rom b u s is the number one cause of emboli. 95% of emboli from DVTs
go to the pulmonary system (pulmonary emboli (PE)).
• B a cteria and T um or can cause tissue destruction and muscle pain.
• A m n io tic fluid em b oli can lead to DIC, especially postpartum.
Shock
Shock is decreased blood perfusion resulting from a reduction of either cardiac
output or circulating blood volume. There are the four types of shock:
C a rd iog en ic: Etiologies include myocardial infarction, ventricular rupture,

arrhythmias, and pulmonary embolisms. The heart fails to pump due to
cardiac cell damage, extrinsic pressure, or outflow obstruction.
H y p o v o le m ic: Clinical examples include hemorrhage and fluid loss from vom
iting, diarrhea, burns, or trauma.
Sep tic: Examples include overwhelming microbial infections or toxic-shock

gram positive septicemia. The main mechanism includes peripheral va
sodilation, leading to pooling of blood.

A n a p h y la ctic: Histamine can cause the following effects during anaphylac

tic shock:
• Cardiovascular: Hypotension and tachycardia.

• Upper Respiratory: Sneezing, itching, hoarseness, and stridor (high-
pitched wheezing).
• Lower Respiratory: Bronchospasm.
• GI: Nausea, vomiting, abdominal pain, and diarrhea.
• Skin: Urticaria, angioedema, and pruritis.
• Neuro: Headache, syncope, and seizure.
■T' v - L ' ,-.-r

r ie u r !'-.v.e.
_if-. -- •■
Aneurysms are localized abnormal dilations of vessels. A true aneurysm is en

closed by complete arterial wall components. The most common aneurysms
occur in the abdominal aorta, iliac, and other large arteries. See Cerebrovas
cular Disease section for more on intracranial aneurysms.
• False aneurysms (pseudo aneurysms) can form with parts of the arterial
wall missing.
• Death due to aneurysm may result from rupture, pressure upon adjacent
structures, occlusion of the proximal vessels, or embolism from mural
thrombosis.
• P u p il-in v olvin g C N II I palsies are most likely the result of an aneurysm
• Abdominal aortic aneurysms are typically found in men older than the
age o f 50.
• The risk of rupture increases with the maximal diameter of the aneurysm
bulge.
r - SECTION 9.10
P ath ology o f the Heart
A th erosclerosis
Slowly progressing disease of the arteries marked by elevated fibrosis and fatty
intimal plaques. These are formed by fat deposits, smooth muscle cell prolif
eration, and synthesis of an extracellular matrix in the intima. Elastic arteries
are involved, principally in the abdominal aorta, coronary arteries, popliteal

352 9.10. PATHOLOGY OF THE HEART
arteries, descending thoracic artery, and internal carotid arteries. Patients are
asymptomatic for decades and can eventually experience shortness of breath
and chest pain (36).
E n doth elial cell injuries may lead to atherosclerosis. Monocytes and leuko
cytes circulating in the bloodstream adhere to the injured vessel endothelium.
They then transform into macrophages, which attract lipids and become foamy
cells. This causes lipoproteins to migrate into the vessel wall at the center of
the endothelial injury. The accumulation of macrophages and the adhesion of
platelets to the injured areas cause a massive plaque or clot to form. This
can lead to reduced blood flow to the heart, ultimately causing a myocardial
infarction (36) (48).
• Atherosclerosis may begin in childhood, but typically appears in middle

age.
• Bisk factors include age greater than 50, family history, hypertension,
smoking, hypercholesterolemia, and diabetes.
• Lab results show increased total cholesterol, decreased HDL, increased

LDL, and increased CRP.
• Disease prevention includes following a low fat diet, exercise, BP moni

toring, and smoking cessation.
• Treatment includes aggressive lipid lowering therapy (using statin medi

cations), diet, and exercise. Stenting of arteries also serves as a secondary
treatment for patients who demonstrate symptoms of coronary artery dis
ease (CAD).
• A rcu s Senilus is the most commonly encountered peripheral corneal

opacity. It is a sign that the patient has or has had high cholesterol. It
does not affect vision (30).
Normal cholesterol values include... Total cholesterol should be less

than 200, HDL should be 40 or higher, LDL should be less than
100, and triglycerides should be less than 150.
C o ro n a ry A rte ry Disease
Characterized by atherosclerosis within the coronary arteries supplying blood

to the heart. Patients can be asymptomatic or have chest pain (angina) and
dyspnea (difficulty breathing). If not treated by diet, exercise, or stenting of

the artery, the patient may suffer a myocardial infarction (MI). If a patient
experiences an MI, 325 m g o f aspirin should be given immediately.
If a patient is found with no pulse or respiratory efforts, cardiopu l

m on ary resu scita tion (C P R ) should be initiated. According to
the 2010 BLS Guidelines, Chest compressions are the most impor
tant element of CPR. Interruptions in chest compressions during
CPR, no matter how brief, result in declines in coronary and cere
bral perfusion pressure. The critical performance standards for
CPR include: Maintain a rate of at least 100 compressions per
minute, compress the chest at least 5 cm (2 inches) with each
down-stroke, allow the chest to recoil completely between each
down-stroke, and minimize the frequency and duration of any in
terruptions. If the rescuer chooses to give ventilations, the AHA
2010 Guidelines recommend that CPR be performed at a ratio of 30
compressions to 2 ventilations until an advanced airway has been
placed. Following placement of an advanced airway, compressions
are continuous, and ventilations are delivered approximately eight
times per minute (8).
C arotid A r te r y D isease
See also Cerebrovascular Disease section. This is atherosclerosis of the carotid

arteries. 25% of strokes are due to a build-up of plaque causing stenosis of the
carotid arteries (58). These patients can present with sensory loss, dizziness,
am aurosis fugax, or complete loss of vision in the ipsilateral eye. They may
also have a high-pitched bruit over the artery (58).
H yperten sive H eart D isease (H T N )
Hypertension is the most common primary diagnosis in America (13). More

than 50% of people 60-69 years old, and approximately 75% of those 70 years
of age and older, are affected (10). The rise in systolic blood pressure (SBP)
continues throughout life, in contrast to diastolic blood pressure (DBP), which
increases until age 50 and then tends to level off.•
• The JNC 7 report introduced a new classification of BP in 2004 that

includes the term p reh y p erten sion , defined as BP ranging from 120 to
139 mmHg systolic and/or 80 to 89 mmHg diastolic. A blood pressure
of 140/90 (hypertension) or higher requires treatment and leads directly
to increased risks o f heart attack, heart failure, stroke, and kidney dis
eases (13).

354 9.10. PATHOLOGY OF THE HEART
• The goal is to lower SBP and DBF to <140/90 mraHg (13). In pa
tients with HTN and diabetes or renal disease, the BP goal is <130/80
mmHg (13).
• The risk of HTN increases with age, family history, race, obesity, dia
betes, smoking, and excessive sodium intake (42) (57). African Americans
have the highest probability of HTN, with Asians maintaining the lowest
risk.
• Treatment includes anti-hypertensive medications, exercise, weight loss,

and low sodium diet.
When taking a blood pressure reading, the patient should be seated

quietly for at least 5 minutes in a chair, with feet on the floor,
and arm supported at heart level. Smoking, caffeine, and exercise
should be avoided for 30 minutes prior to blood pressure measure
ment (13). An appropriately sized cuff (cuff bladder encircling at
least 80 percent of the arm) should be used to ensure accuracy. At
least two measurements should be made and the average recorded.
SBP is the point at which the first of two Korotkoff sounds is heard,
and the disappearance of the Korotkoff sound is used to determine
DBP (13).
H y p erten siv e retinopathy is characterized by narrowing of the

retinal arterioles. In acute or advanced hypertension, the retinal
vasculature may be injured enough to cause occlusion or leakage.
These changes may be seen as nerve fiber layer infarcts (soft exu
dates or cotton-wool spots), extravascular edema (hard exudates),
intraretinal hemorrhages, and retinal arterial macroaneurysms.
Hypertensive choroidopathy is often found in young patients with
acute hypertension. These findings can include E lschnig sp ots
and Siegrist streaks. Severe HTN can cause optic neuropathy and
may present with flame hemorrhages, venous congestion, and mac
ular exudates (13) (62) (2). P ap illedem ea is found in stage 4
hypertensive retinopathy (malignant hypertension).
C on gestive H eart Failure (C H F )
• CHF is a chronic disease that is defined by the heart’s:

1. Inability to fill with blood (diastolic heart failure), or

2. Inability to pump sufficient amounts of blood through the body
(systolic heart failure).
• Patients may have left-sided CHF, right-sided CHF, or both.
1. Left Sided Heart Failure

— When the left side of the heart fails, blood backs up into the
lungs, causing them to fill with fluid (pulmonary edema).
— The most common cause of left-sided CHF is Ischemic Car
diomyopathy resulting from coronary artery disease (myocar
dial infarctions).
— The primary symptom is shortness of breath (dyspnea on exer
tion) .
2. Right Sided Heart Failure
— Inability to pump blood into the lungs, causing blood to back
up in the abdomen (ascites) and legs (lower extremity edema).
— Symptoms include edema, chest discomfort, and shortness of
breath.
— The most common cause of right-sided CHF is left-sided CHF.
Other causes include pulmonary hypertension, COPD, and right
sided myocardial infarctions.
* Risk factors include coronary heart disease, cigarette smoking, hyperten

sion, obesity, diabetes, and valvular heart disease.
• Diagnostic findings of CHF include elevated BNP (Brain Natriuretic Pep

tide), cardiomegaly on chest x-ray, and changes on echocardiogram.*
* Treatment includes beta blockers, ACE inhibitors, diuretics, and correc

tion of any underlying causes.
R h eu m a tic Fever
Generally affects persons aged 5-15; results from untreated pharyngeal infec
tions with group A beta hemolytic streptococci (Strep pyogenes). This disease
can alter the shape of the heart valves. In 75 — 80% of cases, the mitral valve
is attacked, often requiring valve replacement later in life (42) (57). Common
signs and symptoms include fever, elevated ESR, red-hot joints, and endocardi
tis.
Bacterial Endocarditis
Bacteria may infect the inner lining of the heart, especially the valves.
• Risk factors include prosthetic heart valves, IV drug use, and age.

356 9.11. NERVOUS SYSTEM AND NEUROMUSCULAR DISEASE
• Patients present with fevers and may have symptoms from arterial emboli
or heart failure, depending on the severity of valvular damage.
• The echocardiogram (ultrasound of the heart) will show “vegetations”

(mixture of bacteria and thrombus) on heart valves or abscesses within
heart tissue (58).
Remember, R o th sp ots may be seen in endocarditis or leukemia.
H eart P alpitations
Heart palpitations are symptoms a patient experiences when the heart has an
atypical rhythm. Most are benign, irregular heartbeats, with the most common
being prem atu re ventricular com p lex es (P V C s). These can increase with
dehydration, stress, decreased sleep, exercise, or pregnancy.
- SECTION 9.11 ---------------------------------------------------------------------------------------------------
Nervous System and Neurom uscular Disease
Cerebrovascular Diseases T \ |
Transient Ischem ic A ttack s (T IA s )
T e m p ora ry neurologic deficits (always less than 24 hours, usually less than
15 minutes) due to inadequate perfusion; as perfusion is restored, patients are
left with no symptoms (58). The most likely cause is an embolism. There are
two types of TIAs:
• C a rotid artery T IA with contralateral hand/arm weakness or sensory

loss and face and leg symptoms. Patients can also have ipsilateral v i
sual sy m p tom s (am aurosis fugax) or aphasia.
* V ertebrobasilar T IA s can result in diplopia, ataxia, vertigo, dysarthria,

and either unilateral or bilateral visual loss (36) (48).
C lin ical N ote... A H ollenhorst plaque is an embolism found in

the retinal vasculature. These patients often have TIAs and should
be referred immediately.

Stroke
Characterized by a sudden onset of neurological deficits reflecting the arteries

involved and the brain structures they supply.
• Main risk factors include h yperten sion , diabetes, hyperlipidemia, to

bacco abuse, age, and family history.
• Auscultation of the subclavian and carotid arteries for a bruit can be a

clue to early diagnosis.
• C T scans are used to determine the size and location of strokes.
Ocular manifestations of strokes depend on the vasculature affected and whether

the macula is involved.
M acu lar Sparing H o m o n y m o u s H em ian opsia
Most commonly from a stroke in the occipital lobe that has affected either the
middle or posterior cerebral artery, but not both.
M a cu la O n ly H o m o n y m o u s H em ian opsia
Most commonly occurs from a tumor that has compressed both blood supplies
to the macular cortex. Almost never occurs from a stroke because occlusion
would have to occur in both blood supplies simultaneously.
T h ere are tw o ty p e s o f strokes: Ischem ic and H em orrhagic.
1. Ischem ic Stroke
Accounting for 80% of all strokes, ischemic strokes result from occlusion of an
artery leading to the brain; embolism of an atherosclerotic plaque is the most
common cause. Treatment involves modification of stroke risk factors (smoking
cessation, medications for hypertension, hyperlipidemia, diabetes, etc.).
2. H em orrh a gic Stroke
Occur as a result of accumulation of blood within the brain due to bleeding

from brain tissue, trauma, and/or vascular malformations. The most common
type of hemorrhagic stroke is a subarachnoid hemorrhage.
Subarachnoid H em orrh ages
• Patients present with sudden severe headaches, p u p il involving C ra

nial N erve III palsies, and nuchal rigidity

(
(
(
(
• 30% of these patients will have changes in consciousness (36) (48). ^
• Aside from head trauma, the most common cause of a subarachnoid hem
orrhage is rupture o f an intracranial aneurysm (32). ^
- Intracranial aneurysms tend to occur at arterial bifurcations and are

usually asymptomatic until they rupture, causing a hemorrhage. ^
— Those that cause Cranial Nerve III palsies tend to occur in the C ir
cle o f W illis between the junction of the posterior communicating {
and internal carotid arteries (58).
(
The C ircle o f W illis is the meeting loop for the basilar artery,
the internal carotids, and the anterior and posterior communicating
(
arteries, which are small arteries bridging the basilar and internal
carotids. The Circle of Willis forms an arterial circle beneath the (
brain and allows for a system of redundancy for the flow of the
blood to intracranial tissue.
(
A rtery Location A rea Vessel Supplies i
A nterior Cerebral Extends upward and Supplies frontal lobe
forward from (controls logical thought, personality, (
the internal and voluntary movement). )
carotid artery
M iddle Cerebral Last and largest Supplies frontal lobe, lateral (
branch of the surfaces of the tem poral and parietal \
internal carotid lobes, and the occipital lobe (controls the primary motor and I
sensory areas of the face, throat, |
hand and arm, and areas for speech and vision). ^
P osterior C erebral Stems from the Supplies tem poral and occipital lobes 1
basilar artery (strokes involving this vessel can cause /
contralateral hemplegia, hemianopsia, \
color blindness, verbal dyslexia, 1
and opposite visual field defects). j
(
These single events may be caused by fevers, headaches, stress, illness, or
neurological defects. (
• Signs and symptoms of seizures include cognitive dysfunction, nuchal
rigidity, staring episodes, and complete shaking of all ligaments. (
• E pilepsy is a condition with recurrent seizures. Status E pilepticus is
a prolonged seizure lasting longer than 5 minutes.•
c
• Treatment includes antiepileptics (phenytoin, phenobarbital, carbamazepine,
valproic acid). Absence seizures are treated with Klonopin.
(
(
(
(
(
S y n co p e
This is an abrupt, transient loss of consciousness lasting a few seconds to a

few minutes due to decreased blood flow to the brain (58). Prompt recovery
to full consciousness follows the syncopal episode. Causes include cardiac ab
normalities (heart rhythm disturbances or valve disorders), vascular problems
(postural hypotension or vasovagal episodes), or neurologic disorders (58). Spe
cific causes can be hard to diagnose and are usually benign.
There are five main types of headaches (36) (48).
C lu ster H eadaches
• Afflict men 30-50 years of age.
• They may be orbital or temporal in location; usually unilateral.
• Often occur in smokers and alcohol drinkers.
• These headaches often wake patients up at night or early in the morning.
• Generally 1 or 2 attacks per day, each lasting less than an hour.
• Often present with red eyes a n d /o r nasal stuffiness and can cause
a transient or perm an en t ipsilateral H orn er’s syn drom e (54),
T ension H eadaches
• Occur in all ages, particularly increased in females.
• May be worse with stress and may precede a migraine headache.
• Presents in a ban d-like d istrib u tion with varying intensities.
M igrain e H eadaches
• Migraines occur in women more often than men and often are started by
certain triggers.
• Usually begin at ages 20-30 and rarely occur after the age of 50.
• Migraines can present with or without an aura, nausea, or photosensitiv

ity.•
• Migraines typically last anywhere from 4-72 hours and are aggravated
by physical activity.
Copyright 201.4 by KMK Educational Services, LLC

T em p ora l A rteritis H eadaches
See Vasculitis Disease Section
B rain tu m ors
• Also cause headaches and can occur in all ages and sexes.
• These headaches are unique because they interrupt sleep.
• They are associated with nausea, vomiting, and visual changes, and
steadily increase in severity with time. Brain tumor causing headaches
tend to be worse in the morning.
• A child with a brain tumor is likely to have 1 or more other physical

symptoms (other than headache) and 1 or more neurological deficits (12).
Less than 1% of patients with brain tumors have headaches as their only
symptom (12).
Infectious Diseases of th e C entral N ervous S ystem ■

M en in gitis
Inflammation of the meninges caused by various infectious agents such as

viruses, bacteria, tuberculosis, fungi, or chemical agents. Viral meningitis is
common and is extremely difficult to treat.
• Affects 3 out of 100,000 persons.
• Often preceded by an upper respiratory tract infection.
• Signs and Symptoms: Classic triad of fever, headache, and neck stiffness
(meningismus). Patients may also have nausea, vomiting, sweats, weak
ness, myalgias, papilledem a, and photophobia. 1/3 of all patients will
have seizures.
N ervoiis System N eoplasm s • 'V/' / ^ j

Brain tumors can be either primary or metastatic. Primary brain tumors can
include a clinical presentation of seizures, dementia, or focal lesions.
G liob la stom a M u ltiform e
• T h e m ost co m m o n prim ary m alignant brain tum or.
• Found in the cerebral hemispheres and can cross the corpus callosum (36).

• The prognosis is grave, with less than one year life expectancy.
The most common brain cancer in adults is from metastasis - lung

and breast are common primary tumor sites.
M en in g iom a
• These arise from arachnoid cells and extend to the brain.
• M o st co m m o n b e n ig n brain tu m or, although it can be malignant as

well!
• Usually found in middle-aged women.
Schw annom a
• Tumor of Schwann cells. Can cause gradual onset of painless, progressive

proptosis.
• Often localized to the eighth nerve (referred to as an acoustic schwan

noma) (36).
• Rare. Most common in young to middle-aged adults.
P itu ita ry A d e n o m a
• Can be functional (hormone secreting) or non-functional. Prolactin-

secreting tumor is the most common functional pituitary adenoma.
• Can cause a b ite m p o ra l h em ianopsia or ju n ction al scotom a visual

field defect.
M u ltip le Sclerosis (M S )
Autoimmune disease marked by recurrent inflammation of the central nervous

system that ultimately results in demyelination. This condition typically af
fects females more than males, with an onset between 20 to 40 years of age.
MS is particularly likely to strike Caucasians living in Northern latitudes and
has genetic components. The diagnosis of multiple sclerosis requires two sep
arate central nervous system lesions on two or more occasions. These lesions
must include involvement of the white matter. Systemic symptoms include

weakness, numbness, tremor, lack of coordination, vertigo, bowel and bladder

dysfunction, and fatigue. Symptoms may occur abruptly and typically last
weeks to months (32).
• The most common presenting symptom of MS is o p tic neuritis (25% of

cases) (54).
• Other ocular findings include pain on eye m ovem ent (90%), affer
ent pupillary defect (APD), internuclear ophthalmoplegia (INO), and
diplopia.
C lin ical N ote.., A multiple sclerosis patient with optic neuri

tis will classically present with a sudden, non-progressive onset of
monocular vision loss. These patients can also report decreased
acuity after an increase in body temperature (U h th o ff’ s p h e
n om en on ).
G u illain -B arre S yndrom e (G B S )
Condition characterized by inflammation and demyelination of peripheral nerves

and motor fibers of the ventral roots. Classically presents with symmetric as
cending muscle weakness that begins in the distal lower extremities. Ocular
findings include:•
• Adie’s tonic pupil, diplopia (from multiple cranial nerve palsies), and
facial diplegia (19).
• Elevated protein in the cerebrospinal fluid can cause papilledem a.
M ya sth en ia G ravis
Autoimmune disease caused by a blockade of neuromuscular signals due to

autoantibodies binding to acetylcholine receptors (58). This affects all ages,
but is more common among younger women and older men (57). It is asso
ciated with a th ym ic tu m or (th ym om a), rheumatoid arthritis, and lupus.
Systemic symptoms include respiratory weakness and weakness of the jaw mus
cles. Ocular findings include:
• P to sis and diplopia secondary to external ocular muscle weakness.
* S y m p tom s are w orse at the end o f the day.

A lzh e im e r’ s D isease
• The exact reason Alzheimer’s disease develops is unknown, but patients

do develop deposits (plaques) of a protein called beta amyloid, and dis
organized masses of protein fibers within the brain cells known as neu
rofibrillary tangles.
• This is the most common form of dementia, affecting up to 10% of Amer

icans over the age of 65 (48).
• It is more prevalent in women, people with head injuries, Down’s syn

drome, prolonged exposure to chemicals, lower educational levels, and
epilepsy.
• There is no cure, but medications such as Aricept® help slow the pro
gression.
Vascular D em en tia
• Patients with vascular dementia have damaged areas of brain tissue sec
ondary to reduced cerebral blood flow (35). This is due to vessels having
blood clots or fatty deposits (cerebral microinfarcts).
• More prevalent among people who are at risk for strokes, especially those
with longstanding high blood pressure and diabetes. It can occur together
with Alzheimer’s disease.
P ark in son ’ s D isease
• Caused by a deficiency of dopamine in the striatum due to degeneration

of neurons in the substantia nigra.
• Classic symptoms include tre m o r at rest, rigidity, akinesia, and

postu ral in stability ( T R A P ) (7). Slowness of movement is often the
first sign of Parkinson’s disease, along with cogwheel rigidity and pill
rolling tremor.
• Treatment includes Levodopa, Bromocriptine, Carbidopa, and Sinemet®.
E pidural H em a tom a
After a closed head trauma like a fall or blow to the head, blood collects
between the skull and dura. The middle meningeal artery is often affected due

to a laceration of the temporal region of the skull. In general, the injury has
three phases: an initial loss of consciousness, a period of lucidity, and another
loss of consciousness.
S u bdu ral H em atom a
Venous blood collects between the dura and the arachnoid space. Patients may
or may not experience symptoms depending on the severity of the causative
trauma. In the elderly, this is commonly seen from a minor head injury, es
pecially if on coumadin. Symptoms vary, though altered mental state and
headache are common.
S y m p tom s t o w atch w ith any head traum a include:
• Changes in pupillary size (a blown pupil may signal an impending uncal

herniation).
• Nausea or vomiting.
• Loss of consciousness.
M iscellaneous D isorders y'V- ■ 1

H o rn e r’ s S yn drom e
• Sympathectomy of the face, which is a lesion above T -l.
• Signs and symptoms include the triad of:
— P to sis - drooping of the eyelid.

— A n h yd rosis - absence of sweating and flushing on the affected side
of the face.
— M iosis - pupil constriction.
• Associated with cluster headaches and P an coast tu m o r (tumor at the

apex o f the lung), which affects preganglionic sympathetic fibers (36).
B e ll’ s P alsy
* Idiopathic condition diagnosed by exclusion after factoring out other

causes of CN VII palsy.•
• Characterized by a sudden deficit of the lower motor neuron in CN VII -

affects the entire side of the face.

• Treatment during the attack includes patching or closing of the eyelid to

decrease exposure keratopathy and corneal dryness. A short course of oral
steroids and/or antivirals has been shown to increase the probability and
speed of recovery, although 71% of patients will have complete recovery
within one year without treatment (58).
- SECTION 9.12 ----------------------------------------------------------------------------------------------------
P ath o lo g y of th e E ndocrine System
T y p e 1 D ia b etes M ellitu s (Juvenile D iabetes)
Accounts for 10 —20% o f diabetic patients and predominantly afflicts younger

people (42) (58). The most common presenting symptoms are polyuria, poly
dipsia, and weight loss. 90% of cases of type 1 diabetes are immune-mediated
and will have a positive HLA association (58). This condition is caused by
a complete lack of insulin production due to b e ta cell destruction, which
can be triggered by environmental insult, virus, or genetic predisposition (58).
Treatment includes insulin injections and careful glucose and diet monitoring.
Complications include:
• D ia b e tic ketoacidosis.
• M icro a n g io p a th y (retin opath y, nephropathy, and neuropathy).
• Cataracts and glaucoma (42) (58).
T y p e 2 D ia b etes M ellitu s
Type 2 diabetes is caused by insulin resistance or abnormal (3 cell secretion of

insulin. Obesity is associated with 80% of cases of type 2 diabetes (42), and
most patients are over the age of 40 (58). Most patients are asymptomatic
at the time of diagnosis. Treatment includes diet monitoring, exercise, oral
glycemic agents, and occasionally insulin.
Appropriate lab tests for diabetics include a fasting glucose level

and elevated glycohemoglobin (h em og lob in A 1 C ). The Hgb A lC
reflects the state of glycemia over the last 90 - 120 days and should
be less than 7% (58). A fasting plasma glucose of 126 m g/dL or
higher is abnormal and warrants further clinical evaluation.

366 9.12. PATHOLOGY OF THE ENDOCRINE SYSTEM
Type 1 Type 2
ID D M N ID D M
Incidence 15% 85%
Insulin Therapy Needed Not always needed
Polyuria, polydipsia, Yes No
weight loss
Age <30 >40
Obesity No Yes
Genetic predisposition Slight Strong
IiLA association HLA DR 3 and 4 No
Islet Cells Severe /3-cell depletion Mild /3-cell depletion
Ketoacidosis Common Rare
Glucose intolerance Severe Mild
Type 1 diabetics should have a dilated fundus examination within

5 years of diagnosis. Type 2 diabetics should be examined upon
diagnosis. In both cases, yearly exams are indicated unless retinal
findings indicate more frequent care. A significant increase in blood
glucose is most likely to induce a myopic shift in the refractive error.
D ia b e te s Insipidus
This is marked by extreme thirst and polyuria resulting from a lack of ADH or
a deficiency in renal response to ADH. Treatment options consist of increased
fluid intake, intranasal desmopressin (ADH analog), indomethacin, or HCTZ
for the nephrogenic causes (57).
H y p o th y ro id ism
Caused by any abnormality (structural or functional) that hinders the appro

priate production of thyroid hormones.
* Symptoms include cold intolerance, hypoactivity, weight gain, fatigue,

lethargy, decreased appetite, constipation, weakness, myxedema, dry cool
skin, and coarse hair.
* Lab values show increased T S H and decreased Free T 4 and T 3 (57).*
* H a sh im o to’ s T h y roid itis is an autoimmune-mediated condition that

attacks the thyroid gland. This is the most common cause of hypothy
roidism in iodine-sufficient areas of the world (60). Common ages of
onset are 45-65. Females are much more commonly affected (ratio of
10:1) (42) (58).

H y p erth y roid ism
85% of hyperthyroidism cases are caused by Graves’ disease, an autoimmune

condition caused by TSH autoantibodies; this results in constant thyroid stim
ulation and excessive production of T3 and T4 hormones (24) (42).
• Classically affects middle aged patients (4th-5th decade); female predilec

tion (8:1) (58).
• 1% of patients have or will develop myasthenia gravis (21).
• Common systemic complaints include heart palpitations, weight loss, heat

intolerance and/or hair loss.
• Diagnostic testing will show an elevated T 4 and decreased TSH .
• Please reference the Ocular Disease chapter for a detailed review of the
ocular effects of this condition.
Recall that p ro p to sis and u p p er lid retra ction are the main oc
ular signs of Graves’ Ophthalmopathy. Su p erior lim bic kerato
con ju n ctivitis is an uncommon, bilateral, inflammatory reaction
associated with thyroid disease.
H y p erp a ra th y roid ism
Primary hyperparathyroidism is marked by hypercalcem ia. This disease is

caused by an over-secretion of parathyroid hormone. Symptoms include bone
pain, pathologic fractures, renal stones, constipation, mental changes, and fa
tigue. Treatment includes parathyroidectomy (47).
H y p op a ra th y roid ism
This is most commonly seen following a thyroidectomy. Symptoms include

tetany, muscle cramps, irritability, carpopedal spasms, convulsions, and mental
retardation (47). The most prominent evidence is decreased serum calcium.
Ocular findings include:
* C ataracts and uveitis.
• Blurry vision.
Copyright 2014 by KM K Educational Services, LLG

368 9.12. PATHOLOGY OF THE ENDOCRINE SYSTEM
A d d is o n ’s D isease
Chronic adrenocortical deficiency that is the result of au toim m u n e atroph y

o f th e adrenal glands. Symptoms include weakness, fatigue, anorexia, weight
loss, nausea and vomiting, diarrhea, abdominal pain, muscle and joint pains,
and amenorrhea. Treatment includes replacement therapy with a combination
of glucocorticoids and mineralocorticoids (42) (57).
C u sh in g’s S yn drom e (H y p ercortisolism )
The term Cushing’s syndrome refers to the effects of excessive corticosteroids

on the body. The majority of cases are the result of chronic, prescribed cor
ticosteroid medications. Patients usually present with central obesity, a
m o o n face, and a buffalo hump. They may also have osteoporosis, hy
pertension, poor wound healing, hyperglycemia, and elevated serum cortisol
levels (42) (57) (47).
P h e o ch ro m o cy tom a
Rare condition caused by a tumor secreting excessive amounts of norepinephrine

and epinephrine. The tumor can be located on one or both adrenal glands or
anywhere along the sympathetic nervous chain (47).
• Can affect any age - most common in 40-60 year old patients.
• Symptoms include elevated blood pressure, papilledem a, severe headache,

perspiration, heart palpitations, and anxiety with a sense of impending
doom.•
• Treatment involves removing the tumor.
P h e o c h r o m o cy to m a should be suspected in patients with hyper

tension accompanied by headache (pain), palpitations, pallor, and
perspiration (40).

i— SECTION 9.13
Renal System
lltehal Failure
A c u te R en al Failure
Acute renal failure is an abrupt decline in renal function with a decrease in

glomerular filtration rate (GFR), Blood tests measuring kidney function in
clude creatinine and blood urea nitrogen (BUN). These metabolic byproducts
accumulate in the blood in acute renal failure.
Remember, in acute renal failure GFR will be decreased. Creati

nine and BUN will be increased.
C h ron ic R en a l Failure
In this condition, the kidneys fail to make urine and excrete nitrogenous wastes.
The main causes of chronic renal failure are d iabetes (most common) and
h ypertension.
llofncrular Disease ■y
.r A-.--.
Inflammation of the glomerulus o f the kidney. There are two types:
1. N ep h ritic S y n d rom e: This is associated with hypertension, edema,

and active urine sediment with hematuria, blood casts, and protein
uria (42).
2. N e p h ro tic S y n d rom e: This is associated with greater than 3.5

gram s o f p ro te in in the urine. It is accompanied by hypoalbumine-
mia, hyperlipidemia, and edema (42).
|tnfections o f the R cnal System .. • •
P ost S tre p to co cca l G lom eru lon ep h ritis
• Renal infection caused by Group A Beta Hemolytic Streptococci (Strep

pyogenes).•
• Occurs 7-21 days after respiratory or skin infections. Most common in

children ages 5-15 years (42) (57).

370 9.11 DISEASES OF THE REPRODUCTIVE SYSTEM
* Symptoms include abrupt onset of hematuria, edema, hypertension, and

reel blood cell casts in the urine.
P yelon ep h r it is
Bacterial infection of the kidneys. "Symptoms include dysuria, frequency, ur

gency, fever, chills, flank pain, costovertebral angle tenderness, and nausea/vomiting.
N eoplasm s of th e U rin ary T ract

R en a l C e ll C arcin om a
Patients are usually asymptomatic, but if symptoms are present, they include
the classic triad of flank pain, hematuria, and abdominal renal mass. The first
diagnostic test is an abdominal ultrasound.
- SECTION 9.14 ---------------------------------------------------------------------------------------------------
Diseases of th e R eproductive S ystem
'Sexually T ran sm itted Diseases

C h lam yd ia
This is the m ost co m m o n bacterial sexually tran sm itted disease in th e

U S, causing cervicitis in women and urethritis and/or epididymitis in men.
The pathogenic organism is Chlamydia trachomatis (53).
* Inclusion conjunctivitis presents as a chronic infection with large inferior,

palpebral conjunctival follicles.
• Treatment includes A zith rom y cin o r D ox ycy clin e.
G on o rrh e a
Gonorrhea is a sexually transmitted disease that is caused by direct contact

with N eisseria gon orrh oeae. 85% of infected female patients are asymp
tomatic. The incubation period is 3-5 days following infection.
• Signs and symptoms can range from no symptoms, to vaginal discharge,

pelvic pain, urethritis, and dysuria or urinary frequency. Males most
commonly are asymptomatic or will have burning upon urination.
• With ocular infection look for severe, hyperacu te, purulent dis
charge.

• Treatment consists of a single dose of C eftriaxon e 125 m g IM plus

D o x y cy clin e 100 m g p .o . b .i.d . x 7 days. Doxycycline is given with
the Ceftriaxone to cover for chlamydia (most common STD), which often
is cohabiting with N. Gonorrhea (42).
H erp es S im plex V iru s
There are two types of herpes simplex, Type I and Type IT. Diagnosis is con
firmed by multinucleated giant cells on a W rig h t-G iem sa stain. Type I is
a mucosal lesion on the lips. Type II is associated with sexually transmitted
disease and is found on the mucosa of the male and female sex organs. Both
types can be found in the eye.
• Both can be symptomatic or subclinical; however, there are prodromal

symptoms that include tingling, irritation, or itching.
• Treatment includes Acyclovir or Famciclovir. There is no permanent cure,

but patients can take medication prophylactically to decrease recurrences.
Syphilis
Sexually transmitted disease caused by the spirochete T repon em a pallidum .

The clinical findings can be grouped into three phases: primary, secondary and
tertiary.
• The primary or early phase is characterized by a chancre (a painless ulcer

in the genital region).
• The secondary lesions can involve the eye, kidney, mucous membranes,
skin, CNS or liver.
• The tertiary phase leads to nervous system and ophthalmic lesions in
cluding an A rg y ll R o b e r ts o n pupil.
Other ocular manifestations of syphilis that can occur at any stage of the
disease include:
• Interstitial keratitis, retinitis, and retinal vasculitis.
• Salt and p e p p e r fundus and flame-shaped retinal hemorrhages.
• U veitis - Syphilis accounts for less than 1% of patients with uveitis (41).
• Cranial nerve and optic neuropathies (4),
• Acute multifocal chorioretinitis and vitritis (panuveitis).

372 9. Uh DISEASES OF THE REPROD UCTIVE SYSTEM
Syphilis is referred to as the “great mimic” because of its variable

presentation. Regardless of uveitic presentation, syphilis should
always be considered in the list of differentials (43).
There are a variety of tests available for syphilis. A simplistic overview of

syphilis evaluation can be thought of as the following:
* Screen in g Tests: Rapid plasma reagin (R P R ) test, venereal disease

research laboratory (V D R L ) test, enzyme immunoassay (E IA ) test.
• D ia g n o stic Tests: Fluorescent treponemal antibody absorption (F T A -

A B S ) test, treponema pallidum particle agglutination assay (T P P A ),
dark field microscopy, microhemagglutination assay (MHA-TP).
R P R and V D R L testing is used to determine if an active syphilis

infection is occurring and will become positive 4-6 weeks after an in
fection (4). F T A -A B S testing determines whether active or latent
disease is present. If a patient has ever had syphilis, the FTA-ABS
will be positive for life. If the FTA-ABS test comes back positive,
but the RPR or VDRL is negative, this means that the patient had
syphilis earlier in life and cleared the infection.
M ale R ep ro d u ctiv e System Ll LA . . LL-i v-,v 1

B en ign P ro sta tic H y p ertrop h y (B P H )
Risk factors include a previous family history in any male over the age of 50.
Men over 50 are checked by a rectal examination.
• Signs and symptoms include increased urinary frequency, urgency, noc

turia, a weak stream, hesitancy, and dribbling.•
• Treatment includes conservative measures with alpha sympatholytic agents

such as Terazosin, which relaxes the prostate muscles. Surgical interven
tion is often necessary.
P ro sta te C an cer
This is the 2nd most common cause of cancer death in males; incidence increases
with age.

• Risk factors include: Age (over 50), positive family history, and African-
American males.
• Rectal examination will reveal a firm, rock-hard, non-tender localized

area (42) (57).
• An elevated P S A (prostate specific antigen) test may indicate prostate

cancer.
P reg n a n cy
• Signs and symptoms include amenorrhea, nausea and vomiting, breast

tenderness and weight gain.
• Lab tests to confirm pregnancy include positive pregnancy tests and in
creased human chorionic gonadotropin hormone (Beta HCG) levels.
• Pregnancy is divided into 3 trimesters: 0-12 weeks, 13-26 weeks, and

27-40 weeks.
• Common tests during pregnancy include a triple screen test to detect

Down’s syndrome (15-18 weeks), STD testing, ultrasounds (18-22 weeks),
diabetic screening (26-28 weeks), Rhogam injection for Rh negative women
(28 weeks), and a group B strep test (36 weeks).
• Pregnancy Complications - There are multiple complications that can

arise during pregnancy. A few include:
1. S pon tan eou s a b o r tio n (m iscarriage) - Occurs at less than 20

weeks.
2. Still b irth - Death to a fetus after 20 weeks of pregnancy.
3. E cto p ic preg n a n cy - Due to a pregnancy within the fallopian tube
or anywhere outside of the uterus. Symptoms include pelvic pain,
fever, mass inside the fallopian tube on ultrasound, and increased
HCG levels.
4. P re-ecla m p sia - Characterized by a triad of blood pressure greater
than 140 mmHg, protein in the urine, and swelling in the lower ex
tremities. Can occur from 20 weeks of gestation to 6 weeks postpar
tum. The best treatment is delivery of the baby. E clam psia occurs
when the above symptoms are present and the patient has seizures.
Both conditions can cause adverse effects in pregnancy, including
stillbirth and maternal death, if not treated appropriately.

374 9.15. CONGENITAL AND NEONATAL ANOMALIES
B reast feeding
Remember from physiology that oxytocin (from the posterior pituitary) allows
milk ejection, and prolactin (from the anterior pituitary) allows for milk pro
duction. The benefits of breast feeding include mother-child bonding and a
transfer of immunoglobulins.
C erv ica l C an cer
This is a common but treatable cancer in women that begins as cervical dys
plasia and progresses over time to malignancy. Risk factors include early sex
and multiple sex partners and a history of H P V (hum an pa p illom a virus).
Diagnostic studies include an abnormal Pap smear (53). Treatment includes
surgical intervention, radical hysterectomy or chemotherapy.
B reast C an cer
There are two main types of breast cancer:
1. Ductal carcinoma - starts in the tubes (ducts) that move milk from the
breast to the nipple.
2. Lobular carcinoma - starts in the parts of the breast, called lobules, that
produce milk.
In many breast cancers, estrogen causes the breast cancer tumor to grow. This
is called estrogen receptor-positive cancer or ER,-positive cancer. Risk factors
include age, family history of breast cancer, or defects in the B R CAl and
BRCA2 genes.
The most common cancers in women in the U.S. by occurrence

(in order) are breast, lung, and colon cancer. The most common
causes of cancer death in women are (in order) lung, breast and
colon cancer. The most common cancers in men in the U.S. by
occurrence (in order) are prostate, lung, and colon cancer. The
most common causes of cancer death in men are (in order) lung,
prostate, and colon cancer.
- SECTION 9.15 ----------------------------------------------------------------------------
C ongenital and N eonatal A nom alies
Neural Tube Defects

Spina B ifida Characterized by defective closure of the posterior vertebral

arches with intact meninges and spinal cord. The site of the defect may be
marked by a small skin dimple or hair. The abnormality can be extremely mild
and have no symptoms (spina bifida oculta). In more severe cases, side effects
may include lower body dysfunction including bowel, bladder, and leg abnor
malities. Decreased learning capacity and enlarged ventricles are common.
Spina Bifida can be significantly reduced with folic acid supplem entation
during pregnancy.
A n en cep h a ly This is the most severe (100% fatal) neural-tube defect dis
order. The orbital bones are nearly normal in size, but there is an absence of
normal brain and cranial bone tissue.
C on gen ital H eart D isease
R igh t to Left Shunt Shunting of deoxygenated blood from the right atrium
or ventricle to the left atrium or ventricle. This results in blue (cyanotic) babies
because the oxygen deficit is immediately problematic. An example is Tetral
ogy of Fallot, a disorder that includes pulmonary stenosis, right ventricular
hypertrophy, an over-riding aorta and ventral defect.
Left to R igh t Shunt Shunting of oxygenated blood from the left atrium or
ventricle to the right atrium or ventricle. This can result in blue (cyanotic)
kids because the shunting does not cause as dramatic of decrease in oxygen
perfusion. Examples include ventral septal defect (VSD), atrial septal defect
(ASD), and patent ductus arteriosus (PDA).
B om m on congenital disorders %; ... •
Fetal A lc o h o l S yn drom e
Due to mothers who consume significant amounts of alcohol during pregnancy.

This is the number one cause of congenital malformation.
C erebral Palsy
Generic term that includes non-progressive varied infections, toxins, and con
genital malformations in infants. Signs and symptoms include mental slowness
or retardation, impaired function of voluntary muscles, seizures, and speech
and sensory defects. Hyperactive reflexes-are also common (36).

376 9.16. GASTROINTESTINAL SYSTEM
R u b e lla
Mothers transfer this to the fetus. Side effects include m icrophthalm ia, glau
com a, and heart defects (58). This is screened for early in pregnancy.
M icrop h th a lm os refers to a small, malformed globe; when the

condition occurs without any other ocular defects, it is called pure
microphthalmos or nanophthalmos (54).
Syphilis
Causes mucous membrane and skin lesions on the fetus. If untreated, the baby
can develop interstitial keratitis and CNS disorders. This is screened for early
in pregnancy.
T oxopla sm osis
If acquired by the fetus, can result in stillbirth. Most will develop brain or eye
problems including retinochoroiditis (58).
Infant cataracts should raise suspicion for rubella or galac

tosemia (30).
- SECTION 9.16 --------------------------------------------------------------
G astro in testin al System
S tom ach an d Esophagus

G a stroesop h a g eal R eflu x D isease (G E R D )
Movement of gastric juice from the stomach into the esophagus due to gas
troesophageal junction incompetence; this results in heartburn. Risk factors
include: alcohol use, hiatal hernias, obesity, pregnancy, scleroderma, and smok
ing.

P e p tic U lcer D isease
This affects 20% of adults (58) and is due to h elicobacter pylori, chronic
N S A ID use, food intolerance, and smoking. Treatment includes H2 blockers,
proton pump inhibitors (PPI), and combination therapy (H2 blocker or PPI
plus two antibiotics) for H pylori (57). Diagnostic studies include an upper
endoscopy and barium swallow studies. There are two main ulcer locations:
• D u od en a l ulcer - symptoms include burning or hunger-like pain, pri

marily in the epigastric area. Pain may occur or worsen when the stomach
is empty and is worse” in the middle of the night when acid secretion is
the greatest.
• G astric ulcer - the main symptom is pain soon after eating.
B a r r e tt’s E sophagus
• Normal esophageal lining is replaced by metaplastic columnar cells; oc

curs as a result of squamous changing to columnar cells.
• Diagnosed via upper endoscopy with biopsy to confirm the cell change.
* Can lead to esophageal adenocarcinoma, which requires surgical resection

of the esophagus.
• Treatment includes long-term proton pump inhibitors.
Inflam m atory B ow el D isease (IB D )
The two main inflammatory bowel diseases are Crohn’s disease and ulcerative
colitis.

C roh n ’ s Disease U lcerative C olitis

Etiology Infectious Autoimmune
Location Any portion of the GI tract C o lo n (hence colitis)
Usually affects the terminal Continuous lesions
ileum, small intestine and R e cta l involvem ent
colon. Rectal Sparing.
S K IP lesions
Morphology Transmural inflammation. Mucosal inflammation.
Cobblestone mucosa, Friable pseudopolyps,
creeping fat, bowel wall crypt abscesses, and ulcers
thickening, ulcers and
fistulas
Complications Strictures, fistulas, perianal Severe stenosis, toxic
disease, malabsorption, and megacolon, colorectal
nutritional depletion. carcinoma.
Ocular Non-granulomatous uveitis Non-granulomatous uveitis
Findings Incidence: 2 — 4% Incidence: 5 — 10%
For C r o h n ’s Disease, think of a fat old crone skipping down a

cobblestone road (7).
C o lo n C an cer
This is the third leading cancer in both males and females (both in terms of
incidence and cancer mortality). Contributing factors include low-fiber, high-
fat diets and exposure to toxins. Risk factors include age, family history of
colon or breast cancer, and familial polyposis (see section on genetic disorders).
The primary screening method is a colon oscop y . Treatment includes surgical
removal, chemotherapy, and radiation (48) (57).
[Diseases of th e Liver .
W ils o n ’ s D isease
This is due to a failure of copper to enter the circulation in the form of ceru
loplasmin. This leads to copper accumulation that is most concentrated in
the liver, brain, and corn ea (K ayser-Fleischer R in g ). Some disease man
ifestations include a sunflower cataract, cirrhosis of the liver, basal ganglia
degeneration, and dementia (7) (42).

P en icillam ine (C u p r im in e ® ) is a chelating agent (binds cop

per) that is used in the treatment of Wilson’s disease. Systemic side
effects are numerous (1/4 or more of patients taking the drug for
Wilson’s disease stop due to adverse effects)! Ocular side effects
include ocular myasthenia (diplopia, ptosis), ocular pemphigoid,
and optic neuritis (58).
A lc o h o lic H epatitis
This causes swollen, necrotic liver cells due to alcohol consumption. Mallory
bodies (hyaline), fatty changes, and sclerosis around the central vein are also
present, with an increase in AST and ALT liver enzymes (42).
A S T and A L T are enzymes contained within liver cells that are

released into the blood in increased concentrations in cases of hep
atitis, regardless o f the etiology.*•
H epatitis
Viral inflammatory condition of the liver parenchyma that leads to necrosis.

Includes Types A through E (42):
• H epatitis A : Vaccine available (0, 6-12 mos), spread via fecal oral route,
limited infection.
• H epatitis B : Vaccine available (0,1, 6 mos), spread via blood, IV drugs,

and sex. Active infection typically has a brief course.
• H epatitis C : No vaccine available. Spreads like Hepatitis B with the

same effects. C h ron ic h epatitis develops in approximately 80% of pa
tients with acute Hepatitis C infection (58).
• H epatitis D : Carried only with Hepatitis B as a superinfection. T his

increases morbidity and mortality.
• H epatitis E: No vaccine available; spread via fecal oral route.

