Ultra-High Resolution Optical Coherence Tomography for Imaging the Anterior Segment of the Eye

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Jianhua Wang, MD, PhD; Mohamed Abou Shousha, MD; Victor L. Perez, MD; Carol L. Karp, MD; Sonia H. Yoo, MD; Meixiao Shen, MSc; Lele Cui, MD; Volkan Hurmeric, MD; Chixin Du, MD; Dexi Zhu, PhD; Qi Chen, MD; Ming Li, MD

ABSTRACT INtrODUctION

Developments in optical coherence tomography Optical coherence tomography (OCT) is a non- (OCT) have expanded its clinical applications for ul- contact and non-invasive imaging modality based on tra-high resolution imaging of the anterior segment the Michelson interferometer.1,2 It has been widely of the human eye. This review presents the latest ad- used in ophthalmology since its development 20 years vances for imaging the anterior segment of the eye us- ago,1 mainly for imaging the posterior segment of the ing ultra-high resolution OCT (UHR-OCT). Unique eye, including the retina and optic nerve head.3-5 Many applications of UHR-OCT technology in clinical and commercially available OCT instruments have been basic scientific laboratory research are discussed and a extremely helpful in the diagnosis of retinal diseases5,6 summary of the results is provided. The authors fo- and for advancing our capability to research and docu- cused on the use of UHR-OCT for imaging of tear ment structural changes in the retina.7-9 In addition to dynamics, contact lens interactions with the corneal retinal imaging, the retinal OCT10,11 and prototype an- surface, and in vivo histological diagnosis of disorders terior segment OCT instruments2,12,13 were used to ex- of the cornea, as well as the future direction in this plore the anterior segment, mainly the cornea, anterior field. [Ophthalmic Surg Lasers Imaging 2011;42: chamber, and chamber angle.14 In 2005, a commer- S15-S27.] cially available anterior segment OCT (Visante; Carl

From Bascom Palmer Eye Institute (JW, MAS, VLP, CLK, SHY, MS, LC, VH, CD, DZ, QC, ML), University of Miami, Miami, Florida; the School of Ophthalmology and Optometry (LC, DZ, QC, ML), Wenzhou Medical College, Wenzhou, Zhejiang, China; and the Department of Ophthalmology (CD), First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Originally submitted February 11, 2011. Accepted for publication February 25, 2011. Supported in part by grants from Vistakon, Allergan, Bausch & Lomb, CibaVision, CooperVision, and Alcon Research Laboratories, and by research grants from NIH Center Grant P30 EY014801 and Research to Prevent Blindness. The authors have no financial or proprietary interest in the materials presented herein. The authors thank Drs. Eduardo Alfonso and Carmen Puliafito for their support, and Dr. Britt Bromberg of Xenofile Editing for providing editing services for this manuscript. Address correspondence to Jianhua Wang, MD, PhD, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building–Room 202, Miami, FL 33136. E-mail: [email protected] doi: 10.3928/15428877-20110627-02

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Zeiss Meditec, Inc., Dublin, CA) was then produced and width with some of the instruments were enough to for anterior segment imaging.15 cover the entire anterior segment.2,14 In this review, we will focus on recent advances for With the recent advances in SD-OCT, which has a imaging the anterior segment of the eye using ultra-high resolution of approximately 5 µm, commercially avail- resolution OCT (UHR-OCT) with resolution below 5 able instruments for retinal scanning could also be used µm. Researchers including our group and companies to scan the anterior segment.31 These included the Cirrus have developed UHR-OCT devices that can image (Carl Zeiss Meditec, Inc.), RTVue (Optovue, Meridian- the anterior segment of the eye in a rapid and patient- ville, AL), Spectralis (Heidelberg Engineering, Dossen- friendly way, with a novel resolution of 1 to 3 µm.16-25 heim, Germany), 3D OCT (Topcon Medical Systems, In this review, we will provide a summary of our results Oakland, NJ), and Bioptigen SD-OCT (Bioptigen Inc., and other published studies using this technology and Research Triangle Park, NC) and others31,42,43 for imaging its unique applications in clinical and basic scientific human eyes. The scan width of approximately 3 to 6 mm laboratory research use. We will discuss how the UHR- for imaging the anterior segment limited some applica- OCT was used for imaging the tear dynamics,20,26,27 tions that demanded a wide scan width, such as imaging contact lens interactions with the corneal surface,26 and the upper and lower tear menisci simultaneously.20 in vivo histological diagnosis of disorders of the cor- The development of UHR-OCT has significantly nea.28 This will also include personal experiences based improved anterior segment imaging capabilities.16-19 on unpublished data using UHR-OCT. Finally, we will In 2001, Drexler et al. reported an image of a normal briefly discuss future directions in this field. human eye using approximately 2-µm axial resolution Although we understand that other published TD-OCT.18 This may be the first demonstration for works have reviewed the use of OCT to study the ante- imaging the Bowman’s layer with UHR-OCT.18 In rior segment, these have mainly covered time-domain 2004, Drexler reported 1-µm axial resolution OCT OCT instruments and high-resolution spectral-domain for imaging the cornea in vitro.17 In 2007, Christo- OCT (SD-OCT).15,29-32 It is important to mention poulos et al. reported the use of corneal UHR-OCT that, simultaneous with the development of UHR- for imaging tear film, corneal epithelium, Descemet OCT for imaging the anterior segment, extended scan membrane, and the endothelium.19 In this report, depth OCT has been developed also for imaging the the trauma with epithelial ingrowth by LASIK has anterior segment, including the anterior chamber and been visualized clearly.19 By using a light source with crystalline lens.33-35 However, the extended scan depth a broad bandwidth of more than 100 nm, ultra-high OCT is not within the scope of this summary. This resolution is achieved with a specifically designed review is focused on the latest clinical applications in spectrometer that detects the fringes collected from anterior segment imaging with UHR-OCT and pro- both reference and sample arms.7,19,20,22-24,26,28,44-47 vides the most recent update in the use of a novel and With a charge-coupled device line scan camera in “futuristic” way to image this part of the eye to add the spectrometer, the speed ranges normally from useful information to the field. 24K to 26K A-scans per second.7,22,23 With a com- plementary metal–oxide–semiconductor line scan UHR-OCT TECHNIQUE camera or ultra-high speed swept source, the speed can be much higher.25,48,49,50 Axial resolution is 2 to The first generation of OCT for imaging the anterior 4 µm in these UHR-OCT instruments.7,20,24,26,28,44-47 segment was the time-domain OCT (TD-OCT). It had Although some instruments have scan widths of ap- approximately 10- to 18-µm resolution and 2K A-scans proximately 5 mm,24 others have wider scan widths per second. The center wavelength was 1,310 nm in the of up to 12 mm.20 Apparently, there are two com- Visante,36 the SL-OCT (Heidelberg Engineering, Heidel- mercially available UHR-OCT devices, including the berg, Germany),37 and other prototypes.38-40 In addition, Bioptigen SD-OCT22,23 and Copernicus HR SOCT modified retinal TD-OCT instruments, such as the Stra- (Optopol Technology SA, Zawiercie, Poland).24 With tus (Carl Zeiss Meditec, Inc.), also were used to image the these commercial and prototype UHR-OCT instru- anterior segment.29,41 With TD-OCT, the speed was low ments, the tear film,20,26 tear meniscus,20 contact and resolution was not very high, although the scan depth lens,20,24,26,45,46 and corneal layers28,51-53 can be im-

