Optical Coherence Tomography Angiographyfor Anterior Segment Vasculature Imaging

Marcus Ang, FRCSEd,1,2 Dawn A. Sim, FRCOphth,3 Pearse A. Keane, FRCOphth,3,4

Chelvin C.A. Sng, FRCSEd,1,5 Catherine A. Egan, FRCOphth,3 Adnan Tufail, FRCOphth,3

Mark R. Wilkins, FRCOphth2,4

Purpose: To evaluate the application of an optical coherence tomography angiography (OCTA) systemadapted for the assessment of anterior segment vasculature.

Design: Cross-sectional, observational study.Participants: Consecutive subjects with normal eyes on slit-lamp clinical examination and patients with

abnormal corneal neovascularization.Methods: All scans were performed using a commercially available AngioVue OCTA system (Optovue, Inc.,

Fremont, CA) using an anterior segment lens adapter and the split-spectrum amplitude decorrelation angiographyalgorithm. Each subject underwent scans from 4 quadrants (superior, inferior, nasal, and temporal) in each eye by2 trained, independent operators.

Main Outcome Measures: Analysis of signal strength, image quality, and reproducibility of corneal vascularmeasurements was performed.

Results: In our study of 20 normal subjects (10 men, 10 women; mean age, 25.3�7.8 years), we found goodrepeatability (k coefficient, 0.76) for image quality score and good interobserver agreement for vasculaturemeasurements (intraclass coefficient, 0.94). After optimization of the angiography scan protocol, vascular mea-surements within the regions of interest were compared in the superior versus inferior quadrants (meanvascular loops, 3.34�1.16 vs. 3.12 � 0.90 [P ¼ 0.768]; segment-to-loop ratio, 4.18�0.71 vs. 4.32�0.87 [P ¼0.129]; fractal dimension [Df] value, 1.78�0.06 vs. 1.78�0.06 [P ¼ 0.94]; vascular loop area, 25.9�14.5 vs.25.9�10.7 � 10�3 mm2 [P ¼ 0.21]) and nasal versus temporal quadrant (mean vascular loops, 2.89�0.98vs. 3.57�0.99 [P < 0.001]; segment-to-loop ratio, 3.94�0.69 vs. 4.55�0.78 [P ¼ 0.897]; Df value, 1.78�0.06 vs.1.77�0.06 [P ¼ 0.14]; vascular loop area, 29.7�15.7 vs. 22.1�7.1 � 10�3 mm2 [P ¼ 0.38]. We then used theestablished OCTA scanning protocol to visualize abnormal vasculature successfully in 5 patients with variouscorneal pathologic features, including graft-associated neovascularization, postherpetic keratitis scarring, lipidkeratopathy, and limbal stem cell deficiency.

Conclusions: This preliminary study describes a method for acquiring OCTA images of the cornea and limbalvasculature with substantial consistency. This technique may be useful for the objective evaluation ofcorneal neovascularization in the future. Ophthalmology 2015;-:1e8 ª 2015 by the American Academy ofOphthalmology.

Since its first in vivo use for the retina, optical coherence to-mography (OCT) imaging has revolutionized our ability toevaluate the eye and its structures on a microscopic level.1 Italso has been established as a useful tool in providing rapid,noncontact evaluation of the cornea and anterior segment.2,3

Further technological developments also have increased theimaging capabilities of OCT in terms of speed, image reso-lution, and,more recently, evaluation of vascular flow.4 Thesenew OCT imaging techniques have been described fornoninvasive evaluation of vessels within the retina and opticdisc.4,5 As opposed to Doppler OCT techniques, whichdepend on axial flow of blood, OCT angiography (OCTA)techniques visualize vessels via motion contrast imaging oferythrocyte movement across sequential B-scans.4

Currently, assessment of the corneal and anteriorsegment vasculature is constrained to slit-lamp photography

� 2015 by the American Academy of OphthalmologyPublished by Elsevier Inc.

