s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

Available online at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/survophthal

Major review

Optical coherence tomography: Imaging of the choroid

and beyond

Sarah Mrejen, MD, Richard F. Spaide, MD*

Vitreous, Retina, Macula Consultants of New York, 460 Park Avenue, 5th Floor, New York, NY 10022

article info abstract

Article history: Seventy percent of the blood flow to the eye goes to the choroid, a structure that is vitally
Received 23 May 2012 important to the function of the retina. The in vivo structure of the choroid in health and
Received in revised form disease is incompletely visualized with traditional imaging modalities, including indocyanine
1 December 2012 green angiography, ultrasonography, and spectral domain optical coherence tomography
Accepted 4 December 2012 (OCT). Use of new OCT modalities, including enhanced depth imaging OCT, image averaging,
and swept-source OCT, have led to increased visualization of the choroidal anatomy. The
correlation of these new anatomical findings with other imaging modalities results increases
Keywords: understanding of many eye diseases and recognises of new ones. The status of the choroid
choroidal thickness appears to be a crucial determinant in the pathogenesis of diseases such as age-related
enhanced depth imaging optical choroidal atrophy, myopic chorioretinal atrophy, central serous chorioretinopathy, chorior-
coherence tomography etinal inflammatory diseases, and tumors. Extension of these imaging techniques has
swept source optical coherence provided insights into abnormalities of the sclera and optic nerve. Future developments will
tomography include blood flow information, 3D rendering of various ocular structures, and the ability to
choroidal imaging evaluate changes in 3D structural information over time (4D imaging).
choroidal anatomy ª 2013 Elsevier Inc. All rights reserved.
choroidal blood flow
choroidal physiology
choroidal histopathology
optic nerve
sclera
subarachnoid space

1. Introduction (εidhs): that looks like. In Latin this word meant network.
Approximately 95% of the blood flow in the eye goes to the
The word choroid comes from the ancient Greek: korio-aydez, uvea, with the choroid accounting for more than 70%.162 The
for korio (corio): a membrane around the fetus, and aydez choroid has the highest blood flow per unit weight of any

Financial Disclosure: Dr Spaide is a consultant to Topcon.

The authors have no other financial or personal relationships with other people or organizations that could potentially and inappro-
priately influence their work.
* Corresponding author: Dr. Richard F. Spaide, MD, Vitreous Retina Macula Consultants of New York, 460 Park Avenue, 5th floor, New
York, NY 10022.
E-mail address: rick.spaide@gmail.com (R.F. Spaide).
0039-6257/$ e see front matter ª 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.survophthal.2012.12.001
388 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
tissue in the body, about 20 to 30 times greater than that of the
retina.2 One main function is to supply oxygen and metabo-
lites to the outer retina, retinal pigment epithelium (RPE), and
possibly the prelaminar portion of the optic nerve,79 and it is
the only source of metabolic exchange for the avascular fovea.
The photoreceptors inner segments, replete with mitochon-
dria, have the highest rate of oxygen use per unit weight of
any tissue.227 The choroid also acts as a heat sink, absorbs
stray light, and, in birds, aids in accommodation.152
Many disease processes originate from the choroid or
materially impact it because of its proximity to the affected
retina or sclera (i.e., age-related macular degeneration, glau-
coma, and diabetic retinopathy). Choroidal neovascularization
(CNV) related to myopia, angioid streaks, multifocal choroidi-
tis, and polypoidal choroidal vasculopathy (a variant of CNV)
originates from the choroid. The high blood flow in the choroid
predisposes the site to metastatic or embolic spread of tumors
and infectious diseases. Some inflammatory disorders
involving the posterior segment of the eye seem to target the
choroid (e.g., Vogt-Koyanaghi-Harada disease, birdshot cho-
rioretinopathy, and choroidal granulomas in sarcoidosis or
tuberculosis). Finally, in animal models emmetropization and
the first steps in control of refractive error are dependent on the
choroid.152 Advances in imaging have greatly increased our
ability to visualize the choroid, allowing better understanding
of the choroid in health and disease.
1.1. Embryology and anatomy of the choroid and sclera
1.1.1. Embryology
The optic vesicles form as outpouchings of the forebrain and
then invaginate and form a double-walled optic cup. The cup
has two distinct layers: one eventually destined to form the
retina and the other the RPE. The inferior portion has two
edges where the cup joins, forming the choroidal fissure. This
potential gap allows the hyaloid artery to enter the eye. The
uvea develops from the mesoderm and migrating neuro-
ectoderm that surround the optic cup. The choroid is the
posterior part of the uvea, the middle tunic of the eye. The
mesodermal cells surrounding the cup start to differentiate
into vessels concomitantly with the RPE. The choriocapillaris
starts to form at about the fifth to sixth week of embryogen-
esis. The basal lamina of the RPE and of the choriocapillaris
define the boundaries of the nascent Bruch’s membrane by
week 6.194 The choriocapillaris becomes organized with
luminal networks well before formation of the rest of the
choroid. The posterior ciliary arteries enter the choroid during
the eighth week of gestation, but it takes until week 22 before
arteries (which have a continuous layer of smooth muscle
cells) and veins become mature. Melanocytes precursors
migrate into the uveal primordia from the neural crest at the
end of the first month and start differentiating in the seventh
month. The pigmentation of the choroid begins at the optic
nerve and extends anteriorly to the ora serrata and is
completed by about 9 months.145 Thus the choroid derives
from different cell lines than the retina and the RPE, both
derived exclusively from neural ectoderm. The sclera is
derived from mesenchymal condensation starting anteriorly
and completed posteriorly by week 12.
1.1.2. Scleral anatomy
The sclera is thickest (1.0 mm) at the posterior pole around the
optic nerve and thinnest (0.3 mm) beneath the insertions of
the rectus muscles, measuring 0.5 mm at the equator. The
sclera is organized in three layers: outer episclera, scleral
stroma, and inner lamina fusca. The superficial episclera is
a connective tissue that contains melanocytes, a few fibro-
blasts, lymphocytes, and relatively numerous blood vessels.
The scleral stroma is the largest portion of the sclera and is
composed of branching bundles of collagen fibers, together
with numerous elastic fibers, extracellular matrix, and a few
fibroblasts. The lamina fusca, the innermost layer, can be
distinguished by its brownish color, due to the presence of
numerous embedded melanocytes, and blends with the
suprachoroidal and supraciliary lamellae of the uveal tract.
Collagen in the lamina fusca is arranged in thin, small
bundles. This layer also contains elastic fibers. The sclera, like
the cornea, is essentially an avascular fibrous structure,
except for the vessels of the superficial episcleral plexus169
and the intrascleral vascular plexus located just posterior to
the limbus. A number of channels, or emissaria, penetrate and
break the continuity of the sclera for the perforating ciliary
nerves, short and long posterior ciliary arteries, anterior
ciliary arteries, and vortex veins. Interesting variations of the
sclera are associated with myopia, particularly high myopia.
Eyes with high myopia have thinning of the sclera, with
a decrease in the amount of collagen in the sclera. The
distribution of collagen fibrils is different from that of
emmetropic subjects, with an increased proportion of
smaller diameter collagen fibrils,32,134,175 and the sclera is
more elastic.135
1.1.3. Posterior ciliary arteries
The ophthalmic artery, the first branch of the internal carotid
artery, branches to form the central retinal artery and the
posterior ciliary arteries (PCAs). There are many variations,
but the posterior choroid is supplied by two major PCAs,
the medial and lateral PCAs, in approximately 90% of eyes.78
From their origin, the PCAs divide into a large number of
branches as they course toward the eye. Two major branches,
called the long PCAs, eventually supply the anterior uvea.
Smaller short PCAs, usually about 20 in number, enter the eye,
particularly around the optic nerve and macular regions.65
1.1.4. Choroidal anatomy
The choroid is primarily composed of blood vessels, but also
has connective tissue, pigment, and intrinsic choroidal
neurons. Birds have fluid-filled lacunae identified as a true
functional lymphatic system in their choroid.140 Schroedl et al
found that humans don’t have typical choroidal lymphatic
vessels, but have macrophage-like cells that stain positively
for a lymphatic endothelium-specific marker (lymphatic
vessel endothelial hyaluronic acid receptor).193 Humans also
have cells with non-vascular smooth muscle-like elements in
the choroid.133,170 Their predominant subfoveal localization
suggested that they may play a role in stabilizing the fovea
against movement caused by the contracting ciliary muscle
during accommodation.42 The human choroid has intrinsic
choroidal neurons, which have been theorized to participate
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
in autoregulation of blood flow.36 It is possible the presence of
lymphatic and intrinsic neuronal cells may be atavistic. The
choroid is attached to the sclera by strands of connective
tissue that are easily separated anteriorly creating a potential
space between them, the suprachoroidal space, and is tightly
adherent to the optic nerve.
The blood from the short PCAs enters the eye and travels
through successively smaller arterioles within the choroid to
arrive at the choriocapillaris. The choroid is traditionally
described as arranged in layers of vessels from the outer to
inner part of the choroid the Haller layer, the Sattler layer,
and the choriocapillaris. The Haller layer contains larger
choroidal vessels, and the Sattler layer has medium-sized
vessels. There is no distinct border between these layers or
even an established definition of what is meant by large or
medium. Blood pressure is reduced from about 75% of
systemic at the short PCAs to that in the choriocapillaris,
measured in rabbits as approximately 5 to 9.5 mm Hg greater
than the intraocular pressure.121 The choriocapillaris is
a planar layer of small vessels with a lumen slightly larger
than a typical capillary. The network of vessels in the cho-
riocapillaris is so tightly arranged in the posterior portion of
the eye that specific capillary tubes are more difficult to
discern. Given the packing density of the choriocapillaris,
along with the larger lumen size of individual tubules, the
summation of the cross-sectional area of the choriocapillaris,
lumens appears to be quite large. In the peripheral portions of
the eye anatomic arrangements representing lobules are
suggested, but there is no specific anatomic lobular structure
in the posterior portion of the eye. There is a controversy
regarding the choroidal angioarchitecture. Anatomically, the
lobular appearance of the choriocapillaris exists only in part of
the posterior pole, as has been demonstrated by Fryczkowski
using vascular casts and scanning electron microscopy.51
Fryczkowski also showed that the choroidal anatomical
lobules are not identical with those observed by fluorescein
angiography. He concluded that two models of choroidal
lobules should be distinguished: anatomical and functional.
The anatomical lobule contains a central collecting venule
and peripherally located feeding arterioles. The functional
lobule is centered by a main feeding arteriole and has
peripherally located draining venules. Using fluorescein
angiography, the functional lobuli are seen as centrally filled
areas even in areas that are anatomically non-homogeneous
structures or non-lobular structures in the posterior pole.51
The vitality of the choriocapillaris is maintained in part by
constitutive secretion of vascular endothelial growth factor
(VEGF) by the RPE.189 The choriocapillaris is highly polarized,10
with the internal surface having localized attenuations of the
capillary wall known as fenestrations. These fenestrations
appear to increase the amount of material leaving the capil-
laries and direct the flow toward the RPE. Similarly sized
vessels in the retina do not have fenestrations. Soluble VEGF
isoforms are required for fenestrations to occur,189 and these
fenestrations disappear with VEGF withdrawal.163
Venous drainage of the choriocapillaris is mainly through
the vortex vein system with minor drainage through the
ciliary body via the anterior ciliary veins. Postcapillary venules
form afferent veins that converge to form the ampullae, which
in turn empty through the vortex veins. There are often four
389
vortex veins per eye, but the number may range from 3 to 8.187
Occasionally highly myopic eyes may have a vortex vein,
called a ciliovaginal vein, located in the posterior pole that
drains near or through the optic nerve. The typical vortex vein
passes obliquely through the sclera for a distance of about 4.5
mm as it exits the eye and drains into the superior and inferior
ophthalmic veins.73
1.1.5. Blood flow within the choroid
Hayreh observed special features of choroidal vasculature in
humans and monkeys.76 The choroidal arteries do not ana-
tomose with one another, and each behaves like an end-
artery. Hayreh quotes Duke-Elder (page 273) “The tendency
for inflammatory and degenerative diseases of the choroid to
show a considerable degree of selective localization, despite
the fact that anatomically the vessels would appear to form
a continuous meshwork, has given rise to speculations
regarding the anatomical isolation of specific choroidal
areas.”76 The flow within the choriocapillaris is a function of
differential pressure gradients, which has the effect of
allowing flow into regions that may have suffered a decrease
in supply from a problem in a feeding choroidal arteriole.
In the early phase of fluorescein angiography, it is common
to see areas of the choroid that do not appear to fill with dye as
quickly as adjacent regions, called watershed zones by Hayreh.
A common watershed zone appears as a stripe, one to several
millimeters wide, running vertically at the temporal border of
the optic disc. This watershed zone is thought to be the
boundary between areas of the choroid supplied by the medial
and lateral PCAs and occurs in 60% of eyes.76 The arteries and
veins supplying each region of the choroid do not have
a parallel course and the segment supplied by an artery does
not correspond exactly with that drained by a vein. There is
always a certain amount of overlap between the adjacent
arterial segments via the veins.77 The peripapillary choroid
has an important role in the blood supply of the anterior optic
nerve, including the optic disc79 and has a segmental blood
supply.
1.1.5.1. The regulation of choroidal blood flow. Almost every
tissue in the body has some form of autoregulation, but the
extent of the autoregulation of the choroid is controversial.
Some investigators have shown the choroid has no auto-
regulation when the perfusion pressure gradient is decreased
by raising the intraocular pressure (IOP).2,50 Others have
shown the choroidal blood flow varies with IOP, perfusion
pressure,102 endogenous nitric oxide production,167 and
vasoactive secretory production of choroidal ganglion cells.119
Various studies have suggested the choroid has some auto-
regulatory capacity during changes in ocular perfusion pres-
sure.168,182,183 Moreover, Polska et al found that the
mechanisms regulating choroidal blood flow in the human
fovea compensate better for an increase in arterial blood
pressure than for an increase in intraocular pressure.168
Autoregulation in regular tissues usually keeps the oxygen
partial pressure at a relatively low, physiologic level. The inner
choroid’s oxygen partial pressure is so high that it is likely that
the choroidal circulation is regulated by additional factors. For
example, CD-36 is a scavenger receptor expressed in the basal
RPE, and Houssier et al showed that CD-36edeficient mice fail
390 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
to induce COX-2 and subsequent VEGF synthesis at the level of
the RPE and develop progressive degeneration of the chorio-
capillaris.89 Therefore, CD-36 binding in the RPE seems to be
one of the factors maintaining the inner choroid.
One explanation proposed for what may appear to be
incomplete autoregulation is that the choroidal blood flow is
much higher than in other tissues, and there is a low oxygen
extraction ratio. Autoregulation is an adaptive compensatory
mechanism to adjust blood flow according to the local needs
of the tissue supplied. The high oxygen partial pressure and
low oxygen extraction imply that the flow in the choroid is
maintained at a level much greater than the local needs of the
choroid or RPE seem to dictate. On the other hand the O2
delivered to the outer retina is all consumed by the mito-
chondria in the inner segments of the photoreceptors, and it
seems unlikely that a direct feedback mechanism exists
between the oxygen utilization by the inner segments of the
photoreceptors and the choriocapillaris because diseases that
cause acute destruction of the outer retina such as acute zonal
occult outer retinopathy are not associated with decreased
thickness of the choroid.56 Indirect trophic mechanisms have
not yet been elucidated.
1.1.5.2. Other choroidal functions. There have been other
reasons proposed for the large blood flow in the choroid. The
high metabolism of the outer retina generates heat, and the
choroidal blood flow may act as a heat sink. The amount of
light energy delivered to the retina by incoming light is
insufficient to cause a significant elevation in temperature
and thus is an unlikely explanation.68 The high metabolism in
the outer retina may produce enough heat to require mecha-
nisms to reduce the local temperature. Even this hypothesis is
suspect because vasodilation occurs in response to increased
temperature, which has not been demonstrated in normal
eyes. The choroid contains melanocytes that improve optical
function by absorbing scattered light, and may also indirectly
protect against oxidative stress. These melanocytes exist in an
environment of high O2 partial pressure that, along with the
light exposure, may be a risk factor for malignant trans-
formation to melanoma.
1.2. Ways the choroid could be imaged
Because of its localization between the overlying pigmented
RPE and the underlying opaque and rigid fibrous sclera, the
choroid is difficult to visualize. Methods using light reflection
or fluorescence generation are impeded by the pigment in the
RPE and choroid. Conventional optical coherence tomography
(OCT) is affected by the effects of melanin and also the scat-
tering properties of the blood and blood vessels.
1.2.1. Angiography
Fluorescein is stimulated by blue light with a wavelength
between 465 and 490 nm and emits a green light with a peak
emission between 520 and 530 nm and a curve extending to
approximately 600 nm. Both the excitation and emission
spectra from fluorescein are blocked in part by melanin
pigment, which acts to decrease visualization of the choroid.
Fluorescein extravasates rapidly from the choriocapillaris and
fluoresces in the extravascular space, and this also prevents
delineation of the choroidal anatomy. The analysis of the
choroid using fluorescein angiography is also limited by light
absorption and scattering by the pigment in the RPE and
choroid and by the blood in the choroid. Indocyanine green
(ICG) absorption peak is between 790 and 805 nm and
fluoresces over a somewhat longer wavelength range,
depending on the protein content and pH of the local envi-
ronment. Longer wavelengths have the attribute of pene-
trating the pigmentation of the eye better than those used
with fluorescein angiography. ICG is 98% protein bound (with
80% binding to larger proteins such as globulins and alpha-
1-lipoprotein6,24,41) and thus is less likely to leak from the
normal choroidal vessels. During the earlier phases of ICG
angiography, the choroidal vessels are fairly easy to discern,
but vertical summation makes it difficult to delineate indi-
vidual layers. ICG angiography allows a precise anatomic and
dynamic evaluation of the choroidal circulation: the arteries,
arterioles, venules, and veins, not only in the posterior pole,
but out to the periphery and the vortex veins. The normal or
abnormal filling of these choroidal vessels can be appreciated.
Over the course of the angiogram some staining of the
extravascular tissue, particularly Bruch’s membrane, occurs,
obscuring visualization of deeper structures later in the
angiographic sequence.
1.2.2. Ultrasonography
Contact B-scan ultrasonography typically uses a 10-mega-
hertz probe placed on the eyelid. The probe used contains
a piezoelectric crystal that is stimulated to vibrate by a short
burst of an electrical current. When the vibration stops, the
piezoelectric crystal is used as a detector. Reflected sound
waves cause the crystal to vibrate, which in turn causes the
production of an electrical current. The reflected sound wave
varies in strength with the position of the reflecting structure
in the eye. Deeper structures produce weaker reflections. The
decrease in signal strength with time of flight is corrected by
increasing the gain of the amplifier during this interval. The
direction of the crystal is moved slightly by a motor within the
probe. Many axial scans, or A-scans, are summed to produce
a two-dimensional image known as a B-scan. The methods
using sound reflection have poor resolution. The axial reso-
lution of A-scan or B-scan ultrasonography is theoretically
about 150 mm. In reality the sound beam produced by
a piezoelectric crystal in a conventional B-scan probe has
a main lobe and several side lobes.80 Even the main lobe can be
1 mm in diameter at the surface of the retina. That means the
image produced by an individual A-scan is a summation of
a wide area of the back of the eye. For example, a typical
B-scan of the optic nerve will not show the cup unless there is
a large cup-to-disk ratio. Another problem with ultrasonog-
raphy is that the exact location of the image obtained is not
known. The general region can be estimated by evaluating
relationships with neighboring structures.
In non-pathologic conditions the reflectivity of the choroid
is difficult to distinguish from the overlying retina and the
underlying sclera. This ambiguity raises questions as to what,
exactly, is being measured when tumor thicknesses are
evaluated by contact B-scan ultrasonography. In diseases that
cause a thickening of the choroid the reflectivity may
decrease, affording increased contrast between the choroid
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
and the retina and sclera. When this thickening decreases,
contrast also decreases. Given the low resolution of contact
B-scan ultrasonography, changes in choroidal thickness
cannot be measured accurately. Contact B-scan ultrasonog-
raphy is good for visualizing larger tumors and gross changes
in ocular curvature such as that seen in pathologic myopia.
1.2.3. Laser doppler flowmetry
Laser Doppler flowmetry, developed by Riva and associates in
1994, is a noninvasive technique for the investigation of local
choroidal blood flow and its regulation in the fovea.181 For
choroidal blood flow evaluation by laser Doppler flowmetry,
the foveal region is chosen as the measuring site because it is
free of retinal vessels, and the patient fixates directly on the
laser light. The resultant Doppler signal arises predominantly
from the choriocapillaris,181 by contributions from the vertical
summation of signals generated by other choroidal vessels.
This technique evaluates only a limited area of the posterior
pole that may or may not be representative of the flow in other
regions of the choroid. Future development of Doppler and
phase variance OCT techniques offer opportunities to eval-
uate the flow within various levels in different regions of the
choroid and are likely to supplant laser Doppler flowmetry.
1.2.4. Optical coherence tomography
1.2.4.1. Interferometry. In dry air the speed of sound is 343.2
meters per second. The sound velocity in an average phakic
eye is 1,555 meters per second.85 The time it takes sound to
travel the length of a phakic eye with an axial length of 24 mm
is approximately 15.4 microseconds, an interval easy to
measure. Because light travels at 3
108 m/sec, it is not
possible to determine the time-of-flight delay on a micron-
scale level of resolution using an external system of time
measurement. The time it takes light to travel several microns
is the same time it would take an electron to travel in a circuit.
Measurement of multiple reflections with a detector and the
subsequent required electronic circuitry requires conduction
paths for electrons that are much longer than the variations in
path length of the photons. An ingenious way to determine
how long light takes to travel a given distance is to use the
wave-like character of the light itself as its own internal clock.
That is what a Michaelson interferometer does; the wave-
length of the light is used as its own timing standard. The
micron-scale resolution is achieved by comparing the time of
flight of the sample reflection with the known delay of
a reference reflection by looking for phase differences in the
light interference.
Coherency of light is a measure of how correlated one wave
of light is with another. Temporal coherency is a measure of
the correlation one wave has with another generated at
a different time. Coherence length is the distance light would
travel during the coherence time. Light produced by
a conventional laser has a long coherence time because the
waves of light are similar. Thus the coherence length of
a typical laser can be longdmeters or more. An interferometer
could be constructed with a conventional laser in which light
reflected from a distant sample is compared with light from
a much shorter reference arm. The differences between the
path length of the sample and reference arms would cause
gross differences in the number of wave lengths of light, but
391
the interference is related more to the fractional differences in
phase of the waves and not the gross differences in whole
number of wavelengths. This approach allows us to measure
small changes in the sample arm path length with great
precision, but the same instrument can’t differentiate that
path length from one multiple wavelengths longer or shorter
with the same fractional phase difference. One example of
how this type of interferometer could be used is a “James
Bond” device that aims a laser light beam at some structure in
a room, such as a picture or even a window, from a great
distance away. Anyone speaking in the room will cause these
objects to vibrate. The small path length changes induced by
the vibrations can be detected by comparing the reflected light
(i.e., the sample arm) to a reference arm. The resultant inter-
ference signal can be used to obtain the original sound infor-
mation, no matter if the reflecting structure is tens or
hundreds of meters away.
1.2.4.2. The basis of time domain optical coherence tomog-
raphy. It is possible to produce light with a short coherence
length. In this situation the waveform of light produced is the
same for all of the light rays produced at any one instance, but
this waveform is different from other waveforms produced at
other times. This approach essentially puts a time stamp on
the waveform. Low coherence light split into a reference arm
can only interfere with light from the sample arm if the path
lengths are the same or are nearly the same. If the reference
arm is varied in length the reflectivity of various points in the
sample arm can be determined. Only light from the small
area, as defined by the coherence length, produces signal. The
smaller the coherence length the smaller the area sampled.
The smaller the area that is sampled, however, the less chance
light rays will be reflected back to the interferometer. The
more light that is sampled by the interferometer the more
certain we can be about the true reflectivity of the sample. To
get enough light to form a good image, the tissue has to be
sampled for a finite time. This concept forms the basis, and
illustrates the limitations, of time-domain OCT. The advan-
tages of time-domain instruments are that they are concep-
tually simple and relatively easy to manufacture. Their chief
disadvantage is that the illuminating beam goes through the
full depth of the tissue even though only one point is sampled
at a time. The total light exposure to the eye is restricted by
safety standards, so there is a limit the signal to noise ratio of
the information obtained by time domain OCT.
1.2.4.3. The basis of spectral domain optical coherence tomog-
raphy. In high school textbooks interference is shown as an all
or nothing event, either light rays constructively or destruc-
tively interfere. In reality the result of interference of coherent
light is a varying brightness depending on the phase rela-
tionship of the two beams. If the two light beams have
a slightly different frequency a new interference or beat
frequency is detectable. Using short coherence length light
interference from various depths of tissue produces a range of
frequencies depending on the depth of reflection. If the
interference pattern is projected through a grating, the various
frequency components will be dispersed. The closer the match
between the two path lengths is, the lower the frequency.
Deeper structures will have a greater path length mismatch
392 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