Figure 1. Ultra-high resolution optical coherence tomography image of the central cornea with a PureVision (Bausch & Lomb, Rochester, NY) lens after instillation of artificial tears. The central cornea was imaged with 6-mm scan on the horizontal meridian. The image was taken immediately after lens insertion and instillation of one drop of artificial tears. The epithelium, including the basal cell layer, and Bowman’s layer, are evident in addition to the pre-lens and post-lens tear films. Total corneal thickness was measured at 526 µm. Bars = 250 µm. (Reprinted with permission from Wang J, Jiao S, Ruggeri M, Shousha MA, Chen Q. In situ visualization of tears on contact lens using ultra- high resolution optical coherence tomography. Eye & Contact Lens. 2009;2:44-49.)

aged, and the axial resolution is sufficient for clear age these is essential to precisely measure the thickness visualization of structures of interest (Fig. 1). Optical of the PLTF and PoLTF. UHR-OCT made it possible distortion of the OCT images needs to be corrected to directly visualize and calculate the tear film as long before the measurement is taken.54 However, we cited as it is thicker than 3 µm.20,26 In a previous study,26 these published and unpublished images, which are dynamic changes of the PLTF and PoLTF after instil- not optically corrected. The image correction has lation of artificial tears were investigated using UHR- been reported in the literature54,55 and the same pro- OCT. Thicknesses less than 3 µm were determined by cedure can be applied to these OCT images obtained indirect calculation. The PLTF and PoLTF were visual- with UHR-OCT. The topic of image correction is not ized immediately after lens insertion. After 3 minutes, within the scope of this review. the PLTF and PoLTF were invisible in almost all of the subjects.26 To understand the dynamic changes of the TEAR FILM AND TEAR MENISCUS PoLTF during lens wear, artificial tears were added on the concave surface of the lens and then the lens was TD-OCT and SD-OCT have been used to image inserted onto the eye (Fig. 2).26 The added tears were the tear film and tear meniscus.56-60 One of the applica- maintained in the post-lens for only several minutes tions using UHR-OCT is to image the tear film and tear during blinking and lens movement. meniscus.19,20,26 Wang et al. reported that the post-lens Using UHR-OCT, both upper and lower tear me- tear film (PoLTF) on the cornea could be directly vi- nisci can be imaged for tracking the tear meniscus vol- sualized using UHR-OCT.20 The continuous exchange ume (Fig. 3).20 The tear meniscus changes with punctal of the tear film on and underneath the lens is needed occlusion. It is an effective treatment for dry eye disease for maintaining the physiology and health of the ocular and dryness associated with contact lens wear,68-70 and surface.20 Thus, quantifying the dynamic changes of the the improvement of tear volume in patients with dry eye pre-lens tear film (PLTF) and PoLTF thicknesses during after this procedure was documented using SD-OCT.71 contact lens wear is important in understanding the eti- Chen et al. found that the tear menisci recovered to near ology of dry eye associated with contact lens wear. normal levels at 1 day after punctal occlusion in patients The thicknesses of the PLTF and PoLTF have with dry eye, and no changes were evident in the tear previously been measured and reported by using vari- menisci of normal subjects.71 They also used SD-OCT ous methodologies, such as interferometry, confocal to compare the effect of upper punctal occlusion and microscopy, and TD-OCT technology.60-67 However, lower punctal occlusion on tear menisci in patients with none of these methods can quickly acquire ultra-high dry eye.72 resolution cross-sectional images of the anterior seg- In a recent study (unpublished data), Li et al. used ment of the eye, including the clear cornea, contact UHR-OCT to determine the changes in tear menisci lens, and tear film between them. The ability to im- after punctal occlusion in contact lens wearers. They

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Figure 2. Changes in pre-lens tear film (PLTF) and post-lens tear film (PoLTF) after lens insertion. (A) A soft contact lens (CL) was inserted onto the cornea (CO) with 1 drop (35 µL) of artificial tears on the concave surface of the lens. Both the PLTF (green *) and PoLTF (red *) were clearly visualized by ultra-high resolution optical coherence tomography immediately afterward. (B–F) After that, the PLTF and PoLTF gradually decreased. (F) At 10 minutes after lens insertion, both the PLTF and PoLTF were still visible. (Reprinted with permission from Chen Q, Wang J, Tao A, Shen M, Jiao S, Lu F. Ultrahigh-resolution measurement by optical coherence tomography of dynamic tear film changes on contact lenses. Invest Ophthalmol Vis Sci. 2010;51:1988-1993. ©Association for Research in Vision & Ophthalmology). Figure 3. The tears on the ocular surface and contact lens. A vertical 12-mm ultra-high resolution optical coherence tomography scan was performed after the instillation of one drop of the artificial tears. (A with enlarged inset) The tear film on the cornea without a lens and the tear menisci around the upper (UL) and lower (LL) eyelids were clearly visualized. (B with enlarged inset) Recovery was evident 5 minutes after the instillation. On the same eye, a PureVision (Bausch & Lomb, Rochester, NY) lens was fitted, and one drop of the artificial tears was instilled. (C to E with enlarged insets) The pre-lens tear film and post-lens tear film (arrows) were imaged. Tear menisci were located around the upper and lower eyelids. Note that the boundary between the tear and lens was not clearly visualized due to the low light scattering. (E) Two minutes after the insertion, the tear films were still visualized, especially underneath the lower part of the lens. (Re- printed with permission from Wang J, Jiao S, Ruggeri M, Shousha MA, Chen Q. In situ visualization of tears on contact lens using ultra-high resolution optical coherence tomography. Eye & Contact Lens. 2009;2:44-49).