or angiography techniques using fluorescein or indocyaninegreen.6 Semiautomatic quantitative techniques to analyzephotographic images have been described,7 withstandardized methods of quantification of cornealneovascularization established and used in several clinicaltrials.8e10 However, underestimation of poorly visibleblood vessels may occur, especially in the presence of densecorneal scars,11 whereas invasive angiography techniquesexpose patients to potential adverse reactions.6 Thus,methods of evaluating abnormal corneal neovascularizationremain important, given its prevalence and potential sight-threatening effects,12,13 where visual loss may ensue fromassociated corneal edema, scarring, and lipid deposition.14

As new antiangiogenic treatments for various cornealpathologic features with associated vascular changes arebeing developed,15 a recent roundtable expert review

1http://dx.doi.org/10.1016/j.ophtha.2015.05.017ISSN 0161-6420/15

Figure 1. Optical coherence tomography angiograms of the cornea andanterior segment. A, C, D, Examples of whole-depth, split-spectrumamplitude decorrelation optical coherence tomography angiograms with enface maximum projection of the corneolimbal vasculature in variousquadrants of the cornea. B, The binary image was processed with a selectivefilter and regions of interest along the corneal vascular arcade using amethod previously described; the white arrow points to an example of amarginal corneal vascular loop.12

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identified the development of new imaging techniques forthe evaluation of corneal neovascularization as animportant, unmet need.16

Therefore, we conducted a proof-of-concept study toevaluate the feasibility of using an OCTA device intendedfor retinal vessel imaging for the corneal and limbalvasculature. Although this imaging technique has been usedto evaluate retinal vascular pathologic features such aschoroidal neovascularization,17 to our knowledge, its rolehas not been reported for use in the anterior segment atthe time of this publication. We then used the derivedOCTA scanning protocol to evaluate and describequantitatively abnormal corneal neovascularization inpatients with various corneal pathologic features in apreliminary clinical study.

Methods

In the first phase of the study, to establish the OCTA scanningprotocol for the anterior segment, we performed OCTA in 20 sub-jects with no ocular history and a normal slit-lamp examination atthe Moorfields Eye Hospital from October 1, 2014, throughDecember 31, 2014. Our study followed the principles of theDeclaration of Helsinki, with ethics approval obtained from the localinstitutional review board. All subjects underwent imaging using thesplit-spectrum amplitude decorrelation angiography algorithm onthe on the AngioVue OCTA system (Optovue, Inc., Fremont, CA)intended for retina imaging (AngioRetina mode), but with theanterior segment optical adaptor lens. Each scan was performed withaxial resolution of 5 mm and a beam width of 22 mm, with a lightsource centered on 840 nm. The instrument captures consecutive B-scans containing 304�304 A-scans at 70 000 scans per second in aslow transverse direction, which constructs a 3-dimensional scancube in approximately 3 to 4 seconds.4 Because the default focus ofthe system is for the retina, the autofocus function was turned off,and manual adjustments to the XYZ focal lengths had to be madeuntil the vessels of interest were seen clearly in focus on thecamera image. Because this often led to the anterior segment lensadapter being just 2 to 4 cm from the subject’s anterior cornealsurface, care had to be taken to prevent contact with the eye. Forthe proof-of-concept phase of the study, all subjects underwentOCTA scans (6�6-mm volume cubes) in 4 quadrants of the cornealimbus (superior, inferior, temporal, and nasal) in both eyes by 2independent trained operators.

