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x Contents
6. Lower Gastrointestinal Tract 85
Sameera Sherwani, Martin Goetz, Hany Osman, and
Andrew Quinn
7. Pancreaticobiliary System 129
Somashekar G. Krishna and Anjuli K. Luthra
8. Lungs 155
Manu Jain, Carolyn Glass, Nasser K. Altorki, and
Navneet Narula
9. Breast 173
Daniel Schmolze
10. Central Nervous System 189
Jennifer M. Eschbacher, Evgenii Belykh, Mark C. Preul, and
Peter Nakaji
11. Head and Neck 205
Daniel Kwon, Brett A. Miles, and Alexandros D. Polydorides
12. Genitourinary System 217
Maria M. Shevchuk, Eugene Shkolyar, and Joseph C. Liao
13. Gynecologic Tract 243
Jelena Mirkovic and Eric Yang
14. Hepatobiliary System 281
Erin Rubin, James Park Dewar, Daniel Schmolze, and
Wei Zheng
15. Molecular Applications 297
Satoru Kudose and Anne Marie Amacher
16. Ex Vivo Applications 307
Daffolyn Rachael Fels Elliott, and Anne Marie Amacher
Index 329
© 2024 World Scientific Publishing Company
https://doi.org/10.1142/9789813206984_0001
Eye, Anterior Chapter
1
Stephen E. Orlin∗and Daniel Saresky
In ophthalmology, advances in imaging have revolutionized the field both
diagnostically and therapeutically. The development of these novel techniques has significantly improved our understanding of ocular anatomy and
the application of this latest technology has availed millions of patients with
vision-saving treatments that were unheard of just a few decades ago.
†
1
Corneal Topography and Tomography
Corneal topography is an imaging modality that uses multiple concentric
rings of a Placido disk reflected onto the surface of the cornea. In areas
where the contour of the cornea is steeper, the reflected rings are close
∗
Scheie Eye Institute, University of Pennsylvania, Perelman School of Medicine,
Philadelphia, PA, USA.
†
Cornea & External Diseases Subspeciality, Cataract & Refractive Surgery, Comprehensive
Ophthalmology, Visionary Eye Doctors, Rockville, MD, USA.
1
2 S. E. Orlin & D. Saresky
49.5
48.5
120
90
60
47.5
46.5
150
30
45.5
44.5
43.5
180
47.3
41.6
0
42.5
41.5
210
330
40.5
39.5
TN
38.5
0.5 D
ATLAS Operator
Figure 1. Corneal topography (symmetrical bowtie pattern in regular astigmatism).
Source: Image courtesy of Dr. Stephen Orlin.
240
270
11.5 mm
300
together, and in the flatter areas, the rings are further apart. A computer
then converts these black and white rings into a color-coded contour map
(Figure 1). Topography has a wide variety of diagnostic and therapeu-
2
tic uses.
In corneal ectatic disorders, such as keratoconus and pellucid
marginal degeneration, the cornea loses its normal curvature and becomes
steeper and thinner. Corneal topography can be used to make the diagnosis, monitor progression, and evaluate the need for therapeutic hard contact
lenses. Refractive eye surgery, such as LASIK and photorefractive keratectomy (PRK), are commonly performed eye operations to decrease the
dependency on eyeglasses or contact lenses. Subtle forms of keratoconus
that cannot be seen clinically can be an absolute contraindication to the
surgeries, and corneal topography is an integral part in the screening of
these patients. Corneal topography also can be used in planning for and
managing astigmatism in cataract surgery, especially in patients who have
previously had refractive surgery. In addition, it is helpful in the detection
of irregular astigmatism after corneal transplantation.
Topographic assessment is limited to the anterior corneal surface, but
tomography creates a three-dimensional image of the cornea that measures
posterior corneal curvature and cornealthickness. Slit scanningtomography
projects a series of slit beams onto the cornea and measures light scatter
Eye, Anterior 3
from both the anterior and posterior surfaces.2These devices can image
other parts of the anterior segment, including the lens.
Ultrasound Biomicroscopy
Ultrasound biomicros copy (UBM) images the eye using high-frequency
ultrasound waves emitted by a contact probe directly on the ocular surface.
Its signal is significantly attenuated by the vitreous, so its use is limited to
the anterior segment. Commercially available devices have a 50 µm lateral
resolution, 25 µm axial resolution, and a depth of penetration of 5.0 mm.
