J Ophthal Inflamm Infect (2011) 1:157–163DOI 10.1007/s12348-011-0037-7ORIGINAL RESEARCHHigh-resolution spectral domain optical coherencetomography and fundus autofluorescence correlationin tubercular serpiginouslike choroiditisReema Bansal & Pandurang Kulkarni & Amod Gupta &Vishali Gupta & Mangat R. DograReceived: 2 July 2011 / Accepted: 31 July 2011 / Published online: 17 August 2011# The Author(s) 2011. This article is published with open access at SpringerLink.comAbstractObjective This study aims to describe changes in highresolution spectral domain optical coherence tomography(SD-OCT) scans with simultaneous fundus autoflorescence(FAF) signals in tubercular serpiginouslike choroiditis (SLC).Methods Simultaneous SD-OCT and FAF imaging of eyesaffected with SLC from acute stage until resolution oflesions was obtained using Spectralis HRA OCT system(Heidelberg Engineering, Heidelberg, Germany).Patients Four eyes (three patients) with SLC were prospectively followed.Results Acute lesions of SLC (diffusely hyperautofluorescent) corresponded to hyperreflective areas on SD-OCTinvolving the retinal pigment epithelium (RPE), photoreceptor outer segment tips (POST), inner segment–outersegment (IS/OS) junction, external limiting membrane(ELM), and outer nuclear layer (ONL) with a minimaldistortion of inner retinal layers. There was no backscattering from inner choroid. During healing, lesions becamediscrete with a hypoautofluorescent border and predominant hyperautofluorescence centrally. The hyperreflectiveSummary statement Simultaneous spectral domain opticalcoherence tomography and fundus autofluorescence findingscorrelated well during the course of acute tubercular serpiginouslikechoroiditis and provided an insight into the ultrastructural changes inthe outer retina as the lesions healed.R. Bansal : P. Kulkarni : V. Gupta : M. R. DograAdvanced Eye Centre,Post Graduate Institute of Medical Education and Research,Chandigarh, IndiaA. Gupta (*)Department of Ophthalmology, Advanced Eye Centre,Post Graduate Institute of Medical Education and Research,Chandigarh 160012, Indiae-mail: [email protected] areas on SD-OCT scans disappeared, and irregular,knobbly elevations of outer retinal layers appeared. TheRPE, POST, IS/OS junction, and ELM could not bedistinguished. The ONL appeared normal. The choroidshowed an increased reflectance. As the lesions healedfurther over the next 3–6 months, they became predominantly hypoautofluorescent with loss of RPE, POST, IS/OSjunction, and ELM in SD-OCT scan.Conclusion The SD-OCT provided an insight into theultrastructural changes in the outer retina during the courseof acute SLC lesions. The changes on OCT correlated withabnormal FAF findings.Keywords Fundus autofluorescence . Spectral domainoptical coherence tomography . Tubercular serpiginouslikechoroiditisSerpiginous choroiditis is a progressive, chronic, recurrentinflammatory disease primarily affecting the inner choroidand retinal pigment epithelial (RPE) cell layer .Serpiginouslike choroiditis (SLC) of presumed tubercularetiology is a distinct clinical entity that begins usually asmultifocal choroiditis lesions that coalesce and progress in aserpiginoid pattern [2, 3]. While the choriocapillaries havebeen shown to be the most affected layer in serpiginouschoroiditis (SC), the primary site of inflammation in SLC isnot yet known and is at best speculated, presumably thechoriocapillaries .The simultaneous recordings of topographic and tomographic images by using a combination of scanning laserophthalmoscopy and optical coherence tomography (OCT)have increased our understanding of the pathogenesis ofvarious diseases of the retina and choroid . TheSpectralis HRA OCT (Heidelberg Engineering, Heidelberg,
158Germany) is a novel multimodal imaging device that enablesus to correlate confocal angiograms, fundus autofluorescence(FAF) images, and other imaging modes with the highresolution spectral domain (SD)-OCT scans.The role of OCT in patients with uveitis is complementary to the conventional fundus photography and fundusfluorescein angiography (FA). More recently, FAF hasemerged as a very sensitive imaging modality to evaluateinflammatory disorders affecting the chorioretinal interface.The combined FAF and OCT signals have been effectivelyused in the evaluation of uveitic macular edema in terms ofvisual outcome . The Spectralis HRA OCT has beenused in imaging the choroid in intraocular inflammationusing the inverted scan technique.We describe the changes in high-resolution SD-OCTscans that were simultaneously obtained with FAF signalson Spectralis HRA OCT in four eyes of three patients withSLC who were followed from the stage of acute lesion tothe healed stage over a period of 3–6 months.MethodsWe prospectively followed four eyes of three patients withactive SLC. The diagnosis of SLC was made in thepresence of multifocal choroiditis lesions with centralhealing and active edges that were hyperautofluorescent inareas of active edges and hypoautofluorescent in healedareas and showed early hypofluorescence and late hyperfluorescence of active lesions on FA. The etiology waspresumed