Optical coherence tomography of the anterior segment of [605311]

Optical coherence tomography of the anterior segment of
the eye
David Huang, MD, PhD *, Yan Li, MS, Sunita Radhakrishnan, MD
Cole Eye Institute, The Cleveland Clinic, Department of Neurosciences NC3, 9500 Euclid Avenue, I20,
Cleveland, OH 44195, USA
Optical coherence tomography (OCT) [1]is a
novel cross-sectional and three-dimensional imagingmodality that uses low-coherence interferometry to
achieve axial (depth) resolutions in the range of 3 to
20mm. OCT has several theoretical advantages
when compared with current imaging modalities forimaging the anterior segment of the eye. Unlike
ultrasound, OCT employs light; therefore, it does
not require fluid immersion or probe contact. Further-more, OCT has a spatial resolution that easily sur-
passes that of even ultrahigh-frequency ultrasound
[2–9] . Although confocal scanning microscopy
[10–15] can obtain even higher resolution than
OCT, it requires short focal distances and can image
only a small area of the eye at a time. OCT usesinterferometry for depth resolution; therefore, it can
have a long working distance and a wide field of
transverse scanning. Slit illumination imaging, suchas Scheimpflug photography [16] or the Orbscan
system [17–21] (Bausch & Lomb, Rochester, New
York), can also provide cross-sectional images, but
accurate biometry is difficult. The angles between theslit illumination, subject anatomic surfaces, and im-
aging axis require complex computations for anatom-
ic reconstruction and measurements. OCT detectsretroreflected light and is more amenable to simple
interpretation and accurate measurements.
The primary limitations of OCT imaging of the
anterior segment are speed and penetration. Commer-cial retinal scanners (Carl Zeiss Meditec, Dublin,
California) have a scanning speed of 100 to 400 axial
scans per second. Each axial scan contributes a ver-tical line to the OCT image. A corneal image pro-
duced by the Zeiss OCT 1 system (Fig. 1) has visible
motion artifacts because the image is acquired over
1 second. It also has coarse pixel grain because it
contains only 100 vertical lines. The 0.8- mm wave-
length employed for retinal scanning is close tovisible wavelengths and cannot directly visualize
angle structures owing to scattering loss through the
limbus [22]. A widely useful anterior segment OCT
system would need to overcome both limitations.
This article presents the results using a high-speed
OCT prototype developed collaboratively betweenProfessor Joseph Izatt (Duke University), Professor
Andrew Rollins (Case University), and the authors at
the Cleveland Clinic Foundation. The system has ascan rate of 4000 lines per second, which is fast
enough for biometric applications. It uses a longer
wavelength of 1.3 mm, which decreases scattering
through turbid tissues and allows visualization ofangle structures [23]. The system is useful in a range
of clinical applications from laser-assisted in situ
keratomileusis (LASIK) surgery to narrow angleglaucoma. OCT of the anterior segment is still in its
infancy; therefore, it is discussed at the end of this
article in a section on future prospects.
Background
The precursor technology of OCT [1], optical
coherence domain reflectometry (OCDR), had its
earliest demonstration in biomedical applicationswith the measurement of corneal thickness [24].
OCDR is an optical ranging technique, or a method
for measuring the distance between the measurement
0896-1549/04/$ – see front matter D2004 Elsevier Inc. All rights reserved.
doi:10.1016/S0896-1549(03)00103-2* Corresponding author.
E-mail address: huangd@ccf.org (D. Huang).Ophthalmol Clin N Am 17 (2004) 1–6

system and a target. In OCDR, an optical probe beam
is directed toward a target sample, and the reflectedlight is recombined with a reference reflection in an
interferometer. Interference occurs when the two
reflections are mutually coherent. Because OCDRuses light with a short coherence length, coherenceoccurs only when the reference and sample reflections
are closely matched in propagation delay. By scan-
ning the delay of the reference reflection and record-ing the resulting fluctuation in interference signal, the
OCDR system resolves the amplitudes of sample
reflections as a function of depth (axial delay). OCTis based on OCDR, with the addition of transverse
scanning of the probe beam to provide at least an-
other spatial dimension for imaging.
Izatt et al published the first report of OCT for
corneal and anterior segment imaging in 1994 [22].