Image Analysis

The best scans were processed automatically to reduce motionartifacts such as transverse saccadic and residual axial motion bythe internal software (ReVue version 2014.2.0.15; Optovue, Inc.).Next, images were exported from the system as a portable networkgraphics image file into ImageJ 1.38X software (National Institutesof Health, Bethesda, MD) for analysis, similar to a previouslydescribed method for quantifying corneal neovascularization.18 Inbrief, we identified the regions of interest (ROIs) in each scan bylabeling 5 contiguous squares (100 pixels; 850 mm) spanning acircumferential arc length of approximately 4 mm, aligned alongthe circumference of the anterior border of the corneal limbus(Fig 1). We then used a selective filter to highlight the linearstructures such as blood vessels and to reduce the surroundingnoise to export the resulting vascular tree as a binary image forfurther processing, similar to a previously described method.19

Each ROI was assessed for the number of vascular loops (asillustrated in Fig 1),6 vessel segments (previously defined as the

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section between 2 branch points or a terminal point),19 fractaldimension (Df) value, and the area enclosed by each vascularloop (square millimeters).19,20 The quality of the scan imageswere assessed using the signal strength index and image qualityscore using a recognized system, that is, 0 to 4 (0, no vesseldiscernible; 1, poor vessel delineation; 2, good vessel delineation;3, very good vessel delineation; 4, excellent vessel delineation) on2 scans per quadrant, performed by 2 independent, masked as-sessors.20 We then used the scan protocol as derived above toperform OCTA imaging in 5 patients with various cornealpathologic features, namely, corneal neovascularization in acorneal graft, pterygium, postherpetic keratitis scar, lipidkeratopathy, and limbal stem cell deficiency.

Statistical Analysis

To evaluate the scan protocol described, we analyzed all scanimages obtained for repeatability, image quality, and vascularmeasurements between quadrants. We calculated the k coefficientvalue for the repeatability of scans using the image quality score,where k � 0.2 was considered slight, k ¼ 0.21 to 0.40 wasconsidered fair, k ¼ 0.41 to 0.6 was considered moderate, k ¼ 0.61to 0.8 was considered substantial, and k ¼ 0.81 to 1.0 wasconsidered almost perfect in agreement.21 The intraclass coefficient(ICC) was calculated for vascular measurements performed by bothindependent assessors, evaluating the mean number of vascularloops and segment-to-loop ratios in the ROI of the scans in eachquadrant. Statistical analysis also included descriptive statistics,where the mean � standard deviation was calculated for thecontinuous variables and compared using the ManneWhitney Utest. A P value less than 0.05 was considered statistically signifi-cant for comparisons between 2 quadrants. Statistical Package forthe Social Sciences software version 17.0 (SPSS, Inc., Chicago, IL)was used to analyze the data.

Figure 2. Optical coherence tomography angiograms showing neovascularization in a corneal graft. Abnormal corneal neovascularization associated withcorneal graft rejection in an eye with a penetrating keratoplasty is much clearer on (B, D) optical coherence tomography angiography scans compared with(A) slit-lamp examination and (C) a red-free image.

Ang et al � Anterior Segment OCT Angiography

Results

The first phase of our study was performed in both eyes of 20subjects (10 men, 10 women; mean age, 25.25�7.87 years) withnormal slit-lamp examination results and no evidence of abnormalcorneal vessels. Overall, we found substantial repeatability of scansin all quadrants in terms of image quality score (k ¼ 0.76), withgood interobserver agreement for vasculature measurements (ICC,0.94). Superior and inferior quadrant scans showed a similar signalstrength index (39.04�15.06 vs. 39.28�16.71; P ¼ 0.89), whereastemporal scans had a higher signal strength index compared withnasal scans (45.23�15.23 vs. 33.09�14.14; P < 0.001). Wecompared vascular measurements within the ROI of the superiorand inferior quadrants (mean vascular loops: 3.34�1.16 vs.3.12�0.90 [P ¼ 0.768]; segment-to-loop ratio, 4.18�0.71 vs.4.32�0.87 [P ¼ 0.129]; Df value, 1.78�0.06 vs. 1.78�0.06 [P ¼0.94]; vascular loop area, 25.9�14.5 vs. 25.9�10.7 � 10�3 mm2

[P ¼ 0.21]), as well as nasal versus temporal quadrants (meanvascular loops, 2.89�0.98 vs. 3.57�0.99 [P < 0.001]; segment-to-loop ratio, 3.94�0.69 vs. 4.55�0.78 [P ¼ 0.897]; Df value,1.78�0.06 vs. 1.77�0.06 [P ¼ 0.14]; vascular loop area,29.7�15.7 vs. 22.1�7.1 � 10�3 mm2 [P ¼ 0.38]).