Figure 4. The edge of a contact lens after instillation of artificial tears. The eye was imaged from a side view as the subject looked 45 degrees na- sally. It revealed the lens edge configuration and its relationship to the ocular surface, as well as the pre-lens tear film and post-lens tear film. The thickness, noted on the image, was measured at the locations marked by the arrows. Bars = 500 µm. (Reprinted with permission from Wang J, Jiao S, Ruggeri M, Shousha MA, Chen Q. In situ visualization of tears on contact lens using ultra high resolution optical coherence tomography. Eye & Contact Lens. 2009;2:44-49).

Figure 5. Contact lens movement. In the cross- sectional view, contact lens (CL) and cornea (CO) were clearly visualized. In 128 continuous frames in the cross-sectional vertical meridian, ultra-high resolution optical coherence tomography captured the movement of the lens edge in two consecu- tive blinks. The cross-sectional dataset was recon- structed to provide the M-mode view of the tracked lens edge. A single point as the tip of the edge was marked as “Edge,” corresponding to the footprint of the lens movement.

found punctal occlusion transiently increased tear me- EVALUATING CONTACT LENS FITTING nisci in contact lens wearers, some of whom had self- reported dry eyes and some of whom were asymptom- UHR-OCT is a promising method for evaluating atic. The increase remained for a longer time in the contact lens fitting because the configuration of the symptomatic group. The increased meniscus volume lens edge can be precisely imaged24 and the indentation was associated with improved ocular comfort for both where it sits on the ocular surface evaluated (Fig. 4).20,46 symptomatic and asymptomatic lens wearers. Wang et In addition to these applications, lens movement and al. used UHR-OCT to determine whether the changes centration can be imaged. The PoLTF and the touch in tear meniscus volume can be precisely evaluated after points underneath the lens imaged with UHR-OCT dry eye treatment with Restasis.27 The results showed can help model the fit relationship between the lens that UHR-OCT is a promising tool for tracking the ef- and ocular surface. Using the information obtained ficacy of dry eye treatment. In a recent study (unpub- with OCT, the prediction of lens mismatch with the lished data), Li et al. used UHR-OCT to determine the ocular surface where too much pressure or too many tear meniscus volume during a typical 8-hour work day pressure points may exist can be tested.73 in patients with dry eye and healthy controls. This dem- Lens movement is an important part in the dy- onstrated its value in determining the fluctuation of tear namic evaluation of contact lens fitting and is critical volume throughout the day. in maintaining ocular health and comfort.74 Tear ex-

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Figure 7. Lens centration. A soft contact lens (CL) with a painted pupil (1-day Acuvue Define, Power 0, Base curve 8.5 mm, Diam- Figure 6. Lens movement of a round-edged soft contact lens. The eter 14.2 mm, etafilcon A) was imaged with ultra-high resolution round-edged soft lens (PureVision; Bausch & Lomb, Rochester, NY) optical coherence tomography to track the lens centration with re- was imaged (CL) on the upper edge when the upper eyelid (UL) was spect to the apex. The en face view was created from 128 frames manually elevated. The lens was pushed up by applying pressure to of optical coherence tomography images that took 2.7 seconds to the lower eyelid (the push-up test), and the motion was recorded with acquire. The lens appeared to be decentered upward. the ultra-high resolution optical coherence tomography. Note the lens moved up toward the upper eyelid. The interaction between the edge and eyelid and the tears around the edge was visualized. micrometers, can provide additional information on movement velocity and amount. The velocity and dis- tance of movement might be good indicators of lens change underneath the lens and the removal of debris fitting, which in turn may be correlated with ocular and cells are facilitated by proper lens movement.75,76 comfort. The tightness of lens fitting may also be tested Movement of the lens is attributable to two different by the push-up test, which uses a finger to push the factors: the contact lens itself and the contour of eye. lens up for testing (Fig. 6). Lens centration, which in- In a study using UHR-OCT,77 Cui et al. tracked the dicates the matching of the lens and ocular surface, is movement of the lens edge during blinking (Fig. 5). another important parameter of contact lens fitting. The lens footprint at the vertical meridian showed a Lenses with a painted pupil/iris or a fiducial mark73 little lowering of the lens at the beginning of the blink can be imaged by UHR-OCT to assess centration and and a lifting of the lens after the blink. This indicates fitting characteristics (Fig. 7). that the upper eyelid pushed the contact lens downward when it descended, followed by an upward movement ULTRA-HIGH RESOLUTION IMAGING OF THE CORNEA as the eyelid began to open. The authors found that lenses with a high modulus78 of elasticity and rounded With high resolution and high speed, UHR-OCT edge showed more movement than lenses with a low is suitable to image the cornea, including the epithe- modulus and angled edge. Less movement in the lenses lium,79 Bowman’s layer,20 and the endothelium.28 Cor- with a low modulus might be attributed to the thin neal swelling during contact lens wear is an important PoLTF that results from the deformation and adher- indicator of corneal hypoxia underneath the lens, es- ence to the ocular surface of these lenses. pecially for overnight lens wear. Hutchings et al. used The footprint of the lens movement, measured in UHR-OCT to examine corneal swelling after lens wear

Figure 8. Topographical thickness of the epithelium. Corneal images were obtained with ultra- high resolution optical coherence tomography at different locations around the horizontal (A, B and C) and vertical (D, E, and F) meridians. The epithelium (EP) and Bowman’s layer (BL) were clearly visualized. The epithelium was not uniform around either of the meridians.