UBM is useful in imaging the anterior chamber angle structures, such
as the iris, ciliary processes, and ciliary body. These structures produce
aqueous humor and control the ability of the lens to accommodate, thereby
changing the focusing ability of the eye. UBM is a useful tool in the evaluation of cysts (Figure 2) and tumors of the ciliary body, such as melanomas,
found in these anatomical locations. Ultrasoundbiomicroscopy is also helpful in the evaluation of angle recession, an anterior chamber abnormality
Figure 2. Cyst scan (ultrasound biomicroscopy image of iris root cyst).
Source: Image courtesy of Dr. Stephen Orlin.
4 S. E. Orlin & D. Saresky
that predisposes to glaucoma, particularly seen following ocular trauma,
because of its ability to scan through opaque corneas and total hyphemas
(blood in the anterior chamber).
UBM has several disadvantagescompared to anterior segmentOptical
Coherence Tomography (OCT)
3
(see the following). It requires a skilled
operator and is more time consuming, and images are less precise. As a
result, its role in visualizing structures anterior to the iris has decreased
with the development of OCT (see the following).
Anterior Segment Optical Coherence Tomography
OCT allows for two-dimensional, cross-sectional images of ocular structures. Its predominant use in ophthalmology is the posterior segment, but it
has also achieved utility in imaging the tear film, cornea, anterior segment,
and iris. Unlike UBM, it does not require a contact probe and images are
technically easier to obtain.
Anterior segment OCT has enormous applications in the evaluation
of the angle structures in the anterior segment of the eye.
particular clinical significance in conditions causing crowding of the angle,
predisposing patients to narrow angle and angle closure glaucoma. Because
of the extremely high resolution of the images obtained, anterior segment
OCT can be used for very precise measurements of the angle between the
posterior corneal surface and iris plane. It can also be used to measure
the anterior chamber depth and thickness of the cornea. This technology
has revolutionized our ability to perform corneal refractive surgery such as
LASIK. Anterior segment OCT can also be used to diagnose complications
in refractivesurgery postoperatively, particularly involving the LASIK flap.
In addition, it has also helped with the pre and postoperative management
of the newer layer-specific corneal transplant surgeries such as Descemet
Stripping Automated Endothelial Keratoplasty(DSAEK), Descemet Membrane Endothelial Keratoplasty (DMEK) (Figure 3), and Deep Anterior
Lamellar Keratoplasty (DALK), looking specifically for detachments of
these grafts which might otherwise be very difficult to see clinically. For
DMEK specifically, a newer intraoperative OCT can be very helpful “real
4
These are of
Eye, Anterior 5
Figure 3. Descemet membrane endothelial keratoplasty, edge lift (optical coherence tomography
image shows the five distinct layers of the cornea).
Source: Image courtesy of Dr. Stephen Orlin.
time” in the unfolding of the new graft which might only be 8–12 µmin
thickness because the correct orientation is crucial to the success of these
procedures.
Other applications include evaluation of contact lens fit,
5
anterior
segment tumors, evaluating the depth of corneal lacerations, or identifying
the size and location of a corneal foreign body.
Confocal Microscopy
Confocal microscopy produces high-resolution in vivo images of the
corneal layers and histological structures, such as nerves, epithelial and
endothelial cells, and keratocytes without requiring fixation or staining
(Figure 4). The microscope involves imaging single points of the tissue
with a point source of light and a camera in the same plane at the same
time. The microscope unit is expensive, and obtaining and interpreting
images require a moderate amount of training.
One of the most exciting clinical applications in ophthalmology
is diagnosing certain corneal infections, such as Acanthamoeba keratitis. Acanthamoeba is a protozoa that can cause catastrophic infections,
typically, but not exclusively, seen in a contact lens wearer exposed to
fresh water. This organism is difficult to grow in cultures, and often the
diagnosis is not made until late in the disease course. Confocal microscopy
6
6 S. E. Orlin & D. Saresky
Figure 4. Confocal microscopy (abnormal branching pattern of corneal nerves).
Source: Image courtesy of Dr. Stephen Orlin.
has been used to identify Acanthamoeba cysts in cases of this infection. The
organisms are highly reflective, ovoid in shape, and seen in the epithelium
and anterior stroma. Although diagnostic utility in other causes of infectious keratitis has been studied, the role of confocal in these diseases is less
clear.
Confocal microscopy has been used to investigate many other disease processes, including corneal dystrophies, corneal deposits, contact
lens changes, and ocular surface disease. In the latter, confocal microscopy
studies have shown corneal nerves to be decreased in patients with dry
eye disease, and corneal nerve fiber lengths have predicted a response to
treatment.
7
Although there has been exciting work using the confocal microscope
to identify corneal pathology, further study is needed to translate these
findings into therapeutic uses.
