Freely Available OnlineJOURNAL OF OPHTHALMIC SCIENCEISSN NO: 2470-0436Research ArticleDOI : 10.14302/issn.2470-0436.jos-19-2480High-Resolution SD-OCT and EDI-OCT in the Evaluation and Management of MultifocalSerpiginoed ChoroditisEman Abo Taleb1,*, Manish P. Nagpal1, Navneet S. Mehrotra11Retina Foundation and Asopalav Eye hospital, Ahmedabad– 380 004 Gujarat, IndiaAbstractPurpose: To describe spectral domain optical coherence tomography (SD-OCT) and enhanced depth image OCT(EDI-OCT) findings of multifocal serpiginoid choroditis (MSC) , including affected layer of retinal involvement,changes at the vitreoretinal interface, and response to therapy.Methods: A retrospective review of 20 eyes (14 patients) with MSC. Each patient underwent a completeophthalmologic examination, fundus photography, fundus autoflorecence (FAF) and OCT imaging of the affectedretina at the initial visit and on each follow-up.Results: In acute stage, SD-OCT showed hyperreflective areas involving the outer retinal layers which includeretinal pigment epithelium (RPE), photoreceptor outer segment tips (POST), inner segment–outer segment (IS/OS) junction, external limiting membrane (ELM), and outer nuclear layer (ONL) with choroidal and intraretinallayer cells infiltrate. EDI-OCT showed increase choroidal thickness.As the lesions began to heal, irregular, knobby elevations of outer retinal layers appeared (RPE, POST, IS/OSjunction, and ELM could not be distinguished) with significant decrease in choroidal and intraretinal cells.On complete healing, loss of RPE, POST, IS/OS junction, and ELM in SD-OCT scan and absent of the choroidaland intraretinal cells and continous hyperreflactivity of the choroid (increased penetrance).Conclusion: SD-OCT and EDI-OCT provides high-resolution detail regarding ultrastructural changes invitreoretinal interface, outer retina and choroid during the course of the lesion. Serial SD-OCT and EDI-OCT alsoprovides further insight into response to therapy by observing choroidal and intraretinal cells.Corresponding author: Eman Abo Taleb, Retina Foundation, Asopalav Eye hospital, Rajbhavan at,India,Phone00967770591258,Email: [email protected] title: SD-OCT and EDI-OCT in Multifocal Serpiginoed ChoroditisKeywords: Serpiginous multifocal choroiditis, Spectral domain optical coherence tomography, Enhanced DepthImage optical coherence tomography.Received: Nov 13, 2018Accepted: Mar 20, 2019Published: Apr 22, 2019Editor: Chang Liu, Johns Hopkins University, JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 1

