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50 I GLAUCOMA TODAY I JANUARY/FEBRUARY 2008

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Glaucoma Today s Innovators column profiles promising technological developments in glaucomaand the companies bringing them to fruition.

Ophthalmologists have long recognized anassociation between the progressive loss of retinal ganglion cells and glaucomatous

changes in the optic disc.Although the standard techniques for evalu-ating the optic discophthalmoscopy andstereoscopic fundus photographywere use-ful for identifying thinning of the neuroreti-nal rim and cupping of the optic nerve,these subjective approaches provided onlyindirect information about the retinal nervefiber layer (RNFL).

The advent of optical coherence tomogra-phy (OCT) in the 1990s enabled ophthalmol-ogists to measure the thickness of the RNFL

objectively. Because this new diagnostic testalso provided insight into how changes in theretina affected the appearance of the opticdisc, this technology quickly became part of clinical studies and practitioners standardglaucoma workup.

The original OCT technology introducedby investigators at the MassachusettsInstitute of Technology (Cambridge, MA) in1991 used time-domain techniques to cap-ture images of the retina. In the past fewyears, researchers have recognized Fourier-

domain OCT as an alternative measuring

technique that facilitates significantly higher scanningspeeds.

Several companies have since brought Fourier-domain OCT systems to market, including Optovue,Inc. (Fremont, CA), which in October 2006 launchedRTVue, the first Fourier-domain OCT system approvedby the FDA.

A Fresh Take onOptical Coherence

TomographyAdvances in optical technology helped Optovue realize the potential of

Fourier-domain OCT for diagnosing glaucoma.

BY JULIA T. LEWANDOWSKI, SENIOR ASSOCIATE EDITOR

Figure 1.The RTVues nerve head map provides quantitative informa-tion about the peripapillary RNFL, the neuroretinal rim, and the optic

discs cup.

( A l l i m

a g e s c o u r t e s y

o f V i k a s

C h

o p r a ,M D . )


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This article describes how Fourier-domain OCT ishelping clinicians and researchers detect early patholog-ical changes in the retinas of glaucomatous eyes.

T H E F U N D A M E N TA L S O F F O U R I E R -

D O M A I N O C T

Two parameters differentiate time-domain and

Fourier-domain OCT: speed and resolution. Becausecommercially available time-domain OCT systemsdepend on the mechanical movement of a referencemirror to measure the reflectance from various layers of the retina, they can only perform 400 A-scans per sec-ond. In contrast, Fourier-domain OCT uses a stationaryreference mirror and a spectrometer to capture informa-tion from all layers of the retina simultaneously thus per-forming the equivalent of 26,000 A-scans per second.

David Huang, MD, PhD, is a co-inventor of OCT,Associate Professor of Ophthalmology and BiomedicalEngineering at the at the University of Southern

California, Los Angeles, the principal investigator of theNIH-funded Advanced Imaging for Glaucoma (AIG)study consortium, and a consultant to Optovue, Inc.During an interview with Glaucoma Today , he statedthat the technological breakthrough that made Fourier-domain OCT a clinically viable diagnostic test for glau-coma was the availability of affordable, high-speed linecameras. I described a Fourier-domain OCT device inmy doctoral thesis in 1993, he said. Although line-scancameras were available then, they were not advancedenough to work in Fourier-domain OCT systems. Thetechnology has caught up with the theory, however,

and as line-scan cameras get faster, we can expect the

performance of Fourier-domain OCT to improveeven more.

The second parameterthat sets the RTVue apartfrom conventional time-domain OCT retinal scan-ners is the resolution of the images they create.Both systems use a super-luminescent diode lightingsource, but the RTVueswider spectral bandwithproduces images that aretwice as detailed (5 m) as

those obtained by time-domain OCT devices (10m).

The RTVues faster scan-ning speed and ability to

capture higher-resolution images overcomes several lim-itations of commercially available time-domain OCTsystems, said Michael J. Sinai, PhD, Optovues SeniorDirector of Clinical Affairs, in an interview with GToday .In addition to allowing us to obtain a lot of data quick-ly, the RTVues higher scanning speed eliminates muchof the motion artifact that can distort images obtained

by time-domain OCT systems, he commented.Rohit Varma, MD, MPH, is the chief of the GlaucomaService at the Doheny Eye Institute, University of Southern California Keck School of Medicine, LosAngeles, and a principal site investigator of the AIGstudy. In an interview with GToday , he stated thatFourier-domain OCT is valuable because it providesmore information about how changes in the inner reti-nal layer affect the appearance of the optic nerve. Theloss of retinal ganglion cells causes thinning of theRNFL, which then translates into greater cupping of theoptic disc, he said. By the time we are able to detect

damage in a patients optic disc or thinning of theRNFL, the patient may have lost a significant number of ganglion cells to glaucomatous progression.