We then used the derived scan protocol to evaluate theOCTA system in various clinical conditions with abnormalcorneolimbal neovascularization. Figure 2 depicts the eye in a55-year-old man who underwent a penetrating keratoplasty forbullous keratopathy and sought treatment 6 months after

surgery, with signs of an early rejection of his corneal graft.Upon slit-lamp examination, there was mild anterior chamberinflammation with an epithelial defect, stromal edema withkeratic precipitates, and early corneal neovascularization at thegraftehost junction from 12 to 3 o’clock (Fig 2A). The OCTAsystem was able to outline the corneal vessels that wereinvading the corneal graft, which were not as clearly visibleon the slit-lamp images (Fig 2B, D). Figure 3A, Bdemonstrates the OCTA scans of a 60-year-old woman with apterygium encroaching on the visual axis, with the abnormalinvasive vessels clearly delineated in the fibrovascular tissue.We also documented a case of previous herpetic keratitis in a28-year-old woman with residual stromal scar and cornealneovascularization and a clear visualization of the abnormalvessels invading the corneal stroma on the OCTA scans thatwere not as clearly seen on slit-lamp images (Fig 3C, D).

We also observed that one of the advantages of using the OCTAfor anterior segment pathologic features is that it provides simulta-neous assessment of the depth of the lesion, as well as its associatedabnormal blood vessels. Figure 4 depicts serial cross-sectionalOCTA images at various depths in the same eye with a nasal pte-rygium from Figure 3, while also showing the incursion of theabnormal fibrovascular tissue into the corneal stroma. The OCTAimages also show the abnormal vascular loops, which now format the head of the pterygium, associated with a relative loss of thenormal corneal vascular arcades at the corneal limbus underneaththe pterygium wing. Another feature of the OCTA technique is

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Figure 3. Slit-lamp images and optical coherence tomography angiograms of clinical examples with aberrant anterior segment vessels. Illustration of theabnormal fibrovasculature structure of a pterygium, where abnormal blood vascular loops at the head of the pterygium are delineated by (B) the opticalcoherence tomography angiography (OCTA) scan using the 3�3-mm scan function, which are less apparent on (A) slit-lamp photography. The fibro-vascular structure of the pterygium may make it difficult to differentiate stromal fibers from blood vessels in the remaining body of the pterygium, limited bythe current built-in image processing software. C, D, A case of postherpetic keratitis scar, where the corneal neovascularization invading the corneal stromais not visualized clearly on (C) slit-lamp examination but is seen clearly on (D) the OCTA scan. However, although the limited field of view from the scansuggests that vascular loops of the marginal arcade of the adjacent limbus are retained, the OCTA is unable to differentiate the origin of the abnormalneovascularization or the margins or demarcation of the normal and abnormal vessels.

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demonstrated in Figure 5: OCTA scans reveal abnormal feedervessels (Fig 5B), which are obscured by the dense lipid depositsand scarring in the slit-lamp images (Fig 5A), in an eye with lipidkeratopathy from previous interstitial keratitis in a 45-year-oldman. The ability to detect subtle vascular changes also is seen inFigure 5C, D, where a localized area of corneal neovascularization isoutlined within the corneal scar on OCTA, with disruption of thenormal corneal marginal vascular arcades inferior to the scar, ofan eye of a 62-year-old man with limited limbal stem celldeficiency from long-standing ocular rosacea.

