Sponsored by NIDEK

Multimodal Imaging:
Implications for Clinical PracticeMultimodal imaging with the Mirante platform
represents the next step forward in diagnosing andfollowing routine and rare pathologic findings.
BY GIOVANNI STAURENGHI, MD; SRINIVAS R. SADDA, MD;
MARIANO COZZI, MSc; and GIULIA CORRADETTI, MD
Improvements in imaging technology
over the past several years have provided
retina specialists with increasingly finite
structural and functional detail about
the tissue of the posterior segment.
Collectively, the variety of imaging modalities used in daily clinical practice improvethe ability to diagnose pathology, follow
it over time, stage disease, and ultimately
assist in making decisions about treatment and determining prognosis. Thefield is now on the precipice of a new era
in imaging capabilities with the market
availability of devices that combine multimodal imaging on a single platform.
The new Mirante (NIDEK) marks astep forward in this regard, providing
an unprecedented number of imaging
modalities in one single device. The
Mirante offers high-definition OCT andconfocal scanning laser ophthalmoscopy(cSLO), both with widefield capabilities.
With this device, clinicians have access toa wide range of imaging modalities: OCT,
OCT angiography (OCTA), fundus color,
contrast angiography (ie, fluorescein[FA] and indocyanine green [ICG]angiography), and green and blue fundus
autofluorescence (FAF). Although certain
pathologic markers, such as subretinal
drusenoid deposits, are best identified
using blue light, there are situations
where using green autofluorescence isadvantageous (ie, for identifying thefoveal edge of geographic atrophy andtracking it over time). Green FAF isabsorbed to a lesser extent comparedto blue FAF by the macular pigment,
and therefore does not produce theclassic dark halo associated with thelatter, thereby improving visualization.
In addition, comparing images fromboth modes may give insight on changes
in the luteal pigment in the macula,such as in an eye with suspected
macular telangiectasia.
One additional mode bears mentioning: Retro mode imaging is analogous toretroillumination that is used in anterior
segment imaging to see subtle featuresof the cornea and lens. Retro mode
imaging is a unique mechanism for discerning pathologic features that might
be missed with other types of imaging.
Beyond the obvious convenience factor of having all of these modalities on
the same device, the fact they are all
integrated and registered to one anotherassures there is strong correlation infindings between different modalities.

WIDEFIELD AND COLOR SCANNING:
IMPORTANCE FOR CLINICAL PRACTICE
Having access to multiple imaging
modalities provides the clinician a means
to understand how pathology is affecting
the structures of the eye at a near histologic level. If OCT can loosely be thoughtof as an optical biopsy, then multimodal
imaging expands this capability to better understand morphologic featuresin situ. The versatility of the Mirante fordiagnosing and following routine andrare pathology is further enhanced by theintegration of color scanning functionality
and widefield capabilities into its varietyof imaging modes. The Mirante has four
separate lasers, each of which penetrates
to different depths: blue (480 nm; reflectedby the nerve fiber layer), green (532 nm;
reflected by the ganglion cell layer), red(670 nm; penetrates through the retina),
and infrared (790 nm; through the choroidal layer). Each of these lasers can scan
the retina through a confocal optical setup
with a small coaxially-placed pinhole thatlets only the light coming from the focal
planes in while discarding back-scatteredand out-of-focus light. This may be useful,for example, in improving detection ofatrophy in an eye with age-related macular degeneration.
Mirante also has a wider field on OCT
imaging compared to other devices at 16.5mm, which is helpful in tracking progression and response to treatment in pathology that spans long distances—such as ininflammatory disorders. There is also anoptional Widefield lens attachment (163°;
measured from the center of the eye) for
the Mirante that is compatible with color,FA, ICG, and Retro mode imaging.
SEPTEMBER 2019 | INSERT TO RETINA TODAY 1

CASESThe utility of multimodal imaging in clinical practice is best understood in the context of how it helps delineate pathologic findings, thereby
assisting the clinician in arriving at or confirming a diagnosis. Following are case examples from the authors that highlight how the various
imaging modalities on the Mirante (NIDEK) were used to diagnose and make treatment decisions.

Case No. 1

Mariano Cozzi, MSc,
and Giovanni Staurenghi, MD• Multimodal imaging is shown in a case of acquired vitelliform
lesions involving the center of the macula associated with cuticulardrusen phenotype of a 65-year-old female. Each imaging modality
highlights different aspects of the disease.

A• A high-definition, cross-sectional OCT image reveals hyperreflective material above the retinal pigment epithelium (arrow)and multiple cuticular drusen (arrowhead) (A).
• Green autofluorescence shows a hyperautofluorescence signal,
which indicates lipofuscin-like material accumulating between theretinal pigment epithelium and neuroretina (B).
• Blue autofluorescence barely displays the macula
hyperautofluorescence signal because the blue wavelength ispartially absorbed by the macular pigment (C).