and consequently will produce an interference signal
composed of higher frequencies. These various signals and
frequencies can be detected simultaneously. Using a Fourier
transform, it is possible to determine where, and how
strongly, different reflections in the sample arm are. In effect
reflections from various depths are frequency encoded. The
decoding process produces useful information from all levels
simultaneously. This forms the basis for spectral-domain
(SD)-OCT. Because the illuminating beam is used efficiently,
as all layers produce a signal during the scan time, it is
possible to capture information faster for any given A-scan
than with time-domain OCT. SD-OCT devices typically scan
with speeds up to 100 times faster than time-domain OCTs.
The two types of Fourier domain detection are SD-OCT and
swept-source domain OCT (SS OCT). These use a different
light source and detection method, but not necessarily
a different wavelength.54 The SD-OCT approach uses an
interferometer with a low coherence light source and
measures the interference spectrum using a spectrometer and
a high-speed line charge coupled device (CCD). The SS-OCT
uses a frequency-swept light source and detectors that
measure the interference output as a function of time.26,27
There are some problems inherent in SD technology. The
deeper tissues produce higher frequency signals, but the way
the grating and detector sample this frequency is not linear.
The higher frequencies are bunched together to a greater
extent than lower frequencies. In addition, the sensitivity of
the detection decreases with increasing frequency. This cau-
ses SD-OCT to have decreasing sensitivity and resolution with
increasing depth.
The peak sensitivity of SD-OCT is where the reference
and sample arms are the same length, called the zero-delay
point. The further in the sample arm from the zero delay
point a reflection originates, the weaker the resultant detec-
ted signal, even if the reflection does not vary in intensity
because the detector decreases in sensitivity (Fig. 1). As
a consequence of the roll-off in sensitivity, images from
deeper in the eye are increasingly dark. Conventionally the
zero delay point is placed at the level of the posterior vitreous.
This is a logical place, because visualizing the vitreoretinal
interface is important in evaluating many diseases. The
vitreous is nearly transparent, and a high sensitivity is needed
to produce useful images. The trade-off is that the choroid
cannot be seen very well.
1.3. Oct modalities to better visualize the choroid
There are several techniques to better visualize the choroid:
enhanced depth imaging OCT, image averaging, SS-OCT and
using a longer wavelength.
1.3.1. Enhanced depth imaging optical coherence tomography
A consequence of using a Fourier transform to decode the
interferometric signal is that two conjugate images are
developed. In practical use only one of these two images is
shown, typically with the retina facing toward the top of the
screen. If the peak sensitivity is placed posteriorly, typically at
the inner sclera, deeper structures such as the choroid can be
seen (Fig. 2). The upside down conjugate image of these
structures is visualized, and the right-side-up image of
structures in the orbit is blank because of the lack of any
imaging information. This method of imaging the choroid is
called enhanced depth imaging (EDI) OCT.207 It is now simply
performed with SD-OCT instruments, for example, by select-
ing the “EDI” button when using the Spectralis (Heidelberg
Engineering, Heidelberg, Germany). This feature is now

Fig. 1 e Relationship between location or depth and sensitivity. A: A reflector is placed at some arbitrary depth and produces
a signal shown as Zs. Note that because of the nature of the Fourier output, there are two images produced with the
conjugate being LZs. B: If the same reflector was placed deeper in the sample arm the signal produced would be Z2s even
though the amount of reflected light could be the same as that obtained to produce Zs. In a practical sense images in SD-OCT
instruments are generally better if they are placed near the top of the imaging space, which is closer to the zero-delay line
(C ). In (D) the image is placed at the bottom and consequently less signal is present. The low signal to noise ratio is evident
by the “snow” in the image. (Reprinted from Spaide200 with permission of Springer-Verlag)
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
Fig. 2 e Enhanced depth imaging. A: In a conventionally acquired OCT image, the peak sensitivity is located at the posterior
vitreous and the sensitivity curve is flipped on its side and overlaid on the SD-OCT image. B: If the OCT instrument is
pushed closer to the eye in order to invert the image, the peak of sensitivity curve is moved to the inner sclera. (Adapted
from Spaide200; used with permission).
available in the software of different OCT devices: the 3D OCT-
2000 (Topcon Inc, Tokyo, Japan), Cirrus with high definition
(HD) OCT machine (Carl Zeiss Meditec Inc, Dublin, CA), and
the RTVue (Optovue Inc, Fremont, CA). These devices can
perform the equivalent of EDI-OCT without requiring the user
to invert the image. The new software version 6.0 for the
Cirrus with HD OCT machine has the ability to capture images
using EDI technique.
1.3.1.1. Mechanism of enhanced depth imaging. With the peak
sensitivity deeper in the eye, the roll-off of sensitivity occurs
in the vitreous, which as a consequence is not visualized well.
With SD-OCT there is then a choice between two modes of
imaging, a conventional scan in which the vitreous is visual-
ized and the EDI mode used to see the choroid. For most eyes,
both cannot be seen optimally at the same time. The increase
in sensitivity using the EDI mode allows penetration of an
additional 500e800 mm deeper into the eye depending on the
amount of pigmentation and other factors. As will be dis-
cussed later, high myopes have thin choroids with little
pigmentation, and the sclera is usually thin as well. As
a consequence it is possible to not only see the full thickness
of the sclera, but also visualize the orbital fat.
Spectral domain devices use a grating that disperses light
onto the CCD. Video cameras commonly use CCDs that are
a two-dimensional array of light sensitive elements. To detect
the interference fringe from SD-OCT, only a single row of
light-sensitive elements is required. These are called line
CCDs. Each light-sensitive spot, sometimes called a well or
a bucket, gathers an electron for each photon of light. The OCT
scan line has to remain “parked” over the sampled tissue until
the wells in the line CCD fill. After a period of detecting light
the wells are dumped out and the electrical charge from each
one is evaluated. The scan speed is restricted in part by the
sensitivity of the CCD, the strength of the light source, the
quantum efficiency of the detector, and the speed at which all
of the individual elements of the CCD can be read. The line
CCD has to be read at fixed intervals, which limits the speed of
the OCT device.
1.3.2. Image averaging
To improve the signal-to-noise ratio and therefore image
appearance, many B-scans can be averaged together, typically
50 to 100. With the Spectralis this can be accomplished using
393
eye tracking, so the same location is sampled from one scan to
the next, but averaging many B-scans is possible without eye
tracking. For example the 3D OCT-2000 uses an alternate
approach by analyzing the degree of matching between many
images, eliminating the ones that don’t match, and averaging
only the ones that do.
1.3.3. Mechanisms of swept source optical coherence
tomography
A third method of generating OCT images uses a laser that
sweeps across a range of wavelengths in an orderly fashion.
The interference of the light from the sample and reference
arms produces a signal that can be read out in nearly real-time
by a photodiode. The SS-OCT uses a light source that is
inherently more complicated than what is used by SD-OCT.
The advantage is gained at the detection end of the instru-
ment. The detector is generally simpler in design and capable
of operating at higher speeds. There are other desirable
features that can be exploited. The falloff in sensitivity for
swept source OCT is much lower than for SD-OCT. In addition
the wavelengths available for swept laser sources are gener-
ally somewhat longer, in the 1 micron region. This longer
wavelength is capable of penetrating tissue to a greater extent
than the relatively shorter wavelengths typically used for SD-
OCT. Thus both the vitreous and choroid can be imaged
simultaneously; there is no need to pick one or the other.
There are trade-offs with swept source OCT. Although
longer wavelengths of light may penetrate tissue better,
particularly tissue containing melanin, the problem is that
water absorbs longer wavelengths of light. This restricts the
range, or bandwidth, of wavelengths that can be used in the
eye, because the vitreous is mostly water. The greater the
bandwidth of the light source, the better the resolution of the
OCT image. If the bandwidth of swept source lasers centered
at, for example, 1050 nm is large, the longer wavelengths will
be attenuated by water absorption. This creates an asym-
metrical profile of the spectrum used to illuminate the retina
and deeper structures, effectively reducing the actual usable
bandwidth of the light source. The light used to illuminate the
retina cannot be increased to compensate, because the
amount of light delivered to the eye is limited by standards
that quantify the amount of light delivered to the cornea. The
second disadvantage is the resolution of the OCT image is
related to the square of the center wavelength of the light. Any
394 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
increase in the wavelength has a detrimental effect on reso-
lution for any given bandwidth. Because there is a limit to the
available bandwidth of light that can be used because of water
absorption, there is an upper limit to the resolution of SS-OCT
instruments operating in the 1 micron region. Given the
relatively good performance of SD-OCT in obtaining choroidal
images, there may be less need to develop commercial devices
in the 1 micron realm. Newer light sources operating at
shorter wavelengths are being explored, and these may avoid
the problem of water absorption. An SS-OCT using a large-
bandwidth light source with a center wavelength of 850 nm
could provide high-speed, high-resolution imaging with little
falloff in sensitivity with depth.
1.4. Volume rendering
OCT pictures are generally shown as 2D B-scan images
acquired through the thickness of the retina. It is simple to
obtain numerous adjacent B-scan images with any typical SD-
OCT. After the successive images are aligned, a 3D volume can
be reconstructed. Noise reduction through averaging can be
done for each component of B-scan prior to creating the 3D
volume. Noise reduction after the 3D volume is assembled can
be completed with a variety of image processing techniques.
Many SD-OCT instruments rely on their inherently fast scan
rate to assemble a series of B-scans with the assumption that
the patient did not make any saccades during the scan
interval. Another approach is to align B-scans after acquisi-
tion, but this can result in image warping and local artifacts
where the images in successive B-scans don’t fit together well.
A third approach is to use eye tracking not only to average
individual B-scans, but also to maintain centration of the
volume scan. An example of 3D volume rendering of the
choroid is shown in Fig. 3. Although 3D rendering has been
available in radiology for decades, there has been remarkably
little penetration into ophthalmology. A B-scan can be infor-
mative, but in many cases can be compared to one page of
a book. Volume rendering allows viewing and measurement
of the choroid and any contained pathology in 3D from any
arbitrary direction and would also be a useful tool to assess
Fig. 3 e Volume rendering of a normal emmetropic eye. A
block of B-scan images was obtained in a 5 3 30 area and
then volume rendering using a raycasting was performed.
The block can be freely rotated in space (white arrow) and
successive sections can be removed from the scleral
surface of the choroid (bottom row). (Reprinted from
Spaide200 with permission of Springer-Verlag).
the three dimensions of any intrachoroidal process, such as
a choroidal tumor or granuloma, and its relationships to
adjacent structures.
2. Imaging the choroid using optical
coherence tomography
2.1. Measurements and reproducibility of choroidal
thickness
In using SD-OCT, whether it is Spectralis using EDI module,
Cirrus with HD, RTVue, or SS-OCT, the outer border of the RPE
and the inner border of the sclera usually are determined
manually by the observer. Digital calipers are placed at the
outer edge of the hyperreflective RPE line and the inner border
of the hyperreflective surface located behind the large
choroidal vessels, which is the scleral/choroidal interface.
These two points are chosen so that the line traced between
them is perpendicular to the RPE line. The measurements
commonly are performed under the geometric center of the
fovea and can be repeated at regular intervals from the center
of the fovea of varying sizes and locations. The subfoveal
choroidal thickness (CT) is defined as the distance between
these two points.
Various studies have evaluated the reproducibility of sub-
foveal CT measurements (Table 1). There is a very good
intersystem,16,96 interobserver, and intervisit reproducibility96
of CT measurements despite the lack of automated
software. The interobserver repeatability is good using
EDI-OCT,16,96,207,213 Cirrus HD OCT,16,122 Optovue RTVue,16 and
SS-OCT.83,96 The intersystem reproducibility of CT measure-
ments has been assessed between EDI-OCT and SS-OCT96 and
also between three different SD-OCT devices: Cirrus HD-OCT,
Spectralis using EDI module, and RTVue.16 The exact values of
correlation coefficients concerning the CT measurements
interobserver, inter-visit, and intersystem reproducibility are
listed in Table 1. For example, Tan et al mentioned not only an
intraclass correlation coefficient for interobserver reproduc-
ibility of 0.994, but also a value of the mean difference between
CT measurements between graders that was 2.0 mm for 24
normal eyes of 12 healthy volunteers.214 This difference was
less than the diurnal variation in the choroidal thickness. On
the other hand, automated segmentation in evaluation and
measurement of other ocular attributes may have large
testeretest variability coefficients213 and variations between
different instruments,105 and errors in automated segmenta-
tion are generally corrected with manual methods.158 Auto-
mated segmentation methods are generally faster and do not
require a high operator skill level, but they substitute idio-
syncrasies and biases of the algorithm coded for the idiosyn-
crasies and biases of a human observer.
2.2. Normal subfoveal choroidal thickness and
variations with age, refractive error, axial length, and sex
The first study measuring the CT in a population of healthy
volunteers using OCT used the EDI technique.124 Margolis and
Spaide investigated 54 normal, non-myopic eyes with a mean
age of 50.4 years using the EDI-OCT and reported a mean
Table 1 e Reproducibility of CT measurements (at the Fovea)
First author Interobserver repeatibility r (p) or ICC (p) or ICC (95% CI) Inter-visit reproducibility ICC (95% CI) Inter-system reproducibility r (p) or ICC (p) or ICC (95% CI)
(reference)
EDI Cirrus -HD RTVue SS EDI SS EDI and Cirrus EDI and Cirrus and EDI and SS