Discussion

In this article we describe an application of OCTA tech-nology for noninvasive imaging of the anterior segmentvasculature. Because this is a relatively new technologydeveloped for retinal use, we initially conducted a proof-of-concept study of eyes of healthy subjects to determine thescan protocol, which produced substantially consistent scansof the corneolimbal vessels (k value, 0.76; ICC, 0.94).Although our corneal vascular measurements were similar

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in terms of consistency with those of a previous cornealindocyanine green angiography (ICGA) study (ICC,0.67e0.83),19 we recognize that several aspects such as age,gender, or other ocular factors may lead to variation in loopsize and branching between subjects, even for similarcorneal quadrants.19 However, the aim of this study wasnot to describe the corneal vasculature in detail, but ratherto demonstrate that this OCTA system may be adapted foranterior segment vasculature imaging with adequateconsistency. We used the same scanning protocol toimage eyes with abnormal corneal vasculature to confirmthat the OCTA could successfully image aberrant bloodvessels amid various important pathologic features, suchas vascularization in a corneal graft that is associated withcorneal graft rejection22 and postherpetic keratitis, whereits treatment is increasingly being evaluated using newantiangiogenic therapies.16

Normal corneal and limbal vasculature anatomic featureshave been described using fluorescein angiography (FA) and,more recently, ICGA.23e25 Because abnormal corneal neo-vascularization may arise from the corneal marginal arcade or

Figure 4. Serial cross-sectional optical coherence tomography angiography (OCTA) scans of a pterygium at varying corneal and scleral depths allow forsimultaneous assessment of the structure, depth of corneal stromal invasion, and the abnormal blood vessels in this fibrovascular lesion. Left and middlecolumns, The OCTA scans delineating stromal fibers and blood vessels with a coronal or en face view at varying depths. (Right column) Scans show thetraditional cross-sectional or B-scan view. The current OCTA built-in software allows the user to examine multiple, consecutive, cross-sectional and en facescans to reconstruct a 3-dimensional evaluation of the lesion and its associated vasculature.

Ang et al � Anterior Segment OCT Angiography

the limbal palisades vessels, objective imaging of the cornealvasculature is important to understand and potentially treat theassociated abnormal vascular supply of corneal pathologicfeatures.25,26 Our findings support previous observations thatvessels in the periphery of the cornea comprise a fine capillarynetwork consisting of vascular loops with 3 to 4 branches,which are not as evident on slit-lamp images.19 Although aprevious study of corneal vascular arcades using ICGA wasdescribed in detail, these measurements were from variousrandom quadrants of the corneal limbus.19 In our study, wecompared scans from each quadrant and found that therewas a higher density of vascular loops in the temporal

marginal corneal arcades compared with those in the nasalquadrants. This may provide interesting insights into thepotential significance of these differences in corneolimbalvasculature, particularly with regard to pathologic features,such as pterygia, that more frequently affect the nasalaspects of the anterior segment. Moreover, in comparing thecorneal vasculature in normal eyes with various pathologicfeatures such as postherpetic scarring and limbal stem celldeficiency, we observed qualitative changes to the normalcorneal marginal arcades, which may have potential forprognostic evaluation in these conditions. However, futureprospective studies of corneal and limbal vascular anatomic

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Figure 5. Slit-lamp images and optical coherence tomography angiograms of clinical examples of abnormal corneal neovascularization. Demonstration ofcorneal neovascularization in a case of lipid keratopathy is clearly imaged by (B) the optical coherence tomography angiography (OCTA) system but is notapparent on (A) the slit-lamp image because of the dense stromal scarring and lipid deposits. Note the artifacts in this scan, produced by the intrastromallipid deposition, which may either obscure or appear as abnormal vessels. This may be discerned from actual vessels by scrolling between scans and variousdepths in the en face function and correlating with slit-lamp photographs. C, Abnormal corneal and limbal vessels are seen easily in a case of localized limbalstem cell deficiency in this example of an eye with ocular rosacea. D, Early signs of disruption of the normal corneal vascular arcades on the OCTA scans arerecognized as being more extensive than on clinical slit-lamp images.

