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Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ioii20 Ocular Immunology and Inflammation ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: https://www.tandfonline.com/loi/ioii20 Anterior Segment Optical Coherence Tomography Angiography and Optical Coherence Tomography in the Evaluation of Episcleritis and Scleritis Scott C. Hau, Kavya Devarajan & Marcus Ang To cite this article: Scott C. Hau, Kavya Devarajan & Marcus Ang (2019): Anterior Segment Optical Coherence Tomography Angiography and Optical Coherence Tomography in the Evaluation of Episcleritis and Scleritis, Ocular Immunology and Inflammation, DOI: 10.1080/09273948.2019.1682617 To link to this article: https://doi.org/10.1080/09273948.2019.1682617 Published online: 12 Nov 2019. Submit your article to this journal Article views: 15 View related articles View Crossmark data

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Page 1: in the Evaluation of Episcleritis and Scleritis

Full Terms & Conditions of access and use can be found athttps://www.tandfonline.com/action/journalInformation?journalCode=ioii20

Ocular Immunology and Inflammation

ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: https://www.tandfonline.com/loi/ioii20

Anterior Segment Optical Coherence TomographyAngiography and Optical Coherence Tomographyin the Evaluation of Episcleritis and Scleritis

Scott C. Hau, Kavya Devarajan & Marcus Ang

To cite this article: Scott C. Hau, Kavya Devarajan & Marcus Ang (2019): Anterior SegmentOptical Coherence Tomography Angiography and Optical Coherence Tomography inthe Evaluation of Episcleritis and Scleritis, Ocular Immunology and Inflammation, DOI:10.1080/09273948.2019.1682617

To link to this article: https://doi.org/10.1080/09273948.2019.1682617

Published online: 12 Nov 2019.

Submit your article to this journal

Article views: 15

View related articles

View Crossmark data

Page 2: in the Evaluation of Episcleritis and Scleritis

ORIGINAL ARTICLE

Anterior Segment Optical Coherence TomographyAngiography and Optical Coherence Tomography in

the Evaluation of Episcleritis and ScleritisScott C. Hau, BSc, MSc, MCOptom

1, Kavya Devarajan, BSc, MSc2, and Marcus Ang, FRCS, PhD

2,3

1NIHR Moorfields Clinical Research Facility, Moorfields Eye Hospital, London, UK, 2Singapore Eye ResearchInstitute, Singapore National Eye Centre, Singapore, Singapore, and 3Department of Ophthalmology and

Visual Sciences, Duke–National University of Singapore Medical School, Singapore, Singapore

ABSTRACT

Purpose: To evaluate the feasibility of using anterior segment optical coherence tomography (AS-OCT) andAS-OCTangiography (AS-OCTA) in assessing patients with episcleritis and scleritis.Methods: Degree of vascularity [vessel density index (VDI)], measured with AS-OCTA, and sclera thickness[conjunctiva epithelium (CE), conjunctiva/episclera complex (CEC), and episclera/sclera complex (ESC)],measured with AS-OCT were compared.Results: A total of 37 eyes (13 episcleritis, 11 scleritis, 13 controls) were analyzed. VDI was lowest for controlsfor the various tissue depths (p < .001). Episcleritis versus scleritis revealed a significant difference in VDI atESC (38.1 ± 11.4% vs 46.4 ± 6.4%; p = .03). Mean sclera thickness was lower in controls for CE (p < .001), CEC(p < .001) but not for ESC (p = .54).Conclusions: The degree of vascularity and tissue thickness were different between episcleritis, scleritis andcontrols. AS-OCTA and AS-OCT may potentially be useful in evaluating patients with scleral inflammation.

Keywords: Anterior segment optical coherence angiography, anterior segment optical coherence tomography,episcleritis, inflammation, scleritis

Scleritis is an inflammatory disease that affects thesclera; it can be classified as nodular or diffuse, andmay affect one or both eyes. The incidence rates forscleritis have been reported to range between 3.4 and4.1 per 100,000 person-years.1,2 In anterior scleritis, boththe superficial episcleral capillary plexus and the deepepiscleral capillary network are affected. In contrast,episcleritis affects only the anterior episcleral tissuewithout involving the deeper episcleral tissue that over-lies the sclera (episclera/sclera complex). The incidenceof episcleritis is more difficult to ascertain due to underreporting as not all patients seek medical care but theestimated incidence rates have been reported to rangebetween 21.7 and 41.0 per 100,000 person-years.1,2