C irrh osis
Characterized by the presence of fibrosis with creation of excessive extracel

lular matrix. Normal blood flow through the liver is hindered and nutrient
and metabolite exchange are thus reduced. The liver initially enlarges, firm
nodules are formed, and then the liver shrinks. The most frequent causes are
alcohol and viral hepatitis; however, drugs, toxins, CHF, biliary obstruction,
and autoimmune complexes may also play a role. Complications include portal
hypertension, GI hemorrhage, and liver failure; the latter frequently results in
death (42).
Jau n dice
Normally liver cells conjugate bilirubin and excrete it into bile (it will eventually
be excreted as urine). Conjugated bilirubin is converted by bacteria to uro
bilinogen. Additional urobilinogen is formed directly from heme metabolism.
Jaundice occurs when the pathway is either obstructed in the liver, or bilirubin
is hemolyzed in the blood or cannot be excreted in the urine due to some other
pathology. The build-up of urobilinogen and bilirubin in the systemic blood
stream causes a yellow ing o f the skin and conjunctiva. This is commonly
seen in cirrhosis, hemolytic disorders, or obstructive gallbladder disorders (36).
D iseases of th e G allbladder .N-

C h olecystitis
Occurs both acutely and chronically as a result of inflammation of the gall

bladder lining secondary to obstructive cholesterol stones, sludge, or infection.
M o s t c o m m o n in overw eight fem ales o f ch ildbearing age. Patients have
pain in the right upper quadrant (especially after meals), and a positive M u r
p h y ’ s sign. Treatment involves surgery to remove the gallbladder (7) (42).
D iseases of th e P ancreas 'b . ... '. y A :: ; :\J

A c u te P an creatitis
Occurs secondary to alcoh ol abuse or gallstones in 70 —80% of cases. Other

causes include trauma, drugs, hyperlipidemia, infection, or tumor. Patients
present with pain around their umbilicus with possible radiation to the back.
Lab studies show an increase in serum amylase and lipase (42).
C h ro n ic P an creatitis
90% of cases are due to chronic alcohol abuse; most of these patients have a
history of recurrent episodes of acute pancreatitis. Periodic or continuous peri
Copyright 2014 by KMK Educational Services, L L C

umbilical pain radiates straight through to the back. Weight loss, steatorrhea
(“fatty stools”), and diabetes are also common (42).
- SECTION 9.17 ---------------------------------------------------------------------------------------------------
H ead an d N eck D isorders
-V .C a® -h ';. V;''
H earing loss: Can be caused by loss of conduction, sensory loss and/or

neural deficits. Loss o f c o n d u ctio n is th e m ost co m m o n form o f hearing
loss and is usually a result of cerumen impaction or trauma. Sensory hearing
loss is due to deterioration of the cochlea, while neural loss is due to damage
of the 8th cranial nerve. Two clinical tests, the W e b e r test and RAnne test,
are used to determine which is the culprit.
O titis m edia: Characterized by pain in the ear. Caused by bacterial infec

tions from Strep. Pneumoniae and H. Influenza (58). Treatment is Amoxicillin
or other gram positive agents. Very common in infants and children.
V ertigo: Disease of the vestibular ear system causing dizziness and nystag
mus. True vertigo is always associated with nystagmus. A condition that can
cause vertigo is M e n ie re ’s D isease, which is associated with episodic and
often severe v ertig o, hearing loss, and tinnitus.
jlSfasopharynx .. v: V . V-
Sinusitis: Inflammation of the paranasal sinuses due to viral, bacterial or
fungal infections. Patients may have anterior and/or posterior mucopurulent
drainage, nasal obstruction, facial pain, pressure and/or fullness, and decreased
sense of smell.
A llergic R h in itis: Characterized by symptoms of a runny nose, sneezing,

conjunctival hyperemia, and watery eyes. Treatment includes histamine re
ceptor blocker,s, nasal sprays and eye drops such as Patanol© for ophthalmic
symptoms.
P h aryn gitis: Signs and symptoms include enlarged cervical nodes, sore throat
and fever. Occurs as a result of viral or bacterial agents. Group A Strepto
coccal infections need to be treated with antibiotics such as penicillin or other
gram positive agents.
Copyright 20.1.4 by KMK Educational Services, LLC

382 9.18. RESPIRATORY SYSTEM
glands ^ ; " " " "ssste V.Si&SM?SrV.. ,r*i i *■'-'-V.ii,--=i'=V..- J .T f & ’C .iV ;;’J
A c u te b a cteria l sialadenitis: Commonly located in the parotid or sub

mandibular gland - swelling and pain of the gland will be present. Often caused
by S. aureus and treated with antibiotics (58). IV nafcillin is often used.
Salivary G la n d Tum ors: 80% of these will involve the parotid gland (58)
and only 50 —60% will be benign (58). These present as an asymptomatic mass
in the gland and can extend deep into the facial nerve area. MRI and CT scans
are used to diagnose the tumor. Treatment involves removal of the tumor.
(Joints
T em p orom a n d ib u la r D isorder (T M J ): Commonly a result of acute and
chronic inflammation secondary to arthritis, trauma, dislocations, developmen
tal anomalies, and other factors. Patients will often complain of headaches,
facial pain, and jaw pain (42).
r - SECTION 9.18
R esp irato ry System
D iseases of th e R esp irato ry System ; -\
C h ron ic O b stru ctiv e P u lm on ary D isease (C O P D )
This is an obstruction of air flow, causing air to be trapped in the lungs. T h e

leading cause o f C O P D is sm oking (57). There are two categories of
COPD:
1. E m ph ysem a (P in k P uffers): This disease is marked by an enlarge

ment of air spaces and a decrease in recoiling because of destruction of
the alveolar walls. Symptoms include shortness of breath (dyspnea), de
creased breath sounds, and tachycardia (57).
2. C h ron ic B ron ch itis (B lue B loaters): This disease is marked by a

productive cough for 3 consecutive months in 2 or more years due to
hypertrophy of mucous-secreting glands in the bronchioles. Common
symptoms include cyanosis of the lingers and toes and wheezing/cradding
of the lungs.
A sth m a
The pathophysiology of asthma has two primary components:

CHAPTER 9, SYSTEMIC DISEASE 383
1. A cu te reversible b ro n ch o co n strictio n - triggered by infection, aller

gens, and stress. Symptoms include coughing, wheezing, dyspnea, and
tachycardia.
2. C h ron ic in flam m ation o f the airways.
Reversible bronchoconstriction is treated with bronchodilators such as albuterol,

isoproterenol and metaproterenol. Chronic inflammation of the airways is
treated with inhaled or oral steroids.
P n eu m ocon iosis
This is a restrictive lung disease secondary to occupational inhalation of dust.

The disease is given different names depending on the particles inhaled such as:
Coal worker’s pneumoconiosis, Asbestosis, Silicosis, and Berylliosis (42) (57).
• Restrictive lung diseases cause shortness of breath and decreased lung

volumes and lung compliance.
• Chest x-ray will show diffuse infiltrates with a ground-glass appearance.
Remember to ask about underlying lung disease before treating

your glaucoma patients with B-Blockers!
jTnfoctious D iseases o f t h e L u n g . : ' V--.- ^ , v '

T u bercu losis
Tuberculosis (TB) is caused by airborne droplets of Mycobacterium tuberculo

sis. The primary symptoms of TB include fever, cough, and night sweats. All
patients thought to have TB need to have a chest x-ray. Treatment includes a
combination of the following drugs: R ifa m p in , Isoniazid, P yrazinam ide,
and E th am bu tol (R IP E ). Ocular findings can include:
• Bilateral anterior granulomatous uveitis.
• C y stoid m acular ed em a (determines acuity in most patients),
• Other less common findings include keratitis, phlyctenules, conjunctival

granulomas and scleritis (non-exhaustive list).

384 9.18. RESPIRATORY SYSTEM
TB and Sarcoidosis are two of the most common etiologies of a

chronic, bilateral, anterior, granulomatous uveitis. Recall that the
tu b ercu losis skin test (P P D test) is used to determine if a pa
tient has TB. 15 mm or more of induration is considered a positive
test in a healthy person with a normal immune system. 10 mm of
induration or more is positive in a health-care worker or someone
who is in contact with a person with active TB. 5 mm or more
is positive in patients who are immunocompromised (HIV or bone
marrow suppression).
B a cteria l P n eu m on ia
Pneumonia is an infection of the lungs usually caused by bacteria or viruses.

The most common cause is Streptococcus pneumoniae (pneumococcus). Symp
toms include productive cough, shortness of breath, and fever. A less com
mon form of pneumonia is “walking pneumonia” caused by agents such as My
coplasma pneumoniae.
Influenza
Acute respiratory illness caused by influenza A or B viruses. Symptoms include

fever, cough, rhinitis, headache, and myalgias.
Lung £3
Main cause of cancer deaths in both men and women. Adenocarcinoma of

the lung is the most common lung cancer. Cigarette smoking is the leading
cause, though 2nd hand smoke can also lead to lung cancer. Patients may
be asymptomatic when the tumor is found, or they may present with cough,
hemoptysis, shortness of breath, and weight loss. Bone pain from metastasis
may be an additional symptom.
A tumor of the apex of the lung is called P a n coa st’ s tu m o r and

may cause H orn er’s syndrom e.

I - SECTION 9.19
Neoplasia
Cancers result from a host of environmental and genetic factors that damage
normal cells. The damaged cells are mutated and give rise to new populations
of mutated cells. Typical cellular defense mechanisms such as apoptosis and
suppressor genes are often inactivated in pre-malignant cells and are therefore
not useful in halting abnormal cell growth. Furthermore, growth promoting
oncogenes facilitate and encourage cancer mutation and growth (36).
[Classification o f M
1. B eh avior; Benign, borderline, or malignant.
2. D egree o f differen tiation : Well-differentiated or poorly-differentiated.
3. E m b ry olog ic origin : Epithelial (adenocarcinoma, squamous cell carci

noma) , lymphoproliferative (leukemia, lymphoma), or mesenchymal (sar
coma) .
4. G ross appearan ce: Well-circumscribed or infiltrative.
B enign Tum ors
Usually slow-growing and well-circumscribed. Examples of benign tumors in

clude:
• Adenomas: Benign epithelial tumors arising in glandular patterns.
• Cystadenomas: Adenomas producing large cystic masses seen in the fat

and ovaries.
• Papillomas: Epithelial tumors that form microscopic or macroscopic finger

like projections.•
• Polyps: Tumor that extends from the mucosa into the lumen of a hollow
organ (36).
M alignant Tum ors
Often aggressive with invasion of adjacent structures and have metastatic po
tential.
• M etasta tic: Cancer that shifts from its origin to another body site (36).
• C arcinom as: Arises from epith elia l cells.

386 9.19. NEOPLASIA
• Sarcom as: Arise from m esenchym al (connective) tissues.
R h a b d o m y osa rcom a is a connective tissue cancer that causes

bone destruction; it is the most common primary orbital malig
nancy (30).
D ysplasia
• D ysplasia refers to abnormal growth of epithelial cells caused by a dis

ruption in cell maturation.
• L ow -g ra d e dysplasia is considered the earliest form of a pre-cancerous

lesion that is recognizable in a biopsy by a pathologist.
• H igh -gra de dysplasia is synonymous with carcinoma in situ (CIN).

Transformation into cancer is high, but treatment is often still effective
(similar to low grade dysplasia).
• Invasive ca rcin om a (“ cancer” ) is the final step in this process - growth

penetrates the epithelial basement membrane to invade the tissue.
M eta p la sia refers to a change from one mature cell type to another
as an adaptive response from chronic irritation or a pathogen or
carcinogen. Treatment aims to reverse cell damage. If left alone,
dysplasia and cancer can result. Squam ous cell carcinom a, the
2nd most common form of skin cancer, results from metaplasia (27).
N eoplasia is abnormal, disorganized “new growth” in a tissue or

organ that leads to the formation of a growth or mass (neoplasm).
Neoplasia can be benign or malignant. M e la n o cy tic nevi are
among the most common benign neoplasms.

Oncogenes
A protein encoding gene that has the potential to cause cancer. Activated
oncogenes allows mutated cells, which normally die secondary to apoptosis, to
survive and proliferate into a cancer. Multiple oncogenes, such as the“Ras”
oncogene, have been found to play a role in specific cancers (58).
Tumor Suppressor Genes
These genes either have a repressive effect on the regulation of the cell cycle
and/or promote apoptosis. They prevent DNA damage and regulate cellular
activities. Loss of tumor suppressor genes, such as the BRCA gene in breast
cancer, can lead to cancer (58).
- SECTION 9.20 ---------------------------------------------------------------------------------------------------
N utritional Disorders
Anorexia Nervosa
These patients have a distorted view of their body image and an overwhelming
fear of being fat. They have decreased body weight (less than 85% of ideal
body weight) and absence o f at least three consecutive menstrual cycles. It
affects more females than males (58).
Bulimia Nervosa
Patients suffering from this disease have episodes of binge eating two times a
week for at least 3 months. They compensate for the binge eating by vomiting,
over-exercising, or by utilizing laxatives (58).
jM alnuirition c "A; ' "■■■ H . ,, • ' L/Vfo/':'

Kwashiorkor
This is a protein malnutrition resulting in skin lesions, anemia, edema and

liver malfunctions. Clinical presentation includes a very swollen belly on a
malnourished appearing patient.
Marasmus
This is a protein calorie malnutrition resulting in tissue wasting. Clinical ap

pearance will be an overall wasting and weight loss in affected individuals.

388 9.21. MENTAL ILLNESS AND BEHAVIORAL DISORDERS
jAlf^bholism
Alcoholism is an addiction to alcohol. Withdrawal causes tremor, tachycardia,
hypertension, nausea, seizures, delirium tremens, and hallucinations. Alco
holics are more prone to gallstones, alcoholic hepatitis, and cirrhosis of the
liver.
• A lc o h o lic cirrhosis is due to long-term alcohol abuse, causing micron-

odular cirrhosis. Presenting symptoms include jaundice, hypo alb umine-
mia, coagulation factor deficiencies, and portal hypertension.
• Alcoholics may also have W ern ick e-K orsak off S yn drom e, which is
associated with vitamin B1 (thiamine) deficiency. See biochemistry and
pharmacology chapters for more details on this condition.
• Alcoholism can lead to a tox ic op tic neuropathy that leads to b i

lateral tem p ora l o p tic nerve pallor.
r - SECTION 9.21 ---------------------------------------------------------------------------------------------------
M ental Illness and Behavioral Disorders *•
There are a multitude of psychiatric disorders. For a patient to be diagnosed

with a psychiatric disease, physical disease and drug abuse must be eliminated
from the differential diagnosis - this often involves lab work and brain scans.
When looking at a specific psychiatric disorder, there are definitive criteria
necessary for diagnosis. These are based on the Diagnostic and Statistical
Manual of Mental Disorders (DSM -IV), a book that mandates the criteria
used to diagnose mental disorders.
M a jo r D ep ression
• Around 30% of patients are affected by depression (58).
• Depression is thought to be caused by inappropriate neurotransmitter

involvement, metabolic abnormalities, or psychological factors. There is
also a strong genetic predisposition (58).
• Symptoms include feelings of worthlessness, guilt, anxiety, fatigue, in

somnia and withdrawal from social situations.
• Treatment includes antidepressant medications, counseling and electro

convulsive therapy (58).

A n x ie ty
• Characterized by symptoms of apprehension, worry, irritability, and dif

ficulty concentrating (58).
• Physical complaints are often present and include insomnia, tachycardia,

HTN, nausea, or diarrhea.
• More common in women than men; symptoms appear in early adulthood.
• Treatment includes benzodiazepines, antidepressants, and counseling.
Schizophrenia
• Due to increased levels of dopamine in the mesolimbic region.
• Characterized by a massive disruption of behavior, mood, and thinking

for at least 6 months (58).
• Treatment includes antipsychotic medications.
P O S IT IV E N E G A T IV E
Delusions Lack of speech and thought
Thought disorders Loss of emotional response
Inappropriate affect No effect
Increase in motor functions Social Isolation
B ip ola r D isorder
• This disorder is characterized by episodes of severe depression alternating

with periods of mania.
• Treatment is the same as with severe depression and may include hospi
talization.
• Manic episodes are characterized by elevated mood, decreased need for

sleep, flighty thought-processes, decreased reasoning skills, increased ac
tivity, and aggressive behavior. Mania is often'followed by periods of
severe depression (58).
Suicide
* Common cause of death in the United States.
* Often caused by serious depression, alcohol and substance abuse, or

stressful life events (58).*
* People who have the highest risk of suicide are white, middle aged and
elderly men, though women and teens report more suicide attempts.

• Treatment includes hospitalization for patients actively trying to commit

suicide, followed by treatment of depression through medications and
counseling efforts.
Substance Abuse
• This involves a triad of compulsive drug use which includes a psycholog

ical dependence (the behavior of needing the drug), physiological depen
dence (physical need of the drug to not have withdrawal symptoms), and
drug tolerance (the need for higher doses of the drug to maintain drug
effects) (58).
• Patients can be addicted to any medication, including prescription drugs

such as pain medications, or illicit drugs such as methamphetamines and
cocaine. Alcohol addiction also fits into this category.
• Treatment includes treating the withdrawal symptoms and then placing

the patient in a facility where no drugs can be obtained. These patients
often need lifetime support and counseling.
References
[1] Altersitz K, Ocular Surgery News U.S. Edition. February 15, 2007.
[2] American Academy of Ophthalmology. J3asic and Clinical Science Course, Section 12, 1999-
2000, San Francisco, CA: American Academy of Ophthalmology; 1999. pp. 68-70.
[3] Arnett FC, et al. ’’The 1987 Revised ARA Criteria for Rheumatoid Arthritis.” Arthritis
Rheum. 1987; sl7,30.
[4] Babcock O ’ Connell C, Zarbock S. A Comprehensive Review for the Certification and Re
certification Examinations for Physician Assistants. 3rd Edition. Lippincott Williams and
Wilkins, Baltimore, 2007.
[5] Bagot CN, Arya R. Virchow and his triad: a question of attribution. Br J Haematol 2008;
143:180.
[6] Bartlett, Jimmy D., Jaanus, Siret D. Clinical Ocular Pharmacology. Boston, Butterwortli,
2008.
[7] Bhushan, Vikas, Le, Tao, Amin, Chirag. First Aid for the USMLE Step 1. New York,
McGraw-Hill, 2003.
[8] Berg RA, Hemphill R, Abella BS, et al. Part 5: adult basic life support: 2010 American Heart
Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular
Care. Circulation 2010; 122:S685.
[9] Blackbourne, Lome H. Surgical Recall 3rd ed. Philadelphia, Lippincott Williams and Wilkins,
2002.
[10] Burt V, et al. Prevalence of hypertension in the US adult population. Results from the Third
National Health and Nutrition Examination Survey, 1988-1991, Hypertension 1995;25:305-13.
[11] Gasser L, Fingeret M, Woodcome T. Atlas of Primary Eyecare Procedures, 2nd ed. Appleton
and Lange, Connecticut, 1997.

[12] Childhood Brain Tumor Consortium. J Neuro-Oncol 1991: 10: 31-46.
[13] Cbo banian A, Bakris G, et al. The seventh report of the Joint National Committee on Pre
vention, Detection, Evaluation, and Treatment of High Biood Pressure: The JNC 7 Report.
JAMA 2003;289:2560 - 2572.
[14] Colin, J. Ganciclovir ophthalmic gel, 0.15: a valuable tool for treating ocular herpes. Clin
Ophthalmol. 2007 December; 1(4): 441U453
[15] Comi AM. Presentation, diagnosis, pathophysiology, and treatment of the neurological fea
tures of Sturge-Weber syndrome. Neurologist 2011; 17:179.
[16] Denniston and L Butler. Ophthalmic Features of Turner’s Syndrome. Eye (2004) 18, 680U684.
Published online, 27 February 2004
[17] Fitzpatrick, Thomas et. al. Color Atlas and Synopsis of Clinical Dermatology, 4th ed. St.
Louis, McGraw-Hill, 2001.
[18] Flegal K, Carroll M, Ogden C, Johnson C. Prevalence and trends in obesity among US adults,
1999-2000. JAMA 2002;288:1723-7.
[19] Friedbert, Mark A. Rapuano, Christopher J. The Wills Eye Manual, 3rd edition. Philadel
phia, Lippincott Williams and Wilkins, 1999.
[20] Friedman N, Kaiser P, Trattler W. Review of Ophthalmology. Elsevier, Philadelphia, 2005.
[21] Friedman, Neil J. Kaiser, Peter K. The Massachusetts Eye and Ear Infirmary, 3rd Edition.
Elsevier, 2009.
[22] Fox, Stuart Ira. Human Physiology, 6th ed. Boston, McGraw-Hill, 1999.
[23] Fnerst D, Tanzer D, Smith R. Rheumatoid diseases. Int Ophthalmol Clin. 1998;38:47U80.
[24] Green, Gopa B. Ed et. al. The Washington Manual o f Medical Therapeutics, 3.1st ed. Philadel
phia, Lippincott Williams and Wilkins, 2004.
[25] Harkins, Timothy. ’’Sexually Transmitted Diseases.” Optometry Clinics Vol. 3, Number 4,
Systemic Disease and the Eye. Eds, John G. Classe and Charles J. Patorgis, Norwalk, Ap
pleton and Lange, 1994.
[26] Harper S, Foster C. The ocular manifestations of rheumatoid disease. International Ophthal
mology Clinics, 1998;38:1 - 19.
[27] http://www.skincancer.org/squamous/index.php
[28] Holland, E>, Cornea, 2nd edition, volume 1, Fundamentals, Diagnosis and Management
(2005), pp 1335-1340.
[29] Jennings, Barbara. ’’Connective Tissue Diseases.” Optometry Clinics Vol. 3, Number 4, Sys
temic Disease and the Eye. Eds. John G. Classe and Charles J. Patorgis. Norwalk, Appleton
and Lange, 1994.
[30] Kanski, Jack. Clinical Ophthalmology 4th ed. Woburn, Butterworth and Heinmann, 1999.
[31] Kared H, Lelievre JD, Donkova-Petrini V, et al. HIV-specific regulatory T cells are associated
with higher CD4 cell counts in primary infection. AIDS 2008; 22:2451.
[32] Kasper,. Dennis L. Harrison’s Manual of Medicine, 16th edition. New York, McGraw-Hill,
2005. Boston, Butterworth, 2008.
[33] Kaufman, Paul. Aim, Albert. Adler’s Physiology of the Eye, 10th ed. St. Louis, Mosby, 2003
[34] Kiss S, Damico F, Young L, Ocular manifestations and treatment of syphilis. Seminars in
Opthamology, 2005, Jul-Sep;20(3):161-7.
[35] Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia
(an evidence-based review). Report of the Quality Standards Subcommittee of the American
Academy of Neurology. Neurology 2001; 56:1143.

[36] Kumar, Vinay, Cotran, Ramzi and Stanley Robbins. Basic Pathology 6th ed. Philadelphia,
WB Stanley Sanders Company, 1997
[37] Lambert J, Wright V. Eye inflammation in psoriatic arthritis, Annals of the Rheumatic
Diseases, 1976;35(4):354-6,
[38] Leigh RJ, Newman SA, Folstein SE, et al. Abnormal ocular motor control in Huntington’s
disease. Neurology 1983; 33:1268.
[39] Lexi-Comp Online, Lexi-Drugs, Hudson, Ohio; Lexi-Comp, Inc.; December 2011.
[40] Manger W , Gifford R. Pheochromocytoma. J Clin Ilypertens (Greenwich) 2002;4:62-72.
[41] Margo C, Harned L. Survey of Ophthalmology. 1992;37(3):203-20.
[42] Noble, John, Ed. Textbook of Primary Care Medicine, 3rd ed. St. Louis, Mosby, 2001
[43] Pavan-Langston D. Manual of Ocular Diagnosis and Therapy, 6th edition. Williams and
Wilkins, Philadelphia, 2008.
[44] Peitersen E, The natural history of Bell’s palsy. Am J Otol 1982;4, 107111 qouted in Roob et
al. (1999) Peripheral Facial Palsy, Etiology, Diagnosis and Treatment. Eur Neurol 1999;4l,39
[46] Primo, Susan. ’’Infectious and Inflammatory Diseases.” Optometry Clinics Vol. 3, Number
4, Systemic Disease and the Eye. Eds. John G. Classe and Charles J. Patorgis. Norwalk,
Appleton and Lange, 1994.
[46] Rapuano, Christopher J, Heng, Wee-Jin. Color Atlas and Synopsis of Clinical Ophthalmology.
Wilis Eye Hospital. Singapore, McGraw-Hill, 2003.
[47] Remington L. Clinical Anatomy of the Visual System. Butterworth-Ileinemann, Boston,

1988.
[48] Robbins, Stanley, et. al. Pathologic Basis of Disease Pocket Companion. 6th ed. Philadelphia,
W B Stanley Sanders Company, 1997
[49] Sayjal J, Patel L, Lundy D, Ocular Manifestations of Autoimmune Disease, Naval Medical
Center, San Diego, California, Am Fam Physician. 2002 Sep 15;66(6):991-998.
[50] Seidel, Henry M. et al. Mosby’s Guide to Physical Examination, 4th ed. St. Louis, Mosby
1999.
[51] Simon, Albert and Anthony Miller. Appleton and Lange’s Outline Review for the Physician
Assistant Examination. St. Louis, McGraw-Hill, 2000.
[52] Stedman’ s Medical Dictionary, 22nd ed. Baltimore, Williams and Wilkins Company, 1972.
[53] Stenchever, Morton et al. Comprehensive Gynecology, 4th ed. St. Louis, Mosby, 2001.
[56] Terry, Jack. Ocular Disease, Detection, Diagnosis and Treatment. Springfield, Charch G.
Thomas, 1984.
[56] Thomas R, Melton R. http://ww w .eyeupdate.com /.
[57] Tierney. Lawrence M., McPhee, Stephen, and Maxine A. Papadakis Eds, Current Medical
Diagnosis and Treatment, 41st ed. New York, McGraw-Hill, 2002
[58] Tierney, Lawrence M., McPhee, Stephen, and Maxine A. Papadakis Eds. Current Medical
Diagnosis and Treatment, 45th ed. New York, McGraw-Hill, 2006,
[59] Webb DW, Clarke A, Fryer A, Osborne JP. The cutaneous features of tuberous sclerosis: a
population study. Br J Dermatol 1996; 135:1.
[60] Weetman AP, McGregor AM. Autoimmune thyroid disease: further developments in our
understanding. Endocr Rev 1994; 15:788.

[61] Weissman, Barry A. Giese, Michael J. Mondino, Bartly J. ’’An Introduction to Ocular Im
munology.” Optometry Clinics Vol. 3, Number 4, Systemic Disease and the Eye. Eds, John
G. Classe and Charles J. Patorgis. Norwalk, Appleton and Lange, 1994.
[62] Wong T> Klein R, Sharrett A, et al. The prevalence and risk factors of retinal microvas-
cular abnormalities in older persons: The Cardiovascular Health Study. Ophthalmology
2003;110:658 - 666.

(' !
f
(C'
((
(C' :
((
(
( !
(
( . i
c(
((
(
((
((
((
((
((
((
((
((
((
((
((
((
((
((
((
((
((
Chapter
Ocular Disease
Kyle M . Cheatham, O .D ., F .A .A .O .
395
(■
(
(
(
c
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
(
CHAPTER 10. OCULAR DISEASE 397
SECTIO N 10.1
Slit L am p Techniques
The following is a summary of biomicroscopy illumination techniques:
1. Sclerotic scatter - Used to evaluate corneal clarity (e.g. corneal cloud

ing secondary to PMMA lenses). The illumination system is moved ap
proximately 60 degrees from the oculars, and positioned to illuminate
the temporal limbus with a parallelepiped beam approximately 1 mm in
width. The cornea is observed with the naked eye from an angle directly
opposite that of the light source.
2. O p tic section - Used to estimate angle depth (e.g, Van Herick) and to
localize the depth o f lesions (e.g. corneal defects). Beam is approximately
0.5 mm wide and the illumination system is moved to optimize an oblique
view of the tissue.
3. C on ica l b ea m - Used to assess the anterior chamber for cells and flare.
Beam width and height is set as small as possible; the examiner should
be dark-adapted.
4. Specular reflection - Used to evaluate the corneal endothelium and

the anterior and posterior lens surfaces. The beam is approximately 1
mm wide. The oculars should be set directly in front of the patient and
the beam moved 45-60 degrees from the oculars. When the oculars and
beam are set at equal angles of incidence and reflection, the anterior and
posterior curvatures of the cornea will act as reflecting surfaces.
5. In d irect illum ination - Used to evaluate non-opaque corneal lesions

(e.g. microcysts, fingerprint lesions) (18). Oculars are focused on the
area adjacent to the beam. The beam is approximately 1.0 mm wide and
moved 60 degrees from the oculars.
The cob a lt blu e filter, in conjunction with fluorescein sodium,

allows better visualization of corneal and tear film integrity (e.g.
tear break-up analysis). When the filter is used without fluorescein,
corneal iron rings will appear black; this is useful in detecting subtle
Fleischer rings in keratoconus (18).

398 10.2. TRAUMA
i— SE C T IO N 10.2
T raum a
jCherriical B urn ;;■/ ^...; T_~/ " ;•••/,"'2 .. 2 '% - ^ y 2 ® ;:2y

• Epidemiology/History: Recent exposure to chemical or thermal agents.
An estimated 66% of chemical ocular burns occur in industrial settings (58)
• Symptoms: Normal or decreased vision, pain, foreign body sensation,

photophobia, tearing, and blepharospasm.
• Signs: Corneal signs range from mild superficial punctate keratitis (SPK)
to sloughing off of the entire epithelium (severe burns). Other signs in
clude conjunctival injection, chemosis, ciliary injection, anterior chamber
reaction, conjunctival hemorrhages, and scleral and limbal blanching
(indicate ischemia in severe burns). Severe burns may increase IOP.
• Pathophysiology/Diagnosis: Alkali burns have a worse prognosis com

pared to acidic burns because they raise tissue pH, causing a breakdown
of fatty acids in the cell membrane for faster penetration (often less than
1 minute) (78). Alkali burns are twice as common because of better
accessibility to consumers.
- Common alkali agents include ammonia (e.g. fertilizers, common

cleaning agents), lye (e.g. drain cleaners), magnesium hydroxide
(e.g. flares, fireworks), lime (e.g. plaster, mortar, cement, white
wash, mouthwash), and airbag residue (12) (41) (58) (84).
- Common acidic agents include hydrofluoric acid (e.g. glass pol
isher, rust remover, industrial cleaners), sulfuric acid (e.g. fertilizer,
explosives, dyes, battery acid), nitric acid (e.g. fertilizers, explo
sives, rocket propellant), chromic acid (e.g. wood preservation),
and PAVA spray (variant of pepper spray that contains pelargonic
acid) (12) (52) (58) (84).*
A lkali injuries are more dangerous than acidic injuries; calciu m

h y d rox id e is the most common cause of alltali burns (12). Re
member, limbal blanching is an indicator of ischem ia and is most
common in alkali burns.
* Epidemiology/History: History of trauma (e.g. fingernail, plant branch).

• Symptoms: Sharp pain (especially after blinking), foreign body sensation,

photophobia, tearing, and blurred vision (depending on location). A mild
anterior chamber reaction and miotic pupil may also occur.
• Signs: Corneal defect that stains with fluorescein with NO underlying

subepithelial infiltrate (SEI).
p y i i j u IT C oi v
•h: , ... :• v :- ,V ^ .. VCTT "a.-. \
• Epidemiology/History: History of trauma (similar causes as corneal abra

sions).
• Symptoms: Pain, foreign body sensation, tearing.
• Signs: May see conjunctival injection or an associated subconjunctival

heme.
p o rn e a l an d C onjunctival Bodies
• Epidemiology/History: History of ocular trauma. Foreign bodies are
either metallic or non-metallic. The most common non-metallic for
eign bodies include vegetable matter, cloth particles, cilia, stone, and
glass (78).
• Symptoms: Foreign body sensation, tearing, redness, photophobia, de

creased vision.
• Signs: Foreign body with or without a sterile infiltrate (most often occurs
in association with foreign vegetable or plant matter) (58). A rust ring
typically surrounds a metallic foreign body. Additional signs may include
corneal edema and a mild anterior chamber reaction.
U pper eyelid foreign b o d ie s often result in linear, vertical

corneal scratches. Always check visual acuity before removing a
foreign body!
(R uptured G lobe and P e n e tra tin g O cular In ju ry : v/ ;

• Epidemiology/History: History of recent trauma. More common in males
(3:1), especially young to middle-aged (52).•
• Symptoms: Pain, blurred vision, redness, photophobia, tearing.

400 10.2. TRAUMA
• Signs (non-exhaustive list): Pull-thickness laceration, severe conjunctival

hemorrhage, extraocular muscle restriction, leakage of intraocular con
tents, low IOP, positiv e S eid el’s sign, hyphem a, co m m o tio retinae,
choroidal rupture, and fractional retinal detachment.
S eid el’s test is used to determine if a wound leak exists. If a leak

exists (positive Seidel’s sign), the fluorescein dye will appear as a
dark stream (diluted by the aqueous) within the green dye of the
tears; the cobalt blue filter should be utilized for analysis.
•Hyphema- ' /• • •. y ; v ';n.
• Epidemiology/History: May have a history of blunt or penetrating trauma

or systemic disease (e.g. sickle-cell retinopathy, clotting disease), but may
also be idiopathic (2).
• Pathophysiology/Diagnosis: Condition typically results from trauma to

the iris and/or ciliary body.
— DO NOT perform gonioscopy or scleral depression on these patients

until 1 month post-injury to avoid rebleeding. Rebleeds tend to be
worse than the original presentation.
- A B -scan is indicated if the hyphema occludes the view of the fun

dus and you are concerned about a retinal detachment.
• Symptoms: Pain, blurred vision.
• Signs: Blood in the anterior chamber. Hyphemas can be red or black and
may be significant enough to be viewed without a slit lamp.
— 8-ball h yphem a - black hyphema encompassing 100% of the ante

rior chamber.
- M icroh y p h em a s - red blood cells suspended in the anterior cham
ber (without layering) that can only be viewed with a slit lamp.
Additional signs include iris sphincter tears, iridodialysis, cataract, lens

subluxation, pigment ring (Vossius ring) on the anterior lens capsule,
commotio retinae, and angle recession (60% of cases) (35).

C orneal b lo o d staining may occur in the late stages of hyphema;

it occurs in approximately 5% of patients and is associated with
large hyphemas, rebleeds, elevated IOP, and compromised corneal
endothelial cells (2).
Significant increases in IOP may occur as RBCs accumulate in the tra

becular meshwork and block aqueous outflow. The patient should elevate
his or her head (optimally at 30 degrees), allowing the RBCs to settle in
teriorly.•
In id iop a th ic hyphem as, always inquire about the use of blood

thinners (e.g. aspirin, NSAIDs) and consider ordering a complete
blood count (CBC), prothrombin time/partial thromboplastin time
(P T /P T T ), and sickle cell screen (2) (33). Sickle-cell and/or clot
ting diseases should be considered in these cases, especially in
African American and Mediterranean patients.
•• /-h . : :
• Epidemiology/History: History of trauma. If the injury is a result of

metal striking metal, or in cases where an object is propelled toward the
eye at high speed, consider an intraocular foreign body. Do NOT order
a magnetic resonance imaging (MRI) test in cases of suspected m etallic
intraocular foreign bodies.
• Symptoms: Pain, decreased vision.
• Signs: Foreign body as seen on a computed tomography (CT) scan and/or

aB-scan, iris transillumination defects (TIDs), distorted pupil, hyphema,
cataract, decreased IOP, p o sitiv e S eid el’s test, and microcystic edema
of the peripheral cornea (53).
Intraocular foreign b o d ie s composed of iron (e.g. BBs), steel,

copper, or vegetable matter often cause significant inflammation.
Glass, stone, precious metals, and plastic are inert materials and
may stay in the eye for prolonged periods of time without causing
inflammation (2) (33).

402 10.2. TRAUMA
'• V. • ' ./V - v -v t v : .

iOrbila]^ " ■-te-: 14;fb c i r:4:'4fe,:' -;.i7 - xbx X xx- .
• Epidemiology/History: History of trauma from a large object (e.g. fist,
tennis ball).
• Pathophysiology/Diagnosis: Orbital floor blow-out fractures are the most

common because the m axillary b on e in the posterior medial floor is the
weakest bone in the orbit and is most susceptible to the sudden increase
in intraorbital pressure during trauma.
• Symptoms: Pain, binocular diplopia, crepitus on palpation of the medial

orbital area or after nose-blowing.
• Signs: Varies according to which wall is fractured. Signs include subcon

junctival hemorrhage, enophthalmos, diplopia, step-off fracture of the or
bital rim, globe ptosis, infraorbital hypoesthesia, asymmetric monocular
PDs (> 3 mm difference), hyphema, and angle recession (non-exhaustive
list) (97).
In orbital wall fractures, look for a trapp ed inferior rectu s (lim

iting upgaze), damage to the infraorbital nerve (causing hypoes
thesia), positive forced ductions, and periorbital crep itu s (aka
orbital emphysema). Do not perform gonioscopy or scleral depres
sion until 4 weeks after the trauma. Patients should not blow their
nose within 48 hours of trauma in order to limit the risk of an
orbital infection.
C om m otio R e tin a e j
• Epidemiology/History: History of recent trauma.
• Pathophysiology/Diagnosis: Trauma causes disruption of the RPE and

photoreceptor outer segments (35) (90). Although the condition usually
resolves without sequelae within 24-48 hours, permanent vision/visual
field loss may occur (41).
• Symptoms: Typically asymptomatic. Patients may experience acute vi

sion loss if trauma occurs within the macula.•
• Signs: Gray-white discoloration that can affect any location of the retina;
it is known as B erlin ’ s edem a when located in the macula. May or may
not be accompanied by retinal hemorrhages or choroidal rupture.

Disinsertion of the iris root from the ciliary body; appears as a peripheral
iris hole that is best seen with retroillumination. Patients should be carefully
monitored for angle recession glaucoma due to possible TM damage secondary
to trauma.
\: .. ,• . ■•••;••••'• ..v. ...... ' : . •:,••••••. v. •. . •

A pigment ring on the anterior lens surface that results from contact with the
posterior pigmented iris epithelium during trauma.
IPurtscfer ’ s retino^ktliy ^
Retinopathy commonly associated with acu te ch est-com pressin g traum a
and characterized by diffuse retinal hemorrhages, exudates, and cotton wool
spots.
JChproidal Pupture
Occurs in 5 — 10% of cases of blunt ocular trauma (23). Most commonly
appears as a single area or multiple areas of subretinal hemorrhage, usually
within the temporal posterior pole, with crescent shaped tears concentric to
the optic nerve head. Choroidal rupture is associated with a long term risk of
development of choroidal neovascularization (CNV) at the margins of the tear,
occurring in an estimated 5 — 10% of patients (23).
jEyelid ecchymosis '• :' v ’•

A bruise or “black eye” resulting from leaking blood vessels in the subcutaneous
tissue that is likely from trauma. Look for underlying ocular damage.
;aijd eprneal lacerations

A tear in the corneal or conjunctival tissue, often secondary to trauma. Seidel’s
test should be performed to determine if an open globe wound is present.
Prognosis is generally good unless the laceration involves the visual axis (35).
O p tic neuropathies can also result from trauma; disc pallor often
takes weeks to appear (33).

404 10.3. OCULAR ADNEXA/ORBIT/EXTERNAL DISEASE
- SECTION 10.3 ----------- --------------------------------------------------------------------
O cular A d n e x a /O rb it/E x te rn a l Disease
jProlapsed Orbital Fat ' ;-x: ' X-.%

• As aging occurs, the orbital septum becomes weaker, allowing extraconal
fat to prolapse into the upper and lower eyelids and surrounding skin.
• Prolapse o f extraconal orbital fat is noted as an outpouching of skin of

the upper and lower lids and adnexa that is soft with palpation.
• Orbital fat lesions are usually asymptomatic and are of cosmetic concern
only. However, large subconjunctival prolapsed fat masses may cause lid
malposition and subsequent exposure keratopathy with possible symp
toms of ocular irritation, redness, tearing, and blurred vision (73).
Preseptal ..Cellulitis: ■ . - - : ^ j
• Epidemiology/History: More common than orbital cellulitis. Also more
common in young adults and children during the winter months (58).
• Pathophysiology/Diagnosis: An infection anterior to the orbital sep

tum (as opposed to orbital cellulitis, which is posterior to the orbital
septum). Most commonly results from the following (non-exhaustive
list) (33) (52):
1. Ocular infection - acute hordeolum, dacryocystitis.

2. Systemic infection - nearby upper respiratory tract or middle ear
infection.
3. Skin trauma - puncture wound, insect bite.
• Signs: Eyelid edema, erythema, ptosis, warmth, no pain to mild tender

ness, hard bump on the eyelid. Will NOT see signs of orbital congestion,
as in orbital cellulitis.
p r b ita l C ellulitis •' ,:•••■ ';/. A - ‘ ' 7 : ; . /.': ; j

• Epidemiology/History: One of the leading causes of exophthalmos in
children (78). Ask about fever, recent sinus or dental infections, or recent
trauma.
• Pathophysiology/Diagnosis: An infection posterior to the orbital sep

tum. Most commonly results from the following (non-exhaustivelist) (33) (102):
1. Sinus infection - especially ethmoid sinusitis (the infection can

easily spread through the very thin lamina papyracea).

2. O rbital in fection - dacryoadenitis, dacryocystitis, progression of

preseptal cellulitis.
3. O rbital fracture.
4. D ental in fection .
Staphylococcus aureus and Haemophilus influenzae are the

most common bacterial culprits in adults and children, respec
tively (102).
• Symptoms: Red eye, pain, decreased vision, headache, fever, general

malaise, reduced color vision, an afferent pu p illary defect (A P D ),
proptosis, and d ip lop ia with pain on eye movement due to E O M re
strictions.
• Signs: Eyelid edema and redness.
• Prognosis:
— Orbital cellulitis is a serious infection that can result in a cavernous

sinus thrombosis, brain abscess, and/or m eningitis if not caught
early and managed appropriately (102).
- Diabetics and immunocompromised patients with orbital cellulitis
can develop m u corm ycosis, an aggressive fungal infection that can
be life-threatening; these patients have a characteristic “ black es
char” (black necrotic tissue) in their mouth and nose (2).
P resep ta l vs. o rb ita l cellulitis: Patients with preseptal celluli

tis will NOT have decreased vision, proptosis, fever, pain on eye
movement, or EOM restrictions, all of which are common in orbital
cellulitis.
jThyroid Eye Disease (G rav e s’ O p h th a lm o p ath y )

• Epidemiology/History: Female predilection (8:1). Most commonly presents
in the fourth to fifth decade of life. 1% of patients have or will develop
myasthenia gravis (35). Cigarette smoking is the strongest risk factor for
the development of thyroid eye disease (2-9X greater risk) (2) (35) (78).

• Pathophysiology: Autoimmune disorder characterized by thyroid-stimulating

(TSH) receptor antibodies directed against the extraocular muscles (EOMs)
and orbital tissue, causing significant inflammation and thickening of the
EOMs and resulting optic nerve compression.
- Antibodies may also affect the thyroid gland, most commonly caus
ing hyperthyroidism. Thyroid eye disease occurs in 30 — 70% of
patients with Graves’ thyroid disease (78).
• Symptoms: Prominent eyes, chemosis, foreign body sensation, tearing,

photophobia, pain, diplopia, decreased vision, and color vision loss (non-
exhaustive list).
• Signs: Unilateral or bilateral (often asymmetric) prop tosis, u p p er lid

retra ction , eyelid erythema and edema, conjunctival/caruncle injection
and edema, decreased color vision, extraocular muscle restrictions, and
an APD. IOP may be elevated in primary and upgaze (2).
T h y ro id eye disease is the most common cause of unilateral OR

bilateral proptosis in middle-aged patients.
The following summarizes the N O SP E C S grading system of thyroid-

related ophthalmopathy (progressively increasing in severity) (42):
N: No signs or symptoms.
O: Only signs but no symptoms. Examples include upper lid retraction
(resulting in a stare appearance); this is referred to as D a lry m p le ’s
sign.
S: Soft tissue involvement such as lid edema and conjunctival chemosis.
P: Proptosis.
E: EOM involvement, resulting in diplopia; inferior rectu s is typically
affected first, followed by the medial, superior, and lateral recti (52).
C: Corneal involvement (e.g. punctate keratitis, superior limbic kera
toconjunctivitis (SLK), ulceration).
S: Sight loss due to optic nerve compression. Enlarged EOMs at the
orbital apex can compress the optic nerve, causing disc edema, an
APD, reduced color vision, and visual field loss; occurs in 5% of
patients (2).

CHAPTER. 10. OCULAR DISEASE 407
- V on G ra e fe ’s sign is upper eyelid lag during downgaze.

- K o c h e r ’ s sign is globe lag compared to lid movement when
looking up.
- D a lry m p le ’s sign is lid retraction resulting in a stare ap
pearance.
• Diagnosis:
- Forced ductions to detect EOM restrictions.

- C T/M R I to detect enlargement of the EOMs (tendons will be spared).
- Exophthalmometry to measure proptosis.
- Visual fields to detect optic nerve compression.
- Blood work (T 3 /T 4/T S H ) to measure thyroid function.
Hertel exophthalmometry norms for adults:
• 12-22 mm for Caucasians.
• 12-18 mm for Asians.
• 12-24 mm for African Americans.
• Abnormal if higher OR presence of >3 mm asymmetry. Make

sure to record the base (18)!
C a rotid-C a vern ou s Fistula (C C F ): Results from an abnormal communi

cation between the arterial and venous systems.
• Most commonly results from closed head trauma (77% of cases) (62).
CCFs may also develop spontaneously (classically from a ruptured carotid
aneurysm) or from cavernous sinus pathology.*
* High pressure blood from the carotid artery builds up in the cavernous
■ sinus and impedes the return of venous blood back to the cavernous sinus;
this leads to a build-up of pressure posterior to the globe and the unique
clinical triad of chem osis, pulsatile p rop tosis, and an ocu la r bruit.
Copyright 2014 by KM K Educational Services, LEG

• Additional signs include episcleral venous congestion, periorbital tissue

swelling, elevated IOP, diplopia secondary to CN 3, 4 or 6 palsies, and
loss of lid/face sensation on the affected side due to CN 5 palsy (2).
p r b ita l T um ors y ^ ; C
The following is an overview of orbital tumors:
C avernous H em an giom a: Most common ben ign orbital tumor in adults (52);
occurs in the fourth to sixth decade and is more common in females (35).
Characterized by progressive, painless, unilateral proptosis as the tumor most
commonly arises posterior to the globe within the muscle cone.
C apillary H em an giom a: Most common ben ign orbital tumor in chil

dren (52); almost all cases are diagnosed by 6 months after birth. Can cause
proptosis and d ep riv ation am blyopia if the visual axis is blocked (52). Char
acterized by rapid growth and spontaneous involution (70-75% of lesions grad
ually involute by age 7) (52) (58).
R h a b d o m y o sa rco m a : Most common prim ary pediatric orbital malignancy.

It is a rapid bone-dest ructing tumor that causes progressive unilateral propto
sis. The average age of diagnosis is 7 years.
N eu rob la stom a : Most common secondary pediatric orbital malignancy

(2nd most common overall malignancy to rhabdomyosarcoma) (35). Most com
monly arises from a tumor in the abd om en , mediastinum, or neck (may have
associated Horner’s syndrome) (2) (35) (52).
O p tic N erve G liom a (juvenile p ilo cy tic astrocy tom a ): Most common
intrinsic tu m o r o f the o p tic nerve (65% of such tumors) (35). Commonly
leads to symptoms within the first decade of life (ages 2-6) (33). Infant cases
of optic nerve glioma are associated with neurofibromatosis type 1 in up to
30-50% of cases (2) (35).
M en in giom a : Most common benign brain tum or; typically occurs in

middle-aged women. Sphenoid meningiomas arise from the sphenoid bone and
are the most common intracranial tumor to invade the orbit (102),
D e rm o id cyst: Commonly located within the superior/temporal quadrant.

Often congenital and diagnosed in early childhood (1st decade) as a result of
noticeable proptosis. A CT scan will show a well-defined mass (2),

L y m p h om a : Most common in patients 50-70 years old (35) (52). Character

istics signs include an afferent pupillary defect (APD) and insidious progressive
proptosis and vision loss. 30-50% of patients with orbital disease develop sys
temic involvement, of which 60% have a 5-year survival rate (2) (35) (71).
N eu rofib rom a : A benign, yellow-white tumor of astrocy tes that is most

common in young to middle-aged adults. A CT scan shows a well-defined
mass that is usually located in the superior orbit. It can be isolated, multiple,
unilateral or bilateral (33) (35). May be associated with neurofibromatosis.
N eu rilem m om a (S chw annom a): A benign tumor of" the Schwann cells
that is most common in young to middle-aged adults. Typically located in the
superior orbit, as the tumor develops within the first division of CN 5. Patients
report a gradual onset of painless, progressive proptosis (2).
O rbital tu m ors frequently result in progressive vision loss, prop

tosis, diplopia, and an APD.
jOrbital In flam m atory D iseases

O rbital P seu d otu m or
• Epidemiology/History: Hare condition. May be acute, recurrent, or

chronic. Most commonly affects y ou n g to m id d le-ag ed patients (20-
50 years old). 3rd most common orbital disorder in adults (2) (78).
• Pathophysiology/Diagnosis: Idiopathic inflammatory process that can

impact any soft tissue component of the orbit. The appearance can
vary significantly depending on the orbital tissue involved; some patients
present in a manner similar to thyroid eye disease, while others have a
clinical appearance that is significantly worse and resembles orbital cel
lulitis.
• Symptoms: Acute onset of unilateral pain, red eye, diplopia, and/or

decreased vision. Bilateral involvement may occur in children (30% of
cases) (52); 50% of affected children will have additional symptoms of
fever, nausea, and vomiting (35).•
• Signs: P rop tosis and/or EOM restrictions (causing external ophthal

moplegia), periorbital swelling, chemosis, lacrimal gland enlargement, lid
ptosis, hyperopic shift, optic nerve swelling (if posterior), increased IOP
on the involved side, and reduced corneal sensation (due to CN V I in
volvement) (non-exhaustive list).