s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
RTVue RTVue

Spaide192 RE
0.93a
(p < 0.001)
LE
0.97a
(p < 0.001)
Manjunath116 0.92a
(p < 0.0001)
Ikuno89 0.97b 0.912b 0.893b 0.893b 0.921b
(0.948e0.985) (0.835e0.958) (0.864e0.916) (0.864e0.916) (0.875e0.948)
Branchini16 0.96a 0.95a 0.93a 0.976a 0.964a 0.965a
(p < 0.0001) (p < 0.0001) (p < 0.0001) (p < 0.0001) (p < 0.0001) (p < 0.0001)
Hirata78 0.968b
(p < 0.001)
Tan202 0.994b

ICC ¼ intraclass correlation coefficient; RE ¼ right eye; LE ¼ left eye.

a
Interclass correlation.
b
Intraclass correlation coefficient.

395
396 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
subfoveal CT of 287 mm. Normal was defined as patients
without any significant retinal or choroidal pathologic
features. They excluded patients with retinal or choroidal
pathology, uncontrolled diabetes or hypertension, and
myopia of more than 6 diopters of spherical equivalent. The
choroidalescleral interface was identified in 100% of partici-
pants.125 Increasing age was correlated significantly with
decreasing CT at all points measured (Fig. 4). The CT was
found to decrease by 15.6 mm for each decade of life.124 Since
this first report, there have been several reports of the foveal
CT in normal eyes obtained by use of various systems. Ikuno
et al investigated 86 non-myopic eyes of healthy Japanese
patients with SS-OCT with a mean age of 39.4 years and found
a subfoveal CT of 354 mm. Ikuno et al found that the CT
decreased by 14 mm for each decade of life.95 The mean sub-
foveal CT has been found to vary among studies from 203.6 mm
in 31 eyes with a mean age of 64.6 years83 to 448.49 mm in 22
eyes with a mean age of 35.72 years.8 The percentage of
identification of the scleral choroidal interface was 74% of 34
eyes in one series122 using Cirrus OCT HD; the potential for
bias in thickness measurements in this sample cannot be
excluded, however, because of the high proportion of eyes
where the scleral choroidal interface could not be visualized.
The eyes in which measurements could not be made may
have been those with thicker choroids. This would bias the
results toward lesser values of CT.
The mean values for subfoveal CT are difficult to compare
from one study to another. One reason is that “normal” was
defined differently. Some studies excluded patients with
ocular disorders,122,124 some excluded patients with ocular
and systemic disorders,38,95 and some mentioned they
excluded patients with systemic disorders that might affect
CT83,124 (such as those that require corticosteroids use or had
diabetes mellitus or any systemic vascular disease). Some
highly myopic eyes with a spherical equivalent error greater
Fig. 4 e The correlation of subfoveal choroidal thickness
with age (scatter plot). The subfoveal choroidal thickness
(SFCT) in microns is negatively correlated with age in
years, SFCT [ 366 e 1.56 3 age (p [ 0.001). The trend line
is shown with 95% confidence interval. (Reprinted from
Margolis and Spaide124 with permission of American
Journal of Ophthalmology).
than e6.00 diopters.38,83,117 The studied populations have
different age, sex, and refractive error distribution, and the
macular CT in normal eyes has been negatively correlated
with age55,83,94,95,122,124 and axial length,8,38,83,117 and posi-
tively correlated with refractive error55,94,95 and male sex in
young people.117 There are several possible reasons for the
decrease in subfoveal CT with age, such as loss of chorioca-
pillaris, a decrease in the diameter of the choriocapillary
vessels, decrease in luminal diameter of blood vessels, and, in
some cases, a diminution of the middle layer of the
choroid.40,176,190 Histologic evaluation of eye bank and autopsy
eyes found a yearly decrease in CT of 1.1 mm per year, which
was less than the amount measured in vivo of 1.56 mm per
year.124 The differences may be related to the fact that the
histologic specimens were autopsy eyes, which by definition
had no blood pressure, and the living choroid is an inflated
structure.40,176,190
2.3. The asymmetric nature of choroidal thickness
Margolis and Spaide also demonstrated the asymmetric
nature of macular CT. They showed that CT varies topo-
graphically within the posterior pole. The choroid was thick-
est under the fovea, with a mean value of 287 microns. The CT
decreased rapidly in the nasal direction and averaged 145
microns at 3 mm nasal to the fovea (Fig. 5). They hypothesized
that the age-related choroidal thinning nasally may
contribute to two common and possibly related clinical
conditions: peripapillary atrophy and glaucomatous optic
neuropathy.
Many reports not only confirmed these findings (choroid
thickest under the fovea and thinnest nasally), but also
showed that the CT was thinner nasally than temporally, and
thinner inferiorly than superiorly.38,83,95,122 Some analyzed
the peripapillary CT in normal eyes with Cirrus HD OCT84 or
Fig. 5 e The asymmetric nature of macular choroidal
thickness. The mean choroidal thickness is measured at
different locations across a horizontal section through the
fovea at 500-mm intervals from 3 mm nasal to 3 mm
temporal to the fovea. The error bars represent 1 standard
deviation. (Reprinted from Margolis and Spaide124 with
permission of American Journal of Ophthalmology).
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 397

Fig. 6 e The internal structure of the normal choroid. Note that the choroidal vessels are decreasing in diameter from the
outer to the inner choroid. The larger vessels (white triangles) are dark in the center with a thick hyperreflective wall (A). The
medium-size vessels (hollow triangles) appear with a smaller hyporeflective area in the center and a hyperreflective wall (A).
As the diameter of the vessels decreases the central hyporeflective area decreases until it is not visible. At that size, the
vessel is just visualized as a white hyperreflective structure (white arrows) (B). Note the delineation of the hyporeflective line
near the junction with the inner sclera, which appears to be in the suprachoroidal space. The red arrow points to a vessel
coursing through the sclera.

EDI-OCT215 and found that the inferior peripapillary choroid visualization of the PCAs and their major veins entrance sites,
was thinner than all other quadrants. The authors hypothe- their course, and their branching network, but does not
sized that it may be attributable to the embryological devel- differentiate choroidal arteries from veins with certainty.144
opment of the eye. The optic fissure is located in the inferior
aspect of the optic cup and is the last part to close. In their 2.5. Correlation of choroidal thickness and choroidal
study, Ho et al found that the CT increases radially from the blood flow
optic nerve in all directions in emmetropic eyes and eventu-
ally approaches a plateau.84 Sogawa et al investigated the relationship between the CT and
choroidal blood flow in 25 eyes of 25 healthy young volunteers,
with a mean age of 30.1  2.8 years and a mean refractive error
2.4. The internal structure of the choroid
of 3.4  3.1 diopters.198 They evaluated subfoveal choroidal
thickness using EDI-OCT, total choroidal blood flow using
EDI-OCT allowed the first study of macular choroid in vivo
pulsatile ocular blood flow with Langham OBF computerized
in 2008, including thickness measurement and internal
tonometry, and subfoveal choroidal blood flow using laser
structure.207 Whereas the choriocapillaris may be too small,
Doppler flowmetry. They found no significant correlation
too densely packed, and too intimately bound to Bruch
between subfoveal choroidal thickness and total choroidal
membrane to be differentiated and identified by the EDI-OCT’s
blood flow or subfoveal choroidal blood flow. The correlation
resolution, Fong et al have hypothesized that hyper-reflective
between the local subfoveal CT and the total choroidal blood
foci visualized beneath the Bruch’s membrane line represent
flow is not known. Regarding the correlation of subfoveal CT
cross-sections of the parallel arterioles and venules.43 The
with foveal choroidal blood flow, it is noteworthy that the
hyperreflective dots’ diameter was measured to be 50 microns
Doppler signal from the foveal region using laser Doppler
by EDI-OCT using digital calipers. The fact that venules and
flowmetry is predominantly caused by the red blood cells
arterioles in this layer measure 35e95 microns and 30e85
moving in the choriocapillaris and to a variable extent the
microns, respectively, seems to support this hypothesis
larger choroidal vessels behind it.181 Moreover, the relation-
(Fig. 6).18
ship between the choroidal blood flow and the CT is not fully
Motaghiannezam et al visualized the vessels through the
resolved at present. Ultimately, Doppler or phase variance
different choroidal layers by extracting depth-resolved en face
techniques should not only enable visualization of the
images from 3D-OCT data sets using SS-OCT in three healthy
choroid, but also provide information about the flow in indi-
volunteers. Comparison of SS-OCT en face images and scan-
vidual vessels.
ning electron microphotographs at the level of the chorioca-
pillaris showed that the capillaris, arterioles, and venules in
the choriocapillaris were smaller than the transverse resolu-
tion of the SS-OCT (around 15 mm) and could not be resolved. 3. Choroidal thickness variations in normal
The other choroidal layers of medium-sized vessels, large- eyes
sized vessels, and suprachoroidal layer could be delineated
and correlated to scanning electron microphotographs. This Brown and associates demonstrated diurnal fluctuations of
technique also allows choroidal thickness mapping, CT measured using a non-contact optical biometer Lenstar LS
398 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
900 (Haag-Streit AG, Köniz, Switzerland).19 Determining CT
was possible only in 28% of the patients with a single
measurement. By repeating measurements and averaging the
partial coherence interferometry signals, a peak of reflectivity
corresponding to the scleral choroidal interface was estimated
in another 70%.19 The authors demonstrated significant
diurnal fluctuations of CT. Chakraborty et al also found that
CT underwent significant diurnal variations using this bio-
meter that is based on the principle of optical low-coherence
reflectometry, a forerunner of OCT.21 They also demon-
strated diurnal variations of axial length and that CT varied
approximately in anti-phase to the diurnal axial length
changes. They performed this study on 30 normal eyes of 30
healthy young adults with a mean age of 25.2 years. There was
no anisometropia greater than 1 D. Tan et al demonstrated
significant diurnal variations of subfoveal CT using EDI-OCT in
24 normal eyes with a mean axial length of 23.9 mm (range,
21.9e26.3 mm) of 12 healthy volunteers with a mean age of 30
years.214 The mean amplitude in diurnal subfoveal CT change
was 33.7 mm (range, 3e67 mm), corresponding to a percentage
of change in CT of 8.5%, with the highest mean CT in at 9 AM
and the lowest at 5 PM. The amplitude of variations of sub-
foveal CT was significantly negatively correlated with age
(r ¼ 0.339), axial length (r ¼ 0.631), refractive error
(r ¼ 0.626), and change in systemic blood pressure (r ¼ 0.508).
This characteristic significant diurnal variation pattern of
subfoveal CT should be taken into account in clinical practice
and clinical trials whenever comparing the measures of CT
over time. It is also noteworthy that this study found a corre-
lation between the amplitude of subfoveal CT variations and
changes in systemic blood pressure in emmetropic normal
young patients, although Li et al found no correlation between
subfoveal CT and arterial blood pressure in normal young
individuals.117
The CT has also been found to fluctuate with defocus in
humans.178 The realization of emmetropia depends on
active mechanisms that sense image blur and then take
steps to improve the image to include moving retina to
reduce the blur, and permanently altering ocular dimen-
sions. An active increase or decrease in CT moves the retina
to the correct position, as shown in laboratory investiga-
tions in chickens226,231 and mammals.91,220 Recently, Read
et al used the biometer to demonstrate that similar changes
in CT occur in humans in response to short-term unilateral
image blur.178 The choroid was found to thicken with the
myopic defocus condition and to become thinner with the
hyperopic defocus.
4. Age-related choroidal atrophy
4.1. Description of a new entity
Spaide described a condition in non-myopes he named age-
related choroidal atrophy (ARCA). Although CT appears to
decrease with age, there are some patients who seem to have
a pronounced loss of CT over time (Fig. 7).203 Despite relatively
preserved Snellen visual acuity, these patients have visual
complaints frequently involving reading and exhibit charac-
teristic fundus changes quite similar to those seen in myopes.
The larger choroidal vessels are easily discerned, many of the
visible choroidal vessels do not appear to be red, but are
yellow or white. There may be pigmentary granularity in the
posterior pole and peripapillary atrophy. There is often mild
optic nerve pallor.
The EDI-OCT shows marked loss of thickness of the
choroid in 28 eyes of 17 patients with a mean age 80.6
years.203 There appears to be loss of the choroidal vessels
such that the remaining larger vessels fill the entire thick-
ness of the choroid. This implies there is a loss of the middle
layers. The larger choroidal vessels are easily visible because
there is a lack of pigmentation found in a choroid of normal
thickness and because there appears to be a loss of the
medium-sized choroidal vessels. These patients can have
normal autofluorescence imaging implying a normal RPE, in
contrast with eyes that have geographic atrophy in which
the RPE is lost in patches. ARCA and age-related macular
degeneration (AMD) are two distinct conditions. The previ-
ously used term non-geographic atrophy might have
referred to ARCA, but non-geographic atrophy was never
clearly defined. Both happen in older adults, and there may
be a higher proportion of both occurring together.211 Eyes
with thinner choroids seem to have a higher risk for glau-
coma203,211 and an association with a predominance of
subretinal drusenoid deposits.203,211
4.2. Age-related choroidal atrophy and geographic
atrophy
The clinical presentations of ARCA and geographic atrophy
are different. Geographic atrophy is recognized as a well-
defined round or oval area of absent RPE pigmentation in
which choroidal vessels are more visible.11 In ARCA there is
a global thinning of the choroid with rarefied choroidal
vessels. Geographic atrophy occurs in the posterior pole,
whereas ARCA is more widespread. There is tessellation of
the fundus in eyes with ARCA. When geographic atrophy
develops, there is a loss of the RPE cells and their pigment,
and as a consequence discrete areas of RPE autofluorescence
loss. Eyes with ARCA lose pigmentation in the choroid.
When geographic atrophy happens in an eye with ARCA, the
patches can look nearly white because there is little inter-
vening tissue between the residual layers of the retina and the
underlying sclera.
4.3. Age-related choroidal atrophy and pattern
dystrophy
Pattern dystrophy has been used to describe dozens of
different phenotypically different appearances in the eye. In
some instances the term is used to describe an autosomally
inherited disorder that may be associated with mutations in
the peripherin-2 gene (also known as the peripherin/RDS
gene) of which there are at least 90 known.230 In general eyes
with pattern dystrophy have a symmetrical alteration of
pigment, or at least have pigmentary figures, sometimes with
concurrent vitelliform deposits.228 These are diseases of the
RPE and outer retina and there is no concurrent abnormality
described in the choroid. There may be pigmentary clumping
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 399