with eye closure.79 Each layer of the cornea, including the endothelial–Descemet’s membrane complex, was measured. Using UHR-OCT to precisely track the changes in thickness may help us understand corneal metabolic function and hydration state in response to lens wear. With new lens materials such as silicone hydrogel lenses, the level of swelling is minimal. Using optical and ultrasonic pachymeters80 may not be able to track the minimal swelling, and UHR-OCT may be the best tool for this purpose. UHR-OCT also has been used to study corneal hydration,81 incision of clear cut,82 and eye bank eyes.83,84 In addition to the measurement of epithelial thick- Figure 9. Comparison of corneal histological and ultra-high resolu- ness at the central location of the cornea, the thick- tion optical coherence tomography (UHR-OCT) images of a patient ness profile of the entire cornea may be evaluated using with Fuchs’ dystrophy. (A) Photomicrograph of the pathology sec- tion of the same Descemet’s membrane in image (B) obtained by UHR-OCT. This could be especially useful for detect- Descemet’s stripping automated endothelial keratoplasty (DSAEK) of ing keratoconus and changes from corneal procedures, the right eye of a patient with Fuchs’ dystrophy. (A) Thickened Des- such as orthokeratology and laser-assisted in situ ker- cemet’s membrane with areas of nodular excrescences correlated atomileusis (LASIK). Due to the limited scan depth with corneal guttae. The average central thickness of the Descemet’s of current UHR-OCT instruments, only the central membrane measured histopathologically by light microscope was 31 µm (Periodic acid-Schiff stain; original magnification 3400). (B) UHR- region of the cornea can be imaged for creating the OCT image of the same Descemet’s membrane appears as a thick- thickness map. Alternatively, the thickness profiles of ened band formed of two opaque lines. The anterior line is smooth the epithelium can be imaged part by part as done pre- and the posterior line has a wavy irregular appearance with areas of viously with TD-OCT85 and optical pachometry.86 localized thickenings that can be correlated to corneal guttae. In vivo In an unpublished study, we used UHR-OCT UHR-OCT measurement of this Descemet’s membrane was 55 µm. to scan the epithelium at the center and periphery at Bar = 50 µm. (Reprinted with permission from Shousha MA, Perez VL, Wang J, et al. Use of ultra-high-resolution optical coherence to- the vertical and horizontal meridians to evaluate topo- mography to detect in vivo characteristics of Descemet’s membrane graphical thickness of epithelium from limbus to lim- in Fuchs’’ dystrophy. Ophthalmology. 2010;117:1220-1227). bus (Fig. 8). High quality OCT images of the epithelium demonstrated that the epithelial profile was not it increased gradually to the mid-periphery and periph- uniform. The thinnest point was at the center, and then ery along the horizontal meridian. Along the vertical

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Figure 10. Corneal intraepithelial neoplasia. (A) The slit-lamp photograph shows an inferior conjunctival and corneal intraepithelial neoplasia (conjunctival and corneal intraepithelial neoplasia, white arrows). The black arrow rep- resents the location and scan direction of the ultra-high resolution optical coherence tomography (UHR-OCT) scan. (B) The UHR-OCT image discloses a thickened hyperreflective epithelial layer (a), Bowman’s layer (b), and the abrupt transition from normal to the hyperreflective epithelium (c).

meridian, the epithelium was thinnest at the edge of course of medical treatment. This technology provides Bowman’s layer in the superior region. It increased in the possibility of an “optical biopsy,” without the limi- thickness toward the center, reaching the thickest point tations of slit-lamp examination, impression cytology, in the inferior pericentral region. or incisional biopsy. Mutapcic et al.88 evaluated the clinical applica- IN VIVO IMAGING OF CORNEAL PATHOLOGY: tions of UHR-OCT in examination, diagnosis, and ROLE IN DIAGNOSIS AND TREATMENT management of various anterior corneal dystrophies and degenerations (Fig. 11). They demonstrated the UHR-OCT has proved to be of great assistance ability of UHR-OCT to non-invasively determine in the diagnosis and management of various corneal the depth and extent of pathology, which allowed for diseases.31,51-53,87-90 The use of this novel imaging tech- better clinical and surgical management. Their study nology has overcome limitations of some traditional revealed significant correlation between UHR-OCT diagnostic techniques and allowed for in vivo, non- images and histopathological specimens, proving that invasive, morphologic analysis of the cornea. Using a UHR-OCT provides an accurate “optical biopsy” UHR-OCT prototype, Shousha et al.28 described the that assists the diagnosis and management of various in vivo thickness of Descemet’s membrane and its char- corneal pathologies. acteristics in patients with Fuchs’ dystrophy. They also In the past 3 years, we have also used the UHR- demonstrated the unique ability of UHR-OCT to de- OCT to evaluate the ocular surface of all patients seen velop diagnostic imagery for corneal dystrophy (Fig. 9). at the Ocular Surface and Inflammation Service at the In another study, they compared the use of that novel Bascom Palmer Eye Institute. Using the anterior seg- diagnostic technique to endothelial cell count measurement UHR-OCT to evaluate the ocular surface has be- ments obtained by specular microscopy, the current come a critical tool to diagnose and monitor responses gold standard methodology.89 That study demonstrat- to therapies of diseases of the cornea (Fig. 12). A ma- ed that UHR-OCT was significantly more successful jor advantage of this image modality is the power of in describing the disease than specular microscopy. allowing the evaluation of the corneal surface with a Conjunctival and corneal intraepithelial neoplasia resolution of 3 µm, giving us the advantage of mak- is the most common ocular surface neoplasia and early ing an in vivo “microscopic” evaluation of the different diagnosis is important. Shousha et al.87 have shown structures of the cornea. Moreover, this analysis and that UHR-OCT can provide an objective and a sensi- images are obtained at the slit lamp, in a non-invasive tive means to diagnose and manage conjunctival and fashion with a fast acquisition time of less than 5 sec- corneal intraepithelial neoplasia (Fig. 10). Thanks to onds. This gives us the opportunity to evaluate patients the ultra-high resolution images, UHR-OCT can de- with discomfort who otherwise would be difficult to tect subtle conjunctival and corneal intraepithelial neo- image. Furthermore, our ability to quantify data ob- plasia and identify residual subclinical disease in the tained from the UHR-OCT images allows us to objec-

Figure 11. Corneal dystrophy of Bowman’s layer type II. (1A) The patient had bilateral, central honeycombed corneal deposits. (1B) Ul- tra-high resolution optical coherence tomography image illustrates extensive “saw-tooth pattern” of hyperreflective material (white arrow) deposited on the surface of Bowman’s layer. (1C) Histopathology of superficial keratectomy specimen reveals fibrocellular material (black arrow) that stained variably positive (Masson trichrome stain with green, original magnification 3400). (Reprinted with permission from Vajzovic LM, Karp CL, Haft P, et al. Ultra-high resolution anterior segment optical coherence tomography in the evaluation of anterior corneal dystrophies and degenerations. Ophthalmology. In press).

tively follow trends and novel observations in disorders of the cornea such as dry eye syndrome, meibomian gland dysfunction, corneal graft rejection, and endothelial dystrophies. As the resolution of this imaging modality continues to improve, we expect to continue to improve our ability to make “in vivo histological” analysis of ocular surface disorders.