C h em osis is typically associated with allergic symptoms. If

chemosis is unilateral and NOT associated with allergic symptoms,
be certain to include idiopathic orbital inflammation in the list of
differential diagnoses (especially in young to middle-aged patients).
• Idiopathic orbital inflammation results in widespread inflammation through

out the orbit, INCLUDING the tendons of the EOMs (as opposed to
thyroid eye disease). A CT/M R I scan may aid in the diagnosis and will
show enlargement of the EOMs AND tendons.
T olosa-H u n t sy n d rom e is a rare type of idiopathic orbital inflammation

that can affect the cavernous sinus and the superior orbital fissure.
• Patients often present with acute and painful exophthalmoplegia and

diplopia due to ipsilateral palsies of cranial nerves 3, 4, and 6.
• Since V I and V2 also travel through the cavernous sinus, loss of sensory
innervation to their areas of distribution may also occur.
B ila tera l orb ita l p seu d otu m or in adults should raise suspicion
for systemic vasculitis (Wegener’s granulomatosis, polyarteritis no
dosa) or lymphoma (33) (35).
P h th isis B ulbi Y. Y ; Y Y)YV) Y v.

Shrinkage and atrophy of the globe as a result of trauma, infection, surgery,
or advanced disease. Typically associated with inflammation, hypotony, and a
blind eye (35).
A nophthalm os ' . \ .. -Y'-..
Absence of ocular tissue within the globe; primary cases are very rare.
M icro p h th alm o s Y 1
Small globe, congenital in nature.

fe n o p littia lm o ^ ' V- ' . • C/ h. ;

Retraction of the globe within the orbit; often results from ocular trauma.
]Oealar prosthesisWk
A prosthesis that fits over an orbital implant and sits behind the eyelids; typ
ically made of methyl methacrylate and designed with iris and conjunctival
details that are similar in appearance to the fellow eye. An orbital prosthe
sis is indicated in cases of anophthalmos secondary to the following surgical
procedures (27):
• Enucleation: Removal of the globe.
• Evisceration: Removal of the inner contents of the eye; sclera and other
orbital contents remain.
• Exenteration: Removal of ALL contents of the orbit, including EOMs

and orbital fat.
(External D isease %- ; <■ : : . ;

O cular R osa cea
• Epidemiology/History: Most common in middle-aged adults of Northern

European ancestry. Women are affected more than men, but men often
have more severe disease. Affects approximately 10% of the population,
including an estimated 50% with acne rosacea (2) (58).
• Pathophysiology/Diagnosis: Condition affects the seba ceou s glands

(including meibomian glands of the eyelids), resulting in chronic ocular
surface disease.
• Symptoms: Redness, burning, foreign body sensation, ocular irritation.
• Signs: Characterized by papules on the cheek and forehead with telang

iectasia, rhxnophym a (sebaceous gland hyperplasia of the nose), and
facial flushing (aka malar or butterfly rash) (58).
— Facial flushing with rosacea is associated with triggers such as

alcoholic beverages, exertion, spicy foods, caffeine, and increased
sun exposure.

O cu lar rosacea causes lid disease (e.g. inspissated meibomian

glands, blepharitis, hordeola, chalazia), which results in ocular
surface disease (e.g. phlyctenules, staph marginal keratitis, SPK,
corneal neovascularization (greatest interiorly), and dry eye syn
drome) .
C on ta ct D erm atitis
• Pathophysiology/Diagnosis: T y p e 4 hypersensitivity rea ction that

typically develops 24-72 hours after exposure to the inciting agent. Clas
sically results from the following:
— C osm etics - Makeup, shampoo, soaps, hairspray, fingernail polish,

perfumes, jewelry, poison ivy, contact lens solutions.
— M e d ica tion s - Aminoglycosides (e.g. gentamicin, tobramycin), tri-
fluridine, cycloplegics/mydriatics (e.g. tropicamide, phenylephrine),
glaucoma medications (e.g. timolol, Alphagan®, Trusopt® ), and
preservatives (e.g. thimerosol, BAK) (12) (35).
• Symptoms: Acute periorbital swelling, redness, itching, tearing.
• Signs: Unilateral or bilateral erythema and crusting of the lid and peri
orbital tissues and significant conjunctival chemosis.
O cular C ica tricial P em p h ig oid
• Epidemiology/History: Rare condition that affects females more than

males (2:1). The average age of diagnosis is 65 years; a significant number
o f these patients develop bilateral blindness an estimated 10-30 years after
diagnosis (58).
• Pathophysiology/Diagnosis: Chronic, system ic, id iop ath ic (likely au

toimmune mechanism) mucous membrane disorder that most commonly
affects the oral and ocular mucous membranes (e.g. con ju n ctiva, mouth,
esophagus, and less commonly the vagina and skin) (35) (58). QCP can
also be drug-induced from tim olol, epinephrine, and pilocarpine (35).
• Symptoms: Sub-acute onset of nonspecific symptoms including redness,

dryness, foreign body sensation, and/or decreased vision.•
• Signs: Conjunctival fibrosis and scarring (seen as fine white striae), bi
lateral sym bleph aron , ankyloblepharon, and stretched inferior fornices
due to shortening of the conjunctival tissue.

CHAPTER 1 0 . OCULAR DISEASE 413
• Prognosis: Progression of the disease results in the destruction of gob

let cells, meibomian glands, the glands of Krause and Wolfring, and the
ducts of the main lacrimal gland, resulting in severe ocu lar surface
disease. Additional late stage findings include entropion and trichia
sis, with resulting corneal ulceration, neovascularization, and keratiniza-
tion (2) (58) (78).
Stevens-Johnson S yn drom e
• Pathophysiology/Diagnosis: A ty p e 3 h y persen sitivity reaction that

affects mucous membranes (typically oral and ocular mucous membranes).
SJS is most commonly d ru g -in d u ced (e.g. sulfonam ide (most com
mon), phenytoin, penicillin, aspirin, barbiturates, isoniazid, tetracyclines,
NSAIDs, immunizing vaccinations), or from an in fectiou s agent (her
pes simplex virus, Mycoplasma pneumoniae, adenovirus, streptococcus
species) (2) (58) (35).
— Characterized by an acute phase (often self-limiting within 2-4 weeks),

which may be followed by a chronic phase (35) (58).
• Acute signs/symptoms: Systemic p ro d ro m e of fever, malaise, headache,

nausea, and vomiting. The prodrome is followed by the development of
skin lesions (e.g. diffuse erythema, classic “target” or “bull’s eye” lesions,
and papules on the palms of the hands and soles of the feet). O cular
lesions also occur in this phase and include:
— Severe, bilateral, diffuse conjunctivitis associated with pseudomem

branes.
— Bacterial conjunctivitis can progress to endophthalmitis in severe

cases.
• Chronic signs/symptoms:
— Eyelid pathology: Entropion, ectropion, trichiasis, meibomian gland

damage.
— Conjunctival pathology: S ym bleph aron , foreshortening of the for-

nices, conjunctival keratinization, and limbal stem cell damage, which
leads to subsequent corneal pathology.
— Corneal pathology: Ulcers, neovascularization, scars, and in some

cases, perforation (58).

414 lO.J,-. LIDS/LASHES/LACRIMAL SYSTEM
— SECTION 10.4 ---------------------------------------------------------------------
L ids/L ashes/L acrim al System
• Common condition in the elderly. It is characterized by redundant upper

eyelid skin that results from a weakened orbital septum, often causing
eyelid ptosis, pseudoptosis, and a loss of typical distinct eyelid creases.
• Advanced cases may cause an apparent superior visual field loss.
• There are two main types of blepharitis: staphylococcal blepharitis

and seborrheic blepharitis. Both can result in anterior and/or poste
rior blepharitis (meibomitis).
• Patients are often asymptomatic, but may report vision that clears af
ter blinking, burning, itching, foreign body sensation, tearing, crusting
(especially in the morning), and mild discharge.
• Seborrheic blepharitis is frequently associated with seborrheic dermati

tis. Seborrheic blepharitis is associated with less lid inflammation, more
oily, greasy scales with flaking, and more eyelash loss (madarosis) and/or
misdirected growth compared to staph blepharitis (78) (105).
Chalazion v -■y j
• Epidemiology/History: Often have a history of similar recurrent lesions.
Ask about acne rosacea and seborrheic dermatitis.
• Pathophysiology/Diagnosis: Chronic, localized, sterile inflammation

of a meibomian gland due to retention of normal secretions. 25% of
chalazia resolve spontaneously without treatment (12).•
• Signs/Symptoms: Characterized by a hard, painless, immobile nodule

without redness that is most commonly located on the upper eyelid. Pa
tients are typically asymptomatic.
Recurrent chalazia warrant an evaluation for possible malignancies

(e.g. seba ceou s gland carcinom a).

HSilMWW&v:
* Epidemiology/History: Often have a history of similar recurrent infec
tions (similar to chalazia) that are successfully self-treated. As with cha
lazia, ask about acne rosacea and sebborheic dermatitis.
• Pathophysiology/Diagnosis: An acute sta p h y lococcu s in fection of the

eyelid glands.
- Internal h ord eolu m - affects the meibomian glands.

— E xternal h ord eolu m - affects the glands of Zeis or Moll. Also
known as a stye.
• Signs/Symptoms: Characterized by a tender, red, warm area of focal

swelling on the lid.
• Benign lesions that develop from the epithelium of the epidermis and
dermal tissues and are often associated with the meibomian, sebaceous,
and sweat glands of the eyelids (93).
• Do not affect visual acuity or cause pain, unless rupture of the cyst leads
to an inflammatory reaction. The most common patient complaint is
poor cosmesis (30)
• Examples include (non-exhaustive list) (95):
— In clu sion cyst: A congenital or acquired lesion (secondary to

trauma or surgery) found on the lid and surrounding adnexal tis
sue that often appears white due to the accumulation of keratinous
debris.
— M ilia: Acquired lesion found on the lid and surrounding adnexal
tissue that may appear white and is due to occlusion of sweat pores
or pilosebaceous follicles.
— D e rm o id cyst: A congenital lesion that is firm and immobile and
usually located on the superior temporal or superior nasal eyelid.
— Sebaceous cy st: Characterized by retention of fluid in the glands
of Zeis or retention of debris in the meibomian glands. They are
usually solitary, smooth lesions that are yellow or opaque.
[Ectropion
• Pathophysiology/Diagnosis: Eversion of the lid away from the globe of
the eye. The most common cause is age-related (involutional) loss of
muscle tone of the orbicularis oculi (85). Other causes include mechanical

416 1 0 .4 . l id s /l a s h e s /l a c r i m a l s y s t e m
(e.g. tumor-related), cicatricial (e.g. scar tissue from trauma, chemical

burns, skin disease, previous lid surgeries), paralytic (e.g. facial nerve
palsy), and congenital (rare) (2).
• Signs/symptoms: E x p osu re keratopathy, epiphora, brow ptosis.
- - k ' - ^ v ; L
>v^vV " ' ^
• Pathophysiology/Diagnosis: Inversion of the eyelid against the globe.

Causes include age-related (involutional), cicatricial (e.g. trachom a,
OCP, Stevens-Johnson syndrome, chemical burns, previous lid surgeries,
trichiasis, distichiasis), and congenital (rare). Entropion can result in
pseudotrichiasis (2).
— Trichiasis: Eyelashes grow posteriorly from their site of origin.

— D istichiasis: A second row of eyelashes arises from the meibomian
gland openings.
• Signs: Range from mild punctate keratitis to corneal ulceration and pan-
nus (in chronic and severe cases).
A large number of cases of blindness in trachoma are due to corneal

ulceration secondary to entropion and trichiasis.
F loppy E yelid S yndrom e '■:> I

• Epidemiology/History: Most common in obese men with ob stru ctiv e
sleep apnea,
• Pathophysiology/Diagnosis: Associated with significant reduction in elastin

within the tarsal plate; this occurs predominantly in face-down sleepers
and is thought to result from mechanical trauma to the tarsal plate from
chronic lid-to-pillow contact (58).
- During sleep, spontaneous lid eversion exposes the superior tarsal

conjunctiva to the bedding, causing a papillary conjunctivitis.
— Systemic disease associations include obstructive sleep apnea, dia
betes mellitus, hyperthyroidism, and hypertension (HTN) (58).•
• Symptoms: Chronic, bilateral (78%) red eyes in the morning upon awak
ening, often with mild mucous discharge (58).
• Signs: Chronic papillary conjunctivitis with loose upper eyelids that ev
ert easily; punctate epithelial keratopathy (50%) and keratoconus are
noteworthy corneal associations (58).

CHAPTER, 10. OCULAR DISEASE 417
jBcmgn Esse B lepharospasm {B E B ) : ; 7, v >

• Epidemiology/History: Most common in ages 50-70, with a mean age
of onset of 56 years (12). Women are affected 2X more commonly than
men (2).
• Symptoms: Involuntary, sustained, repetitive bilateral twitching and/or

forceful closing of the eyelids that is less common during sleep.
• Signs: Spasms of the orbicularis oculi, procerus, and corrugator muscu

lature (12).
• Pathophysiology/Diagnosis: Most commonly idiopath ic, although can

be a result of corneal or conjunctival irritation. 78% of patients with BEB
initially have random episodes of increased blinking that last seconds
to minutes, with eventual progression to involuntary spasms with eyelid
closure.
- Over 50% of patients have an ocular surface disorder (most com

monly dry eye syndrome) that may be exacerbating the spasms (12).
M e ig e ’s syn drom e is characterized by BEB AND lower facial

abnormalities (e.g. difficulty chewing and opening the mouth, jaw
spasms, jaw pain, etc.) (12) (35). Approximately 50% of patients
with BEB have Meige’s syndrome (2).
* Characterized by unilateral tw itch in g (NOT eyelid closure) of the or

bicularis oculi; does not affect the procerus or corrugator muscles.•
• Commonly caused by sleep deprivation, too much caffeine, and/or stress.
C om pa rison o f B E B to M y ok y m ia :
1. B E B = idiopathic, bilateral, affects three muscles.
2. M y ok y m ia = classic causes, unilateral, affects one muscle.

418 10.1 LIDS/LA SUES/LA CRIMAL SYSTEM
M alignant v A- ;
Basal C ell C a rcin om a (B C C )
• Epidemiology/History: The most common skin cancer in the United

States (58). Affects males more than females (2:1) (29). BCC is the
most common eyelid cancer, accounting for over 90% of all eyelid ma
lignancies (52). It is associated with fair skin and ultraviolet exposure, es
pecially in the UV-B range (290-320 nm). Patients often report a chronic
lesion that occasionally bleeds and will not heal.
• Pathophysiology/Diagnosis: Malignancy of the basal cell layer of the epi

dermis. Increased sun exposure in childhood and adolescent years is a
critical risk factor for the development of BCC later in life (58).
— BCC is minimally invasive; the incidence of metastasis is less than

0.1% (58).
• Signs: Varies in appearance. Most commonly presents as a shiny, firm

p e a rly n o d u le w ith superficial telangiectasia. If not recognized
and treated at an early stage, progression occurs and central ulceration
develops (“ rod en t u lcer” ). Most commonly located on the lower eyelid
(50 — 66%) and the medial canthus (25 — 30%) (58).
S quam ous C ell C a rcin om a (S C C )
* Epidemiology/History: More common in males (2:1) (58). SCC is the

2nd most common eyelid cancer, but it is 40-50 times less common than
BCC.
• Pathophysiology/Diagnosis: Malignancy of the stratus spinosum layer

of the epidermis. Associated with ultraviolet exposure (especially in the
UV-B range of 290-320 nm), actinic keratosis, fair skin, prior radiation,
burn scars, chemical exposure (e.g. smoking), and other forms of chronic
irritation.
A c tin ic keratosis is the most common precancerous skin lesion

and is a precursor to SCC. It is an elevated, commonly pink or red,
scaly lesion on sun-exposed skin that does not heal. 25% of cases
of actinic keratosis develop into squamous cell carcinomas (35).
• SCC is more aggressive than BCC; 13% to 24% of SCCs undergo metas
tasis to nearby lymph nodes (35).

• Signs: Variable presentation; often appears similar to BCC but WITH

OUT surface telangiectasia. Classically described as an erythematous
plaque that appears rough, scaly, and/or ulcerated, and may be flat or
elevated. Most commonly located on the lower eyelid or lid margin.
S C C and B C C are both associated with chronic exposure to sun

light; they can appear very similar, but SCC rarely contains surface
vascularization (52).
K era toa ca n th om a is usually found in sun-exposed areas and has

an early appearance (often a central plaque or ulcer) that is similar
to BCCs and SCCs. Keratoacanthoma tumors grow very quickly
to a large size (1-2 cm) before they slowly shrink and often spon
taneously resolve (33) (35).
Seba ceou s G lan d C arcin om a
• Epidemiology/History: Rare, with a similar incidence to SCC. More com

mon in elderly females. Patients may have a history of chronic unilateral
blepharitis or recurrent chalazia.
• Pathophysiology/Diagnosis: A neoplasm o f the sebaceous glands of the

eyelids (m eibom ian glands and glands of Zeis) that may be associated
with prior radiation therapy (35). Sebaceous gland carcinoma has a poor
prognosis; if the lid lesion is greater th an 2 cm , the mortality rate is
60%. If symptoms have been present longer than 6 months, the mortality
rate is 38% (35). The overall mortality rate is 10% (52).
• Signs: Varies. The tumor is often hard and yellow. It is associated with
madarosis, thickened and red lid margins (most common on the upper
eyelid), and lymphadenopathy (35).
M alignant m elanom a
• Epidemiology/History; Rare (<1% of all eyelid malignancies) but most

lethal primary skin cancer (35).•
• Pathophysiology/Diagnosis: Malignancy of melaiiocytes, the cells that

produce pigment within the skin. Risk factors include age, skin color,
family history, repeated irritation, and sun exposure.

420 10.4. LIDS/LASHES/LA GRIMAh SYSTEM
• Signs: Characteristics of suspicious skin lesions for malignant melanoma

include the following:
— A : Asymmetry.
— B : Border irregularity.
— C : Color differences (i.e. uneven pigmentation).
— D : Large diameter.
— E: Enlargement of the lesion.
• The depth of invasion and lesion size are the two most important prog
nostic factors for malignant melanoma (32).
L acrim al S y s t e m D isorders '' ' •/•''../ ; : viL/Aj

D acryoa den itis
• Epidemiology/History: More common in children and young adults. Ask

if acute or chronic symptoms and if there is any history of a recent fever
or systemic infections.
• Pathophysiology/Diagnosis: Dacryoadenitis is an inflammation of the

lacrimal gland that can be acute or chronic in nature.
1. A c u te in fection s: Most commonly a result of an in fection by

bacteria (Staphylococcus aureus, Neisseria gonorrhea, Streptococci)
or viruses (mumps, mononucleosis, influenza, herpes zoster).
2. C h ron ic infections: More common than acute infections. Results
from in flam m a tory disorders including sarcoidosis, tuberculosis,
Graves’ disease, and idiopathic orbital inflammation (12) (33) (35);
25% of patients with idiopathic orbital inflammation will have lacrimal
gland involvement (52).
• Signs/Symptoms: Swelling of the outer l/3 rd of the temporal upper eye

lid (region near the lacrimal gland). Signs may vary in acute and chronic
presentations:
1. Acute: Classically presents with an S-shaped ptosis, temporal up

per eyelid pain, redness, and swelling, preauricular lymphadenopa-
thy, an occasional fever, and an elevated W BC count.
2. Chronic: Presents as temporal upper eyelid swelling with less red
ness, swelling, and pain compared to acute dacryadenitis. Chronic
cases may lead to inferonasal globe displacement and proptosis.

CHAPTER 10. OCULAR DISEASE 4 21
C analiculitis
• Pathophysiology/Diagnosis: Inflammation o f the canaliculi that can be

caused by bacterial, viral, or fungal infections. The most common culprit
is A ctin o m y ce s Israeli (Streptothrix), which is characterized by yellow
sulfur granules after expression of the canaliculi (102).
— Other culprits include Staphylococcus aureus, Candida albicans, As

pergillus, Nocardiaasteroides, Herpes Simplex or Herpes Zoster (33) (35).
— Canaliculitis may also occur after surgery, trauma, and secondary
to neoplastic disorders (12).
• Symptoms: Smoldering, unilateral red eye that is often unresponsive to

antibiotic treatment; often misdiagnosed as recurrent conjunctivitis (12).
• Signs: Tenderness over the nasal portion o f the upper or lower eyelid, a
swollen puncta (“ p o u tin g p u n cta ” ) and mucopurulent discharge that
occurs with palpation over the lacrimal sac region.
D a cry ocy stitis
• Epidemiology/History: Ask about concomitant ear, nose, or throat in

fections.
• Pathophysiology/Diagnosis: L acrim al sac in fection that occurs when

the lacrimal drainage system is obstructed (e.g. NLDO), resulting in a
backflow of bacteria in the lacrimal sac from the lacrimal lake (12).
— Common causative agents include Staphylococcus aureus, Staphylo

coccus epidermidis, Pseudomonas, and H. influenzae in children (12) (35).
- Characterized by swelling below the medial canthal tendon; note
that swelling ABOVE the medial canthal tendon should raise suspi
cion for a lacrimal sac tumor (33).•
Chronic cases of dacryocystitis should raise suspicion for epithelial

carcinomas and malignant lymphomas, unfortunate pathology that
are often overlooked; carcinomas can express blood into the tear
film with palpation of the lacrimal sac (12).
• Symptoms: Pain, often with crusting and tearing, occasional fever.
* Signs: Prominent edema and tenderness over the lacrimal sac area.

422 10.4- LIDS/LASHES/LACRIMAL SYSTEM
D a cry o cy stitis typically has more swelling, tenderness and pain

than canaliculitis.
DO NOT refer for surgery or attempt to irrigate the lacrimal sys

tem during an acute dacryocystitis infection. Treatment should be
initiated first.
P u n cta l stenosis
• Acquired punctal stenosis is defined as a narrowing or occlusion of the

puncta o f the upper and/or lower lids. It is most commonly associated
with older age, where progressive narrowing and occlusion of the puncta
occur.
• There is no consensus on the clinical definition of punctal stenosis. The

most common definitions used in the literature define punctal stenosis as
a punctal diameter less than 0.3 mm, or as the inability to intubate the
puncta with a 26 gauge cannula.
• The most common symptom is epiphora, although patients may also

report nonspecific complaints of ocular irritation (100).
N asolacrim al D u ct O b stru ction
• Epidemiology/History: Can be congenital or acquired. Acquired NLDO

is more common in females (2:1) (35).
• Pathophysiology/Diagnosis: Obstruction of the nasolacrimal duct.
— Involutional stenosis: The most common cause of NLDO in older

patients. Additional etiologies in older patients include chronic sinus
disease, dacryocystitis, and naso-orbital trauma.
- Membranous blockage at the valve of Hasner: The most common
cause of congenital NLD obstruction; occurs in up to 30% of new
borns (78) (102). Spontaneous opening of the valve of Hasner fre
quently occurs 1-2 months after birth. If spontaneous opening does
not occur, digital massage can be performed (35).•
• Symptoms: Unilateral tearing, discharge, crusting, and recurrent con

junctivitis.

• Signs: Epiphora, mucous reflex from the puncta after compression of the
lacrimal sac, medial lower eyelid erythema, and mild to no redness or
tenderness around the puncta.
A secondary dacryocystitis is not uncommon in cases of con geni

tal N L D O due to the stagnant tears in the lacrimal sac (12).
JO N E S I and II T E S T IN G
These are tests used to evaluate the ability of the tears to pass through the
lacrimal drainage system.
J on es I test: Tests the patency of the nasolacrimal system. Fluorescein is

instilled in the inferior fornix and should drain off the ocular surface within
five minutes if the nasolacrimal system is functioning properly.
• P ositive Jones 1 = P atent system . This is confirmed by the presence

of fluorescein in the back of the patient’s throat or by having the patient
blow their nose and seeing fluorescein on the tissue.
Jon es II test: Nasolacrimal irrigation with saline following a negative

Jones I test (no fluorescein noted).
• Reflex of fluid through the same punctum indicates an obstruction within

the upper or lower canaliculus (i.e. proximal to the common canaliculus).
• Retrograde flow through the opposite canaliculus and punctum indicates

nasolacrimal blockage (i.e. obstruction distal to the common canalicu
lus) (35).
• If the patient tastes saline, performs a gag reflex, or if fluid is recovered

from the nose, the obstruction has been cleared.
• If the Jones II test fails to open the nasolacrimal drainage system, a

dacryocystorhinostomy (DCR.) is the best treatment option.
- SE C T IO N 10.5 -------------------------------------------------------------------------------------------------------------------
C onjunctiva
1. C on ju n ctiva l C yst

• A common, benign, fluid-filled (typically clear) sac on the conjunctiva

that may cause irritation (94). Also referred to as an inclusion or reten
tion cyst.
2. C on ju n ctiva l C on cretion s
• Superficial, whitish-yellow deposits of mucous secretions and epithelial

cells in the palpebral conjunctiva. Conjunctival concretions are also
known as ocular lithiasis.
• Patients are typically asymptomatic, but may experience a foreign body

sensation.
3. C o n ju n ctiv a l N evus
• Rare, benign proliferation of melanocytes that presents around puberty

or early adulthood (within the 1st two decades of life). During puberty,
it is not uncommon for the size and darkness of the nevi to increase.
• Conjunctival nevi are typically unilateral, solitary, flat (or slightly ele
vated), freely mobile, and are occasionally non-pigmented (30%) (52).
In clu sion cysts within the lesion are diagnostic for a conjunctival ne
vus (2).
• The most common location for a conjunctival nevus is the juxtalimbal

area, followed by the plica and caruncle (52).
4. P rim a ry A cq u ired M elan osis (P A M )
• Rare, unilateral, acquired pigmentation that is more common in elderly

white patients.*
* The patches, which can be located anywhere on the conjunctiva, are

usually flat with indistinct margins. Although PAM can be benign, it
also has prem alignant potential; 30% of cases progress to m alignant
m ela n om a (102). Nodular lesions with increased vascularity and/or
increased growth are most suspect for possible malignancy (2). A biopsy
is warranted to determine whether the lesion is malignant.
5. C on ju n ctiva l M elan om as
• Conjunctival melanomas are secondary to the uncontrolled proliferation

o f melanocytes. They are found almost exclusively in Caucasians and
usually develop around age 50 (2).

• Malignant melanomas of the conjunctiva can be pigmented or non-pigmented

and m ost co m m o n ly arise from P A M (50 — 75% of cases), less com
monly from a pre-existing nevus (33% of cases), and rarely de novo (35) (102).
• The most important prognostic indicator for progression to malignancy

is the thickness of the lesion (102). The most common site of metastasis
is the liver (58).
6. C on ju n ctiva l Intraepithelial N eoplasia (C IN )
• Although rare, CIN is the m ost co m m o n con ju n ctival m alignancy in

the United States (31). It is also known as Bowen’s disease or conjunctival
squamous dysplasia (58).
• CIN is a unilateral, prem alignant condition that can progress to squa

m ou s cell ca rcin om a (although the risk is low as the basement mem
brane most often remains intact) (58). Bisk factors for development in
clude UV-B exposure, smoking, exposure to petroleum derivatives, fair
skin, xeroderma pigmentosa, HIV, and HPV (2) (58).
• Presentation can vary, but the most common appearance is an elevated,

gelatinous mass with neovascularization; approximately 10% of cases ex
hibit leukoplakia (keratinization) (34). 95% of cases are found at the
limbus within the interpalpebral fissure (102). CIN can progress onto the
cornea.
P A M can progress to a con ju n ctival m elanom a. C IN can

progress to a squam ous cell carcinom a.
7. C on ju n ctiva l Squam ous C ell C arcin om a
* Rare, slow-growing, malignant tumors that typically present in elderly

Caucasian (90%) males (81%) (35). Most commonly derived from C IN
and typically associated with ultraviolet radiation and I-IPV (58).*
* Conjunctival squamous cell carcinoma is usually found at the limbus and

may involve the adjacent cornea. The lesion commonly contains a feeder
vessel.
8. P y o g e n ic G ranulom a
* A pedunculated, benign, red, vascular lesion of the palpebral conjunc

tiva that results from trauma, surgery, a chalazion, or other sources of
chronic irritation.

9. Conjunctival Granuloma
• Inflammed area (white, yellow, translucent, or brown), located within

the conjunctival stromal tissue that results from retained foreign bodies,
surgery, trauma, infections (e.g. Parinaud’s oculoglandular syndrome),
or associated systemic conditions (e.g. sarcoidosis) (58).
• Patients may be asymptomatic or complain of ocular irritation and for

eign body sensation (92).
jBaeterial C o ^
Bacterial conjunctivitis can be divided into simple bacterial conjunctivitis and
gonococcal conjunctivitis.
1. Simple Bacterial Conjunctivitis
• Epidemiology/History: More common in children than adults.
• Pathophysiology/Diagnosis: H. influenzae is the most common cause of

bacterial conjunctivitis in young children (58). S. epidermidis and S.
aureus are the most common culprits in adults.
• Symptoms: A cu te onset of redness that usually begins in one eye and

becomes bilateral. Additional symptoms include foreign body sensation
and eyelids stuck together upon awakening. Symptoms typically subside
in 10-14 days, even without treatment (58).
• Signs: Variable discharge (typically moderate to severe) that is often ini

tially serous before becoming mucopurulent (most common) or purulent.
Corneal signs and preauricular lymphadenopathy are rare.
S. aureus, which is prevalent in all age groups, is the most com

monly isolated organism and the most frequent cause of bacterial
conjunctivitis worldwide due to its high association with blephari
tis (58).
2. Gonococcal Conjunctivitis
• Epidemiology/History: Sexually transmitted ocular disease that is most

common in young adults with a history of multiple sexual partners. May
also be transmitted to infants as they pass through the vaginal birth canal
in infected mothers.

• Pathophysiology/Diagnosis: Neisseria gonorrhea is the most common

causative agent. The T h a y er-M a rtin agar is used for diagnosis (18).
Gram stain for N. gonorrhea will show gram-negative intracellular diplo-
cocci.
• Symptoms: Characterized by a h y p eracu te on set of severe purulent

discharge. Additional symptoms include redness, foreign body sensa
tion, and eyelids stuck together upon awakening; the condition usually
begins in one eye and becomes bilateral over time.
• Signs: Severe purulent discharge, conjunctival chemosis (often with

pseu dom em bran es), a severe papillary reaction, m arked preauricu-
lar lym p h aden op ath y, and tender and swollen eyelids. Remember that
N. gonorrhea can invade an intact corneal epithelium and may result in
peripheral corneal ulceration in severe cases.
• Systemic symptoms include the following:
- M en : Purulent urethral discharge that occurs after a 3-5 day incu

bation period.
— W om en : Discharge is less common; approximately 50% of patients
are asymptomatic (52).
• All patients should also be evaluated for a co-existing chlam ydial sys
tem ic in fection (the most common co-infection with gonorrhea).
N . gon orrh ea is the only bacterial conjunctivitis that commonly

causes preauricular lym p h a d en op a th y and p seu d om em
branes, findings that are typically associated with viral conjunc
tivitis (102).
jViral C otijunctiyitis
1. A d en ov ira l C on ju n ctivitis
• Epidemiology/History: More common in adults than children.
• Pathophysiology/Diagnosis: Most adenoviral infections result from up

p e r respiratory tract or nasal mucosa infections (12). Approximately
1/3 of serotypes (there are over 45 recognized serotypes) are associated
with ocular infections (35). Transmission occurs from direct contact (e.g.
respiratory or ocular secretions, contaminated towels, equipment) and is
highly contagious for 12-14 days (35) (52). Classic adenovirus syndromes
include acute nonspecific follicular conjunctivitis, pharyngoconjunctival
fever (PCF), and epidemic keratoconjunctivitis (EKC) (35).

1. A c u te n on sp ecific follicular con ju n ctivitis: Results from serotypes

1-11 and 19 and is the most common type of adenoviral infec
tion (35).
— Presents with a diffuse red eye, conjunctival follicles in the infe
rior fornices, tearing, and mild discomfort; corneal involvement
is rare.
2. P C F results from serotypes 3-5 and 7. It is also referred to as “swim
ming pool conjunctivitis.” PCF more commonly affects children and
is highly contagious.
— Diagnosis of PCF is based on a triad of acute follicular conjunc
tivitis (occasionally hemorrhagic), mild low grade fever, and
pharyngitis (mild sore throat) (12). Corneal involvement is not
common.
3. E K C is the most serious form of adenoviral conjunctivitis and re
sults from serotypes 8, 19, and 37. This condition is well known for
pain and corneal involvem ent (80% of cases) (52).
— Clinical symptoms classically occur 8 days after initial expo
sure to the virus (58). Superficial keratitis is common during
the acute phase (1-2 weeks), while subepithelial infiltrates
(SE Is) commonly occur in the 3rd week, after the active por
tion of the disease has subsided (i.e. the patient is no longer
contagious) (105).
— P reau ricu lar lym p h ad en op ath y is almost always present in
EKC patients. They may also have pseudomembranes.
• Symptoms: Rapid onset of redness, tearing, mild discomfort, and preau

ricular lym p h aden op ath y. The condition typically starts in one eye
before spreading to the other.•
• General Signs: A cu te follicular con ju n ctivitis (follicles are most com

mon in the inferior fornices), marked conjunctival injection, p seu d om em
bran e form ation , preauricular lym phadenopathy (classic for EKC),
and diffuse keratitis (particularly in EKC).
SEIs may be infectious (e.g. viral, chlamydial, bacterial) or non-

infectious (e.g. graft rejection, solution hypersensitivity, hypoxia).
The presence of a palp able n od e in a patient with suspected ade

noviral infection is virtually always pathognomonic for E K C (105).

2. M ollu scu m C on tagiosu m
• Epidemiology/History: Rare. Common in communities with noted poor

hygiene. Most common in children and young adults.
• Pathophysiology/Diagnosis: Chronic infectious skin condition caused by

the D N A p o x virus that is spread through direct contact. If multiple
molluscum nodules are present, consider human immunodeficiency virus
(HIV) or other immunodeficiency conditions.
• Signs/Symptoms: Characterized by single or multiple dome-shaped, um-

bilicated, waxy nodules located on the lid or lid margin. Patients are
usually asymptomatic but may complain of a mild mucous discharge.
Rupture of the molluscum nodules may lead to an associated chronic
follicular conjunctivitis and superficial pannus.
H erpes S im plex is another cause of viral conjunctivitis that clas

sically presents with an unilateral follicular conjunctivitis with a
watery discharge.
lAliei'gic Disorders o f the Gonj unc t iva

1. A lle rg ic C on ju n ctivitis
• Epidemiology/Pathophysiology: Common condition that affects all ages.

A history of allergies is common. Allergic conjunctivitis can be divided
into categories of seasonal allergic con ju n ctiv itis and perennial al
lergic con ju n ctivitis.
1. Seasonal allergic con ju n ctiv itis: A ty p e 1 h ypersensitivity

reaction triggered by airborne allergens (e.g, pollen) (35).
2. P erennial allergic con ju n ctiv itis: A less common type 1 hyper
sensitivity reaction to household allergens (e.g. dust mites, animal
dander) (52).•
• Signs/Symptoms: Conjunctival chemosis, papillae, itching, tearing, wa

tery discharge.
2. V ernal K e ra to co n ju n ctiv itis (V K C )
• Epidemiology/History: Very rare condition (accounts for less than 1% of

allergic conjunctivitis cases) (35). Classically affects young males under
the age of 10 that live in hot, dry climates. The condition occurs for 2-10
years before resolving around puberty (58).

• Pathophysiology/Diagnosis: VKC occurs in patients predisposed with

a to p ic sy stem ic con d ition s (e.g. rhinitis, asthma); 40—75% of patients
with VKC have eczema or asthma, and 40 —60% of patients have a family
history of atopy (58). Seasonal outbreaks during the warm months are
common, although patients may have symptoms year round.
• Symptoms: Intense itching and photophobia (most common complaints),

ptosis, thick mucous discharge. The initial outbreak is the most severe;
symptoms decrease in intensity over time.
• Signs: The classic sign is bilateral prom inent papillae, either on the
limbus (Trantas D ots) or the upper palpebral conjunctiva (cob b leston e
papillae). Can also have corneal involvement that begins with punctate
epithelial keratitis that eventually coalesces into large erosions, leading
to plaque formation and localized ulceration (shield nicer).
V K C signs are predominately in the conjunctiva and cornea. The

eyelid margin and skin of the outer eyelids is relatively unaffected
in VKC compared to AKC (58).
3. A to p ic K e ra to co n ju n ctiv itis (A K C )
• Epidemiology/History: Rare (3% of allergic conjunctivitis cases) (35).

AKC is most common in young to middle aged adults (teens to 40s) with
a history o f atopic conditions, especially atop ic derm atitis (52).
A to p ic derm atitis (A D ) is a type of chronic eczema that starts

in early infancy (within the first two months). 60% of patients are
diagnosed within the first year of life (32). Hallmark signs include
pruritus and a rash. An estimated 25-42% of patients with atopic
dermatitis have ocular involvement (2). 10% of patients with severe
AD develop a cataract between the ages of 15 and 30 (52).
• Pathophysiology/Diagnosis: AKC is NOT seasonal. It is thought to re

sult from Type 1 and Type 4 hypersensitivity mechanisms (58).•
• Symptoms: Bilateral itching of the eyelids (the main symptom). Other

common associated symptoms include watery discharge, redness, photo
phobia, and pain.

CHAPTER 10, OCULAR DISEASE 431
• Signs include the following:
— Prominent outer eyelid (scaly, thickened, swollen) and periorbital

involvement, including D en n ie’ s lines (an extra crease under the
lower lid due to periorbital edema), and “atopy shiners” (bags under
the eyes from constant eye rubbing).
— Papillae are classically more prominent in feriorly (as compared to
superior papillae in VKC and GPC), although conjunctival signs
may be very mild, causing the inferior conjunctiva to appeal’ “fea
tureless” (102).
— Corneal neovascularization, cataracts (10%) and keratocon u s are
more common in AKC (52).
— Symblepharon formation of the inferior fornices may occur in severe
cases and mimic ocular cicatricial pemphigoid.
T ox icity to topical medications or contact lens solutions can result

in an allergic con ju n ctivitis that is characterized by a follicular
reaction.
R E V IE W O F P A P IL L A E A N D F O L L IC L E S :
1. P apillae: Inflamed areas of elevated conjunctiva that con

tain a central vessel that serves as the source for infiltration
of eosinophils, mast cells, neutrophils and lymphocytes (12).
• Range in size from very small (less than 1 mm) to very

large (as in GPC and VKC) (12).
• N on -sp ecific to any condition, but are commonly as
sociated with allergic or bacterial conjunctivitis (12).
2. Follicles: Avascular, white-gray nodules typically located in

the tarsal and fornix conjunctiva.
• Immature lymphocytes and macrophages concentrate in

the center of the nodule.
• Follicles are associated with chlamydia, toxic, or viral
infections.

432 10A. CONJUNCTIVA
4. G iant P a p illa ry C on ju n ctiv itis (G P C )
• Epidemiology/History: Can result from contact lens wear (95%), exposed

sutures, glaucoma filtering blebs, scleral buckles, and ocular prosthet
ics (33) (58). Although GPC can occur with any type of contact lens, it
is most commonly associated with extended-wear soft contact lenses.
— Obtain a detailed contact lens history (replacement schedule, clean

ing system, recent switch to silicone hydrogel lens?). Risk fac
tors for hydrogel lenses include extended wear, high water-ionic
lenses, higher modulus of elasticity, and poor replacement compli
ance (13) (108).
— The average length of time with soft lenses before development of
GPC is 8 months (58), although it may develop as early as 3 weeks
depending on the type of lens, wearing schedule, etc.
• Pathophysiology/Diagnosis: Non-infectious inflammatory disorder asso

ciated with m echanical trau m a and an im m une response to con
tact lens surface deposits (most commonly protein) or environmental fac
tors (52) (58).
• Symptoms: Itching, scant mucous discharge (early), ropy mucous dis

charge (late), decreased contact lens wearing time, photophobia. Symp
toms are often more severe after removing contact lenses.
• Signs: Mild to severe papillae of the upper (tarsal) conjunctiva and eyelid,
ptosis, and mucous throughout the eye and/or on the contact lens.
— GPC is characterized by papillae > 0.3 mm in diameter. Giant

papillae (defined as > 1.0 mm) form when neighboring papillae
break down septae and coalesce together after prolonged inflam
mation (102).
A d d itio n a l C on ta ct L en s-R elated D isorders
1. S olu tion H y p erse n sitiv ity /T o x icity : Patients may have very sub
tle complaints and no signs to very obvious signs and symptoms that
most commonly occur after a recent switch to a new lens cleaning sys
tem. Severe reactions are most often in response to solutions containing
chlorhexidine or thimerosal, although newer solutions may also cause re
actions.•
• Symptoms: Redness and burning upon lens insertion after clean

ing, solution change weeks to months prior with chronic redness
and discomfort, reduced contact lens wear time due to dryness or
discomfort.
• Signs: Conjunctival injection and diffuse SPK.

If a previously asymptomatic patient complains of increased dry

ness throughout the day, and no signs or symptoms of dryness are
present without the contact lens, remember to ask about a recent
change in disinfecting solution (13).
2. C orn ea l neovascularization: Results from chronic hypoxia; watch for

superior pannus. According to the FDA, corneal neovascularization larger
than 1.5 mm is abnormal and of concern; stromal scarring and hemor
rhage are uncommon but can occur.
3. C orn ea l warpage: Alteration in corneal shape due to the contact lens

material that is classically seen in long-term PMMA wearers or GP wear
ers with poorly fitting lenses; in rare cases, it can be seen with soft contact
lens wear (typically low Dk, extended wear, toric lenses).
• Initially, patients often report that vision is clear in contact lenses

but blurry in glasses (33). They also note ghost images and diplopia.
• Irregular astigmatism, which can mimic keratoconus, is evident on
topography (35). A high riding lens classically causes inferior steep
ening of the cornea over time (107).
Corneal warpage can be distinguished from kerato conus in that

corneal warpage will not have other corneal findings consistent with
keratoconus and will improve with discontinuing/refitting of con
tact lenses.
4. Su p erior lim bic k e ra tocon ju n ctiv itis (S L K ): Due to a contact lens

hypersensitivity reaction (especially thimerosal) or a poor contact lens
fit.
• Signs include superior bulbar and upper tarsal conjunctival injec

tion. Papillary reaction and corneal filaments are uncommon, unlike
SLK in thyroid disease.
5. C on ta ct lens dep osits: Common in contact lens abusers who are not
replacing lenses on schedule or who are not cleaning their lenses properly.•
• On GP lenses, if deposits are diffuse, consider a stronger cleaner or

adding an enzyme cleaner weekly.

• If deposits are localized to the back surface of the lens, the patient
may be using the thumb and pointer finger to clean instead of the
finger and palm of hand. If this is the case, care and handling can
be re-instructed.
Deposits on GP lenses will appear as plaques, while deposits on

hydrogel lenses will appear as je lly bum ps.
6. T igh t-len s sy n d rom e (T L S ): Contact lens that does not move with
blinking and appears “stuck-on” to the cornea.
• TLS is more common in high myopes (> —8.00D), hyperopes and

aphakes. It is also more common in patients fitted in lenses that are
too steep or have an OAD that is < 13.0 mm or > 15.0 mm (89).
• Symptoms: Redness that worsens after the lens is removed, hazy
vision, halos, dryness.
• Signs: Mild to severe corneal edema or corneal blebs, as well as in
jection or indentation around the limbus and distorted keratometry
mires that clear with blinking. An anterior chamber reaction may
develop and a corneal abrasion may occur when the lens is removed.
7. 3 and 9 o ’ clo ck Staining: The most common complication of GP

contact lens wear. Classically due to low-riding GP lenses that leave
portions of the cornea uncovered by the lens, causing subsequent blinks
to no longer adequately spread the tears across this area. Chronic 3 and 9
o ’clock staining can lead to corneal vascularization, pseudopterygia and
dellen formation (13). Patients may be asymptomatic or complain of
horizontal redness.
Remember, a classic complication of lenses that ride too high is

corneal warpage. A classic complication of lenses that ride to low
is 3 and 9 o ’clock staining.
8. Su p erior E pithelial A rcu ate Lesion (S E A L ): Typically occurs with

extended wear hydrogel lenses that are too tight, but can also be caused
by loose lenses that chafe* below the upper lid. SEAL may also be asso
ciated with lenses with poor wettability (13).

• An estimated 30% of cases are asymptomatic. Symptoms include

foreign body sensation, irritation, and corneal underlying infiltrates
(40%) (28).
9. D im p le V eiling: Occurs when small bubbles get trapped under a con

tact lens (typically an RGP). The lens then pushes the bubbles into the
cornea, creating a divot for fluorescein to pool. Dimple veiling is NOT
staining of the cornea, the dye has just collected in the corneal depres
sion. This can be confirmed by placing a drop of saline in the eye - if
the fluorescein is still taken up by the cornea after the rinse, it is stained
(meaning there is an epithelial break). If the pooling is gone after the
rinse, there is no epithelial break and pooling was the cause of the finding.
K era to co n ju n ctiv itis implies simultaneous inflammation o f the

cornea and conjunctiva. Bacterial infections, viral infections, her
pes simplex, herpes zoster, fungal infections, atopy, allergic, ver
nal, toxic reactions, and factitious disease may cause simultaneous
inflammation of the conjunctiva and cornea, leading to the diag
nosis of keratoconjunctivitis rather than keratitis or conjunctivitis
alone (2) (58).
Uiictiviiis;/h5 ;
1. C h lam ydial - A d u lt In clu sion C on ju n ctiv itis
• Epidemiology/History: Rare. Occurs predominantly in sexually active

young adults; chlamydia is the most common sexually transmitted disease
in the United States. Ask about a history of multiple sexual partners and
pain during urination.
• Pathophysiology/Diagnosis: Adult inclusion conjunctivitis is the ocular

manifestation of urogenital disease and is caused by chlamydia serotypes
D -K (58). It is most commonly spread via direct inoculation (genital-
hand-eye, genital-eye), although there have been reported cases of trans
mission through contaminated swimming pool water or shared cosmet
ics (24); ocular manifestations begin approximately 5-14 days after inoc
ulation (58). 54% of men and 74% of women will have an active genital
infection.•
• Symptoms: A cu te follicular con ju n ctiv itis that becomes chronic

(this prompts patients to seek medical attention); most infections be
gin unilaterally, but bilateral involvement often develops. The infection
can persist for 3-12 months if not treated (52).

