clinical applications of corneal optical coherence … · clinical applications of corneal optical...

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Clinical Applications of Corneal Optical Coherence

Frontiers in Optics/Laser Science XXVIIIRochester, NY, Oct 14-18, 2012

Corneal Optical Coherence Tomography

David Huang, MD, PhDWeeks Professor of Ophthalmic Research

Professor of Ophthalmology & Biomedical Engineering

Casey Eye Institute, Oregon Health & Science University

Portland, Oregon

Financial Interests:Dr. D. Huang has a significiant financial interest in Optovue, a company that may have a commercial interest in the results of this research and technology. This potential individual conflict of interest has been reviewed and managed by OHSU.Optovue, Inc.: stock options, patent royalty, grants, speaker honorarium & travel supportCarl Zeiss Meditec, Inc.: patent royalty

New OCT Technology Lead to An Explosion of New Products for Anterior Segment Imaging

Zeiss Cirrus Optovue RTVue

Bioptigen Envisu

Zeiss Visante Optovue iVue

Heidelberg Spectralis

Optopol Copernicus

Heidelberg SL-OCT

Tomey CASIA

David Huang, MD, PhD www.COOLLab.net

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Anterior Segment OCT Systems

Dedicated systems scan wider (12-16 mm)

Systems converted from retinal scanners have

and deeper (6-7 mm)

Zeiss Visante

Heidelberg SL-OCT

Tomey CASIA

limited scan ranges (~6mm width & 2mm depth)

Optovue RTVue

Optovue iVue

Zeiss Cirrus

H id lb S t li Heidelberg Spectralis

Bioptigen Envisu

Optopol Copernicus


Wavelength Matters

1310 nm gives deeper penetration.

830 nm systems have higher axial resolution.

(Axial resolution: 17-18 µm)

Zeiss Visante

Heidelberg SL-OCT

Tomey CASIA

(Axial resolution: 3-5 µm)

Optovue RTVue

Optovue iVue

Zeiss Cirrus

Heidelberg Spectralis

Bioptigen Envisu Bioptigen Envisu

Optopol Copernicus


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Better penetration at 1310 nm Greater resolution achieved w/ 830 nm systems

830 nm1310 nm

Schwalbe’s line

Scleral spur

Epithelium

Endothelium

Angle recess


Visante TD-OCT RTVue FD-OCT

Fourier vs. Time Domain

Time domain systems are slower

Fourier domain systems are much faster

Zeiss Visante (2 kHz)

Heidelberg SL-OCT (200 Hz)

Optovue RTVue (26 kHz)

Optovue iVue (26 kHz)

Zeiss Cirrus (27 kHz)

Heidelberg Spectralis (40 kHz)

Bi ti E i (17 kH ) Bioptigen Envisu (17 kHz)

Optopol Copernicus (20 kHz)

Tomey CASIA (30 kHz)


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Clinical Applications of Corneal OCT

Keratoconus DetectionLASIK planning FS Laser AK

Guiding PTK IOL Power Calculation Intacs


Keratoconus Diagnosis with OCT

Bing Qin, MD, PhD

Yan Li, PhD


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Forme fruste keratoconus is the most important risk factor for post-LASIK corneal ectasiaBinder P, Analysis of ectasia after LASIK: risk factors, J Cat Refract Surg 33:1530, 2007

T h N l S i i Ab l T t l

Topography does not screen out all eyes at risk

Randleman JB et al. Risk assessment for ectasia after corneal refractive surgery. Ophthalmol 2007; 115:37-50

Topography Normal Suspicious Abnormal Total

# Ectasia Cases

25 27 33 93

Percent 27% 29% 41% 100%

OCT could provide more accurately map corneal thickness, epithelial thickness, and corneal cuvatures

1.5mm 1.5mm

Rp Ra

Dn0 = 1

n1 = 1.376

n2 = 1.336

aa R

nnK 01

pp R

nnK 12


RTVue (Optovue, Inc.)

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Corneal Mapping over 8 Meridians(8 x 1019 A-scans) in 0.31 Second

RTVue FD-OCT(Optovue, Inc.)


Detecting Keratoconic Thinning with OCT Pachymetric Indices

General thinning Min Min

Focal thinning Minimum - median

Asymmetric thinning I-S IT-SN

Minimum = 404 µmY = -710 µm

Y location of the Minµ

Li Y, Meisler M, Tang M, Lu A, Thakrar V, Reiser B, Huang D. Keratoconus diagnosis with optical coherence tomography pachymetry mapping. Ophthalmology 2008;115:2159-2166.

