A lthough the question of why thepupil is black had attracted theattention of writers dating back
to the time of Ancient Rome, it was notuntil 1851 that Herman Ludwig vonHelmholtz unlocked the door to the backof the eye by inventing the Augenspiegel,or ophthalmoscope (Fig. 1). Von Helm-holtz’s groundbreaking invention enabledexamination of both normal and diseasedeyes. It also allowed drawings to be madeof the fundus. The first images of the retinawere useful to physicians for communicat-ing both normal and unusual findings totheir colleagues.1
In 1961, another milestone in exami-nation techniques was achieved with thedevelopment of fluorescein angiography,2
a technique which detects relative leakageof intravenous fluorescein sodium dyefrom diseased or damaged blood vessels.The development of fluorescein angiogra-phy dramatically improved our under-standing of retinal vascular diseases by al-
lowing doctors to image the normal anddiseased vasculature in the fundus.
Cross-sectional examination of the eyewas limited to microscopic examination ofexcised specimens until the invention ofthe slit lamp by Gullstrand in 1921. Withsome modifications of the focusing lenses,examination of the macula is also possiblewith the slit-beam technique. An additionto retinal exam in the 1950s and early1960s was the development of ophthalmicultrasound, which provides two-dimen-sional imaging of the retina, but at a low-er resolution than is possible with opticaldevices.
Today, the introduction of optical co-herence tomography (OCT) to the oph-thalmic armamentarium is rapidly chang-ing the world of retinal examination. Theuse of low-coherence interferometry pro-vides information on relative reflectivityand on the location of ocular structures. Itallows non-invasive, cross-sectional imag-ing of the macula at high resolution, with
Hazem Rashed, Joseph Izatt, and
Cynthia Toth
Optical Coherence Tomography of the Retina
Optical Coherence Tomography of the Retina
Figure 1. The Helmholtz ophthalmo-scope (circa 1851), a groundbreaking in-vention in the history of ophthalmology.
no need to ascertain the existence of vas-cular leakage before rendering a diagnosisof disease.
The emergence of OCT has shed newlight on the participation of non-vascularstructures in many retinal disease process-es. OCT studies have demonstrated fibrot-ic bands within the vitreous gel, the vitre-oretinal interface, the structures withinthe retina, and the subretinal tissues. Bet-ter understanding of the relationship ofthe posterior segment structural compo-nents will likely change the diagnosticgrouping of diseases and the treatment ofretinal conditions.
OCT applied to retinal imagingIn OCT imaging of the retina, low-coher-ence light from a superluminescent diode(SLD) source is coupled into a fiber-opticMichelson interferometer. Infrared light at843 nm is divided at a coupler into refer-ence and sample paths. Light retroreflect-ed from a variable reference delay is com-bined in the coupler with the lightbackscattered from the subject’s eye. Aphotodiode detects temporal informationfrom the interference signal, which is thenprocessed, and a longitudinal profile simi-lar to an ultrasound A-scan is obtained.3
Different layers of the posterior pole of theeye reflect and scatter light in differentways, yielding both longitudinal and later-al spatial information as well as informa-tion on reflectivity. Cross-sectional imagesare built from a sequence of single longi-tudinal reflectivity profiles obtained byscanning the probe beam across the retina.Today’s commercial scanners acquire 100longitudinal A-scans in 1-2.5 sec.3,4
Imaging the normal retinaLight at 843 nm is minimally absorbed bythe vitreous and anterior structures in thevisual pathway, thus allowing the signalenergy necessary to reach the layers of theretina (Fig. 2). OCT is useful for findingabnormalities within these layers, whichhave contrasting structure and reflectivity.Higher reflectivity appears to correlatewith horizontally oriented layers, such asthe nerve-fiber layer and the plexiformlayers. Lower reflectivity correlates withnuclei and vertical structures, such as pho-toreceptors.5
Scientists’ ability to analyze OCT im-ages is causing a major shift in our under-standing of the interaction, in retinal dis-
Figure 2. (a) Commercial retinal OCT imager, with artist’s rendition of its function. (b)Retinal layers as seen in histopathology correlate with the higher and lower reflectivelayers on (c) the corresponding OCT image [From Ref.5]. (d) Conventional ophthalmicappearance of a normal macula and (e) an OCT scan passing through the fovea.
ease, of the vitreous gel, the retina, and thesubretinal tissue. Next we will describeseveral applications of OCT in the vitre-ous, the retina, and the subretinal space.
Imaging vitreoretinal disordersIn the normal aging eye, the vitreous bodyliquifies and may eventually separate fromthe retina. This posterior vitreous separa-tion may be incomplete, creating sites ofvitreoretinal adhesion. OCT has recentlybeen used to demonstrate the normal evo-lution of vitreous separation in the poste-rior pole.6 With OCT, researchers havealso identified vitreous adhesions and therole they play in the development of mac-ular diseases such as macular hole, cystoidmacular edema, and diabetic retinopathy.7
Prior to OCT, it was thought that macularholes evolved secondary to tangential trac-tion along the retinal surface. The adventof OCT has allowed ophthalmologists torecognize the more important action ofanteroposterior forces.8
It can be difficult to differentiate small,round, central foveal lesions, such as mac-
ular cysts, full-thickness macular holes,and partial-thickness macular holes. Dif-ferentiation is important, since the treat-ments for these lesions differ. Imaging incross section clearly shows the differencebetween the lesions. OCT imaging has alsobeen useful in objectively demonstratinghole closure postoperatively.9
Cystoid macular edema (CME), thethickening of the retina with fluid-filledcysts, can be the end result of many differ-ent eye diseases—diabetic retinopathy, in-flammatory disease, or macular degenera-tion. The thickening can result either fromleakage of fluid from abnormal blood ves-sels or from traction by the vitreous gel.