Episcleritis is often self-limiting with no underlyingsystemic association whereas uncontrolled scleritis canprogress to ischemia, necrosis, and in some cases,

perforation. Clinical examination of the anteriorsegment is typically performed to differentiate thetwo conditions; the vascular engorgement in epi-scleritis tends to produce a distinct red hue whereasin scleritis, the vascular engorgement involves thewhole episcleral vascular network resulting ina characteristic bluish-violet hue.3 However, clinicalassessment is mainly subjective which makes differ-entiating the two conditions not always thatstraightforward, especially in a general ophthalmol-ogy setting. Patient symptoms can aid in the diag-nosis, globe tenderness and severe pain is oftenassociated with scleritis but not all patients withscleritis present with pain especially in those whotake non-steroidal anti-inflammatory drugs.

Anterior segment fluorescein and indocyanine greenangiography (ICG) have been shown to produce

Received 25 October 2018; revised 15 October 2019; accepted 16 October 2019Correspondence: Marcus Ang Singapore National Eye Centre, 11 Third Hospital Avenue 168751, Singapore. E-mail: [email protected] versions of one or more of the figures in the article can be found online at www.tandfonline.com/ioii.

Ocular Immunology & Inflammation, 2019; 00(00): 1–8© 2019 Taylor & Francis Group, LLCISSN: 0927-3948 print / 1744-5078 onlineDOI: 10.1080/09273948.2019.1682617

1

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distinctive patterns in episcleritis and scleritis but itsvalue is limited by the invasive nature of theprocedure.4–6 Previous studies have shown that ultra-sound biomicroscopy (UBM) and anterior segment opti-cal coherence tomography (AS-OCT) are potentiallyuseful in characterizing scleral inflammation and indifferentiating episcleritis from scleritis.7–11 However,there are limitations with these technologies includingthe lack of accurate delineation of the different tissuelayers with UBM because of the relatively poorer reso-lution and the difficulty with penetration of light inopaque, edematous tissue with AS-OCT.7–11

Optical coherence tomography angiography(OCTA), a non-contact imaging system that detectsphase variation in reflectivity to detect vascular flow,has been shown to be useful in detecting blood ves-sels in retina, choroidal and optic nerve conditions.12

More recently, it has been shown that OCTA, adaptedfor the cornea, is able to image the cornea and limbalvasculature,13 serial monitoring of corneal vasculari-zation in clinical evaluation of keratitis,14 and alsocomparable to ICG for quantifying area of cornealvascularization.15 As the degree and depth of vascu-larity for episcleritis and scleritis are potentially dif-ferent, we conducted a pilot study to evaluate thefeasibility of using anterior segment OCTA (AS-OCTA) in conjunction with AS-OCT in evaluatingscleral inflammation.

MATERIALS AND METHODS

Consecutive patients with episcleritis and scleritis,presenting to the A&E and uveitis department, atMoorfields Eye Hospital, were prospectively recruitedbetween March to September 2017. All patients werenewly diagnosed and have not had any previoustreatment for their ocular inflammation. The inclusioncriteria were patients over the age of 18 years withclinical signs of either episcleritis or scleritis. Theexclusion criteria were patients with other causes ofocular disease and inflammation including trauma,contact lens associated complication, post-surgery,inflamed pterygium or pinguecula, conjunctivitis, ker-atitis and uveitis. Clinical diagnosis of either condi-tion was made based on the appearance and on thepresenting symptoms for each patient. A diagnosis ofepiscleritis was made based on mild edema of theepiscleral tissue and vascular engorgement of thesuperficial episcleral blood vessels, associated withmild ocular discomfort.16 Scleritis was diagnosed onthe symptoms of ocular pain that radiate to the brow,jaw or sinuses associated with signs of edema affect-ing the episclera and scleral regions.16 Episcleritis wascategorized into diffuse or nodular and scleritis wasclassified into diffuse, nodular, necrotizing withinflammation and necrotizing without inflammation

(scleromalacia perforans). The degree of scleralinflammation was defined from 0 to 4+,17 and ifmore than one quadrant was affected, the most severeaffected region was used for the final grading classi-fication. Age-matched healthy controls, with no his-tory of ocular or systemic disease, were recruitedfrom staff members within the A&E department andone eye from each subject, chosen from random, wasselected for imaging. Anterior segment photos in fourquadrants were taken in all eyes with a digital camera(Topcon ATE-600, with D1X digital camera, NikonCorp) with a diffuse illumination, ×10 magnification,flash power 4.5 at 45° angle. The study received localinstitutional ethics committee approval and adheredto the tenets of Declaration of Helsinki. Informedconsent was obtained from all patients.