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features correlating OCTA with established imagingtechniques used in clinical trials of antiangiogenic drugs forcorneal vasculature8e10 probably are required to study theseobservations in greater detail using quantitative assessments.

Although FA and ICGA have been useful in visualizingareas of corneal neovascularization,20 these invasive testsare performed infrequently for the anterior segmentcompared with the posterior segment. Although FApotentially is able to detect abnormal corneal vesselmaturity and inflammatory activity, the leakage of dyemay affect vessel evaluation and measurements.6

However, indocyanine green is a larger molecule thatstays within the corneal vasculature, thereby improvingdelineation of blood vessels, even in the presence ofcorneal stromal scars.20 Nevertheless, both FA and ICGAare invasive procedures that can be both time consumingand relatively difficult to perform, with a significantlearning curve, exemplified by one corneal ICGA study inwhich up to 40% of images had to be excluded.20

Moreover, patients may have contraindications to dyeinjections, and clinicians have to be prepared for rare butserious adverse reactions associated with the intravenousadministration of fluorescein or indocyanine green dyes.27,28

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Optical coherence tomography angiography provides apromising rapid and noninvasive alternative to FA andICGA that already has useful clinical indications such asdetecting and monitoring inflammation, vascularization, orareas of damage that are not clinically visible.25 However,one of the added benefits of OCTA is that it acquireshigh-resolution cross-sectional images, simultaneouslyproviding information on the depth of both the cornealpathologic features and the penetration of its associatedabnormal vessels. This potentially aids preoperative surgicalplanning for corneal lesions, such as deciding on the depthand location of feeder vessel diathermy before anteriorlamellar keratoplasty for postherpetic scars or a quickassessment of an invasive pterygium to evaluate the depth ofthe fibrovascular incursion into the corneal stroma (Fig 4).With the use of image processing and objectiveassessment of areas of vessel invasion,6 OCTA also maybe useful for monitoring vascular changes before and aftertreatment when assessing new therapies for abnormalcorneal neovascularization.16 Furthermore, the potentialclinical applications of anterior segment OCTA may notbe limited to the cornea; for example, evaluatingconjunctival and scleral vasculature may add further

Ang et al � Anterior Segment OCT Angiography

information to bleb morphologic features after glaucomasurgery assessed by OCT.29

The OCTA system used in this study uses decorrelativetechniques to detect phase variations and OCT signal in-tensity that result from blood flow, which are independent offlow orientation over a larger range of flow velocities.4

Using the scanning protocol described above, we foundthat corneal vessels were outlined in the presence ofsuperficial corneal scarring or lipid deposition. However,deeper vessels in corneal opacities may not be delineatedas clearly by the OCTA system, and this requires furtherstudy in a larger series of cases with corneal pathologicfeatures, with comparisons of FA and ICGA. Cliniciansalso should note that current OCTA technology mayproduce scans that contain artifacts that appear asabnormal vessels (Fig 5). These artifacts may bedistinguished from actual abnormal corneal vessels byexamining multiple consecutive scans in the en facefunction and correlating with slit-lamp photographs. Otherlimitations of this OCTA system include an image resolu-tion that is insufficient for distinguishing normal vesselsfrom abnormal vessels, the inability to demonstrate vesselleakage, and a limited field of view compared with currentangiography techniques. Thus, in its current iteration, thesystem may not be useful for evaluating large areas ofneovascularization compared with standardized slit-lampphotography techniques established for clinical trials.9