• Signs: F ollicles (limbal or palpebral) that are most concentrated in

the in ferior palp ebral con ju n ctiva and fornices, preauricular lym-
phadenopathy, scant mucopurulent discharge, and matting of the lids.
Corneal involvement occurs in 30-85% of patients and includes punctate
keratitis, superior pannus, and subepithelial infiltrates (more peripheral
in location compared to EI<C) (24).
O ph th alm ia n eon a toru m is acute conjunctivitis in newborns

from any source (e.g. HSV, gonorrhea, chlamydia) (58); the leading
cause in the United States is chlam ydia.
2. C hlam ydial - T rach om a C on ju n ctivitis
• Epidemiology/History: Most prevalent between the ages of 1 and 5 (58),

Trachoma is the leading cause of preventable blindness worldwide (3rd
most common cause o f blindness worldwide after cataract and glaucoma).
The primary risk factor is living in a community with poor hygiene (78).
Most infections spread directly from eye to eye, but fomites, flies, and
shared cosmetics are other routes of transmission (58).•
• Pathophysiology/Diagnosis: Caused by chlamydia serotypes A -C . Pre

sentation begins in early childhood with a follicular and papillary conjunc
tivitis of the superior tarsal conjunctiva that ultimately spreads through
out the entire conjunctiva. It is almost always bilateral (58)
• Signs/Symptoms:
— Early: F ollicular con ju n ctivitis predominantly on the superior

tarsal conjunctiva, mucopurulent discharge, lymphadenopathy, and
m ild su p erior pannus.
- Late: A rlt Lines (white scarring of the superior tarsal conjunc
tiva) and H e r b e r t’ s pits (depression on the limbal conjunctiva
after resolution of limbal follicles); progressive tarsal conjunctival
scarring can lead to distortion of the eyelids and subsequent corneal
ulceration from trichiasis.
The etiology for trachoma and inclusion conjunctivitis differs only

by the chlamydia serotype involved. Remember, trA-Chom a is
caused by serotypes A -C , inclusion conjunctivitis is caused by
serotypes D -K (58).
Copyright 2014. by KMI< Educational Services, LLC

3. S u p erior L im bic K e ra to co n ju n ctiv itis (S L K )
* Epidemiology/History: Uncommon condition that most often affects fe

males (3:1) with a mean age of diagnosis of 50 (58). History likely to
include recurrent episodes.
• Pathophysiology/Diagnosis: Chronic inflammatory reaction most com

monly associated with keratoconjunctivitis sicca (25%), thyroid disease
(20 — 50%), and contact lens wear. The exact etiology is unknown. SLK
is characterized by flare-ups and remissions that eventually cease over
time (52) (58).
1. K era to co n ju n ctiv itis sicca - Drying effect between the upper eye
lid and bulbar conjunctiva enhances friction and creates an environ
ment where natural turnover and replacement of mature superior
bulbar conjunctival cells does not occur.
2. T h y roid disease - May result from continual friction of the superior
palpebral conjunctiva against the superior bulbar conjunctiva as a
result of tight apposition from exophthalmos.
3. C on ta ct lens w earers and those with tight upper eyelids also have
increased friction and thus have an increased risk of SLK.
* Symptoms: Redness, foreign body sensation, frequent blinking, no dis

charge. Symptoms are often worse than the signs; in these cases, instil
lation of a vital dye (e.g. sodium fluorescein dye, rose bengal, lissamine
green) can reveal prominent staining and pathology that is otherwise
difficult to visualize on clinical examination.
• Signs: Characterized by thickened, red, su p erior bulbar conjunctiva that

is most prominent at the limbus and is often bilateral, with adjacent SPK
and filamentary keratitis. The upper tarsal conjunctiva can have a velvety
appearance as a result of diffuse papillary hypertrophy.
4, P h lycten u la r K e ra to co n ju n ctiv itis
• Epidemiology/History: Most common in teenage years with a higher oc

currence in females (58). Ask if the patient has had similar eye infections
in the past and whether he/she has a history of TB.
• Pathophysiology/Diagnosis: Most commonly a result of a T y p e -4 hy

persen sitivity reaction to staphylococcus (blepharitis is the most com
mon culprit), tuberculoprotein, and acne rosacea.
• Symptoms: Tearing, foreign body sensation, and itching associated with

conjunctival and corneal phlyctenules; significant photophobia is common
with corneal phlyctenules (58).•
• Signs: Phlyctenules can be located on the conjunctiva or cornea (58):

1. C on ju n ctiva l phlyctenules most commonly occur at the limbus

and classically appear as pink, fleshy nodules with conjunctival in
jection.
2. C orn eal ph lycten u les most commonly occur near the limbus as a
small, white (lymphocytic) nodule with adjacent conjunctival injec
tion.
Recall that the P P D test for TB should be read within 48-72 hours
of injection.
5. L igneous C o n ju n ctiv itis
• Epidemiology/History: Rare. Starts during childhood.
• Pathophysiology/Diagnosis: Ocular manifestation of a systemic disorder;

is associated with systemic plasm inogen deficiency (84). May affect
mucous membranes throughout the body (e.g. mouth, ear, vagina).
• Signs: Thick, white, “woody” membranous plaque of the superior tarsal

conjunctiva.
• Symptoms: Chronic tearing, foreign body sensation, photophobia; con

stant discomfort and cosmetic concerns are typical in advanced disease (58)
Recall from the histology chapter that plasmin (derived from plas
m in ogen ) catalyzes the breakdown of fibrin, which stops unwanted
clot formation within healthy vessels throughout the body (84).
6. P a rin a u d’s O cu loglan du lar S yndrom e
• Epidemiology/History: Rare. Ask about contact exposure to cats, dogs,

rabbits, squirrels, and ticks (58).
• Pathophysiology/Diagnosis: Common causes include the following (58):
— C a t-scratch fever (most common cause) - caused by Bartonella

henselae, which can be transmitted by a cat scratch to the eye or
through cat flea bites to the eye.
— T ularem ia - typically transmitted via ticks, rabbits, and squirrels.

- T u bercu losis and syphilis are other noteworthy causes.
• Symptoms: Red eye, foreign body sensation, mucopurulent discharge.
• Signs: U nilateral, granulom atous, follicular, palpebral conjunctivitis,

visibly swollen preauricular / subm andibular lym p h a d en op a th y (33).
May also have a fever and rash.
7. P hthiriasis p a lp eb ra ru m (p ed icu losis ciliaris)
• Pathophysiology/Diagnosis: Results from Phthirus pubis, known as the

crab louse, found in the hair follicles of the genital region. Infection of the
eyelashes, eyebrows, and facial hair may occur through direct contact with
infected individuals or infected clothing or linen (2). May be unilateral
or bilateral.
- Differs from demodicosis, a common parasitic mite hair follicle in

fection associated with blepharitis that classically causes sleeving of
the base of the eyelash (35).
• Symptoms: Range from mild itching of the eyelids to marked inflamma

tion with resultant burning, itching, tearing, and blurred vision.
• Signs: Transparent lice and white nits (egg sacs) attached to the eye
lashes, blood-tinged debris on lids and lashes, mild to severe chronic
follicular .conjunctivitis, and preauricular lymphadenopathy (2) (25).
8. S u b con ju n ctiv a l h em orrh age
• Blood underneath the conjunctiva that typically results from valsalva

(e.g. coughing, straining), medications (e.g. aspirin, Coumadin), hyper
tension, or a blood clotting disorder (e.g. sickle cell).
• Remember to consider ordering CBC, P T /P T T , and sickledex for idio

pathic and recurrent cases, especially in patients of African or Mediter
ranean descent.
|Conjunctiyal Degenerations ' •. . : ..

P te ry g iu m /P in g u e cu lu m
• Epidemiology/History: Associated with environmental exposure and UV

radiation; common in individuals who work outdoors.•
• Pathophysiology/Diagnosis: U ltraviolet light ex p osu re (leading cause)

and chronic dryness are believed to cause degeneration of collagen fibrils
within the conjunctival stroma (52) (102).

440 10.6. EPISCLERA/SCLERA/ANTERIOR AND POSTERIOR UVEA
• Symptoms: Range from asymptomatic to irritation, redness, and de

creased vision (depending on the location of the pterygium).
• Signs: Both conditions are typically located at 3 and 9 o ’clock.
- P in gu ecu lu m - yellow-white (typically raised) deposit adjacent to

the limbus (but not on the cornea).
— P te ry g iu m - triangular fibrovascular growth of bulbar conjunctiva
that extends onto the cornea, destroying B ow m a n ’s m em brane
and often leading to ATR astigmatism (35). S tock er’ s line (iron
deposit) may be present at the anterior (leading) edge of the ptery
gium.
- SECTION 10.6 ----------------------------------------------------------------------------------------------—
E p isclera /S clera /A n te rio r and P o sterio r U vea
E piscleritis -V'. ;
• Epidemiology /History: Most common in young adults (peak incidence
in 2nd-4th decades). History of frequent recurrences (60-67%) is com
mon (35) (58).
«. Pathophysiology/Diagnosis: Benign, self-limiting inflammation of the

episclera; often idiopathic, but can be associated with systemic dis
ease (up to 26 — 36% of cases), including the following (non-exhaustive
list) (58):
- Collagen vascular/inflammatory diseases - rheumatoid arthri

tis, lupus, ulcerative colitis, Crohn’s disease, reactive arthritis, anky
losing spondylitis, psoriatic arthritis.
- Spirochetes - syphilis, Lyme disease.
— Viruses - herpes zoster, herpes simplex, mumps.
— Metabolic diseases - gout.
— Vasculitic diseases - temporal arteritis, Wegner’s granulomatosis,
Behcet’s disease, polyarteritis nodosa.
- Dermatological diseases - acne rosacea.
• Symptoms: Acute unilateral (66%) red eye, occasional mild pain (35).
• Signs: Injection that is typically sectoral (70%) (35). The condition can
be simple (80%) or nodular (20%); the nodule can be moved slightly with
a cotton tip applicator (unlike in scleritis) (35).

:-^r- „ V •.• ■: •
• Epidemiology/History: Female predilection (peak incidence in the 4th-

6th decades). Scleritis is much less common than episcleritis. Anterior
scleritis occurs in 98% of cases (2% of cases are posterior) (35). An
terior scleritis can be divided into n on -n ecrotizin g and necrotizin g
scleritis (78):
1. N o n -n ecrotizin g Scleritis (85%)

— D iffuse (60%): Most common type o f anterior scleritis and the
most benign form of the disease; associated with the least severe
systemic conditions (33). Characterized by diffuse hyperemia.
— N od u la r (25%): Characterized by deep, focal, painful, injected
immobile nodule.
2. N ecrotizin g Scleritis (15%)
— N ecrotizin g w ith inflam m ation (5% ): The worst form of
scleritis, as 33% of patients may die within a few years as a
result of severe au toim m une disease. 40-82% of patients will
lose vision (34) (84); 60% have ocular or systemic complications,
including anterior uveitis, sclerosing keratitis, peripheral corneal
melt, scleral thinning, cataracts, and glaucoma (34).
— N ecrotizin g w ith ou t inflam m ation (S clerom alacia P er-
forans) (10%): Typically a result of ch ron ic rh eu m atoid
arthritis. The condition is characterized by almost complete
lack of symptoms and minimal injection (33); asymptomatic,
large, gray-blue patches of scleral thinning (due to exposure of
the underlying uvea) may be seen (34).
• Pathophysiology/Diagnosis: Granulomatous inflammation of the sclera

in which 50% of cases are associated with an underlying systemic dis
ease (52) (84); 30% of the cases that result from systemic disease (15—18%
total) are caused by collagen vascular disease; rh eu m atoid arthritis is
the most common, followed by Wegener’s granulomatosis (35).
• Symptoms: Severe, b o rin g ocu la r pain (hallmark for scleritis) that

can radiate to the ipsilateral forehead, brow, or jaw and awaken the
patient during the night. Additional symptoms include a gradual onset
of redness and a decrease in vision (except for scleromalacia perforans!).•
• Signs: Sectoral or diffuse inflammation of the large, deep vessels that

cannot be moved with a cotton swab. Edematous or th in sclera with
a classic bluish hue under natural light. Signs are frequently bilateral
(compared to unilateral signs in episcleritis) (84).

442 10.6. EPISCLERA/SCLERA/ANTERIOR AND POSTERIOR UVEA
Remember, sclerom alacia perforan s = scleritis in a patient with

rheumatoid arthritis.
H yaline plaques are benign, oval-shaped areas of scleral thin

ning that occur with age and allow underlying visibility of the
uvea.
Episcleritis must be differentiated from the much more serious scleritis. Scleritis
can be distinguished from episcleritis by the following (35) (58) (105):
• Scleritis is typically gradual in onset, unlike the acute nature of episcleri

tis, but results in more significant ocu lar pain and more severe ocular
complications.
• Scleritis often has a characteristic bluish-hue under natural light (due

to scleral thinning), as compared to the red appearance of episcleritis.
• 2.5% ph en ylephrine will result in conjunctival blanching in a patient

with episcleritis. If the redness persists, 10% phenylephrine may be used
and will blanch the superficial episcleral vessels (i.e. episcleritis will ap
pear less red), but NOT the deeper episcleral vessels (i.e. scleritis will
remain injected) (58).
• Scleritis findings are frequently bilateral and diffuse injection is more

common; episcleritis signs are typically unilateral and sectoral injection
is more common (84).
• Scleritis is much less common than episcleritis and is more commonly

associated with an underlying systemic disorder.
Differentials for severe ocu la r pain include scleritis, uveitis, acute

angle-closure glaucoma, and corneal pathology (e.g. abrasions, ero
sions, ulcers).
[A-xenfeld’s N erve Eoop . ■’-j

A congenital anomaly characterized by a focal, pigmented, elevated area where
the posterior ciliary nerve loops are visible in the sclera; can be painful.

• Epidemiology/History: Affects 15/100,000 per year; there are 45,000 new

cases per year in the United States (78). Anterior uveitis frequently
occurs in you n g adults (peak incidence in the 2nd-4th decades); it rarely
occurs in individuals older than 70 (common causes in this age group
include toxoplasmosis and herpes zoster) (78).
• Pathophysiology/Diagnosis; Uveitis occurs secondary to a breakdown in

the blood aqueous barrier. 50% of patients with acute anterior uveitis are
HLA-B27 positive (70% if the condition recurs) (58). 50% of new onset
acute anterior uveitis cases have an associated sp on d y loa rth rop a th y;
80% of these patients have ankylosing spondylitis (58).
— Spondyloarthropathy conditions include (but are not limited to) in

flammatory bowel disease (Crohn’s disease, ulcerative colitis), reac
tive arthritis (formerly Reiter’s syndrome), ankylosing spondylitis,
and psoriatic arthritis.
Remember, associate HLA-B27 positive with C R A P : Crohn’s dis

ease, Reactive arthritis, Ankylosing spondylitis, Psoriatic arthri
tis.
• Terminology: Can be acute, chronic, or recurrent, and classified by cell

type (granulomatous vs. non-granulomatous), location (anterior, inter
mediate, posterior, panuveitis), and laterality (unilateral, bilateral, or
alternating).
— 75% of uveitis cases are anterior (iritis, iridocyclitis), 8% are in

termediate (pars planitis), and 17% of cases are. posterior or panu
veitis (78).
A cu te anterior uveitis is defined as a self-limited disease of

less than 3 m onths duration; it may be characterized by recur
rent attacks. C h ron ic anterior uveitis persists for more than 3
months; it may have periods of exacerbations, but it never fully
resolves (58).

444 10.6. EPISCLEllA/SCLERAfANTERIOR AND POSTERIOR UVEA
• Symptoms: Pain, redness, photophobia, lacrimation, and mildly decreased

vision (especially with cystoid macular edema). Patients with chronic
anterior uveitis may be asymptomatic or report blurred vision or a dull
ache.
P ain with acute anterior uveitis is a result of congestion and irri

tation of the anterior ciliary nerves (58).
* Signs: Diagnosed based on the presence or absence of white blood cells

(WBCs) in the anterior chamber (or elsewhere for other locations of
uveitis).
— Main threats to vision include posterior- synechiae (PS), p erip h

eral anterior synechiae (PAS), cy sto id m acular edem a, and
cataract form ation (most commonly PSC and associated with
chronic cases).
- Other prominent anterior segment signs include flare, hypopyon,
circumlimbal injection of the conjunctival vessels, decreased IOP in
the involved eye (in early stages), and keratic precipitates (KPs) on
the endothelium.
* Note that although IOP is decreased during the early stages of
uveitis due to ciliary body inflammation, IOP may also be ele
vated in the later stages of uveitis from a variety of factors (e.g.
the eye getting better, trabeculitis, P S (leading to acute an
gle closure), P A S (leading to chronic angle closure), significant
inflammation, topical steroid treatment, chronic TM damage).
Cyclitic membranes may be present in chronic uveitis; they are

fibrovascular membranes that extend from the ciliary body into
the posterior chamber and may involve the lens.
— Fine KPs are characteristic of a non-granulomatous etiology.

- A granulomatous etiology, in comparison to non-granulomatous, is
more commonly infectious (e.g. tuberculosis, syphilis) and chronic in
course with an increased predilection for the posterior chamber (78).
“Mutton-fat” KPs and iris stromal nodules (e.g. Koeppe, Busacca)
is highly suggestive of a granulomatous etiology (58).

* M u tton -fa t K P s: Collections of macrophages with a greasy

appearance; typically located in the middle and lower cornea.
* K o e p p e n odules: Located on the pupillary margin; associated
with granulomatous AND non-granulomatous uveitis.
* B u sacca n odules: Located within any part of the iris stroma
except the pupillary margin; pathognomonic for a granuloma
tous etiology (58).
KPs are the most common corneal findings in anterior uveitis (58).
Stellate K P s are observed in Fuchs’ heterochromic iritis (most
commonly) and herpetic uveitis.
We now summarize the classic presentation of conditions commonly associated

with anterior uveitis (note that patients will not always appear with the charac
teristics listed). Please see systemic disease for further details on the conditions.
A cu te , n on -gra nu lom atou s, anterior uveitis may be associated with the
following conditions (non-exhaustive list):
• In flam m atory bow el disease: Usually bilateral with a posterior uveitis

component (35). Characterized by chronic intermittent diarrhea with
alternating episodes of constipation. Uveitis is rare in Crohn’s disease
(2.4%), but is more common with ulcerative colitis (5 — 10%) (35).
• R e a ctiv e arthritis: Young males with urethritis, polyarthritis, and con

junctivitis (with iritis).
• A n k ylosin g sp on dylitis: More commonly affects males (3:1) in the

3rd decade. Characterized by lower back pain (although patients can be
asymptomatic); symptoms improve with exercise (58).
• P soria tic arthritis: Characterized by asymmetric, peripheral, small

joint pain and psoriatic lesions on the knees, elbows, and scalp.
• B e h c e t’s disease: Most common in young adults of Asian and Middle

Eastern descent. Characterized by acute, recurrent hypopyon iritis and
mouth and genital ulcers. May also be associated with retinal vasculitis,
cataracts, and glaucoma.
• L ym e disease: Patients may have a history of tick bites, a skin rash,

and/or arthritis (33).•
• G la u co m a to cy clitic Crisis (aka Posner-Schlossman syndrome): Mild

iritis with recurrent, self-limiting episodes of elevated IOP (30-40s) sec
ondary to trabeculitis, fine KPs, and an open angle on gonioscopy.

446 10.6. EPISCLER.A/SGLERA/ANTERIOR AND POSTERIOR UVEA
C h ron ic, gran u lom atous, anterior uveitis may be associated with the
following conditions (non-exhaustive list):
• S arcoidosis: More common in females and African Americans. Uveitis is

typically bilateral and may be posterior or panuveitis. Patients typically
have an abnormal chest radiograph and increased angiotensin converting
enzyme (ACE) levels.
• T u bercu losis: Positive PPD test, abnormal chest x-ray, night sweats.
May have posterior or panuveitis.
• H erpes S im p le x /H e rp e s Zoster: Associated with increased 10P in

the involved eye. May have stellate KPs, corneal edema, and/ or epithelial
defects. Zoster will present with vesicles along the affected dermatome.
• Syphilis: May have an associated interstitial keratitis. Characterized by

a maculopapular rash (on the palms and/or soles), a positive VDRL or
RPR, and a positive FTA-ABS or MHA-TP.
- Interstitial keratitis is stromal inflammation WITHOUT primary

involvement of the epithelium or endothelium (52) (84).
* IK is characterized by acute stromal inflammatory edema and
neovascularization. Progression results in diffuse stromal neo
vascularization that often spares the line of sight.
* During the late stages of IK, stromal vessels may partially clear,
leading to ghost vessels, corneal scarring, and irregular astigma
tism (58).
— The most common causes of IK are congenital syphilis (90%),
tuberculosis, and herpes simplex (35).
* Stromal keratitis is the most common sign of late congenital
syphilis (58).
* A cq u ired syphilis rarely results in keratitis. If present, stro
mal keratitis in these patients is similar to congenital syphilis,
but is unilateral and less severe (58).
C on gen ita l Syphilis Triad = H u tch in son ’ s teeth (small,

widely spaced teeth), deafness, and interstitial keratitis (33).
Additional signs of congenital syphilis include saddle-nose defor
mity and frontal bossing (prominent forehead) (33).
C h ron ic, n on -granu lom atou s, anterior uveitis may be associated with
the following conditions (non-exhaustive list):

• Juvenile idiopath ic arthritis (formerly JR A): Most common known

cause of uveitis in children. Classic presentation is a bilateral uveitis in
young girls. Patients typically have a negative rheumatoid factor (RF)
and positive antinuclear antibody (ANA).
• Fuchs’ h e teroch rom ic irid ocy clitis: More common in patients with
blue eyes. Characterized by a unilateral (90%) mild uveitis with fine, stel
late KPs, angle neovascularization, and iris heterochromia. Associated
with glaucoma (15%) and cataracts (70%); patients are often asymp
tomatic (35).
Recall that rifabutin, system ic sulfonam ides, and cid ofov ir

can cause anterior uveitis (12).
Pars planitis is a chronic intermediate uveitis characterized by inflammation

over the pars plana (known as “snowbanking”) and peripheral retina; it is NOT
associated with systemic conditions.
P o ste rio r U veitis ■ ■"£ V ; ■;

• Results from a breakdown in the blood aqueous barrier that results in
WBCs within the vitreous. Patients may complain of floaters and/or
decreased vision,
* Ask about rashes, tick bites, risk factors for AIDS, breathing difficulties,
and recent travel to the Ohio-Mississippi River Valley.
We now summarize the classic presentations of conditions commonly associated

with posterior uveitis. Please see systemic disease for further details. P o ste
rior uveitis may be associated with the following conditions (non-exhaustive
list):
T oxoplasm osis
• Epidemiology/History: Toxoplasmosis is the most common cause of pos

terior uveitis in the United States (78).•
• Pathophysiology/Diagnosis: P arasitic in fection caused by Toxoplasma

gondii, an obligate intracellular intestinal parasite. May be congenital or
acquired:

448 10.6. EPLSCLERA/SCLERA/ANTERIOR AND POSTERIOR. UVEA
1. C on gen ital: Occurs through transplacental transmission. This is

by far the most common form of toxoplasmosis, accounting for 90%
of cases (35) (78).
— Toxoplasmosis is transferred to the fetus in 40% of cases when
the mother contracts the acute form during pregnancy (78). If
the mother is affected PRIOR to pregnancy, the baby will not
become infected (52).
— There is a wide spectrum of clinical presentations for congenital
toxoplasmosis. In 10% of cases, severe systemic involvement
results in the triad of convulsions, cerebral calcifications, and
chorioretinitis (3). Most cases are mild and only result in small,
insignificant chorioretinal scars.
2. A cq u ired : Results from inhalation of the parasite in cat feces
and/or through eating u n dercook ed m eat (78).
• Signs/Symptoms: Recurrence of an old, stable, congenital ocular toxo

plasmosis lesion is the most common cause of infectious retinitis (52).
Acquired and reactivated congenital lesions present in a similar fashion:
- Young healthy patient with recent onset of unilateral redness, photo

phobia, floaters, uveitis, vitritis, and decreased vision. The average
age of onset for these recurrences is 25 (ranges from 10-35) (52).
- Characterized by a focal, fluffy, yellow-white retinal lesion adjacent
to an old inactive scar with an overlying vitritis (35) (52).
- The chorioretinal lesion is often difficult to view clearly due to the
dense overlying vitritis; viewing the lesion through this haziness is
often referred to as “ headlights in the fo g .”
Remember, toxoplasmosis is the most common cause of posterior

uveitis!
H istoplasm osis causes choroiditis that DOES NOT lead to pos

terior uveitis. The condition results in multifocal “punched-out”
yellow-white lesions in the periphery with associated peripapillary
atrophy and maculopathy (including choroidal neovascularization);
common in the Ohio-Mississippi River Valley.
Less common causes of posterior uveitis include:

• Sarcoidosis: Granulomatous panuveitis associated with the following

findings (35):
— Retinal vitritis: Diffuse vitritis or white, fluffy opacities in the

inferior vitreous (“ cotton-ball opacities”),
— Retinal vasculitis: Sheathing around retinal veins and yellow-
white exudates caused by periphlebitis (“candle-wax droppings”) .
• Syphilis: Secondary syphilis may result in acute multifocal chorioretini

tis with vitritis or panuveitis (35).
• Cytomegalovirus: The most common ocular infection and the leading

cause of blindness in AIDS (44). Results in white patches of necrotic
retina with hemorrhagic retinitis and vascular sheathing. Most likely to
occur in patients with C D 4 counts less than 50. Must be differen
tiated from toxoplasmosis and progressive outer retinal necrosis
(P O R N ):
— CMV has more intravitreal hemorrhage and less vitritis than toxo
plasmosis.
— PORN has minimal amounts of vitritis (similar to CMV) and hem
orrhage (less than CMV) (78).
Iris C olobom a : . b£ 5 ^ ' ; ■ - . '(CC

• Pathophysiology/Diagnosis: Localized defect or notch in the iris tissue
resulting from incomplete closure of the embryonic fissure of the
optic vesicle during gestation (40).
• Signs: Typically located in the inferior nasal quadrant, corresponding

to the location of the embryonic fissure within the optic vesicle.
— Complete iris coloboma - full thickness defect that may extend from
the pupillary margin to the peripheral cornea, resulting in a “key
hole” pupil, or involve only the pupillary margin, causing an oval
shaped pupil,
— Incomplete coloboma - partial thickness defect that is visible as an
iris transillumination defect on retroillumination.
Iris colobomas are often associated with other ocular colobomata

including ciliary body, zonular, choroidal, retinal, or optic nerve
coloboma.

450 10. 7. CORNEA/REFRA CTIVE S UR GER Y
pDi^ y^W-S-M
• Pathophysiology/Diagnosis: Malignant tumor that arises from abnormal
proliferation of melanocytes within the iris stromal tissue (2). Most iris
malignancies are thought to arise from iris nevi (2% of cases within 5
years) (96).
• Signs: Iris melanomas may be pigmented or amelanotic and are located

within the iris stromal tissue in the inferior quadrant in 80% of cases (54).
Irregular “feathery” margins and a diameter greater than 3 mm are classic
for the condition (96).
Any iris lesion found in younger patients (< 40 years of age) with
high risk characteristics, including associated hyphema, ectropian
uvea, angle involvement, inferior iris location, and diffuse feathery
margins, should be evaluated for potential iris melanoma (96).
— SECTION 10.7 ------------------------------------------------------------------
C o rn ea/R efractiv e Surgery
M iscellaneous K e ra to p a th ie s !
D ellen
• An area of the cornea that wets poorly, leading to stromal dehydration

and corneal thinning, with resulting p o o lin g o f fluorescein within the
affected area; seen adjacent to areas of elevation such as pterygia, filtering
blebs, tumors, and poor fitting RGP lenses,
• Patients may be asymptomatic or complain of an occasional foreign body

sensation and other dry eye symptoms.
E x p osu re K e ra top a th y
• Pathophysiology/Diagnosis: Abnormal or in com plete lid closure due

to Bell’s palsy (idiopathic 7th nerve palsy), eyelid surgery (causing ec
tropion), cerebrovascular accident, aneurysm, multiple sclerosis, herpes
simplex, herpes zoster, thyroid eye disease, nocturnal lagophthalmos, and
floppy eyelid syndrome.
• Symptoms: Redness, foreign body sensation, and burning; symptoms are

typically worse in the morning.

• Signs: Vary from mild SPK (commonly located in the inferior 1/3 or
interpalpebral region of the cornea) to corneal ulceration. Decreased
corneal sensitivity is common.
F ila m en tary K era top a th y
• Epidemiology/History: Chronic symptoms of irritation and dryness are

common. Patient often reports a history of multiple episodes.
• Pathophysiology/Diagnosis: Caused by chronic inflammation of the cornea

and/or any disorder that disrupts the ocular surface:
- K era to co n ju n ctiv itis sicca (most common cause), SLK, corneal

abrasions, erosions, penetrating keratoplasty, contact lens overwear,
and neurotrophic keratopathy (58).
• Symptoms: Mild to severe foreign body sensation with photophobia,

epiphora, blurred vision (depending on location), and blepharospasm (58).
• Signs: Filaments composed of degenerated epith elial cells and m u

cou s that remain attached to the epithelial surface. Range in size from
0.5 to 10 mm and may appear short, long, or stringy. Filaments will stain
with fluorescein (58).
Superficial P u n cta te K eratitis (S P K )
• Pathophysiology/Diagnosis: Non-specific inflammation of the corneal ep

ithelium associated with contact lens wear, corneal infections, dry eye
syndrome (interpalpebral SPK), blepharitis, corneal exposure secondary
to lid malposition (e.g. CN VII palsy, ectropion, thyroid eye disease),
chemical burns, allergic response to topical medications (e.g. BAK,
aminoglycosides), trichiasis, distichiasis, floppy eyelid syndrome, super
ficial foreign bodies (linear SPK with upper eyelid foreign bodies), ex
posure to intense ultraviolet light, and LASIK (due to decreased corneal
sensation) (33) (88).•
• Signs/Symptoms: Characterized by pinpoint defects in the corneal ep

ithelium that stain with fluorescein. Pinpoint defects may be localized,
scattered, or confluent (severe cases). Patients may be asymptomatic in
mild cases, or may complain of blurred vision, irritation, foreign body
sensation, photophobia, redness, and tearing.
T h y g e s o n ’s Superficial P u n cta te K era top a th y
• Epidemiology/History: Rare. Most common in the 2nd-3rd decade. Pa

tients often have a history of recurrent episodes with similar symptoms.
There is no sex predilection.
Copyright 2014 by KMK Educational Services, LLO

452 10.7. CORNEA/B.EFRACTIVE SURGERY
• Pathophysiology/Diagnosis: Unknown etiology, although may be viral or

autoimmune (35) (58). The condition has no known associations with
other ocular or systemic diseases (58).
• Symptoms: F oreign b o d y sensation, photophobia, tearing, and oc

casional blurred vision (58). Overall the eye is relatively quiet with no
anterior chamber reaction or conjunctival injection. Symptoms are typi
cally chronic and almost always bilateral (but asymmetric).
• Signs: B ilateral (90%), .small, multiple, asymmetric gray-white clusters

of superficial, intraepithelial, raised central corneal lesions (average of
15-20) (34) (58). The condition is characterized by periods of exacerba
tions and remissions without serious sequelae over a period of 10-20 years
before it permanently resolves.
— A cu te attacks (exacerbations) - last 1-2 months (if untreated) be

fore resolving; lesions will stain lightly with fluorescein. Exacera-
tions often recur within 6-8 weeks (58).
— R em ission s - periods of inactive disease in between acute attacks;
lesions do not stain with fluorescein during remission.
N e u ro tro p h ic K era top a th y
• Epidemiology/History: Ask about past surgical procedures, contact lens

wear, systemic diseases, and medications.
• Pathophysiology/Diagnosis: Trigem inal nerve n europathy (C N V I )

that results from damage to sensory nerve supply anywhere from the
trigeminal nucleus to the corneal nerve endings (58). This condition
results in decreased corneal sensitivity and a subsequent decline in
corneal regeneration and wound healing.
- Common causes include h erpes sim plex, herpes zoster, diabetes,

LASIK, contact lens wear, and conditions causing chronic corneal
epithelial injury (e.g. recurrent erosions, corneal dystrophies).
- Tumors (e.g. acoustic neuroma), CVA, and medications (e.g. timo
lol, betaxolol, diclofenac sodium).
- Surgical procedures - ablative procedures for trigeminal neuralgia,
acoustic neuroma surgery, or maxillary fracture repair.
Recall that CN V contains three branches - VI, V2, and V3. The
n asociliary nerve is a branch of V I that innervates the cornea.
Neurotrophic keratopathy results from damage to the nasociliary
nerve.

* Symptoms: Redness, tearing, decreased vision, foreign body sensation,

and swollen eyelids. C orn eal findings are often w orse than w hat
sy m p to m s indicate.
• Signs: D ecreased corn eal sensitivity (hallmark of the condition).

Early signs include SPK with associated perilimbal injection. Late signs
include a sterile inferior oval ulcer (often with an associated iritis) without
signs of significant inflammation (33).
— This condition is characterized by non-healing epithelial defects; if

not treated appropriately, the corneal defects will ulcerate, which
may lead to corneal perforation (58).
C otton -sw a b testing can be used to assess corneal esthesiometry.

Decreased corneal sensitivity causes a decrease in reflex tearing and
a lower blink rate, increasing the risk of corneal ulceration (58).
R e cu rre n t C orn eal E rosion (R C E )
• Pathophysiology/Diagnosis: RCEs result from poor hemidesmosome at

tachments to the underlying basement membrane; they are often a result
of superficial trauma (corneal abrasions), corneal dystrophies (most
commonly E B M D ), and/or age-related thickening or reduplication of
the BM (4).
— The risk for recurrent corneal erosion increases when the previous
abrasion results from an organic etiology (e.g. wood, fingernail).
• Symptoms: Recurrent episodes of acute pain that most often occur in the
m orn in g u p on awakening. Additional symptoms include lacrimation,
photophobia, and blurred vision.
• Signs: A corneal abrasion of varied size that stains with fluorescein.
T h e rm a l/U ltra v io le t K era top a th y
• Epidemiology/History: History of prolonged sun exposure, welding, ski

ing, or using a sunlamp without protective eye wear,•
• Pathophysiology/Diagnosis: Recall that the epithelium and Bowman’s

layer absorb wavelengths below 300 nm; excessive absorption of this short
wavelength light can result in hyperactivation of K + channels, with re
sulting loss of intracellular I<+ and cell death (85).

454 10.7. CORNEA/REFRACTIVE SURGERY
• Symptoms: Ocular pain, photophobia, and blurred vision. Symptoms are

typically worse 6-12 hours after the incident.
• Signs: Confluent SPK within the interpalpebral region of the cornea that
stains with fluorescein.
p r y Eye Disease
The term dry eye is synonymous with keratoconjunctivitis sicca (KCS) (58).
D efin ition o f D ry E ye; According to the International Dry Eye Workshop

(DEWS), dry eye syndrome is a “multifactorial disease of the tears and
ocular surface that results in symptoms of discomfort, visual disturbance,
and tear film instability with potential damage to the ocular surface (61).”
• Epidemiology/History: More common with aging, especially in post

menopausal women. Ask about the following;
- M ed ica tion s
* Drugs with anticholinergic effects: Atropine, scopolamine, tri
cyclic antidepressants (TCAs) (12).
* Antihistamines, chlorpr omazine, thioridazine, isotretinoin, B-
blockers, oral contraceptives, hormone replacement therapy, ADHD
medications, and diuretics (12).
- S ystem ic diseases: Thyroid eye disease and collagen vascular dis
eases (e.g. rheumatoid arthritis, Sjogren’s syndrome, systemic lupus
erythematosus).
- E n viron m en tal factors: Ceiling fans, dusty environment, low hu
midity.
• Symptoms: Burning, dryness, tearing, itching, increased blinking, photo

phobia, contact lens intolerance, and foreign body sensation. Symptoms
are often worse at the end of the day.
• Signs: Thin tear meniscus (<1 mm in height is abnormal), decreased

Schirmer findings, decreased TBUT (less than 10 seconds), decreased
findings on phenol red thread test, con ju n ctival hyperem ia, debris in
the tear film, corneal filaments, signs of underlying conditions (e.g. acne
rosacea, blepharitis), variable corneal and/or conjunctival staining with
fluorescein, and lissam ine green staining (classically inferior and at 3
and 9 o ’clock).
1. Schirm er 1 Testing: Performed without anesthetic; measures the basal

and aqueous tear secretions (18).

• Normal: > 10 mm wetting in 5 minutes

• Borderline: 5-10 mm wetting in 5 minutes
• Abnormal: < 5 mm wetting in 5 minutes
2. S chirm er 2 T esting: Performed with anesthetic; measures only basal

aqueous secretion.
• Normal: > 5 mm wetting in 5 minutes
Remember, there are 3 types o f tearing — reflex, emotional and

basal. Schirmer’s 2 testing allows for isolation of basal tearing.
3. The p h en ol red th read (P R T ) test is an alternative method of as

sessing aqueous tear production that utilizes a cotton thread with pH
sensitive phenol red. A normal result is > 10 mm of wetting (thread
turns red) after 15 seconds (12).
Recall that rose bengal and liss amine green stain d ead an d d ev i
talized con ju n ctival and corneal cells, as well as cells that have
lost their mucous covering (58) (102). Fluorescein pools within ep
ithelial defects; it also collects within the aqueous portion o f the
tears and is useful for evaluating the thickness of the tear meniscus.
The primary mechanisms behind dry eye disease include:
1. Tear hyperos m olarity - Results in an inflammatory cascade that dam

ages the ocular surface and releases inflammatory mediators into the
tears. Aqueous tear-deficient dry eye and evaporative dry eye can cause
tear hyperosmolarity.
T earL ab T ech n ology measures tear osmolarity and may become

a new “gold standard5’ in the diagnosis of dry eye syndrome because
of its high sensitivity and specificity (58).

2. Tear film instability - Can arise secondary to tear hyperosmolarity, or

can be the initiating event in the disease process (e.g. reduced lipid layer
in meibomian gland disease) (61).
A q u eou s tear-deficien t dry eye results in increased tear osmo

larity (hyperosmolarity) - even though water evaporates from the
ocular surface at a normal rate, there is a reduced aqueous layer of
the tears (61).
Dry eye disease, with definitions and classifications listed below from the DEWS
study, can be divided into the following categories: A queous tear-deficient
dry eye and eva porative disease (61).
1. A Q U E O U S T E A R -D E F IC I E N T D R Y E Y E (A D D E )
This is also referred to as tear deficient dry eye or lacrimal tear deficiency and
can be divided into Sjogren’s Syndrome Dry Eye and Non-Sjogren’s Syndrome
Dry Eye (61):
S jog ren ’s S y n d rom e D ry Eye
Consists of primary and secondary divisions:
1. P rim a ry S jog ren ’ s: Aqueous deficient dry eye with symptoms of a dry
mouth, evidence of reduced salivary secretion, a positive focus score on
a minor salivary gland biopsy, and presence of autoantibodies (61). 95%
of patients with primary Sjogren’s syndrome dry eye are females (58).
S jog ren ’ s disease is the 2nd most common autoimmune rheum at-
alogic disease (rheumatoid arthritis is the first) (58).
2. S econ d ary S jog ren ’ s: Primary Sjogren’s AND features of an autoim

mune connective tissue disease (e.g. rheumatoid arthritis, systemic lupus
erythematosis, polyarteritis nodosa, Wegener’s granulomatosis) (61). Ac
counts for 50% of cases of dry eye syndrome (58).

S econ d ary S jog ren ’s includes the classic triad of dry eyes, dry
mouth, AND autoimmune disease (classically rheumatoid arthri
tis).
N o n -S jo g r e n ’s S yn drom e D ry Eye
Aqueous-deficient dry eye secondary to lacrimal gland dysfunction in the ab

sence of Sjogren’s syndrome. Non-Sjogren’s syndrome dry eye is due to the
following causes - prim ary lacrim al gland deficiencies and secon d ary
lacrim al gland deficiencies:
1. P rim a ry lacrim al gland deficiencies
Includes age-related dry eye syn drom e, the most common type of Non-
Sjogren’s Dry Eye (61). With increasing age, pathology within the lacrimal
gland ducts (e.g. stenosis, acinar cell atrophy, ductal fibrosis) can result in
aqueous deficient dry eye. Overall, dry eye syndrome affects 5 — 30% of the
population over 50 years of age (35).
2. S econ d a ry lacrim al gland deficiencies
Includes the following categories for etiology:
• Inflammatory infiltration of the lacrimal gland (e.g. sarcoidosis, lym

phoma, AIDS, Graft vs. host disease).
• Obstruction of the lacrimal gland ducts (e.g. trachoma, pemphigoid,

erythema multiforme, chemical and thermal burns).
• Reflex hyposecretion (e.g. contact lens wear, diabetes, CN VII damage,

systemic drugs, neurotrophic keratitis, infection (e.g. herpes simplex,
herpes zoster), corneal surgery (e.g, LASIK, PRK, RK)).
Approximately 50% of contact lens wearers have dry eye symp

toms (35).
2. E V A P O R A T IV E D R Y E Y E
Results from excessive water loss in the presence of normal lacrimal secretory
function. Can be divided into intrinsic and extrinsic categories:

Intrinsic causes: Excessive evaporation can result from pathology in lid

structure or dynamics.
• Meibomian gland dysfunction: The most common cause of evaporative

dry eye; results in meibo-mian gland obstruction and excessive tear evap
oration.
P o ste rio r blepharitis and meibomian gland dysfunction (MGD)

are often used interchangeably in medical practice, but this is an
incorrect use of clinical terminology. Posterior blepharitis is a gen
eral term that refers to inflammatory conditions of the eyelid and
may be caused by several conditions. In the later stages of MGD,
if inflammatory signs (e.g. redness) are present, an MGD-related
posterior blepharitis is the appropriate diagnosis (75).
• Lid position disorders: Proptosis (e.g. thyroid eye disease, craniosteno

sis), nocturnal lagophthalmos.
• Low blink rate: Intense concentration (e.g. chronic computer use), Parkin
son’s disease (e.g. decrease in the dopaminergic neuron pool of the sub
stantia nigra) (61).
E xtrin sic causes: Excessive evaporation can also occur independent of lid
pathology.
• Ocular surface disease: V ita m in A deficien cy (xerophthalmia), top

ical anesthetics (e.g. reduced blink rate, reduced reflex lacrimal gland
secretion), topical preservatives (e.g. benzalkonium chloride).•
• Contact lens wear; Chronic lens wear can reduce the number and length of
meibomian glands (58). Contact lenses with a lower overall water content
are typically more comfortable for patients with dry eye syndrome.
V ita m in A is essential for goblet cell and glycocalyx development.

Vitamin A deficiency can also result in aqueous tear-deficient-dry
eye as a result of lacrimal gland acinar damage (61), It is associated
with B it o t ’s sp ots on the conjunctiva (33).

jGorric^lEcte -VA;:' :i.: . • : . . .
K e ra to co n u s
• Epidemiology/History: Usually sporadic, but 6-13,5% of cases will have a

positive family history with autosomal dominant inheritance (58) (109).
The condition most commonly begins around puberty. Ask about fre
quent changes in eyeglass prescriptions and a history of eye rubbing,
— 53% of patients in the Collaborative Longitudinal Evaluation of Ker

atoconus (CLEK) Study reported a history o f atopy (109).
• Pathophysiology/Diagnosis: Non-inflammatory, progressive and degener

ative disease of unknown etiology that initially damages Bowman’s mem
brane. The condition results in the following:
— Strom al collagen fibril displacem ent due to a loss of adhesion

between fibrils.
— C orn eal thinning and protru sion likely from enzymatic (matrix
metalloproteinases (MMPs)) degradation (10) (85).
Keratoconus is associated with eye rubbing, atopy, contact lens wear, and
ocular and systemic conditions (35) (52):
— A sso cia te d ocu la r con d ition s - vernal keratoconjunctivitis (VKC),

atopic keratoconjunctivitis (AKC), floppy eyelid syndrome, Fuchs’
endothelial dystrophy, posterior polymorphous dystrophy, granular
dystrophy, lattice dystrophy, aniridia, retinitis pigmentosa, Leber’s
congenital amaurosis, retinopathy of prematurity, and cone dystro
phy (58).
— A sso cia te d system ic con d ition s (“T-DOME”) - Turner syndrome,
Dow n’s syndrome, Osteogenesis imperfecta, M arfan’s syndrome,
Ehlers-Danlos syndrome; a top ic derm atitis and m itral valve
prolapse are additional associated conditions.
• Symptoms: Progressive decreased vision, photophobia, glare, monocular

diplopia, and ghost images. Patients will experience acute vision loss and
pain if hydrops develops.
• Signs: Classic clinical signs include inferior, central, or paracentral stro

mal thinning that is typically bilateral, asymmetric, and progressive. As
the condition progresses, irregular astigmatism occurs and is poorly cor
rected with glasses or soft contact lenses.
— E arly signs: F leisch er’ s ring (iron deposits at the base of the cone
that is best seen with a cobalt blue filter (appears dark)), scissors
reflex on retinoscopy, irregular mires on keratometry, and inferior
steepening on topography (58).

460 10,7. CORNEA/REFRACTIVE SURGERY
- L ate signs: V o g t’s striae (vertical lines in deep stroma), M u n

so n ’ s sign (lower lid protrusion on downgaze), R izz u ti’ s sign (con
ical reflection on the nasal cornea when a light is shown from the
temporal side), and h y d rop s (tears in Descemet’s membrane that
result in edema and rupture of the epithelium) (84). 53% of patients
with moderate to severe keratoconus develop corneal scarring in one
or both eyes (52).
Keratoconus is classified as m ild (less than 48D), m od erate (48-

54D) and severe (greater than 54D).
P ellu cid M argin al D eg en era tion (P M D )
• Epidemiology/History: Most commonly presents in early adulthood (ages

20-40). There is no sex predilection.
• Pathophysiology/Diagnosis: Thinnest area of the cornea is in a crescent-

shape distribution inferiorly; corneal protrusion occurs right above this
area of thinning (not within the area of thinning as with keratoconus).•
• Signs/Symptoms: Patients typically do not experience pain. Character

ized by bilateral, inferior corneal thinning (4 to 8 o ’clock) 1-2 mm from
the limbus that leads to high amounts of A T R astigm atism . Classic
corneal topography findings include “ kissing doves” or “ crab-claw s”
pattern of inferior thinning.
P M D vs. K era tocon u s: Unlike keratoconus, there is no cone,

no Fleischer’s ring, and no Vogt’s striae found in PMD. However,
patients with PMD can develop sudden vision loss from hydrops
(although it is less common than keratoconus). Corneal scarring is
also more common in keratoconus (52).
K era tog lob u s
• Epidemiology/History: Rare. Onset typically at birth (52). Congenital

inheritance is most common (autosomal recessive), although it may be
acquired from an advanced keratopathy (e.g. keratoconus), trauma or
exophthalmos (79).

• Pathophysiology/Diagnosis: Associated with Ehlers-Danlos syndrome (35),

blue sclera (79), and Leber’s congenital amaurosis (52).
• Signs: Diffuse corneal thinning most concentrated in the periphery, result

ing in a globular shape. Can result in acute corneal edema due to rupture
of Descemet’s membrane; corneal perforation can occur with only minor
incidents of trauma (79).
1. E pith elia l B asem ent M em bran e D y strop h y (E B M D , M a p -D o t,

F in gerp rin t, A B M D , C o g a n ’ s m icro cy stic d y strop h y )
• Epidemiology/History: The most common anterior corneal dystrophy (58).

Autosomal dominant inheritance. Slightly more common in females (35).
• Pathophysiology/Diagnosis: EBMD results in abnormal epithelial ad

hesion and excessive basem ent m em brane production, causing ma
turing corneal epithelial cells to become trapped beneath the basement
membrane instead of reaching the corneal surface (34) (58).
• Symptoms: Patients are typically asymptomatic and the condition is

usually not progressive. However, vision loss, pain, and photophobia can
result from central corneal changes or from recu rrent erosions.
• Signs: Characterized by negative staining of map-lines, dots, and/or

fingerprints of the corneal epithelium (best seen with retroillumination).
10% of patients with ABMD develop recurrent corneal ero

sions (35). 50% of patients with corneal erosions will have
ABMD (102).
2. M e e sm a n ’ s D y strop h y
• Epidemiology/Pathophysiology: Rare, autosomal dominant inherited dys

trophy of the corneal epithelium that is notable within the 1st year of life.
• Symptoms: Often asymptomatic. Symptoms may occur from ruptured

cysts or recurrent corneal erosions (both of which are not likely to occur
before middle-age).•
• Signs: Characterized by extensive (100s), bilateral, clear intraepithelial

cysts that are diffusely spread across the entire cornea (most dominant
in the inter palpebral region) (58).

462 10.7. CORNEA/REFRA CTIVE SURGERY ‘
3. R eis-B u ck ler D y strop h y
• Epidemiology/History: Rare autosomal dominant condition that is often

diagnosed early in life due to patient reports of ocular pain.
• Pathophysiology/Diagnosis: Characterized by the abnormal development

and replacement of B ow m a n ’ s layer with collagen.
• Symptoms: Painful episodes due to recurrent corneal erosions are rela

tively common early in life; fewer episodes of recurrent erosions occur
with age.
• Signs: Bilateral, symmetric, sub-epithelial gray reticular opacities that

are most concentrated in the central cornea and spare the peripheral
cornea; these opacities typically get worse with age.
STR O M A L C O R N E A L D Y S T R O P H IE S
1. M acular D y strop h y
* Epidemiology/History: Rare autosomal recessive condition. Macular dys

trophy is the least common but most severe of the stromal dystrophies
and will affect visual acuity much earlier (58).
■ • Symptoms: Progressive vision loss and episodes of irritation and photo

phobia (secondary to recurrent corneal erosions); severe vision loss occurs
by the age of 20-30 (58).
• Signs: Characterized by diffuse, superficial, central stromal haze between

3 and 9 years of age. Progression results in diffuse stromal opacification
(i.e. cloudy cornea), stromal thinning, and multiple gray-white opaci
ties (m u cop oly sacch arid e d ep osits) with irregular borders that are
present in all layers of the cornea and extend to the limbus (58).
2. Granular D y strop h y
• Epidemiology/History: Autosomal dominant condition. Onset is during

the 1st decade, although patients will not experience a loss of vision until
middle-age (58).•
• Signs/Symptoms: Small snowflake granules (hyaline d ep osits) in the

central stroma. The deposits eventually spread towards the epithelium
and deep stroma, becoming confluent and resulting in decreased visual
acuity. Recurrent erosions are rare.