AS-OCTA and AS-OCT Image Acquisition

AS-OCTA images of the affected eye were performedby one operator (SH) with the AngioVue OCTA system(Optovue Inc., Fremont, California, USA) using the longcornea adaptor module in the Cornea Angio setting.The specification of the machine has been describedpreviously.18 The 6 mm x 6 mm scan setting was usedand only the affected region of the eye was scanned foreach patient. To ensure optimum image quality, theinstrument was positioned so that the scanning lightwas directly perpendicular to the region of interestand the images were obtained midway between thelimbus and site of insertion of the rectus muscle. Foreach image acquisition, a series of imageswere obtainedin the coronal plane starting from the superficial con-junctiva all the way to the sclera stroma. Three imagecomposites were acquired for the affected quadrant andthe best series of images were used for the blood vesseldensity or vessel density index (VDI) analysis. In addi-tion, three corresponding AS-OCT line raster cross-sectional images of the affected area were also obtainedand the best image showing the full extent of the scleratissue, with minimal posterior shadowing, was used forscleral thickness measurement. In obtaining theAS-OCT images, care was taken to ensure the scanninglight was directly perpendicular to the affected area andthat the anterior border of the sclera was as parallel tothe horizontal axis as possible. Imageswhere the poster-ior scleral limitwas not clearly seenwere excluded fromthe analysis. If more than one quadrant of the eye wasaffected, the above imaging acquisition steps wererepeated for each quadrant. The machine hasa scanning speed of 70 000 scans/second, 840nm wave-length light source, and the optical resolution is 3 µmaxial and 15 µm in the lateral direction. The images areprocessed using the split-spectrum amplitude de-corr-elation angiography algorithm.19

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AS-OCTA and AS-OCT Image Analysis

Manual segmentations of the images were performedto delineate the different layers of the sclera asdetected by the corresponding AS-OCT images. Thedegree of vascularity was analyzed by dividing eachimage into the following anatomical layers: conjunc-tiva epithelium – defined by the border of the mostanterior layer; conjunctival/episclera complex –

defined by the most anterior layer to the posteriorlimit of the areas of hyporeflectivity seen within theconjunctival/episclera region; and episclera/scleracomplex – defined by the posterior limit of hypore-flectivity to the most posterior edge of the image,Figure 1. One image showing the best quality ofblood vessels, with the least amount of motion artifactwas selected for each tissue layer and exported asa portable network file and analyzed using a customcode written in Matlab R2016a 64-bit (TheMathworks, Inc., Natick, MA, USA). If more thanone quadrant was affected then one image corre-sponding to each tissue layer from each effectedquadrant was exported and the average vascularityand tissue thickness obtained during image analysis.For the corresponding scleral tissue thickness mea-surements, for each raster AS-OCT scan three read-ings of the anterior to posterior limit of each tissuelayer, over a horizontal chord length of 3 mm, wereobtained and then averaged to provide the tissuethickness measurement for each tissue layer to reducevariability in measurements. For control eyes, animage corresponding to each tissue layer of the fourquadrants was obtained and then averaged for bothvascularity and tissue thickness.

All images were analyzed by one observer (KD)who was masked to the diagnosis. Pre-processingsteps to eliminate speckle noise and motion artifactswere performed by applying Gaussian and band-passfiltering. Subsequently, top-hat filtering was done toimprove the Signal-to-Noise Ratio while preservingthe image features. Local phase-based filter for opti-mal enhancement of segmented vessels was applied;thereafter, where an infinite perimeter active contourmodel to partition the enhanced image into a binaryimage (vessel pixels, 1; background, 0) wasperformed.20,21 The VDI, expressed as a percentage,was then derived as the ratio of the total area ofbinarized vessel pixels to the total pixel area of theraw image ×100.

