FEASIBILITY AND CLINICAL UTILITY OF

ULTRA-WIDEFIELD INDOCYANINE GREEN

ANGIOGRAPHY
MICHAEL A. KLUFAS, MD,* NICOLAS A. YANNUZZI, BA,* CLAUDINE E. PANG, MD,
SOWMYA SRINIVAS, MD, SRINIVAS R. SADDA, MD, K. BAILEY FREUND, MD,
SZILRD KISS, MD*

Purpose: To evaluate the feasibility and clinical utility of a novel noncontact scanning
laser ophthalmoscope-based ultra-wideeld indocyanine green angiographic system.
Methods: Ultra-wideeld indocyanine green angiographic images were captured using
a modied Optos P200Tx that produced high-resolution images of the choroidal
vasculature with up to a 200 eld. Ultra-wideeld indocyanine green angiography was
performed on patients with a variety of retinal conditions to assess utility of this imaging
technique for diagnostic purposes and disease treatment monitoring.
Results: Ultra-wideeld indocyanine green angiography was performed on 138 eyes of
69 patients. Mean age was 58 16.9 years (range, 2485 years). The most common ocular
pathologies imaged included central serous chorioretinopathy (24 eyes), uveitis (various
subtypes, 16 eyes), age-related macular degeneration (12 eyes), and polypoidal choroidal
vasculopathy (4 eyes). In all eyes evaluated with ultra-wideeld indocyanine green angiog-
raphy, high-resolution images of choroidal and retinal circulation were obtained with suf-
cient detail out to 200 of the fundus.
Conclusion: In this series of 138 eyes, scanning laser ophthalmoscope-based ultra-
wideeld indocyanine green angiography was clinically practical and provided detailed
images of both the central and peripheral choroidal circulation. Future studies are needed
to rene the clinical value of this imaging modality and the signicance of peripheral
choroidal vascular changes in the diagnosis, monitoring, and treatment of ocular diseases.
RETINA 35:508520, 2015

H istorically, imaging of the peripheral retina has been

difcult to obtain; however, recent improvements in
technology have allowed improved visualization of the
peripheral ocular fundus.1 In 1995, wide-angle angiogra-
phy (including indocyanine green angiography [ICGA])
with up to 160 eld of view was described using a con-
From the *Department of Ophthalmology, Weill Cornell Medical
College, New York, New York; Vitreous Retina Macula Consul-
tants of New York, New York, New York; Department of Ophthal-
mology, Keck School of Medicine, University of Southern California,
Los Angeles, California; and Department of Ophthalmology, New
York University School of Medicine, New York, New York.
Weill Cornell Ophthalmology received an unrestricted depart-
mental grant from the Research to Prevent Blindness (RPB) foun-
dation. Supported in part by the LuEsther T. Mertz Retinal
Research Center, New York, NY.
S. Kiss is a consultant for Optos, PLC. The other authors have
no conicting interests to disclose.
Reprint requests: Szilrd Kiss, MD, Department of Ophthalmol-
ogy, Weill Cornell Medical College, NewYork-Presbyterian
Hospital, 1305 York Avenue, 11th Floor, New York, NY 10021;
e-mail: szk7001@med.cornell.edu
tact lens system and fundus camera.2,3 Other notable sys-
tems1 for wide-angle imaging include the Pomerantzeff
Camera/Equator-plus,4 Panoret-1000,5 the Staurenghi
lens,68 and RetCam 3 system.9 However, these platforms
can be limited by cumbersome contact-based systems,
poor resolution, illumination difculties, optic aberrancies
limiting angiographic capabilities, and autouorescence
acquisition and are not capable of ultra-wideeld imaging
(up to 200) of the ocular fundus. Noncontact options for
wide-angle imaging include standard fundus photography
with montage assembly but do not allow real-time imag-
ing, given the images come from multiple different phases
of a single study. In 2005, noncontact ultra-wideeld
uorescein angiography system (Optos 200 MA/200Tx)
capable of imaging up to 200 of the ocular fundus was
reported.10 Recently, a new noncontact lens used with the
Heidelberg system also allows ultra-wideeld angiogra-
phy in real time.11 Technological advances continue to
allow improved imaging of the peripheral retina.