A v ellin o d y strop h y is a rare variant of granular dystrophy that

is characterized by granular AND lattice-like deposits within the
central stroma. It is also known as granular-lattice dystrophy (58).
3. L a ttice D y stro p h y
* Epidemiology/IIistory: Autosomal dominant stromal dystrophy.
• Signs/Symptoms: Anterior stromal haze with branching, retractile, lattice

like lines (am yloid d ep osits). Patients typically report decreased acuity
(in the 3rd decade) resulting from significant corneal scarring and haze.
Recurrent corneal erosions are common.
There is significant debate in the literature regarding whether gran

ular or lattice is the most' common stromal dystrophy. However,
researchers do agree that granular, lattice, and avellino dystrophies
are a result of a mutation in the tran sform in g grow th fa ctor
b e ta 1 (T G F B 1 ) gene (also known as BIGH3). Macular stromal
dystrophy IS NOT associated with a TGFB1 mutation (58).
4. S ch n y d er’s D y strop h y
• Epidemiology/History: Very rare autosomal dominant dystrophy. Ask

about current or past high cholesterol.
• Pathophysiology/Diagnosis: The condition has a strong association with

hyperlipidemia, xanthelasma, and corneal arcus, and is typically non
progressive (33) (35) (58).•
• Signs/Symptoms: Characterized by a fine yellow-white ring of stromal

crystals with haze in the central stroma. Patients are usually asymp
tomatic.
Remember the type of deposits for the stromal dystrophies

- Marilyn M onroe Got Hers in Los Angeles (Macular-
Mucopolysaccharide, Granular-Hyaline, Lattice-Amyloid).
Copyright. 2014 by KMK Educational Services, LLC

The most common symptoms associated with anterior/stromal

corneal dystrophies are d ecreased vision and painful recurrent
corn eal erosions.
P O S T E R IO R C O R N E A L D Y S T R O P H IE S ;
1. Fuchs’ E n doth elial D y stro p h y
• Epidemiology/History: Autosomal dominant inherited condition. Female

predilection, more common in patients 60 years or older (postmenopausal
women). 30% of patients have a positive family history of the condi
tion (78).
• Pathophysiology/Diagnosis: Recall that Descemet’s membrane consists

of an anterior lamina (produced in the embryo) and a posterior lamina
(secreted by the endothelium throughout life). In Fuchs’ dystrophy, the
posterior lamina is produced in excess and is seen as clumps (guttata)
of basement membrane on Descemet’s membrane with an associated de
crease in en doth elial cell den sity (hallmark of Fuchs’) (85).
• Symptoms: Most patients remain asymptomatic until later on in life

(50-60s); progression results in blurred hazy vision that is worse in the
morning with pain and glare.
• Signs: Often apparent early in life (age 30-40). Characterized by D e

creased en doth elial cell d en sity associated with pleomorphism (change
in cell shape) and polymegathism (change in cell size), endothelial gu t
ta ta that have a “beaten metal” appearance, and thick pachmetry find
ings.
- The primary concern in this condition is strom al edem a, which

develops when the endothelial cell pumps are no longer able to main
tain the proper osmotic balance. Stromal edema most commonly oc
curs when endothelial cell counts are less than 500 cells/mm2 (58).
As the condition progresses, stromal edema can spill over into the
epithelium, leading to painful bullae and scarring.
Recall that corneal endothelial cells have N a + /K -f- p u m p s that

play an important role in maintaining appropriate corneal thick
ness. Loss of these pumps leads to stromal edema in Fuchs’ en
dothelial dystrophy.

— C ataract surgery can increase endothelial cell loss and accelerate

the condition, especially at endothelial cell counts less than 1000
cell/mm2 (58).
E n doth elia l cell cou n t in children ranges between 3,000 to 4,000

cells/mm2; by age 80, the average endothelial cell count is 1,000-
2,000 cells/mm2. A minimum, of 400-700 cells/mm2 are required
to prevent corneal edema (85).
2. P o ste rio r P olym orp h ou s D y strop h y
• Epidemiology/History: Autosomal dominant inherited condition that oc

curs within the 2nd or 3rd decade of life, although it may manifest as a
cloudy cornea at birth (rare) (58),
• Symptoms: PPD is typically slowly progressive or non-progressive and

most patients are asymptomatic; thus, most patients with PPD are not
identified with the condition until 30-50 years of age (26). Decreased vi
sion secondary to corneal edema is the most common symptom in patients
with PPD (84).
• Signs: Characterized by bilateral, but often asymmetric, findings that

occur at the level of DescemePs membrane and the endothelium (58).
Findings include subtle patches of vesicles (hallmark of PPD), band
lesions (linear “ train track lesions’ 5) and diffuse opacities. In severe
cases (rare), corneal edema and bullae lead to painful vision loss.
PPD results in metaplasia of endothelial cells and an epithelial-

like endothelium (26) (35). These endothelial cells have the po
tential to spread over the iris and angle architecture, resulting in
angle-closure glaucoma (15%) from peripheral anterior synechiae
formation (34).
j£O N G E N IT A L A N T E R IO K :S E G M E N T A N O M A L IE S
1. M e g a lo co rn e a
• Rare, X-linked inherited condition that almost always affects males.

466 10.7. GORNEA/REFRACTIVE SURGERY
• Characterized by a bilateral corneal horizontal diameter of 13 m m or

greater (35) (52). Patients will be highly myopic with steep corneas,
but often have good acuity with correction.
• The stretching of ocular tissue can lead to lens subluxation and angle
abnormalities, resulting in glaucoma.
• Systemic associations include Marfan’s syndrome, Ehlers-Danlos syn

drome, and osteogenesis imperfecta (among others) (52).
2. M icro co rn e a
• Very rare autosomal-dominant or recessive inherited condition that may

be unilateral or bilateral.
• Characterized by a horizontal diameter of less than 10 m m (35) (52).
• Patients are most commonly h y p erop ic (although they may have any
refractive error depending on axial length), and are at risk for angle
closure glaucoma due to shallow anterior chambers (58).
3. C orn ea P lan a
• Epidemiology/History: Rare autosomal dominant or autosomal recessive

inherited condition.
• Pathophysiology/Diagnosis: A corneal curvature equal to the scleral cur

vature is pathognomonic for this condition; corneal plana is associated
with sclerocornea and microcornea (35).•
S clerocorn ea results from bilateral scleralization (i.e. opacifica

tion and vascularization) of the peripheral and/or central cornea.
80% of cases are associated with cornea plana (35).
• Signs: Bilateral fiat corneas (less than 38D and often as low as 20-30D);
characterized by hyperopia, shallow anterior chambers, and an increased
risk of angle-closure glaucoma (35).

4. Aniridia
• Rare, bilateral condition that is most commonly autosomal dominantly

inherited. The degree of aniridia can vary from partial to complete loss
of iris tissue.
• Ocular manifestations include corneal lesions (e.g. opacity, microcornea,

pannus), lenticular changes (e.g. cataract, lens subluxation), and poste
rior segment abnormalities (e.g. glaucoma in approximately 75% of cases,
foveal hypoplasia, disc hypoplasia, choroidal colobomas) (52) (102).
5. Haab’s striae•
* Results from con gen ital glaucom a. Characterized by horizontal cracks

(clear parallel lines) in Descemet’s membrane from increased IOP (as
opposed to vertical cracks in Descemet’s due to forceps delivery during
birth) (35) (58).
6. A x e n fe ld -R ie g e r S yn drom e Condition characterized by a continuum of

disorders, including posterior embryotoxin, Axenfeld anomaly, Rieger anomaly,
and Rieger syndrome. These patients suffer from anterior segment developmen
tal abnormalities that affect the anterior chamber angle. Approximately 50%
of patients with Axenfeld-Rieger syndrome develop glaucoma (58).
1. P o ste rio r em b ry otoxin (P E ) - Anteriorly displaced Schwalbe’s line.

Hallmark of Axenfeld-Rieger Syndrome.
• Up to 15% of normal healthy eyes have a PE. These patients do not

carry an increased risk of glaucoma (58).
2. A x e n fe ld anom aly - PE + angle abnormalities + increased glaucoma

risk.
• Angle abnormalities include prominent iris processes that travel to

the level of PE, often obscuring the scleral spur (58).
3. R ie g e r anom aly - PE + angle abnormalities -f increased glaucoma risk

+ iris stromal abnormalities.
• Iris stromal abnormalities include a displaced pupil (corectopia) and

iris hypoplasia with resulting holes within the iris tissue (polycoria).
4. R ie g e r sy n d rom e - PE -f angle abnormalities H- increased glaucoma

risk + iris stromal abnormalities + systemic abnormalities.
• Systemic abnormalities include mental retardation, dental, cran

iofacial, genitourinary, and skeletal abnormalities (non-exhaustive
list) (35).

7. P e te r’ s anom aly
• Rare condition in which patients are born with central white corneal opac
ities (leukoma) with iris adhesions (58). 80% of cases are bilateral (35).
• Although some consider the condition to be part of the Axenfeld-Rieger

syndrome continuum, Peter’s anomaly rarely occurs in conjunction with
these disorders; it is best to consider the condition separately (58). 50 —
70% develop secondary glaucoma (35). Patients may also develop corneal
edema and cataracts (58).
8. Lim bal d erm oid
• Normal dense connective tissue with hair follicles and sebaceous glands
that is displaced to an abnormal location; most commonly located at the
inferotemporal limbus (58).
C O R N EA L IN F E C T IO U S; K E R A T IT IS .;.
R isk factors for all types of corneal infectious keratitis include

contact lens wear, dry eye, exposure keratopathy, neurotrophic ker
atopathy, trauma, lid abnormalities, and bullous keratopathy
1. B acterial K eratitis
• Epidemiology/History: Bacterial keratitis is the most common etiology

for infectious keratitis. Contact lens wear, especially extended-wear, is
a common predisposing factor for bacterial keratitis. Consider bacterial
etiology first with any corneal infection associated with contact lens wear.
— The most common microbes involved are P seu d om on as aerug

inosa, Staph epidermidis, Staph aureus, Haemophilus influenzae,
and Moraxella catarrhalis.
P seu d om on as aeruginosa is the most common gram (-)

pathogen found in severe bacterial keratitis (58). It is characterized
by significant, thick mucopurulent discharge (often green in color),
hypopyon, a dense stromal infiltrate, and rapid progression (can
perforate the cornea within 48 hours!) (35).

• Pathophysiology/Diagnosis: Remember that most bacteria require an ep

ithelial defect for invasion and subsequent corneal ulceration. Noteworthy-
bacteria that can invade an intact epithelium include the following:
- “Canadian National Hockey League” - Corynebacterium diphthe-

riae, Neisseria gonorrhea and meningitidis, Haemophilus, and Listeria (52) (35).
• Symptoms: Severe pain, red eye, photophobia, and decreased vision.
• Signs: By definition, a corn eal ulcer refers to a corneal infiltrate(s) with

an overlying epithelial defect.*•
An infiltrate is a sign of your patient’s immune system attacking

an antigen via antibodies. In isolation, it is an immune-mediated
response and NOT a sign of infection.
Corneal infiltrates can be mistaken for corneal ulcers. Melton and Thomas
overview key differences (105):
• F lu orescein staining area to lesion ratio with corneal ulcers is typ

ically 1:1 (105); the staining area for infiltrates is usually less than the
lesion size.
• C orn ea l ulcers classically result in m od era te to severe pain with a

mild anterior chamber reaction and diffuse conjunctival injection; infil
trates are less painful with multiple lesions, no anterior chamber reaction,
and a sectoral injection pattern (105).
2. Fungal K eratitis
• Epidemiology/History: The most common type of corneal ulcer after

traumatic corneal injury, especially from v egetable m atter (e.g. tree
branch) (33).
• Pathophysiology/Diagnosis: C an d id a infections often occur in eyes

with chronic corneal disease (e.g. chronic dry eye, herpes keratitis, expo
sure keratopathy), or in im m u n ocom p rom ised or severely debilitated
patients. Aspergillus and Fusarium species are more commonly the cul
prit after v egeta ble m atter traum a (102), Culture of fungi should be
performed on S a b ou ra u d ’s agar.

470 10. 7 CORNEA/REFRACTIVE SURGERY
C an dida is part of the normal human flora and rarely causes harm
ful effects; however, Candida infections in immunocompromised
patients can be deadly.
• Symptoms: Pain, photophobia, tearing, and decreased vision.
• Signs: An epithelial defect is usually noted with an underlying gray-

white corneal infiltrate with feathery edges and possible surrounding
satellite infiltrates (classic for Aspergillus and Fusarium). The presen
tation can also be similar to a bacterial corneal ulcer (classic for Can
dida) (52) (84). Additional signs include an anterior chamber reaction
and hypopyon.
3. A ca n th a m oeb a K eratitis
• Epidemiology /History: Rare parasitic infection associated with inade

quate contact lens hygiene (e.g. tap water, homemade saline solution,
swimming or hot tub use while wearing contact lenses),
• Pathophysiology/Diagnosis: Acanthamoeba is one of the most common

protozoa found in soil and is also frequently found in water and within
the oral cavity of humans. Compromise of the corneal epithelium allows
acanthamoeba to invade the corneal epithelial and stromal tissues. Infec
tions progress slowly and are often misdiagnosed early in management.
Culture should be performed with a non-nutrient agar with heat-killed
E .C o li (102).
• Symptoms: Blurred vision, pain, and minimal discharge.
— E arly: Punctate or pseuclodendritic epithelial defects (may be con

fused with herpes simplex keratitis) associated with severe pain
ou t o f p ro p o rtio n to th e signs.
— Late: Radial keratoneuritis (inflammation of the corneal nerves)

and patchy anterior stromal infiltrates that gradually progress to
form a ring ulcer.

Smears and Cultures for Infectious Keratitis:
1. Gram stain (smear) - tests for Bacteria.
2. KOH or Giemsa stain (smear) - tests for Fungi/Yeasts.
3. Sabaroud’s agar culture plate - tests for Fungi.
4. Chocolate agar culture plate - tests for Haemophilus and Nis-

seria.
5. Thioglycolate culture broth - tests for Aerobic and Anaerobic

bacteria.
6. Non-nutrient agar culture plate with E. coli overlay - tests

for Acanthamoeba.*•
4. Herpes Simplex Virus (HSV)
• Epidemiology/History: DNA virus that is most common in young pa

tients. Ask about a history of previous episodes and/or cold sores.
— Primary exposure - occurs in children age 6 months to 5 years.

Patients are most commonly asymptomatic, but they may experi
ence mild virus-type symptoms (52) (58).
— Recurrent H S V infections - result from reactivation of a latent
infection in the trigeminal ganglion. Can be triggered by physical
or emotional stress from sun exposure, fever, and immunosuppres
sion (non-exhaustive list) (35).
• Pathophysiology/Diagnosis: Tissue damage in HSV occurs either by di

rect invasion from the virus, neurotrophic mechanisms, or by the immune-
system response to HSV.
• Symptoms: Pain, redness, serous discharge, tearing, photophobia, and

decreased vision.
• Signs: Decreased corneal sensitivity is common in these patients.
• Primary exposure usually results in blepharitis and/or conjunctivitis.
— Blepharitis - Focal vesicular lesions with crusting located on the

eyelids and periorbital area.
— C on ju n ctivitis - Acute unilateral follicular conjunctivitis with wa
tery discharge and preauricular lymphadenopathy.
• Recurrent H SV infections can be classified into the following:

1. E pithelial D isease
Includes corneal vesicles, dendritic ulcers, geographic ulcers, and marginal ul
cers. Due to direct invasion of corneal epithelial cells by HSV.
• C orneal vesicles - small epithelial lesions often referred to as punctate

epithelial keratopathy. Represent the earliest epithelial signs of reacti
vated HSV (58).
• D en d ritic ulcers - most common presentation of HSV keratitis. The

edges of an HSV dendrite (active viral cells) stain well with rose bengal;
the center ulceration stains well with fluorescein.
• G eograph ic ulcers - similar to a dendritic ulcer but wider (no longer lin
ear) in appearance; associated with previous use of topical steroids (58).
• M argin al ulcers - located close to the limbus; presents as a stromal in

filtrate with an overlying epithelial defect and associated limbal injection.
2. N eu rotrop h ic k eratopathy
Results from red u ced corn eal innervation and decreased tear secretion,
leading to poor cornea1 wound healing (58).
• Occurs in patients who have had infectious epithelial keratitis; unique

because etiology is not immune-mediated or infectious.
• A neurotrophic ulcer appears as an oval defect with smooth borders. It is

often preceded by punctate epithelial erosions that then progress to form
an ulcer.
N eu rotrop h ic ulcers are typically inferior in location and oval

in appearance with smooth borders. G eog rap h ic ulcers result in
irregular epithelial defects with scalloped borders (58).
3. Strom al D isease
Accounts for only 2% of initial episodes of ocular HSV disease, but 20 —48% of
recurrent ocular HSV disease (58). There are several types of stromal disease
in HSV keratitis:•
• Interstitial keratitis (IK ) - Characterized by an infiltrate with dif

fuse neovascularization, an immune ring (e.g. Wessley ring), stromal
thinning, and subsequent scarring.

— In herpetic disease, IK is thought to result from an antigen-antibody-

complement cascade against a live virus or viral antigen retained
within the corneal stroma (58).
— By definition, IK is stromal inflammation WITHOUT primary in

volvement of the epithelium or endothelium (52) (84).
Remember that most patients are born with IK as a result of c o n

gen ital syphilis (90%). In the United States, IK is typically a
tesultro fh er pet krdi sense:•
• N e cro tizin g strom al keratitis - Rare keratitis that results from direct
virus invasion into the stroma. Results in severe stromal inflammation
with necrosis that can lead to corneal thinning and perforation.
H S V strom al keratitis is concerning because it may lead to sig

nificant stromal scarring and decreased acuity.
4, E n d oth eliitis (D isciform K eratitis)
Secondary stromal edema due to an immune reaction against a viral antigen

or live virus within the corneal endothelium (58).
• D iscifo rm en doth eliitis - most common form of endotheliitis. Char

acterized by focal, disc-shaped, stromal edema overlying keratic precipi
tates. Often accompanied by a mild to moderate iritis (58).
Unlike interstitial keratitis, stromal infiltrates and neovasculariza

tion are not present in disciform endotheliitis (58),

474 10,7. CORNEA/B.EFR,ACTIVE SURGERY
5. H erpes Zoster V iru s (H Z V )
• Epidemiology/Pathophysiology: Varicella zoster virus (VZV) is the initial

invading organism, affecting 95% of children by the age of 5 in the United
States, After the primary infection (chickenpox), VZV is transported to
the trigeminal ganglia and other neural cell bodies, where it becomes dor
mant. O lder age, trauma, neurodegeneration, or im m unosuppresion
may contribute to reactivation of the virus and resulting herpes .zoster
infection.
HZV primarily affects the elderly and is rare in children or young

patients. If HZV occurs in patients younger than 50, consider a
medical evaluation to determine if the patient is immunocompro
mised (52). HZV is contagious for those who have not had chicken
pox.
• Signs: Vary depending on involvement of the cornea. Symptoms are more

severe in immunocompromised patients. HZV infection is unilateral and
follows the affected dermatomes.
— “ P re -zo ste r” is characterized by a cluster of warning signals (e.g.

tingling, malaise, fever) known as a p rod rom e.
- “ A ctiv e -z o ste r” is characterized by skin involvement that respects

the dermatomes and does NOT cross the midline. Vesicles can form
on the lid margin, resulting in b lep h arocon ju n ctivitis; episcleritis
is also relatively common.
Activation along the ophthalmic branch of the trigeminal ganglion leads to

ophthalmic manifestations and is referred to as h erpes zoster ophthalm icus
(HZO).
• C orneal signs occur in 65% of patients with acute HZO (58).
— Common signs: Punctate epithelial keratitis, pseudodendritic kerati

tis, anterior stromal keratitis, keratouveitis/endotheliitis, and neu
rotrophic keratopathy.
— Less common signs (non-exhaustive list): Exposure keratopathy, dis

ciform keratitis, interstitial keratitis.

H Z V keratitis begins with small, stellate lesions that can progress

to p seu d od en d rites (tapered ends with no term in al bulbs)
with a “stuck-on” appearance. The entire lesion stains with rose
bengal (compared to just the edges in HSV) (84). HZV lesions DO
NOT stain well with fluorescein (unlike HSV) (33).
• U veitis occurs in up to 40% of patients with acute HZO (58).
- Can be granulomatous or non-granulomatous and typically associ-

atVcl^witirsighifica'nfTKPs, corneaFedema, and posterior synecliiae (58).
* O th er H Z O findings include trichiasis, ectropion, entropion, madaro-

sis, poliosis, episcleritis, scleritis, retinitis, vasculitis, optic neuritis, cra
nial nerve palsies, glaucoma, and cataracts (35) (58).
H u tch in son ’ s sign is a rash on the tip of the nose as a result of

reactivation of the virus along the terminal branch o f the nasocil
iary nerve of CN VI. It indicates a high risk of ocular involvement
(34-76%) (58).
“ P o st-z o ste r” is characterized by post-herpetic neuralgia (PHN) and depres

sion.
• P H N - defined as pain persisting beyond 1 month after rash onset or

rash resolution. PHN is the most common complication of herpes zoster
and affects 10 — 30% of patients (58).
• Severe P H N affects about 7% of patients; PHN is the leading cause of

suicide in patients over 70 years of age with chronic pain (58),
iPE IU PH EH A 1, ULOERATJ V 15 K E R A T IT IS
1. M o o r e n ’s U lcer
• Epidemiology/History: Rare condition that is more common in men and

older patients (40-70, although may occur at all ages). The classification
of Mooren’s ulcer is disputed within the literature; Wood and Kaufman
describe the following categories (58):

476 10.7. CORNEA/REFRA CTIVE SUR GER Y
1. Benign (typical or limited) M ooren’s ulcer (75%) - unilateral,

affects the elderly, mild to moderate symptoms, responds well to
treatment (35) (58).
2. Malignant (atypical) M ooren’s ulcer - bilateral, affects younger
patients (especially black males), severe symptoms, responds poorly
to treatment, and progresses relentlessly (58).
• Pathophysiology/Diagnosis: Painful, progressive, chronic vasculitis of the

limbal blood vessels that leads to ischemic necrosis and peripheral ul
cerative keratitis (102).
— Mooren’s ulcer is idiopathic in nature, but is likely autoimmune

mediated (58). By definition, the condition occurs independent of
any diagnosable systemic disorder that could be responsible for the
progressive corneal pathology (91).
— Associated with systemic hepatitis C viral infection or hookworm
infestation (33) (58).
• Symptoms: The most common symptom is pain, which is often se

vere (58). Additional symptoms include redness, tearing, and photopho
bia. Decreased vision can result from irregular astigmatism, associated
iritis, or if the ulcer is central in location (58).
• Signs: The classic presentation is an unilateral peripheral crescent

shaped gray infiltrate in an older patient that progresses to an ulcer.
The ulcer is concentric to the limbus and has a unique overhanging edge.
The ulceration may be self-limited or may spread circumferentially and/or
centrally in the late stages of the condition (33) (52).
2. Staphylococcal Marginal Keratitis
• Epidemiology/History: Common condition. Ask about a history of sim

ilar recurrent acute episodes.
• Pathophysiology/Diagnosis: Type III hypersensitivity response to

staphylococcus aureus; typically occurs in patients with chronic staphy
lococcal blepharitis. Recurrences are common unless the underlying ble
pharitis is treated appropriately.
• Symptoms: Patients may be asymptomatic or complain of acute photo

phobia, pain, tearing, redness, and decreased vision.•
• Signs: Corneal stromal infiltrates (usually multiple and bilateral) located

in the periphery; classically occur at the 2, 4, 8, and 10 o’clock posi
tions where the lid margin makes contact with the limbus (58). Look for
associated phlyctenule, signs of blepharitis, and/or acne rosacea. Resid
ual thinning, superficial neovascularization, and peripheral scarring are
common.

Remember, an infiltrate is a sign of your patient’s immune system

attacking the staphylococcus antigens via antibodies. In isolation,
it is an immune-mediated response and NOT a sign of an infection.
3. C olla gen Vascular D isorders
• Recall that collagen vascular disorders such as rheumatoid arthritis, sys

temic lupus erythematosus, polyarteritis nodosa, and Wegener’s gran-
_____ nlamatosis-(-non=exhausti-ve-list-)-ean-eause-per-ipheral-corneal-thinning
and/or ulcers (52).
• Patients can be asymptomatic or may report significant pain, redness,

and decrease in vision.
• Corneal findings include peripheral corneal thinning/ulcers with or with

out inflammation. The condition can be unilateral or bilateral. The ulcers
may progress to encompass the entire peripheral cornea. Corneal findings
may be associated with scleritis, episcleritis, and k era tocon ju n ctiv itis
sicca.
iCorncal D eposits
• Corneal deposits may occur secondary to normal aging changes within
the cornea, corneal surface irregularities, foreign bodies, use of certain
systemic medications, and various systemic diseases.
• Corneal deposits may be pigmented, refractile, metallic, or non-pigmented

in color. They can occur within any layer of the cornea, from the surface
epithelium to Descemet’s membrane.
• Noteworthy examples include:
— W horl keratopathy - seen in Fabry’s disease and with use of

chloroquine, hydroxychloroquine, amiodarone, indomethacin, tamox
ifen.
— Fleischer’s Ring - iron ring at the base of the cone in keratoconus.
— Rust rings - result from metallic foreign bodies.
— Hudson Stahli lines - common in the elderly; iron deposits found
at the junction between the middle and lower third o f the cornea.
Do not cause symptoms and have no clinical significance.
— Stocker’s line - iron deposits on the leading edge of a pterygium.
— Ferry’s line - iron deposits on the leading edge of a filtering bleb.

— K ayser-F leischer R in g - accumulation of copper that occurs in

patients with certain liver disorders, most notably Wilson’s disease.
- B an d keratopathy - Calcium deposits within Bowman’s layer (white
spots form a “swiss-cheese pattern”).
G O R N EA L D E G E N E R A T IO N S :'j
1. T errien ’ s M arginal D eg en era tion
• Epidemiology/History: Rare. Most commonly in men (3:1); typically

presents between the ages of 20-40 (58).
• Pathophysiology/Diagnosis: Idiopathic inflammatory degenerative con

dition that results in slowly progressive periph eral strom al thinning.
Perforation occurs in approximately 15% of cases (58).
• Symptoms: Often asymptomatic, although progression can lead to irreg

ular astigmatism (classically ATR) and decreased acuity.
• Signs: Characterized by superonasal, bilateral (typically asymmetric),

slowly progressive peripheral thinning with an associated vascularized
pannus. In most cases, there is no anterior chamber reaction, no con
junctival injection, and no overlying epithelial defects (58).
Mooren’s ulcer can have a similar presentation as Terrien’s

marginal degeneration, but WITH an overlying epithelial defect.
2. Salzm ann’ s N od u la r D eg en era tion
• Epidemiology/History: Rare. Female predilection. Often occurs within

the 6th decade.
• Pathophysiology/Diagnosis: Degenerative disease that follows episodes of

keratitis (58). Associated with significant corneal inflam m atory dis
ease, including meibomian gland dysfunction, trachoma, phlyctenulosis,
VKC, keratoconjunctivitis sicca, and interstitial keratitis (non-exhaustive
list) (58), although it can be idiopathic.•
• Symptoms: Typically asymptomatic, although patients may experience

pain if recurrent corneal erosions develop in epithelial cells overlying the
nodule; vision may be reduced if the nodule is located within the visual
axis.

• Signs: H yaline plaque d ep osits located between the epithelium and

Bowman’s membrane (58) that clasically appear as mid-peripheral, ele
vated blu e-gra y or yellow-white nodular lesions. May be unilateral or
bilateral and single or multiple in number. Nodules are often located
within or adjacent to an old corneal scar or corneal pannus.
3. W h ite L im bal G ird le o f V og t
* Epidemiology/History: Age-related condition that is very common; af

fects 55% of patients 40-60 years of age, and nearly 100% of patients over
80 (58).
•“ Signs/Symptoms: C har acterizeddby bilateral chalk-like linear opacities of

nasal limbus (typically at 3 and 9 o ’clock). Patients are asymptomatic.
4. B a n d K e ra top a th y
• Pathophysiology/Diagnosis: Results from the following:
— O cular con d ition s that cause chronic inflammation and ocular sur
face disease (e.g. uveitis, dry eye syndrome, exposure keratopathy).
— After trau m a (e.g. multiple ocular surgeries).
— System ic con d ition s that cause increased serum calcium or phos
phorus levels, including gou t (check uric acid levels), h y p erca l
cem ia, sarcoidosis, and renal failure (check blood urea nitrogen and
creatinine levels).
• Symptoms: Patients are often asymptomatic because the calcium plaques

are usually located in the periphery at the 3 and 9 o ’clock positions.
Although uncommon, the plaques may move centrally and cause a foreign
body sensation and decreased vision.
• Signs: Calcium deposits on the anterior surface of Bowman’s membrane

or in the sub-epithelial space that appear as white spots with a “swiss-
cheese pattern;” usually most concentrated within the inter palpebral re
gion of the cornea.
5. A rcu s senilis
• Epidemiology/History: The most common peripheral corneal opacity (52).

Arcus is prominent in the elderly and affects almost 100% of patients over
the age of 80 (58). Higher incidence in males and African Americans (58).*
* Pathophysiology/Diagnosis: Associated with aging and high choles

terol. Lipid deposition begins on Descemet’s membrane and is subse
quently deposited on Bowman’s layer before extending into the stroma.

• Signs: Usually bilateral and symmetric circumferential 1 mm band within

the peripheral cornea, with a clear zone of separation to the limbus.
Arcus is typically of little concern, unless:
• U nilateral arcus is rare and is associated with carotid dis

ease on the side WITHOUT the arcus.
• Arcus in patients younger than 50 is associated with an in

creased risk of coronary artery disease; a lipid profile is war
ranted in these cases (58).
6. C r o c o d ile Shagreen
• Signs: Bilateral, gray-white, polygonal stromal opacities (“cracked ice”

appearance) either near Bowman’s layer (anterior crocodile shagreen) or
occasionally near Descemet’s membrane (posterior crocodile shagreen).
Opacities are caused by irregularly arranged folds of collagen (58).
• Symptoms: Usually asymptomatic and benign.
7. C orn eal Farinata
• Bilateral “flour dust” deposits that are most commonly located in the
central deep stroma. May be due to aging or an autosomal dominant
condition. Patients are typically asymptomatic (52) (84).
|Corneal G raft R ejection ' v t ; y - p A b.; i

T y p e IV h ypersensitivity resp on se to the donor cornea (84). 30% of
patients will have rejection within one year (35). Characterized by decreased
vision, mild pain, redness, and photophobia.
1. E pithelial rejection - rare; appears as an elevated, irregular epithelium.
2. Strom al rejection - associated with subepithelial infiltrates known as

K ra ch m e r’s spots.
3. E n doth elial rejection line - characterized by WBCs on the endothe

lium that form a K h o d a d o u st line.

Refractive surgery is an elective procedure that modifies the refractive status

o f the eye by lenticular or corneal modifications. We start our review by summa
rizing the absolute and relative contraindications of refractive surgery (33) (35) (78).
A b s o lu te con train dica tion s
• Younger than 18 years of age with an unstable refractive error within the
last year (58).
• Unrealistic expectations - will reduce dependence on glasses (but NOT *•

glasses free), will experience post-op glare and dryness.
• Keratoconus, active herpes simplex keratitis, contact lens warpage.
• Connective tissue disease (e.g. keloid formers), collagen vascular disease,

immunocompromised disease (e.g. chronic steroid use).
R e la tiv e con train dica tion s
• Blepharitis, dry eye syndrome, chronic eye rubbing, ocular surface dis
ease, large pupils.
• Diabetes mellitus - fluctuating blood glucose levels can change the refrac
tive error, which makes the amount of treatment needed unclear.
• Primary open angle-glaucoma (if not well-controlled) - IOP elevates (as

high as 65 mmHg) during placement of the suction cup during surgery,
which could be dangerous if a patient already has uncontrolled or ad
vanced glaucoma (5).
• Pregnancy.
• Retinal thinning/lattice degeneration may increase the risk of retinal

tears during or after surgery. Although a clear link has not been es
tablished, caution should be taken (9).
C on ta ct lens w earers - soft spherical contact lens wearers need

to be out of their lenses for 3-14 days prior to surgery; soft toric and
RGP lens wearers need to be out of their lenses for at least 14-21
days (5). A dry and cycloplegic refraction should be peformed to
determine whether the patient is overminused.

482 10.7. CORNEA/REFR.ACT1VE SURGERY
ly R adial K eratotoiriy (R K );ATL:A*-■A )'At' )AAA AAAj

• Radial incisions are made with a diamond knife to flatten the periph
eral corneal stroma; the normal IOP then pushes the weakened periph
eral cornea outward, causing the central cornea to flatten to reduce my
opia (78).
• No longer performed due to better options; RK was difficult to titrate,

caused significant instability in the refractive error, and led to p rogres
sive h y p erop ic shifts.
j2. Photorefraetive K erat ectom y (P R K ) :;;Aa.A y/A A I

• The corneal epithelium, Bowman's layer, and superficial stromal tissue
are removed (no flap) and excimer laser is applied directly to the central
cornea (for myopia) or mid-peripheral cornea (steepens the central cornea
to correct hyperopia).
• Treatment range: -8D to +4D, up to 4D of cylinder (5).
• 400 um residual cornea is required after treatment (64).
• PRK requires a longer healing time (1-2 weeks) compared to LASIK be
cause the entire corneal epithelium must regrow. Patients will experience
extremely poor vision and pain (controlled with NSAIDs and BCL) in
the immediate post-op period.•
• The risk of stromal haze is greatest with higher prescriptions and can be
reduced by using mitomycin C during the procedure.
PRK is ideal for patients who are at risk for trauma (e.g. military,
athletes (especially boxers and martial arts)) because there is no
risk of flap complications. PRK is also associated with less risk for
corneal ectasia, less induction of higher order aberrations, less post
op dryness, requires less corneal thickness, and is cheaper compared
to LASIK (69).

p. L aser-assisted in situ keratom ileusis (L A SIK )

• An epithelial flap is made with a microkeratome, an excimer laser is
applied to the anterior strom al bed, and the flap is then reattached.
• Treatment range: -10D to +4D, up to 5D cyl (58). C lear lens ex tra c

tio n can be performed on patients who exceed LASIK refractive error
requirements.
• T h ickn ess requirem ents (64):
- 250 um must remain under the flap to maintain corneal integrity.

------------ ÂLhe T apTtself-is-ab ouh460-200-um-thi ck- (deter-mined-by-infer-aop er-
ative pachymetry) (58).
— Ablation depth is 15 um/diopter.
Total pachymetry minus the flap thickness (160-200 um) minus the
ablation depth (15 um/diopter) should be at least 250 um (64).
• LASIK patients heal faster (1-2 days), experience less pain, and have less
post-op corneal haze compared to PRK patients.
F em tosecon d Laser F lap: The same procedure as LASIK but the flap is
made with a fem tosecon d laser (e.g. Intralase©) instead of a microkeratome.
A femtosecond laser flap is thinner, leaving behind more tissue to ablate. It
also removes the risk of mechanical malfunction of the microkeratome and is
associated with less post-op dry eye.
Laser epith elia l keratom ileusis (L A S E K or E -L A S IK ): Same proce

dure as LASIK but the flap is made with dilute alcoh ol instead of a micro
keratome.
E p i-L A S IK : This is another version of LASIK where a blunt plastic blade

is used to create the epithelial flap rather than a microkeratome.
V^pn'dUctive k erato p lasty (C K ) L;-k . . A- :A ;iA A . : - ' ’

* Used to treat presbyopia, low hyperopia, and for treating residual astig
matism after previous surgeries (58).

• Uses radio frequency energy to shrink the collagen fibers in the peripheral
corneal stroma, allowing the central cornea to steepen. Regression is
expected after about 2-3 years; the surgery can be repeated.
• Treatment range: +0.75D to +3.00D with less than 0.75D of astigma

tism (5).
|5. In tra stro m a l C orneal R ings (Irita c s® ) ; j § y TV § . ;j

• PMMA rings are inserted into the peripheral stroma to flatten the cornea
(shortens the corneal arc length); rings can be removed or exchanged.
• Approved for use with keratoconus.
• Treatment range: -0.75D to -3D; does not treat hyperopia (5)
6. C lear Lens E x tra c tio n ^ T

• Essentially cataract surgery without a cataract! The IOL that is selected
reduces the refractive error.
• No residual accommodation remains unless a multifocal or accommodat

ing IOL is used.
• Large treatment range.
7. Phakic IOL (Im p lan tab le C o n tact Lens) A;

• Intraocular lens implantation in a phakic eye. The lens is implanted to
alter the total power of the eye.
• The IOL is angle supported, iris supported, or sulcus supported (5). Re
quires a peripheral iridotomy.
• Can be used to treat a larger range of refractive errors compared to

corneal surgery and the IOL is removable. Also preserves natural accom
modation (unlike clear lens extraction).
B. A stigm atic k erato to m y (A K )

Corneal incisions are made with diamond blades to relax the cornea in the
steepest meridian.

|9 .
• Reduces higher order aberrations (e.g. coma, spherical aberrations) in

addition to correcting the refractive error (i.e, lower order aberrations,
which account for 90% of all aberrations).
• Can be done with LASIK and PRK and theoretically results in better
quality vision with improved contrast and acuity and less glare.
In refractive surgery, success is generally considered 20/40 visual

-aeuit-y-on b ette iv-Imth o se-with-lo w-refr active_erro r r a b o u t - g 0-99%
achieve this level. About 75% achieve 20/25 or better (47) (65).
iPO T E N T IA L LA SIK C O M PL IC A T IO N S
X. Pain in the first 24 hours
• Due to the corneal wound; severe pain may be due to flap complications
(e.g. dislocation of the flap).
2. Serious infection
• Typically occurs at day 1-3 (47). Can lead to corneal melting, irregular
astigmatism, and scarring (5).
• Bacteria are usually gram (+ ) or mycobacteria (5).
• Risk with PRK — 1/1000-1/3500 (47).
• Risk with LASIK - 1/5000 (47).
3. Flap complications
Flap complications include free caps, button holes, flap folds, irregular flaps,
corneal perforation, and flap subluxation.
• Button holes (cap perforation, a hole in the flap) are more common with
very steep corneas or deep set eyes. The steep cornea can buckle in the
suction ring, causing a hole as the keratome moves across the cornea.
• Free caps (no hinge made) are more common with very flat corneas and
are the result of an inadequate amount of cornea in the ring, causing the
blade to cut off the hinge.

486 10.7 ; CORNEA/REFRA CTIVE SURGERY
• Flap folds occur in 56% of cases at day 1 (usually within the first hour),
and 95% of cases within week 1 (5).
— Flap folds are called m acrostriae if they are full-thickness with

undulating, parallel stromal folds; they result from slippage or mal-
positioning during surgery. They typically require treatment of the
flap by lifting and repositioning.
— M icrostria e are fine, irregular, multidirectional folds in Bowman’s

layer that typically resolve on their own; they are treated only if they
are visually significant (5).
• Flap dislodgment is more common with keratome flaps than with fem
tosecond laser flaps and is usually due to accidental touch to the eye or
eyelid. Dislodged flaps can be repositioned.
4. C orn eal ectasia
• Anterior protusion of the cornea due to thinning. Patients with high

myopia (more cornea is ablated), undetected keratoconus, or forme fruste
lceratoconus are more at risk. Corneal ectasia may occur at any time
following the surgery.
5. R esidu al refractive error
• Patients may be over or under-corrected or may have regression after

surgery (more common in refractive error > -8D).
• Patients can be fit with RGPs or reverse geometry lenses after approx
imately 8-12 weeks (may fit sooner with soft CLs). Refractive surgery
enhancement may also be considered (47).
Loss of best corrected acuity occurs in 1% of patients. Blindness is

extremely rare (47).
6. Glare
Worse glare is expected with small ablation zones, large pupils, monovision
correction, and-higher refractive errors.

7. Dry Eye
The most common side effect of LASIK surgery; occurs in up to 33% of all
refractive surgery patients (5).
• Corneal nerves are severed during the LASIK procedure; the resulting
decrease in corneal sensitivity results in decreased neural feedback to the
lacrimal gland. Dry eye often improves or resolves within 1-2 months (47).
8. Diffuse lamellar keratitis (DLK or Sands of the Sahara)___________ *•
• Description: Rare (1/200 to 1/500 cases) (58), inflammatory, non-infectious

reaction that occurs at the lamellar interface (between the corneal flap
and the stroma). It is characterized by a fine, granular, sand-like infil
trate that typically presents within 2-3 days after surgery. The etiology
is poorly understood, but may be a response to toxins (e.g. blade debris,
microkeratome oil) (58). DLK is less common with disposable microker-
atomes.
• Symptoms: May be asymptomatic or experience photophobia, blurred

vision, foreign body sensation, and pain. Can lead to vision loss (from
corneal scarring and corneal melt) if not properly managed (46).
9. Epithelial ingrowth
Rare (less than 3% of surgical cases) (5).
• Late postoperative LASIK complication that is most commonly observed

at the one month post-op visit as a faint gray line or white, milky deposits
within 2 mm of the flap edge interface (58).
• The patient is typically asymptomatic and the condition is not treated

unless progression is documented, the visual axis is obstructed, greater
than 2 mm o f ingrowth occurs from the flap edge, or results in corneal
astigmatism (47) (58).
Epithelial ingrowth is the most common complication associated

with a LASIK enhancement.

488 10.8. LENS/CATARACT/IOL PRES-AND POST-OPERATIVE CARE
10. Corneal haze
• The prevalence of long-term haze with LASIK is 0.1%, and with PRK
is 1% in those with refractive errors below 6D. The risk increases with
higher refractive errors (47).
• Remember, corneal haze is normally present for several weeks after PRK.
Retreatment criteria for enhancement
The earliest time for retreatment is 3 months, but 6 months is preferred to

allow the refractive error to stabilize. Criteria for enhancement include the
following:
• Astigmatism > 0.75D causing symptoms.
• Refractive error > or equal to 0.75D from target in an unhappy patient.
• Uncorrected VA of 20/30 or worse in an unhappy patient (7).
L on g-term M an agem ent
• IOP readings will always be falsely low due to thin corneas.
• Gonioscopy and retinal evaluations are still necessary in patients with a

history o f high hyperopia and myopia, respectively.
• Patients should wear eye protection during contact sports to avoid dis
lodging the corneal flap and to block UV radiation (7).
- SECTION 10,8 --------------------------------------------------------------- :-----------------------------------
L e n s/C a ta ra c t/IG L P re -an d P o st-o p erativ e care
The American Optometric Association defines a cataract as “an opacification

of the lens that leads to measurably decreased visual acuity and / or some func
tional disability as perceived by the patient (6).” An estimated 20.5 million
(17,2%) of Americans older than 40 years have a cataract in either eye, and 6.1
million (5.1%) have pseudophakia/aphakia. The total number of persons who
will have a cataract is estimated to rise to 30.1 million by 2020 (103),
T ypes of C a ta ra c ts U%-,; \ ' ' . ' ■■■- •. ;

• N uclear Sclerosis - Most common aging cataract. Typically causes a
myopic shift; elderly patients often report “second sight” because of their
improved ability to read without spectacles.

• C o rtica l C ataract - Radial spoke-like opacities that commonly induce

a hyperopic shift.
• A n te rio r Subcapsular C ataract - Located directly underneath the

anterior lens capsule.
• P o ste rio r Subcapsular C ataract (P S C ) - Located directly in front

of the posterior lens capsule; often affects near vision more than distance
vision and is commonly a result of system ic or top ica l steroid s and
X-rays.
"Mild P S C s can cause significant reduction in acuity and are typ

ically associated with worse glare compared to other cataracts.*•
• Infant C ataracts - Associated with galactosemia and rubella (52) (78).

The most common type of congenital or infantile cataract is a lamel
lar (zonular) cataract that consists of a lens opacity that surrounds the
embryonic nucleus (102).
A cerulean cataract is a type of congenital cataract that rarely

affects visual acuity. It appears as tiny dot-like or flake-like white
or bluish-green opacities.
• P resen ile C ataracts - Associated with diabetes me 11it us >myotonic dys

trophy (PSC Christmas tree cataracts), Wilson’s disease, hypocalcemia,
and atopic dermatitis (52) (78).
• T rau m atic C ataracts - Rossette cataract. Also look for a Vossius ring
(iris pigment on the anterior lens capsule).
• T o x ic cataracts include the following:
— Anterior subcapsular effects: Chlorpromazine (stellate cataracts),

amiodarone (deposits), miotics (vacuoles) and gold salts (gold de
posits).
— Posterior subcapsular cataracts: Corticosteroids (12) (78).
• S econ d a ry C ataracts - Common causes include chronic anterior uveitis

(most common), high myopia, retinitis pigmentosa, and gyrate atrophy.

490 10.8. LENS/CATARAGT/IOL PRE-AND POST-OPERATIVE CARE
E picapsular stars are residual remnants of the tunica vasculosa

lentis and appear as small, star-shaped, pigmented deposits on the
anterior capsule of the lens.
jPrc an d PosL-O perative C are •

C ataract im pact on visual fu n ction and patient sym ptom s
Cataracts cause blurred vision, glare, reduced contrast, and refractive error
shifts, all of which result in difficulty with activities of daily living such as
reading, recognizing faces, watching television, and driving.
Testing
• P oten tial acuity m eter (P A M ) testing can help determine how much
the lenticular changes are impacting acuity in order to better predict
post-op visual acuity.
• B rightness A cu ity T ester (B A T ) is used to assess glare disability.
• A x ia l len gth is determined by an A-scan or 10L Master (uses partial

coherence interferometry); axial length and keratometry measurements
are used to calculate the appropriate IOL power based on the desired
final refractive error.
• B -scan ultrasound helps to determine if posterior segment abnormali

ties are present when cataracts (or other opacities) are so dense that the
fundus cannot be viewed.
The average axial len gth is 24 mm; a 1 mm error in axial length

measurement corresponds to a 3D error in the calculated IOL
power (102).
Special C on siderations
Special considerations unique to each patient should be considered prior to

surgery:

• If the cataract is m on ocu lar, before referring for surgery consider the
age of the patient and whether lens removal would impact accommodative
status (for pre-presbyopes) and post-operative refraction.
• If the patient is m on ocu la r and having surgery in the good eye, con
sider the severity of the cataract and discuss the risk/benefit ratio with
the patient.
• Each patient should have a careful pre-op era tiv e evaluation by their
medical doctor prior to cataract surgery; medications should also be re
viewed carefully - anticoagulants (e.g. coumadin), alph a-block ers
(e.g. Flomax), and prostaglandins are of particular concern.
F lom a x is an alpha-blocker that can cause flop p y iris syn drom e,

which is characterized by poor pre-operative pupil dilation, iris
billowing and prolapse, and progressive intraoperative miosis. This
occurs in up to 90% of patients who are currently on the medication
or have been at any time in the past (21).
• O cu lar co n d itio n s should be considered prior to referral, including his

tory o f acute or chronic uveitis, severe blepharitis, Fuchs’ endothelial
dystrophy (e.g. bullous keratopathy), and pseudoexfoliation (risk of poor
dilation and/or lens subluxation).
[Types of C a ta ra c t S urgery : ; ^
1. Intracapsular cataract e x tra ction (IC C E )
• The entire lens and capsule is removed, requiring a large incision.
• Resulted in aphakia and the need for “cataract glasses” (approximately

+12D ), which caused distortion of images. Secondary IOLs could be
implanted with a second surgery.•
• ICCE was associated with a higher risk of retinal detachment (R,D) (49).
It also required a surgical peripheral iridotomy (PI) to prevent vitreous
prolapse and pupillary block.
• This surgery has been replaced by newer and safer techniques.
2. E xtracapsu lar cataract ex tra ction (E C C E )
• The lens is removed but the lens capsule remains. The incision must still
be large because the lens is removed as a whole (9-11 mm) (14). An IOL
is typically inserted into the capsule.

492 10.8. LENS/CA TARA CT/IOL P RE-AND POST-OPERATIVE CARE
3. P h acoem u lsification
• A form of ECGE where the lens is fragmented with ultrasound before

removal. Allows for a much smaller incision (1-3 mm) that rarely requires
sutures, as the aqueous will push against the corneal flap to close it.
• Typically utilizes a clear corneal incision for lens removal.
4. F em tosecon d Laser
• A fairly new addition to the traditional cataract surgery performed by

some surgeons. It is used for corneal incisions (including relaxing incisions
for astigmatism), anterior capsulorhexis, and lens fragmentation (makes
phacoemulsification easier).
T ypes of In trao c u la r Im p la n ts '

• Types: Toric (u pto4D ), aspheric, multifocal/bifocal (reSTOR®, Technis®,
and reZOOM ©), accommodating (Crystalens®, Trulign©), monovision
design.
• Design: Foldable, rigid, or injectible.
• Placement: Anterior chamber, iris fixed, ciliary sulcus fixed, scleral fixed,
or in the capsular bag (most common).
P ost-O p era tiv e C om p lica tion s
About 95% o f the time there are no complications (77).
1. Striate keratopathy: Post-op corneal edema and folds in Descemet’s

membrane; typically resolves without treatment within days.
2. A cu te p ost-op era tiv e bacterial en dop h th alm itis: Rare complication

that occurs in 1/1000 cases; however, even with early treatment, 50% of eyes
become blind (52).
• Symptoms occur within days (2-4) of the procedure and include progres
sively decreased vision, redness, and increasing eye pain.•
• 70% of cases are gram (+ ) bacteria, including Staph epiderm idis (most
common) and Staph aureus. The normal bacterial flora from the eyelids
and conjunctiva are the most likely sources of infection.