Freely Available Onlineincreased interest in the role of FAF in the assessmentIntroductionSerpiginous choroiditis is a progressive, chronic,recurrent inflammatory disease primarily affecting theinner choroid and retinal pigment epithelial (RPE) celllayer.1 Serpiginoid multifocal choroiditis (MSC) is adistinct clinical entity that begins usually as multifocalchoroiditis lesions that coalesce and progress in aserpiginoid pattern.(MSC) a designation that betterand follow-up of inflammatory diseases of retina andRPE choroid complex.6We describe the changes in high-resolutionSD-OCT scans that were simultaneously obtained withFAF signals on Spectralis HRA OCT in 14 patients withMCS who were followed from the stage of acute lesionto the healed stage over a period of 3–6 months.In an attempt to explore the extent of choroidalreflects the clinical features of presumed tubercularetiology and is preferable to the previously lvementduringtubercular MSC.affected layer in serpiginous choroiditis (SC), the primaryMethodsbest speculated, presumably the choriocapillaries.3Since its introduction in 1991, optical coherencetomography (OCT), has found its place as a widelyaccepted imaging technique, especially in ophthalmologyand other biomedical applications. It represents aging technique offering millimetre penetration withsubmicrometre axial and lateral resolution.4phasesofMSC,weprospectively studied the EDI-OCT changes in eyes withchoriocapillaries have been shown to be the mostsite of inflammation in MSC is not yet known and is atvariousWe retrospectively review of 20 eyes (14patients) with MCS. The diagnosis of MCS was made inthe presence of multifocal choroiditis lesions with centralhealing and active edges that were hyperautofluorescentin areas of active edges and hypoautofluorescent inhealed areas and showed early hypofluorescence andlate hyperfluorescence of active lesions on FAF. Theetiology was presumed to be tubercular if there was atleast two of the following criteria(1) a positiveThe simultaneous recordings of topographic andtuberculin skin test (2) QuantiFERON-TB Gold test (3)tomographic images by using combination of scanningabnormal chest radiography (4) history of relative wholaser ophthalmoscopy and optical coherence tomographyhas TB (5) a favorable therapeutic response to(OCT)theantitubercular therapy . We exclude of all other knownpathogenesis of various diseases of the retina andcauses of infectious uveitis except tuberculosis andchoroid.3noninfectious uveitic sHeidelberg,understandingHRA OCTGermany)of(Heidelbergisanovelmultimodal imaging device that enables us to correlateconfocal angiograms, fundus autofluorescence (FAF)images, and other imaging modes with the tralis HRA OCT has been used in imaging thechoroid in intraocular inflammation using the invertedscan technique.The role of OCT in patients with uveitis iscomplementary to the conventional fundus photographyand fundus fluorescein angiography (FA).In the lastyears, noninvasive FAF imaging has been introduced intothe ophthalmological clinical practice, providing for thefirst time a qualitative measure of the status of RPElayer in terms of function and structure. 5 This has beenshown to especially useful for the evaluation of variousretinal disorders. As a result, there has been JOSCC-licenseBesides a complete clinical evaluation thatincluded best-corrected visual acuity (BCVA), intraocularpressure (IOP), slit lamp biomicroscopic examination,and conventional imaging methods (digital photographyand FA, when required, onVisupac 450 Plus, Carl Zeiss, Jena, Germany),thesepatientsHRA ctralisHeidelberg,Germany) imaging with simultaneously obtained FAFand OCT images at all follow-ups. The Spectralis systemuses Heidelberg Eye Explorer Software Version 1.5.0with Image Capture Module Version 1.1.0. An infraredfundus image was acquired parallel to OCT scan toensure correct placement of image before acquiring FAFimages simultaneous with OCT scans. The pupils weredilated before acquiring all scans. The Spectralis scansDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 2

Freely Available Onlinealong with the FAF images were obtained before doingpatients except one case was diagnosed by chest CT-FA, using the 30 field-of-view mode. All images werescan. Presentingrecorded using the automatic real time mode. The image(mean0.40 0.63). 8 patient present at acute stage , 6acquisition was done by selecting the dense volume scanat healing stage and only one case at healed stage. Thetype over a scan angle of 20 or 30 and by the width/mean follow-up was10.53 11.78 months (median, 4height of the OCT scan(depending upon the extent ofmonths; range, 2–42 months) Table 1.the lesions in the fundus).BCVA Rt (mean 0.63 0.79) and LtDuring the course of the disease in patients withWe routinely perform dense volume scan withMSC, we observed a progressively changing pattern onsimultaneous FAF and SD-OCT mode. We use infraredSD-OCT scans that was consistent with the abnormalmode to focus the fundus image, and once focused, weFAF signals detected simultaneously.switch to combined FAF and SD-OCT mode and capture1. In an acute lesion of MCS, there was an ill-definedthe images simultaneously.area of increased autofluorescence around the lesion.An integrated eye tracking allowed for liveThe SD-OCT passing through the area showed aaveraging of FAF images and the SD-OCT scans. Thelocalized, fuzzy area of hyperreflectivity in the outerbaseline FAF-OCT images were defined as the referenceretinal layers involving the RPE, photoreceptor outerimages to enable acquisition of images at the same sitesegmentduring follow-up visits. Patients were seen every 2segment–outerweeks until the lesions healed.limiting membrane (ELM), and the outer nuclear layerIn addition to oral corticosteroids, all patientsreceivedfour-drug antitubercular therapy includingisoniazid (5 mg/kg/day), rifampicin (450 mg/day if bodyweight was 50 kg and 600 mg/day if body weight was 50 kg), ethambutol (15 mg/kg/day), and junction,innerexternal(ONL). The lesion was localized external to the outerplexiform layer with a mild distortion of the inner retinallayers. Choroidal and intra retinal layer cells infiltratewith corresponding increase thickness of choroid andinner retinal layers more obvious in EDI-OCT. There was(25 to 30 mg/kg/day) initially for 3 to 4 increased backscattering from the inner choroid.Thereafter, rifampicin and isoniazid are used for another2. As the lesions started to heal, they became well9–14 months. Pyridoxine supplementation was given erapyuntilcessation of therapy.The corticosteroids were tapered dependingupon the clinical response. All patients were receivingantitubercular therapy until their last visit and did notshow any recurrence of inflammation. Demographicdetails and treatment response to oral corticosteroidsand antitubercular therapy were also noted. The OCTscans were analyzed and correlated with FAF/FA weddisappearance of the hyperreflective fuzzy areas thatwere replaced by irregular, hyperreflective knobblyelevations of the outer retinal layers. The RPE, thePOST, IS/OS junction, and the ELM could not bedistinguished. The ONL appeared normal. At this stage,there was an increased reflectance from the choroidalin acute as well as healing stages.layers due to attenuating RPE–photoreceptor complex.Results3. As the lesions healed further over the next 3–6We studied 20 eyes (14 patients) with activeMSC, who were followed-up from acute stage up to thefinal healed stage. Ten patients had unilateral activeMSC, and 4 patients had bilaterally active disease at thetime of presentation to our clinic. There were 8 men andmonths, they appeared stippled with predominantlyhypoautofluorescence. The SD-OCT scan showed loss ofRPE, POST, IS/OS junction, and ELM with absent of thechoroidal and intraretinal cells. The increased reflectancefrom the choroid persisted.6 women. The mean age was 34.35 10.77 yearsCase Example(range, 19–53 years). TB Mantox test was positive in JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 3