508
 WIDE-FIELD INDOCYANINE GREEN ANGIOGRAPHY  KLUFAS ET AL
Early detection of retinal and choroidal disease
through diagnostic imaging may be useful for optimal
diagnosis and treatment to minimize vision loss. One
such imaging modality is ICGA. The longer wave-
lengths of the ICG dye allow for better penetrance of
ocular structures (more so than uorescein angiogra-
phy), making it the best modality to image the
choroidal vasculature, which is paramount in certain
conditions such as neovascular age-related macular
degeneration (AMD) and disorders with choroidal
neovascular membranes.1215 Furthermore, the peri-
pheral retina is an important site for the screening,
diagnosis, monitoring, and treatment of vitreoretinal
disease. With the advent of ultra-wieldeld imaging,
multiple studies have shown important diagnostic and
treatment implications for conditions including dia-
betic retinopathy,1621 retinal vascular occlusions,2226
sickle cell retinopathy,27 white without pressure,28
choroidal lesions including tumors,2931 retinal detach-
ment,32,33 AMD,34,35 retinopathy of prematurity,36,37
and uveitis.3843
The Optos P200Tx (Optos PLC, Dunfermline,
Scotland) imaging system is a scanning laser ophthal-
moscope (SLO) that can image up to 200 of the ocular
fundus in a single image. For this study, an Optos
P200Tx imaging platform was modied to perform
ultra-wideeld indocyanine angiography (UWF-ICGA)
with a module capable of emitting 805-nm laser light
and a lter with a cutoff of 835 nm to collect the cya-
nescence. To the best of our knowledge, this is the
rst report on the clinical feasibility of noncontact
UWF-ICGF using the Optos P200Tx.
Methods
We conducted a retrospective review of a consecutive
series of UWF-ICGA performed on patients at 3
institutions (Weill Cornell Medical College, New York
University/Vitreous Retina Macula Consultants of New
York, and Keck School of Medicine, University of
Southern California) between 2009 and 2013 who
underwent UWF-ICGA using the prototype Optos
200Tx imaging system. The research received IRB
approval at all sites and was performed in compliance
with local and national IRB guidelines. Health Insurance
Portability and Accountability Act (HIPPA) compliance
was maintained. Care of the patients in this study was in
accordance with the Declaration of Helsinki and all
federal and state laws.
Angiography was performed with 25 mg of indoc-
yanine green with 5% sodium iodide powder (Akorn,
Inc, Lake Forest, IL) diluted in 2 mL of sterile water
and administered intravenously as a bolus with a total
509
volume of 2 mL. Sequential time-stamped images
were obtained for each eye during transit and comple-
tion of choroidal lling. Given limited ophthalmic
photographer resources and patient time limitations, not
all patients had late-frame (.30 minutes from infusion
of indocyanine green) images acquired. Images were
digitally captured using the Optos V2 Vantage Review
Software and subsequently compressed into high-
quality JPEG/TIFF les. To compare images obtained
from the Optos UWF-ICGA with traditional ICGA, an
outline of these elds were superimposed on the Optos
image using Photoshop CS5 software (Photoshop CS5;
Adobe, San Jose, CA). Additionally, some patients
received additional imaging with other modalities
including uorescein angiography (wide-eld and
non-wideeld), optical coherence tomography, and tra-
ditional nonwide angle fundus photography, as clini-
cally indicated.
Three experienced trained readers (S.K., K.B.F., and
S.R.S.) independently analyzed each UWF-ICGA image
at their respective institutions for the presence of retinal
pathology. Special attention was paid to the peripheral
retina, especially regarding the area outside the 50 to
60 area of view with the traditional ICGA platforms.
A review of electronic medical records was performed
in which demographic data, medical history, ocular
history, visual acuity, slit-lamp examination, dilated
fundus examination, and other ancillary testing includ-
ing fundus photography, optical coherence tomography,
and uorescein angiography were collected and
reviewed.
Results
One hundred and thirty-eight eyes of 69 patients (30
women and 39 men) were imaged with pathologies
including uveitis, AMD, polypoidal choroidal vascul-
opathy, central serous chorioretinopathy (CSCR)
among other conditions (Table 1). All UWF-ICGA
performed were captured with sufcient quality and
resolution to be included in this analysis. Age ranged
from 24 to 85 years (mean, 58 16.9 years).
A review of images revealed the presence of
peripheral (outside the 5060 view of standard ICGA
imaging systems) changes on ultra-wideeld indocya-
nine green imaging in 67.4% of eyes. A review of
specic peripheral imaging ndings is presented in
Table 2.
Eight representative cases are presented in Figures
18. In neovascular AMD (Figure 1, A and B), Optos
UWF-ICGA showed excellent visualization of poste-
rior pole choroidal hyperuorescence consistent with
classic choroidal neovascularization (CNV), which
510 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2015  VOLUME 35  NUMBER 3