REFRACTIVE SURGERY

SD-OCT has been used to create pachymetric mapping,91 visualize LASIK flap displacement,91 and calculate corneal power.92 UHR-OCT imaging gives us the ability to visualize in vivo morphology of the cor- Figure 12. (A) Ultra-high resolution optical coherence tomography (UHR-OCT) image of the cornea of a patient with a non-healing nea in the clinical practice of refractive surgery. There neurotrophic epithelial defect at the time of treatment with ban- are two important functions of this novel imaging sys- dage contact lens, autologous serum tears, and cyclosporine. (B) tem. First, it allows us to measure the thickness of the UHR-OCT follow-up images 3 months after therapy demonstrat- cornea. Second, it makes possible non-invasive histo- ing healed epithelium. Note the change of the endothelium, which logical sampling, which is similar to a living biopsy. may indicate Fuchs’ dystrophy. This gives us the opportunity to demonstrate unique properties of all clinical conditions involving structural can help the surgeon minimize intraoperative flap-re- changes in the cornea.52 lated complications. It can also be used to analyze the One of the most interesting clinical applications of morphology of some of the other intraoperative phe- UHR-OCT is its use in femtosecond-assisted LASIK nomena seen during FS-LASIK. We have analyzed the (FS-LASIK) surgery. Because UHR-OCT is a non-in- in vivo structure of the opaque bubble layer with this vasive imaging technique, it can be performed at all novel imaging system.53 We have demonstrated that stages of FS-LASIK surgery. It can be used to analyze the opaque bubble layer located above the flap inter- the structure and the integrity of the corneal flap, which face was a sign of a partially dissected flap and a con-

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Figure 13. (A) Ultra-high resolution optical coherence tomography Figure 14. (A) Ultra-high resolution optical coherence tomography imaging of a patient with opaque bubble layer. Green arrows: flap imaging of a patient with suction loss during femtosecond laser- interface; white arrows: Bowman layer. Vertical bar corresponds assisted flap preparation. The image has been acquired before the to 100 µm. Asterisk corresponds to the area with opaque bubble flap lift was performed. White arrows: flap interface. Vertical bar layer located above the flap interface. This area was undissected corresponds to 100 µm. Flap structure was normal (B) Slit-lamp and the flap lift was completed with the help of a #15 blade. (B) photograph of the same patient before flap lift. White arrows cor- Slit-lamp photograph of the same patient at postoperative day 1. respond to the flap irregularity that occurred with suction loss. Flap White arrows correspond to the area with flap irregularity. lift was completed successfully. traindication to flap lifting. The opaque bubble layer epithelial cells in the side-cut that we had observed in located above the flap interface resulted in unsuccessful our case with LASIK flap melt. Although our results flap lifting in two patients (Fig. 13). We also have used need to be confirmed with a larger study group, our ultra-high-resolution OCT to confirm flap integrity preliminary results suggest that residual epithelium at in a patient with suction loss during FS-LASIK (Fig. the LASIK side-cut may be responsible for the develop- 14). After suction break, the suction was reapplied and ment of epithelial ingrowth and flap melt (Fig. 15). the femtosecond laser cut was completed. We have UHR-OCT also helps us to document the in vivo performed UHR-OCT imaging before flap lifting and morphology of the cornea after refractive surgery simi- demonstrated that the flap structure was normal. Flap lar to a living biopsy. This novel technique gives us new lifting was uneventful in this patient. information about the pathogenesis of complications UHR-OCT can also be used to understand wound and wound healing after refractive surgery. UHR-OCT structure and wound healing after refractive surgery. has the potential to be used as a tool to prevent flap- We have observed residual epithelium penetrating into related complications in FS-LASIK. Further studies are the LASIK flap side-cut in a patient with an epithelial needed to confirm these new clinical applications of defect. This resulted in peripheral flap melt on postop- UHR-OCT in refractive surgery. erative follow-up. Subsequently, we investigated flap side-cut struc- FUTURE DIRECTIONS ture with UHR-OCT. This pilot study included 22 eyes of 15 patients who underwent uneventful FS-LASIK. UHR-OCT of the anterior segment enables us We scanned the patients at postoperative day 1 and our to image the tear film, detailed layers in the cornea of results suggested that none of the patients had similar normal subjects, and patients with various anterior seg-

imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol. 1994;112:1584-1589. 3. Goebel W, Kretzchmar-Gross T. Retinal thickness in diabetic reti- nopathy: a study using optical coherence tomography (OCT). Retina. 2002;22:759-767. 4. Spiritus A, Dralands L, Stalmans P, Stalmans I, Spileers W. OCT study of fellow eyes of macular holes. Bull Soc Belge Ophtalmol. 2000;275:81-84. 5. Wang M, Luo R, Liu Y. Optical coherence tomography and its ap- plication in ophthalmology [article in Chinese]. Yan Ke Xue Bao. 1998;14:116-120. 6. Stanga PE, Bird AC. Optical coherence tomography (OCT): prin- ciples of operation, technology, indications in vitreoretinal imaging and interpretation of results. Int Ophthalmol. 2001;23:191-197. 7. Ruggeri M, Wehbe H, Jiao S, et al. In vivo three-dimensional high- resolution imaging of rodent retina with spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2007;48:1808-1814. 8. Huang Y, Cideciyan AV, Aleman TS, et al. Optical coherence tomography (OCT) abnormalities in rhodopsin mutant transgenic swine with retinal degeneration. Exp Eye Res. 2000;70:247-251. 9. Cense B, Nassif N, Chen T, et al. Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography. Opt Express. 2004;12:2435-2447. 10. Wang J, Fonn D, Simpson TL, Jones L. Relation between optical coherence tomography and optical pachymetry measurements of corneal swelling induced by hypoxia. Am J Ophthalmol. 2002;134:93-98. 11. Feng Y, Varikooty J, Simpson TL. Diurnal variation of corneal and corneal epithelial thickness measured using optical coherence tomography. Cornea. 2001;20:480-483. 12. Radhakrishnan S, Rollins AM, Roth JE, et al. Real-time optical coher- Figure 15. (A) Ultra-high resolution optical coherence tomography ence tomography of the anterior segment at 1310 nm. Arch Ophthal- mol. 2001;119:1179-1185. imaging of a patient with epithelial ingrowth. White arrows: epithe- 13. Baikoff G, Lutun E, Ferraz C, Wei J. Static and dynamic analysis of lial ingrowth at the flap interface. Vertical bar corresponds to 100 the anterior segment with optical coherence tomography. J Cataract µm. (B) Slit-lamp photograph of the same patient. Refract Surg. 2004;30:1843-1850. 14. Radhakrishnan S, Rollins AM, Roth JE, et al. Real-time optical coherence tomography of the anterior segment at 1310 nm. Arch Ophthal- ment diseases. The technique enables taking an “opti- mol. 2001;119:1179-1185. 15. Jancevski M, Foster CS. Anterior segment optical coherence tomogra- cal biopsy” of anterior segment pathology and a clear phy. Semin Ophthalmol. 2010;25:317-323. image of tear and contact lens dynamics. In the near 16. Fujimoto JG. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat Biotechnol. 2003;21:1361-1367. future, we will move toward developing higher reso- 17. Drexler W. Ultrahigh-resolution optical coherence tomography. J lution instruments for improving imagery of the tear Biomed Opt. 2004;9:47-74. film. Currently, resolution below 2 µm is feasible by 18. Drexler W, Morgner U, Ghanta RK, Kärtner FX, Schuman JS, Fuji- moto JG. Ultrahigh-resolution ophthalmic optical coherence tomog- using a light source with a bandwidth of more than raphy. Nat Med. 2001;7:502-507. 180 nm. Improving lateral resolution may be another 19. Christopoulos V, Kagemann L, Wollstein G, et al. In vivo corneal high-speed, ultra high-resolution optical coherence tomography. Arch way to visualize structures at the cellular level, as dem- Ophthalmol. 2007;125:1027-1035. onstrated in a full-field OCT that can resolve epithelial 20. Wang J, Jiao S, Ruggeri M, Shousha MA, Chen Q. In situ visualiza- 31 tion of tears on contact lens using ultra high resolution optical coher- cells. In the contact lens field, lens movement and ence tomography. Eye Contact Lens. 2009;35:44-49. centration can be imaged with the modalities, and 21. Chen Q, Wang J, Tao A, Shen M, Jiao S, Lu F. Ultra-high resolution measurement by optical coherence tomography of dynamic tear film further modeling the lens interactions with the ocular changes on contact lenses. Invest Ophthalmol Vis Sci. 2010;51:1988- surface may be possible. With further improvement of 1993. optical resolution, scan speed, and more robust image 22. Fine JL, Kagemann L, Wollstein G, Ishikawa H, Schuman JS. Direct scanning of pathology specimens using spectral domain optical co- processing, UHR-OCT will have increasing applica- herence tomography: a pilot study. Ophthalmic Surg Lasers Imaging. tions for use in clinical care and in the laboratory for 2010;41(suppl):S58-S64. 23. Godara P, Siebe C, Rha J, Michaelides M, Carroll J. Assessing the the anterior segment of the eye. photoreceptor mosaic over drusen using adaptive optics and SD- OCT. Ophthalmic Surg Lasers Imaging. 2010;41(suppl):S104-S108. 24. Gonzalez-Meijome JM, Cervino A, Carracedo G, Queiros A, Garcia- REFERENCES Lázaro S, Ferrer-Blasco T. High-resolution spectral domain optical coherence tomography technology for the visualization of contact lens 1. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. to cornea relationships. Cornea. 2010;29:1359-1367. Science. 1991;254:1178-1181. 25. Kaluzny BJ, Gora M, Karnowski K, Grulkowski I, Kowalczyk A, 2. Izatt JA, Hee MR, Swanson EA, et al. Micrometer-scale resolution Wojtkowski M. Imaging of the lens capsule with an ultrahigh-reso-

Ophthalmic Surgery, Lasers & Imaging · Vol. 42, No. 4 (Suppl), 2011 S25 i m a g i n g i m a g i n g