Visante Prototype (Carl Zeiss Meditec, Inc.)

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OCT Keratoconus Pachymetric VariablesParameter Explanation Keratoconus Cutoff

(1 percentile)IT-SN Average thickness of the IT octant minus that of the SN

octant< -51 μm

I-S Average thickness of the inferior (I) octant minus that of the superior (S) octant

< -49 μm

Min Minimum corneal thickness < 455 μm

Min - Med Minimum corneal thickness-median corneal thickness <-29 μm

Y Min Y coordinate of minimum corneal thickness Y < -1.35 mm

Based on 66 normal and 52 keratoconus subjects from the

Yan Li, PhD; David Huang, MD, PhD www.COOLLab.net

Based on 66 normal and 52 keratoconus subjects from the following:

David Huang, MD, PhD, Doheny Eye Institute, Los AngelesQinmei Wang, MD, Wenzhou Medical College, WenzhouRobert Brass, MD, Brass Eye Center, New York

RTVue FD-OCT (Optovue, Inc.)

OCT pachymetry map-based keratoconus score table

0 1 2 3 OD OS

Minimum >499 499 ~ 476 475 ~ 455 <455Minimum 499 499 476 475 455 455

Minimum- Median >-21 -22 ~ -25 -26 ~ -29 <-29

I-S >-30 -30~-40 -41~-49 <-49

IT-SN >-33 -33~42 -43~-51 <-51

Y location of the min >-734 -734 ~ -1069 -1070 ~ -1353 <-1353

Sum

mat

ion

Keratoconus Risk Score

Each variable will be assigned a score of 1, 2, 3 if it exceeds 20, 5, 1 percentile thresholds.The keratoconus risk score of the eye is the summation of all scores.

Keratoconus risk score = 0~1: low risk; 2~3: moderate risk; ≥4: high risk.


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Histogram of the Keratoconus Score

80

90 Diagnostic criterion:Keratoconus score ≥ 4

20

30

40

50

60

70

80

Normal

Keratokonus

Num

bero

f Eye

s

Sensitivity = 86% Specificity = 94%

AROC = 0.951

0

10

0 1 2 3 >=4


Epithelial Thinning Over Cone

Epithelial Thickness Pachymetry Axial Power

58 µm47 µm

Epithelial mapping software pending FDA Approval

58 µm47 µm


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Epithelial Thickness Map by FD-OCT

Magnified corneal OCT image Epithelial thickness map

Central

D=2 5 mm

Superior

Inferior

2 group of subjects: normal and keratoconus Exclusion criteria: eyes with late keratoconic

changes such as scar or hydrops

D=2,5 mm


Epithelial Map Repeatability

N Central Superior Inferior

Normal 103 0.7 µm 0.8 µm 0.7 µm

Keratoconus 35 1.0 µm 1.0 µm 1.0 µm

pooled standard deviation (SD)

Li Y, Tan O, Brass R, Weiss JL, Huang D. Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography. Ophthalmology; 2012 Aug 20, Epub ahead of print.

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Average epithelial thickness maps show inferotemporal thinning

Normal

thinning over apexthinning over apex

Keratoconus


Epithelial Map Variables Minimum epithelial thickness in µm

Minimum – maximum (MIN-MAX) focal thinning in µm

Map standard deviation (MSD) in µm Map standard deviation (MSD) in µm

Pattern standard deviation (PSD)

Minimum MIN-MAX MSD PSD

Normal 45.9 ± 4.7 -8.9 ± 3.4 2.1 ± 0.7 0.031±0.008

40 0 6 0* 18 8 0* 4 2 0* 0 10 0 030*Keratoconus 40.0±6.0* -18.7±8.0* 4.7 ± 2.0* 0.105±0.030*

AROC 0.84 0.88 0.89 1.0


* Statistically significant difference was detected between normal and keratoconic eyes.AROC = area under the receiver operating characteristic curve.

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Pattern Standard Deviation (PSD) of epithelial map was highly accurate in forme fruste keratoconus (FFK) detection

Pilot study 17 FFK eyes

17 normal eyes

AROC = 1 0 for FFK detection AROC = 1.0 for FFK detection 100% sensitivity

100% specificitivity


Conclusions

OCT measures many variables that provide accurate keratoconus diagnosis Pachymetry map variables

Epithelial thickness map variables

Anterior curvature

Posterior curvature


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OCT for the LASIK surgeon

Camila Salaroli, MD

Jose Luiz B. Ramos, MD

Yan Li, PhD


Flap thickness varies from setting

138-165 µm

RS035KA, OD

IntraLase 120 µm setting 117-131 µm

RSAA, OS


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OCT Flap & Bed Thickness Measurements are Precise