Table 1. Clinical Indications for UWF-ICGA other cases displayed prominent dilated vessels (Fig-
Number of
ure 2, A and B), with late frames showing hyperuor-
Clinical Indication Eyes (N) escence corresponding to those areas as well as other
areas of hypouorescence (Figure 2B). These areas
CSCR 24
Uveitis 16 with dilated vessels on ICGA correspond not only to
Sarcoidosis 3 the areas of leakage on uorescein angiography but
Systemic lupus erythematous 3 also with the areas that appeared normal on fundus
Posterior uveitis 3 photography and uorescein angiography, consistent
Birdshot chorioretinopathy 3 with the diffuse choroidal hyperpermeability charac-
Other: cytomegalovirus retinitis, 4
panuveitis, VKH, unknown/chorioretinal teristic of this disorder and highlighted by ICGA.
scarring In polypoidal choroidal vasculopathy, early UWF-
AMD 12 ICGA images showed a dilated network of vessels
Neovascular AMD 10 (Figure 3A) consistent with an abnormal inner choroidal
Nonneovascular AMD 2 vascular network, resulting in clinically visible reddish-
Polypoidal choroidal vasculopathy 4
Pigment epitheliopathy* 3 orange polyps on clinical examination and fundus
Myopic degeneration 2 photography. Later frames showed hyperuorescence cor-
Ocular syphilis 2 responding to the areas of these dilated vessels secondary
Other (Susac syndrome, adult vitelliform 6 to slow leakage from the abnormal choroidal vasculature
dystrophy, PXE, AZOOR, MFC, (Figure 3B). In other polypoidal choroidal vasculopathy
vitreous degeneration)
Total 69 cases, far peripheral networks of polyps were prominently
seen in the mid-phase ICGA, which displayed character-
AZOOR, acute zonal occult outer retinopathy; MFC, multifocal
choroiditis; PXE, pseudoxanthoma elasticum; VKH, VogtKoyanagi istic washout in the later-phase ICGA images.
Harada. In uveitis, a variety of conditions exhibited a wide
*Secondary to deferoxamine toxicity (1), old CNV in both eyes range of peripheral pathologic choroidal vasculature
complicating punctate inner choroidopathy (1), and choroidal
nevus associated with a CSCR-like syndrome (1). changes. Ultra-wideeld indocyanine angiography
showed multiple prominent areas of choroidal hypouor-
escence in birdshot chorioretinopathy (Figure 4) corre-
was comparable with other non-UWF platforms sponding to white lesions on clinical examination
including the Heidelberg Spectralis. Other prominent consistent with holes in the uorescence of the chorio-
peripheral changes on Optos UWF-ICGA in neovas- capillaris. Multiple round areas of choroidal hypouores-
cular AMD included mid-phase hypouorescent areas cence consistent with a choroidal vasculature lling defect
up to one disk diameter in size consistent with extra- and/or blockage from retinal granulomas were observed in
macular serous pigment epithelial detachment without systemic sarcoidosis (Figure 5). In ocular syphilis, numer-
CNV. Peripheral hyperuorescence with and without ous peripheral ICGA ndings were observed including
adjacent dilated vessels was also observed in the mid-phase diffuse round areas of hypouorescence
periphery consistent with extramacular early occult (Figure 6G), mid-phase posterior pole hyperuorescence
CNV, also referred to as vascularized pigment epithe- consistent with vascular anastomosis versus retinal cystic
lial detachment, in a select number of cases. Addition- changes (Figure 6F), and late-phase frames showing infe-
ally, in nonneovascular AMD, peripheral areas of rior hypouorescence and lling defect of a choroidal
hypouorescence consistent with blockage from vessel consistent with nonperfusion (Figure 6I).
peripheral drusen or retinal pigment epithelium atro- Among white dot syndromes imaged in this series,
phy were noted on UWF-ICGA images. Peripheral quiescent multifocal choroiditis UWF-ICGA images
angiographic features appear to be present in both non- showed peripheral dilated vessels and hypouorescent
neovascular and neovascular AMD on UWF-ICGA. spots consistent with punched out peripheral chorior-
Given peripheral ICGA ndings in patients with etinal lesions in early and late frames (Figure 7). Addi-
AMD has not been previously focused on, the clinical tionally, in late frames, a mix of hypouorescent and
signicance of these imaging characteristics remains hyperuorescent spots in periphery was also observed
unknown. However, it is important to note that periph- consistent with both the persistence of hypouores-
eral ndings on UWF autouorescence imaging are cence from chorioretinal lesions and hyperuorescent
increasingly recognized, perhaps having some clinical foci that do not correspond to the areas of visible
implications for patients with AMD.34,35 pathology on clinical examination or uorescein angi-
In CSCR, Optos UWF-ICGA revealed patchy areas ography. In acute zonal occult outer retinopathy, early
of hyperuorescence in early- and mid-phase frames, Optos UWF-ICGA and late images showed peripapil-
which faded in later frames (Figure 2A). Additionally, lary zonal areas of hypouorescence (Figure 8), which
 WIDE-FIELD INDOCYANINE GREEN ANGIOGRAPHY  KLUFAS ET AL 511