lution spectral optical coherence tomography prototype based on a 2006;25:960-965. femtosecond laser. Br J Ophthalmol. 2010;94:275-277. 48. Potsaid B, Baumann B, Huang D, et al. Ultrahigh speed 1050nm 26. Chen Q, Wang J, Tao A, Shen M, Jiao S, Lu F. Ultrahigh-resolution swept source/Fourier domain OCT retinal and anterior segment measurement by optical coherence tomography of dynamic tear film imaging at 100,000 to 400,000 axial scans per second. Opt Express. changes on contact lenses. Invest Ophthalmol Vis Sci. 2010;51:1988- 2010;18:20029-20048. 1993. 49. Grulkowski I, Gora M, Szkulmowski M, et al. Anterior segment im- 27. Wang J, Conway TM, Yuan Y, Shen M, Cui L. Tear meniscus volume aging with Spectral OCT system using a high-speed CMOS camera. measured with ultra-high resolution OCT in dry eye after Restasis Opt Express. 2009;17:4842-4858. treatment. ARVO Meeting Abstracts. 2010;51:6266. 50. Gora M, Karnowski K, Szkulmowski M, et al. Ultra high-speed swept 28. Shousha MA, Perez VL, Wang J, et al. Use of ultra-high-resolu- source OCT imaging of the anterior segment of human eye at 200 tion optical coherence tomography to detect in vivo characteris- kHz with adjustable imaging range. Opt Express. 2009;17:14880- tics of Descemet’s membrane in Fuchs’ dystrophy. Ophthalmology. 14894. 2010;117:1220-1227. 51. Suh LH, Shousha MA, Ventura RU, et al. Epithelial ingrowth after 29. Simpson T, Fonn D. Optical coherence tomography of the anterior Descemet stripping automated endothelial keratoplasty: description segment. Ocul Surf. 2008;6:117-127. of cases and assessment with anterior segment optical coherence to- 30. Ramos JL, Li Y, Huang D. Clinical and research applications of ante- mography [published online ahead of print November 23, 2010]. rior segment optical coherence tomography: a review. Clin Experiment Cornea. Ophthalmol. 2009;37:81-89. 52. Hurmeric V, Yoo SH, Karp CL, et al. In vivo morphologic characteris- 31. Maeda N. Optical coherence tomography for corneal diseases. Eye tics of Salzmann nodular degeneration with ultra-high-resolution op- Contact Lens. 2010;36:254-259. tical coherence tomography. Am J Ophthalmol. 2011;151:248-256. 32. Friedman DS, He M. Anterior chamber angle assessment techniques. 53. Hurmeric V, Yoo SH, Fishler J, Chang VS, Wang J, Culbertson WW. Surv Ophthalmol. 2008;53:250-273. In vivo structural characteristics of the femtosecond LASIK-induced 33. Furukawa H, Hiro-Oka H, Satoh N, et al. Full-range imaging of eye opaque bubble layers with ultrahigh-resolution SD-OCT. Ophthalmic accommodation by high-speed long-depth range optical frequency Surg Lasers Imaging. 2010;41(suppl):S109-S113. domain imaging. Biomed Opt Express. 2010;1:1491-1501. 54. Westphal V, Rollins A, Radhakrishnan S, Izatt J. Correction of geo- 34. Shen M, Wang MR, Wang J, Yuan Y, Chen F. Entire contact lens metric and refractive image distortions in optical coherence tomogra- imaged in vivo and in vitro with spectral domain optical coherence phy applying Fermat’s principle. Opt Express. 2002;10:397-404. tomography. Eye Contact Lens. 2010;36:73-76. 55. Ortiz S, Siedlecki D, Grulkowski I, et al. Optical distortion correc- 35. Shen M, Wang MR, Yuan Y, et al. SD-OCT with prolonged scan tion in optical coherence tomography for quantitative ocular anterior depth for imaging the anterior segment of the eye. Ophthalmic Surg segment by three-dimensional imaging. Opt Express. 2010;18:2782- Lasers Imaging. 2010;41(suppl):S65-S69. 2796. 36. Leung CK, Li H, Weinreb RN, et al. Anterior chamber angle mea- 56. Zhou S, Li Y, Lu AT, et al. Reproducibility of tear meniscus measure- surement with anterior segment optical coherence tomography: a ment by Fourier-domain optical coherence tomography: a pilot study. comparison between slit lamp OCT and Visante OCT. Invest Oph- Ophthalmic Surg Lasers Imaging. 2009;40:442-447. thalmol Vis Sci. 2008;49:3469-3474. 57. Wang J, Aquavella J, Palakuru J, Chung S. Repeated measurements 37. Mueller M, Schulz-Wackerbarth C, Steven P, et al. Slit-lamp-adapted of dynamic tear distribution on the ocular surface after instillation of Fourier-domain OCT for anterior and posterior segments: prelimi- artificial tears.Invest Ophthalmol Vis Sci. 2006;47:3325-3329. nary results and comparison to time-domain OCT. Curr Eye Res. 58. Palakuru JR, Wang J, Chung S. Tear Distribution on Ocular Surface 2010;35:722-732. of Blepharospasm. ARVO Meeting Abstracts. 2006;47:4957. 38. Izatt JA, Hee MR, Swanson EA, et al. Micrometer-scale resolution 59. Palakuru JR, Wang J, Aquavella JV. Effect of blinking on tear vol- imaging of the anterior eye in vivo with optical coherence tomogra- ume after instillation of midviscosity artificial tears.Am J Ophthalmol. phy. Arch Ophthalmol. 1994;112:1584-1589. 2008;146:920-924. 39. Wang J, Thomas J, Cox I. Objective measurements of corneal light 60. Wang J, Fonn D, Simpson TL, Jones L. Precorneal and pre- and scatter after LASIK using optical coherence tomography. Optom Vis postlens tear film thickness measured indirectly with optical coher- Sci. 2003;80:15. ence tomography. Invest Ophthalmol Vis Sci. 2003;44:2524-2528. 40. Palakuru JR, Wang J, Aquavella JV. Effect of blinking on tear dynam- 61. Prydal J, Campbell F. Study of precorneal tear film thickness and ics. Invest Ophthalmol Vis Sci. 2007;48:3032-3037. structure by interferometry and confocal microscopy. Invest Ophthal- 41. Wang J, Fonn D, Simpson TL, Jones L. The measurement of corneal mol Vis Sci. 1992;33:1996-2005. epithelial thickness using the OCT in response to hypoxia by soft 62. Prydal J, Artal P, Woon H, Campbell F. Study of human precorneal contact lens and eye closure (Abstract). Optom Vis Sci. 2000;77:170. tear film thickness and structure using laser interferometry. Invest 42. Scott AW, Farsiu S, Enyedi LB, Wallace DK, Toth CA. Imaging the Ophthalmol Vis Sci. 1992;33:2006-2011. infant retina with a hand-held spectral-domain optical coherence to- 63. King-Smith PE, Fink BA, Fogt N, Nichols KK, Hill RM, Wilson mography device. Am J Ophthalmol. 2009;147:364-373. GS. The thickness of the human precorneal tear film: evidence from 43. Leite MT, Rao HL, Zangwill LM, Weinreb RN, Medeiros FA. Com- reflection spectra.Invest Ophthalmol Vis Sci. 2000;41:3348-3359. parison of the diagnostic accuracies of the Spectralis, Cirrus, and RT- 64. Wang J, Aquavella J, Palakuru J, Chung S, Feng C. Relationships be- Vue optical coherence tomography devices in glaucoma [published tween central tear film thickness and tear menisci of the upper and online ahead of print March 4, 2011]. Ophthalmology. lower eyelids. Invest Ophthalmol Vis Sci. 2006;47:4349-4355. 44. Wojtkowski M, Srinivasan V, Fujimoto JG, et al. Three-dimensional 65. Doane M. An instrument for in vivo tear film interferometry. Optom retinal imaging with high-speed ultrahigh-resolution optical coher- Vis Sci. 1989;66:383-388. ence tomography. Ophthalmology. 2005;112:1734-1746. 66. Fogt N, King-Smith PE, Tuell G. Interferometric measurement of 45. Kaluzny BJ, Fojt W, Szkulmowska A, Bajraszewski T, Wojtkowski M, tear film thickness by use of spectral oscillations. J Opt Soc Am A Opt Kowalczyk A. Spectral optical coherence tomography in video-rate Image Sci Vis. 1998;15:268-275. and 3D imaging of contact lens wear. Optom Vis Sci. 2007;84:1104- 67. Brennan N, Efron N, Bruce A, Duldig D, Russo NJ. Dehydration of 1109. hydrogel lenses: environmental influences during normal wear. Am J 46. Kaluzny BJ, Kaluzny JJ, Szkulmowska A, et al. Spectral optical coher- Optom Physiol Opt. 1988;65:277-281. ence tomography: a new imaging technique in contact lens practice. 68. Goto E, Yagi Y, Kaido M, Matsumoto Y, Konomi K, Tsubota K. Im- Ophthalmic Physiol Opt. 2006;26:127-132. proved functional visual acuity after punctal occlusion in dry eye pa- 47. Kaluzny BJ, Kaluzny JJ, Szkulmowska A, et al. Spectral optical co- tients. Am J Ophthalmol. 2003;135:704-705. herence tomography: a novel technique for cornea imaging. Cornea. 69. Dursun D, Ertan A, Bilezikci B, Akova YA, Pelit A. Ocular surface