Subtle degrees of CME are difficult todiagnose clinically: fluorescein angiogra-phy is often used to look for leaking bloodvessels and fluorescein dye pooled in thecysts [see Fig. 4(a)]. When CME is causedby structural, nonvascular factors, OCTcan show both the structure and the loca-tion of intraretinal cysts, thus allowingdoctors to diagnose specific cases of ede-ma.10 One disadvantage of OCT is that it
does not show leaking blood vessels; fluo-rescein angiography does.
OCT can show the height of retinalthickening [extrapolated to estimate vol-ume, see Fig. 4(b)]. It can also be used tomonitor the volume of edema, and thusthe effectiveness of treatment. Severalstudies have found that the decrease incentral vision is proportionate to the ex-tent of macular thickening.11,12
The use of OCT has helped identifyCME in a higher number of cases of oth-erwise unexplained vision loss by identify-ing nonvascular, structural causes. Fluo-rescein angiography still has a role, howev-er, in identifying leaking vasculature inthis disease, as well as in treatment. Man-agement of many cases of CME may re-quire assessment using both OCT and flu-orescein angiography.
Age-related macular degeneration(AMD) is the leading cause of legal blind-ness in individuals 65 years of age or olderin western societies. Many treatmentmodalities are being tried, with differentrates of success. In the wet or neovascularsubgroup, most treatment is directed atsubretinal neovascularization, the cause ofthe majority of serious vision loss in thesepatients.
Fluorescein angiography has been themainstay in the diagnosis of neovascularAMD. Some aspects of this disease, how-ever, can only be shown using OCT imag-ing. In particular, doctors have foundOCT useful in assessing:
• the state of the vitreoretinal interfaceand sites of attachment to the macula;
• intraretinal pathology in terms ofthickness and the presence of intrareti-nal cysts;
• the subretinal space for neovasculariza-tion, geographical atrophy, and thepresence of blood or fluid.
We have recently documented in-traretinal morphology associated withneovascular AMD. In a study of 61 pa-tients with AMD, retinal edema associatedwith loss of vision was present in 46% ofpatients with subfoveal neovasculariza-tion.13 Recently, we have also shown a correlation between vitreous attachment to the macula and the development oftears in the retinal pigment epithelium(RPE) over subfoveal neovascularization.14
The use of optical cross-sectional im-aging has allowed us to identify new fac-
OCT IN OPHTHALMOLOGY
50 Optics & Photonics News ■ April 2002
Figure 3. OCT in macular holes and cysts. (a) Color fundus photograph of a full-thicknessmacular hole. (b) OCT imaging through the fovea of the same patient showing evidence oftangential traction. (c) Color fundus photograph of a macular cyst. (d) OCT scan throughthe fovea demonstrating the outline of the cyst.
(a)
(b)
(c)
(d)
tors causing vision loss in patients withAMD. These findings may one day lead tonew treatments for this serious disease.
In summary, OCT imaging of the reti-na marks a shift from our traditional viewof macular disease to improved cross-sec-tional documentation of pathology in-volving the posterior vitreous, retina, andsubretinal structures. OCT also has im-proved our understanding of the causes ofmacular diseases. Yet the research is still ata relatively early stage and there is muchground left to cover.
The first commercial unit, released in1996, is still in use, despite its limitations:if the subject does not remain immobilefor 1-2.5 sec, motion artifacts can be gen-erated during image acquisition; reflec-tions from microstructures of importance,such as the RPE, cannot be identified atcurrent resolution levels of 10-15 �m.
Researchers are striving to develop sys-tems with higher resolution as well asfaster image-acquisition time. These arejust two of the many opportunities beingpursued to expand on the informationavailable from this optical technology.
AcknowledgementsThis work was supported by NIH grant7R24EY13015. The authors thank GregoryHoffmeyer and Ellen Styers for help withthe OCT and fundus photos, Katrina Win-ter and Mark Cahill for help with manu-script preparation, and Robert Machemerfor the ophthalmoscope image.
The references to this article appear on p. 60,OPN's reference page.
Hazem Rashed is a research fellow in the Departmentof Ophthalmology, Joseph Izatt is an associate profes-sor of biomedical engineering, and Cynthia Toth is anassociate professor in ophthalmology and biomedicalengineering at Duke University.
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April 2002 ■ Optics & Photonics News 51
Figure 4. OCT in cystoid macular edema (CME). (a) Fluorescein angiography demonstratesvascular leakage and dye in cysts. (b) Composite analysis of multiple OCT images quantifiesretinal thickness, (c) individual, cross-sectional OCT scan shows detailed structure of cysts.
Figure 5. OCT in age-related maculardegeneration (AMD). (a) Color fundusphotograph of subretinal neovascularmembrane in AMD. (b) Fluorescein an-giography demonstrates vascular sub-retinal changes. OCT imaging shows(arrow in c) vitreous changes, (arrow in d) retinal changes and (arrow headsin c & d) subretinal pathology.