BCDE

• A color confocal image allows the ability to visualize a yellowish
foveal material with presence of multiple drusen nearly filling themacular area (D).
• Retro mode infrared illumination image dramatically highlights thetopographic distribution of cuticular drusen, which are known to bestrongly associated with acquired vitelliform lesions (E).

RETRO MODE IMAGING
Many of the capabilities of theMirante will already be familiar to retina
physicians, even if they are performed ina slightly different manner. However, theMirante also introduces a new imaging
mode, Retro mode imaging, which ispoised to enhance the ability to detect
abnormalities.
In a typical imaging set-up with cSLO
using a confocal aperture, direct backscattered light returning from the fundus
is gathered, while other sources of lightscatter are blocked, thereby yielding a
representative image of the confocal
plane of interest. In Retro mode, an
2 INSERT TO RETINA TODAY | SEPTEMBER 2019

aperture with a central stop is used to do
the opposite: a laterally-oriented (either
right- or left-deviated), oval-shaped
opening prevents direct light reflection
from entering the image processor, while
scattered light from a single direction
passes through the aperture. As thismode uses an infrared light source,
the detector acquires images from thesurface to the deep retinal layers, thereby
producing an image with a shadowadjacent to any abnormal features.
The result is a pseudo-3D image thatdelineates abnormalities in the deeper
retinal and choroidal tissue planes. Of
interest, both right- and left-deviatedapertures can be used in imaging toassure more complete data collection.
Retro mode is a modification of indirect (or dark-field) imaging, in which an
aperture with a central stop is used toblock direct light and gather other sourcesof scattered light, but it is more so analogous to retroillumination principles usedin anterior segment imaging. The simplest
way to understand Retro mode is thatthe resulting image is as though the retina
were being lit from behind.
In previous research, Retro mode has
been used to characterize morphologic
features in a variety of clinical entities,including, but not limited to, cystoidCASES
Case No. 2

Giulia Corradetti, MD,and SriniVas R. Sadda, MD• Multimodal imaging is shown in a case of choroidal neovascularization associated with age-related macular degeneration with some
central serous chorioretinopathy (CSCR)-like features in an 85-yearold male.

ABCDEF• Widefield and Ultra-Widefield color fundus photographs captured
with the Mirante (NIDEK) confocal scanning laser ophthalmoscopy
are shown using three different channels (blue, green, and red)with central angles of 89° and 163°, respectively (A, B). Both images
show a smooth and well-circumscribed yellowish fibrovascularpig­ment epithelial detachment (PED) involving the central macula.
• Green autofluorescence shows a central area of mottled hypoautofluorescence highlighting the presence of retinal pigment
epithelium alterations in the region of the PED, with adjacent hyperautofluorescence inferiorly corresponding to the subretinal fluid(C). Early phase fluorescein angiography shows irregular, stippled
hyperfluorescence corresponding to the fibrovascular PED (D).
• Retro mode left-deviated, Widefield, and Ultra-Widefield images,
respectively, show a vertical oval-shaped slightly hyper-reflective
region with a rim of hyporeflectivity, which corresponds to the neurosensory detachment (E, F). The vertically-oblong shape suggests
the gravitational nature of the fluid distribution. The Retro modetechnology, using an eccentric confocal aperture, provides theadditional contrast to display the fluid and its extent.
• An ultrafine cross-sectional spectral-domain OCT image throughthe foveal center (120x averaged) demonstrates a fibrovascular PED
with secondary elevation of the overlying retina and subretinal
fluid (G). Note, the internal characteristics of the PED are visible,
with fibrovascular tissue at the apex of the PED and subretinal pigment epithelium fluid at the base. The full extent of the choroid isvisualized and appears to be thick given the patient’s age.

macular edema secondary to polypoidal
choroidal vasculopathy, retinitis pigmentosa, and retinal vascular disorders;macular retinoschisis in eyes with highmyopia and foveal schisis in eyes with
X-linked retinoschisis; drusen and othersubretinal deposits (indeed, Retro mode
imaging depicts significantly more drusenG

than conventional fundus photography);retinal pigment epithelium alterations
in central serous chorioretinopathy;
leaking microaneurysms in diabetic retinopathy; sites of subthreshold laser scars;
and abnormalities in a variety of retinal
dystrophies.1 Ongoing research will help
to elucidate how such findings may be

used in the clinical setting, and there arestill many unanswered questions regarding how to interpret findings identified
using Retro mode imaging. Nevertheless,there is strong potential to use this novel
modality to highlight features that are
currently undetectable using standard
imaging.
SEPTEMBER 2019 | INSERT TO RETINA TODAY 3