changes in keratoconjunctivitis sicca with silicone punctum plug oc- 82. Rao B, Zhang J, Taban M, McDonnell P, Chen Z. Imaging and investi- clusion. Curr Eye Res. 2003;26:263-269. gating the effects of incision angle of clear corneal cataract surgery with 70. Kojima T, Ishida R, Dogru M, et al. A new noninvasive tear stability optical coherence tomography. Opt Express. 2003;11:3254-3261. analysis system for the assessment of dry eyes. Invest Ophthalmol Vis 83. Akiba M, Maeda N, Yumikake K, et al. Ultrahigh-resolution imaging Sci. 2004;45:1369-1374. of human donor cornea using full-field optical coherence tomogra- 71. Chen F, Shen M, Chen W, et al. Tear meniscus volume in dry eye after phy. J Biomed Opt. 2007;12:041202. punctal occlusion. Invest Ophthalmol Vis Sci. 2010;51:1965-1969. 84. Brown JS, Wang D, Li X, et al. In situ ultrahigh-resolution optical 72. Chen F, Wang J, Chen W, Shen M, Xu S, Lu F. Upper punctal occlu- coherence tomography characterization of eye bank corneal tissue sion versus lower punctal occlusion in dry eye. Invest Ophthalmol Vis processed for lamellar keratoplasty. Cornea. 2008;27:802-810. Sci. 2010;51:5571-5577. 85. Wang J, Fonn D, Simpson TL. Topographical thickness of the epi- 73. Hofmann G, Wang J, Shen M, Perez J, Riley C. Feasibility of in- thelium and total cornea after hydrogel and PMMA contact lens wear vivo lens and corneal shape measurements with lens position using with eye closure (Abstract). Optom Vis Sci. 2001;78:S303. long scan optical coherence tomography. ARVO Meeting Abstracts. 86. Swarbrick HA, Wong G, O’Leary DJ. Corneal response to orthokera- 2010;51:3418. tology. Optom Vis Sci. 1998;75:791-799. 74. Young G. Evaluation of soft contact lens fitting characteristics.Optom 87. Shousha M, Karp C, Perez V, et al. Diagnosis and management of Vis Sci. 1996;73:247-254. conjunctival and corneal intraepithelial neoplasia using ultra high 75. Kracher GP, Stark WJ, Hirst LW. Extended wear contact lenses for resolution optical coherence tomography. Ophthalmology. In press. aphakia. Am J Optom. 1981;58:467-471. 88. Mutapcic L, Karp C, Haft P, et al. Ultra-high resolution anterior seg- 76. McNamara NA, Chan JS, Han SC, Polse KA, McKenney CD. Ef- ment optical coherence tomography in the evaluation of anterior cor- fects of hypoxia on corneal epithelial permeability. Am J Ophthalmol. neal dystrophies and degenerations. Ophthalmology. In press. 1999;127:153-157. 89. Shousha, MA, Yoo, SH, Wang, J. A novel technique to evaluate 77. Cui L, Wang J, Wang MR, Shen M. Dynamic evaluation of contact Fuchs endothelial dystrophy: ultra high resolution optical coherence lens movement and its interaction with blinking and ocular surface. tomography vs. specular microscopy. Presented at: American Society ARVO Meeting Abstracts. 2010;51:3431. of Cataract and Refractive Surgery Symposium and Congress; April 78. Gasson A, Morris J. The Contact Lens Manual: A Practical Guide to 9-14, 2010; Boston, MA. Fitting. Boston: Butterworth-Heinemann; 2003:214-215, 90. Kaluzny BJ, Szkulmowska A, Szkulmowski M, Bajraszewski T, Kow- 79. Hutchings N, Simpson TL, Hyun C, et al. Swelling of the human alczyk A, Wojtkowski M. Fuchs’ endothelial dystrophy in 830-nm cornea revealed by high-speed, ultrahigh-resolution optical coherence spectral domain optical coherence tomography. Ophthalmic Surg La- tomography. Invest Ophthalmol Vis Sci. 2010;51:4579-4584. sers Imaging. 2009;40:198-200. 80. Giasson C, Forthomme D. Comparison of central corneal thickness 91. Li Y, Tang M, Zhang X, Salaroli CH, Ramos JL, Huang D. Pachy- measurements between optical and ultrasound pachometers. Optom metric mapping with Fourier-domain optical coherence tomography. Vis Sci. 1992;69:236-241. J Cataract Refract Surg. 2010;36:826-831. 81. Wu Y, Clarke D, Mathew A, Nicoud I, Li X. Noninvasive optical 92. Tang M, Chen A, Li Y, Huang D. Corneal power measurement with coherence tomography monitoring of structure and hydration chang- Fourier-domain optical coherence tomography. J Cataract Refract es of human corneas in different preservation media. J Biomed Opt. Surg. 2010;36:2115-2122. 2011;16:026015.

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