Fig. 7 e Multimodal imaging of the left eye of an 82-year-old woman with age-related choroidal atrophy. This patient was
referred because she was thought to have choroidal neovascularization. The color photograph (A) and magnification of the
fovea (B) show the hallmarks of age-related choroidal atrophy. Note the slight optic nerve pallor, the peripapillary atrophy
present even though she was emmetropic, and the tesselated fundus appearance with some of the choroidal vessels
adopting a yellowish appearance. On the magnified color photograph of the macula (B) note the paucity of vessels except for
a few red choroidal vessels. The fluorescein angiogram (C ) ruled out choroidal neovascularization. In two EDI-OCT sections
(D) note the thinness of the choroid with a few remaining vessels filling the full-thickness of the choroid (arrows). (Reprinted
from Spaide200 with permission of Springer-Verlag).

in some eyes with more advanced ARCA, but these pigmen-
tary clumps often appear to be in the choroid.
5. Choroidal imaging in central serous
chorioretinopathy
5.1. Choroidal hyperpermeability in CSC
Since its first description by von Graefe in 1866, the under-
standing of central serous chorioretinopathy (CSC) patho-
physiology has evolved. In the 1960s, Maumenee used
fluorescein angioscopy to visualize the leaks from the level of
the RPE. In 1967, Gass proposed that choriocapillaris hyper-
permeability was the source of the fluid leak.58 Later in the
1980s, Marmor performed experiments on healthy rabbits and
found that the RPE pumped fluid and that there was a normal
flow of fluid from the vitreous to the choroid.44 He also pointed
out that the tissue osmotic pressure was higher in the choroid
than in the vitreous and causes passive fluid flow from the
vitreous towards the choroid.44,150,151 Thereafter theories of
RPE cells pumping the opposite way were developed to explain
CSC.126,210 In the 1990s, ICG angiography demonstrated
choroidal hyperpermeability in CSC and confirmed Gass’s
original idea.
There are many different clinical presentations of CSC:
the two main ones are classic CSC, a circumscribed area of
subretinal fluid associated with one or several focal leaks
seen on fluorescein angiography, and chronic CSC, a wide-
spread area of RPE changes associated with many ill-defined
angiographic leaks. Choroidal hyperpermeability as demon-
strated by ICG angiography is the unifying feature of all types
of CSC, independent of the age of the individual, chronicity,
sub-type of CSC, or relationship of the CSC to corticosteroid
treatment or past organ transplantation.92,202 Gass hypoth-
esized that, in CSC, excessive tissue hydrostatic pressure
within the choroid from the vascular hyperpermeability may
lead to mechanical disruption of the RPE barrier and
abnormal egress of fluid under the retina.58 Later, studies
using ICG angiography have shown multifocal areas of
choroidal vascular hyperpermeability,74,93,164,204 vascular
congestion,171 venous dilation.93,171 These areas of choroidal
vascular hyperpermeability on ICG angiography were more
widespread than the areas of leakage visualized on the
fluorescein angiography.74,204 The ICG findings of choroidal
vascular hyperpermeability persisted after resolution of
leakage from the RPE93 and have been found in the majority
of unaffected fellow eyes.93,204 If CSC is caused by choroidal
vascular hyperpermeability, then one would expect the CT to
be altered as well.
400 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

5.2. Choroidal thickness in CSC 5.3. Choroidal thickness after treatment in CSC

Imamura and associates examined the subfoveal CT in 28 eyes
of 19 patients with CSC.99 Among these patients, 16 had chronic
CSC. The mean age was 59.3 years, and 12 had bilateral clinical
disease. The mean subfoveal CT was 505 mm, significantly
greater than that of normal eyes (p < 0.001) (Fig. 8). The CT in
these CSC patients did not show the normal age-related decline.
In a majority of chronic CSC cases in that study, the thickening
of the subfoveal choroid was present in both eyes, even if the
manifestations of CSC were present in only one eye.99
The subfoveal choroid in the fellow eyes of patients with
CSC was found to be thicker in the eyes with choroidal
vascular hyperpermeability and not thicker in the fellow eyes
without hyperpermeability on the ICG angiography.131
Choroidal thickness was correlated with choroidal hyper-
permeability. EDI-OCT is useful to evaluate the subclinical
choroidal abnormalities in CSC, especially in fellow eyes.
Furthermore, the increase in CT is not restricted only to the
areas of choroidal vascular hyperpermeability as demon-
strated by ICG angiography, but is generalized.238 Therefore,
measuring choroidal thickening has become a test to help
diagnose CSC (Fig. 8).46
Maruko and associates evaluated subfoveal CT as assessed by
EDI-OCT and choroidal vascular hyperpermeability as demon-
strated by ICG angiography after treatment either with laser
photocoagulation or half-dose verteporfin photodynamic
therapy (PDT) for CSC.130 They analyzed 12 eyes in the laser
group and 8 eyes in the PDT group. The serous subretinal fluid
resolved in both groups after treatment. In the laser group, the
mean subfoveal CT was not significantly different from a mean
of 345 mm at baseline to a mean of 340 mm at 4 weeks (p ¼ 0.2). In
the PDT group, the mean CT increased significantly from a mean
of 389 mm at baseline to a mean of 462 mm (p ¼ 0.008) by 2 days
after treatment, and then fell rapidly to 360 mm (p ¼ 0.001) at 1
week and to 330 mm (P < 0.001) after 4 weeks as compared with
baseline. The choroidal vascular hyperpermeability as demon-
strated by ICG angiography decreased only in the PDT group at 4
weeks after treatment (Fig. 9). The reduction in the subfoveal CT
remained stable at the 1-year follow-up after treatment.127
These results have potential clinical implications. Laser photo-
coagulation of leaks in CSC may shorten the duration of any one
episode, but has no effect on recurrences. Although there is
limited information available about the long-term outcomes of

Fig. 8 e Multimodal imaging of both eyes of a 56-year-old man with central serous chorioretinopathy in the left eye. The
patient complains of vision loss in the left eye for 3 months. The vision is 20/50 in the left eye and 20/20 in the right eye. The
color photograph of the left eye (B) shows a shallow foveal neurosensory detachment with dot-like subretinal yellowish
precipitates, pigmentary mottling, and some atrophy. The color photograph of the right eye (A) shows pigmentary changes
in the superior-temporal macula. EDI-OCT foveal scans of both eyes (C, D) show bilateral subfoveal choroidal thickening
(double arrowhead ) measured at 400 microns in the left eye and 450 microns in the right eye, even though the central serous
retinal detachment is only in the left eye.
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 401

Fig. 9 e Multimodal imaging of the left eye of a 49-year-old man with persistent central serous chorioretinopathy treated
with half-fluence verteporfin PDT. The color photograph (A) shows macular serous retinal detachment with vitelliform
material, corresponding to hyper-autofluorescent lesion on the fundus autofluorescence imaging (B). The fluorescein
angiogram (C ) does not show any focal leak but does show diffuse hyperfluorescent areas of leakage. The mid-phase
indocyanine green angiogram (D) shows multifocal hyperfluorescent areas of inner choroidal staining. The half-fluence
PDT was ICG-guided, targeting the large macular area of hyperfluorescence. The conventional OCT scans before (E ) and 1
month after (F ) PDT show complete resolution of central serous retinal detachment. The EDI-OCT scans before (G) and
after (H ) PDT show that the choroid was thickened initially at 465 microns (G, double arrowhead) and decreased to 145
microns 1 month after PDT (H, double arrowhead ). The vision improved from 20/40 to 20/20. There was no recurrence at 1
year follow-up.

PDT for CSC, it appears that recurrences are distinctly
uncommon. Laser photocoagulation does not appear to address
the underlying problem, namely, choroidal vascular hyper-
permeability, whereas PDT does.
5.4. Other relevant findings about CT and CSC
5.4.1. Glaucoma and CSC
In a case-control study, Imamura et al found that glaucoma is
less frequent in patients with CSC,98 suggesting that alter-
ations in the choroid may influence the risk for glaucoma.
Increased blood supply from the choroid to the optic nerve in
CSC patients may be a contributing factor.
with six controls.137 The authors reported the variance
between the two measurements was greater in the sildenafil
group. An EDI-OCT study of eight healthy patients found that,
at 1 and 3 hours after ingestion of sildenafil, there was
a significant increase in CT.224 These findings suggest the
potential for pharmacologic manipulation of the CT, and by
inference the choroidal blood flow, may be possible.
6. Choroidal imaging in age-related macular
degeneration
6.1. AMD

5.4.2. Sildenafil, choroidal thickness, and CSC At the time when the genetic basis of AMD is being unraveled,
An ultrasound study measured the thickness of seven eyes some important questions concerning its pathogenesis
before and 1.5 hours after taking sildenafil citrate as compared remain unsolved. One of these questions is how the choroid
402 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

modulates the expression of AMD. Geographic atrophy and
age-related choroidal atrophy are both related to aging. Even
though they can occur concomitantly, they are not necessarily
associated.203 Histologic evidence regarding CT in AMD is
mixed, with some studies suggesting a reduction in the cho-
riocapillaris diameter and density138 or a reduction in macular
CT, especially in the advanced stages of the disease,190 and
another study showing no significant change in foveal CT,
even in advanced AMD.176 Being able to measure and monitor
the CT in vivo early in the natural course of the disease may
provide insight into the earliest structural changes occurring
in AMD and determine risk factors for progression.
Wood et al analyzed macular CT in early AMD with SS-
OCT.232 The CT was measured at the fovea and at 500-mm
intervals to a maximum of 2.0 mm nasally, temporally,
superiorly, and inferiorly. They found that CT in early disease
was not significantly different from controls. Early AMD was
defined as the presence of soft drusen greater than 125
microns in diameter, pigment changes, or drusenoid pigment
epithelial detachment in the absence of any feature of
advanced wet or dry AMD. In this study, the presence of
drusen in the control eyes was allowed if they were less than
125 mm in diameter. Switzer et al included other key features
in their analysis of CT in early AMD with EDI-OCT,211 espe-
cially subretinal drusenoid deposits (also called pseudo-
drusen) (Fig. 10). They found that thin choroid was associated
with tessellation of the fundus, subretinal drusenoid deposits,
glaucoma, b-zone peripapillary atrophy, and lack of conven-
tional drusen.208 These results suggest that there is a highly
significant association of CT with several key features of AMD,
each of which have been shown previously to have different
risk profiles for progression to late AMD (Fig. 11). There are
many theories about how the earlier manifestations of AMD
develop, but it is clear that there are interactions with the
choroid, and these merit further investigation.
Manjunath et al analyzed retrospectively macular
choroidal thickness at 11 points in 57 eyes with dry and wet
AMD using the Cirrus-HD OCT without using the EDI tech-
nique.123 The subfoveal CT was measured at 194.6  92.2 mm
in 40 eyes with wet AMD (mean age, 78.6 years) and at
213.4  92.2 mm in 17 eyes with dry AMD (mean age, 78.2
years). The subfoveal CT was within the normal range (2
standard deviations) except for two eyes with a choroid
thicker than 2 standard deviationsdone with dry AMD and
one with wet AMD. There was no significant correlation
between CT and the number of anti-VEGF injections,
number of years of disease, and visual acuity. Eyes with dry
AMD demonstrated a significant negative correlation with
age whereas eyes with wet AMD showed a weak negative
correlation with age that was not statistically significant.
This included seven patients with wet AMD previously
treated with photodynamic therapy at least once, which
may have biased the results towards lesser values of CT in
the wet AMD group. The authors did not mention the
percentage of identification of scleralechoroidal interface in
that study.
6.2. Pigment epithelial detachments in AMD: formation,
RPE tears
There have been numerous theories concerning the
formation of pigment epithelial detachments (PEDs) in
AMD. Different sequences of events have been proposed,
involving different structures: CNV,59 decreased hydraulic

Fig. 10 e Multimodal imaging of the right eye of an 80-year-old white woman with subretinal drusenoid deposits. The color
fundus photograph (A) shows numerous subretinal drusenoid deposits. Their visualization is enhanced on the blue color
channel (B). The near infrared can sometimes help in their visualization (C ). These drusen are seen clearly using EDI-OCT
(D) to lie above the RPE and under the neurosensory retina ( yellow arrow), sometimes distorting or extending through the
external limiting membrane. This patient had a subfoveal choroidal thickness of 106 microns. (Reprinted from Switzer
et al211 with permission of Retina).
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 403

Fig. 11 e Multimodal imaging of the left eye of an 82-year-old woman with fibrovascular PED and its response to
ranibizumab treatment. A: This patient was seen emergently because of a 3-day history of visual acuity change. The color
photograph shows intra- and subretinal hemorrhages overlying a PED. The early fluorescein angiogram (B) shows
generalized hypofluorescence of the PED with two areas of increased fluorescence, one contiguous with the retinal
hemorrhages and a second area inferiorly. The two lines correspond to sections examined with the EDI-OCT scans shown
in Fig. 12B. Late fluorescein angiogram (C ) shows a generalized increase in fluorescence within the PED. Early during the
indocyanine green (ICG) angiographic sequence there are two hyperfluorescent areas (triangles) that corresponded to what is
in the fluorescein angiogram. Because the pigmentation in the RPE is thought not to represent a major impediment to the
passage of near infrared light used in ICG angiography, the hyperfluorescent areas were considered to represent actual
neovascularization and not transmission defects through the RPE. (Reprinted from Spaide205 with permission of American
Journal of Ophthalmology).

conductivity of Bruch membrane,12 the anastomosis of
retinal vessels with underlying occult CNV,110,197 and retinal
vascular proliferation without any choroidal vascular
involvement. This was first described as deep retinal
anomalous complexes75 and later renamed retinal angio-
matous proliferation (RAP).235 Gass proposed that patients
who appeared to have RAP actually had early occult cho-
rioretinal anastomosis with CNV and retained his earlier
idea that exudation from occult CNV extended laterally with
the development of an adjacent PED.62
One difficulty in producing an adequate and unifying
hypothesis to explain the structure and pathogenesis of PEDs
is the lack of information concerning their contents as a result
of difficulty visualizing them with conventional imaging
techniques.205 EDI-OCT enables visualization of the contents
of PEDs.205 Analysis of PEDs in AMD by EDI-OCT found that
PEDs that appeared to be “hollow” by conventional OCT were
actually filled with layers of hyperreflective material sugges-
tive of a multilamellar scar (Figs. 11, 12).205 In all 22 eyes
examined with PEDs related to AMD, material was visualized
within the PED: either solid material with lamellar structures
and cleft, or hyporeflective material along the back surface of
the PED.205 Analysis of this internal structure and correlation
with fluorescein and ICG angiography show that this material
is, at least in part, afibrovascular proliferation. These findings
support the neovascular origin of the PEDs, and the term
“fibrovascular PED” is appropriate. Untreated PEDs often
appear to have fibrovascular proliferation coursing up the
back surface of the detached RPE. Treated cases appear to
contain material consistent with multilamellar scar-
containing vessels, similar to reported histopathology.69
Fibrovascular PEDs pose a risk for RPE tears. The mecha-
nism by which RPE tears occur in fibrovascular PEDs has been
debated for more than 30 years. Bird proposed that RPE tears
do not occur because of neovascularization, but rather occur
because the RPE pumped enough fluid to cause hyperbaric
rupture of the PED.13,87 Gass proposed that patients with RPE
tears had underlying CNV,63 the tear occurred on the far side
of the PED away from the CNV secondary to hyperbaric pres-
sure in the PED,63 and that laser photocoagulation may induce
shrinkage to accelerate this process.60 None of these theories
explains why RPE tears develop following anti-VEGF injec-
tions.22,23 Anti-VEGF injections used as an adjunctive agent of
surgery in severe proliferative diabetic retinopathy5,159 and
404 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