Table 2. Peripheral Pathology Identied on UWF-ICGA

Percent of Eyes With Peripheral
Clinical Indication Findings (%) Peripheral Finding (Number of Eyes)
CSCR 64.6 Dilated vessels (25), late hyperuorescence
(21), late hypouorescence (6)
Uveitis 59.4
Sarcoidosis 50.0 Hypouorescent patches (3)
Systemic lupus erythematous 66.7 Hypouorescent patches (2), hyperuorescent
vessels (2)
Posterior uveitis 66.7 Vessel lling defect (2), hypouorescent
spots (2)
Birdshot chorioretinopathy 66.7 Diffuse hypouorescent spots/patches (4)
Other: cytomegalovirus retinitis, VKH, 50.0 Dilated vessels (4), hypouorescence (4)
panuveitis, unknown/chorioretinal
scarring
AMD 80.0
Neovascular AMD 75.0 Hypouorescence (15), dilated vessels (6),
hyperuorescence (2)
Nonneovascular AMD 50.0 Hypouorescence (2)
Polypoidal choroidal vasculopathy 37.5 Choroidal neovascularization/vessel leakage
(3), late hypouorescence (1)
Pigment epitheliopathy* 100 Dilated vessels (4), hypouorescent patches (2)
Myopic degeneration 100 Late hypouorescence (4)
Ocular syphilis 100 Vessel wall hyperuorescence (2), patchy
hypouorescence (4), Inferior blocking
defect (2)
Other (Susac syndrome, adult 75.0 Patchy hypouorescence (7; 2 vitreous
vitelliform dystrophy, PXE, AZOOR, degeneration, 2 AZOOR, 1 vitelliform, 1 MFC,
MFC, vitreous degeneration) 1 Susac), dilated vessels (4; 2 PXE, 2
AZOOR), hyperuorescence (1 vitreous
degeneration), vessel luminal lling defect
(1 Susac)
Total 67.4
AZOOR, acute zonal occult outer retinopathy; MFC, multifocal choroiditis; PXE, pseudoxanthoma elasticum; VKH, VogtKoyanagi
Harada.
*Secondary to deferoxamine toxicity (1), old CNV in both eyes complicating punctate inner choroidopathy (1), and choroidal nevus
associated with a CSCR-like syndrome (1).