Eye, Anterior 7
Specular Microscopy
The inner-most layer of the cornea is comprised of a single layer of
endothelial cells laid out in a hexagonal mosaic configuration. The cells are
most important and act as a pump to keep the cornea in a state of relative
dehydration. At birth, we have approximately 3,000–4,000 cells/mm
their density declines with age to an average of 1,500–3,500 cells/mm
in adults. Our bodies do not have the capacity to regenerate new cells.
2
and
2
Figure 5. Specular microscopy (corneal endothelial cells with dark punched-out spots consistent
with corneal guttae in Fuchs dystrophy).
Source: Image courtesy of Dr. Stephen Orlin.
8 S. E. Orlin & D. Saresky
Decreased cell density (fewer than 1,000 cell/mm2) portends a higher risk
of corneal decompensation, particularly following intraocular surgery.
Specular microscopy is a technique in which the innermost layer of
cells on the cornea can be imaged (Figure 5). With this technology, light
is reflected from an optical interface between the corneal endothelium and
the aqueous humor allowing imaging of the normally hexagonal corneal
endothelial cells. This technique allows for assessment of the density of
cells, as well as morphologic variability and percentage of hexagonal cells.
Specular microscopy is also used postmortem to evaluate the health
of the endothelium of donated corneas to screen for suitability for corneal
transplants.
References
1. Weisenthal,R.W.,Daly,M.K.,Feder,R.S.,Orlin,S.E.,Tu,E.Y.,VanMeter,W.S.,
Verdier, D. D., and de Freitas, D. Chapter 2: Examination techniques for the external
eye and cornea. In Basic and Clinical Science Course: External Disease and Cornea,
American Academy of Ophthalmology, 8 (2017). https://fliphtml5.com/lluzx/qfnn/
2018-2019_Basic_and_Clinical_Science_Course%3A_Section_8-_External_Dise
ase_and_Cornea-American_Academy_of_Ophthalmology.2018/.
2. Ambrósio, R. Jr., and Belin, M. W.Imaging of the cornea: Topography vs tomography.
Journal of Refractive Surgery, 26: 847–849 (2010).
3. Dada, T., Sihota, R., Gadia, R., Aggarwal, A., Mandal, S., and Gupta V. Comparison
of anterior segment optical coherence tomography and ultrasound biomicroscopy for
assessment of the anterior segment. Journal of Cataract & Refractive Surgery, 33:
837–840 (2007).
4. Han, S. B., Liu, Y. C., Noriega, K. M., and Mehta, J. S. Applications of anterior
segment optical coherence tomography in cornea and ocular surface diseases. Journal
of Ophthalmology, 2016: 1–9 (2016). doi:10.1155/2016/4971572. Epub 2016 Sep 19.
PMID: 27721988; PMCID: PMC5046038.
5. Luo, Z. K. and Jacobs, D. S. Current and potential applications of anterior segment
optical coherence tomography in contact lens fitting. Seminars in Ophthalmology, 27:
133–137 (2012).
6. Kaufman, S. C., Musch, D. C., Belin, M. W., Cohen, E. J., Meisler, D. M., Reinhart, W.
J., Udell, I. J., and V an Meter, W . S. Confocal microscopy: A report by the American
Academy of Ophthalmology. Ophthalmology, 111: 396–406 (2004).
7. Kheirkhah, A., Dohlman, T. H., Amparo, F., Arnoldner, M. A., Jamali, A., Hamrah, P.,
and Dana, R. Effects of corneal nerve density on the response to treatment in dry eye
disease. Ophthalmology, 122: 662–668 (2015).
© 2024 World Scientific Publishing Company
https://doi.org/10.1142/9789813206984_0002
Eye, Posterior Chapter
2
Neepa Shah∗and Anton Orlin
†
Optical Coherence Tomography: Background and Principles
Optical coherence tomography(OCT) was first introduced as an ophthalmic
1
imaging modality in 1991
imaging of various ocular tissue including the retina. It relies on the principle of light interference to produce cross-sectional images of the retinal
microstructure that is equal or superior to histological sections. As light
travelsthrough transparent or semitransparent tissue, the intensity and echo
time delay of backscattered light can be measured.
nificant media opacity, OCT provides a fast, non-invasive way to evaluate
for retinal disease and visualize pathology that may not have otherwise
been noted previously by clinical exam alone. It has been instrumental in
detecting various retinal abnormalities and monitoring disease progression
and response to treatment.
and provides high-resolution cross-sectional
2
In the absence of sig-
∗
Kaiser Permanente Riverside Medical Center Riverside, CA.
†
Mid Atlantic Retina/Wills Eye Physicians Plymouth Meeting, PA.
9