Data Analysis

Data analysis was performed with SPSS software(IBM SPSS Statistics V24, USA). As this was a pilotstudy to evaluate the feasibility of using AS-OCTA inassessing scleral inflammation, no prior power calcu-lation was performed to estimate sample size so theresults would need to be interpreted with caution anddescribed as exploratory. Descriptive statistics wereused for patient demographic data. Normality of thedata was checked with the Shapiro-Wilk’s test andinspection of the histograms. One way ANOVA wasused to compare the mean VDI values of the variousanatomical layers for all the groups followed by theLevene’s test to check for homogeneity of variance,and then post hoc analysis performed with theBonferroni test. A value of p < .05 was deemed statis-tically significant.

RESULTS

A total of 26 consecutive patients (26 eyes) with eitherepiscleritis or scleritis were recruited in this pilotstudy. Two eyes with scleritis were excluded fromthe analysis due to the difficulty in delineating thedifferent tissue layers and the posterior scleral marginaccurately. The remaining 24 patients (24 eyes) wereanalyzed. The mean age of the patients was 42 years ±10.0, and 12 (52.2%) were female. Diffuse scleritis wasfound in 7 eyes, nodular scleritis in 4, diffuse episcler-itis in 11, and nodular episcleritis in 2 eyes. There wasa systemic association in three cases of scleritis: onegranulomatosis with polyangiitis, one HLAB27-related, and one with C-ANCA related vasculitis.Apart from these three patients, the remaining casesof scleritis and all of the episcleritis were diagnosed asidiopathic. Thirteen normal controls (13 eyes) wererecruited; their mean age was 40 ± 8.7 and 6 (46.2%)were female.

FIGURE 1. Representative anterior segment optical coherencetomography image of a case of anterior diffuse scleritis show-ing the definition of the different tissue layers for the purposeof manual segmentation: Conjunctiva epithelium (diamondshapes) – defined by the boundary of the most anterior layerof hyporeflectivity; Conjunctiva/episclera complex (dashedtwo-headed arrow) – defined by the measurement from themost anterior layer to the posterior limit of the areas of hypor-eflectivity within the conjunctival/episclera region; Episclera/sclera complex (dotted two-headed arrow) – defined by theposterior limit of hyporeflectivity of the conjunctiva/episcleraregion to the most posterior edge of the image.

AS-OCT Angiography in Scleral Inflammation 3

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VDI Analysis

Figure 2 shows a composite image indicating the ves-sel density at the conjunctiva epithelium, conjuncti-val/episclera complex, and episclera/sclera complex,for diffuse episcleritis (A-D), nodular episcleritis(E-H), diffuse scleritis (I-L), nodular scleritis (M-P),and control (Q-T). AS-OCTA revealed the VDIincreased with increasing scleral depth and therewas a significant difference in values between thethree groups for the various tissue depths, Table 1.Post hoc comparison revealed a significant difference

between both episcleritis and scleritis versus controlat all the layers: conjunctiva epithelium (p < .001),conjunctiva/episclera complex (p < .001) and epi-sclera/sclera complex (episcleritis, p = .001; scleritis,p < .001). By contrast, post hoc comparison did notreveal any significant difference in AS-OCTA betweenepiscleritis and scleritis at the conjunctiva epithelium(p = .99), conjunctiva/episclera complex (p = .73) butthere was a significant difference in VDI at the epi-sclera/sclera complex (p = .03).

For AS-OCT tissue thickness measurement, therewas a significant difference between the three groups

FIGURE 2. Composite image showing the anterior segment optical coherence tomography angiography vessel density imagesobtained at the different tissue layer for four cases of anterior scleral inflammation and one control. Slit lamp image of a case ofsectoral diffuse episcleritis (a) with corresponding vessel density image at the conjunctiva epithelium (b), conjunctiva/episcleracomplex (c), and episclera/sclera complex (d). Slit lamp image of a case of nodular episcleritis (e) with corresponding vessel densityimage at the conjunctiva epithelium (f), conjunctiva/episclera complex (g), and episclera/sclera complex (h). Slit lamp image of a caseof diffuse scleritis (i) with corresponding vessel density image at the conjunctiva epithelium (j), conjunctiva/episclera complex (k),and episclera/sclera complex (l). Slit lamp image of a case of nodular scleritis (m) with corresponding vessel density image at theconjunctiva epithelium (n), conjunctiva/episclera complex (o), and episclera/sclera complex (p). Slit lamp image of a healthy control(q) with corresponding vessel density image at the conjunctiva epithelium (r), conjunctiva/episclera complex (s), and episclera/scleracomplex (t).