• Signs include a significant anterior chamber reaction (more cells than typ
ically present post-operatively) that can be accompanied by hypopyon,
vitritis, chemosis, eyelid edema, fibrous exudate, mucous discharge, corneal
edema, and a reduced red reflex.
3. D elayed p o s t-o p e ra tiv e bacterial endophthalm itis: Symptoms oc

cur within a week to one month after the procedure. Vision loss is insidious and
pain gradually worsens. Fungal p o s t-o p endophthalm itis is also commonly
a delayed complication.
-T ox ic-a n t e r-io ivseg'm entsyndr o m e (TA-S S) r— A-st e lu lein flam m ator y

rea ctio n that leads to toxic damage to anterior segment structures. Typi
cally a result of chemical exposure during surgery (e.g. denatured viscoelastic,
preservatives, bacterial endotoxins, cleaners, etc.)
• Typically presents 12-48 hours post-operatively with decreased vision, no

to mild pain, diffuse limbus to limbus corneal edema, hypopyon, fibrous
membrane, no vitritis (or mild spillover), and increased IOP.
• MUST rule out infectious endophthalmitis!
5. Lens su blu xation : Rare in cataract surgery. Caused by pupillary capture

and poor capsular support, findings that are common in PXF or Marfan’s
syndrome.
• Trauma is the most common cause of lens subluxation.
• Systemic conditions that can cause lens subluxation include Marfan’s syn
drome, Ehlers-Danlos syndrome, Weill-Marchesani syndrome, and homo-
cystinuria (35) (52).
E h lers-D an los sy n d rom e and O steogenesis im p erfecta cause

similar ocular effects including keratoconus, blue sclera, and nrega-
locornea; Ehlers-Danlos differs in that it can also cause lens sub
luxation (102). In M a rfa n ’s Syndrom e, retinal detachments are
common and are the most serious ocular complication (52).

494 10.8. LENS/CATARACT/IOL PRE-AND POST-OPERATIVE CARE
6. P o sterior Capsular O pacification (P C O ): PCO is the most com

mon post-operative complication following cataract surgery (41-51% of pa
tients) (102). It is also referred to as a secondary cataract,
• Equatorial epithelial cells migrate to and proliferate over the posterior

capsule, resulting in opacification most commonly within 2-6 months after
surgery.
• E lschnig pearls are a type of PCO that is most common in children

who undergo cataract extraction.
7. C y sto id M acular E dem a (C M E ): One of the most common reasons

for decreased acuity after cataract surgery. The surgical trauma results in
inflammation; with the disruption of the lens/vitreous interface, inflammatory
cells have an easier time getting to the posterior pole to cause inflammation.
• The most common cause of CME is post-cataract surgery (referred to

as Irvine-G ass S yndrom e). Remember that CME develops within the
outer plexiform layer (Henle’s fiber layer).
• Peak incidence is within 6-10 weeks following surgery (33), CME is com
mon on fluorescein angiogram (FA), but only about 1.5% of patients have
significant and symptomatic CME with modern surgical procedures (36).
FA will show hyperfluorescent leakage within the macula (petaloid pat
tern) and around the optic nerve.
• Most cases resolve with treatment within 6 months (78).
C M E can occur after intraocular surgery or in diabetic retinopa

thy, retinal vein occlusions, uveitis, retinitis pigmentosa, ARMD,
ERM, retinal vasculitis (e.g. sarcoidosis, Behcet’s syndrome), and
Coats’ disease.
S. R etin a l D etachm ent: Uncommon complication (1.5-2%) that is most

likely to occur in patients with high myopia, lattice degeneration, a history of
RD in the fellow eye, or a family history of RD.
9. W ou n d Leak: Occurs early in the post-op period and may be initiated

by valsalva maneuver, trauma, or suture failure.•
• Signs include a positiv e Siedel sign, hypotony, iris prolapse (will point
towards the wound), choroidal detachment (fluid accumulates in the supra-
choroidal space), and a shallow anterior chamber.

• Patients with an open wound are at risk for endophthalmitis and should
be promptly treated.
10. S u p ra ch oroida l h em orrh age: Rare complication characterized by the

accumulation of blood between the choroid and sclera during surgery. This
is a devastating complication that is more common in the elderly and has an
unknown etiology.
11. E levated IO P : May be caused by retained viscoelastic, steroid response,

inflammatory debris or red blood cells clogging the trabecular meshwork, pupil-•
Iarv block, or retained lens material,
12. C orn ea l edem a: Typically an early complication charaterized by folds

in Descemet’s membrane, bullae, and/or microcysts that slowly resolve (14).
Potential causes include:
• High IOP - can cause microcystic edema.
• Low IOP - can cause Descemet's folds.
• Surgical trauma - causes edema due to the shock waves from phacoemul
sification. This is less common with the intraoperative use of viscoelastic
material.
• Pre-existing corneal disease predisposes patients to corneal edema.
• Bullous keratopathy (occurs later in the post-op period) is more common

in aphakia and with anterior chamber IOLs.
• Haptic rubbing on the endothelium can cause damage and edema.
13. D ip lop ia : Occurs in approximately 3% of cases. May be secondary to a

decompensating pre-existing strabismus, EOM restriction/paresis, monocular
diplopia, central fusion disruption, or idiopathic (74).
14. P to sis: Permanent ptosis can be due to levator dehiscence (damage) by

the lid speculum. A temporary ptosis may be due to post-operative swelling
or use of local anesthesia.
15. U veitis, glau com a, h yph em a sy n d rom e (U G H ): Most likely due

to an ill-fitting anterior chamber IOL that rubs on the iris, causing hyphema
and uveitis. The accumulation of red and white blood cells in the TM cause
an elevated IOP. Very uncommon complication now that AC-IOLs are less
commonly used.
Copyright; 2014 by KMK Educational Services, LLC

496 10.9. FUNDOSCOPY UTILIZING AUXILIARY LENSES
16. In d u ced corneal astigm atism : May be pre-existing or secondary to

sutures or a wound leak.
17, Iritis: Secondary to surgical trauma, retained lens material (will appear
as fluffy, white material behind the iris), endophthalmitis, or occurs in an eye
that is predisposed to uveitis and is then aggravated again by surgery (14).
- SECTION 10.9 ---------------------------------------------------------------------------------------------------
Fundoscopy U tilizing A uxiliary Lenses •
The following is a brief summary of key points regarding auxiliary lenses:
H ru by Lens
• Indications: Noncontact examination of the optic disc, macula, poste

rior pole, and central vitreous.
• In terp reta tion : Provides a stereoscopic, erect, and magnified image.
T h ree-M irror Lens
• Indications: Examination of the retina extending from the optic disc

to the ora serrata. Performed in patients with peripheral retinal con
cerns such as peripheral vascular disease (e.g. neovascularization), his
tory of blunt trauma, and those at risk or with symptoms of a retinal
break/ detachment.
• In terpretation: Provides a stereoscopic, reversed (anterior-posterior di

rection), and magnified image of the retina 180 degrees away from the
position of the mirror. Mirrors include:
— T rapezoidal m irror (angled at 73 degrees from the corneal plane)

- used to evaluate the equator region.
— Square m irror (angled at 67 degrees from the corneal plane) - used
to evaluate the area between anterior equator and ora serrata.
— B ullet m irror (angled at 59 degrees from the corneal plane) - used
to evaluate the anterior chamber angle and the ora serrata.
3-mirror views are not displaced laterally, as with BIO evaluation.

7 8 /9 0 D lens
• In d ica tion s: Routine posterior segment evaluations. Easier to use than

the Hruby lens and the three-mirror. Image magnification and field of
view are directly proportional to the pupil diameter and the dioptric
power of the lens (18).
• In terp reta tion : Provides a real, inverted, and reversed magnified image.
E)espite~aii~inverted~an<:Rreversed image w itlr78/90DNenses and"

BIO lens evaluation, the quadrant you are examining is the true
quadrant the image is located in.•
B in o cu la r In d irect O p h th a lm oscop y (B IO )
• In d ica tion s: Routine comprehensive evaluation and similar indications

as three-mirror evaluation.
• In terp reta tion : Provides a real image that is magnified, reversed left
to right, inverted top to bottom, and located between the examiner and
the condensing lens.
- When performing BIO, position yourself 180 degrees away from the
fundus area that you wish to assess and instruct the patient to look
toward the area that you wish to view.
— Move as a unit (you and the lens) towards the structure you are
attempting to view. For example, if you are attempting to view a
retinal hemorrhage that is displaced toward the right portion of your
condensing lens, you would pivot yourself and the lens to the right
to center the image in your lens.
The green filter (red-free) allows easier differentiation of the

nerve fiber layer (e.g. NFL bundle defects), choroidal lesions (e.g.
choroidal nevus), and retinal vasculature (e.g. small hemorrhages).
A red-free filter will cause a choroidal nevus to become more diffi
cult to visualize or disappear.

498 10.10. VITREOUS
Scleral D epression
• In dication s: Similar indications as three-mirror evaluation. Scleral de

pression allows oblique viewing of retinal tissue, which increases contrast
and allows easier identification of abnormalities (18).
• Scleral depression should NOT be performed on patients with recent in

traocular surgery or patients with a penetrating ocular injury, hyphema,
or ruptured globe (18).
- SECTION 10.10 --------------------------------------------------------------------------------------------------
V itreous •
A ste ro id H yalosis
• Epidemiology/History: Associated with aging; occurs in 0.5% of the pop

ulation over 60 years of age (35).
• Symptoms: Asymptomatic - does not interfere with vision or cause floaters.
• Signs: Numerous small, yellow-white, refractile particles (calcium -phosphate

soaps) attached to collagen fibrils in an essentially normal vitreous; uni
lateral in 75% of cases (35).
Synchysis Scintillans
• Pathophysiology/Diagnosis: Rare condition that occurs after chronic uveitis,

vitreous hemorrhage, and/or trauma (35).
• Signs: Unilateral, golden-brown, refractile ch olesterol crystals that are

freely mobile in the vitreous cavity (often settle interiorly) (35).
P osterior V itreou s D etachm ent (P V D )
• Epidemiology/History: More common in females. Prevalence approxi

mates age after 50 years old (e.g. 50% by age 50, 65% by age 65) (35).
- PVDs occur an average of 20 years earlier in myopes than in em-

metropes (78).
— Other risk factors include diabetes, intraocular surgery, intraocular
inflammation, vitreous hemorrhage, and trauma.
• Pathophysiology/Diagnosis: The hyaluronic acid-collagen complex in the

vitreous is disrupted with age, causing the collagen to clump up in bun
dles. Liberated collagen can contract within the complex, causing the pos
terior hyaloid to detach from the retina. Pockets of liquefaction (“sy cere-
sis”) can travel through the hole in the posterior hyaloid and cause a

separation between the vitreous and retina (78), The vitreous detach-
ment can be localized, partial or total.
• Symptoms: Acute onset of floaters (change position with eye movement),

flashes of light (photopsia), and decreased vision.
P h o to p s ia in eyes with acute PVD is thought to result from trac

tion at the sites of vitreoretinal adhesion (52).
• Signs: W eiss ring (black or gray ring-shaped vitreous opacity over the
optic nerve) and anterior displacement of the posterior hyaloid; may also
see vitreous pigment cells (“tobacco dust”/Shafer’s sign) and a vitreous
hemorrhage.
V itre o u s tra ctio n during a PVD can result in epiretinal mem

branes, macular holes, vitreous and retinal hemorrhages, and reti
nal breaks. 10 — 15% of patients with an acute symptomatic PVD
will have a retinal break (35); this risk increases to 70% if a vitreous
hemorrhage is present. Retinal pigment epithelium can be released
into the vitreous (Sh afer’s sign) after a retinal tear, which can
aid in the diagnosis.
P r e r e tin a l/V itr e o u s H em orrh age
• Epidemiology/History: Ask about trauma and pertinent ocular and sys

temic diseases, especially diabetes mellitus and hypertension.
• Pathophysiology/Diagnosis: Preretinal and vitreous hemorrhages result

from trauma or from conditions that cause retinal neovascularization.
These include the following (non-exhaustive list):
— D ia b e tic retin opath y, retinal vein occlusion, sickle cell retinopa

thy, retinopathy of prematurity (ROP), and ocular ischemic syn
drome.
— In each of these cases, the neovascularization is preretinal in loca
tion and the newly formed vessels lack endothelial tigh t ju n c
tions. The location (preretinal) and strength (leaky) of these vessels
creates a situation where vitreous traction can cause shearing of the
vessel, resulting in hemorrhage formation.

500 10.11. RETIN A/CHOROID
• Symptoms vary depending on the type of hemorrhage:
— A pre-retinal hemorrhage usually does not cause symptoms unless it

involves part of the macula (results in sudden loss of vision or part
of the visual field).
— A vitreous hemorrhage usually causes sudden, painless vision loss
and/or black spots that can have corresponding flashing lights.
• Signs vary depending on the type of hemorrhage:
— P reretinal h em orrh age - located between the retina and an intact

posterior vitreous face; appears very red and often has a keel shape.
— V itreou s hem orrhage - located within the vitreous (anterior to
the posterior vitreous face). A mild vitreous hemorrhage will be
characterized by blood that obscures only part of the fundus. Se
vere hemorrhages will completely obscure the view of the fundus.
Chronic cases will appear yellow.
— A B -scan is indicated if the fundus cannot be viewed through the
vitreous hemorrhage.
D ia b e tic retin opath y is the most common cause of a sponta

neous vitreous hemorrhage (31 — 54% of cases) (84).
I - SECTION 10.11
R e tin a / C horoid
jRetinaJ Vascular Disease ; / A A'A A ' ' . AyA: y •• . A y ./ A
C entral R etin al V ein O cclu sion (C R V O )
• Epidemiology/History: Prevalence of 0.1 — 0.4% (17). CRVOs are the

3rd most common vascular cause of vision loss (diabetic retinopathy is
the most common) (80). An estimated 7% of patients will haye a CRVO
in the fellow eye (90).
- R isk factors for CRVO include HTN (61%), diabetes, cardiovascu

lar disease, and open-angle glaucoma (non-exhaustive list) (78).

Glaucoma is the ocular disease that is most commonly associ

ated with CRVOs; up to 40 — 60% of patients with CRVO have
POAG (33) (45).
— Consider the following etiologies in young patients with a CRVO or

BRVO: oral con tra cep tiv e pills, protein S/protein C/antithrombin
III deficiency, factor XII deficiency, antiphospholipid antibody syn
drome, collagen vascular disease, and AIDS (35).
Pathophysiology/DiagnosisTCRVOs resultl'rom compression of an artery

on a vein; this leads to turbulent blood flow, venous vessel wall damage,
and th rom b u s form ation. CRVOs are usually caused by a thrombus
at or near the lamina cribosa (57).
• Symptoms: Characterized by sudden, unilateral, painless vision loss in an

elderly patient (90% of patients with CRVO are > than 50 years old) (35).
• Signs: Thrombus formation leads to ischemia and release of V E G F

with characteristic retinal signs including retinal hemorrhages in all 4
quadrants, collaterals, dilated tortuous retinal veins, cotton-wool spots
(CWS), and optic disc edema.
Recall that veins drain blood from the retina, thus vein occlusions
present with intraretinal hemorrhages. C R V O s result in hemor
rhages in all four quadrants, while B R V O s will have hemorrhages
in the area of distribution of the occluded vessel.
C ollatera l veins become visible over several weeks to months;

they are often on the disc and permit blood flow between the reti
nal and choroidal circulations, helping to accelerate drainage of
excessive fluid (retinal edema) into the choroidal circulation after
a CRVO (78).
• Vision threatening complications include m acular disease and compli

cations from neovascularization. VEGF stimulates neovascularization
of the posterior and anterior segment and has been proven to cause cap
illary leakage leading to macular edema (57).

502 10.11. RETINA/CHOROID
1. M acu lar D isease - macular ischemia) macular edema, and intra-

macular hemes.
2. N eovascularization - neovascular glaucom a, preretinal/vitreous
hemorrhage, and tractional retinal detachment.
• N eovascular glaucom a is a major concern in patients with CRVOs and

is most likely to develop within the first 3 months of diagnosis (“90-day
glaucoma”). 60% of ischemic cases develop iris neovascularization, and
up to 33% develop neovascular glaucoma (102). 6% of non-ischemic cases
develop rubeosis or angle neovascularization (78).
M acular ed em a is the leading cause of vision loss in both ischemic

and non-ischemic CRVOs (57).
• CRVOs can be grouped into n on -isch em ic (67%) and ischem ic cate

gories (35).
— Ischemic CRVO is defined as 10 disc diam eters or more of non

perfusion on fluorescein angiography. 90% of cases present with
20/200 vision or worse, and the prognosis is poor (final VA CF or
worse) (17) (84). 16% of nonischemic cases progress to ischemic
CRVOs.
B ranch R etin a l Vein O cclu sion (B R V O )
• Epidemiology/History: BRVOs are by far the most common retinal vas

cular occlusive disease; patients have a similar health history as patients
with CRVOs.
- R isk factors for BRVO include HTN (50 — 70%), cardiovascular

disease, increased body mass index at 20 years, and open-angle glau
coma (non-exhaustive list) (35) (78).•
• Pathophysiology/Diagnosis: BRVOs are usually caused-by a th rom bu s

after compression of an artery on a vein at an arteriovenous (AV) cross
ing. 60% occur at an AV crossing within the s u p e rio r/te m p o ra l quad
rant (78).

B R V O s that do not occur at an AV crossing should be evaluated

for vasculitis (33) (78). Remember that retinal arteries and veins
share a common adventitia at arteriovenous crossings; this allows
a thickened artery to compress the vein (52).
• Symptoms: BRVOs are characterized by sudden, unilateral, painless vi

sual field loss, blurred vision or no symptoms (if the macula is spared).
•_Signs: Retinal signs occur in the area of distribution of the occluded vessel•
and include dilated torluons_mtinal_veins,_cotton=wool-sp ots^Gollat,eral—
vessels, and intraretinal hemorrhages.
• Vision threatening complications include macular disease and compli

cations from neovascularization:
1. Macular disease - macular ischemia, macular edema, and intramac-

ular hemorrhage.
2. Neovascularization complications - preretinal/vitreous hemorrhage.
Central Retinal Artery Occlusion (CR AO )
• Epidemiology/History: Ask about transient loss of vision (amaurosis

fugax). Commonly occurs in elderly patients. Patients have a 10% risk
of a CRAO occurring in the fellow eye (34).
— Risk factors for CRAO include HTN (67%), diabetes mellitus

(33%), carotid occlusive disease (25%), and cardiac valve disease
(25%) (non-exhaustive list) (35).
— Consider the following etiologies in young patients with CRAOs: IV
drug usage and birth control.
• Pathophysiology/Diagnosis: CRAOs most commonly arise from heart

and/or carotid artery emboli:
1. Calcific emboli - large, dangerous emboli from calcified heart valves

often located in the CRA near the optic nerve.
2. Carotid emboli - smaller cholesterol plaques (Hollenhorst. plaques).
Patients with retinal emboli should be evaluated for underlying

carotid artery and cardiac disease with a carotid doppler and
EKG/Echo, respectively.

504 10,11. RETINA/CHOROID
• Although retinal em b oli are by far the most common etiology for ar
terial occlusions, there are several other culprits to consider, including
giant cell arteritis (G C A ), acute elevation in IO P , collagen vas
cular diseases, intravenous (IV) drug use, oral contraceptives, siclde-cell
disease, and syphilis (non-exhaustive list) (78).
* Symptoms: Acute, profound vision loss (often 20/400 or worse), unless

a cilioretinal artery is present to spare the macula. If visual acuity is
LP or worse, strongly consider an ophthalmic artery occlusion (33).
A cilioretinal artery branches from the SPCAs of the choroid and

allows the macula to remain functional in a CRAO. It is present in
15 — 30% of patients.
• Signs: Superficial whitening of the inner retinal layers (returns to the

normal color after perfusion is restored but does not regain function!),
narrowed arterial vasculature, a ch erry red sp ot in the foveola (due
to visibility of the underlying choroid), and an afferent pupillary defect
(APD) (secondary to optic disc pallor from orthograde degeneration of
RGC axons). Hollenhorst plaques or other emboli are also noted in 20 —
40% of cases (90).
Neovascular glaucoma is rare in arterial occlusions - only 5%

of patients develop iris neovascularization and neovascular glau
coma (102).
B ranch R etin a l A rtery O cclu sion (B R A O )
• Epidemiology/History: Similar risk factors as CRAOs.
• Pathophysiology/Diagnosis: 90% of cases are caused by retinal emboli

(H ollen h orst plaques (most common), calcium, fibrin, and platelet
emboli) (34) (35).•
• Symptoms: Often asymptomatic; may complain of a visual field defect

or sudden unilateral painless vision loss if the area of occlusion is close
to or involving the macula.

• Signs: Superficial whitening of the retina in the distribution of the af

fected vessel (90% o f cases involve temporal vessels) due retinal infarction
and edema; Hollenhorst plaques or other emboli are found within the area
of occlusion in 62% of cases (35). The edema and retinal whitening even
tually resolves within weeks, but the retinal tissue remains non-functional
and the patient will have a perm anent visual field defect.
Recall that arteries supply blood to the retina; thus, arterial occlu
sions present with an ischemic (white) retina; C R A O findings will
classically reveal infarction in all four quadrants, while a B R A O
'wilThave infarction in the area of distribution of the occluded ves
sel.•
M y e lin a te d nerve fibers are congenital, benign, white patches in

the superficial retina with feathery edges that represent abnormal
myelination of ganglion cell axons anterior to the lamina cribrosa.
Myelination follows the distribution of the axons, can obscure the
retinal vessels, and is typically located near the optic nerve. Dif
ferential diagnoses include B R A O and CWS (35).
D ia b e tic R e tin o p a th y (D R )
• Indications for a diabetic retinal examination include the following:
1. Initial examination should be done w ithin 3-5 years after diagnosis

of type 1 diabetes, and at the tim e of diagnosis for type 2 diabetes.
2. For patients with no diabetic retinopathy, repeat examinations every
year.
3. For patients with mild to moderate retinopathy, repeat examinations
every 6-12 months.
4. For patients with severe NPDR or PDR, repeat examinations every
2-4 months (20).
• Epidemiology/History: DR is the leading cause of new cases of blindness

in the United States for adults ages 20-74 (33).
— The most important risk factor the development of DR in patients

with IDDM is the du ration o f disease.

506 10.11. RETINA/GHOROID
— Patients who are diagnosed with diabetes before age 30 have a 2%

risk per year for developing DR,; after 7 years, 50% will have DR,,
and after 25 years, 90% will have DR (78).
• Pathophysiology/Diagnosis: DR, occurs because of a loss of pericytes and

damage to the retinal capillary basement membranes, resulting in a break
down of the blood-retinal barrier. DR can be divided into Nonprolifera
tive Diabetic Retinopathy (NPDR or background DR) and Proliferative
Diabetic Retinopathy (PDR):
1. N P D R
Can be divided into the following categories (1):
• M ild - 5% risk of progression to PDR.
• M o d e ra te - 15% risk of progression to PDR.
• Severe - 52% risk of progression to PDR.
The diagnosis of severe NPDR is made when the patient meets one of the three
criteria of the 4-2-1 rule:
1. Severe retinal hemorrhages in 4 quadrants.
2. Venous beading in 2 quadrants.
3. IRMA in 1 quadrant.
V ery severe N P D R - 75% risk of progression to PDR. Diagnosis of very

severe NPDR is made when the patient meets two or more of the criteria
within the 4-2-1 rule.
2. P D R
PDR occurs in 5% of patients with DR and is diagnosed based on the presence

of neovascularization (78). If left untreated, PDR can progress to devastat
ing visual outcomes (see below for threats to vision with neovascularization).
Patients with PDR who are most at risk for vision loss have H igh R isk C har
acteristics (H R C s), which are defined as any of the following:
1. Neovascularization of the Disc (NVD) greater than 1/4 disc diameter

(DD) within 1DD of the optic nerve.
2. Any NVD or Neovascularization Elsewhere (NVE) with an associated

vitreous or preretinal hemorrhage.

• Symptoms: Patients are often asymptomatic or may experience blurred

vision and metamorphopsia.
• Signs: Although there are numerous signs of DR, the most important
threats to vision include m acular disease and neovascularization.
1. M A C U L A R D IS E A S E
Threats to vision from macular disease include the following:
1. M a cu la r ischem ia: May look normal or thickened; a fluorescein an-

_____ giogram—can-b-e-used—to-differentiate-maeulai—isehemia—from—maeular
edema (macular ischemia will appear as an enlarged foveal avascular zone
(hypofluorescent)).
2. M a cu la r edem a : The most common cause of legal blindness in DR. It

can occur at any stage of diabetic retinopathy. C linically significant
m acular ed em a (C S M E ) is based on the following three criteria (based
on the presence of retinal thickening within the fovea):
a) Retinal thickening within 500 um (1/3 DD) of the foveal center.

b) Hard exudates within 500 um of the foveal center with adjacent
retinal thickening.
c) Retinal thickening of at least 1 DD within 1 DD of the foveal center.
The patient only needs to have one of the three criteria to be diagnosed
with C S M E .
2. N E O V A S C U L A R IZ A T IO N
Threats to vision from neovascularization include the following:
1. P re r e tin a l/v itr e o u s hem orrhage (most common).
2. N eovascu lar glau com a.
3. T ra ction a l retin al detachm ent,
H y p erten siv e R e tin o p a th y
• Epidemiology/History: 60 million Americans over 18 years of age have

HTN; more prevalent in African Americans (78). Essential HTN accounts
for 95% of all cases of HTN and is defined as elevated blood pressure with
no known cause (3).

508 10.11. RETINA/GHOROID
• Pathophysiology/Diagnosis: Recall that retinal arteries are able to au-

toregulate their vessel diameter based on changes in blood pressure; au
toregulation is altered at extremely high or chronically elevated systolic
pressures and retinopathy results. Systemic blood pressure must typically
be at least 140/110 for the latter stages of HR to occur (84).
• Symptoms: Commonly asymptomatic. Vision is typically unaffected un

less vascular changes cause macular edema (macular star), papilledema,
a serous retinal detachment, or a vein occlusion.
• Signs: Typically bilateral but asymmetric. Categorized based on the

Keith-Wagener-Barlcer classification system (1-4 with 4 being worst):
1. Stage 1: Mild to moderate diffuse narrowing of the retinal arteries

(but no focal constriction).
2. Stage 2: Stage 1 plus focal constriction of the retinal vasculature
(arteriovenous nicking) and exaggeration of the arterial light reflex.
3. Stage 3: Stage 2 plus retinal hemorrhages, cotton wool spots, hard
exudates (likely in a star configuration within the OPL radiating
away from the fovea), and retinal edema (78).
4. Stage 4: Stage 3 plus pap illedem a (m alignant H T N ). Patients
with malignant hypertension must be hospitalized immediately due
to a high risk of stroke! BP at this stage is usually >220/120.
• HTN is associated with numerous secon d ary con d ition s that can lead
to vision loss, including vascular occlusions, retinal macroaneurysm, NAION,
ocular motor nerve palsies, and worsening of diabetes (34).
Elschnig sp ots are choroidal infarcts that occur in severe hyper

tensive retinopathy (102).
R etin a l A rte ry M acroan eu rysm
• Epidemiology/History: More common in elderly women (7th decade)

with HTN or atherosclerosis.
• Symptoms: Usually asymptomatic, but can have gradual vision loss from
macular edema or sudden vision loss from a vitreous hemorrhage.•
• Signs: Unilateral focal area of dilation in a retinal artery (100-250 um

in diameter) with multi-level hemorrhages (subretinal, intraretinal, pre-
retinal and/or vitreous hemorrhage) from a ru ptu red aneurysm with
surrounding circinate exudates; often located at an arteriovenous cross
ing (35) (90).

V en ou s Stasis R e tin o p a th y /O cu la r Ischem ic Syndrom e
• Epidemiology/History: More common in men (2:1) ages 50-80 (33).
• Pathophysiology/Diagnosis: Caused by occlusion of the internal carotid

and/or ophthalmic artery (less common), usually secondary to ath eroscle
rosis; may also occur as a result of giant cell arteritis.
• Symptoms: Common symptoms include gradual vision loss (90%), dull

periorbital pain or headache (40%), and amaurosis fugax (35).
• Signs: U nilateral (80%) dot/blot hemorrhages of the m id p erip h eral

fundus, dilated non-tortuous retinal veins, narrowed retinal arteries, and
______pQSsibIe_neavascularization-of-the-disG-and-/or-aEterior-segment-(6-7-%rof
patients with OIS have NVI/NVA at the time of diagnosis) (90).
— If a patient has these retinal findings and carotid artery obstruction,

but no anterior segment signs, the condition is called venous stasis
retin opath y.
— The presence of both posterior and anterior segment signs and symp
toms is referred to as ocu lar ischem ic syn drom e (OIS) (70). OIS
is most common in male (2:1) patients 50-70 years old (mean = 65
years) (35).
— OIS is commonly associated with systemic HTN, diabetes mellitus
and cardiac disease; the latter is the most common cause of a 40%
5-yr mortality rate in these patients (84).
A m a u rosis fu gax is transient monocular vision loss that typically

lasts seconds to minutes; vision returns to normal after the ischemic
event. A carotid artery embolus is the most common cause.
H y p e rv isco sity R e tin o p a th y
• Pathophysiology/Diagnosis: Hyperviscosity is an increase in resistance to

blood flow secondary to elevated levels of plasma proteins, red blood cells,
and/or white blood cells, resulting in impaired circulation of blood and
oxygen through the microvasculature. As blood flow decreases, blood
vessel walls become damaged, causing leakage of fluid and retinal is
chemia (90).
— The most common cause of hyperviscosity retinopathy is h yper-

globu lin em ia , a condition found in Waldenstrom’s macroglobu-
linemia, multiple myeloma, serum positive rheumatoid arthritis, sys
temic lupus erythematous, and HIV infection (38).

• Signs: Retinal venous dilation, retinal hemorrhages, cotton wool spots,

and exudates (90), Central retinal vein occlusion may also occur and is
bilateral in 10% of patients (38).
H IV Retinopathy
• The most common ocular manifestation of IIIV/AIDS. Signs include cot

ton wool spots and retinal hemorrhages, similar in appearance to DR and
early CMV retinitis.
• Patients are typically asymptomatic. The condition is non-infectious in

origin (33).
Interferon Retinopathy
• Patients on interferon therapy can develop retinal findings similar to di

abetic retinopathy, including cotton wool spots and retinal hemorrhages
within the posterior pole.
• Retinopathy typically occurs within 3-5 months after interferon is started,

and tends to resolve without treatment after interferon has been discon
tinued (76).
• Patients on interferon therapy without retinopathy should be followed

every 4-6 months; if retinopathy is present, follow ups should occur more
frequently.
Talc Retinopathy
• Presents bilaterally in IV drug users who use talc as a filler.
• The talc gets caught in the retinal capillaries and will appear as multiple,
yellow, retractile deposits that tend to be clustered near the macula.
• The talc may cause capillary occlusion and retinal ischemia.
Vascular Sheathing/Periphlebitis
• An inflammatory condition characterized by exudates around the ves

sels (seen as white cuffing of the vessels). Retinal edema, ischemia, and
hemorrhaging may also occur. Vessel walls will stain on FA.
• The most common causes include syphilis, sarcoidosis (known as candle-

wax drippings), pars planitis, and sickle cell disease (33).•
• Diagnostic systemic lab testing should be done based on the review of

systems and case history to determine the systemic cause of the vascular
sheathing.

Id iop a th ic J u x ta fov eola r R etin al Telangiectasis
• Pathophysiology/Diagnosis: Abnormal perifoveal capillaries present within

the juxtafoveal region (1-199 urn from the center of the fovea) (35). IJXT
is divided into three categories (35):
1. U nilateral con g en ital form - occurs in men in the 4th decade;

results in 20/25 - 20/40 acuity.
2. U n ilateral id io p a th ic form - occurs in middle-aged men; results
in 20/25 or better acuity.
3. B ila tera l acq u ired form - equal sex distribution in the 5th or 6th•
decades. Poor visual prognosis.____________________________________
• Symptoms: Decreased vision.
• Signs: Right-angle venules and dilated tortuous vessels, hemes, varying

degrees o f exudate (moderate to none at all) within or nearby the fovea,
macular edema, and/or CNVM.
C o a ts f D isease
• Epidemiology/History: Peak incidence in males (85%) less than 20 years

old; 2/3 of cases present prior to age 10 (35). Progression is more rapid
in children under 4 years of age, simulating retinoblastoma (78).
• Pathophysiology/Diagnosis: Idiopathic peripheral vascular disease. If

left untreated, Coats’ disease will gradually progress to a total exudative
retina] detachment.
• Symptoms: Decreased vision (43%), strabismus (23%), leukocoria (20%) (90).
• Signs: Unilateral (80 — 95%), telangiectatic dilated vessels that display

a characteristic “lightbulb” appearance (35). Progression of the disease
can lead to m arked hard exudates (classic for Coats’), intraretinal
hemorrhages, exudative retinal detachment, and neovascular glaucoma
(results in a red, painful, and potentially blind eye).
R e tin o p a th y o f prem a tu rity (R etrolen ta l fibroplasia)
• Epidemiology/History: Occurs in premature infants (less than 36 weeks)

or low birth weight infants (2,000 g or less) who have received oxygen
therapy.
• Pathophysiology/Diagnosis: Immature blood vessels vasoconstrict and

stop developing in response to high oxygen concentration, leading to
proliferative retinopathy. Threats to vision include preretinal/vitreous
hemorrhages and tractional retinal detachments (85).

• Signs: Leukocoria, strabismus, vitreoretinal traction, preretin al/ vitreou s

hem orrhages, and traction al retinal detachm ents (85).
L eu k ocoria is a white pupillary reflex that results from fibrovas-

cular scarring secondary to a tractional RD in cases of ROP.
The anterior tem p ora l retin a is the last area of the retina to
achieve mature vascular development during the 9th month of ges
tation. This area is most susceptible to neovascularization and
subsequent tractional retinal detachments in pre-term infants with
ROP,
R etin ob la stom a
• Epidemiology/History: The m ost co m m o n intraocular m alignancy

in children (1/20,000) (34) and the 2nd most common of all age groups
(choroidal melanoma is most common) (52). 95% of cases are diagnosed
by 5 years of age (35). The condition has no gender or race predilection.
• Pathophysiology/Diagnosis: Retinoblastoma is a tumor derived from cells

in the developing retina (retinoblasts) as a result of mutations in the
retinoblastoma (Rb) tumor-suppressor gene (84).
— H eritable retin oblastom a (40%) - All bilateral cases and about

10 —20% of unilateral cases of retinoblastoma are hereditary. How
ever, only 6% of these patients have a positive family history of the
condition because the tumor has such a high spontaneous mutation
rate (52) (78). Bilateral affected patients have a 50% chance of
passing the disease on to each offspring (52) (78).
- N on -h eritable retin ob la stom a (60%) - 85% of all unilateral cases
of retinoblastoma are non-heritable (52). Affected patients will not
pass the disease on to their offspring.
"• Signs/symptoms: L eu k ocoria (50%), strabism us (18%), intraocular

inflammation, and decreased vision (depends on tumor size and loca
tion) (35).

Differentials for leu k ocoria include Coats’ disease, toxocariasis,

retinoblastoma, and R.OP.
C on g en ita l H y p e rtro p h y o f the R etinal P igm en ted E pith eliu m (C H R P E )
• Epidemiology/History: The lesions are thought to be congenital with no

race or sex predilection (84).
• Signs: Benign, pigmented (brown to black), non-progressive lesions with*•

sharp borders and centmLhypopigmenteddacunae.-— — ------------------ ----------
— CHRPEs are typically unilateral and solitary, measuring 1-6 mm in

diameter. Bilateral multifocal (4 or more) CHRPEs are associated
with G a rd n e r’s syn drom e.
C h o ro id a l N evu s
• Epidemiology/History: Common condition that occurs in 1 — 6% of the

population and is most common in whites (84).
• Pathophysiology/Diagnosis: Common benign focal accumulation of melanocytes

within the choroid (3). Choroidal nevi are thought to be present at birth
and are typically non-progressive (52).
~ Growth during puberty is not unusual, but any growth in an adult

should raise concern for conversion to malignant melanoma.
— 10% of suspicious nevi progress to malignant melanoma (35).
• The most significant risk factors for transformation into choroidal melanoma
include:
— “T o Find Small Ocular Melanomas, Use Helpful Hints” (94):

— T = thickness (elevation > 2 mm).
— F = fluid (subretinal).
— S = symptoms (e.g. blurred vision, floaters),
— O = orange pigment (lipofuscin on the surface of the lesion).
— M = margins (irregular borders).
— U H = ultrasonographic hollowness (acoustically hollow with low
internal reflectivity).
— H = halo absence.
— The nevus should also arouse suspicion if it has a large diameter (>
4DD or 6 mm) or if it’s in close proximity to the optic nerve (16) (22).

514 10.11, RETINA/CHOROID
• Signs: The lesion is typically flat or slightly elevated, less than 5 mm in

size (52), and often contains overlying drusen.
C h oroid a l m elanom a is the most common prim ary intraocu

lar m alignancy (35).
Âcquired D isorders w ith P o te n tia l for M aoulopathy

A g e -R e la te d M acular D egen eration (A R M D )
Macular degeneration is a progressive disease of the retinal pigmented epithe

lium (RPE), Bruch’s membrane, and chorio capillar is (35).
• ARMD is most common in patients over the age of 50. It is the 2nd
leading cause of blindness for patients 45-64 years old (diabetes is 1st);
exudative ARMD is the chief cause of vision loss in patients over the age
of 50 (50).
• The Framingham Eye Study revealed that 6.4% of patients 65-74 years
old and 19.7% of patients > 75 years of age had signs of ARMD (63).
• Risk factors include increasing age (especially 75 years and older), eth
nicity (Caucasians most at risk), positive family history, light iris color,
cigarette smoking, hyperopia, HTN, hypercholesterolemia, female gender,
and cardiovascular disease (35).•
• Nutritional factors and light toxicity are believed to play a role in patho
genesis (35).
H y p e ro p ia greater than 0.75D is associated with a 2.5X increased

risk of exudative ARMD (48). 10 — 20% of patients with ARMD
have at least one first-degree family member with vision loss from
ARMD (37) (48). C urrent sm okers are 2.5X more likely to de
velop ARMD and 1.7-2.2X more likely to have a recurrence of
choroidal neovascularization (CNV) compared to those who have
never smoked (15).

1. N on exu d a tiv e A R M D
Accounts for 85 — 90% o f cases of ARMD (35) (52).
• Dry ARM D is characterized by the presence of drusen (hallmark of

ARMD); associated RPE abnormalities (mottling, granularity, focal hy
perpigmentation) may also be present.
• Most patients with dry ARMD do not have severe vision loss; metamor-
phopsia, gradual vision loss (over months to years), and blurred vision
are common complaints.•
• 12%_QLalljdry_ARMD-patients-w-ill-de-velop-sever-e-vision-loss-(-defined-as
loss of >6 lines) (35); the majority of these cases result from g eograp h ic
a troph y.
The M a cu la r P h o to co a g u la tio n S tudy G rou p established four

main risk factors that increase the risk of progression from dry to
wet ARMD (67):
1. M u ltip le soft drusen (especially if confluent)
2. F ocal h yper pigm en t at ion
3. H T N
4. Sm okin g
2. E xu da tive A R M D (w et A R M D )
Accounts for 10 — 15% of cases of ARMD; 88% of legal blindness attributed to

ARMD is caused by the wet form (35) (52).
• Common symptoms of wet ARMD include metamorphopsia, central sco

toma, and rapid vision loss.
• Characterized by drusen that are associated with signs of a choroidal

neovascular membrane (C N V M ) (84). CNVMs can leak 1) blood or
2) plasma into two potential places: 1) sub-RPE space or 2) subretinal
space. This creates four potential presentations of wet ARMD:
1. S u bretin al h em orrh age (blood under the retina).

2. S u b -R P E h em orrh age (blood under the RPE).

3. Subretinal detachm ent (plasma under the retina, also known as

a serous retinal detachm ent).
4. S u b -R P E detachm ent (plasma under the RPE, also known as a
pigm ent epithelial detachm ent (P E D )).
• P E D s can also occur with dry ARMD due to a build-up of confluent soft
drusen on Bruch’s membrane, creating a space between the RPE and the
choroid. This type of sub-RPE detachment is called a dru senoid p ig
m ent epithelial detachm ent. CNVMs can develop over time within
drusenoid PEDs.
• Fluorescein angiography can be used to detail exact areas of leakage and

to classify CNVMs as classic or occult:
— Classic C N V M s are characterized by a well-defined membrane

that fills with dye during the early phases of FA.
— O ccu lt C N V M s are characterized by a poorly-defined membrane
with late appearing and less intense leakage (52) (84).
— Most patients with wet ARMD have a CNVM with a combination of
classic and occult features (84). The term “ pred om in an tly clas
sic” means that over 50% of the entire lesion is composed of a classic
CNVM (35).
The incidence of involvement of the fellow eye with wet ARMD is

estimated to be 28 — 36% during the first 2 years; the annual rate
of bilaterality is about 6 — 12% per year for the next 5 years (48).
The overall 5 year risk ranges from 40 — 85% (84).
C entral Serous C h oroid op a th y (C S R )
• Epidemiology/History: Commonly occurs in young to middle-aged men

(20-50) with a type A personality; associated with stress, pregnancy,
steroid use, hypochondriasis, and HTN (35). A history of similar episodes
is common - recurrences occur in as high as 50% of cases (34) (84).
• Pathophysiology/Diagnosis: Unknown etiology. CSR results in RPE

and/or choroidal dysfunction, with resulting accumulation of submacular
serous fluid.•
• Symptoms: Unilateral sudden onset of blurred vision (20/20 to 20/200);

metamorphopsia and a relative scotoma may also occur. Patients may
have symptoms even if acuity is 20/20.

• Signs: Localized m acular serous detachm ent; 3% of cases will have an

RPE detachment as well (35). Fluorescein angiography (FA) will reveal a
gradual pooling o f fluorescein into a pigment epithelial detachment (90%
of cases) or a “smokestack” appearance (10% of cases) (35). Optical
coherence tomography (OCT) can also be used to diagnose and monitor
the condition (now used more frequently than FA). Patients may also
have a hyperopic shift and loss of the foveal light reflex.
• Patients often have permanent residual RPE changes within the macula
after resolution of the condition. Most patients improve without treat
ment by 1 to 3 m onths; 94% of patients will regain > 20/30 acuity (35).
66% of patients achieve 20/20 acuity (34).•
H istopla sm osis
• Epidemiology/History: Rare in African Americans. Most common in the

Ohio-Mississippi River Valley.
• Pathophysiology/Diagnosis: Infection caused by Histoplasma capsula-

tum, a fungus that grows in soil and material contaminated with bird
o r bat d rop p in gs.
— Recurrences of histoplasmosis (30% of cases) occur through preex

istent histo spots (35) (52).
— If spots are present in the disc or macular area, the chance of a
symptomatic recurrence is approximately 20% over 3 years (78).
• Symptoms: Asymptomatic unless maculopathy develops; the earliest

symptom is metamorphopsia (52).
• Signs: Characterized by ch oroid itis and the clinical triad of peripapil

lary atrophy of the optic nerve, multifocal lesions in the periphery, and
maculopathy (including CNV). The vitreous is always clear in histoplas
mosis (78).
— CNV is a late manifestation; if it occurs, it is most likely to happen

between the ages of 20 and 45 (52).
P a th olog ica l M y o p ia
• Epidemiology/History: Pathological myopia has a genetic predisposition,

with elongation of the globe beginning in early childhood (110). Occurs
in 2% of the U.S. population, most commonly in women during young
adulthood (35) (52) (78). The condition is also referred to as myopic
degeneration (35).

518 10.11. RETINA/CHOR OID
• Pathophysiology/Diagnosis: Defined as a refractive error > -6.00D with

an axial length > 26 mm. Axial lengthening in the antero-posterior di
rection results in scleral thinning and choroidal atrophy (78).
• Symptoms: Patients may be asymptomatic or complain of decreased vi

sion and metamorphopsia.
• Signs: P osterior staphylom a is the hallmark of pathological myopia

and represents posterior bulging of the weakened sclera. Other signs in
clude oblique insertion of the optic disc, Fuch’s spots (focal sub-retinal
hyperpigmentation secondary to scarring or CNVM), lacquer cracks,
macular holes, premature cataracts (NS and especially PSC), extensive
vitreous syneresis, posterior vitreous detachment, peripheral retinal de
generations (e.g. lattice, snail-track, pavingstone), retinal breaks, and
retinal detachments.
• Lacquer cracks: Occur in about 5% of high myopes. They

appear as fine, yellow irregular lines that represent large
breaks in Bruch’s membrane. Choroidal neovascularization
can result and lead to severe vision loss (52). Lacquer cracks
frequently present in young males, and may be one of the
earliest findings in pathological myopia (68).
• P avingstone degeneration: Discrete, circular areas of

yellow-white chorioretinal atrophy in the retinal periphery.
Also referred to as cobblestone degeneration. This condition
is not a predisposing factor for a retinal detachment and has
no clinical importance.
E piretinal M em bran e (E R M )/M a c u la r P ucker
• Epidemiology/History: More common in females (3:2). Prevalence in

creases with age; occurs in 2% of patients older than 50, and 20% of
patients older than 75 (35).
- The condition is often idiopathic but may also be caused by P V D s,

retinal breaks, cataract or other intraocular surgeries, and trauma
(non-exhaustive list).*
* Pathophysiology/Diagnosis: ERMs result from glial cell proliferation

on the internal limiting membrane (ILM). Vitreous traction can result in

residual glial cells from the posterior hyaloid (back of the vitreous) on
the internal limiting membrane, or can cause small pores to develop in
the ILM; this allows intraretinal glial cells to gain access to the anterior
side of the ILM for proliferation (84).
• Symptoms: May be asymptomatic or complain of decreased vision and/or

metamorphopsia.
• Signs: Mild ERMs are characterized by a line, glistening membrane (cello

phane maeulopathy). Advanced ERMs appear as thick, gray-white mem
branes with associated retinal folds (macular pucker).•
Most patients with ERMs have P V D s (84).
M acu lar H ole
• Epidemiology/History: 83% of cases are associated with aging (50-70

years old); w om en (3:1) are more commonly affected (35) (84).
• Pathophysiology/Diagnosis: Results from posterior vitreous traction on

the macula. Most commonly idiopathic (senile), but may also develop
after trauma (10%), surgery, cystoid macular edema (CME), or inflam
mation (34) (35). The condition has a bilateral onset in 25 — 30% of
cases (34). The risk of developing a macular hole in the fellow eye varies
from 5-16% (there is no risk if a PVD has occurred) (90).
• Symptoms: Decreased vision and/or metamorphopsia. Pull-thickness

macular holes are associated with 20/200 or worse acuity.
• Signs: Condition is characterized by a round, red, well-delineated spot

in the macula. Macular holes are classified according to the following
stages:
1. Stage 1 ~ Impending hole with loss of the foveal depression and a

yellow^ sp o t or ring at the fovea.
2. Stage 2 - Round, small, full-thickness hole with a pseudo-operculum.
3. Stage 3 - Large, full-thickness hole with an operculum. Patients
will report a positive W atzk e-A llen sign (34) (35).
4. Stage 4 - Stage 3 plus a PVD.

A positive W atzk e-A llen test is characterized by a complete break

in the middle of a thin line of light projected within the macula (78).
M acu lar P h otostress Test: Determine the patient’s best cor

rected visual acuity (BCVA) prior to starting the test. Hold a
bright light 2 cm from the patient’s eye and instruct the patient to
look at the light for 10 seconds. Measure the time it takes for the
patient to read one line less than his/her BCVA. Normal recovery
time is less than 60 seconds.
C h oroid a l Folds
• Waves within the choroid, Bruch’s membrane, and retinal pigment ep
ithelium (RPE) that develop secondary to mechanical stress on or within
the choroid (2). Characterized by alternating light and dark striations
within the fundus. Macular involvement may lead to symptoms of meta-
morphopsia and reduced visual acuity (2).
• Commonly the result of ocular or systemic conditions that cause mechan

ical stress on the choroid, including choroidal, optic nerve, or orbital tu
mors, posterior scleritis, choroidal detachment, choroidal inflammation,
orbital pseudotumor, thyroid related ophthalmopathy, orbital myositis,
hypotony, and intracranial hypertension.
A lb in ism
• Pathophysiology/Diagnosis: Albinism is a group of disorders charac

terized by a mutation in the genes responsible for the production of
m elanin. Albinism may affect the skin and eyes (oculocutaneous al
binism) or the eyes only (ocular albinism).
• Signs: Characterized by hypopigmentation of the skin and fundus, iris

translucency, foveal hypoplasia, nystagmus, strabismus, and mis-routing
of the temporal optic nerve fibers through the optic chiasm.•
• Symptoms: Photophobia and reduced visual acuity, with severity depen

dent on the degree of iris/fundus hypopigmentation and foveal hypopla
sia (2).