According to Dr. Sinai, the RTVue has several scanpatterns specifically designed to detect glaucomatousdamage. The nerve head map scan (NHM4) (Figure 1)and GCC maps (Figure 2) provide comprehensive infor-mation that is invaluable to the clinician for detectingand managing glaucoma, he said.

G L A U C O M A A N D T H E M A C U L A

Vikas Chopra, MD, Assistant Professor of

Ophthalmology at the University of Southern California

Figure 2. The RTVues GCC Scan provides quantitative information about the retinal layerspreferentially affected by glaucoma.This image shows the automated segmentation analysisof a normal (top) and a glaucomatous (bottom ) eye.Note the thinner GCC (arrows) in theglaucomatous eye.


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Keck School of Medicine is investigating the RTVuesutility for detecting early glaucomatous changes in themacula as part of the AIG study.

Structurally, the macula is a logical place to look atchanges in the RNFL and GCC, because the highest con-centration of ganglion cells occurs in this area of theretina, he told GToday . Unfortunately, measuring thetotal thickness of the macula with time-domain OCTtechnology does not provide sensitive enough informa-tion about glaucomatous change, because the diseasepreferentially affects the inner retinal layer.

During the 2006 AAO Annual Meeting in Las Vegas,Dr. Chopra and his colleagues presented the results of astudy that compared the sensitivity of the Stratus OCT(Carl Zeiss Meditec, Inc., Dublin, CA) and the RTVue for

detecting the focal loss of retinal ganglion cells in theeyes of patients with glaucoma. 1

We found that peripapillary RNFL thickness scansobtained with both OCT systems successfully differenti-ated between normal and glaucomatous eyes in a sub-set of eyes from the AIG study, said Dr. Chopra. TheRTVues novel macular grid scan pattern, however, pro-vided a more detailed, reproducible map of a larger areaof the macula that allowed us to measure the thicknessof the inner retinal layers. We were also able to detectthe focal loss of ganglion cells with the high-resolutionimages obtained by the RTVues proprietary macular

thickness scan.In addition to using the data from macular scans to

create quantitative thickness maps of individualpatients maculae, the RTVue compares this informa-tion against a large age-adjusted normative database to

create deviation and significance maps that alert the cli-nician to areas with likely damage.This information allows us to determine the percent-

age of ganglion cells a patient has lost relative to macu-lae of normal thickness (deviation) and the likelihoodthat the patient is developing glaucoma (significance),said Dr. Chopra. These reports have helped us detectcharacteristic patterns of focal ganglion cell loss in thesuperior and inferior poles of the optic nerves of patients with preperimetric glaucoma (Figure 3). Whenthis information is analyzed by the RTVues GCCProgressional Analysis function, we can detect progres-

sive changes in macular thickness over time.Dr. Sinai also believes that the RTVue can providevaluable information about the progression of glauco-ma. Because the RTVue is based on Fourier-domainOCT technology, we can quantify the thickness of themacula in microns, he said. This degree of precisionallows us to detect small, consistent changes in theRNFL that cannot be visualized with even the best qual-ity stereophotograpic fundus photographs.

Dr. Huang is working with Optovue to implementadvanced diagnostic scan patterns for glaucoma andfaster [[Dr. Huang: OK?]] image processing software

into the RTVue.The most recent results of my research show that

Figure 3.Figure 3.The RTVues fractional deviation map (right) is derived by comparing the GCC thickness map of the subjectwith the same data complied from a large, age-adjusted normative database (normal map). Red hatching indicates areaswhere the patient has lost a significant number of ganglion cells. The fractional deviation map shown here indicates character-

istic glaucomatous thinning of the GCC in the inferior arcuate pole.


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the RTVues GCC and RNFL scans provide diagnosticparameters that are significantly better than those pro-duced by standard time-domain OCT systems, 2,3 he

said. I believe this is just the beginning of a long learn-ing curve, however, and that we will benefit even morefrom Fourier-domain OCT as the technology matures.