Freely Available OnlineA 34-year-old male presented with decreasedtypically mild or absent. The choroiditis of MSC tends tovision in Right eye since one and half month. Onbegin as multiple, discrete lesions in the posterior poleexamination, the BCVA was 6/ 60 and 6/6 in the rightand mid-periphery, which then coalesce over time. dofsystemiccorticosteroidsandunremarkable anterior segment and multifocal lesions ofantituberculosis treatment (ATT) is highly effective atactive as well as inactive choroiditis in the posterior polecontrolling the inflammation and preserving the visualof Right eye and healed choroditis on left eye (Fig.1).acuity.7Simultaneous FAF and SD-OCT imaging of the right eyerevealed findings as explained in the “Results” Section(1.) (Fig.2). The tuberculin skin test was positive. Hereceived four-drug antitubercular therapy with oralcorticosteroids. About 2 weeks later, the lesions startedto heal and appeared as described in “Results” Section(2.) (Fig.3). Three months later, the lesions healedfurther and appeared as explained in “Results” Section(3.) (Fig.4). Fig.5, Fig.6diagnosis of the SC and MSC remain a challenge, ium tuberculosis (MTB) play a role in patientswith MSC.2 The main histological findings described inSC are atrophy of the choriocapillaries, the RPE, and eported to be the most affected layer that appearedacellular, the large choroidal vessels were unremarkable.DiscussionModerate, diffuse lymphocytic infiltration of the choroidTuberculosis –Infectious causes of what mightclinically be called SC have been referred to as both‘‘serpiginous-likeAlthough pathogenesis, etiology, and ifocal serpidinoid choroiditis (MSC).7 In North India,MSC is frequently bilateral, typically associated withhas been reported, with predominant RPE atrophy.Occasionally, RPE hypertrophy has been seen correlatingwith areas of pigment clumping clinically.8,9 On the otherhand, clinicopathological correlation in tubercular MSC isstill not known.vitreous inflammation, and affects young to middle-agedClinically, MSC appears to involve primarily themen predominantly. Anterior chamber inflammation isinner choroid and the RPE. However, isolation ofFigure 1. Color photograph of the right eye of patient 1shows an active MSC (blue arrows) and left eye showshealed MSC from her initial JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 4

Freely Available OnlineFigure 2. FAF (left) and corresponding eye-tracked SD-OCT image (right) of patient 1 an acute stage of the righteye shows fuzzy area of hyperreflectivity in the outer retinal layers involving the RPE, photoreceptor outer segmenttips (POST), photoreceptor inner segment–outer segment (IS/OS) junction, external limiting membrane (ELM), andthe outer nuclear layer (ONL) with vitreal and choroidal JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 5