1 week post-iLASIK

Position -2,5mm -1,5mm -0,5mm +0,5mm +1,5mm +2,5mm

POOLED SD (μm)

2.3 1.3 3.1 3.0 2.0 2.3

Consecutive series of 17 eyes of 10 patients, Intralase 110 m settingDavid Huang, MD, PhD www.COOLLab.net

Routinely use OCT to check flap thickness one week after LASIK and calculate statistical upper bound

Post-LASIK 1 week

• Intralase 110 µm setting (my surgeries)• OCT measurements in 21 eyesOCT measurements in 21 eyes

• Mean = 124 µm • standard deviation (SD) = 7 µm

• Upper bound = mean + 2 SD = 138 µm• < 5% of flaps will exceed this thickness


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Before enhancement, use OCT to predict residual stromal bed thickness

Residual bed thickness = 451 – 143 – 37 = 271 µm

OCT map minimumCentral flap thickness

Ablation depth

David Huang, MD, PhD www.COOLLab.net>250

Post-LASIK interface fluid & epithelial ingrowth

Epithelial ingrowth Fluid

Fibrosis

Epithelial ingrowth Fluid

Ramos JLB, Zhou S, Yo C, Tang M, Huang D, High-resolution imaging of complicated LASIK flap interface fluid syndrome. Ophthalmic Surg Lasers Imaging 2008;39:S80-2

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Planning Phototherapeutic Keratectomy

Nehal Samy, MDCatherine Cleary, MD Yan Li, PhD


Not A Candidate for PTK

Full thickness scar -> PK needed


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Nodular degeneration is peeled

Nodular scar above Bowman’s layerStromal scar peripheral

Peel and then polish using laser with masking agent


Example: Granular Corneal Dystrophy

Before PTK


UCVA: 20/80-1 BSCVA: 20/50-2MR: -2.00+2.00x100° Sim-K: 42.2/44.8@98°

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PTK SimulationAblation map

•Transepithelial PTK

6.0 mm AZ circle, 64µm

•Refractive correction

-3D+2.2Dx100°

6mmx4.5mm


Simulation software is experimental and not commercially available

Comparison of Simulated and Actual PTK Outcome en face

Before PTK

Actual OutcomeSimulated OutcomePost-PTK Slitlamp photoYan Li, PhD; David Huang, MD, PhD www.COOLLab.net

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Comparison of simulated and actual PTK outcome in cross-section

Before PTK

Simulated Outcome445 µm

531 µm505 µm

544 µm619 µm593 µm

Actual Outcome


2.5 mm2.5 mm

446 µm497 µm 519 µm

OCT ablation efficiency analysis

VISX S4 excimer laser

Laser ablation efficiency = actual ablation depth / nominal ablation setting

Central (average within 1 mm diameter): 120%

Periphery (5 mm diameter ring): 126%


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Epithelial thickness profile predicts spherical equivalent refractive change

Refractive change = -0.29 + 0.141*(PTK depth - CET) - 0.159*(CET-PET) –refractive ablation setting

CET = central epithelial thickness

PET = peripheral epithelial thicknessDavid Huang, MD, PhD www.COOLLab.net

OCT is Useful in PTK Planning

Is PTK the best option?Deep opacity > keratoplasty is needed Deep opacity -> keratoplasty is needed

Opacity above Bowman’s layer -> peel

Plan transepithelial ablation Measure opacity depth

Measure actual laser ablation depth

Calculate ablation needed to remove opacity

Measure epithelial thickness distribution

Predict refractive outcome


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Maolong Tang, PhD

Intraocular Lens Power Calculation


The problem with keratometry after laser vision correction

Measurement

Pre-LASIKExtrapolation

Post-LASIK

The extrapolation no longer works!David Huang, MD, PhD www.COOLLab.net

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OCT-based IOL Power Formula

Position Vergence (D)

Back of IOL V1 = 1000 / (AL-ELP-CCT-0.15)/n2

Front of IOL V1’ = V1 – IOL power

IOL power ECP

Back of cornea V2 = 1000/ [1/V1’ + (ELP+CCT)/n2]

Front of cornea V2’ = V2 – ECP

n2 = refractive index of vitreous and aqueous (1.336)

AL = axial eye length (mm)

ELP ff ti l iti ( )

V1 V1’ V2 V2’

ELP = 0.711 * (ACD-CCT) – 0.25 * Pp + 0.623 * ALadj + pACD – 8.11ACD = Anterior chamber depth (mm)

CCT = Central corneal thickness (mm)Pp = posterior corneal power (D)

ALadj = sqrt(AL) if AL < 24.4mm= sqrt(AL+0 8*(AL 24 4)) if AL > 24 4mmELP = effective lens position (mm)

CCT = central corneal thickness (mm)

ECP, effective corneal power (D)

= 1.0208 * net corneal power – 1.6622 (for myopic laser vision correction)2

= 1.1 * net corneal power – 5.736 (for hyperopic laser vision correction)3

1. Tang M, Li Y, Huang D. An intraocular lens power calculation formula based on optical coherence tomography: a pilot study. J Refract Surg 2010; 26:430-437 2. Tang M, Wang L, Koch DD, Li Y, Huang D, Intraocular Lens Power Calculation after Previous Myopic Laser Vision Correction Based on Corneal Power Measured by

Fourier-Domain Optical Coherence Tomography, J Cataract Refract Surg. In press.3. Tang M, Wang L, Koch DD, Li Y, Huang D, Intraocular Lens Power Calculation after Myopic and Hyperopic Laser Vision Correction Using Optical Coherence Tomography.

Saudi Journal of Ophthalmology. 2012 Feb; 26: 19-24

= sqrt(AL+0.8 (AL-24.4)), if AL > 24.4mmpACD = ACD-constant

= [(A-constant*0.5663)-65.6+3.595]/0.9704

Input VariablesPartial coherence biometer

(e.g. IOL-Master, Carl Zeiss Meditec) or ultrasound A-scan

1) ACD – anterior chamber depth

2) AL – axial eye length

3) Net corneal power

4) Anterior corneal power

5) Posterior corneal power

6) Central corneal thicknessFourier-domain OCT

(RTVue, Optovue, Inc.)

Maolong Tang, PhD; David Huang, MD, PhD www.COOLLab.net

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Prospective clinical study on post-laser vision correction cataract surgery

Clinical SiteMyopic LVC

(eyes)Hyperopic LVC

(eyes)(eyes) (eyes)

Cullen Eye Institute 12 6

Doheny Eye Institute 10 3

Total 22 9Total 22 9

LVC = laser vision correction

Postoperative manifest refraction spherical equivalent was evaluated at 1 month

Tang M, Wang L, Koch DD, Li Y, Huang D, Intraocular Lens Power Calculation after Myopic and Hyperopic Laser Vision Correction Using Optical Coherence Tomography. Saudi Journal of Ophthalmology. 2012 Feb; 26: 19-24

Accuracy of OCT-based IOL power calculation compared with Haigis-L after myopic LVC

Keratometry Method

IOL Formula

Prediction Error (D)

Range (D)

MAE (D)

Within 1D

IOL-Master Haigis-L -0 35 ± 0 94 (-2 32 1 30) 0 73 73%O aste a g s -0.35 ± 0.94 (-2.32, 1.30) 0.73 73%

OCT OCT 0.07 ± 0.80 (-1.24, 2.15) 0.57 82%

p = 0.19. n = 22 eyes of 16 subjects.

Maolong Tang, PhDDavid Huang, MD, PhD

www.COOLLab.net

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Accuracy of OCT-based IOL power calculation compared with other methods after myopic LVC at the Doheny Eye Institute

Keratometry IOL Formula

Prediction Range MAEMethod

IOL FormulaError (D) (D) (D)

Clinical History Hoffer-Q 0.31 ± 2.52 -1.47 to 2.09 1.78*

CL Overrefraction Holladay II 0.01 ± 2.08 -3.09 to 3.19 1.46*

IOL-Master Haigis-L -0.28 ± 1.19 -2.32 to 0.98 0.88

Orbscan II Holladay II 0.17 ± 1.61 -2.72 to 1.51 1.28

OCT OCT-based 0.49 ± 0.64 -0.33 to 1.58 0.60

*p<0.05 compared to OCT. N = 10 eyes.The standard IOL formula that provided the smallest MAE was used for all keratometry methods except OCT.

OCT-based IOL calculation was significantly better than clinical history and contact lens over-refraction methods.

Maolong Tang, PhD, David Huang, MD, PhD www.COOLLab.net

Conclusion

The predictive accuracy of OCT-based IOL power calculation is equal to or better than p qcurrent standards for post-LVC eyes.