Dr. Chopra cites the RTVues ability to objectivelymeasure early glaucomatous changes in the ganglioncell complex as one of its greatest strengths. The key tomanaging glaucoma is early detection, he said. TheRTVue FD-OCT may help us identify patients at risk andintervene before significant vision loss occurs.

F O U R I E R - D O M A I N O C T F I N D S A C L I N I C A L

N I C H ESince Optovue introduced the RTVue in October

2006, several other companies have brought Fourier-domain OCT devices to market. Physicians who areinterested in incorporating this imaging modality intotheir practice can choose from several FDA-approveddevices: the Spectralis HRA + OCT (HeidelbergEngineering GmbH), the Spectral OCT/SLO(Ophthalmic Technological Industries , Inc., Toronto,Ontario, Canada), the Cirrus HD-OCT (Carl ZeissMeditec, Inc.), and the 3D-OCT 1000 (Topcon MedicalSystems, Inc., Paramus, NJ). The SOCT Copernicus

(Reichert, Inc., Depew, NY), is currently awaiting 510(k)clearance.Dr. Huang acknowledged that Fourier-domain OCT

devices have similar performance parameters, and hesuggested that the best way for potential buyers to dif-ferentiate systems is to consider the reliability of theirengineering and the clinical utility of their software.

Several factors influence the clinical utility of a par-ticular Fourier-domain OCT system including thedevices scan patterns, their ability to analyze images,and how efficiently they extract diagnostic parametersfrom raw data, he said.

Dr. Varma is excited about the RTVues clinical utilityoverall, but he thinks the units user interface could beimproved. Compared with devices that use time-domain OCT technology, the RTVue gives us a morecomprehensive view of how the glaucomatous processdamages the retina and the optic nerve, he said. Iwould, however, like to see the indicators that describethe reliability and variability of the scans displayed moreprominently and clearly on the RTVues printouts.Increasing the visibility of these indicators, he added,would remind physicians to check the quality of thescan before analyzing the data.

Dr. Varma, Joel Schuman, MD, Chairman of the

Department of Ophthalmology at the University of Pittsburgh School of Medicine and Director of the UPMCEye Center and other glaucoma specialists are helping Dr.

Sinai and his colleges at Optovue refine the RTVuesgraphic user interface so that clinicians can quickly andefficiently access critical diagnostic parameters.

The RTVue came out of the gate with full retinal andglaucoma capabilities, because we envisioned it as atool that could give generalists and specialists the infor-mation they need to diagnose manage ocular disease, said Dr. Sinai. Our latest update, which includes a largeage-adjusted normative database, new printouts andprogression analysis, provides the flexibility that clini-cians need to perform expands the users ability to per-form complex analyses or to gather basic clinical infor-mation.

The Advanced Imaging for Glaucoma is sponsored by National Eye Institute Grant R01EY013516.

Dr. Chopra acknowledged no financial interest in the properties or companies mentioned herein. He may bereached at (323) 442-6428; vchopra @usc.edu

Dr. Huang receives stock options, research support, and patent royalties from Optovue, Inc. He also receives royalty payments from an OCT patent licensed to Carl ZeissMeditec, Inc. Dr. Huang may be reached at (323) 442-6710; [email protected].

Dr. Sinai may be reached at (760) 473-3305;

[email protected]. Varma has received research support from Optovue,Inc. He may be reached at (323) 442-6411;[email protected].

1. Chopra V, Tan O, Huang D, Advanced Imaging for Glaucoma Study Group. Glaucomadetection using high-speed high-resolution optical coherence tomography. Paper pre-sented at: The AAO Annual Meeting; November 14, 2006; Las Vegas, NV.2. Tan O, Chopra V, Lu A, et al. Glaucoma diagnosis by mapping the macula with high-speed, high-resolution Fourier-domain optical coherence tomography. Paper presented at:The ARVO Annual Meeting; May 6, 2007; Fort Lauderdale, FL.3. Huang D, Schuman JS, Garway-Hea th, Medeiros FA. Quantitative imaging for glau-coma. Course presented at: The AAO Annual Meeting; November 12, 2007; New Orleans,LA.

I N N O VAT O R S

The RTVUE FD-OCT may helpus identify patients at risk and intervene

before significant vision loss occurs.Vikas Chopra, MD

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