Fig. 12 e The EDI-OCT scans on the left (A, C, E ) correspond to the upper line in the early phase fluorescein angiogram
(Fig. 11B) and the ones on the right correspond to the second line (B, D, F ). Prior to treatment the section through the
‘hotspot’ on both the fluorescein and ICG angiograms (A) shows a small collection of material posterior to the RPE within the
PED. Note that the hyperreflective line corresponding to the RPE has variable thickness throughout the extent of the PED. A
section taken inferiorly (B) shows a more extensive accumulation of material along the back surface of the PED. There was
an accumulation near the edge of the PED of similar material, but the extent of hyperfluorescence in the fluorescein and ICG
angiograms cannot be attributed solely to this accumulation, implicating the material on the back surface of the PED as
being fibrovascular in nature. One week after intravitreal ranibizumab injection (C, D) there was a partial collapse of the PED.
Note the separation of the hyperreflective line (triangle) from the back surface of the PED (C, D). The correspondence in shape
between the pretreatment and 1-week-post-treatment accumulation within the PED is more evident inferiorly (D). Note the
separation and straightening of the sub-RPE material after the ranibizumab injection even though the PED is collapsing.
This implies there was tensile traction within the detached material. One month after injection there was complete
flattening of the PED over a hyperreflective material suggestive of a multilamellar scar (E, F ). (Reprinted from Spaide205 with
permission of American Journal of Ophthalmology).

retinopathy of prematurity86 can induce a rapid contraction of
the fibrovascular material and subsequent development or
progression of tractional retinal detachment. EDI-OCT reveals
that contracture of fibrovascular material seems to happen
after anti-VEGF injections in fibrovascular PEDs as well, such
that the material could form sheets across the inner chord
diameter of the fibrovascular PED.205 Following anti-VEGF
therapy, a contracture of the vascular proliferation under
the back surface of a PED could also cause a tear in the over-
lying RPE monolayer (Figs. 13e15)205 and causes the RPE to
retract and scroll. Histopathologic analyses of RPE tears per-
formed by Toth et al219 and Lafaut et al111 were consistent
with this observation. They both showed that the under
surface of the torn RPE was adherent to a contiguous under-
lying plaque of CNV.
The contracture of the vascular proliferation could also
cause radial chorioretinal folds in the surrounding tissue,
radiating from the retracted borders of the treated fibrovas-
cular PED (Fig. 16). During the course of anti-VEGF therapy,
persistent or recurrent fluid exudation secondary to CNV may
appear at the back surface of the hyperreflective material at
the base of the fibrovascular PED. The fluid can appear as
a hyporeflective area between the hyperreflective posterior
border of the material within the PED and anterior border of
the choroid if visualized using EDI-OCT (Fig. 16).
6.3. Polypoidal choroidal vasculopathy: its relationship
to AMD and CSC
Polypoidal choroidal vasculopathy (PCV) characteristically
shows multiple, recurrent, serosanguineous detachments of
RPE and neurosensory retina secondary to leakage and
bleeding from choroidal vascular lesions.233 The exact rela-
tionship between PCV, typical exudative AMD, and choroidal
hyperpermeability is not yet completely understood. There is
disagreement as to whether PCV is a subset of AMD or
a separate entity: Some researchers have suggested that the
peculiar choroidal vascular lesion seen in PCV can be
considered a variant of the CNV in typical exudative
AMD,112,120,223 whereas others have suggested that PCV
exhibits inner choroidal vessels abnormalities distinct from
CNV.148,206,234 The presence of drusen or focal hyperpigmen-
tation is not common among patients with PCV.237 Patients
with PCV are younger and seem to have a better natural
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 405

Fig. 13 e Multimodal imaging of the right eye of a 75 year-old man with fibrovascular PED who developed an RPE tear. A: Pre-
treatment characteristics. The midphase fluorescein angiogram shows a heterogeneously filled PED (arrow). The ICG
angiogram (B) shows a hyperfluorescent plaque located to the nasal side of the PED (arrow). EDI-OCT scans taken through
the superior border of the PED (C, corresponding to the superior arrow on the fluorescein angiogram) and a little bit further
down (D, inferior arrow on the angiogram) show material along the back surface of the nasal side of the PED. (Reprinted from
Spaide200 with permission of Springer-Verlag).

history.237 PCV and typical exudative AMD therefore have
a different demographic risk profile and visual prognosis, but
they share the same genetic associations,70,118 have similar
histopathologic findings with the exception of the vessel
size,186 and respond to the same treatments.
ICG angiography allowed identification of two basic
vascular abnormalities associated with PCVda branching
network of vessels and vascular dilations at the border of the
network206dbut ICG angiography cannot define their exact
depth or the precise location of the polypoidal abnormalities
in relation to the choriocapillaris.206 In the earliest descrip-
tions of PCV, the vessels were thought to be in the choroid.233
Simultaneous SD-OCT and ICG angiography has localized the
polypoidal lesions and their branching network between
Bruch’s membrane and the RPE (Fig. 17).
Two studies, one in Korea and one in Japan, found that the
CT was thickened in PCV patients compared with typical
exudative AMD patients.29,108 In the Korean study, Chung
et al found that the choroid of fellow uninvolved eyes of PCV
was also markedly thickened.29 They concluded that these
bilateral changes in CT might indicate involvement of
systemic factors such as hypertension in the evolution of
PCV. In the Japanese study, Koizumi et al compared the
subfoveal CT of 23 eyes with PCV and 22 treatment-naı̈ve
eyes with typical exudative AMD. They excluded patients
with retinal angiomatous proliferation and high myopia.
They found that the subfoveal CT was significantly greater in
eyes with PCV (293 mm) than in eyes with AMD (245 mm) after
adjusting for age, refractive error, and sex (p ¼ 0.045). They
also found that eyes with subfoveal CT of 300 mm or more
were 5.6 times more likely to have PCV compared with eyes
with less CT.108
Multifocal choroidal vascular hyperpermeability, a charac-
teristic finding of CSC, was detected in the mid-phase ICG
angiogram in 9.8% of eyes with PCV as compared with only 2%
of eyes with exudative AMD.191 Koizumi and associates found
that 34.8% of 89 eyes with PCV had choroidal vascular
hyperpermeability, and these eyes more frequently demon-
strated an increased subfoveal choroidal thickness and
a history of CSC.107 PCV has been thought to masquerade as
CSC;236 some cases of what was diagnosed as CSC, however,
have been followed for many years and only later found to be
harboring small polypoidal lesions. It seems unlikely that the
polypoidal lesions could have caused CSC-like findings for
decades without growing large. Thus, it is possible that CSC
may lead into PCV.
406 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
Fig. 14 e One month after one intravitreal ranibizumab
injection, the fundus autofluorescence photograph (A)
shows a hypoautofluorescent defect with an area of
increased autofluorescence from scrolled retinal pigment
epithelium (arrow). Corresponding EDI-OCT scans taken
through the same areas (B, C ) as in Fig. 13 show a gap in
the RPE line (triangles) with subsequent increasing light
penetration to the choroid. The corrugated retinal pigment
epithelial monolayer sits on the reflective material seen in
the pre-rip EDI-OCTs seen in Fig. 13A. (Reprinted from
Spaide200 with permission of Springer-Verlag).
7. Choroidal thickness in posterior uveitis
Many inflammatory diseases in the posterior segment of the
eye are known to originate from, or at least involve, the
choroid. The monitoring of CT may prove to be an accurate
way to evaluate inflammatory processes and potentially
to monitor the response to treatment in a non-invasive
manner.
7.1. Vogt-Koyanagi-Harada
Vogt-Koyanagi-Harada (VKH) syndrome, a granulomatous
inflammatory disorder that occurs frequently in patients of
Asian, American Indian, or Hispanic descent,35 affects the
eyes, meninges, and skin and has been clinically divided
into prodromal, acute, chronic, and chronic recurrent
stages. Evaluating choroidal involvement is crucial to assess
treatment efficacy and sub-clinical recurrences in VKH
disease. ICG angiography enables visualization of the
choroidal vessels, but its utility is limited for VKH disease
because there is diffuse leakage of dye from the choroidal
vessels, partially obscuring them. Also, ICG angiography is
Fig. 15 e Pre- and post-rip comparison. A: The pre-rip EDI-
OCT with a red line drawn through the center of the RPE
monolayer shows the portion that filled with fluorescein to
be the ballooned region to the left. The area corresponding
to the hyperfluorescent plaque is seen on the right with the
overlying retinal pigment epithelium showing
corrugations. After the rip (B), which appeared to occur in
the ballooned area of the detachment, the retinal pigment
epithelium was thrown into more obvious folds. This
suggests contraction of the underlying choroidal
neovascularization. (Reprinted from Spaide200 with
permission of Springer-Verlag).
invasive and inconvenient to perform repeatedly, and the
angiographic results offer little help in estimating the
needed corticosteroid dose.
Two studies examined the EDI-OCT findings of patients
with VKH. In one, of six patients with VKH in the acute and
convalescent stages43 the CT of the acute patients was greater
than those in the convalescent stage. There was no significant
difference in CT between convalescent eyes and controls. The
choroid of eyes with VKH was thought to have a decrease in
hyperreflective dots in the inner choroid as compared with
healthy controls. The nature of the dots was not elucidated,
but the authors proposed there may be pericapillary arteriole
and venule loss from inflammation.43 In a study of 16 eyes of
eight patients with acute VKH, the choroid was markedly
thickened by EDI-OCT, with a mean subfoveal CT of 805 mm at
presentation.128 After 3 days of intravenous corticosteroids
the mean subfoveal CT decreased to 524 mm. The patients
continued treatment using oral corticosteroids, and the mean
subfoveal CT was 341 mm at 2 weeks. One patient had
a unilateral detachment, but was found to have bilateral
choroidal thickening. The CT in each eye responded rapidly to
corticosteroid treatment.128
Treatment of VKH can be difficult because of the lack of
feedback information. Patients are treated with very high
dose corticosteroids acutely and then the dose is tapered.
The amount of reduction is usually a matter of clinical
experience. If the dose of corticosteroids is decreased too
much the patient can have a recurrence of the detachment,
although it is possible that some patients are given too
much corticosteroids. Following patients with an imaging
modality that permits simple, accurate, and reproducible
measurements of the choroid would allow treating physi-
cians to gauge drug dosing. If a patient has a normal CT,
a lower dose of corticosteroids may be possible. If the
choroid was found to be thickening, the dose could be
increased (Fig. 18).
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 407

Fig. 16 e Multimodal imaging of the right eye of a 95-year-old man with treated fibrovascular PED who developed
chorioretinal folds. Color (A) and red-free (B) photographs show chorioretinal folds ( green arrows) radiating from the
retracted borders of a fibrovascular PED treated with intravitreal anti-VEGF therapy. C: The conventional OCT scan does not
show much exudation except for a few intraretinal cystic changes. Note the multilamellar hyperreflective structure at the
back-surface of the partly collapsed PED. D: The EDI-OCT scan shows recurrent fluid exudation secondary to CNV at the back
surface of the hyperreflective lamellar material at the base of the fibrovascular PED.

7.2. Multifocal choroiditis and panuveitis
Unpublished data from our group about SD-OCT in multi-
focal choroiditis with or without panuveitis show the char-
acteristic finding is mound-like sub-RPE lesions that contain
homogeneously moderately reflective material. A second
characteristic finding in acute phases of inflammation is
eruption of the sub-RPE lesions and infiltration of the outer
retina. Eyes with infiltration of the outer retina often have
much larger regions of disruption of the inner segment

Fig. 17 e Multimodal imaging of the left eye of an 84-year-old woman with polypoidal choroidal vasculopathy. A: The color
photograph shows lipid deposition and sub-retinal and sub-RPE hemorrhages. B: The early ICG angiogram shows multiple
polyps and their vascular branching network but cannot assess their exact depth. C: Conventional OCT scan through one
polyp visualized on ICG angiography shows an irregular elevation of the RPE line. D: EDI-OCT scan through the same
location shows a round to ovoid structure with a hyporeflective center and a hyperreflective wall corresponding to the polyp
and located between Bruch’s membrane and the RPE lines.
408 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
Fig. 18 e Enhanced depth imaging SD-OCT of the right eye
of a 17-year-old girl with Vogt-Koyanagi-Harada disease.
The patient was given intravenous methylprednisolone
1,000 mg for 3 days followed by tapered oral prednisolone
starting at 40 mg/day. A: At baseline there is serous retinal
detachment fluid and the sub-foveal CT is measured at 611
microns. At day 1, the CT decreased to 433 microns. At day
3, the CT decreased to 356 microns. At day 14, the CT
decreased to 289 microns and there was complete
resolution of the serous retinal detachment. (Reprinted
from Maruko et al128 with permission of Retina).
ellipsoid band, known as the ellipsoid zone (EZ) that was
formerly known as the IS/OS boundary.208 The curious
finding is the nearly complete absence of any direct
choroidal involvement in multifocal choroiditis, despite its
name. Treatment of the eyes with corticosteroids caused
prompt flattening of the sub-RPE lesions; in some of these
eyes the underlying choroid decreased in thickness. This
implies there may be some underlying choroidal involve-
ment, perhaps by proximal effects from the overlying focus
of inflammation (Fig. 19). Although some authorities differ-
entiate multifocal choroiditis with panuveitis from multi-
focal choroiditis without panuveitis, and from punctate
inner choroidopathy, the EDI-OCT and autofluorescence
findings of all of these conditions appear to show identical
abnormalities in the outer retina and sub-RPE space. The
involvement, as evidenced by OCT, occurs independently of
any cells being visible in the vitreous or anterior chamber.
Given that all of these entities target the same location, that
the visually significant abnormalities induced by these
conditions occur in the outer retina and subretinal space,
and that each may have CNV as a frequent complication, the
clinical utility of trying to differentiate among them seems
minor. In the past trying to gauge disease activity by quan-
tifying cells in the vitreous and anterior chamber may have
been useful, but current imaging modalities are able to
visualize the exact sites of involvement and damage.
7.3. Acute zonal occult outer retinopathy
Acute zonal occult outer retinopathy (AZOOR) was described
by Gass as a unilateral or bilateral acute loss of outer retinal
function with minimal ophthalmoscopic change.57,61 Fuji-
wara et al evaluated the fundus autofluorescence and
SD-OCT findings in AZOOR in 19 eyes of 11 patients.56 All
presented with photoreceptor abnormalities, as assessed by
abnormalities of the EZ band, and thinning of the outer
photoreceptors layer in SD-OCT imaging. RPE abnormalities
as assessed by fundus autofluorescence were detected in
89% of patients. Eighty-nine percent had retinal arteriolar
attenuation and 63% had abnormalities in the inner retinal
structure on SD-OCT, and these abnormalities occurred in
areas of severe alterations of the outer retina. The CT was
normal, and no abnormality in choroidal structure was seen
using EDI-OCT. These findings raised a new concept of the
pathophysiology of AZOOR: the outer retina is damaged
with major photoreceptor loss, and the choroid blood supply
appears to be normal, at least in early stages. Therefore,
large amounts of oxygen are delivered from the intact
choroid to the inner retina through the areas of photore-
ceptors loss, which is the reason retinal vessels appear
attenuated in AZOOR, a disease of the outer, not inner,
retina. The retinal vessels autoregulate because of the high
oxygen tension delivered from the choroid. This excessive
oxygen has the potential to cause damage to the middle and
inner retina, as OCT alterations in these layers have been
identified in AZOOR patients.56
7.4. Birdshot chorioretinopathy
Birdshot chorioretinopathy is a chronic posterior uveitis
characterized by deep cream-colored, ill-defined lesions
scattered throughout the fundi in both eyes, with minimal
anterior and vitreous inflammation.188 The diagnostic criteria
established by an international consensus are bilateral
involvement, three or more peripapillary lesions inferior or
nasal to the optic disk in at least one eye, and low-grade
anterior segment and vitreous inflammation. HLA-A29 is
a supportive finding, but is not necessary, as are retinal
vasculitis and cystoid macular edema.116 Even though the
onset can be insidious, severe visual loss almost invariably
occurs.31 ICG angiography visualizes the choroidal lesions as
hypofluorescent spots, but cannot assess their exact
depth.39,90 The pathogenesis is unknown, and there is no
consensus on how to monitor disease activity. Many
uveitis specialists follow the disease activity using
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 409