After that report, little attention was paid to ante-rior segment applications until the Lubeck groupdescribed OCT imaging of laser thermokeratoplasty
lesions in 1997 [25,26] , and Maldonado et al [27–29]
reported imaging of the LASIK flap in 1998. Sincethen, the rapid popularization of corneal refractive
surgery has spurred investigators to apply OCT to
corneal imaging and to refine the instrumentationfor anterior segment OCT.
In most published reports of anterior segment
OCT applications, the commercial retinal OCT scan-ner has been used [27–44] . Although visualization of
corneal surgical anatomy and thickness measurements
are possible, the imaging speed, penetration, and field
of view are very limited with the retinal scanner.
Ocular imaging with the 1.3- mm wavelength was
first reported by Radhakrishnan et al using a system
developed by Izatt’s group [23]. The Izatt system
takes full advantage of the higher power that can beused safely at the longer wavelength to achieve a
high acquisition rate of 4000 axial scans per second.This high-speed OCT engine has been used in several
anterior segment OCT scanners to generate the clini-
cal results discussed herein.
High-speed corneal and anterior segment optical
coherence tomography at 1.3- Mm wavelength
Using a longer wavelength of 1.3 mm for corneal
and anterior segment (CAS) OCT provides importantadvantages when compared with the 0.8- mm wave-
length commonly used for retinal imaging. Because
scattering loss is much lower at the longer wave-length, 1.3- mm OCT can penetrate the limbus and
sclera to provide a view of the angle. The absorption
by water is also much stronger at 1.3 mm (9.3-mm
absorption length) [45]. For an eye of average length,
91% of 1.3- mm light that falls on the cornea will be
absorbed by the ocular media, leaving only 9% toreach the retina. This absorption allows the use ofmuch higher optical power without damaging the
retina. The permissible exposure level at the 1.3- mm
wavelength is 15 mW according to the current stan-dard set by the American Laser Institute and the
American National Standards Institute (ANSI 2000)
[46]. This level is 20 times higher than the 0.7-mW
limit at the 0.8- mm wavelength [46]. As a result,
CAS OCT can use much higher power and achieve
much higher scan rates. The authors developed sev-eral CAS OCT systems using a high-speed OCT en-gine (4000 A-scans per second) with a 1.3- mm super
luminescent diode (SLD) light source.
The final version of the CAS OCT scanner was
mounted on a slit lamp base and used a charge couple
device (CCD) camera to visualize the scan area in real
time. The scan geometry was telecentric (rectangular),with adjustable scan widths of 4 to 15 mm and scan
depths of 3.25 or 6 mm. Eight image frames were
acquired and displayed per second in real time, eachwith 500 axial scans. The axial resolution was 14 mm
full-width-half-maximum in cornea. The main advan-
tage of the telecentric system was its wide fieldcapability, which was essential for corneal and ante-rior chamber studies. This system was used for all of
the studies described herein except for the initial angle
assessment study.
Laser-assisted in situ keratomileusis anatomy
The 1.3- mm wide-field CAS OCT system was
used to examine post-LASIK eyes (Fig. 2) . The scan
dimensions are 12 mm wide and 3.25 mm deep
Fig. 1. OCT of the cornea with 6.5-mm scan width
performed with the Zeiss OCT 1 system. The image hasnot been corrected for aspect ratio and the divergent beamscan path; therefore, the thickness and corneal curvature
are exaggerated.D. Huang et al / Ophthalmol Clin N Am 17 (2004) 1–6 2

(in air). When compared with the corneal image
(seeFig. 1 ) obtained with a 0.8- mm wavelength retinal
scanner, there are several improvements. There is noapparent motion artifact at the higher image acquisi-
tion rate of eight frames per second. The image detail
is much finer with 500 axial scans per frame com-pared with 100 axial scans per frame. The telecentric
design allows the capture of corneal details over a
much wider scan width.
Many useful anatomic features relevant to LASIK
surgery can be identified in the image (Fig. 2) . The
anterior surface reflection is strong at the perpen-
dicular incidence and produces a vertical flare thatdefines the corneal apex. Finer features, such as the
epithelial–Bowman and the flap lamellar boundaries,
are best visualized with a slight off-normal beamincidence angle in the midperiphery. The flap internal
reflectivity is stronger than that of the posterior
stroma. The thickness of the cornea, flap, and poste-rior stromal bed can be measured accurately from
the tomograph.