4 S. C. Hau et al.

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for conjunctiva epithelium and conjunctiva/episcleracomplex but not for episclera/sclera complex, Table 1.Post hoc analysis revealed a significant difference intissue thickness between control and scleritis at theconjunctiva epithelium (p = .02) but not for controlversus episcleritis (p = .71) or episcleritis versus scleritis(p = .37). Similarly, there was a significant difference intissue thickness between control versus scleritis at theconjunctiva/episclera complex (p = .01) and episclera/

sclera complex (p = .05) but not for control versus epi-scleritis (p = .21) or episcleritis versus scleritis (p = .74).

AS-OCTA and AS-OCT images for three represen-tative cases: one diffuse episcleritis, one nodular scler-itis, and one control are shown in Figure 3. At theconjunctiva/episcleral layer, pockets of circular oroval shape hyporeflectivities were seen in episcleritis,whereas in scleritis, the hyporeflectivities appeared tobe more continuous, thicker and band-like, with the

TABLE 1. Comparison of AS-OCTA mean vessel density index and AS-OCT mean thickness measurement between episcleritis,scleritis, and control.

Anatomical layer

AS-OCTA vessel density index (%) AS-OCT thickness (µm)

Episcleritis(n = 13)

Scleritis(n = 11)

Control(n = 13) p Value*

Episcleritis(n = 13)

Scleritis(n = 11)

Control(n = 13) p Value**

Conjunctivaepithelium

26.7 (SD 13.9) 27.3 (SD 10.7) 3.3 (SD 2.0) <0.001 73.3 (SD 31.8) 106.4 (SD 24.0) 57.6 (SD 7.4) <0.001

Conjunctiva/episcleracomplex

36.8 (SD 9.9) 39.4 (SD 7.6) 19.7 (SD 4.9) <0.001 376.3 (SD 68.9) 426.4 (SD 98.1) 188.2 (SD 46.3) <0.001

Episclera/scleracomplex

38.1 (SD 11.4) 46.4 (SD 6.4) 23.3 (SD 3.7) <0.001 509.2 (SD 29.5) 523.7 (SD 23.7) 500.7 (SD 35.8) 0.54

AS-OCTA, anterior segment optical coherence tomography angiography; AS-OCT, anterior segment optical coherence tomogra-phy; SD, standard deviation. *Comparison of the VDI in different anatomical layers with AS-OCTA; **Comparison of tissue thicknessin different anatomical layers with AS-OCT.

FIGURE 3. Composite image showing one case of episcleritis, one case of scleritis and one normal control. (a) Slit lamp photo ofa case of episcleritis, (b) Anterior optical coherence tomography (AS-OCT) reveals mild episcleral edema (horizontal arrow) withdilatation of the episcleral blood vessels (arrow heads). (c) The corresponding anterior optical coherence tomography angiography(AS-OCTA) taken at the episclera/sclera complex level showing a lower vessel density index (VDI) compared to scleritis in imageF. (d) Slit lamp photo of a case of nodular scleritis. (e) ASOCT image reveals a much greater band of heterogeneous hyporeflectivityindicating probable edema at the conjunctiva/episclera complex compared to episcleritis. (f) The corresponding AS-OCTA taken atthe episclera/sclera complex level showing a much higher VDI compared to episcleritis in image C. (g) Slit lamp photo of a case ofcontrol, (h) Anterior optical coherence tomography (AS-OCT) reveals normal subconjunctival/episcleral blood vessels (arrow heads)and the vertical arrow indicates the demarcation between the subconjunctival space above and the episclera/sclera complex below. (i)The corresponding AS-OCTA taken at the episclera/sclera complex level for comparison.