Fig. 19 e Multimodal imaging of the left eye of a 34-year-old woman with multifocal choroiditis. A: Color fundus photograph
shows multiple macular white-yellow to grayish lesions of various sizes. B: Fundus autofluorescence imaging shows
numerous hypo-autofluorescent lesions corresponding to the white lesions on the color photograph. Early (C ) and late (D)
phase fluorescein angiograms show the multiple lesions as hyperfluorescent. Note the two bigger ones above the macula
appear as early hyperfluorescent round spots (white arrowheads, C ) with leakage at the late phase (white arrowheads, D).
Note also the ring of hyperautofluorescence around these spots on the fundus autofluorescence imaging (white arrowheads,
B). These lesions are probably a combination of scar, old CNV, and inflammatory material. E: Note that an SD-OCT scan
through the most superior of these two lesions shows inflammatory infiltration into the outer retina as a hyperreflective
area (white arrowhead ) above the RPE that is disrupted focally. The ellipsoid zone (EZ) is largely absent at the level of this
lesion. F: An SD-OCT scan through multiple lesions shows from the left to the right multiple sub-RPE mound-like lesions
with various degrees of disruption of the outer retina. Over the first one (empty triangle), the EZ is intact. Over the second one
(white triangle), the EZ is focally disrupted. The two following lesions (white arrows) infiltrate the outer retinal layers, with
total absence of the EZ band. Note that the choroid is visualized and does not seem disrupted.

electroretinography (ERG), but this detects changes only in which consequently would be prior to any ERG abnormalities.
patients who have suffered significant retinal damage. Ideally The analysis of birdshot chorioretinopathy using EDI-OCT
treatment could be undertaken prior to any retinal damage, and SS-OCT (Fig. 20) found that the typical cream-colored
410 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
Fig. 20 e Multimodal imaging of the left eye of a 61-year-
old man with bilateral birdshot chorioretinopathy. A: Note
the multiple creamy white lesions evenly distributed
throughout the fundus on the color photograph. The image
is somewhat hazy because of vitreous cells. B: An EDI-OCT
horizontal scan through a lesion located infero-temporal to
the fovea shows a hyporeflective area larger than the
lesion on the color photograph (white arrows). C: An EDI-
OCT horizontal scan at the same level taken after 6 months
of local corticosteroid therapy and oral mycophenolate
mofetil shows a near-complete resolution of the focal
choroidal hyporeflective infiltrate. D: An EDI-OCT scan
through the fovea shows normal subfoveal choroidal
thickness with no apparent lesion.
lesions on the fundus correspond to low-reflective to hypo-
reflective areas of infiltrates in the choroid that appear
somewhat larger than what is ophthalmoscopically visible.
The overlying area corresponding to the choriocapillaris does
not seem disrupted. There is a paucity of vessels within the
infiltrated areas.
There are only two histopathological reports of birdshot
chorioretinopathy,67,154 and one is of an eye that was in
phthisis for 2 years before enucleation.154 Gaudio and
associates described one eye with birdshot chorioretinop-
athy. They found multiple foci of lymphocyte aggregates in
the deep choroid sparing the choriocapillaris, and “abutting
Fig. 21 e Multimodal imaging of the right eye of a 40-year-
old man with toxoplasmic retinochoroiditis. A: Color
fundus photograph shows an ill-defined white lesion at
the border of a pigmented scar surrounded by subretinal
fluid. B: Swept source OCT horizontal scan through the
lesion shows numerous hyper-reflective dots in the
vitreous (white arrows). The lesion corresponds to an area
of retinal and choroidal thickening with major disruption
of the retinal layers and focal disruption of the RPE line.
The adjacent choroid is normal. The area in the white
square is magnified to show that there are also white dots
within the substance of the lesion ( yellow arrows); these
white dots are the same size as the ones in the vitreous,
suggesting they too may be inflammatory cells. Also, note
that there is thickening of the RPE line at the level of the
lesion causing posterior shadowing (B).
the choroidal vessels”, with additional areas of lymphocytic
aggregation in the optic nerve head and along retinal
vessels.67 These findings correspond very well to the local-
ization, reflectivity, and relationship to the choroidal vessels
of the inflammatory infiltrates as assessed with EDI-OCT.
The other study reported one phthsical eye suspected to
have birdshot chorioretinopathy, with diffuse granuloma-
tous inflammation involving mainly the retinal outer layers
and, to a lesser extent, the choroid.154 The radiating pattern
seen ophthalmoscopically may have an anatomic correlate.
EDI-OCT images involvement in the outer choroid, near the
larger choroidal blood vessels, which normally radiate
outward toward the vortex veins. This may constrain the
distribution of the infiltrative lesions.
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 411

In birdshot chorioretinopathy it is uncertain whether the 7.5. Toxoplasmic retinochoroiditis

retinal involvement is contiguous and secondary to
choroidal involvement or independent. A fundus auto-
fluorescence study106dand the fact that abnormalities on
the fluorescein angiography and abnormalities on the ICG
angiography do not co-localize39dsuggests that the
RPEeretina and the choroid may be damaged by an inde-
pendent topographic distribution of inflammation.
Toxoplasmic retinochoroiditis, the most frequent cause of
posterior uveitis in immunocompetent patients,14 is most
often the result of a congenital infection, with possible reac-
tivation later in life.17 The encysted form of the parasite is
called bradyzoites and the proliferative form is called tachy-
zoite. Toxoplasma cysts can remain latent in the chorioretinal

Fig. 22 e Multimodal imaging of the left eye of a 57-year-old woman seen for a second opinion for what was diagnosed as
unilateral serpiginous choroiditis. A: The color fundus photograph shows a whitish polygonal area of chorioretinal scarring
surrounded by a subtle yellow infiltration of the choroid. Note the general paucity of visible vessels in the yellow infiltrated
region. B: Early-phase ICG angiography shows an absence of choroidal vessels in the region of the yellow infiltrate seen in
the color photographs. C: EDI-OCT horizontal scan through the superior border of the scar shows large hyporeflective areas
within the choroid with nearly no visible choroidal vasculature (white triangles). A large choroidal vessel is visualized
through the infiltrated area (white arrow). D: An EDI-OCT horizontal scan taken at the same level after 2 months of oral
corticosteroid therapy shows a resolution of the diffuse choroidal infiltration (white triangles), but the choroid is extremely
thin. E: EDI-OCT scan of the fellow eye shows normal choroidal thickness and structure.
412 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

Fig. 23 e Multimodal imaging of the left eye of a 52-year-old man with posterior scleritis. A: The patient presented with
rapid vision loss to 20/200 in the left eye. The color and red-free photograph (B) show widespread radiating interconnected
choroidal folds. The choroidal details were visible, indicating there was no subretinal fluid. His intraocular pressure was
10 mm Hg in both eyes. C: The fundus autofluorescence imaging shows areas of granular hyper- and hypo-autofluorescence
spreading around the optic disk. D: Contact B-scan ultrasonography shows that the eye wall was markedly thickened. The
choroid cannot be differentiated from the sclera. He had fluid in Tenon’s space (arrows). F: An EDI-OCT scan showed the
subfoveal choroidal thickness was 180 microns, which then left thickening of the sclera as the cause of the eye wall
thickening seen in the ultrasonogram. The full thickness of the choroid could not be visualized by ordinary OCT (E ).

scar or adjacent tissue for years.100 The primary locus of the
infection is the retina, and the choroid is secondarily involved
along with the sclera and the vitreous.100 The main histo-
pathological findings are areas of granulomatous inflamma-
tion involving the retina, the choroid, and sometimes the
sclera.47 Some have found a focal disruption or necrosis of the
RPE.17,177 At the center of the lesion the retina, and sometimes
the choroid, have been found to be necrotic and the parasites
present in the necrotic portion, at times within pseudocysts.47
Histopathological studies have identified cysts full of brady-
zoites as well as tachyzoites within the retinal lesions using
immunohistochemistry techniques.17,177 Clusters of pigment-
laden epithelioid cells have been identified in the subretinal
space.17
Lesions of toxoplasmic retinochoroiditis were analyzed
using EDI-OCT and SS-OCT (Fig. 21). The white large
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
inflammatory lesion shown in Fig. 21 developed at the edge
of a pigmented scar. The SD-OCT analysis found numerous
hyperreflective dots in the vitreous corresponding to
vitreous cells, overlying the retinochoroidal lesion. The
same hyperreflective dots were seen within the retinal and
the choroidal lesions. The retinal architecture was dis-
rupted, with almost no normal retinal layers. There was
disruption of the RPE line and marked thickening of the
underlying choroid.
7.6. Sarcoidosis
Sarcoidosis is a multisystem disease whose histologic hall-
mark is the presence of non-caseating granulomas.209
Choroidal lesions are common in ocular sarcoidosis.209 The
choroidal involvement in sarcoidosis can be assessed using
EDI-OCT and SS-OCT. As an example, a 57-year-old woman
with evidence of systemic sarcoidosis with unilateral serpig-
inous choroiditis-like lesions underwent multimodal imaging
with ICG angiography, EDI-OCT, and SS-OCT (Fig. 22). There
was low-reflective to hyporeflective homogeneous areas of
diffuse infiltration of the choroid at the edges of the chorior-
etinal atrophic areas on EDI-OCT. There were large vessels
visualized through the lesion. These diffuse infiltrated areas
visualized on the EDI-OCT corresponded to confluent hypo-
fluorescent areas at the early and mid-phase of the ICG angi-
ography where there was an almost complete disappearance
of medium size and large size choroidal vessels. These find-
ings led to the hypothesis that the choroidal vessels may be
compressed or obliterated by the inflammatory infiltrates in
these areas.
7.7. Other types of posterior uveitis
One study of CT in multiple evanescent white-dot syndrome
found the choroid to be thicker in the acute phase than the
convalescent phase in both the affected and opposite unaf-
fected eyes, suggesting that an inflammatory reaction might
affect the choroid, directly or indirectly.4 Posterior scleritis is
a rare, but underdiagnosed, inflammation of the sclera in the
posterior pole that has many manifestations including cho-
rioretinal folds, choroidal detachment, ciliochoroidal effu-
sion with angle-closure glaucoma, and exudative retinal
detachment. On occasion posterior scleritis appears as a cir-
cumscribed mass lesion. The typical symptoms include a dull
aching pain and decreased visual acuity. Posterior scleritis
causes a thickening of the sclera as seen by contact B-scan
ultrasonography, and fluid is commonly see in Tenon’s
space. The differentiation of thickened sclera from thickened
choroid may be difficult, but is important in establishing the
correct diagnosis. Multimodal imaging can help in defini-
tively establishing the presence of scleral thickening (Fig. 23).
Fluorescein angiography demonstrates the chorioretinal
folds, as would autofluorescence imaging, but fluorescein
angiography can also show leaks from the level of the retinal
pigment epithelium if a serous detachment of the retina is
present. Posterior scleritis is typically treated with nonste-
roidal anti-inflammatory medications, with corticosteroid
treatment and sometimes immunosuppression required for
severe cases.9
413
8. Choroid in inherited retinal dystrophies
Inherited retinal dystrophies comprise a large number of
disorders, some better characterized than others. Phenotypi-
cally disparate conditions may share the same underlying
genetic defect. In addition patients with the same genetic
mutation may have large variations in disease severity.
Whereas some disorders, such as dominantly inherited reti-
nitis pigmentosa (RP), involve rhodopsin mutations, implying
the potential for rod damage, many of these eyes will go on to
also show cone, RPE, and, in the end stage, choroidal abnor-
malities. The defects seen by simple analysis of the choroid
are therefore dependent on the exact nature of the inherited
disorder, the severity of disease, and how long the disease has
been present. Broad comparisons may not be clinically
useful, but may help in understanding underlying disease
pathogenesis.
Yeoh et al analyzed the subfoveal CT in various retinal
dystrophies using EDI-OCT in 20 patients.239 They found that
the subfoveal CT was normal in 10 patients, had various
degrees and patterns of thinning in 9 patients, and thickened
in one patient with undetermined macular dystrophy. The
refractive errors of the patients were not mentioned. They did
not find any correlation between subfoveal CT and visual
function as assessed with either visual acuity test or electro-
physiology.239 Inherited retinal dystrophies may follow the
same pattern as seen in AZOOR cases. The loss of the outer
retina may precede changes in the choroid. With loss of the
outer retina oxygen originating from the choroid may diffuse
to the middle and inner retinal layers. The retinal circulation
autoregulates and would be expected to constrict. This has
been proposed as an explanation for arteriolar attenuation in
AZOOR and the same principle may be germane in RP.56
9. Choroid in high myopia
9.1. Chorioretinal atrophy in high myopia
In many developed countries, a major cause of vision loss is
high myopia, which is often defined as 6 or more diopters
spherical equivalent myopic correction. High myopia is asso-
ciated with excessive and progressive elongation of the globe
and results in a variety of fundus changes that lead to visual
impairment, including lacquer cracks in Bruch’s membrane,
CNV, and chorioretinal atrophy.33,82,88,103,104,113,142,157 Myopic
chorioretinal atrophy is a common and serious problem, and
yet the mechanisms and pathologic course are not well
understood. If retinal stretching was the main mechanism for
visual impairment in highly myopic eyes, we would expect the
visual function to be well correlated with the amount of
myopia; clinically, however, visual function in highly myopic
patients tends to be more correlated with age than degree of
myopia.192,225
Okabe et al analyzed three eyes with chorioretinal atrophy
and pathologic myopia enucleated for various reasons:
herpetic keratitis and secondary glaucoma, intraocular
hemorrhage, and painful filamentous keratitis.157 One eye had
20 D of myopia and the amount of myopia was not defined
414 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

for the two other eyes. Histopathological observations showed
the choroid was thin with vessels present in some areas but
completely absent in others.157 They hypothesized that the
choriocapillaris was obstructed and disappeared earlier than
the other choroidal vessels and that the choriocapillaris
obstruction occurs in a lobulated fashion.157 The associated
diseases in these eyes may have affected their choroidal
ultrastructure. There are no data on the ultrastructural
modifications present at the early stages of high myopia.
Animal models of myopia show decreased choriocapillaris
density and diameter.82 The photoreceptor packing density is
decreased in high myopes.28 Both photoreceptors and cho-
riocapillaris are rarefied as compared with emmetropic eyes.
Angiographic studies of the choroid with ICG reveals that the
choroidal vasculature is altered in highly myopic eyes.143,172 A
color Doppler ultrasonographic study found that the choroidal
circulation was decreased in highly myopic eyes.1 As the
choroid supplies oxygen and nutrition to the retinal pigment
epithelial cells and the outer retina, compromised choroidal
circulation may account, in part, for the retinal dysfunction
and vision loss that is seen in high myopia.
OCT study, subfoveal CT was found to decrease by 12.7 mm for
each decade of life and by 8.7 mm for each diopter of myopia.55
The quantification of choroidal biometric changes may be
useful for monitoring the progression and for estimating the
relative risks for future development of the disease. A large
proportion of patients with high myopia develop some visual
deficit, and even modestly reduced visual acuities to the 20/30
or 20/40 level can have a significant impact on their quality of
life.153 The visual deficit developed in highly myopic eyes
increases with age and amount of myopia. Nishida et al
evaluated predictive factors for visual acuity using EDI-OCT in
145 highly myopic eyes with no macular pathology.153 They
evaluated subfoveal CT, foveal thickness, outer nuclear layer
thickness, and inner segment to RPE aggregate thickness. The
mean subfoveal CT was 158.6 mm. The subfoveal CT was
inversely correlated with visual acuity and was also the only
significant predictive factor of visual acuity in the pooled
data.153
9.3. Imaging the highly myopic disk