Angle assessment
Gonioscopy is the gold standard for evaluating the
anterior chamber angle; however, it is highly subjec-
tive and requires specialized training. Cross-sectionalimaging of the anterior chamber angle with ultra-
sound biomicroscopy or OCT is easier to interpret.
Furthermore, objective quantification of the angle canbe obtained from a cross section. Ultrasound biomi-
croscopy [47] and Scheimpflug photography [48]
have been used for quantitative angle evaluation.OCT can provide the same detailed angle anatomywith the added advantage of being noncontact and
easy to perform.
A 1.3- mm high-speed CAS OCT system was used
to assess the angle width. Computer image processing
was performed to obtain correctly dimensioned
images, with adjustments for the scan geometry andrefraction of the OCT beam at the anterior eye sur-
face. Images of an open angle and an occludable an-
gle are shown in Figs. 3 and 4 , respectively. Corneal,
scleral, and iris anatomy are visualized in detail.
Features in the limbus and angle are clearly shown,including the scleral spur, ciliary body band, angle
recess, and iris root. For angle measurements, it is
particularly useful that the scleral spur is highlyreflective and easily identified on OCT.
A clinical study was performed to compare OCT
and ultrasound biomicroscopy angle parameters withgonioscopic grading by glaucoma specialists. A total
of 31 eyes in 28 subjects were examined. Eight eyes
were judged to be occludable on gonioscopy. Sub-jects underwent OCT and ultrasound biomicroscopyimaging of the nasal and temporal anterior chamber
angles. OCT and ultrasound biomicroscopy had ex-
cellent correlation with gonioscopy in terms of theidentification of occludable angles. The best OCT
parameters were slightly better than ultrasound bio-
microscopy parameters, with 100% sensitivity and95.7% specificity for detecting gonioscopically oc-
cludable angles.
Anterior chamber width and other biometric
parameters
Optical coherence tomography is well suited for
ocular biometry owing to its high image resolution.When compared with ultrasound, the noncontact
nature of OCT eliminates discomfort and distortion
from probe contact or immersion. The authors’ high-speed wide-field OCT prototype was able to produce
detailed images of the entire anterior chamber without
any visible motion artifact (Fig. 5) . This characteristic
Fig. 2. OCT of an eye 1 day after LASIK surgery.
Fig. 3. High-speed 1.3- mm wavelength OCTof an open angle.D. Huang et al / Ophthalmol Clin N Am 17 (2004) 1–6 3

makes the accurate measurement of anterior cham-
ber width and other biometric parameters possible.
Anterior chamber width measurement is clini-
cally important for sizing angle-supported anterior
chamber intraocular lenses. With the increasing useof refractive phakic intraocular lenses, accurate sizing
becomes an important issue. An intraocular lens that
is too large can press on the iris root and produce pupilovalization; an intraocular lens that is too small can
lead to lens movement, decentration, corneal endo-
thelial damage, and iritis [49]. The traditional method
for sizing uses the external corneal diameter, whichis assumed to correspond to the internal anterior
chamber width. Typically, the intraocular lens length
is chosen to be the corneal diameter plus a constantsuch as 1 mm.
When the wide-field CAS OCT system was used,
it was possible to measure the internal width of theanterior chamber directly (Fig. 5) . Anterior chamber
width as measured by OCT was compared with
corneal diameter measured by a Holladay corneagauge in 20 normal subjects. The anterior chamber
width was 12.53 F0.47 mm (mean FSD). The
difference of the anterior chamber width from thecorneal diameter was 0.75 F0.44 mm with a rangeof 1.84 mm. The improvement of the SD from 0.47
to 0.44 mm was minimal and showed that intraocularlens sizing using the corneal diameter would be only
marginally better than using the same size for all eyes.
OCT can improve the accuracy of intraocular lenssizing several fold. The reproducibility of anterior
chamber width measurements from OCT images was
assessed by an analysis of variance. The variation ofanterior chamber width between images was small(SD = 0.10 mm), but disagreement between the three
human graders was larger (SD = 0.29 mm). The
authors are developing an automated anterior cham-ber width measurement software that will remove
the need for a human grader to place cursors at the
angle recesses. Anterior chamber depth and the crys-talline lens vault were also measured from the OCT
images with high reproducibility.