More improvement are possible Aberration measurement or ray tracing

Better prediction of IOL position

Prediction of astigmatism outcomeg

Maolong Tang, PhD, David Huang, MD, PhD www.COOLLab.net

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Grant & Material Supports

NIH R01 EY018184: Guiding The gTreatment of Anterior Eye Diseases with Optical Coherence Tomography

Unrestricted grant from Research to Prevent BlindnessPrevent Blindness

Grant & material support from Optovue, Inc.

www.COOLLab.net

David Huang, MD, PhD

Maolong Tang, PhD

Ou Tan, PhD

Yimin Wang, PhD

Yan Li, PhD

Xinbo Zhang, PhD

Jason Tokayer, MS

Janice Van Norman, COT

Yali Jia, PhD

Kathleen S. Torok, MA

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New Technologies from The Laboratory

HIGHER SPEED GREATER DEPTH RANGE

Anterior Segment Imaging and Extraction of Biometric Parameters

• James G. Fujimoto, Massachusetts Institute of Technology

Volumetric OCT data

OCT registration

3D refraction correction

3D OCT biometry

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Pachymetry Map

I. Grulkowski et al., Volumetric anterior segment biometry using OCT registration and refraction correction techniques, manuscript in preparation

Topography


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360° Anterior Chamber Angle Survey


Anterior Segment Imaging Using VCSEL

• VCSEL technology

• Long coherence length

1 mm

I. Grulkowski et al., Retinal, anterior segment and full eye imaging using ultrahigh speed swept source OCT with vertical-cavity surface emitting lasers, Biomed. Opt. Express 3, 2733 (2012).

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Full Eye Imaging for Non-Contact Ocular Biometry

Cornea Intraocular DistancesCentral Corneal

0 527±0 003mm

50ms

Crystalline Lens

Thickness0.527±0.003mm

Aqueous Depth 3.305±0.030mm

Anterior Chamber Depth

3.831±0.029mm

Lens Thickness 3.880±0.030mm

Vitreous Depth 18.674±0.018mm

Axial Eye

5 mm

Retina

Axial Eye Length

26.384±0.016mm

IOL Master – 20 umImmersion Ultrasound – 100 um

Speckle free imaging – cornea in-vivo

a.

a. Epithelium & Bowman’s Layer

b. b. Endothelium

c. c.Epithelium & Bowman’s Layer

d.d.

Endothelium

Courtesy of Maciej Wojtkowski, Nicolaus Copernicus University, Torun, Poland

M. Szkulmowski,et al. "Efficient reduction of speckle noise in Optical Coherence Tomography," Opt. Express 20, 1337, 2012

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Speckle free imaging – eye lens in-vivo

Segmented tomogramSegments: 1000Averaging: 1Tomo. lines: 1000Acq. time: 250 ms

Segmented tomogramSegments: 1000Averaging: 16Tomo. lines: 1000Acq. time: 250 ms

Capsule

Epithelium


M. Szkulmowski,et al. "Efficient reduction of speckle noise in Optical Coherence Tomography," Opt. Express 20, 1337, 2012

CornealTopography

Placido Tomography

Scheimpflugcamera

SS‐OCT

Keratoplasty

Corneal Penetrating Keratoplasty

Anterior surfaceK1 (ax)K2 (ax)

38.38 D (165°)43.88 D (80°)

9.64 mm 35.0 D (146.5°)7.98 mm 42.3 D (56.5°)

9.44 mm 45.8 D (146°)6.82 mm 49.5 D (56°)

Posterior surfaceK1 (ax)

N.A.( )

K2 (ax) 8.39 mm -4.8 D (146.5°)5.73 mm -7.0 (56.5°)

7.03 mm -5.7 D (154.0°)5.29 mm -7.6 D (64.0°)

Pachymetrymin. Thickness

519 µm 572 µm


K. Karnowski, B. J. Kaluzny, M. Szkulmowski, M. Gora, and M. Wojtkowski, Biomedical Opt Express, 2 (9), 2709-2720, 2011

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Large scale 3-D imaging

M. Gora et al. Optics Express 17(17), 14880-14894, 2009, I. Grulkowski et al..Opt Express, 17 (6), 4842-4858, 2009.

S. Ortiz et al. Biomed. Opt. Express 2, 3232-3247 (2011) , S. Ortiz et al., Opt Express, 18 (3), 2782-2796, 2010.

K. Karnowski et al., Biomedical Opt Express, 2 (9), 2709-2720, 2011


Conclusions

Future commercial OCT systems will be faster

Accurate topography of optical surfaces Accurate topography of optical surfaces Optical modeling and ray tracing

High quality 3D imaging Contact lens fitting

Implant fitting

3D angle evaluation 3D angle evaluation

Surgery simulation


clinical applications of corneal optical coherence … · clinical applications of corneal optical...

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