corresponded to the areas of zonal atrophy on optical
coherence tomography. In the periphery, conuent pin-
point areas of hypouorescence were also observed,
consistent with early stages of outer retinal atrophy.
Discussion
Ultra-wideeld indocyanine angiography with the
Optos platform allows visualization of up to 200 of the
peripheral retina in a single frame. To the best of our
knowledge, this is the rst report of UWF-ICGA (200)
of the ocular fundus. Obtaining UWF-ICGA with the
noncontact Optos system was clinically feasible and com-
parable with obtaining traditional nonwide-eld ICGA.
Indocyanine green is a water-soluble dye that was
rst approved for human use in 1956 by the Food and
Drug Administration to visualize the hepatic and
cardiac circulations. In the late 1960s, Kogure et al44
rst described intraarterial injection of indocyanine
green in monkeys to perform choroidal absorption
angiography. In 1971, David was the rst to perform
intraarterial ICGA in human patients.45,46 In 1972,
Flower and Hochheimer47,48 were the rst investiga-
tors to perform intravenous ICGA in humans. The next
year, this pair of investigators also reported combined
indocyanine green and uorescein angiography to
simultaneously visualize the retinal and choroidal cir-
culation.49 In 1985, Bischoff and Flower50 reported
their 10 years experience with ICGA, highlighting
500 clinical cases with angiographic ndings and an-
giograms in 180 normal control volunteers. As the
technology to image the choroidal vasculature evolved
and proved clinically useful,13,15 studies investigated
videoangiography51,52 to better visualize choroidal
vasculature (particularly choroidal neovascular mem-
branes) and also incorporating other advances such as
the SLO53 and digitization.13,14 In 1992, a landmark
study pointed out the particular usefulness of ICGA in
occult choroidal neovascular membranes.13
512 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2015  VOLUME 35  NUMBER 3

Fig. 1. A. Neovascular AMD. Heidelberg (a) and Optos autouorescence (b) of the left eye showing mottled areas of hyperautouorescence consistent
with drusen and hypoautouorescence consistent with retinal pigment epithelium atrophy. Heidelberg FA/ICG of the left eye showing staining of
drusen on uorescein angiography and hyperuorescence consistent with CNV (arrows) on ICGA (c). Optos UWF-ICGA shows excellent visualization
of posterior pole choroidal hyperuorescence consistent with three distinct areas of CNV. Inset demonstrates macular quality is comparable with
Heidelberg (d). Optical coherence tomography showing areas diffuse drusenoid pigment epithelial detachments and intraretinal uid (e). B. Neovascular
AMD. Optos UWF-ICGA of the right eye showing early (a) and late (b) hyperuorescence of a classic plaque in Type 1 CNV in the macula and
peripheral hypouorescence (arrows). Optos UWF-ICGA of the left eye showing early (c) and late (d) hyperuorescence of a classic plaque in Type 1
CNV in the macula in addition to peripheral hypouorescence (arrows). Optical coherence tomography of the right eye (e) through green line in (b)
showing Type 1 CNV. Optical coherence tomography (f) of the left eye through green line in (d) showing Type 1 CNV.