Albinism may be associated with severe systemic conditions includ

ing Hermansky-Pudlak and Cliediak-Higashi syndromes (55).
(H ereditary I ^ n d u s D ystrophies • , . , ' . ;.

R etin itis P igm en tosa (R P )
• Epidemiology/History: RP is the m ost com m on retinal d y strop h y

and can be non-heritable or heritable (most commonly autosomal domi-
------ —nant) po Hmasso ciatlon-withm ncom mom syste mkrdisor ders-f78) pU s he r ’s
sy n d ro m e (5% of RP patients) is the most common associated systemic
condition (35). The average age of diagnosis is 9-19.
U sh er’ s sy n d rom e is an autosomal recessive condition associated

with con g en ita l h earing loss.
• Pat ho physio logy/Diagnosis: RP is a generic term given to a group of

hereditary conditions (29 loci associated with various phenotypes) charac
terized by progressive loss of photoreceptor and RPE function (3) (35) (52).
Although rods and cones are involved, rod damage is more dominant (52).
There is tremendous variability in presentation, which correlates with the
mode of inheritance.
• Symptoms: N igh t blindness (most common symptom) and periph eral

v ision loss (only in dim light in early stages). It often takes years to
decades for symptoms to develop; by 30 years of age, over 75% of patients
are symptomatic (52).
• Signs: Classic clinical triad of retinal b on e-sp icu le p igm en tation

(pigment clumping in the mid-periphery), arteriolar attenuation, and
w axy o p tic disc pallor.
- Other signs include posterior subcapsular cataracts (35 —51%), optic

disc drusen (10%), macular changes (atrophy, CME, ERMs), kera-
toconus, myopia, and progressive contraction of the visual field (e.g.
annular scotomas that may progress to central vision loss in late
stages of RP) (90).•
• ERG can be utilized for diagnosis; in the early stages of RP, the sco to p ic
E R G is redu ced, and the photopic ERG is relatively normal (78).

522 10.11. RETINA/CHOR OID
S ta rg a rd t’s D isease
• Epidemiology/History: Stargardt’s disease is the m ost com m on hered

itary m acular d y strop h y (35). The onset is typically in the first or
second decade of life, most commonly between the ages of 6 and 20. The
inheritance is typically autosomal recessive. There is no sex predilection.
stARgardt’s = A R condition
• Pathophysiology/Diagnosis: Fundus flavimaculatus and Stargardt’s dis

ease are considered variants of the same disorder.
— Fundus flavimaculatus diagnosis is reserved for patients WITHOUT

macular dystrophy signs; it often presents later in life (4th-5th decade).
Patients are commonly asymptomatic (35) (52), although vision loss
can still occur if fleck-lesions involve the macula.
• Symptoms: Rapid vision loss and color vision abnormalities. The level
of decreased vision is often out of proportion with the fundus appearance
in the early stages of the disease. Acuity is typically 20/200 by the third
decade and is stable or slowly progressive thereafter (35).
• Signs: Early stages are characterized by bilateral yellow flecks scattered

in a pisciform (fish-tail) configuration throughout the posterior pole and
mid-periphery. Non-specific RPE mottling of the macula may also be ap
parent. Late stages are characterized by a classic “beaten-bronze” macular
appearance (“bull’s eye maculopathy”) and “salt and pepper” pigmentary
changes in the periphery.
• The ERG is normal in the early stages of the disease, but becomes ab
normal as the condition progresses.
C h oroid erem ia
• Epidemiology/History: Inheritance is X -lin k ed recessive, so only males

are affected and all daughters are carriers. Onset is typically within the
1st decade.
• Pathophysiology/Diagnosis: Due to a deficiency in rab geranyl-geranyl

transferase, an enzyme utilized in membrane metabolism (35).•
• Symptoms: Night-blindness and peripheral vision loss. Night-blindness

occurs early in life in males and progresses to total night-blindness within
a period of 10 years (78). Most patients have good vision until 50-60 years
of age (52). In females, the condition is benign and non-progressive.

• Signs: Progressive, bilateral, diffuse atrophy of the RPE and choriocap-

illaris, causing exposure of the underlying sclera. The macula is often
spared until the late stages of the disease. The optic disc and retinal
blood vessels are often unaffected.
Differential diagnoses for night-blindness include gyrate atro

phy, ch oroid erem ia , and retinitis pigm entosa (non-exhaustive
list).
C o n e D y stro p h y
• Epidemiology/History: Onset within the 1st to 3rd decade. Inheritance

is variable, but most commonly autosomal dominant.
• Symptoms: Slowly progressive decrease in central vision, severe photo

phobia and severe color vision loss; symptoms are worse during the day.
Cone dystrophy has a poor prognosis, with vision deteriorating to 20/400
by the 4th decade (35).
- Early - normal fundus appearance but abnormal cone function on

the ERG.
— Late - central geographic atrophy of the RPE with a bull’s eye macu
lar appearance, vessel attenuation, and temporal pallor of the optic
nerve (similar to RP) with severe deutan-tritan color defects, an
abnormal photopic ERG, and fine nystagmus.
Differential diagnoses for b u ll’s eye m aculopathy include Star-

gardt’s disease, progressive cone dystrophy, chloroquine and hy
droxychloroquine toxicity, and thioridazine toxicity.
B e st’s D isease (V ite llifo rm d y strop h y)
• Epidemiology/History: Uncommon condition. Inheritance is autosomal

dominant. The age of onset varies but the condition classically presents
in early childhood (5-10 years old).•
• Pathophysiology/Diagnosis: Due to the abnormal accumulation of mate

rial (possibly lipofuscin) in the RPE.
Copyright 2014 by KM.K Educational Services, LLC

• Symptoms: The majority of cases are detected with little or no patient

symptoms (75% better than 20/40) (78). Patients eventually complain
of decreased vision.
• Signs: Characterized by a bilateral, yellow, round, subfoveal (“egg-yolk”)

lesion.
The eg g-y olk is thought to be an abnormal accumulation of lipo-

fuscin within RPE cells (3). The egg-yolk can remain stable for
years,with only a mild reduction in visual acuity (20/30 to 20/50)
into midlife (3).
The condition is classified according to the following stages:
- Stage 1 (p re-v itelliform ): Characterized by an abnormal EOG

with a normal fundus in an asymptomatic patient.
- Stage 2 (v ite llifo rm ): Egg-yolk macular lesion appears; this is
most likely to occur between the ages 3-15 (35).
- Stage 3 (p seu d oh y p op y on ): The entire lesion can become ab
sorbed with little to no effect on vision.
- Stage 4 (v itelliru p tiv e): The egg-yolk starts to break-up and a
“scrambled-egg” appearance results; mild visual loss is expected at
this stage.
- Stage 5 (en d -stage): Characterized by moderate to severe vi
sion loss due to choroidal neovascularization, hemorrhage, atrophy,
and/or macular scarring.•
• Patients will have a normal ERG but an abn orm al E O G (even prior to
vision loss or fundus signs) (3).
A d u lt foveom acular v itelliform d y strop h y presents in pa

tients aged 30-50. Although signs are similar to Best’s disease,
the overall prognosis is better with minimal metamorphopsia, mild
acuity loss, a normal EOG and ERG, and a slight tritan color de
fect (78).

CHAPTER. 10. OCULAR DISEASE 525
G y ra te A tro p h y
• Epidemiology/History: Inheritance is autosomal recessive. Symptoms

are prevalent in most patients by age 10 (52),
• Pathophysiology/Diagnosis: Bilateral chorioretinal degeneration due to

a deficiency in the mitochondrial enzyme ornithine am inotransferase.
Ornithine blood plasma levels will be high and can help in the diagonsis
if the clinical picture is unclear.
• Symptoms: Nyctalopia (night-blindness), decreased vision, constricted

visual fields.
— •-Sig-nse-Mult-iple—well-definedyscallopedTireas of periphefal^lrofioretinal
atrophy; the lesions begin in the midperiphery during childhood and then
coalesce to engulf most of the posterior pole, with the macula being spared
until the 4th to 7th decade (33). Associated with posterior subcapsular
cataracts, high myopia, and astigmatism.
R h e g m a to g e n o u s R etin a l D etachm ents (R R D )
• Epidemiology/History: Occur more often in males, typically over the age

of 45 years. Risk factors for RRDs include:
~ P re v io u s o cu la r su rgery (e.g. cataract surgery). Pseudophakic

RDs often result from small retinal holes at the vitreous base (84).
— P o ste rio r vitreou s detachm ent: 10 — 15% of patients with an
acute symptomatic PVD will have a retinal break (35).
— T raum a (5 — 10%) (35).
— Fam ily h istory of RRD or previous occurrence of RRD. Both eyes
are eventually involved in about 10% of cases (52).
— M y o p ia : 40% of all RDs occur in myopic eyes (52).
— L a ttice degen era tion : (30%) (35) (see below for additional infor
mation) .•
• Pathophysiology/Diagnosis: Rhegmatogenous retinal detachments result

from retin al breaks (full-thickness retinal defects) that allow vitreous
into the subretinal space, leading to separation of the sensory retina from
the underlying RPE. Breaks include atrophic holes and vitreo-retinal
traction tears.
The term retinal B R E A K — atrophic H OLES and traction

T E A R S . Thus, an RRD refers to a retinal detachment that was
caused by a hole or tear.

1. A tro p h ic holes: Round, often small, full-thickness defects that

are NOT associated with vitreoretinal traction and therefore have a
low risk for subsequent detachment. Holes are caused by ch ron ic
atroph y of the sensory retina and are most likely to be located in
the temporal retina (superior > inferior quadrant) (52).
2. R etin al tears: Caused by vitreou s traction. Types of retinal
tears include flap (horseshoe) tears and operculated tears.
- F lap tears - the flap is present because of uneven vitreou s
traction; vitreoretinal traction often persists in these cases (vit
reous stays attached to the flap), increasing the risk of a, retinal
detachment compared to operculated tears.
— O percu lated tears - the initial vitreoretinal traction results
in an even, symmetric tear. After forming the tear, the vitreous
pulls away and vitreoretinal traction no longer persists, reducing
the risk for a retinal detachment.
• Symptoms: Classic symptoms include vitreous floaters, flashing lights

(photopsia), a curtain or veil over the vision, and decreased acuity.•
The quadrant location in which a patient reports flashes o f light

is of no value in predicting the location of the primary retinal break;
however, the quadrant location for visual field defects is often valid.
For example, if the field defect is reported in the inferior nasal
quadrant, a superior temporal retinal break is expected (52).
• Signs: Vary in acute and chronic RDs.
- Acute RD - Convex undulating retina with clear subretinal fluid

that does not shift with body position; Shafer’s sign (pigment cells
in the anterior vitreous, also called “tobacco dust”) may or may not
be present. Additional signs may include a mild iritis and lower IOP
in the affected eye.
— Chronic RD - pigm ent dem arcation line will be present (takes 3
months or longer to develop). Additional signs include intraretinal
cysts (take 1 year or longer to develop), fixed folds, and/or subretinal
precipitates (35) (52).
The superior tem p ora l quadrant is the most likely location for a
retinal break in patients with an RRD (60%) (52). 50% of eyes with
an RRD will have more than one retinal break; in most of these
cases, the breaks are located within 90 degrees of one another (52).

L attice D eg en era tion
• Lattice is present in 6 — 10% of patients; 20 —33% of patients with rheg-

matogenous retinal detachments will have lattice degeneration; however,
only 1% of patients with lattice degeneration develop a retinal detach
ment (78).
• Lattice is an area of peripheral retinal thinning that is typically circum

ferential (often cigar-shaped) and concentric with the ora serrata (84).
• The inner portion of the lesion is atrophic (thin), while the outer margins
of the lesion have a firm adhesion to the vitreous. The majority of lesions
----- —D 0 -N OT- eontain-t-he-eris s- cro ss-p att ern- o Twhittr scl erosed- ves seIsponly
12% of patients have this classic appearance (34).
• Lattice degeneration is often bilateral (33-50% ) (35) and more commonly

located temporal (than nasal) and superior (than inferior) (52).
• Lattice degeneration will contain an atrophic hole in 25% of cases; retinal

tears can also result from vitreoretinal traction on the atrophic, thinned
retina (35).
Patients with Marfan’s syndrome, Stickler syndrome, and Ehlers-

Danlos syndrome can have lattice-like lesions (“atypical lattice”)
that increase the patient’s risk of an RD (52).
V itre o re tin a l tu fts are small, focal areas of vitreous traction lo
cated in the retinal periphery. They occur in 5% of the population
and are the second most common peripheral retinal lesion asso
ciated with retinal detachments (lattice is 1st); less than 1% of
patients with vitreoretinal tufts develop a retinal detachment (34).
N o n -R h e g m a to g e n o u s R etin a l D etachm ents
Non-rhegmatogenous RDs include serous (exu dative) R D s and tra ction

R D s. By definition, these RDs are NOT caused by retinal breaks.

1. E xu dative R D s - result from subretinal disorders that damage the RPE

and allow fluid accumulation under the retina (52). Examples include
A R M D (most common), inflammatory conditions (e.g. scleritis), vascu
lar conditions (e.g. Coats’ disease), neoplasms (e.g. choroidal melanoma),
and miscellaneous causes (e.g. coloboma) (84). Patients with exudative
RDs are usually asymptomatic, unless the detachment involves the mac
ula.
2. T ra ction R D s - most commonly caused by PDR, ROP, and prolifer

ative sickle cell retinopathy (52). Patients with TRDs usually do not
have complaints of flashes and floaters and may be completely asymp
tomatic (52). Possible symptoms include decreased vision or progressive
visual field defects (may remain stationary for months to years) (52).
M iscellaneous R etinal f Choroidal C onditions -

A g e -R e la te d D egenerative R etinoschisis
• Epidemiology/History: Occurs in 4 —7% of the general population; more

common in patients 40 years or older.
• Pathophysiology/Diagnosis: Denegerative process that results from a

splitting of the outer plexiform layer and the inner nuclear layer, resulting
in elevation of the inner retina that mimics a retinal detachment.
• Symptoms: Typically asymptomatic; vision loss is rare.
• Signs: Dome-shaped bullous elevation most commonly located inferior/temporal

(70% of cases) (35). Unlike a.retinal detachment, the retina is immobile,
bilateral findings are common (50 — 75%), and an absolute visual field
defect will correspond to the area of elevation.
— 70% of patients are hyperopic (35) (52).

— “Snowflake” or “frosting” and sheathed retinal vessels occur in the
elevated retinal layer of a retinoschisis.
— Inner wall breaks and outer wall breaks can occur in a retinoschisis.
Outer wall breaks are more dangerous - they are required to cause
a retinoschisis-associated RD, Outer wall breaks will appear “pock
marked” on scleral depression. They can be surrounded with laser
treatment to prevent an RD (rare).
A n g io d Streaks
• Pathophysiology/Diagnosis: Large breaks in Bruch’s membrane that re

sult from damage to the elastic core of Bruch’s membrane. 50% of cases
are idiopathic; the remaining cases are caused by systemic disease.

CHAPTER 10, OCULAR DISEASE 529
Remember P E P S I for the most common causes of angioid streaks:

P seu d ox a n th om a ela sticu m (by far the most common cause),
Ehlers-Danlos syndrome, Paget’s Disease, Sickle-cell disease, and
Idiopathic.
• Symptoms: May be asymptomatic or have profound vision loss from

choroidal neovascularization (CNVM). 70% of patients will eventually
have some form of vision loss (52).
• Signs: Spoke-like (around the optic disc), linear, well-demarcated red/orange

-------- owbrownUines^clepending upon the amount of pigment involved) within
the elastic core of Bruch’s membrane.
T oxocariasis
• Pathophysiology/Diagnosis: Caused by Toxocara canis or cati, which is

an intestinal nematode in dogs or cats. The condition is most common
in children and young adults who are infected by eating dirt or infected
vegetables, meat, or water, or through contact with infected puppies or
kittens. After ingestion, the larvae penetrate the intestinal wall and travel
to organs such as the eye, brain, skin, liver, and lungs.
• Symptoms: Patients may complain of floaters and blurred vision.
• Signs: Ocular infection causes a significant unilateral inflammatory re

sponse, resulting in optic nerve edema, retinal detachment, vitritis, en
dophthalmitis, and subretinal granulomas. Large, white chorioretinal
scars are present after the active infection has resolved (35).
C h orioretin itis is a form of posterior uveitis that is character

ized by inflammation of the chorioid and retina. Examples in
clude toxoplasmosis, toxocariasis, sarcoid, syphilis, CMV, serpigi
nous choroidopathy, birdshot chorioretinopathy, tuberculosis, and
onchocerciasis (33).
A cu te P o ste rio r M u ltifo ca l P la coid P igm ent E pith eliop ath y
* Occurs acutely in young adults, typically after a viral illness. Charac

terized by bilateral, yellowish, flat, subretinal lesions. Disc edema and
retinal detachment may also occur.•
• Usually resolves without treatment after a few weeks.

530 10.12. NEUR 0 - OPHTHALMIC DISORDERS: GLA UCOMA
C entral A reola r C h oroidal D y strop h y
* An autosomal dominant condition characterized by bilateral large areas

of geographic atrophy in the macula. Will cause vision loss in the 4th-5th
decade. Poor prognosis (35).
Senile ch oroidal atroph y results in choroidal thinning and may

cause an exaggerated tigroid fundus appearance due to increased
visibility of the choroidal vasculature.
- SECTION 10.12 --------------------------------------------------------------------------------
N euro-O phthalm ic D isorders: G laucom a •
Glaucoma is the most likely source of an optic neuropathy. It is a leading

cause of irreversible blindness worldwide. In the United States, it is estimated
that 2.79 million people have primary open-angle glaucoma (POAG), and this
number is expected to increase in the future (82). The following will focus
on subjects related to glaucoma (please see chapter 2 for additional neuro-
ophthalmic conditions).
O cular H yperten sion
Defined clinically as an IOP greater than 21 (IOP > 24 per the Ocular Hyper
tension Treatment Trial) qn consecutive visits in a patient with an open angle
and without glaucomatous optic neuropathy. The most important risk factors
for conversion into P O A G include the following:
• IOP - the only risk factor we can control!
• Race - African Americans 4-5X more likely to develop glaucoma (104).
• Family history - overall proportion of POAG related to genetics is around

16% (104). Having a first degree relative (parent, sibling, child) with
glaucoma is associated with a 3 to 4-fold increase risk of POAG (51) (106).
• Age - greater than 90% of those with glaucoma are over the age of 55 (82).
• Thin corneas.

CHAPTER 10. OCULAR, DISEASE 531
Glaucoma risk interpretation based on CCT (19):
• <555um= higher risk
• 555-588um= no change of risk based on CCT
• >588um= lower risk
P rim a ry O p en A n g le G la u com a •
The most common type of glaucoma that occurs in 0.5-2.1% of those oyer age
40 (35). POAG is defined as glaucomatous optic nerve damage with corre
sponding visual field loss that occurs with IOPs greater than 21 mmHg with
an open angle on gonioscopy. The exact cause of the increased IOP is not
known.
• The most important sign for detection of POAG is dam age to th e

o p tic nerve. Larger C /D s, asymmetry between the optic nerves, focal
vertical thinning or notching, nerve fiber bundle defects, and vascular
signs (baring, hemorrhages) are important clinical signs. Recall that the
larger the optic disc, the larger the expected cup size.
• The ISN’T rule suggests that normal optic nerves should have the most
rim tissue in the inferior quadrant, followed by the superior, nasal, and
the temporal quadrant (thinnest). However, glaucoma may initially the
damage the inferior OR, superior rim.
• Initial field loss is variable, but nasal steps are the most common (52).
Paracentral and arcuate defects are also relatively common.
• Patients with POAG are usually asymptomatic until later stages when
significant peripheral or central vision is lost.
P o r t-W in e Stains are vascular birthmarks that have a high as

sociation with ipsilateral glaucoma (45% of cases). It is rarely
associated with systemic disorders - most notably Sturge-Weber
Syndrome (5% of cases) (52).

532 10.12. NEURO- OPHTHALMIC DISORDERS: GLA UCOMA
S econ d a ry O p en A n gle G laucom as
P se u d oex folia tion Syndrom e: An age-related system ic con d ition that

is most common in Caucasians, especially those of Scandinavian decent. Pseu
doexfoliation is the most common identifiable cause of elevated 10 P and resul
tant glaucoma (87).
• It is characterized by abnorm al, w h ite, flaky d ep osits whose exact

composition and cause of formation remain unknown (60). The flaky
deposits are found throughout the body and may have systemic implica
tions.
• In the eye, these deposits can be found on the pupillary margin, on the
lens capsule in a b u ll’s eye pattern, on the lens zonules, and in the
trabecular meshwork.
• Gonioscopy often reveals a S am paolesi’ s line due to the accumulation

of pigment that is released as the deposits rub against the posterior iris
epithelium.
Sam paolesi’ s line is increased pigmentation anterior to

Schwalbe’s line; it is associated with pseudoexfoliation syndrome
and pigment dispersion syndrome (35).
• PXF is associated with poor pupil dilation and an increased risk of lens
subluxation and cataract surgery complications due to weak lens zonules,
• The majority of patients present with unilateral or bilateral asymmetric

pseudoexfoliative glaucoma. The risk of developing glaucoma is 15%
within 10 years (35).
P igm en ta ry D ispersion G laucom a: Condition that is usually bilateral,

more common in Caucasians, and presents in young patients (30-40s). The
condition is more common in myopes and males (2:1) (52).
• Pigmentary dispersion syndrome is thought to result from a higher ante

rior chamber pressure that causes excessive bowing of the iris posteriorly,
resulting in more contact between the iris and lens zonules; this leads to
pigment shedding off the posterior edge of the iris.•
• Patients are often asymptomatic, but may have blurred vision and halos
around lights after exercising or pupil dilation.

* Common signs include transillumination defects (TIDs), Krukenberg’s

spindle (vertically oriented pigment lines on the corneal endothelium),
pigment on the anterior capsule of the lens and the iris surface, and
trabecular meshwork hyper pigmentation.
* Pigment dispersion syndrome may burn out over time as the lens thickens,
resulting in less contact between the posterior iris epithelium and lens
zonules.
* The risk of glaucoma at 5 years is 10%; the risk at 15 years is 15% (98).•
A n g le recession glau com a: Angle recession is characterized by a wide open

angle with a recessed iris and a widened ciliary body band. It is most often
unilateral and results from blunt trauma. Although the angle appears wide
open, the TM is damaged, resulting in an increased risk of glaucoma over time.
10% of patients with angle recession involving at least 2/3 of the angle will
develop glaucoma (35).
N orm a l T en sion G la u com a
Normal tension glaucoma (NTG) is considered a type of POAG (makes up 16%

of cases) in which NFL damage occurs at lower pressures; most define the con
dition as IOP less than 21 with an open angle on gonioscopy and glaucomatous
optic nerve damage with corresponding visual field loss (52).
• Females are at a greater risk and the condition has the highest prevalence
among Japanese patients (102). Additional risk factors include vascular
disorders such as Raynaud’s phenomenon or migraines, low blood pres
sure, sleep apnea, hyper coagulation, and taking BP medications before
bedtime (may decrease ocular perfusion pressure).
• Before diagnosing NTG, it is important to take diurnal IOP readings to

ensure the diagnosis is truly NTG rather than POAG. Those who develop
NTG typically have IOPs in the high teens.
• Signs o f NTG are similar to those in POAG, but drance hem orrhages
are more common in NTG. Initial visual field defects in NTG are usually
more focal (but more dense) and closer to fixation because the temporal
and inferotemporal rim tissue is more commonly affected first (compared
to POAG) (102).

534 10.12. NEURO-OPHTHALMIC DISORDERS: GLA UCOMA
Since IOP is within the normal range in NTG, it is important to

rule out other possible sources of the optic neuropathy, especially in
cases of suspected unilateral N T G . Consider asking about a his
tory of hemorrhagic shock, myocardial infarction, anemia, syphilis,
and vasculitis (102).
P rim a ry A n g le C losure G lau com a
Can be acute or intermittent (sub-acute) and occurs as a result of the pos

terior pressure in the posterior chamber pushing the peripheral iris anteriorly
into contact with the TM, blocking part or all the TM and impeding aqueous
outflow. The pupil may or may not be blocked in angle closure glaucoma.
• The two causes of primary angle closure glaucoma are pupillary b lock
and plateau iris syndrom e, with the latter being much less com
mon (52).
— Pupillary block occurs in patients with anatomically narrow angles

(often in hyperopes) when the aqueous flow through the pupil is
blocked (usually by the lens but can also be the vitreous). Patients
are most at risk for angle closure when the pupil reaches the mid
position after coming down from dilation, as this is the point of
greatest iris-lens contact.
* Risk factors for angle closure secondary to pupillary block in
clude hyperopes, advancing cataracts, Asians and Eskimos,
and lens subluxation.
* 5% of the population over age 60 have occludable angles, but
only 0.5% will develop angle closure (35).
— Plateau iris is characterized by anteriorly positioned ciliary processes
that push the peripheral iris forward into contact with the TM.
Slit lamp and gonioscopy reveals a flat iris plane, a normal central
anterior chamber depth, but a convex peripheral iris (52).
A peripheral iridotomy or iridectomy can be performed to differen

tiate pupillary block from plateau iris configuration; in the latter,
the peripheral iris proximity to angle structures will be unchanged
after the procedure.

• S u b -a cu te or chronic angle closure occurs when part of the angle closes,

causing episodes o f elevated IOP w ith ou t patient sym ptom s. Sub
acute angle closure is more common than acute angle closure. Chronic
angle closure should be expected in patients with an oeelu dable angle
and any of the following signs:
— P A S or pigment splotching on the TM.

— Progressive optic nerve damage with corresponding visual field loss.
• A c u te angle closu re is defined as angle closure (no TM visible with

goniooscopy) causing an acute elevation in IO P (50-100 mmHg) and*•
patien t sy m p tom s. Signs and symptoms include:____________________
— Vomiting, intense ocular pain, headaches, halos, nausea, and pro

gressive vision loss.
— Prominent signs include a hazy cornea, mid-dilated pupil that re
sponds poorly to light, ciliary flush, and glaucomflecken.
— IOP must be quickly lowered so that corneal edema will resolve,
allowing for a peripheral iridotomy.
G lau com fleck en are anterior subcapsular opacities that result

from lens epithelial cell ischemia and necrosis secondary to high
IOP (35).
• T h e greatest threat to vision in acute angle closure is a C R A O

(occurs when IOP is higher than the perfusion pressure of the central
retinal artery).
Topamax®(topiramate), which is used for treating migraines,

weight loss, and epilepsy, can cause acute secondary angle closure.
It causes supraciliary effusion, which moves the lens and iris for
ward into contact with the TM, resulting in angle closure. This
typically occurs within the first month of use or if the dosage is
increased.

536 10.12. NEURO-OPHTHALMIC DISORDERS: GLAUCOMA
Patients with a history of angle closure are at a higher risk for

developing an open angle component of glaucoma due to TM and
optic nerve damage. This will manifest as elevated IOP with optic
nerve damage with an open angle on gonioscopy, and may occur im
mediately or years later after treatment of angle closure. Patients
with a narrow angle AND open angle component of glaucoma have
m ixed-m echanism (combined) glaucoma.
S econ d ary A n gle C losure G lau com a
N eovascular G laucom a: Serious condition that frequently results in severe

vision loss and a painful eye. Neovascular glaucoma most commonly occurs
with conditions that result in severe retinal ischemia.
* C entral retinal vein occlu sion is the most common cause of NVG,
followed by proliferative d ia b etic retinopathy. Ocular ischemic syn
drome and retinal detachments may also lead to NVG.
• Carotid artery disease and central retinal artery occlusions are less com
mon causes of NVG.
The most important sign to recognize for the prevention of neovascular glau
coma is rubeosxs o f the iris. The pupillary margin should be examined
closely for capillary tufts or early signs of neovascularization. Progression of
this process into the anterior chamber angle can cause secondary angle closure
via two mechanisms:
1. Neovascularization of the angle is always accompanied by fibrous tissue

that forms a membrane over the TM, preventing aqueous outflow. A
significant fibrovascular membrane can develop even with only 1-2 vessels
in the angle.
2. The fibrovascular membrane can stick to the iris, pulling it into contact
with the TM and causing secondary angle closure. This is known as
“zippering of the angle.”
U veitic G lau com a: Occurs as a result of peripheral anterior synechiae (PAS)

and posterior synechiae (PS) formation in uveitis. Remember that uveitis
causes the iris to become inflamed and sticky. The iris can stick to the lens
(forming PS) or to the TM (forming PAS).
Copyright 2014 by KMK Educational Services, L L G

• Posterior synechiae will only cause an elevation in IOP when there is

360 degrees of attachment between the iris and lens. This results in iris
b o m b e and pupillary block, which moves the iris anteriorly into contact
with the TM.
• PAS will cause varying degrees of IOP elevation depending on the extent
of angle involvement.
It is very important to manage uveitis aggressively to prevent the formation

of PS and PAS. If PS occur during the current episode of inflammation, every
effort should be made to break them. Once the current uveitis episode resolves,
-BS-can_only-b eu-©move d-su r-g-ieall-y------------ ------------ —■— -------------------- “
Congenital glaucoma
Onset is typically from birth to 3 months of age; the condition is most often
bilateral and is more common in males. Congenital glaucoma results from a
developmental abnormality in the anterior chamber angle that impedes aqueous
outflow.
B u p h th a lm os is an enlarged eye with a corneal diameter > 1 2 mm

that occurs by one year of age in patients with congenital glaucoma
as a result of elevated IOP.
ICE (iridocorneal endothelial) Syndromes
ICE syndromes are a group of disorders characterized by an abnormal corneal

endothelium that grows onto the iris or in the angle, increasing the risk for
glaucoma (108). Signs include corneal edema, iris atrophy, PAS, and angle
closure. ICE syndromes are more common in females and patients age 20-50;
they include the following conditions:
• Essential Iris Atrophy - Iris thinning with resulting heterochromia, poly-

coria, corectopia, and ectropion uvea,
• Chandler’s Sydrome - The corneal endothelium will have a “beaten metal”

appearance with corneal edema and corectopia.•
• Iris-Nevus Syndrome (Cogan-Reese Syndrome) - Nodules will be present

on the anterior iris surface.

538 10.12. NEURO-OPHTHALMIC DISORDERS: GLA UCOMA
In flam m atory G lau com a
G la u cora a tocyclitic Crisis: Also known as Posner-Schlossman syndrome.

This condition is characterized by acute trabecu litis that results in an acute
elevation of IOP (40-60 mmHg). There will be few cells in the anterior chamber,
and gonioscopy will reveal an op en angle. The condition occurs most often
in young to middle-aged patients and is characterized by recurrent unilateral
episodes that often burn out over time.
Fuchs’ H ete ro ch rom ic Irid ocy clitis: Chronic, non-granulomatous, low

grade anterior uveitis with stellate keratic precipitates. Additional signs in
clude iris heterochromia and iris/angle neovascularization. Patients have an
increased risk of glau com a (due to chronic TM damage) and cataracts due
to chronic inflammation.
P h a co ly tic glaucom a: Results from a hyperm atu re cataract that leaks

lens material into the anterior chamber, resulting in blockage of aqueous outflow
through the TM. Cells, flare, and iridescent lens particles will be present within
the anterior chamber.
■ Diagnostic Tests for G laucom a j

Glaucoma is characterized by retinal ganglion cell death and corresponding
retinal nerve fiber (RNFL) loss. Upon clinical exam, the RNFL loss can be
difficult to see, especially if it is early or mild. In an effort to detect structural
optic nerve damage earlier, computerized instruments have been developed to
detect mild changes in the RNFL. They may also be helpful to detect progres
sion.
* The imaging instruments available incldue the GDx (Laser Diagnostics

Technology), OCT (Zeiss, Heidelberg, Optovue), and HRT (Heidelberg
Engineering).
— GDx uses scanning laser polarimetry to detect thinning of the RNFL.

— OCT uses optical coherence tomography.
— HRT uses confocal scanning laser ophthalmoscopy for a topograph
ical evaluation of the optic nerve and peripapillary retina.
• With all instruments, after the first data collection, the patient’s results
are compared to a normative database matched for age and race. At sub
sequent visits, the patient’s results can be compared to his/her baseline
scan as well.
The OCT Stratus (Zeiss) is a time domain system, and the Spectralis (Heidel
berg) and Cirrus (Zeiss) are spectral domain systems. Spectral domain results

in better resolution and is faster and more sensitive. Swept source, the newest
technology, is even better than spectral domain because of higher sensitivity
and speed.
M a cu la r E valuation in G la u com a Remember that the retinal ganglion

cells are densest in the macula; studies have shown that patients with glau
coma show thinner areas in the macula that correspond with visual field loss.
There are three instruments that are capable of analyzing macular ganglion
cell thickness: RTVue Ganglion Cell Complex Analysis (Optovue), Spectralis
Posterior Pole Asymmetry Analysis (Heidelberg), and Cirrus Ganglion Cell
Analysis (Zeiss).*•
• The RTVue measures the three innermost macular layers and compares
the patient’s data to a normative database.
• The Spectralis does NOT have a normative database but allows for inter
and intra-eye asymmetry analysis.
• The Cirrus measures only the ganglion cell-IPL complex and compares
results to a normative database.
Although macular analysis has not been proven to be diagnostic for glaucoma, it
does give the practitioner one more tool to assess for glaucomatous damage (8)
G o n io sco p y
Gonioscopy must be performed in order to diagnose the appropriate type of

glaucoma. Additional indications include narrow angles on Van Herick, signs
of pigment dispersion (TIDs and Krukenberg’s spindle), iris neovascularization,
suspicious iris lesion, history o f ocular trauma, or when following a CRVO.
• 3 mirror lens - Goldmann, requires Gonak®or Celluvisc®.
• 4 mirror - Posner, Zeiss or Sussman (no handle).
Remember that the structures seen will be 180 degrees away from the mirror
position. Document the iris insertion in relation to the trabecular meshwork
(steep/flat/concave) and the most posterior structure seen in all four quadrants.
Also note any PAS, neovascularization, iris processes, pigmentation, or angle
recession.
Remember the structures of the angle (posterior to anterior): I

Can See The Stupid Line —> Iris, Ciliary Body, Scleral Spur, TM,
Schwalbe’s line.

540 10.12. NEURO-OPHTHALMIG DISORDERS: GLAUCOMA
V isu al fields (P erim etry)
Visual fields are used to diagnosis glaucoma and to monitor for progression.
There are multiple types of visual fields:
• Static Automated Perimetry (SAP): The Humphrey visual field is the

most popular SAP threshold test.
• Short Wavelength Automated Perimetry (SWAP): Uses a yellow back

ground with blue stimuli to detect early glaucomatous damage that is
not detected with SAP.
• Frequency Doubling Technology (FDT): A fast (90 seconds per eye)

screening field that uses sinusoidal gratings as the stimulus.
Approximate extent of a norm al visual field: 100 degrees tem

poral, 60 degrees nasal and superior, and 70 degrees inferior. The
blind spot is located 15 degrees temporal and is 7.5 degrees in di
ameter (83).
We now summarize interpretation of the Humphrey Visual Field (18):
• R elia b ility indices: Include fixation losses, false positives, false nega
tives, and short-term fluctuations (STF).
- STFs are determined by randomly retesting certain points. Poor

performance on STFs could indicate poor reliability or early glau
coma.
- Fixation losses > 20% or false positive or false negative errors > 33%
may be flagged by the instrument as “abnormally high sensitivity”
or “reduced reliability.”
• G rayscale: This is a gross representation of the visual field. The darker

areas indicate reduced sensitivity. This can be used for patient education
but has m inim al value in interpretation.
• T otal deviation: Compares how well the patient performed compared

to the database of healthy, age-matched samples.
- A zero indicates the patient scored the same as the normative database.
A positive number means the patient performed better than ex
pected. A negative number means the patient performed worse than
expected.

— The darker the probability box on the total deviation probability

plot, the greater the patient’s response deviated from the expected
response.
• P a ttern d ev ia tion : Filters out diffuse loss (e.g. cataracts) to show only
foca l areas o f d e v ia tio n that are more typical in glaucoma.
• G la u co m a H em ifield Test: Compares sensitivity levels between the

upper and lower hemifields. Remember that glaucoma often causes asym
metric ONH damage, resulting in an asymmetric field loss above and be
low the horizontal midline. The GHT will state WNL, borderline, ONL,
or reduced sensitivity.*•
• V isu a l F ield In d e x ( V F I ) : This gives a measure of the rate of visual

field loss over time and is given as a % of normal. 100% means no loss of
the visual field; 0% means total blindness.
• M e a n D e v ia tio n ( M D ) : Represents the average of the differences be

tween the patient’s overall sensitivity and the overall sensitivity of the
normative database. MD is an indication of diffuse loss; the more nega
tive the MD, the more general depression in the visual field.
• P a ttern Standard D e v ia tion (P S D ): Compares the patient’s shape

of the hill of vision to the shape of the hill of vision of the normative
database. PSD indicates focal areas of depression that are typical in
glaucoma. It is always an absolute value; higher PSD values represent
greater focal visual field loss.
R eferences
[1] Aiello LM. Perspectives on diabetic retinopathy. Am J Ophthalmol. 2003 4u];13G(l);122-35.
[2] Albert DM, Miller JW, Azar DT, Blodi BA, Cohan JE, Perkins T, Albert and Jakobiec’s
principles and practice of ophthalmology, 3rd ed. Philadelphia: Saunders, 2008.
[3] Alexander L. Primary Care of the Posterior Segment, 3rd ed. McGraw-Hill, 2002.
[4] Alvarado J, Murphy C, Juster R. Age-related changes in the basement membrane of the
human corneal epithelium. Invest Ophthalmol Vis Sei. 1983 Aug;24(8):1015-28.
[5] American Academy of Ophthalmology Basic and Clinical Science Course, Refractive Surgery,
Section 14, 2004-2005.
[6] AO A clinical practice guidelines. Care of the Adult Patient with Cataract, revised 2004.
www.aoa.org.
[7] AOA Clinical Practice recommendations for co-management of refractive surgery,

www.aoa.org/documents/co-management.pdf
[8] Aref A, Measuring Macular Thickness in Glaucoma. Glaucoma Today, April 2013.

542 10.12. NEURO-OPHTHALMIC DISORDERS: GLA UGOMA
[9] Arevalo, et al. Rhegmatogenous retinal detachment after LASIK for the correction of myopia.
Retina. 2000;20(4);338-41,
[10] B al asu b raman ian SA, Pye DC, Willcox MD. Are proteinases the reason for keratoconus?
Curr Eye Res, 2010 Mar;35(3):185-91,
[12] Bartlett, Jimmy D., Jaanus, Sh’et D. Clinical Ocular Pharmacology. Boston: Butterworth,
2008.
[13] Bennett E, Weissman B. Clinical Contact Lens Practice. Lippincott Williams Wilkins, 2005.
[14] Bezan D, Halverson K, Schaffer K, Thomas P, Optometric Guide to Surgical Co-Management.

Butterworth Heinemann, Boston, 1992.
[15] Blumenkranz M, Russell S, Robey M, et al. Risk factors in age related maculopathy compli
cated by choroidal neovascularization. Ophthalmology 1986; 93:552-8.
[16] Butler P, Char DH, Zarbin M, Kroll S. Natural history of indeterminate pigmented choroidal
tumors. Ophthalmology, 1994 Apr;.101(4):710-6.
[17] Byrnes, Michael J., Combination Therapy for the Treatment of Retinal Vein Occlusion.
Retina Today, March 2009, page 53.
[18] Casser, L, Fingeret, M, Woodcome, T. Atlas o f Primary Eyecare Procedures, 2nd ed. Apple-
ton and Lange, Connecticut, 1997.
[19] Chaglasian, M. An Overview of Diagnosis. Part of “A Brief Look at Current Thoughts on

Glaucoma Management and Diagnosis.” Review of Optometry, August 2010.
[20] Chakrabarti R, Harper CA, Keeffe J. Diabetic Retinopathy Management Guidelines, Expert
Rev Ophthalmol. 2012;7(5):417-439.
[21] Chang DF, Oslier RH, Wang L, Koch DD. A prospective multicenter evaluation of cataract
surgery in patients taking tarnsulosin (Flomax). Ophthalmology 2007; 114:957-964.
[22] Char DH. Ocular melanoma. Surg Clin North Am. 2003;83(2):253-74.
[23] Chen Y, Zhao M, Zhou P. Traumatic chorioretinopathies. In; Ryan, SJ. Retina. 5th ed.
Philadelphia 2012: Saunders-Elsevier Inc. 1564-1570.
[24] Copeland RA, Afshari NA. Principles and practice of cornea. New Dehli: Jaybee Brothers
Medical Publishers, 2013.
[25] Couch JM, Green WR, Hirst LW, De La Cruz, ZC. Diagnosing and treating Phthirus Pubis
palepbrarum. Surv Ophthalmol 1982;26:219-225.
[26] Coupal, D. Posterior Polymorphous Corneal Dystrophy. Online J, Medscape.

http://emedicine.medBcape.com/article/1197057-overview. 2010.
[27] Deacon, B, Journal of Ophthalmic Medical Technology, Orbital Implants and Ocular Pros-
theses: A comprehensive review, www.JOMTonline.com.
[28] du Toit R, Sweeney D, Fonn D, et al. Managing Silicone Hydrogel Complications. Contact
Lens Spectrum. May 2002.
[29] h ttp ://sk la ca n cer.dermis.net/content/e04tvpesof/el48/el49/lndex_eng.html.
[30] Elkington AR, Khaw PT. Eyelid and lacrimal disorders, Brit Med J 1988;297:473-477.
[31] Esquenazi, S, Fry, C L, Holley, E. Treatment of biopsy proved conjunctival intraepithelial

neoplasia with topical interferon aifa-2b. Br J Ophthalmol 2005;89;1221
[32] Fitzpatrick, T, et. al. Color Atlas and Synopsis of Clinical Dermatology, 4th ed. McGraw-Hill,
St. Louis, 2001.
[33] Friedbert, M. Rapuano, C. The Wills Eye Manual, 3rd edition. Philadelphia: Lippincott
Williams and Wilkins, 1999.

[34] Friedman, N. Kaiser, P. Trattler, W. Review of Ophthalmology. Philadelphia: Elsevier, 2005.
[35] Friedman, N. Kaiser, J. The Massachusetts Eye and Ear Infirmary, 3rd Edition. Elsevier,
2009.
[36] Garg A, Fry L. Clinical practice in small incision cataract surgery phaco manual. Jaypee
Brothers Medical Publishers, United Kingdom, 2004.
[37] Gass JDM. Drusen and disciform macular detachment and degeneration. Arch Ophthalmol
1973; 90:206-17.
[38] Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med 1995;10:128-141,
[39] Grayson’ s Diseases of the Cornea, Arffa, R. Third Edition, Mosby, St. Louis, 1991.
[40] Gregory-Evans CY, Williams MJ, Halford S, Gregory-Evans K. Ocular coloboma: a reassess
ment in the age of molecular neuroscience. J Med Genet 2004;41:881-891,
[4T] Grogg, Jane Ann. Ocular Injuries. Contemporary Optometry, Vol 6. Number 9. September
2008.
[42] Grossman, Ashley, (1998). C lin ic a l E n d o c r in o lo g y , 2nd edition, Blackwell Science.
[43] Harkins, Timothy, Clinical Geriatric Eyecare. Ch. 6: Geriatric Ocular Disease. Aston, Sheree
J. Maino, Joseph H. Boston: Butterworth-Heinemann, 1993.
[44] Harkins T. "Sexually Transmitted Diseases.” Optometry Clinics Vol. 3, Number 4, Systemic
Disease and the Eye. Eds. Classe J, Patorgis J. Appleton and Lange, Norwalk, 1994.
[45] Hayreh SS, Zimmerman MB, Ben M, Podhajslty P. Intraocular pressure abnormalities asso
ciated with central and hemiretinal retinal vein occlusion. Ophthalmology 2004;111:131-141.
[46] Hoffman R, Fine H, Packer M, Incidence and outcomes of LASIK with diffuse lamellar ker
atitis treated with topical and oral corticosteroids. J Cataract Refract Surg 2003:29.
[47] Horn, M. LASIK, Clinical Co-Management. Butterworth Heinemann, Boston, 2001.
[48] Hyman LG, Lilienfeld AM, Ferris FL III, Fine SL, Senile macular degeneration: a case control
study. Am J Epidemiol 1983; 118:213.
[49] Jaffe NS, Clavman IIM, JafTe MS: Retinal detachment in myopic eyes following intracapsular
and extracapsular cataract extraction. Am J Ophthalmol 1984; 97: 48-52.
[50] Kahn HA, Moorehead IIB, Statistics on blindness in the model reporting areas, 1969-1970.
DHEW publication no. (NIH) 73-427. Washington DO: U.S. Government Printing Office,
1973.
[51] Kang J, W illett W , Rosner B, et al. Prospective study of alcohol consumption and the risk
of primary open-angle glaucoma. 2007. Ophthalmic Epidemiol 14: 141-7.
[52] Kanski, Jack. Clinical Ophthalmology 4th ed. Woburn: Butterworth and Heinmann, 1999.
[53] Kaufman, P. Aim, A. Adler’s Physiology of the Bye, 10th ed, St, Louis: Mosby, 2003.
[54] Khan S, Finger PT, Yu G, Razzaq L, Jager MJ, et al. Clinical and pathologic characteristics
of biopsy-proven iris melanoma. Arch Ophthalmol 2012;130(l):57-64.
[55] Kinnear PE, Jay B, Witkop CJ. Albinism. Surv Ophthalmol 1985;30:75-101.
[56] Kline, Foroozan, (2007). Optic Nerve Disorders, 2nd edition, Oxford.
[57] Kooragayala, Lakshmana M. Central Retinal Vein Occlusion.

http://emedicine.medscape.com/ai-ticle/1223746-overview.
[58] Krachmer JH, Manms MJ, Holland EJ, Cornea. 2nd ed, Philadelphia: Mosby, 2011.
[59] Krafchak, C. Mutations in TCF8 Cause Posterior Polymorphous Corneal Dystrophy and Ec
topic Expression of COL4A3 by Corneal Endothelial Cells. Am J Hum Genet. 2005 November;
77(5): 694-708.
Copyright 201,4 by KMK Educational Services, LLC

544 10.12. NEURO-OPHTHALMIC DISORDERS: GLAUCOMA
[60] Lemmela, Forsman, Sistonen, Eriksson, Fovsius, Jarvela, Genome-Wide Scan of Exfoliation
Syndrome, IOVS; Sept. 2007, VoL 48, No, 9; 4136-4142.
[61] Lemp, Michael A. The Definition and Classification of Dry Eye Disease: Report of the
Definition and Classification Subcommittee of the International Dry Eye Work Shop 2007.
The Ocular Surface. 2007; 5(2).
[62] Leppien, A, Rudolf, E, Pohlenz, O. CT findings of Carotid Cavernous Fistula: A case report.
J, Neurosurgical Review. 1998; 11: 293-296.
[63] Leibowitz IIM, Krueger DE, Maunder LR, et al. The Framingham Eye Study Monograph: an
ophthalmoiogical and epidemiological review of Cataract, Glaucoma, Diabetic Retinopathy,
Macular Degeneration, and Visual Acuity in a General Population of 2631 Adults, 1973-1975.
Survey o f Ophthalmology 1980;24:614-620,
[64] Machat J, Slade S, Probst L. The Art of Lasik, Slack Incorporated, 1998.
[65] Machat J. Excimer Laser Refractive Surgery; Practice and Principles. Thorofare, NJ: Slack,
1996.
[66] Macular Photocoagulation Study Group: Occult choroidal neovascularization. Influence on

visual outcome in patients with age-related macular degeneration. Arch Ophthalmol 114:
400-412, 1996.
[67] Macular Photocoagulation Study Group: Risk factors for choroidal neovascularization in the
second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary
to age-related macular degeneration. Arch Ophthalmol 115: 741-747, 1997,
[68] Malagola R, Pecorella I, Teodori C, et al. Peripheral lacquer cracks as an early finding in
pathological myopia. Arch Ophthalmol. 2006 Dec;124(12) :1783-4,
[69] Mangan R. Cornea) Refractive Surgery: Coming Full Circle, Review of Optometry, November
15, 2010, p. 110-6.
[70] Mendrinos E, Machinis T, Pournaras C. Ocular Ischemic Syndrome. Survey of Ophthalmol

ogy, Volume 55, Issue 1, January-February 2010, Pages 2-34.
[71] Menon-Mehta S. Ocular lymphoma. Medscape. 2013 June,

http://emedicine.medscape.com/artlcle/1219134-overview.
[72] Miller NR, Newman NJ, Biousse V, Kerrison JB, (2008). Walsh and Hoyt’ s Clinical Neuro
ophthalmology: The Essentials, Second edition. Lippincott, Williams, and Willdns.
[73] Monner J, Benito JR, Zayuelas J, Faloma V, Castro V, Serra JMR. Transconjunctival her
niation of orbital fat. Ann Plast Surg 1998;41:658-661,
[74] Najak H, et al. Diplopia following cataract surgery: a review of 150 patients. Eye
2008;22:1057-1064.
[75] Nichols, K., et.al. The International Workshop on Meibomian Gland Dysfunction: Executive
Summary. Invest. Ophthalmol. Vis. Sci. March 30, 2011 vol. 52 no. 4 1922-1929.
[76] Okuse, C., Yotsuyanagi, H., Nagase, Y., Kobayashi, Y ., Yasuda, K., Koike, K., lino, S,,
Suzuki, M., Itoli, F. Risk Factors for Retinopathy Associated with Interferon alpha-2b and
Ribavirin Combination Therapy in Patients with Chronic Hepatitis C, World J Gastroenterol
2006;12:3756-3769.
[77] Patalano, V. The Risks and Benefits of Cataract Surgery. Digital Journal of Ophthalmology,
2011.
[78] Pavan-Langston, Deborah. Manual of Ocular Diagnosis and Therapy, 6th edition. Philadel
phia, Williams and Wilkins, 2008.
[79] Pouliquen Y, Dhermy P, Espinasse MA, Savoldelli M. Keratoglobus. J Fr Ophtalmol.