Freely Available OnlineFigure 3. FAF (left) and corresponding eye-tracked SD-OCT image (right) of patient 1 during healing stage of theright eye shows hyperreflective knobbly elevations of the outer retinal layers. The RPE, the POST, IS/OS junction,and the ELM could not be distinguished. The ONL appeared normal with increased reflectance from the JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 6

Freely Available OnlineFigure 5. FAF (left) and corresponding eye-tracked SD-OCT image (right) of an example of transition area of anactive MSC (between red arrows) with no backscattering from the choroid .Figure 4. FAF (left) and corresponding eye-tracked SD-OCT image (right) of patient 1 healed stage of the left eyeshows showed loss of RPE, POST, IS/OS junction, and ELM with increased reflectance from the choroidal layers.absent of the choroidal and intraretinal JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 7

Freely Available OnlineFigure 5. FAF (left) and corresponding eye-tracked SD-OCT image (right) of an example of transition area of anactive MSC (between red arrows) with no backscattering from the choroid .Figure 6. EDI-OCT in acute stage of MSC reveled increase choroidal JOSCC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 8

Freely Available OnlineMycobacterium tuberculosis from the RPE in an eye withfuzzy areas on SD-OCT scans disappeared, and irregular,tubercular panuveitis has strongly suggested preferentialknobbly elevations of outer retinal layers appeared. Thelocalization of the mycobacteria in the RPE, even in eyesRPE, POST, IS/OS junction, and ELM could not bewith panuveitis or related intraocular inflammation,distinguished. The ONL appeared normal. The choroidincludingmultifocalshowed an increased reflectance. As the lesions rther over the next 3–6 months, they becameHigh-speed, high-resolution OCT, by providingpredominantly hypoautofluorescent with loss of RPE,unprecedented details, has enhanced our understandingPOST, IS/OS junction, and ELM in SD-OCT scan.2of the ultrastructure of the retina.3Absence of any demonstrable changes in the innerHossein Nazari and et al study OCT features ofactive SC lesions and they observe disruption ofphotoreceptor layer associated with outer retinal andchoriocapillaris hyperreflectivity.2 In active choroiditis,the outer retina shows a uniform increased reflectivity,but the inner retina is usually spared. Outer retina mayappear hyperreflective in healed lesions also, but tivity in healed lesions originates from RPEproliferation and migration. Consequently, outer retinalhyperreflectivity in healed lesions is more granular andchoroid during the active stage of the lesion on OCTscans may suggest a primary involvement of the RPEand not the choroid in tubercular MSC lesions.2 In our 8patients during the course of MSC SD-OCT observationreveled the same observation of what Reema Basnal andet al observe with the addation of our observation of thevitreal, intraretinal and choroidal cells which has beenseen in acute stage of the disease with absent vation of MSC conform the clinical finding of severvitritis.7non-uniform. Retinal and RPE inflammation in activeAlso our EDI-OCT observation demonstrated achoroiditis is often associated with limited subretinaldiffuse choroidal thickening as well as localized changesfluid overlying the area of choroiditis. Also, retinalin the deeper choroid beneath the active as well asthickness is normal or slightly increased in the activehealedchoroiditis phase, but in a healed lesion, it is mildlyinvolvement deeper to choriocapillaris. we believe that aattenuated because of outer retinal atrophy.2OCT. This increased choroidal reflectivity is described asa “waterfall effect” and is attributed to inflammatory cellinfiltration of the Choroid. The choroidal hyperreflectivityin healed SC lesions is attributed to enhanced lighttransmission through overlying RPE atrophy.Reema Bansal and et al in their prospectivestudy of 3 patients during active and heald phase theyobserve eyes with active lesions of MSC in their patientsillustrate the progressive changes in the outer retinallayers on OCT scans that correlated with the ) corresponded to hyperreflectiveareas on SD-OCT involving RPE, POST, IS/OS, ELM, andONL with a minimal distortion of inner retinal layers.There was no backscattering from inner choroid. ithimmunological trigger. The predominant and an earlyinvolvement of RPE may indicate the infective triggerwhich is go with Yeh et al who have hypothesized thatRPE may be the site of primary insult and hence, moreseverely damaged in presumed tuberculosis-associatedserpiginous-like choroidopathy based on the report ofthe isolation of mycobacterial DNA from RPE cells .11Panagiotis Malamos et al in their correlation offundus autofluorescence (FAF) with indocyanine greenangiography (ICGA) in patients with various posterioruveitis disorders they found in 4 eyes of 4 pations of TB-serpigious like choroditis that Choriocapillaris and RBEare the Primary insult with predominat RPE involvementwhich is Similar evidence that has been recentlyreported by Gupta et al.12,13Takahashi and associates used (EDI-OCT) toaevaluate a 40-year-old woman with active, ntSC with testing for known infectious causes of MSC veunrevealing in their study. They found that Prior JOSdiscreteThisdiffuse increase in choroidal thickness may indicate anChoroid may also appear hyper-reflective onchanges.2lesions.CC-licenseDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 9