In 1996, Japanese investigators began acquiring wide-
angle (up to 70) ICGA with a hand-held 30 diopter lens
and SLO to study the hemodynamics of the peripheral
choroid including the study of a peripheral choroidal
watershed zone.2 Likewise, in the United States in
1998, Spaide et al3 reported the use of a wide-angle
contact lens (Volk SuperQuad 160, Volk Optical Inc.,
Mentor, OH) in combination with a fundus camera to
further evaluate the hemodynamics of the peripheral
choroid with the potential to improve management of
tumors, dystrophies, vascular, degenerative, or inam-
matory conditions. The authors noted the presence of
choroidal neovascular membranes outside the vascular
arcades and peripheral choroidal vascular permeability
in CSCR that would not have been apparent with tradi-
tional nonwide-angle ICGA. Of note, the authors of
this study comment that the contact lens system was
poor for wide-angle uorescein angiography because
of autouorescence of the crystalline lens.3 Additional
advantages of the wide-angle ICGA technique were the
simultaneous imaging of all areas of the vasculature,
which was not possible with manually assembled mon-
tages, which (by default) are taken at different time
points in the angiographic sequence.3,54 In 2005, a sim-
ilar system in concept was introduced by Staurenghi
et al6 using a contact lensbased SLO to perform real-
time wide-angle (up to 150) angiography including
ICGA. In 2005, a noncontact SLO that allowed ultra-
wideeld uorescein angiography with up to 200 eld
of view of the ocular fundus was introduced,10 and an
adapted version of this device, which is the focus of this
report, now allows novel noncontact ultra-wideeld in-
docyanine green angiography of the ocular fundus.
This series illustrates the clinical feasibility of ultra-
wideeld ICGA in a wide variety of clinical condi-
tions. Images were of excellent quality (Figures 18),
 WIDE-FIELD INDOCYANINE GREEN ANGIOGRAPHY  KLUFAS ET AL
and acquisition was performed in a similar manner and
time as ultra-wideeld fundus photography and ultra-
wideeld uorescein angiography. Likewise, image
resolution was comparable with other imaging modal-
ities such as the Heidelberg Spectralis. For instance,
choroidal neovascular membranes of the posterior
pole in AMD were well visualized (Figure 1A) with
the noncontact UWF-ICGA and comparable in quality
with standard ICGA (Figure 1A) imaging produced by
the Heidelberg Spectralis (Heidelberg Engineering,
Inc., Heidelberg, Germany). In AMD, the most signif-
icant uses of ICGA are imaging of CNV for charac-
513
Fig. 1. Continued
terizing pigment epithelial detachments and subretinal
and choroidal retinal angiomatous proliferation le-
sions.55 Peripheral retinal abnormalities have been
documented in AMD using UWF fundus
autouorescence,35 and corresponding changes on
UWF-ICGA may further enhance our knowledge and
understanding of peripheral fundus changes in AMD.
Furthermore, the increased visualization of the peri-
pheral choroid with UWF-ICGA in this study showed
areas of choroidal vascular permeability in the periph-
ery in CSCR that would not have been
otherwise imaged with non-wide angle ICGA
514 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2015  VOLUME 35  NUMBER 3

Fig. 2. A. Chronic CSCR. Optos UWF-

ICGA of the right eye showing patchy
areas of hyperuorescence (arrow) (a).
The right eye did not have currently
active CSCR but had changes consistent
with old CSCR. Optos UWF-ICGA of the
left eye showing patchy areas of hyper-
uorescence and hypouorescence (b).
The left eye had active CSCR and an ex-
pansile dot pattern of leakage on uorescein
angiography with choroidal hyper-
uorescence at the same location on UWF-
ICGA. Heidelberg FA/ICGA showing area
of hyperuoresence consistent with ex-
pansile dot pattern of CSCR (c). Optical
coherence tomography of the left eye
showing subretinal uid (d). B. Central
serous chorioretinopathy (a) early Optos
UWF-ICGA showing dilated vessels (ar-
rows) (b) late Optos UWF-ICGA showing
late hyperuorescence (arrows) correspond-
ing to the areas of dilated vessels in (a).
 WIDE-FIELD INDOCYANINE GREEN ANGIOGRAPHY  KLUFAS ET AL
(Figure 2, A and B). In CSCR, ICGA can be used to
identify abnormalities in choroidal circulation
including vessel dilation, hypouorescent areas
associated with nonperfused choriocapillaris and
hyperuorescent areas near leaks, and areas of cho-
roidal hyperpermeability.56
515
Fig. 3. Polypoidal choroidal
vasculopathy. A. Early Optos
UWF-ICGA showing polyps and
dilated network of vessels. B.
Late Optos UWF-ICGA show-
ing hyperuorescence corre-
sponding to the areas of dilated
network of vessels in (A). C.
Optical coherence tomography
of the left eye showing polyps
(through green line in B).
In uveitic conditions including birdshot chorioretin-
opathy (Figure 4), ocular sarcoidosis (Figure 5), ocular
syphilis (Figure 6), multifocal choroiditis (Figure 7),
and acute zonal occult outer retinopathy (Figure 8),
signicant choroidal pathology was visualized in the
periphery (outside standard nonwide angle imaging),
Fig. 4. Birdshot chorioretinop-
athy: (A) Optos color fundus
photograph with areas of hypo-
pigmentation and (B) auto-
uorescence. C. Fluorescein
angiography shows hyperuores-
cence at the optic disk and along
retinal veins consistent with phle-
bitis. D. UWF-ICGA shows mul-
tiple prominent areas of choroidal
hypouorescence highlighted in
the inset.
516 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2015  VOLUME 35  NUMBER 3