9.3.1. Intrachoroidal cavitation

In 2003, Freund et al recognized peripapillary detachment in
9.2. Biometric choroidal changes in highly myopic eyes
pathologic myopia.45 They reported an elevated, well-
and clinical significance
circumscribed, dome-shaped, yellow-orange lesion inferior
to the optic disk along the inferior margin of the myopic
The choroid of highly myopic patients is significantly thinner
conus. Toronzo and Gaudric renamed this anomaly
than the choroid of non-myopic eyes (Fig. 24).55,94 A group of
18 patients (31 eyes), with a mean age of 51.7 years and a mean
refractive error of 15.5 D was evaluated with regular SD-OCT.
The mean subfoveal CT was 100.5 mm, thinner than in
emmetropic eyes, and the eyes underwent further thinning
with increasing age and posterior staphyloma height.94 The
authors defined staphyloma height as the sum of four vertical
measurements on SD-OCT foveal scans: the distance from the
RPE line beneath the fovea to the nasal, temporal, superior,
and inferior edges of the OCT image.94 They do not mention
how the presence, shape, and exact location of the posterior
staphyloma were determined. The posterior pole of any eye,
whether it is myopic or not, is not a flat structure, and as such
it should have some “height” as it is defined by this SD-OCT
method of measurement. The height measured in this study
is a reflection of the global curvature of the eye itself and does
not necessarily imply any outpouching, as is required to
define a posterior staphyloma. Conventional SD-OCT allows
a relatively good visualization of the choroidal/sceral interface
in highly myopic eyes because of the dramatic choroidal
thinning.94 Ikuno et al reported that the choroidal/scleral
interface is generally undetectable in eyes with a CT greater
than 300 mm with regular SD-OCT.94 This probably also
depends on other factors, such as the degree of pigmentation
of the RPE and choroid.
Another group of 31 patients (55 eyes) with a mean age of
59.7 years and a mean refractive error of 11.9 D was evalu- Fig. 24 e Multimodal imaging of the left eye of a 35-year-
ated with EDI-OCT. The mean subfoveal CT was 93.2 mm, and old highly myopic man. A: The color photograph shows
was negatively correlated with age (p ¼ 0.006) and refractive a tilted disc with 360 peripapillary atrophy. B: The EDI-
error (p < 0.001).55 Eyes with a history of choroidal neo- OCT scan shows a very thin choroid with no sharp
vascularization also had a thinner choroid (p ¼ 0.013), but the transition to where the clinically observed peripapillary
patients in this study were treated with photodynamic atrophy starts (arrow). (Reprinted from Spaide200 with
therapy, which may have damaged the choroid.55 In this EDI- permission of Springer-Verlag).
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 415

intrachoroidal cavitation based on OCT analysis: a large intra-
choroidal hyporeflective space with a flat RPE,217 a finding
present in 4.9% of 632 highly myopic eyes in a Japanese
study.196 Some authors postulated that intrachoroidal cavi-
tation is another cause of visual field defects in high
myopia,196 along with primary open-angle glaucoma, normal
tension glaucoma, tilted disk syndromes, myopic conus, and
macular atrophy. Wei et al, using Stratus-OCT, identified
direct communication between the intrachoroidal cavity and
the vitreous space in 6 out of 13 cases and hypothesized that
liquid vitreous might be the source of the disruption of the
choroid and fluid accumulation.229 EDI-OCT allowed identi-
fying intrachoroidal cavitation that had been unrecognized
clinically.161
Spaide et al201 evaluated 16 eyes of 13 patients with peri-
papillary intrachoroidal cavitation using mainly SS-OCT and
in one eye EDI-OCT and volume rendering. The patients had
a mean age of 50.3 years and a mean refractive error of 12.5
D. All had a tilted disk with myopic conus. In all of the eyes,
the sclera was bowed posteriorly focally below the region of
the intrachoroidal cavitation, whereas the curvature of the
RPE line overlying the lesion was not modified (Fig. 25).
Therefore there was no internal elevation of the lesion. There
was full thickness defect in the retina, RPE, and inner choroid
at the inferior border of the conus in only four eyes, indicating
a direct communication between the vitreous cavity and the
intrachoroidal cavity. They proposed that the primary cause
of intrachoroidal cavitation formation was the posterior
bowing of the sclera in the region of the conus that extended
around the nerve to involve the choroid secondarily. In more
exaggerated cases the posterior deflection of the sclera could
allow fluid to enter through a full thickness defect in the
overlying retinaeRPEeBruch’s membrane at the border of the
conus.201
9.3.2. Analysis of the subarachnoid space
Ohno-Matsui et al analyzed the subarachnoid space (SAS) of
133 eyes with pathologic myopia with SS-OCT and analyzed 32
normal emmetropic eyes of healthy controls.155 The SAS was
visible in 124 highly myopic eyes (93.2%) but in none of the
emmetropic eyes. The mean age of these 72 highly myopic
patients was 53.2 years with a mean refractive error of e15.2
D. The SAS was thought to be dilated, with a width ranging
from 263 to 1850 mm and a triangular shape with the base
toward the eye surrounding optic nerve in the region of the
scleral flange. The meningeal sheaths, the dura mater and the
pia mater, as well as the arachnoid trabeculae, were only
visible surrounding the SAS in highly myopic eyes and not in
emmetropic ones (Fig. 26). There was a change in the scleral
curvature at the attachment of the dura mater of the SAS to

Fig. 25 e Peripapillary intrachoroidal cavitation. A: Color photograph showing a yellowish region (blue arrows) in which the
underlying choroidal details are not visible. Note how the vein from the inferotemporal arcade dips down below the level of
the retina. Sections taken with an SS-OCT instrument are shown in images C and D. B: Fluorescein angiogram showing
some accumulation within the yellow pocket (blue arrows). Note the edge of the visible retina ( yellow arrow). C: The conus
region of this eye was seen by ophthalmoscopy to bulge outwards. There is a defect of the inner retina, RPE, Bruch’s
membrane, and choroid visible at the inferior border of the conus on the OCT scan (orange arrow) and the sclera outpouching
is seen well below the plane of the retina. D: The intrachoroidal cavitation is visible as a hyporeflective space above
a posteriorly distended sclera. This is shown by the red line, which is drawn through the center of the sclera. The straight
blue dashed line demonstrates the retinal pigment epithelium and Bruch’s membrane complex is not significantly elevated
toward the center of the eye.
416 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

Fig. 26 e Sub-arachnoid space and the change of scleral curvature at the site of attachment of the dura mater of the SAS to
the peripapillary sclera. A: Color fundus photograph of the optic disc with a large annular conus. B: SS-OCT slice scanned
along the green line in (A) shows the SAS temporal to the optic disk. There is a change of the scleral curvature at the
attachment site of the dura mater of SAS to the peripapillary sclera (white arrow). C: Color fundus photograph of the optic
disk showing a large annular conus. D: SS-OCT slice scanned along the green line in (C ) shows the SAS temporal (delineated
by three black arrows) and nasal to the optic disk. There is a change of the scleral curvature at the attachment of the dura
mater of SAS to the peripapillary sclera (white arrows). E: Schematic drawing showing the change of the scleral curvature at
the attachment of the dura mater (arrow) of SAS (arrow) to the peripapillary sclera (arrow). The peripapillary sclera is
continuous with the pia mater (arrow) along the inner boundary of the SAS and with the dura mater (arrow) along the outer
boundary of the SAS. dotted line [ lamina cribrosa.

the peripapillary sclera. The location and extent of visibility of formation. The area exposed to the cerebrospinal fluid pres-
the SAS correlated with the location and extent of the conus, sure is increased in these highly myopic eyes, and the tissues
suggesting that the expansion of the SAS may be related to the exposed to the pressure differential between intracranial and
expansion of the posterior eye wall in the process of conus intraocular pressure, such as lamina cribrosa and
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
peripapillary sclera, are thinner than in emmetropic eyes.
These parameters may modulate staphyloma formation and
glaucoma manifestation in highly myopic eyes.155
10. Diseases involving the sclera
With EDI-OCT it is possible to visualize the full thickness of
the sclera in high myopes. The choroid is thin and often has
sparse pigmentation, and the sclera is likewise thin. With
SS-OCT the sclera can be visualized to a greater extent, and in
some lightly pigmented eyes (albeit with low myopia) the
outer boundary of the sclera can sometimes be appreciated.
There are a number of potential interactions between the
choroid and sclera that may influence ocular pathology and
with improved technology these relationships may be
elucidated.
10.1. Dome-shaped macula
Gaucher et al described a new entity in eyes with high
myopia.66 The central portion of the macula appeared to bow
inwards, unlike typical staphylomas in high myopia, which
bow outwards. They called this disorder the dome-shaped
macula. They proposed that there was localized thickening of
the choroid. Later, in a letter to the Editor, two additional
possibilities were suggested, first that the dome shape was to
the result of vitreous traction and second that there really was
collapse of the posterior portion of the eye such that the sclera
bowed inward.139 Vitreous traction was seen on the OCTs, and
the eyes with dome-shaped macula have normal intraocular
pressure, making eye collapse very unlikely. Imamura et al
examined the posterior anatomic structure of a group of 15
patients (23 eyes) with dome-shaped macula with EDI-OCT.97
The mean age of the patients was 59.3 years and the mean
refractive error was 13.6 diopters. The mean subfoveal
scleral thickness in these eyes was 570 mm, and that in 25 eyes
of myopic patients with staphyloma, but without dome-
shaped macula, was 281 mm (p < 0.001) even though both
groups had similar refractive error. The scleral thickness 3,000
mm temporal to the fovea was not different between the eyes
with dome-shaped macula (337 mm) and the eyes with
staphylomas (320 mm) (Fig. 27).97
Dome-shaped macula is the result of regional thickness
differences of the sclera under the macula in highly myopic
eyes and does not correspond to any of the known types of
staphyloma. Some patients with dome-shaped macula may
have focal collections of subretinal fluid, which may occur
because of the obstruction of outflow of choroidal fluid by the
thickened slcera.97
10.2. Tilted disk syndrome and inferior staphyloma
Maruko et al evaluated the macular choroidal changes in
tilted disk syndrome (TDS) with EDI-OCT and the associated
scleral changes using SS-OCT in 24 eyes. TDS is a stationary
congenital optic disk anomaly where the optic nerve enters
the eye at an oblique angle, and the optic disk appears to
have a variable degree of rotation around its axis.15 Among
these 24 eyes with TDS and inferior staphyloma, 7 had
417
Fig. 27 e Dome-shaped macula. A 12-mm SS-OCT of an eye
with dome shaped macula shows the local variations of
thickness of the sclera with relative thickening of the
submacular sclera as compared with the sclera from
adjacent regions. This causes what appears as an elevation
of the macula.
macular subretinal fluid.129 The subfoveal choroid was rela-
tively thin and the subfoveal sclera thickened in TDS with
a staphyloma at the macula. They also found that the
macular area at the superior edge of staphyloma had
a granular hyperfluorescent pattern on fluorescein angiog-
raphy and a belt-like hypofluorescence on ICG angiography.
The authors hypothesized that the subfoveal scleral thick-
ening in TDS might induce choroidal thinning and abnormal
choroidal circulation at the fovea. Another possibility is that
the fovea was along the portion of curvature where the
normal curvature of the eye merged with the curvature of the
staphyloma. As such it was located in the region of the
smallest radius in the posterior pole and the RPE and choroid
may have just been mechanically stretched in this region.
The authors thought secondary RPE atrophy could cause
breakdown of the blooderetinal barrier and a subsequent
serous retinal detachment.129 Another possibility is that
chronic subretinal fluid could cause subsequent RPE atrophy
with choriocapillaris atrophy as a consequence. This would
explain the hypofluorescence in ICG angiography. In any case
the mechanisms of subretinal fluid accumulation do not
appear to depend on choroidal vascular hyperpermeability as
is seen in CSC. One possible explanation of subretinal fluid
accumulation in dome-shaped macula, nanophthalmos, and
potentially tilted disk is a thicker sclera that resists normal
outflow.
10.3. Uveal effusion syndrome
A uveal effusion is an abnormal collection of fluid that
expands the suprachoroidal space, producing internal
elevation of the choroid. When no cause exists, patients are
thought to have a distinct primary abnormality of the
choroid, the sclera, or both, called idiopathic uveal effusion
syndrome. Histopathologically scleral modifications
contribute to scleral inelasticity and to an increased scleral
resistance to protein diffusion, leading to choroidal fluid
accumulation caused by altered osmotic pressures.222 Har-
ada et al studied the CT in idiopathic uveal effusion
syndrome by means of EDI-OCT in one case and found low-
reflective areas in the outer choroid. The subfoveal CT was
787 mm. It would also be interesting to analyze the effects of
treatment such as scleral windows222 on the CT.
418 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

with EDI-OCT, and each type of tumor demonstrated one or

11. Imaging choroidal tumors with OCT
11.1. General information
OCT features of choroidal tumors have been extensively
documented but are limited mostly to their effects on the
overlying retina. Using conventional OCT, the choroidal find-
ings in choroidal nevi are limited to the anterior surface.195
EDI-OCT of the choroid allows characterization of the thick-
ness and reflective quality of small (less than 0.9 mm thick)
non-pigmented choroidal lesions. We can roughly estimate
the thickness of pigmented choroidal tumors in an indirect
manner, by determining if there is a degree of distension of
the adjacent sclera posteriorly. Some quantitative measure-
ments of the tumor are also possible if it has a diameter less
than 9 mm and a thickness less than 1 mm.218 Small
non-pigmented tumors undetectable by ultrasound might
therefore be identified and measured by EDI-OCT. EDI-OCT
technique is capable of distinguishing the tumor from
surrounding tissues, including anteriorly from the hyper-
reflective Bruch’s membrane/RPE layer and laterally from the
normal choroid. The interphase between the posterior limit of
the tumor and the inner sclera is only visible when the height
is less than 0.9 mm,218 and also varies with the amount of
pigmentation and subsequent shadowing.
In a pilot study, Torres et al described the intrinsic optical
characteristics of choroidal tumors imaged with EDI-OCT
technique and correlated tumor measurements with ultraso-
nography in 23 patients.218 They identified the tumor in all cases
more specific EDI-OCT findings. All melanocytic tumors
demonstrated a highly reflective band within the chorioca-
pillaris with posterior shadowing. We have seen some choroidal
nevi using EDI-OCT that have a thin hyporeflective band at the
location where the choriocapillaris is expected to be. Moreover,
we know from histology that choroidal nevi do not necessarily
affect the overlying choriocapillaris.149 Amelanotic nevi
appeared homogeneous with a medium reflective band associ-
ated with visible choroidal vessels within the tumor (Fig. 28).218
Choroidal melanomas showed a highly reflective band in the
anterior choroid with lack of visibility of either the choroidal
vessels or inner sclera. Circumscribed choroidal hemangiomas
appeared as a medium to low reflective band with a homoge-
neous signal and intrinsic spaces.218 Blood vessels and the
contained blood are excellent at scattering light, which causes
loss of coherency data in OCT imaging. The outer portion of
larger hemangiomas and the full thickness in small ones are
hyperreflective, in our experience. Choroidal metastasis
revealed a hyporeflective band in the deeper choroid causing
enlargement of the suprachoroidal space,218 but this is probably
highly dependent on the type of metastasis.
11.2. Low grade B-cell lymphoma (reactive lymphoid
hyperplasia of the choroid)
EDI-OCT can also be helpful to visualize and measure
lymphomatous collections. Benign reactive lymphoid
hyperplasia of the choroid is a rare clinical syndrome that

Fig. 28 e Choroidal nevus. A: This amelanotic nevus was seen to have an adjacent area of subretinal fluid and the retina had
a yellowish appearance. B: Autofluorescence imaging showed the area with the fluid was hyperautofluorescent. C: EDI-OCT
shows the expansion of the choroid by the nevus with obscuration of any contained vessels. There is subretinal fluid and
a thickened accumulation of shed outer segments at the outer portion of the retina. Accumulation of this material has been
linked with hyperautofluorescence from the outer retina in a wide variety of diseases.199
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9 419

may resemble malignant choroidal tumors such as meta-

static carcinoma of the choroid, diffuse malignant
lymphoma of the uveal tract, diffuse amelanotic melanoma,
or diffuse uveal melanocytic proliferation associated with
systemic carcinoma. This entity that has been called benign
reactive lymphoid hyperplasia of the choroid appears to be
a low grade B-cell lymphoma.30 In some respects reactive
lymphoid hyperplasia resembles a MALT lymphoma.
Systemic evaluation usually fails to detect evidence of
widespread involvement with this lymphoid tumor.64
Patients should have a careful conjunctival evaluation for
the presence of pink episcleral nodules that are easy to
biopsy to establish the diagnosis of lymphoid proliferation.72
Patients with benign reactive lymphoid hyperplasia of the
choroid were analyzed with EDI-OCT. In one case a large
lesion produced a homogeneous, smooth, low-reflective
thickening of the choroid (Fig. 29). There was no visualiza-
tion of the normal choroidal vascular vessels in the infil-
trated areas on EDI-OCT. This absence of visualization of the
normal choroidal vessels is not due to an optical shadowing
defect because the choroidal sclera interface is well identi-
fied. This implies that there are no choroidal or intrinsic
vessels within the lymphomatous infiltration, but in that
case, some choroidal vessels are still visualized anteriorly to
the hyporeflective lymphomatous collection. The choroidal
vessels may be compressed in the areas infiltrated by the
lymphomatous collection.
Fig. 29 e Multimodal imaging of the right eye of a 63-year-old
man with unilateral reactive lymphoid hyperplasia of the
11.3. Radiation choroidopathy choroid, a condition that actually represents a B-cell
lymphoma. A: The color photograph shows multiple yellow-
Radiation choroidopathy is a difficult diagnosis on conven- white infiltrates evenly distributed throughout the fundus. B:
tional imaging with fluorescein angiography and conven- One EDI-OCT scan taken through the inferior macula ( green
tional SD-OCT, especially when associated with radiation line) shows two large lesions producing homogeneous,
retinopathy. ICG angiography may show large vessels with smooth, low-reflective thickening of the choroid measured
vascular wall staining,3 associated with obliteration of at 350 mm. No choroidal vessel is visualized within these
choroidal vasculature in a wider area than that affected by infiltrated areas. The choroidal vessels may be compressed
radiation retinopathy, with possible remodeling of the in the areas infiltrated by the lymphomatous collection. The
choroidal veins.212 EDI-OCT can assist the diagnosis by foveal EDI-OCT scan of the left eye (C ) shows a normal
demonstrating a very thin choroid in these patients (Fig. 30). choroidal thickness measured at 135 mm.
This is consistent with previous histopathological studies of
radiation damage to the choroid that showed atrophy and
occlusion of the vasculature.141