DETECTION AND CHARACTERIZATION OF DRUSEN
USING MULTIMODAL IMAGING
By Mariano Cozzi, MSc, and Giovanni Staurenghi, MD
We recently conducted a prospective
observational study to assess the contribution of Retro mode imaging in the detection
and characterization of drusen and subretinal drusenoid deposits.1
For the study, 38 eyes of 31 consecutive
patients with different types of drusen or
subretinal drusenoid deposits (mean age,78.8 years) were imaged using various
modalities on the Mirante (NIDEK), including
infrared reflectance, fundus autofluorescence, real confocal color fundus imaging,
OCT, and Retro mode imaging using botha right- (DR) and left-deviated (DL) annular aperture.
Overall, retinal color fundus imaging was
superior to other imaging for detecting soft
drusen and ribbon subretinal drusenoiddeposits. Our clinical impression was thatRetro mode imaging readily depicted the3D shape of the various types of drusen anddeposits while also helping to appreciate thegeographic distribution of the drusen at theback of the eye. However, there were some
important differences in the appearance ofdifferent types of drusen using DR and DLCONCLUSION
There is a growing sentiment in retina
practice that OCT, and perhaps OCTA,
are sufficient for understanding andmaking decisions about pathology. We
would contend that they are necessary,
but not entirely sufficient. Rather, thegrowing variety of imaging modalitiesavailable for clinical use provides uniqueinsights about different areas of the retina
in the X-, Y-, and Z-planes; each different
modality has a role in understanding
how different disease states are affecting
different parts of the globe. Collectively,
they improve the ability to understandimportant details that can help us become
better diagnosticians. When they are
all available on the same platform, it
4 INSERT TO RETINA TODAY | SEPTEMBER 2019

apertures, with DR mode depicting cuticularand soft drusen as tiny and wide depressions, respectively, whereas in DL mode,
they appear as mounds of different sizes.
Moreover, ribbon subretinoid deposits wereidentified with both modalities, showing aclassic reticular pattern. Although DR mode
appeared to barely differentiate dot subretinoid deposits from cuticular drusen, the DL
modality showed a more precise identification of both entities.
It is hoped that this data will help to build
on previous studies that suggest that different kinds of drusen are associated with different clinical outcomes. It may be the casethat using multimodal imaging will help toidentify different types of drusen and subretinal deposits, which at the current time
is useful for understanding prognosis andpotential for progression. In the future, andas new forms of treatment become available,
such findings may be useful for directing
appropriate intervention strategies.
1. Monteduro D, Cozzi M, Parrulli S, Staurenghi G.Topographic detection andcharacterization of drusen and subretinal drusenoid deposits: contribution of Retromode modality in a multimodal imaging approach. Abstract 3471. Presented at:
ARVO 2019; April 28-May 2, 2019; Vancouver, British Columbia, Canada.

makes it more efficient to use them; italso provides greater correlation between
separate modalities due to registration andtracking software.
The former does not suggest that clinicians should work through each modality
while building a differential diagnosis;
instead, it underscores that relying on one
imaging modality may provide incomplete
information regarding the status of theretina. Admittedly, having access to somany different imaging techniques does
create practical challenges, and there may
be a learning curve associated with adopting multimodal imaging into practice. On
the other hand, this can be shortenedby understanding how each mode captures images and at what planar level.

Understanding what each modality provides, including its limitations, will allow
the clinician to home in on the specificmodality that will be useful in a given clinical situation.
In some ways the capabilities and clinical utility of the Mirante are ahead of thescience. The availability of Retro mode
imaging is somewhat reflective of this, as it
is more so an exciting research tool at thispoint and time. And yet, the potential todiscover and detect pathology using Retromode imaging that would be missed withother imaging techniques also exemplifies
what is truly revolutionary about multimodal imaging. The more data clinicians
have at their disposal, the better equipped
they will be to diagnose pathology early
and initiate intervention strategies that will
help patients save vision. n
1. Lee WJ, Lee BR, Shin YU. Retromode imaging: review and perspectives. Saudi JOphthalmol. 2014;28(2):88-94.

Giovanni Staurenghi, MDn Luigi Sacco Hospital, University of Milann giovanni.staurenghi@unimi.itn Financial disclosure: Alcon, Allergan, Bayer,Boheringer, Carl Zeiss Meditec, Centervue, Genentech,GSK, Heidelberg Engineering, Nidek, Novartis, Ocular
Instruments, Optos, Optovue, Quantel Medical, Roche
SriniVas R. Sadda, MD
n Doheny Eye Institute, Los Angeles
n ssadda@doheny.org
n Financial disclosure: Centervue, Heidelberg
Engineering, Nidek, Optos, Topcon
Mariano Cozzi, MSc
n Luigi Sacco Hospital, University of Milann mariano.cozzi88@gmail.com
n Financial disclosure: Bayer, Carl Zeiss Meditec,Centervue, Heidelberg Engineering, Nidek
Giulia Corradetti, MD
n Doheny Eye Institute, Los Angelesn giulia.corradetti@gmail.com
n Financial disclosure: None