Optical coherence tomography appears to be a
reproducible, convenient, and noncontact technique
to perform biometry of anterior chamber dimen-
sions. Further studies are needed to determine whetherit can contribute to a reduction of complicationsthrough better fitting of intraocular lenses for the
anterior chamber.
Future developments
Optical coherence topography is a versatile tool
for visualization and measurement of corneal and an-terior segment anatomy. It has the potential for im-proving the functions currently served by Placido-ring
corneal topography, slit-scanning corneal topography,
ultrasound imaging, and ultrasound pachymetry.
Keratorefractive surgery, anterior chamber bio-
metry, and angle assessment are some of the appli-
cations that should benefit from CAS OCT. Thecommercialization and general availability of this
technology should increase applications through the
ingenuity of many practitioners.
Fig. 5. Anterior chamber (AC) imaged with the wide-field (15-mm) setting on the slit lamp–mounted high-speed CAS OCT
system. The AC width is measured between angle recesses; its depth is measured from the corneal apex to lens apex.
Fig. 4. High-speed 1.3- mm wavelength OCT of an occlud-
able angle.D. Huang et al / Ophthalmol Clin N Am 17 (2004) 1–6 4

References
[1] Huang D, Swanson EA, Lin CP, et al. Optical coher-
ence tomography. Science 1991;254(5035):1178–81.
[2] Allemann N, Chamon W, Silverman RH, et al. High-
frequency ultrasound quantitative analyses of corneal
scarring following excimer laser keratectomy. ArchOphthalmol 1993;111(7):968–73.
[3] Pavlin CJ, Easterbrook M, Harasiewicz K, Foster FS.
An ultrasound biomicroscopic analysis of angle-closure
glaucoma secondary to ciliochoroidal effusion in IgAnephropathy. Am J Ophthalmol 1993;116(3):341–5.
[4] Reinstein DZ, Silverman RH, Coleman DJ. High-fre-
quency ultrasound measurement of the thickness ofthe corneal epithelium. Refract Corneal Surg 1993;9(5):385–7.
[5] Reinstein DZ, Silverman RH, Trokel SL, Allemann N,
Coleman DJ. High-frequency ultrasound digital signalprocessing for biometry of the cornea in planningphototherapeutic keratectomy [letter] [published erra-
tum appears in Arch Ophthalmol 1993 Jul;111(7):926].
Arch Ophthalmol 1993;111(4):430–1.
[6] Reinstein DZ, Silverman RH, Trokel SL, Coleman DJ.
Corneal pachymetric topography. Ophthalmology
1994;101(3):432–8.
[7] Reinstein DZ, Silverman RH, Rondeau MJ, Coleman
DJ. Epithelial and corneal thickness measurements by
high-frequency ultrasound digital signal processing.
Ophthalmology 1994;101(1):140–6.
[8] Riley SF, Nairn JP, Maestre FA, Smith TJ. Analysis
of the anterior chamber angle by gonioscopy and by
ultrasound biomicroscopy. Int Ophthalmol Clin 1994;
34(3):271–82.
[9] Reinstein DZ, Silverman RH, Sutton HF, Coleman
DJ. Very high-frequency ultrasound corneal analysis
identifies anatomic correlates of optical complica-
tions of lamellar refractive surgery: anatomic diagno-sis in lamellar surgery. Ophthalmology 1999;106(3):
474–82.
[10] Jalbert I, Stapleton F, Papas E, Sweeney DF, Coroneo
M. In vivo confocal microscopy of the human cornea.Br J Ophthalmol 2003;87(2):225–36.
[11] Bauer NJ, Wicksted JP, Jongsma FH, March WF, Hen-
drikse F, Motamedi M. Noninvasive assessment ofthe hydration gradient across the cornea using confo-cal Raman spectroscopy. Invest Ophthalmol Vis Sci
1998;39(5):831–5.
[12] Lemp MA, Dilly PN, Boyde A. Tandem-scanning
(confocal) microscopy of the full-thickness cornea.
Cornea 1985;4(4):205–9.