AS-OCT Angiography in Scleral Inflammation 5

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Page 7: in the Evaluation of Episcleritis and Scleritis

nodular form showing a much greater tissue thick-ness (Figure 3b & e). At the episclera/sclera complex,the difference in VDI between episcleritis and scleritisappeared to be the greatest, which suggests the dif-ference in vascularity was highest just anterior to thesclera stroma between the two conditions (Figure 3c &f). The scleral stroma in scleritis showed further bandsof hyporeflectivity, indicating probable sclera edemaand inflammatory cellular infiltration, which were notpresent or they were much less prominent in episcler-itis. Despite these changes, the episclera/sclerastroma thickness in scleritis was not that much highercompared to episcleritis or controls, Table 1. Indeed,the thickness difference appeared to be the greatest atthe conjunctival/episclera complex, where the degreeof edema was much more prominent in scleritis(Figure 3e and Table 1). For comparison, the controlcase did not show any swelling in the conjunctiva/episclera region (Figure 3h). The mean total scleralthickness (MTST) for episcleritis, scleritis, and controlwas 973.3 µm ± 122.4, 1042 µm ± 128.4 and 749.7 µm ±84, respectively. There was a statistical significant dif-ference in MTST between control and scleritis (p = .01)but not between control and episcleritis (p = .14) orbetween episcleritis and scleritis (p = .75). Categorizingthe episcleritis and scleritis into nodular and non-nodular form, a slightly higher VDI and tissue thick-ness measurement at the various anatomical layerwere found in the nodular form for both type of scleralinflammation but we did not perform inferential sta-tistics to look for significant difference due to the smallsample size, especially with the nodular episcleritisgroup, Table 2. The MTST for the nodular and diffusephenotype were nodular episcleritis 988.5 µm, diffuseepiscleritis 943 µm, nodular scleritis 1161.5 µm, anddiffuse scleritis 962.4 µm.

DISCUSSION

AS-OCT has many applications in ophthalmology,22

whereas by contrast, OCTA is a relatively new tech-nology and currently, most of the OCTA systems areoptimized for imaging the retina. Adaptation of thecommercial OCTA systems for the anterior segment(AS-OCTA) has been shown to be potentially usefulin diagnosing and monitoring corneal neovascularisa-tion and it compares well with anterior segmentICGA in quantifying new blood vessels on thecornea.13,15 In the present pilot study, we haveshown that it is possible to image the vascular net-work at various anatomical planes of the sclera withthe AngioVue OCTA system. The increase in VDIseen with increasing depth occurred in all eyes andwe found the vascular density to be significantlylower in controls than in eyes with episcleritis orscleritis. T

ABLE2.

Com

parisonof

AS-OCTA

meanve

ssel

den

sity

index

andmeanAS-OCTscleraltissue

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essbe

tweentheno

dular

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form

forep

iscleritis

andscleritis.

Ana

tomical

laye

r

Episcleritis

Scleritis

Nod

ular

(n=2)

Diffuse

(n=11)

Nod

ular

(n=4)

Diffuse

(n=7)

VDI(%

)Thickne

ss(µm)

VDI(%

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ss(µm)

VDI(%

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ss(µm)

VDI(%

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ss(µm)

Con

junc

tiva

epithe

lium

29.9

(SD

2.3)

82.5

(SD

38.9)

26.1

(SD

15.2)

55(SD

12.4)

33.2

(SD

12.4)

128.5(SD

0.7)

27.9

(SD

8.7)

91.7

(SD

18.5)

Con

junc

tiva

/ep

iscleracomplex

39.1

(SD

0.6)

380.5(SD

33.8)

36.3

(SD

10.7)

368(SD

16.1)

41.6

(SD

10.7)

511.0(SD

29.4)

39.2

(SD

5.9)

381(SD

74.5)

Episclera/sclera

complex

41.7

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518.5(SD

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37.4

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500.7(SD

28.7)

49.7

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527(SD

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44.5

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AS-OCTA,a

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iation

.

6 S. C. Hau et al.

Ocular Immunology & Inflammation

Page 8: in the Evaluation of Episcleritis and Scleritis

The sclera stroma is considered to be an avasculartissue and inflammatory cellular migration comespossibly from a combination of three sources, theconjunctival/episcleral capillaries, choroidal circula-tion, and the vessels that transverse the sclera.23 Incontrast, the episclera is well vascularized, and thisreflects the highest VDI values found in the region ofthe episclera/sclera complex in all three groups. Withepiscleral/scleral inflammation, the degree of vascu-larity increases further in all of the anatomical planesresulting in the higher VDI values seen in both epi-scleritis and scleritis. Although the VDIs were notsignificantly different between episcleritis and scleri-tis in the superficial anatomical layers, the greatervascularity detected in the episclera/sclera complexand the comparatively higher amount of edema seenin the conjunctiva/episclera complex with scleritis,suggest these findings may potentially be useful indifferentiating the two conditions. These observationsare consistent with the fact that the deeper vascula-ture is more affected in scleritis.