Moreover, current OCTA systems are optimized for retinalimaging; thus, we had to make adjustments to thescanning technique while using the anterior segmentadapter. Because the lens had to be relatively close to thesurface of the cornea for the vessels to be in focus, imageacquisition was relatively easier in the temporal quadrantscompared with the nasal quadrants, as illustrated by thedifferences in signal strength index. Nonetheless, ourinitial experience with the AngioVue OCTA systemrevealed a relatively easy learning curve, rapid acquisition(3e4 seconds per scan) of images of the cornea, and goodoverall reproducibility. As a noninvasive imagingtechnique that is acquired with relative ease, it has thepotential to be implemented easily as part of routineclinical evaluation. This is encouraging because furtherstreamlining and development of OCTA technology andits software, in particular for the anterior segment, mayimprove image resolution, shorten acquisition time with alarger field of view, or even measure variations in oxygensaturation within the vessels.30

We recognize limitations of our preliminary cross-sectional study, adapting the use of this OCTA system forthe cornea and anterior segment. A large prospective studyof various corneal pathologic features with comparisonswith slit-lamp photography, invasive angiography tech-niques, or histologic images would have been ideal toevaluate this OCTA technology specifically for the anteriorsegment. Moreover, the existing OCTA image analysissoftware comes with inherent limitations, such as inability toanalyze serial scans at fixed landmarks on the cornea(registration or labeling is not available currently), as-sumptions of the vascular plane, and the underestimation ofvessel density or smaller vessels because of the threshold

method used.19 Future challenges to improve the clinicalapplication of OCTA for corneal vasculature include theneed to develop standardized techniques with filters oralgorithms to highlight linear structures and reducesurrounding noise in the images, with analysis andmonitoring of changes in neovascularization over time forvarious corneal pathologic features. Nevertheless, wepresent unprecedented study findings that suggest thisrapid, noninvasive OCTA system has the potential toproduce consistent images of the anterior segmentvasculature, which may aid in further understanding of therole of abnormal neovascularization in various corneal,conjunctival, and scleral diseases.24

In summary, we describe results from a preliminaryevaluation of an OCTA system, potentially useful for theimaging of both normal and abnormal corneal vessels. Ourstudy suggests that the prospects of this rapid, noninvasiveangiography technique for wider clinical applications in theanterior segment are promising. Further studies are requiredto confirm whether this imaging technique is useful for theobjective evaluation of corneal neovascularization comparedwith other angiography techniques.

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Footnotes and Financial Disclosures

Originally received: April 4, 2015.Final revision: May 9, 2015.Accepted: May 12, 2015.Available online: ---. Manuscript no. 2015-555.1 Department of Cornea and External Eye Diseases, Singapore EyeResearch Institute, Singapore National Eye Center, Singapore.2 Department of External Eye Diseases, Moorfields Eye Hospital NHSFoundation Trust, London, United Kingdom.3 Department of Medical Retina, Moorfields Eye Hospital NHS FoundationTrust, London, United Kingdom.4 Institute of Ophthalmology, University College London, UnitedKingdom.5 Department of Ophthalmology, National University Hospital, Singapore.

Financial Disclosure(s):The author(s) have made the following disclosure(s): A.T.: Nonfinancial,technical support e Optovue, Inc., Fremont, CA.

Author Contributions:

Conception and design: Ang, Sim, Keane, Sng, Egan, Tufail, Wilkins

Analysis and interpretation: Ang, Sim, Keane, Sng, Egan, Tufail, Wilkins

Data collection: Ang, Sim, Keane, Tufail, Wilkins

Obtained funding:

Overall responsibility: Ang, Sim, Keane, Sng, Egan, Tufail, Wilkins

Abbreviations and Acronyms:Df ¼ fractal dimension; FA ¼ fluorescein angiography; ICC ¼ intraclasscoefficient; ICGA ¼ indocyanine green angiography; OCT ¼ opticalcoherence tomography; OCTA ¼ optical coherence tomography angiog-raphy; ROI ¼ region of interest.

Correspondence:Marcus Ang, FAMS, FRCSEd, Singapore National Eye Centre, SingaporeEye Research Institute, 11 Third Hospital Avenue, Singapore 168751,Republic of Singapore. E-mail: marcus.ang.h.n@snec.com.sg.