[13] Masters BR, Farmer MA. Three-dimensional confocal
microscopy and visualization of the in situ cornea.Comput Med Imaging Graph 1993;17(3):211–9.
[14] Masters BR, Paddock S. In vitro confocal imaging of
the rabbit cornea. J Microsc 1990;158(Pt 2):267–74.
[15] Ichijima H, Petroll WM, Jester JV , Cavanagh HD.
Confocal microscopic studies of living rabbit cornea
treated with benzalkonium chloride. Cornea 1992;
11(3):221–5.[16] Boker T, Sheqem J, Rauwolf M, Wegener A. Ante-
rior chamber angle biometry: a comparison of Scheim-pflug photography and ultrasound biomicroscopy.
Ophthalmic Res 1995;27(Suppl 1):104–9.
[17] Yaylali V, Kaufman SC, Thompson HW. Corneal
thickness measurements with the Orbscan Topog-raphy System and ultrasonic pachymetry. J Cataract
Refract Surg 1997;23(9):1345–50.
[18] Lattimore Jr MR, Kaupp S, Schallhorn S, Lewis RT.
Orbscan pachymetry: implications of a repeated mea-
sures and diurnal variation analysis. Ophthalmology
1999;106(5):977–81.
[19] Auffarth GU, Tetz MR, Biazid Y, V olcker HE. Measur-
ing anterior chamber depth with Orbscan Topography
System. J Cataract Refract Surg 1997;23(9):1351–5.
[20] Boscia F, La Tegola MG, Alessio G, Sborgia C. Accu-
racy of Orbscan optical pachymetry in corneas withhaze. J Cataract Refract Surg 2002;28(2):253–8.
[21] Cairns G, McGhee CN, Collins MJ, Owens H, Gamble
GD. Accuracy of orbscan II slit-scanning elevation to-pography. J Cataract Refract Surg 2002;28(12):2181–7.
[22] Izatt JA, Hee MR, Swanson EA, et al. Micrometer-
scale resolution imaging of the anterior eye in vivowith optical coherence tomography. Arch Ophthalmol1994;112(12):1584–9.
[23] Radhakrishnan S, Rollins AM, Roth JE, et al. Real-time
optical coherence tomography of the anterior segmentat 1310 nm. Arch Ophthalmol 2001;119(8):1179–85.
[24] Huang D, Wang J, Lin CP, Puliafito CA, Fujimoto JG.
Micron-resolution ranging of cornea anterior chamber
by optical reflectometry. Lasers Surg Med 1991;11(5):419–25.
[25] Koop N, Brinkmann R, Lankenau E, Flache S, Engel-
hardt R, Birngruber R. [Optical coherence tomography
of the cornea and the anterior eye segment]. Ophthal-mologe 1997;94(7):481–6.
[26] Asiyo-V ogel MN, Koop N, Brinkmann R, et al. [Imag-
ing of laser thermokeratoplasty lesions by optical lowcoherence tomography and polarization microscopyafter Sirius Red staining]. Ophthalmologe 1997;94(7):
487–91.
[27] Maldonado MJ. Undersurface ablation of the flap for
laser in situ keratomileusis retreatment. Ophthalmol-ogy 2002;109(8):1453–64.
[28] Maldonado MJ, Munuera JM, Garcia-Layana A,
Moreno J, Aliseda D. Optical coherence tomography(OCT) evaluation of the corneal cap and stromal bed
features after LASIK for high myopia. Presented at the
American Academy of Ophthalmology Annual Meet-ing. New Orleans, November 8–11, 1998.
[29] Maldonado MJ, Ruiz-Oblitas L, Munuera JM, Aliseda
D, Garcia-Layana A, Moreno-Montanes J. Optical
coherence tomography evaluation of the corneal capand stromal bed features after laser in situ kerato-mileusis for high myopia and astigmatism [In Pro-
cess Citation]. Ophthalmology 2000;107(1):81 –7
[discussion: 88].
[30] Muscat S, McKay N, Parks S, Kemp E, Keating D.
Repeatability and reproducibility of corneal thicknessD. Huang et al / Ophthalmol Clin N Am 17 (2004) 1–6 5

measurements by optical coherence tomography. In-
vest Ophthalmol Vis Sci 2002;43(6):1791–5.