The MTST of the normal controls found in thisstudy (749.7 µm) is similar to those found in previousstudies with a range of 747 to 790 µm being reportedin the literature.8–10 Shoughy et al. found that the totaltransconjunctival sclera is thicker in cases of scleritiscompared to episcleritis,8 whereas Kuroda et al.found the sclera stroma thickness to be similar andit is the conjunctival/episcleral complex that is thick-ened in scleritis rather than sclera stroma.9 The reasonfor the discrepancy is because the total transconjunc-tival scleral thickness was quoted by Shoughy et al.8

rather than just the thickness of the sclera stroma,which was quoted by Kuroda et al.9

TheMTST found in these studieswere 822.8 µm, 989.9µm (difference 167);9 825 µm, 882 µm (difference 57);8 and952 µm, 1006 µm (difference 54)10 for episcleritis andsclerits, respectively. The MTST values found in ourstudy are comparable to Axmann et al.10 but slightlyhigher than in the other studies. Our cohort, similar toAxmann et al.,10 had cases of both nodular and diffusemorphology; the nodular form, being greater in values,contributed to the higher overall MTST for both diag-noses. However, different instrumentations such as OCTtechnology and software, case selection, and segmenta-tion methods could all contribute to the difference inscleral thickness found between studies. The greater tis-sue thickness found in the nodular form also corre-sponded to the higher VDI values seen in thisphenotype, suggesting a greater degree of vascularitycompared to the diffuse type, though the comparison islimited by the small sample size in the nodular episcler-itis group in our study. Despite the higher MTST foundin scleritis compared to both episcleritis and controls, themean episclera/sclera complex thickness values for allthree groups were not statistically significant. Indeed,

these values are comparable to those found in normaluninflamed sclera24 and it suggests that in scleritis, it isthe conjunctival/episcleral complex that is thickenedrather than the sclera stroma.9 Although the scleralstroma did not appear to be significantly thicker in scler-itis, we found bands of hyporeflectivity deep into thescleral stroma, probably indicating intra-scleral edemaand separation of collagen lamellae, and these findingsare consistent with previous findings.8–11

There are several limitations in this pilot studyincluding its small sample size, single assessor with norepeatability assessment of the data performed.However, wemitigated these limitations by performingmultiple measurements and followed protocols fromprevious studies that already established goodrepeatability.19 From an imaging perspective, it isimportant to note that AS-OCT suffers from a greaterdegree of scatter and posterior shadowing with increas-ing inflammation and this is reflected in the inability tomeasure the tissue layer accurately in two eyes.Furthermore, although the AS-OCTA software hasbeen developed for imaging the anterior segment,motion or projection artifacts, limitations with softwareand a limited field of view may not include the entirelesion in one scan and also affect segmentation forexample in nodular scleritis. Moreover, the need formanual segmentation of the different tissue layers, andthe reduction in quality of the images on scanning deepinto the sclera stroma could all affect the accuracy ofmeasurements obtained in this study. We founda statistically significant difference in VDI at the epis-cera/sclera complex between episcleritis and scleritisbut this would need to be interpreted with caution dueto the exploratory nature of the study design.Notwithstanding these limitations, the aim of this pilotstudy is to evaluate a novel AS-OCTA system and toassess its feasibility and value in imaging the vascularnetwork in patients with scleral inflammation. If estab-lished, this technology may potentially be utilized ina general ophthalmological setting to help clinicians indifferentiating the different types of scleral inflamma-tion. Further prospective studies with larger samplesizes are needed to evaluate the role of AS-OCTA insuch patients.

In summary, our pilot study suggests that, AS-OCTA,in conjunction with AS-OCT, may be useful adjunctivetools in differentiating superficial from deep scleralinflammation by determining the degree of vascularityand tissue thickness of the different tissue layers.

DECLARATION OF INTEREST

The authors report no conflicts of interest. Theauthors alone are responsible for the content andwriting of the article.

AS-OCT Angiography in Scleral Inflammation 7

© 2019 Taylor & Francis Group, LLC

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ORCID

Scott C. Hau http://orcid.org/0000-0001-6913-6107

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