Freely Available Onlinetreatment subfoveal choroid was found to be markedlyGeorgalas,etthickened (average713.3 4.5 microns) and EDI-OCTAutofluorescence Imaging in the Study of the Courselocalized the active peripapillary placoid lesions to justof Posterior Uveitis Disorders. BioMed Researchbeneath the RPE, supporting published pathologicalInternational Volume 2015, Article ID 247469, 11studies showing diffuse choroidal inflammation withpagesprimary involvement of the choriocapillaris in areas ofactive placoid lesions in eyes with SC. Followingtreatment, subfoveal thickening decreased dramaticallyto 330 microns. This finding support the cilinicalevidence that choroidal involvement is primary and thepredominat insult in SC.12.13The advantage of this study that all vitreoretinallayers, choroidal thickness vitreal and retinal cellsinfiltrate were observed during different stages of MSCby using SD-OCT and EDI-OCT. This observation canplay a role into differention between infectious and noninfectous cause of serpiginous choroditis and give us aclue to start the patient on anti-tuberculosis treatmentor no.1. Schatz H, Maumenee AE, Patz A (1974) icalpresentation and fluorescein angiographic findings.Trans Am Acad Ophthalmol Otolaryngol arsing A Rao. oid2013;58(3):203–232.3. Reema Bansal , Pandurang Kulkarni , Amod Gupta etal.High-resolutionspectraldomainopticalcoherence tomography and fundus autofluorescencecorrelation in tubercular serpiginouslike choroiditis. JOphthal Inflamm Infect (2011) 1:157–1634. M J Gallagher, T Yilmaz, R A Cervantes-Castan .FundusAmodTheGuptaCreepingChoroiditides –Serpiginous and Multifocal SerpiginoidChoroiditis. Ocular Immunology & Inflammation,2014; 22(5): 345–3488. horoidalneovascularization. Retina 9:292–3019. Gass JDM (1987) Stereoscopic atlas of maculardiseases: diagnosis and treatment, vol 1, 3rd edn.Mosby, St. Louis, pp 136–14410. RaoNA,SaraswathyS,SmithRE(2006)Tuberculous uveitis: distribution of MycobacteriumReferences2. Hossein7. Emmettal.Thecharacteristicfeaturesoftuberculosis in the retinal pigment epithelium. ArchOphthalmol 124:1777–177911. Yeh S, Forooghian F, Wong WT et al (2010) s. Arch Ophthalmol 128:46–5612. PanagiotisMalamos,PanosMasaoutis,IliasGeorgalas et al.The Role of Fundus AutofluorescenceImaging in the Study of the Course of PosteriorUveitis Disorders. BioMed Research International2015, Article ID 247469, 11 pages13. A. Gupta, R. Bansal, V. Gupta, and A. horoiditis,” Retina, vol. 32, no. 4, pp. 814–825,2012.opticalcoherence tomography in posterior uveitis. Br JOphthalmol 2007;91:1680–1685.5. r, and J. J. Weiter, “Invivo fluorescence of the ocular fundus exhibitsretinal pigment epithelium lipofuscin characteristics,”Investigative Ophthalmology and Visual Science, vol.36, no. 3, pp. 718–729, 1995.6. PanagiotisMalamos, JOSPanosMasaoutis,2CC-licenseIliasDOI : 10.14302/issn.2470-0436.jos-19-2480Vol-2 Issue 2 Pg. no.– 10

choroid.3 The Spectralis HRA OCT (Heidelberg Engineering, Heidelberg, Germany) is a novel multimodal imaging device that enables us to correlate confocal angiograms, fundus autofluorescence (FAF) images, and other imaging modes with the high resolution spectral domain (SD)-OCT scans.3The