[31] Neubauer AS, Priglinger SG, Thiel MJ, May CA,
Welge-Lussen UC. Sterile structural imaging of donor
cornea by optical coherence tomography. Cornea 2002;21(5):490–4.
[32] Nozaki M, Kimura H, Kojima M, Ogura Y. Optical
coherence tomographic findings of the anterior seg-
ment after nonpenetrating deep sclerectomy. Am JOphthalmol 2002;133(6):837–9.
[33] Priglinger SG, Neubauer AS, May CA, et al. Optical
coherence tomography for the detection of laser in situkeratomileusis in donor corneas. Cornea 2003;22(1):46–50.
[34] Toth CA, Chiu EK, Winter KP, et al. In-vivo response
to free electron laser incision of the rabbit cornea. La-sers Surg Med 2001;29(1):44–52.
[35] Ucakhan OO, Tello C, Liebmann JM, Ritch R, Asbell
PA. Optical coherence tomography of Intacs. J Cataract
Refract Surg 2001;27(10):1535.
[36] Ustundag C, Bahcecioglu H, Ozdamar A, Aras C, Yil-
dirim R, Ozkan S. Optical coherence tomography for
evaluation of anatomical changes in the cornea afterlaser in situ keratomileusis. J Cataract Refract Surg2000;26(10):1458–62.
[37] Wang J, Fonn D, Simpson TL, Jones L. Relation be-
tween optical coherence tomography and optical pa-chymetry measurements of corneal swelling inducedby hypoxia. Am J Ophthalmol 2002;134(1):93–8.
[38] Wang J, Fonn D, Simpson TL, Jones L. The measure-
ment of corneal epithelial thickness in response tohypoxia using optical coherence tomography. Am JOphthalmol 2002;133(3):315–9.
[39] Wong AC, Wong CC, Yuen NS, Hui SP. Correlational
study of central corneal thickness measurements onHong Kong Chinese using optical coherence tomogra-
phy, Orbscan and ultrasound pachymetry. Eye 2002;
16(6):715–21.[40] Bagayev SN, Gelikonov VM, Gelikonov GV, et al.
Optical coherence tomography for in situ monitoringof laser corneal ablation. J Biomed Opt 2002;7(4):
633–42.
[41] Bechmann M, Thiel MJ, Neubauer AS, et al. Central
corneal thickness measurement with a retinal opticalcoherence tomography device versus standard ultra-
sonic pachymetry. Cornea 2001;20(1):50–4.
[42] Feng Y , Varikooty J, Simpson TL. Diurnal variation of
corneal and corneal epithelial thickness measured
using optical coherence tomography. Cornea 2001;
20(5):480–3.
[43] Hirano K, Ito Y , Suzuki T, Kojima T, Kachi S, Miyake
Y. Optical coherence tomography for the noninvasive
evaluation of the cornea. Cornea 2001;20(3):281–9.
[44] Hirano K, Kojima T, Nakamura M, Hotta Y. Triple
anterior chamber after full-thickness lamellar ke-ratoplasty for lattice corneal dystrophy. Cornea 2001;
20(5):530–3.
[45] van den Berg TJ, Spekreijse H. Near infrared light
absorption in the human eye media. Vision Res 1997;
37(2):249–53.
[46] Laser Institute of America. American National Stand-
ard for Safe Use of Lasers. Orlando: Laser Institute ofAmerica, American National Standards Institute, Inc.;
2000 [ANSI Z136. 1-2000].
[47] Pavlin CJ, Harasiewicz K, Sherar MD, Foster FS.
Clinical use of ultrasound biomicroscopy. Ophthal-mology 1991;98(3):287–95.
[48] Chen HB, Kashiwagi K, Yamabayashi S, Kinoshita T,
Ou B, Tsukahara S. Anterior chamber angle biometry:quadrant variation, age change and sex difference.Curr Eye Res 1998;17(2):120–4.
[49] Saragoussi JJ, Othenin-Girard P, Pouliquen YJ. Ocular
damage after implantation of oversized minus poweranterior chamber intraocular lenses in myopic phakic
eyes: case reports. Refract Corneal Surg 1993;9(2):
105–9.D. Huang et al / Ophthalmol Clin N Am 17 (2004) 1–6 6