Fig. 5. Systemic sarcoidosis

with ocular involvement Optos
fundus photograph of the (A)
right and (B) left eyes showing
multiple chorioretinal lesions
in the periphery outside the
macula. Ultra-wideeld in-
docyanine angiography of the
(C) right eye showing blockage
by chorioretinal lesions and (D)
left eye showing staining of
chorioretinal lesions and late
leakage at the disk. Ultra-wide-
eld indocyanine angiography
of the (E) right and (F) left eye
showing multiple round areas
of choroidal hypouorescence.

which may have important implications in the man-
agement and treatment of these conditions. In ocular
sarcoidosis, ICGA is important in the identication of
peripheral choroidal granulomas and macular edema.57
Ultra-wideeld uorescein angiography has been
shown to be important in the early detection of periph-
eral inammation and monitoring efcacy of treatment
in patients with intermediate uveitis.43 Indocyanine
green angiography has been used to diagnose and
monitor disease progression in birdshot chorioretinop-
athy where it appears as hypouorescent round dots,
sometimes with widespread involvement up to the
equator, often best seen early in the study.58 Tradition-
ally, a fundus camera-based system has been preferred
by some clinicians over a scanning confocal laser oph-
thalmoscope because of increased depth of eld, better
visualization of the periphery, and superior quality
late images; however, newer SLO technology chal-
lenges these benets. Likewise, in acute syphilitic
posterior placoid chorioretinitis, early-phase uores-
cein angiography may demonstrate scattered hypo-
uorescent spots, referred to as leopard spotting,
whereas mid- and late-phase FA may show progres-
sive hyperuorescence.59,60 Early-phase ICGA may
reveal hypouorescent areas near lesions, and these
changes may persist throughout the study.59 Late-
phase hyperuorescence has also been observed.6163
In multifocal choroiditis, ICGA aids in diagnosis, pro-
vides information that is not detectable on clinical
examination or uorescein angiography, and is useful
in evaluating the natural course of the condition and
response to therapy.64 Indocyanine green angiography
 WIDE-FIELD INDOCYANINE GREEN ANGIOGRAPHY  KLUFAS ET AL
Fig. 6. Tertiary syphilis Optos fundus photograph of the (A) right and
(B) left eye showing diffuse areas of peripheral chorioretinal whitening
concentrated inferiorly in both eyes and sclerotic vessels temporally in
the right eye. Seven standard elds overlayed in black. Optos auto-
517
in multifocal choroiditis shows characteristic hypo-
uorescence up to the late phase when the condition
is active and more extensive involvement than is visible
on ophthalmoscopy and uorescein angiography.65
Likewise, characteristic ICGA patterns of hypouores-
cence during all phases with no increase in the number
of lesions between early and late phases is seen when the
disease is inactive.65 Angiographic ndings in acute
zonal occult outer retinopathy including an annular
scotoma with a circumferential ring on ICGA may
also aid in timely and proper diagnosis.66,67 In acute
zonal occult outer retinopathy, ICGA studies have
suggested that damage to the choriocapillaris occurs
in areas corresponding to scotomas at the onset of
disease68 and disease progression causes atrophy of
the choriocapillaris.69
Our study does have limitations that should be
considered when interpreting our ndings. First, the
sample size is relatively small and analysis was performed
retrospectively; however, this is only an initial feasibility
study. Second, although the appearance of the choroidal
circulation in the posterior pole of normal eyes is well
known, the variation in ICG features in the normal retinal
periphery is not as well established. This could result in
an underestimation or overestimation of abnormal nd-
ings in the disease cohort collected in this feasibility
study. Third, most of the subjects were collected from
tertiary referral retinal practices; this could potentially
create an ascertainment bias about types of disease and
frequency of abnormalities, which were observed. At the
same time, this study has several strengths including the
use of the same instrument with a similar imaging
protocol, with demonstration of feasibility at multiple
clinical sites.
Conclusion
Ultra-wideeld indocyanine angiography with
the Optos system is clinically practical and provides
uorescence of the (C) right and (D) left eye showing inferior areas of
hypoautouorescence bordered by areas of hyperautouorescence
consistent with areas of retinal pigment epithelium atrophy. Ultra-wi-
deeld indocyanine angiography of the right (E) and left (F) eyes with
areas of peripheral nonperfusion of both eyes, leakage in the periphery
and macula of the right eye (zoomed inset and red arrow), cystoid
macular edema in the left eye (zoomed inset and red arrow), and leakage
from the disk of both eyes (E and F). Mid-phase UWF-ICGA of the (G)
right eye showing diffuse round areas of hypouorescence and vascular
anastomosis (zoomed inset and red arrow). Mid-phase UWF-ICGA of the
(H) left eye demonstrating mild hyperuorescence consistent with chronic
intraretinal cystic changes. Late-phase UWF-ICGA of the (I) right eye
showing inferior hypouorescence and lling defect of a choroidal vessel
consistent with nonperfusion (zoomed inset and red arrow). Late-phase
UWF-ICGA of the (J) demonstrates excellent resolution of the macula
despite wideeld. Optical coherence tomography of the right (K) and left
(L) eyes showing intraretinal cystic changes of both eyes.
518 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2015  VOLUME 35  NUMBER 3