12.1. Choroidal thickness and glaucoma

12. Choroid in glaucoma
Glaucoma is the world’s leading cause of irreversible blind-
ness.180 Theories of glaucomatous damage to ganglion cell
axons usually focus on a mechanical etiology at the level of
the lamina cribrosa, impairment of blood flow to the optic
nerve and peripapillary area, or both. Some studies report an
impairment of blood supply prior to demonstrable glaucom-
atous visual field defects, suggesting that the neuronal
damage does not cause the impaired optic nerve blood flow.165
EDI-OCT in glaucoma allows analysis of CT as an indirect way
to evaluate impairment of blood flow to the optic nerve and
also mechanical damage to the nerve fiber layer at the level of
the lamina cribrosa.
There are conflicting results concerning CT in glaucoma. Both
histologic studies and EDI-OCT studies of older patients
showed a decreased mean subfoveal CT in glaucomatous eyes
as compared with eyes without glaucoma.109,203,211,240 In
a group of 74 patients (37 with glaucoma, and 37 glaucoma
suspects), Maul et al found that age, axial length, central
corneal thickness, and diastolic ocular perfusion pressure
were significantly associated with CT in glaucoma suspects
and glaucoma patients. Degree of glaucomatous damage was
not consistently associated with CT.132 In a study of normal
eyes, normal tension glaucoma, and primary open-angle
glaucoma no differences were found in CT after adjusting
for age, axial length, and intraocular pressure.146 This is
somewhat misleading in that when variables are entered into
420 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9

Fig. 30 e Multimodal imaging of the left eye of a 51-year-old woman with radiation retinopathy and associated radiation
choroidopathy. A: This patient had radiation for a retinoblastoma in childhood. The fluorescein angiogram shows a typical
ischemic retinopathy with vascular remodeling and telangiectasias contiguous to areas of capillary dropout. These findings
are consistent with the diagnosis of radiation retinopathy. B: The early ICG angiogram shows defects in choroidal filling and
rarefaction of choroidal vasculature. C: The EDI-OCT scan through the fovea helps the diagnosis of associated radiation
choroidopathy by demonstrating a very thin choroid measured at 103 mm. Note also the macular edema.

a regression equation, the strength of an association of highly
colinear variables with the dependent variable is distorted. For
example, CT is highly correlated with age and refractive error
(or axial length).55 Entering CT into a regression after axial
length and age are already entered would evaluate the effect
of CT, minus any colinear interaction that age and axial length
has on the choroid, for contributions towards explaining
variation in the dependent variable. An analogy would be
concluding that falling from the top of the Empire State
Building is not more dangerous than falling from a chair after
controlling for the distance of the fall.
The proportion of normal-tension glaucoma (NTG) is
30e40% of all types of glaucoma and this proportion increases
with age. Some studies have found that highly myopic patients
have a higher risk of developing glaucomatous optic nerve
damage,25,34,71,166 sometimes despite an IOP in the normal
range. The number of patients with myopic NTG is increasing
because of the larger number of people with high myopia.221
The CT has been found to be significantly thinner (50%) in
highly myopic eyes with NTG compared with highly myopic
eyes without glaucoma using SS-OCT.221 Measuring CT may be
a helpful diagnostic parameter for myopic NTG, and also
a monitoring parameter for progression of the disease.
Doppler OCT technology is a future modality to measure the
blood flow, and this type of study is needed to confirm if the
choroidal blood flow actually decreases in myopic NTG.
12.2. Imaging the deep optic nerve complex in glaucoma
and analysis of the lamina cribrosa
There is growing evidence that the laminar region of the optic
nerve head is an important site of the nerve fiber insult in
glaucoma.7,173,174 EDI-OCT has advantages over the standard
mode of SD-OCT for visualizing and assessing the anatomical
features of the deep optic nerve complex structures in glau-
coma, including the lamina cribrosa, especially its posterior
border, and vessels including the short posterior ciliary artery,
central retinal artery, and central retinal vein,161 the peri-
papillary choroid and sclera, and the SAS around the optic
nerve.160,161
In a cross-sectional study of 137 glaucoma patients
(49 healthy controls), the EDI-OCT imaging of optic nerve head
showed significantly better intraobserver, interobserver,
intravisit, and intervisit reproducibility than standard
imaging.160 EDI-OCT modality allowed detection of differ-
ences in the lamina cribrosa thickness by glaucoma type: it
was thinner in NTG patients than primary open-angle glau-
coma patients with similar stages of damage, and the NTG
patients with disk hemorrhages had thinner laminas than the
ones without hemorrhage.160 In a prospective study, about 73
glaucoma patients (139 eyes), Park et al were able to visualize
the lamina cribrosa pores with various shapes and sizes in
76% of the eyes. Localized lamina cribrosa lesions visualized
on optic disk photographs were identified as focal lamina
cribrosa defects or tears on EDI-OCT (Fig. 31).161 These tears in
the lamina cribrosa may be associated with the splinter
hemorrhages of the optic nerve. Eyes with high myopia seem
to have a greater propensity for these tears in the lamina
cribrosa.156 Clinically detectable thickness differences of
lamina cribrosa may precede functional visual field loss. The
pressure differential between intracranial and intraocular
pressure acts across the lamina cribrosa and can lead to its
deformation, with subsequent damage of the axons of the
retinal ganglion cells.
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
Fig. 31 e Lamina cribrosa tear. An EDI-OCT horizontal scan
of the right eye of a 61-year-old highly myopic patient with
primary open-angle glaucoma shows a hyporeflective gap
at the junction of the lamina cribrosa and the temporal
peripapillary sclera representing a lamina cribrosa tear
( yellow arrow).
Burgoyne et al proposed the generalized concept of the
optic nerve head as a biomechanical structure, assuming
that IOP-related stress (force/cross sectional area) and strain
(local deformation of the tissues) are central determinants
of both the pathophysiology of the optic nerve head tissues
and its blood supply at all levels of IOP.20 From this
perspective, EDI-OCT can expand the knowledge of optic
nerve head biomechanics in glaucoma by describing new
anatomical findings such as: the lamina cribrosa thinning or
defects, scleral thinning around the disk, multiple micro-
optic pits, dilated SAS with subsequent impaired circula-
tion around the disk, and concentration of toxic
substances.155
13. Optic nerve head drusen: enhanced
visualization and analysis of adjacent optic
nerve fibers
Optic nerve head drusen are acellular deposits, primarily
composed of proteins, mucopolysaccharides, and calcium,
that characteristically occur bilaterally in small, crowded
optic nerve heads.114 They have been clinically observed in
0.3% of the population, although autopsy studies suggest an
incidence of 2%.48 This discrepancy suggests clinical under-
estimation of the real incidence of optic nerve head drusen.
Buried optic nerve head drusen, especially small ones, cannot
be easily visualized by conventional ophthalmoscopic exam-
ination. When they are buried within the optic nerve head, the
optic disc appearance ranges from normal to pseudopapille-
dema.114 If there is sufficient suspicion of optic nerve head
drusen, contact B-scan ultrasonography may be done to look
for calcium, with a good sensitivity. But ultrasonography will
not be performed if there is a normal optic nerve appearance.
Optic nerve head drusen are diagnosed more commonly since
the use of autofluorescence imaging, because they appear as
hyperautofluorescent.
In a histopathological study, Friedman et al showed that
optic nerve head drusen (ONHD) are calcified and varied in
size (from 50e750 microns) and in number.49 This retrospec-
tive histopathological study contains bias related to age
because it was mainly performed on autopsy eyes and it does
not reflect the age distribution of optic nerve head drusen in
living patients. The smallest size of optic nerve head drusen
reported in histopathological study reaches the limit of
421
ultrasound resolution, but highly reflective structures such as
calcium are imaged by signal strength of the reflected ultra-
sound, which is not dependent on resolution.
Both exposed and buried ONHD can be associated with
loss of the associated nerve fiber layer and can be associated
with visual field defect.216 Therefore, patients with unde-
tected ONHD are frequently diagnosed as having glaucoma.
EDI-OCT increases the visualization of buried ONHD (Fig. 32).
Conventional SD-OCT has been evaluated to differentiate
optic disk edema and ONHD,101,115 to differentiate RNFL
modifications pattern related to optic nerve head drusen and
glaucoma.184,185 EDI-OCT may be able to visualize and
localize buried ONHDs and therefore assess more accurately
the correlation of ONHDs to possible RNFL thinning over
time.
14. Choroid in diabetes
Many histological studies have identified consistent vascular
changes in the choroid of the diabetic patient52,53,81 that are
quite similar to those seen in diabetic retinopathy: increased
vascular tortuosity, vascular outpoutchings, microaneurysm
formation, areas of nonperfusion, dilations and narrowing of
vascular lumens, and choroidal neovascularization. The
vessels involved are mainly the choriocapillaris, but also the
larger choroidal vessels.52,81 Early vascular changes involved
the peripheral choriocapillaris and later choroidal vascular
changes were more marked in the temporal area between the
equator and ora serrata.52
Nagaoka et al evaluated the changes in choroidal blood
flow in the foveal region in 70 patients with type 2 diabetes
using laser Doppler flowmetry.147 The subfoveal choroidal
blood flow was significantly reduced in all the diabetic
patients, especially those with nonproliferative diabetic reti-
nopathy and diabetic macular edema. These results suggest
that the circulatory changes in the choriocapillaris in the
foveal region may precede the clinical manifestations of dia-
betic retinopathy, and the authors hypothesized that the
decreased blood flow in the choriocapillaris may cause retinal
tissue hypoxia and subsequent increased expression of VEGF,
which is one of the mechanisms implicated in the pathogen-
esis of diabetic macular edema.147
Three OCT studies have evaluated the choroidal thickness
in diabetic patients in vivo using different techniques, with
inconsistent results.37,136,179 McCourt et al evaluated the sub-
foveal CT of 194 consecutive eyes from 102 patients, including
30 eyes with diabetic retinopathy, using EDI-OCT.136 In this
study with no mention of the axial length, refractive error,
type of diabetes, stage of diabetic retinopathy and presence of
diabetic macular edema, the authors found no significant
correlation between the subfoveal CT and diabetic retinop-
athy.136 Esmaeelpour et al evaluated the choroidal thickness
of 63 eyes from 42 patients with type 2 diabetes using 3D SS-
OCT at 1,060 nm.37 Choroidal thickness maps of 36
36
field of view were generated based on manual segmentation.
The authors did not mention how they measured the 36 field
of view. Choroidal thickness maps revealed significant central
and inferior thinning compared with healthy eyes in all dia-
betic groups, regardless of disease stage, including the eyes
422 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
Fig. 32 e Multimodal imaging of the right eye of a 64-year-
old woman with buried optic nerve head drusen. A: The
color photograph shows exposed ONHD appearing as
a glistening white image at the superior border of the right
optic nerve (white arrow). B: The fundus autofluorescence
picture reveals hyperautofluorescent ONHD. C: The vertical
EDI-OCT scan through the nasal border of the optic nerve
( green arrow) shows multiple confluent ONHD appearing
as round or oval hyporeflective masses stippled with
hyperreflective flecks.
without diabetic retinopathy. The groups of patients and
healthy controls were matched for age and axial length.
Systemic hypertension may have been a confounding factor in
this study, considering that the ratio of patients in the healthy
group with systemic hypertension was considerably lower
than in the diabetic group.37
Regatieri et al evaluated CT in 49 eyes with diabetic
retinopathy of 49 patients with type 2 diabetes using Cirrus
HD OCT.179 The scleral choroidal interface could be reliably
identified in 75.3% of eyes examined. The subfoveal CT was
thinner in eyes with diabetic macular edema, or eyes with
proliferative diabetic retinopathy previously treated with
laser pan-retinal photocoagulation. There was no significant
difference in subfoveal CT between normal eyes and eyes
with mild or moderate nonproliferative diabetic retinop-
athy. The axial length or refractive error was not mentioned
in this study. The authors mention that the laser treatment
may be a confounding factor because the laser therapy
could thin the choroid. Even though the authors mention
that any treatment for diabetic macular edema within 6
months is an exclusion criterion, they did not report
whether or not these patients received previous laser
therapy for macular edema. Systemic hypertension could be
a confounding factor in this study because these data are
“not applicable” in the control group and varies in the other
diabetic groups.179
Some studies indicate that there may be diabetic choroid-
opathy before the onset of diabetic retinopathy,37,147 and
others do not.136,179 Vascular changes occurring in the cho-
riocapillaris may not be depth-resolved using OCT current
technology, explaining why some OCT studies do not find
choroidal thinning in the early stages of diabetic retinop-
athy.179 The vascular changes in diabetic choroidopathy
predominate in the mid-periphery,52 whereas choroidal OCT
analyzes mainly the posterior pole.
The exact relationship between diabetic retinopathy and
diabetic choroidopathy remains unknown. It has been sug-
gested that diabetic choroidopathy could be a predicting,
modulating, or causative factor of diabetic retinopathy or
diabetic macular edema. Moreover, the diabetic vascular
changes, whether they are at the level of the choroid or the
retina, may be modulated by the presence of other concomi-
tant cardiovascular risk factors such as systemic hypertension
for example, complicating the understanding of their exact
relationship.
15. Conclusion
The choroid is the main blood supply to the eye and should be
considered in the pathogenesis of eye diseases. There are now
methods to visualize the choroid: EDI-OCT and SS-OCT tech-
niques allow visualization in nearly every patient. The CT in
normal eyes can be measured and used as comparison to that
found in various disease states. CT is negatively correlated
with age, varies during the day, and possibly fluctuates with
defocus over the course of a few minutes. The choroid is an
extremely dynamic structure and should be evaluated in vivo
in real time.
CT analysis has led to the description of new entities such
as age-related choroidal atrophy, has become a key diagnostic
criterion in some retinal diseases such as central serous
chorioretinopathy, and is a major monitoring parameter in
inflammatory disorders involving the choroid such as VKH.
 s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 3 8 7 e4 2 9
EDI-OCT and SS-OCT provide easily structural analysis and
biometric measurements. Studies of choroidal circulation
may be needed to correlate CT with perfusion, such as
Doppler OCT technology to measure the blood flow. The
method of EDI-OCT is limited in terms of acquisition time and
patient cooperation. There is currently no widespread use of
automated software to measure CT, and therefore all
measurements are performed manually; there is good inter-
observer and intervisit reproducibility with this technique,
however. With the faster scanning of SS-OCT, acquisition
time is reduced, and it is possible to generate choroidal
volume scans.
Not only can the thickness of the choroid be measured, but
also qualitative criteria can be analyzed, with a particular
interest in choroidal tumors to analyze the reflectivity of the
tumor, the presence of abnormal intrinsic vessels, or normal
choroidal vessels within the tumor. EDI and SS-OCT will also
enable measurements of small choroidal tumors undetected
by ultrasound. In order to validate this diagnostic tool in
choroidal tumors, it will be necessary to correlate OCT find-
ings with histology.
Deep optic nerve complex structures in glaucoma,
including lamina cribrosa, short posterior ciliary artery,
central retinal artery, central retinal vein, peripapillary
choroid and sclera, and SAS around the optic nerve can be
investigated by EDI-OCT and SS-OCT for their visibility and
anatomic characteristics. Therefore, choroidal imaging with
OCT offers a novel perspective and opportunity for the in vivo
evaluation of glaucomatous neurodegeneration and its
relationship to the structures of the optic nerve complex
structures.
16. Method of literature search
The authors conducted a search of Medline with PubMed.
Even though the development of OCT methods to image the
choroid is relatively recent since 2008, the search for choroidal
anatomy, physiology, and histopathology goes back earlier,
from April 1962. We stopped the search in September 2012.
Search words were choroidal thickness, enhanced depth imaging
optical coherence tomography, choroidal optical coherence tomog-
raphy, swept-source optical coherence tomography, choroidal blood
flow, choroidal physiology, choroidal anatomy, choroidal imaging,
choroidal histopathology. The authors included original articles,
review articles, and case reports that revealed new aspects of
choroidal imaging with OCT. There was no translation of non-
English literature for this review. Some articles were found
because they were in the reference list of the articles found
with the previously described method.
17. Disclosure
Dr Spaide is a consultant to Topcon.
The authors have no other financial or personal relation-
ships with other people or organizations that could potentially
and inappropriately influence their work.
423
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