1985;8(1).*43-54.
[80] Priglinger SG, Wolf AH, Kreutzer TC, et al. Intravitreal bevacizumab injections for treatment
of central retinal vein occlusion; six-month results of a prospective trial, Retina. 2007;27;1004-
1012.

[81] Purves,D. Augustine, G, Fitzpatrick, D. et. al. Neuroscience, 2nd Ed. Sinauer Associates,
Inc, 2001.
[82] Quigley H and Broman A. The number of people with glaucoma worldwide in 2010 and 2020.
2006. Br J Ophthalmol 90: 262-7.
[83] Ramulu P. Standard Automated Perimetry. 2012. Available from www.eyewiki.aao.org
[84] Rapuano, Christopher J. I-Ieng, Wee-Jin. Color Atlas and Synopsis of Clinical Ophthalmology.
Wills Eye Hospital. Singapore: McGraw-Hill, 2003.
Heinemann, 1988.
[86] Rhee, Pyfer, (1999). W ill’s Eye Manual, 3rd edition, Lippincott, Williams, and Wilkins.
[87] Ritch R, Schlotzer-Schrehardt, Konstas, Why is glaucoma associated with exfoliation syn
drom a?—Rrogress-in-Ret i nal-an d-Eye -Resear ch-22-(2003)~253=2757
[88] Roat MI. 2012 Nov. Superficial punctate keratitis. Merck Manuals.
http://www.merckmanuals.com. Accessed 2014 Feb 03.
[89] Roth H. Contact lens complications: etiology, pathogenesis, prevention, therapy. Thieme,
2003.
[90] Ryan SJ, Sadda SR, Hinton DR, Schachat AP, Wilkinson CP, Wiedemann P, Retina. 5th ed.
Philadelphia: Saunders Elsevier, 2013.
[91] Sangwan, Virender; Zafirakis, Panayotis; Foster. Mooren’s nicer: Current concepts in man
agement. Indian Journal of Ophthalmology. January 01, 1997.
[92] Schmack I, Kang SJ, Grossniklaus HE, Lambert SR. Conjunctival granulomas caused by
synthetic fibers: Reports of two cases and review of literature. J AAPOS 2005;9:567-571.
[93] Shetlar DJ, Saornil MA, Kurban RS, Westfall CT, Mihm MC. Pathology of the lids. In:
Albert DM, Miller JW. Albert and Jakobiec’s principles and practice of ophthalmology. 3rd
ed. Philadelphia 2008: Saunders-Elsevier Inc. 3737-3751.
[94] Shields CL, Furuta M, Berman EL, et al. Choroidal nevus transformation into melanoma:
analysis of 2514 consecutive cases. Arch Ophthalmol. 2009. Aug;127(8):981-7.
[95] Shields, Shields. Eyelid, Conjuctival and Orbital Tumors, Lippincott Williams and Wilkins,
2008.
[96] Shields CL, Kalild S, Hutchinson A, Nickerson S, Patel J, et al. Iris nevus growth into
melanoma: analysis of 1611 consecutive eyes. Ophthalmology 2013;120:766-772.
[97] Shingleton BJ, Ilersli PS, Kenyon KR, Eye Trauma. St. Louis: Mosby Year Book, 1991.
[98] Siddiqui Y, Ten Iluizen R, Cameron J, Hodge D, Johnson D. What is the risk of develop
ing pigmentary glaucoma from pigmentary dispersion syndrome? Am J Ophthalmol. 2003.
June;135(6): 794-9.
[99] Smith, J.L. The Pupil, SeJf-published - no longer printed. Unknown location, 1971.
[100] Soiberman U, Kakizaki H, Selva D, Leibovitch I. Punctal stenosis: definition, diagnosis, and
treatment. Clin Ophthalmol 2012;6:1011-1018.
[101] Spoor, T, (1992). Atlas of Optic Nerve Disorders, Raven Press.
[103] The Eye Diseases Prevalence Research Group. Archives of Ophthalmology 2004;122:487-494.
[104] The Glaucoma Handbook, Optometric Glaucoma Society. Review of Optometry, August
2008.
[105] Thomas, R. Melton, R. http://w w w .eyeupdate.com /

546 10.12. NEURO-OPHTHALMICDISORDERS: GLAUCOMA
[106] Tielsch J, Katz J, Sommer A, et al. Family history and risk of primary open angle glaucoma.
The Baltimore Eye Survey, 1994. Arch Ophthalmol 112: 69-73.
[107] Watanabe FL Clinical cases in contact lenses, Bultcrworth-Heinemann, 2002.
[10S] YanoJT M, Duker J, Ophthalmology. Mosby, 2009
[109] Zadnik K, Barr JT, Edrington TB, Everett DF, Jameson M, McMahon T T , Shin JA, Sterling
JL, Wagner II, Gordon MO, Baseline findings in the Collaborative Longitudinal Evaluation
of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci. 1998 Dec;39(l3):2fi37-46,
[110] Zejmo M, Forminska-Kapuscik M, Pieczara E, et al. Etiopathogenesis and management of

high myopia. Part II. Med Sci Monit. 2009 Nov; 15(11):RA252-5.

Index
78/90D lens, 497 allopurinol, 332

Alzheimer’s disease, 363
A-scan ultrasound, 490 amacrine cells, 142
abducens nerve, 158 amaurosis fugax, 509
palsy, 67 amblyopia
acanthamoeba, 301 types of, 200
acne rosacea, 335 amino acids
actinic keratosis, 418 essential, 223
actinomyces israeli, 421 nonessential, 223
actinomycetes, 283 anaerobic respiration, 237
action potential anaphylactic shock, 350
neuron summary of, 46 anemia
acute dacryoadenitis, 82 aplastic, 343
acute inflammation, 323 iron deficiency, 343
Addison’s disease, 368 sickle cell, 341
adenovirus, 289 anencephaly, 375
ADH, 16 aneurysms, 351
Adie’s tonic pupil, 64 angiod streaks, 132, 528
adrenal gland, 14 angle
against the rule astigmatism, 105 structures of, 119
age-related macular degeneration, 133, angle recession, 533
514 angular vein, 99
aging aniridia, 107, 123, 467
general characteristics of, 212 anisocoria, 63
vision changes of, 213 ankylosing spondylitis, 330, 445
AIDS, 333 anophthalmos, 410
AION, see ischemic optic neuropa anorexia nervosa, 387
thy anterior basement membrane dys
albinism, 28, 225, 520 trophy, 461
albumin, 19, 41 anterior chamber, 118
alcoholism, 388 anterior ciliary veins, 98
alkali corneal burn, 107 anterior hyaloid, 135
547
548 INDEX
anterior iris stromal leaf, 123 Best’s disease, 523

antibiotic susceptibility testing beta oxidation, 246
methods of, 286 bilateral integration, 209
antibodies, 226 binocular indirect ophthalmoscopy
summary of various types of, (BIO), 497
226 biomicroscopy, 397
structure of, 307 illumination techniques, 397
antigen, 307 bipolar cells, 142
antigen presenting cell, 313, 314 bipolar disorder, 389
antinuclear antibody test, 319 bitemporal hemianopsia, 88, 174
anxiety, 389 blepharitis, 414
APD, see swinging flash light test bacterial, 414
aphakia, 491 herpetic, 471
apocrine secretion, 12 seborrheic, 414
apoptosis, 326 blepharoconjunctivitis
arcus senilis, 479 herpes zoster, 474
Argyll-Robertson pupil, 63, 64, 284 blood
aspergillus fumigatus, 296 composition of, 19
asteroid hyalosis, 498 blood chemistry, 332, 366, 372
asthma, 382 bone
astigmatic keratotomy, 484 cells of, 23
astrocytes, 147 bordatella, 282
atherosclerosis, 351 bowman’s layer of the cornea, 107
atopic keratoconjunctivitis, 430 branch retinal artery occlusion, 504
Auerbach’s plexus, 36 branch retinal vein occlusion, 98,
autoclave, 287 148, 502
AxenfeId’s nerve loop, 442 Broca’s area, 49
Axenfeld-Rieger syndrome, 467 Bruch’s membrane, 132
buffer, 234
B-scan ultrasound, 490 bulbar conjunctiva, 112
bacillis anthracis, 280 bulimia nervosa, 387
band keratopathy, 107, 479 buphthalmos, 537
Barrett’s esophagus, 377 busacca nodules, 445
basal cell carcinoma, 338, 418
stratum basal cell layer, 27 c-reactive protein test, 319
basophils, 20 calcarine fissure, 171
becker-shaffer grading system, 119 calcitonin, 24
Behqet’s, 337 canal of hannover, 126
Behcet’s disease, 445 canal of petit, 126
bell’s palsy, 160, 364 canaliculitis, 421
benign essential blepharospasm, 417 cancer, 264
benign prostatic hypertrophy (BPH), colon, 378
372 genes of, 264
Berger’s space, 135 lung, 384
Bergmeister’s papillae, 136 most common for men and women,
berlin’s edema, 402 374

INDEX 549
Candida albicans, 294, 296 chalazion, 414

capillary hemangioma, 92, 408 Chandler’s Syndrome, 537
capsid, 287 chemical bonds, 222
carbohydrates, 235 types of, 222
structures of, 235 chemical burn, 398
carcinoma, 385 cherry red macula, 8
carotid artery disease, 353 chlamydia, 284, 285, 370
carotid-cavernous fistula, 102, 407 cholesterol
caruncle, 113 normal values of, 352
cataract role within eukaryotic cells, 3
anterior supcapsular, 488 chorda tympani nerve, 159
congenital, 488 choriocapillaris, 132______
cofticalTUSS chorioretinitis, 529
lamellar, 489 choroid, 130
posterior subcapsular, 488 blood supply of, 133
cataract surgery innervation of, 133
corneal edema, 495 layers of, 131
diplopia, 495 choroidal atrophy
ECCE, 491 senile, 530
ICCE, 491 choroidal detachment, 495
iritis, 496 choroidal folds, 520
phacoemulsification, 492 choroidal melanoma, 131
post-op complications, 492 choroidal neovascular membrane, 133
types of, 491 choroidal nevus, 513
.cavernous hemangioma, 92, 408 choroidal rupture, 403
cavernous sinus, 101 choroideremia, 522
cell, 219 chromosome analysis, 267
organelles of, 219 chronic bronchitis, 382
cell communication, 220 chronic inflammation, 323
cell cycle, 265 chronic obstructive pulmonary dis
cell structure, 219 ease, 382
cellophane retinopathy, 518 ciliary body, 126
central areolar choroidal dystrophy, blood supply of, 130
530 functions of, 127
central nervous system innervation of, 130
divisions of, 50 regions of, 127
central retinal artery, 95 ciliary muscle, 128
central retinal artery occlusion, 503 cilioretinal artery, 147, 504
central retinal vein, 98, 147 circle of Willis, 55
central retinal vein occlusion, 98, circle of willis, 358
500 circle of Zinn, 96
central serous chorioretinopathy, 163 cirrhosis, 380
central serous choroidopathy, 516 clear lens extraction, 484
cerebellum, 53 clinically significant macular edema,
cerebral hemispheres, 53 507
cerebral palsy, 375 Cloquet’s canal, 136

550 INDEX
CMV, 529 conjunctival melanoma, 424

CN 3, see oculomotor nerve conjunctival nevus, 424
CN 4, see trochlear nerve conjunctivitis
CN 6, see abducens nerve adenoviral, 427
Coats’ disease, 511 allergic, 429
Cogan-Reese Syndrome, 537 bacterial, 278
collagen, 226 chlamydial - inclusion, 435
disorders of, 227 chlamydial - trachoma, 436
structure of, 18 epidemic keratoconjunctivitis (EKC),
synthesis of, 226 289, 427
collagen vascular disorders, 477 giant papillary(GPC), 432
coloboma, 181 gonococcal, 426
iris, 449 ligneous, 438
color vision molluscum contagiosum, 335, 429
development of, 197 pharyngoconjunctival fever (PCF),
common tendinous ring, 85, 89 427
commotio retinae, 402 phlyctenulosis, 437
competitive inhibition, 229 simple bacterial, 426
complement pathway, 311 superior limbic keratoconjunc
complete blood count, 319 tivitis (SLK), 437
conductive keratoplasty, 483 contact dermatitis, 336, 412
cone dystrophy, 523 contact lens
cones, 140 defect, 433
confluence o f the sinuses, 103 fitting problem, 433, 434
congenital glaucoma, 467 fitting problems, 434
congenital hypertrophy of the reti contact lens related complications
nal pigmented epithelium 3- and 9-o’clock staining, 434
(CHRPE), 513 contact lens deposits, 433
congestive heart failure, 354 corneal warpage, 433
congruity with visual field defects, dimple veiling, 435
173 SEAL, 434
conjunctiva, 111 solution hypersensitivity, 432
blood supply of, 113 solution toxicity, 432
lymphatics of, 80, 113 superior limbic keratoconjunc
nerves of, 113 tivitis, 433
conjunctival tight lens syndrome, 434
concretions, 424 contrast sensitivity
cyst, 423 development of, 197
granuloma, 426 cornea, 104
hemorrhage, 439 acanthamoeba keratitis, 470
laceration, 403 bacterial keratitis, 468
lesions, 423 blood supply of, 109
squamous cell carcinoma, 425 development of, 185
conjunctival abrasion, 399 endothelial dystrophies, 464
conjunctival intraepithelial neopla epithelial dystrophies, 461
sia (CIN), 425 fungal keratitis, 469

INDEX 551
graft rejection, 480 culture

herpes simplex keratitis, 471 methods of, 286
herpes zoster, 337, 474 cuneus gyrus, 171
innervation of, 110 Cushing’s syndrome, 368
interstitial keratitis, 472 custom cornea, 485
layers of, 105 cyclitic membrane, 444
phlyctenulosis, 437 cystoid macular edema, 490
refractive surgery, 481 cystoid macular edema (CME), 494
Salzmann’s nodular degenera cytokines, 316
tion, 478 cytomegalovirus, 290, 334, 447, 448
staphylococcal marginal kerati
tis, 476 dacryoadenitis, 420
stromaTHystrop hies, 462 dacryocystitis, 83, 421
superior limbic keratoconjunc decompensating phoria, 495
tivitis (SLK), 437 dellen, 450
Terrien’s marginal degeneration, demodex, 298
478 demodicosis, 439
cornea plana, 466 depression, 388
corneal dermatochalasis, 414
deposits, 477 dermoid cyst, 408, 415
ectasia, 486 descemet’s membrane of the cornea,
edema, 495 108
laceration, 403 desmosomes, 10
striae, 486 development
corneal abrasion, 398 cognitive and social, 204
role of nocireeeptors, 28 emotional, 206
corneal farinata, 480 gross and fine motor, 203
corneal haze, 488 infant and child, 191
corneal hydrops, 459 language, 207
corneal neovascularization, 472 summary chart of child, 209
corneoscleral meshwork, 121 developmental tests, 208
corona ciliaris, 127 diabetes insipidus, 366
coronary artery disease, 352 diabetes mellitus, 365
corrugator muscle, 80, 87 diabetic
CPR, 353 screening, 505
cranial nerve III palsy, 77 diabetic eye exam, 505
cranial nerve X palsy, 151 diabetic papillopathy, 56, 59
cranial nerve XII palsy, 151 diabetic retinopathy, 505
cranial nerves, 151 diencephalon, 181
crepitus, 401 summary of, 53
critical period, 200 dimple veiling, 435
crocodile shagreen, 107, 480 directionality, 209
Crohn’s disease, 377 disc edema, 56
croynebacterium diptheriae, 280 disinfection, 287
cryptococcus neoformans, 296 DLK, 487
Crystalens, 492 DNA

552 INDEX
structure of, 256 epithelial ingrowth, 487

DNA mutation Epstein-Barr Virus), 289
types of, 263 erythrocyte sed rate, 319
DNA mutations, 263 escherichia coli, 282
DNA repair, 263 ethmoid bone, 92
DNA replication, 257 evisceration, 411
dominant optic atrophy, 61 exenteration, 411
dorsal nasal artery, 97 exposure keratopathy, 450
Down’s syndrome, 339 external carotid artery, 93
dry eye, 454, 487 branches of, 93
evaporative, 457 external jugular vein, 100
Sjogren’s syndrome, 456 external limiting membrane, 141
Duane’s syndrome, 67 extraocular muscles
Duchenne muscular dystrophy, 342 blood supply of, 87
dural sinuses of the head, 101 nerve supply of, 87
dysplasia, 386 summary of, 87
eyebrows, 80
E-LASIK, 483 eyelid, 73
EBMD, 461 arterial supply of, 79
ectropion, 415 cysts of, 415
Edinger-Westphal nucleus, 152 ecchymosis, 403 1
Ehler’s Danlos syndrome, 117 layers of, 73
electron transport chain, 238 nerves of, 79
embolism, 350 veins of, 80
embolus, 350
embryonic nucleus, 185 Fabry’s Disease, 342
emmetropization, 194 facial nerve, 158
emphysema, 382 fatty acid synthesis, 246
endophthalmitis, 490, 495 femtosecond laser, 492
endothelium layer of the cornea, 109 fetal fissure, 181
energy reactions fetal nucleus, 185
types of, 232 filamentary keratopathy, 451
enophthalmos, 411 Fleischer’s ring, 459
entropion, 416 floaters, 135
enucleation, 411 Flomax, 491
enzyme regulation, 231 floppy eyelid syndrome, 416
enzymes floppy iris syndrome, 491
mechanisms of, 228 fluorescein angiography (FA), 516
eosinophils, 20 Fluorescent Treponemal Antibody
Epi-LASIK, 483 Absorption Assay (FTA-ABS),
epicapsular star, 136 372
epicapsular stars, 490 folic acid deficiency, 344
epidural hematoma, 363 follicles, 431
epiretinal membrane, 145, 518 foramen ovale, 89
episcleral veins, 122 foramen rotundum, 89
episcleritis, 440 foramen spinosum, 89

INDEX 553
forebrain, 181 glaucomatocyclitic crisis, 445,

foreign body 538
intraocular, 401 inflammatory, 538
superficial, 399 mixed mechanism, 536
Tbster Kennedy syndrome, 60 neovascular, 536
fovea, 149 normal tension, 533
foveal avascular zone, 149 ocular hypertension, 530
foveala, 149 phacolytic, 538
frontal bone, 91 pigmentary dispersion, 532
frontal lobe, 49 primary open angle, 531
frontal nerve, 156 pseudoexfoliation syndrome, 532
frontal vein, 99 secondary angle closure, 536
“frontalis muscle7~8"0 uveitic, 536
Fuchs endothelial dystrophy, 464 glossopharyngeal nerve, 160
Fuchs’ heterochromic iridocyclitis, gluconeogenesis, 240
538 glycocalyx, 4
fundoscopy, 496 glycogenesis, 241
fungi, 292 glycogenolysis, 241
laboratory examination of, 292 glycolysis, 236
reproduction of, 293 glycosaminoglycans, 18
Golgi apparatus, 7
ganglion cell layer, 143 gonioscopy, 539
ganglion cells, 143, 144 Goldmann lens, 539
gap junctions, 9 Posner lens, 539
Gardner’s syndrome, 341 Sussman lens, 539
gastroesophageal reflux disease, 376 Zeiss lens, 539
GDx, 538 gonorrhea, 370
gene expression, 262 gout, 332
regulation of, 262 granular dystrophy 462
gene therapy, 268 Graves disease, 60
genetic disorders, 339 graves’ ophthalmopathy, 405
genomics, 266 gray matter, 50
giant cell arteritis, 58 greater petrosal nerve, 159
giardia, 299 Guillain-barre syndrome, 362
Gibbs free energy, 232 gyrate atrophy 525
glands of Krause, 82
glands of Wolfring, 82 haab’s striae, 109, 467
glaucoma, 530 haemophilus influenzae, 281
angle recession, 533 halier’s layer, 132
angle-closure, 534 Hashimoto’s thyroiditis, 366
congenital, 187, 537 hassall-henle bodies, 109
diagnostic tests, 538 HDL
Fuch’s heterochromic iridocy function of, 245
clitis, 446 headaches, 359
Fuchs’ heterochromic iridocy heart
clitis, 538 congenital diseases of, 375

554 INDEX
congestive heart failure, 354 hypertension, 353

palpitations of, 356 hypertensive retinopathy, 507
shunts of, 375 hyperthyroidism, 367
helper t cell, 313-315 hyperviscosity retinopathy, 509
heraidesmosomes, 10 hyphema, 400, 495
hemorrhage hypoparathyroidism, 367
types of, 348 hypothyroidism, 366
Henderson-Hasselbalch equation, 235 hypotony, 495
Henlels fiber layer, 149
henle’s fiber layer, 142 idiopathic intracranial hypertension,
hepatitis, 290 see pseudotumor cerebri
types of, 290, 379 idiopathic juxtafoveolar retinal telang
herpes simplex, 446 iectasia, 511
herpes simplex keratitis, 155 impetigo, 336
herpes simplex virus, 289, 336, 371, implantable contact lens, 484
471 inclusion cyst, 415, 423
herpes zoster, 446 inferior oblique, 86
herpes zoster keratitis, 156 inferior ophthalmic vein, 98
herpes zoster ophthalmicus, 474 inferior petrosal sinus, 102
herpes zoster virus, 337, 474 inferior rectus, 85
heterochromia, 124 inferior sagittal sinus, 103
hippocampus, 50 infiltrate, 469, 477
histogram, 198 inflammatory bowel disease, 445
histoplasmosis, 295, 299, 447, 517 Crohn’s disease, 377
HIV retinopathy, 510 ulcerative colitis, 377
Hodgkin’s lymphoma, 345 infraorbital nerve, 157
Hollenhorst plaque, 356 infraorbital vein, 99
holocrine secretion, 12 inner nucleur layer, 142
homonymous visual field defects, 173 inner plexiform layer, 143
hordeolum, 415 Intacs, 484
horizontal cells, 142 treatment range, 484
Horner’s syndrome, 65, 163, 364 interferon retinopathy, 510
horner’s syndrome, 77 interferons, 309
HRT, 538 interleukins, 316
Hruby lens, 496 internal carotid artery, 94
human leukocyte antigen (HLA-B27), aneurysm of, 95
332 branches of, 94
human papillovirus (HPV), 290 internal jugular vein, 100
Huntington’s chorea, 340 internal limiting membrane, 145
Hutchinson’s pupil, 65 interplexiform cells, 142
hutchinson’s sign, 156 interstitial keratitis, 284, 472
hyaloid artery, 136 intralase, 483
hyaluronic acid, 18 intraocular lens
hydrops, 109 types of, 492
hyperparathyroidism, 367 intrastromal corneal rings, 484
hypersensitivity reactions, 326 intrinsic factor, 37

INDEX 555
iridocyclitis Krause glands, 78

acute, subacute, 443 krebs cycle, 237
iridodialysis, 403 kwashiorkor, 387
iriodcyclitis
chronic, 443 lacquer cracks, 518
iris, 122 lacrimal artery, 95
atrophy, essential, 537 lacrimal bone, 92
coloboma, 449 lacrimal gland, 81
color of, 124 lacrimal nerve, 156
layers of, 124 lacrimal sac, 82
malignancy of, 450 lacrimal system, 81
prolapse, 495 lamina cribosa, 166
iris collarette, 123 lam ina cribrosa, 118
iris cyst, 126 lamina papyracea, 92
iris dilator muscle, 125 large intestine
iris sphincter muscle, 125 summary of, 38
ischemic optic neuropathy, 56, 58 LASEK, 483
Laser-assisted in situ keratomileu
jaundice, 380 sis (LASIK), 483
Jones I and II testing, 423 LASIK, 107
junctional scotoma, 174 treatment range, 483
juvenile idiopathic arthritis, 329 lateral geniculate nucleus, 167, 170
juvenile rheumatoid arthritis, 329, lateral rectus, 85
446 lateral rectus palsy, 158
juxtacanalicular tissue, 121 laterality, 209
lattice degeneration, 527
keratitis lattice dystrophy, 463
chemical, 432 Leber’s optic neuropathy, 57, 61
filamentary, 437 lens, 113
intersital, 472 composition of, 114
interstitial, 446 crystallins, 115
superficial, 451 development of, 184
Keratoacanthoma, 334 posterior capsular opacification,
keratoacanthoma, 419 490
keratoconjunctivitis, 435 pre and post-operative care, 490
keratoconjunctivitis sicca, 454 summary of cataracts, 488
keratoconus, 107, 397, 433, 459, 486 lens subluxation, 493
keratoglobus, 460 lens zonular fibers, 128
keratopathy lens zonules, 115
bullous, 495 leukemia, 345
ketone bodies, 246 leukocoria, 512
kidney limbal dermoid, 468
diseases of, 369 limbus, 112
klebsiella pneumoniae, 282 Lineweaver-Burke equation, 229
Klinefelter’s syndrome, 339 lingual gyrus, 171
koeppe nodules, 445 lipids, 242

556 INDEX
digestion of, 244 medial longitudinal fasciculus, 152

types of, 242 medial rectus, 85
types within plasma membrane, medulla
3 upper and lower, 52
liver megalocornea, 465
diseases of, 378 meibomian glands, 78
roles of, 241 Meige’s syndrome, 417
summary of, 39 Meissner’s plexus, 36
long posterior ciliary arteries, 97 melanocytes, 27
long posterior ciliary nerves, 156 melanocytoma, 62
summary of, 163 membrane biochemistry, 247
lupus, 328 meningioma, 361, 408
lyme disease, 445 meningitis, 360
lymph nodes, 31 merocrine secretion, 12
lymphocytes mesoderm, 187
B, 312 Messman’s dystrophy, 461
T, 313 metaplasia, 386
lymphoma, 408 metazoa, 297
lysosomes, 7 meyer’s loop, 170
Michaelis-Menten equation, 228
macroaneurysm, 508 microcornea, 466
macrostriae, 486 microglial cells, 147
macula, 148, 171 microphthalmos, 376, 410
age-related macular degenera microstriae, 486
tion, 514 midbrain, 52
epiretinal membrane, 518 milestones, 202
photostress test of, 520. milia, 415
macula only defect, 174, 357 minerals, 249
macular dystrophy, 462 functions of, 254
macular hole, 519 minimum inhibitory concentration
macular involving defect, 174 (MIC), 286
macular photostress test, 520 mitochondria, 8
macular sparing defect, 174, 357 Mittendorf’s dot, 136
madarosis, 73 molds, 293
major arterial circle of the iris, 97, moll glands, 12, 78
124 molluscum contagiosum, 290
malaria, 298 monocytes, 20
malignant HTN, 60 Mooren’s ulcer, 475
malignant melanoma, 28, 337, 419 moraxella, 282
marasmus, 387 morning glory syndrome, 61
Marcus Gunn, see swinging flash mucor, 296
light test Muller cells, 146
Marfan’s syndrome, 340 multiple sclerosis, 59, 361
maxillary artery, 93 Munson’s sign, 459
maxillary bone, 91 muscle
maxillary vein, 100 types of, 24

INDEX 557
muscle of horner, 74 noncompetitive inhibition, 230

muscle of Muller, 76 nonspecific immunity, 309, 310
muscle of riolan, 74 normal visual field, 540
muscular artery, 95 northern blot, 267
myasthenia gravis, 362 nuclear sclerosis, 213, 488
mycobacteria, 283 nucleolus, 5
mycoplasma, 285 nutrition, 248
mycoses nutritional disorders, 387
cutaneous, 294 nystagmus
subcutaneous, 295 optokinetic, 192
superficial, 294
systemic, 295__________________ occipital lobe, 50______________ __
myelin, 26 occipital sinus, 103
myelinated nerve fibers, 505 occipital vein, 100
myokymia, 417 OCT, 538
myopia spectral domain, 539
pathological, 517 swept source, 539
myopic degeneration, 517 time domain, 539
ocular
NAION, see ischemic optic neuropa lithiasis, 424
thy prosthesis, 411
nasociliary nerve, 156 ocular cicatricial pemphigoid, 412
nasolacrimal drainage system, 82 ocular dominance columns, 172
nasolacrimal duct, 84 ocular dominance histogram, 198
nasolacrimal duct obstruction, 422 ocular hypertension, 530
natural killer cell, 310, 319 ocular ischemic syndrome, 97, 509
necrosis, 325 ocular myasthenia, 68
neisseria gonorrhea, 281 ocular rosacea, 411
neisseria meningitidis, 282 oculocutaneous albinism, 124
neoplasia, 385, 386 oculomotor nerve, 152
neovascularization divisions of, 153
corneal, 433 pupil-involving palsy, 154
nerve fiber layer, 144 pupil-sparing palsy, 154
neural ectoderm, 181 oculomotor palsy, 66
neuro-ophthalmic disorders, 55, 530 oculomotor system
neuroblastoma, 408 development of, 195
neurofibromatosis, 340 oligodendrocytes, 26
neuroglial cells, 146 omega-3 fatty acids, 248
neuroretinitis, 59 omega-6 fatty acids, 248
neur otr ansmitters onchocerciasis, 529
summary of, 47 ophthalmia neonatorum, 285, 436
neurotrophic keratitis, 110 ophthalmic artery, 95
neurotrophic keratopathy, 452, 472 muscular branches of, 87
neutrophils, 20, 323 optic chiasm, 168
nocireceptors, 28 orientation of fibers, 168
non-pigmented ciliary epithelium, 129 optic disc, 165

558 INDEX
orientation of fibers at, 167 oxidative phosphorylation, 238

optic nerve, 152, 164 oxygen radicals, 255
blood supply of, 165 oxytocin, 16
general characteristics of, 164
glioma, 408 pain in and around eye, 442
lesions of, 175 palatine bone, 91
sections of, 166 Palisades of Vogt, 107
optic nerve coloboma, 61 palisades of Vogt, 112
optic nerve glioma, 62 palpebral conjunctiva, 112
optic nerve head drusen, 61 pancreas, 38
optic nerve hypoplasia, 61 diseases of, 380
optic nerve pit, 61 function of, 13
optic nerve sheath meningioma, 62 papillae, 431
optic nerve: neuro-ophthalmic dis papilledema, 57, 165
orders, 55 papillomacular bundle, 144, 167
optic neuritis, 56, 59, 165 papillophlebitis, 56, 59
optic neuropathy parafovea, 149
Leber’s, 8, 343 parasites
traumatic, 403 laboratory identification of, 301
optic radiations, 170 parasympathetic nervous system
optic tract, 168 description of pathway, 161
optical coherence tomography, 538 parathyroid gland, 14
optokinetic nystagmus, 192 parathyroid hormone, 24
ora serrata, 128, 150 parietal lobe, 50
orbicularis ciliaris, 127 parietal lobe lesion, 173
orbicularis oculi muscle, 80 Parinaud’s oculoglandular syndrome,
orbit 438
adipose tissue, 84 Parkinson’s disease, 363
bones of, 91 pars plana, 127
contents of, 84 pars planitis, 447
extraocular muscles, 84 pars plicata, 127
foramens of, 90 pavingstone degeneration, 518
orbital cellulitis, 75, 404 pediculosis, 298, 439
orbital fascia, 88 pellucid marginal degeneration(PMD),
orbital floor fracture, 92, 401 460
orbital nerves, 151 penetrating ocular injury, 399
orbital pseudotumor, 409 Penicillamine, 379
orbital septum, 75, 414 pentose phosphate shunt, 240
orthograde degeneration, 25 peptic ulcer disease, 377
osteoblasts, 23 pericytes, 17
osteoclasts, 23 perifovea, 150
osteocytes, 23 peripheral nervous system
osteogenesis imperfecta, 117, 342 summary of, 48
outer nuclear layer, 141 periphlebitis, 510
outer plexiform layer, 141 Peter’s anomaly, 468
oxidation-reduction reactions, 233 phakic IOL, 484

INDEX 559
pheochromocytoma, 368 pregnancy, 373

phlyctenulosis, 437 complications of, 373
photoreceptors, 139 preseptal cellulitis, 75, 404
photorefractive keratectomy (PRK), pretectal nucleus, 167
482 primary acquired melanosis (PAM),
phthiriasis palpebrarum, 73, 439 424
phthisis bulbi, 410 primary visual cortex, 171
Piaget’s right left awareness test, prions, 292
209 PRK, 107
pie in the sky defect, 173 treatment range, 482
pie on the floor defect, 173 procerus muscle, 80
pigment dispersion syndrome, 126 prolapsed orbital fat, 404
■pigmehte3_ciliary epithelium, 129 prostate
pingueculum, 439 conditions of, 372
pituitary adenoma, 361 proteins, 223
pituitary gland, 15, 16 structural levels of, 225
plasma membrane, 3 types within plasma membrane,
platelets, 20 4
plica semilunaris, 112 proteomics, 266
pneumoconiosis, 383 proteus mirabilis, 282
pneumocystic pneumonia, 334 pseudomonas aeruginosa, 280, 469
Pneumocystis jiroveci, 301 pseudophakia, 492
pneumocytes, 35 pseudotumor cerebri, 57, 60, 67
poliosis, 73 pseudoxanthoma elasticum, 132
polymerase chain reaction (PCR), Psoriatic arthritis, 331
266 pterygium, 107, 439
Polymyalgia Rheumatica, 331, 360 pterygoid venous plexus, 100
pons, 52 ptosis
portal triad, 39 acquired, 495
Posner-Schlossman syndrome, 538 punctal
post-operative complications stenosis, 422
cataract surgery, 492 pupil, 123
refractive surgery, 485 pupillary ruff, 125
posterior capsular opacification (PCO), purtscher’s retinopathy, 403
493 pyogenic granuloma, 425
posterior cerebral artery, 172
posterior chamber, 126 radial keratotomy, 482
posterior embryotoxin, 122 radicals, 255
posterior facial vein, 100 rapid plasmid reagin (RPR), 372
posterior iris stromal leaf, 123 reactive arthritis, 330
posterior ischemic optic neuropathy, reactive arthritis syndrome, 445
56 recognition acuity
posterior polymorphous dystrophy, development of, 193
465 recurrent corneal erosion, 10, 106,
posterior vitreous detachment, 135, 453
498 red-cap desaturation, 56

560 INDEX
reflexes retinopathy of prematurity, 511

non-survival, 202 retinoschisis, 142, 528
survival, 202 retrobulbar optic neuritis, 56
refractive error retrograde degeneration, 25
development of, 194 retrolental fibroplasia, 511
refractive surgery, 481 reverse APD, 63
enhancement, 488 reZOOM, 492
flap complications, 485 rhabdomyosarcoma, 386, 408
glare, 486 rheumatoid arthritis, 328
infection risk, 485 rhinophyma, 335, 411
long term management, 488 rhizopus, 296
residual refractive error, 486 ribosomes, 6
success, 485 rickettsia, 285
wave-front guided, 485 RNA
Reis-buckler dystrophy, 462 function of, 258
reis-buckler’s dystrophy, 107 structure of, 258
Reiter’s syndrome, 330 types of, 258
renal cell carcinoma, 370 RNFL, 538
restasis, 317 rods, 140
reSTOR, 492 Roth spot, 356
retention cyst, 423 rough endoplasmic reticulum, 7
retina, 136 rubella, 376
artery macroaneurysm, 508 ruptured globe, 399
blood supply of, 147
diabetic retinopathy, 505 Salzmann’s nodular degeneration, 478
hypertensive retinopathy, 507 Sands of the Sahara, 487
hyperviscosity retinopathy, 509 sarcoidosis, 329, 446-448, 529
layers of, 137 sarcoma, 385
lesions of, 176 sattler’s layer, 132
neuroglial cells of, 146 scabies, 298
retinal Schirmer’s test, 454
detachment schizophrenia, 389
non-rhegmatogenous, 527 Schlemm’s canal, 122
ischemia, 509, 510 Schnyder’s dystrophy, 463
pigment epitheliopathy, 529 schwalbe’s line, 122
vasculitis, 510 schwann cells, 26
retinal defects NFL, 538 schwannoma, 361
retinal detachment, 494, 525 sclera, 116
retinal nerve fiber layer, see RNFL emissaria of, 118
retinal pigmented epithelium, 137 general characteristics of, 116
retinitis layers of, 116
cytomegalic, 529 scleral depression, 498
retinitis pigmentosa, 521 scleral spur, 119
retinoblastoma, 184, 512 scleritis, 441
retinopathy sclerocornea, 466
atheriosclerotic, 507 scleroderma, 332

INDEX 5 61
scleromalacia perforans, 328, 441 straight sinus, 103

sebaceous cyst, 415 streptococcus pneumoniae, 279
sebaceous gland carcinoma, 419 streptococcus pyogenes, 279
seborrheic keratosis, 334 stroke, 357
secondary angle closure glaucoma, effects on facial muscles, 160
536 SturgeUWeber syndrome, 338
sedimentation rate, 58 subarachnoid hemorrhage, 357
Seidel’s test, 400 subdural hematoma, 364
seizures, 358 suicide, 389
sella turcica, 88 superficial punctate keratitis (SPK),
serpigionous choroidopathy, 529 451
serratia marcescens, 283 superficial temporal arteritis, 93, 360
Jsfibck superficial temporal artery, 93
types of, 350 superficial temporal vein, 100
short posterior ciliary arteries, 96 superficial veins o f the orbit, 99
short posterior ciliary nerves, 156 superior colliculus, 167
summary of, 163 superior limbic keratoconjunctivitis
sickle cell anemia, 341 (SLI<), 433
sigmoid sinus, 103 superior oblique, 86
signal transduction, 221 trochlea, 86
Sjogren’s syndrome, 13, 329 superior oblique palsy, 154
sleep apnea, 416 superior ophthalmic vein, 98
small intestine superior orbital fissure, 89
summary of, 38 superior palpebral levator muscle,
smooth endoplasmic reticulum, 7 75
southern blot, 266 superior petrosal sinus, 102
space occupying lesion, 158 superior rectus, 85
specific immunity, 312 superior sagittal sinus, 102
overview of, 313 suprachoroid al hemorrhage, 495
sphenoid bone, 88 supraorbital vein, 99
spina bifida, 374 supratrochlear artery, 97
spinal cord, 50 swinging flash light test, 62
spiral of tillaux, 86 symblepharon, 412
splinter hemorrhages, 533 sympathetic nervous system
spondyloarthropathies, 443 description of pathway, 161
squamous cell carcinoma, 338, 418 synapses
stratum spinosum cell layer, 27 types of, 46
staphylococcal marginal keratitis, 476 synchysis scintillans, 498
staphylococcus aureus, 277 syphilis, 284, 371, 376, 446-448, 529
staphylococcus epidermidis, 278 rapid plasmid reagin (RPR), 372
Stargardt’s disease, 522 venereal disease research labo
stereopsis ratory (VDRL), 372
development of, 196 systemic lupus erythematosus, 328
sterilization, 287
Stevens-Johnson Syndrome, 413 T killer cell, 314, 316
Stevens-Johnson syndrome, 107 talc retinopathy, 510

562 INDEX
tarsal plate, 77 trochlear nerve palsy, 66

Tay-Sachs disease, 8, 342 tuberculosis, 383, 446
Tfecnis, 492 Tuberous sclerosis, 338
telecanthus, 73 Turner’s syndrome, 339
temporal arteritis, 331
temporal lobe, 50 UGH syndrome, 495
temporal lobe lesion, 173 ulcerative colitis, 377
temporal vision usher’s syndrome, 521
development of, 197 uveitis
temporomandibular disorder (TMJ), anterior, 443
382 posterior, 447
Tenon’s capsule, 117 uveoscleral meshwork, 121
Tensilon test, 68
Terrien’s marginal degeneration, 478 valve of hasner, 84
thermal/ultraviolet keratopathy, 453 van herick grading system, 119
three-mirror lens, 496 varicella zoster virus, 289
thrombus, 350 vascular sheathing, 510
Thygeson’s superficial punctate ker venereal disease research laboratory
atopathy, 451 (VDRL), 372
thymus, 32 venous drainage of the eye, 98
thyroid venous stasis retinopathy, 509
related eye disease, 405 vernal keratoconjunctivitis, 429
thyroid gland, 14 vernier acuity-
thyroid-related ophthalmopathy, 84 development of, 192
tight junctions, 9 vertebral artery, 54
Tolosa-Hunt syndrome, 410 vertigo, 381
tolosa-hunt syndrome, 102 viroid, 291
toxic anterior segment syndrome, 493 virus
toxic optic neuropathy, 57, 60 capsid, 287
toxic shock syndrome, 278 classification scheme of, 288
toxocariasis, 529 genetic mechanisms of, 288
toxoplasmosis, 299, 334, 376, 447, replication of, 288
529 viscoelastic, 495
trabecular meshwork, 120 visual acuity
transcription, 259 development of, 191
translation, 260 visual analysis, 209
transverse sinus, 103 visual attention, 209, 211
treponema pallidum, 283 visual field, 538
trichiasis, 73 visual fields, 540
trichomonas vaginalis, 301 FDT, 540
trigeminal nerve, 155 glaucoma hemifield test, 541
mandibular division of, 157 grayscale, 540
maxillary division of, 157 interpretation, 540
ophthalmic division of, 155 mean deviation, 541
trochlea, 154 pattern deviation, 541
trochlear nerve, 154 pattern standard deviation, 541

INDEX 563
reliability indices, 540 xanthelasma, 245

SAP, 540 xanthophyll, 148
SWAP, 540
total deviation, 541 yeast, 293
visual information processing, 209
visual motor integration skills, 212 zeis glands, 78
visual motor-integration, 209 zygomatic bone, 91, 92
visual pathway, 167 zygomatic nerve, 157
blood supply of, 172 zyloprim, 332
pathology of, 173
visual perceptual development
anomalies of, 209
visual processing, 211
visual spatial skills, 209
visual-analysis skills, 209
visual-spatial skills, 209
vitamin B12 deficiency, 344
vitamins, 249
fat soluble, 252
water soluble, 249
vitelliform dystrophy, 523
vitreoretinal tuft, 527
vitreous, 134
attachments to retina and lens,
135
content of, 134
hemorrhage of, 499
posterior vitreous detachment,
498
Von Hippel Lindau disease, 340
vortex veins, 98, 147
Vossius ring, 400
vossius ring, 403
Wegener’s granulomatosis, 331

Weiss ring, 498
weiss ring, 135
Wernicke’s area, 50
western blot, 267
white limbal girdle of Vogt, 479
white matter, 50
Wilbrand’s knees, 168
Wilson’s disease, 378
with the rule astigmatism, 105
Wolfring glands, 78
wound healing, 324

The KMK Part One Applied Science
Review Guide is a concise, organized
resource specifically tailored to board
exam preparation. Formatted with a
focus on exam review, the text offers
a structured approach to study,
including summary diagrams, con-
densed scientific explanations, arid
an increased emphasis on clinical
applications. As a companion text
for board exam preparation or an
additional resource for classroom
success, the KMK Part One
Applied Science Review Guide is a
single, compact resource ideal for
self-study and student achievement.

National Board of Examiners in Optometry (NBEO) Part One (Applied Science) - KMK Board Review Guide (2014), Vol. 1 (Etc.)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

National Board of Examiners in Optometry (NBEO) Part One (Applied Science) - KMK Board Review Guide (2014), Vol. 1 (Etc.)

Uploaded by

Copyright:

Available Formats

Part One

K M K Part I Applied Science Review

Copyright 2014 by KMK Educational Services, LLC

The National Board of Examiners in Optometry (NBEO) is a registered trade­

The following is copyrighted material. It is unlawful to distribute without

Copyright 2014 by KMK Educational Services, LLC

K y le M . C h eath am , O .D ., F .A .A .O . graduated from Centre College with

M elissa A . C h eath am , M P A S , P A -C graduated from the University of

K e v in B . W o o d , P h .D . graduated Magna Cum Laude from Centre College

Sarah D o u g h e rty W o o d , O .D ., M .S ., F .A .A .O . graduated Magna Cum

Copyright 2014 by KMK Educational Services, LLC

A d d ition a l con tribu tors:

The authors would like to thank C had R ea d e, M .D ., C hris W olfe, O .D .,

Copyright 2014 by KMK Educational Services, LLC

C hief M edical E d ito r

K e n d ra R . D a lto n , O .D . graduated from Emory University in Atlanta, GA

Copyright 2014 by KMK Educational Services, LLC

Special T hanks to:

Larry Alexander, O.D.

Copyright 2014 by KMK Educational Services, LLC

Copyright 2014 by KMK Educational Services, LLC

Copyright 2014 by KMK Educational Services, LLC

Larry J. Alexander, O.D.

Copyright 2014 by KMK Educational Services, LLC

K M K Educational Services, LLC

Copyright 2014 by KMK Educational Services, LLC

3.19 Visual P athw ay............................................................................... 167

4 O cular E m b ry olog y 179

6 B ioch em istry 217

9 System ic D isease 321

Copyright 2014 by KMK Educational Services, LLC

9.9 Cardiovascular Hemodynamic D iso rd e rs.................................. 347

10 Ocular Disease 395

Copyright 2014 by KMK Educational Services, LLC

Copyright 2014 by KMK Educational Services, LLC

C o m m e n t o n sou rces: The following is a compilation of facts that are well-

The general organization of the body is as follows: Cells Tissues

There are three types of lipids prevalent in the PM:

1. Phospholipids: These amphipathic molecules have hydrophilic heads (po­

2. Glycolipids: Lipids attached to a sugar side chain,

3. Cholesterol: Found only in eukaryotic cells. Plays a critical role in

Copyright 2014 by KMK Educational Services, LLC

Normal cholesterol values:

• T ota l ch olesterol less than 200.

• T riglycerides less than 150.

• LD L less than 130.

Proteins are classified according to their position in the PM:

• Structural: Interacts with cholesterol to maintain membrane struc­

• Channels: Act as passive transporters or active pumps that move

Carbohydrates are covalently attached to other structures (e.g. lipids and

The g ly co ca ly x refers to all the sugar components (glycolipids

Copyright 2014 by KMK Educational Services, LLC

All forms of RNA must come from transcription of a DNA template

N u cleolu s: Although commonly mistaken for a separate compartment, this

• rRNA is produced in the nucleolus and combines with proteins to

• Transcription — DNA to mRNA

• Translation — mRNA to protein

Most cells have one nucleus.

Copyright 2014 by KMK Educational Services, LLC

• Osteoclasts and skeletal muscle cells are raultinuclear.

• R B C s are the on ly anuclear cells in th e b o d y .

• Ribosomes produce a phenomenon known as cy top la sm ic basophilia.

Antibiotics often target ribosomal subunits to inhibit protein pro­

The National Board of Examiners in Optometry (NBEO) is a registered trade

1. Phospholipids: These amphipathic molecules have hydrophilic heads (po

• Structural: Interacts with cholesterol to maintain membrane struc

Antibiotics often target ribosomal subunits to inhibit protein pro

Tay-Sachs disease is an autosomal recessive disorder character

M icrofilam en ts (A ctin ): Component of muscles that forms the core of m i

2. Macular adherens (i.e. desmosomes): Functions like a “spot weld,” pro

Hemidesmosomes connect basal cell layers to the underlying basement mem

— P seu d ostra tified colu m n ar epithelium : A type of simple colum

• The corneal epithelium is composed of five to six layers of simple squa

Transitional epithelium : Three to seven layers of stratified epithelium lo

• The e x o crin e pancreas produces the main digestive en

Signs of h yperth yroid ism include nervousness, heart palpita