Fig. 7. Multifocal choroiditis

quiescent multifocal choroidi-
tis. A. Early Optos UWF-IC-
GA showing dilated vessels
superior to disk and macula
and hypouorescent spots in
periphery, inferonasal quadrant.
B. Late Optos UWF-ICGA
showing hypouorescent spots
in periphery, inferonasal quad-
rant and hyperuorescent spots
in the far nasal periphery (red
boxed area in B shown in mag-
nied view in C).

high-resolution imaging of the peripheral and posterior
pole choroidal vasculature sufcient for diagnosis,
evaluation, and follow-up of a variety of vitreoretinal
disorders. Ultra-wideeld indocyanine angiography
reveals abnormalities in the peripheral retina that
may otherwise be missed on conventional ICGA
imaging. This technology is still in the developmental
stages, and certain features remain to be improved.
Although there are multiple standard options to image
the choroidal circulation of the posterior pole, there is
no other method that allows single-image analysis of
the far peripheral choroidal circulation to the extent of
this UWF-ICGA device. Further UWF-ICGA imaging
on additional normal controls and patients with
vitreoretinal disorders will aid in the classication
and spectrum of peripheral choroidal pathology. The
clinical signicance of these peripheral ndings and
the impact on the diagnosis, treatment, and follow-up

Fig. 8. Acute zonal occult

outer retinopathy. Early Optos
UWF-ICGA (A) and late Optos
UWF-ICGA (B) showing zonal
areas of hypouorescence. C.
Optical coherence tomography
showing zonal atrophy (scan
through green line in B).
 WIDE-FIELD INDOCYANINE GREEN ANGIOGRAPHY  KLUFAS ET AL
of patients with retinal and choroidal disorders will
require larger prospective studies.
Key words: ultra-wideeld imaging, ultra-wide-
eld, wide-eld, imaging, retinal imaging, indocya-
nine green angiography, wide-eld uorescein
angiography, age-related macular degeneration, central
serous chorioretinopathy, sarcoidosis, syphilis, bird-
shot chorioretinopathy, multifocal choroiditis, acute
zonal occult outer retinopathy, polypoidal choroidal
vasculopathy.
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