to be tubercular if there was (a) corroborativeevidence (such as a positive tuberculin skin test orQuantiFERON-TB Gold test), (b) exclusion of all otherknown causes of infectious uveitis except tuberculosis andnoninfectious uveitic syndromes, and (c) a favorabletherapeutic response to antitubercular therapy. All patientsunderwent chest radiography that was normal. Besides acomplete clinical evaluation that included best-correctedvisual acuity (BCVA), intraocular pressure (IOP), slit lampbiomicroscopic examination, and conventional imagingmethods (digital photography and FA, when required, onVisupac 450 Plus, Carl Zeiss, Jena, Germany), thesepatients additionally underwent Spectralis HRA OCT(Heidelberg Engineering, Heidelberg, Germany) imagingwith simultaneously obtained FAF and OCT images at allfollow-ups. The Spectralis system uses Heidelberg EyeExplorer Software Version 1.5.0 with Image CaptureModule Version 1.1.0. An infrared fundus image wasacquired parallel to OCT scan to ensure correct placementof image before acquiring FAF images simultaneous withOCT scans. The pupils were dilated before acquiring allscans. The Spectralis scans along with the FAF images wereobtained before doing FA, using the 30 field-of-viewJ Ophthal Inflamm Infect (2011) 1:157–163mode. All images were recorded using the automatic realtime mode. The image acquisition was done by selectingthe dense volume scan type over a scan angle of 20 or 30 and by adjusting the width/height of the OCT scan(depending upon the extent of the lesions in the fundus).We routinely perform dense volume scan with simultaneousFAF and SD-OCT mode. We use infrared mode to focus thefundus image, and once focused, we switch to combinedFAF and SD-OCT mode and capture the images simultaneously. An integrated eye tracking allowed for liveaveraging of FAF images and the SD-OCT scans. Thebaseline FAF-OCT images were defined as the referenceimages to enable acquisition of images at the same siteduring follow-up visits. Patients were seen every 2 weeksuntil the lesions healed. In addition to oral corticosteroids,all patients received four-drug antitubercular therapy including isoniazid (5 mg/kg/day), rifampicin (450 mg/day ifbody weight was 50 kg and 600 mg/day if body weightwas 50 kg), ethambutol (15 mg/kg/day), and pyrazinamide(25 to 30 mg/kg/day) initially for 3 to 4 months. Thereafter,rifampicin and isoniazid are used for another 9–14 months.Pyridoxine supplementation was given to all patientsreceiving antitubercular therapy until cessation of therapy.The corticosteroids were tapered depending upon theclinical response. All patients were receiving antituberculartherapy until their last visit and did not show any recurrenceof inflammation.Demographic details and treatment response to oralcorticosteroids and antitubercular therapy were also noted.The OCT scans were analyzed and correlated with FAF/FAimages in acute as well as healing stages.ResultsDuring the course of the disease in patients with SLC, weobserved a progressively changing pattern on SD-OCTscans that was consistent with the abnormal FAF signalsdetected simultaneously.1. In an acute lesion of SLC, there was an ill-defined areaof increased autofluorescence around the lesion. TheSD-OCT passing through the area showed a localized,fuzzy area of hyperreflectivity in the outer retinal layersinvolving the RPE, photoreceptor outer segment tips(POST), photoreceptor inner segment–outer segment(IS/OS) junction, external limiting membrane (ELM),and the outer nuclear layer (ONL). The lesion waslocalized external to the outer plexiform layer with amild distortion of the inner retinal layers. There was noincreased backscattering from the inner choroid.2. As the lesions started to heal, they became well definedand acquired a thin border of hypoautofluorescence
AS anterior segment, SLC serpiginouslike choroiditis, TST tuberculin skin test, M male, CF counting fingers, ND not done, AF autofluorescence, SD-OCT spectral domain optical coherencetomography, RPE retinal pigment epithelium, POST photoreceptor outer segment tips, IS–OS junction inner segment–outer segment junction, ELM external limiting membrane, ONL outer nuclearlayer6/66/6363CF 1 m6/95PredominantlyhypoautofluorescentIrregular, knobbly elevationsof outer retinal layers thatare indistinct. The ONLappears normal.Central hyperautofluorescentwith hypoautofluorescentborder21Loss of RPE, POST, IS–OS junction, and ELMFinal visual acuityFollow-up (months)SD-OCT of healed lesionFAF of healed lesionSD-OCT of healing lesionFAF of healing lesion35M3159PatientNDPositiveFuzzy, hyperreflective areasinvolving RPE, POST,photoreceptor IS–OSjunction, ELM and ONLDiffuse, 122019RightRightLeftLeftCF 1 ft6/96/66/9 gativeSD-OCT of acute lesionFAF of acutelesionQuantiFERONTB Gold testTSTType of SLC lesionsVitreous cellsASinflammationInitial visualacuityEyeAgeSexPatientTable 1 Clinical details of patients with active tubercular serpiginouslike choroiditis along with findings on combined fundus autofluorescence and Spectralis domain optical coherencetomography imaging as the lesions evolved from an acute stage up to healed stageJ Ophthal Inflamm Infect (2011) 1:157–163while remaining predominant hyperautofluorescentcentrally. The SD-OCT scan through the hyperautofluorescent area showed disappearance of the hyperreflective fuzzy areas that were replaced by irregular,hyperreflective knobbly elevations of the outer retinallayers. The RPE, the POST, IS/OS junction, and theELM could not be distinguished. The ONL appearednormal. At this stage, there was an increased reflectance from the choroidal layers due to attenuatingRPE–photoreceptor complex.3. As the lesions healed further over the next 3–6 months,they appeared stippled with predominantly hypoautofluorescence. The SD-OCT scan showed loss of RPE,POST, IS/OS junction, and ELM. The increasedreflectance from the choroid persisted.The clinical details and the findings on FAF and SDOCT during the healing of lesions are listed in Table 1.These changes are illustrated in Figs. 1 and 2.Case examplePatient 2: A 19-year-old male presented with decreased visionin both eyes since 3 months. On examination, the BCVAwas 6/9 and 6/6 in the right and left eyes, respectively. The IOP were14 and 12 mmHg in the right and left eyes, respectively. Botheyes showed unremarkable anterior segment and multifocallesions of active as well as inactive choroiditis in the posteriorpole (Fig. 1a–f). Simultaneous FAF and SD-OCT imaging ofthe right eye revealed findings as explained in the “Results”Section (1.) (Fig. 2a). The QuantiFERON-TB Gold test waspositive. Other laboratory tests were normal. He receivedfour-drug antitubercular therapy with oral corticosteroids.About 2 weeks later, the lesions started to heal and appearedas described in “Results” Section (2.) (Fig. 2b). Threemonths later, the lesions healed further and appeared asexplained in “Results” Section (3.) (Fig. 2c). Likewise, lefteye imaging also showed a similar pattern of FAF and SDOCT changes during acute, healing, and healed stages of thelesions (Fig. 2d–f).DiscussionTubercular SLC can be clinically differentiated from SC bythe frequent presence of vitritis and multifocal choroiditislesions in posterior pole and periphery, often sparing thejuxtapapillary region . The lesions in SC are, however,usually around the optic disk and spread contiguously to themacula. People with SLC are from areas endemic fortuberculosis, have positive uveitis work-up for tuberculosis,and respond favorably to antitubercular therapy with oralcorticosteroids.
160J Ophthal Inflamm Infect (2011) 1:157–163Fig. 1 a–f Right eye fundus picture of patient #2 with inactive and active (arrows) lesions of serpiginouslike choroiditis (a) that appearedhypofluorescent in early (b) and hyperfluorescent in late-phase fluorescein angiogram (c). The left eye showed similar lesions (d–f)The main histological findings described in SC areatrophy of the choriocapillaries, the RPE, and the photoreceptors [4, 7]. While the choriocapillaries was reported tobe the most affected layer that appeared acellular, the largechoroidal vessels were unremarkable. Moderate, diffuselymphocytic infiltration of the choroid has been reported,with predominant RPE atrophy. Occasionally, RPE hypertrophy has been seen correlating with areas of pigmentclumping clinically [4, 7]. On the other hand, clinicopathological correlation in tubercular SLC is still not known.Clinically, SLC appears to involve primarily the innerchoroid and the RPE. However, isolation of Mycobacteriumtuberculosis from the RPE in an eye with tubercularpanuveitis has strongly suggested preferential localizationof the mycobacteria in the RPE, even in eyes withpanuveitis or related intraocular inflammation, includingmultifocal choroiditis or serpiginouslike choroiditis .High-speed, high-resolution OCT, by providing unprecedented details, has enhanced our understanding of theultrastructure of the retina . Distinct scattering bandscorrespond to photoreceptor IS/OS junction, photoreceptorouter segment tips, and the RPE and represent the thickscattering bands of outer retina . The SD-OCT changes inhealed scars of SLC have shown disruption of the outerretina at the site of scars with loss of junction between theinner and outer segments of photoreceptors and thinning ofRPE/Bruch membrane complex and a correspondent increase in light reflectivity from the choroid . Areas ofthickening of RPE/Bruch membrane complex have alsobeen shown in the regions of scars. However, there is noreport of SD-OCT changes in any active and healing stagesof SLC lesions.All eyes with active lesions of SLC in our patientsillustrate the progressive changes in the outer retinal layerson OCT scans that correlated with the FAF changes. TheFAF images obtained simultaneously demonstrated thetransition from initial hyperautofluorescent of acute lesionsto predominant hypoautofluorescent in the healed stage.Absence of any demonstrable changes in the inner choroidduring the active stage of the lesion on OCT scans maysuggest a primary involvement of the RPE and not thechoroid in tubercular SLC lesions. The FAF signals providea strong clue to the status of RPE cells in various degenerative,inflammatory, and neoplastic disease processes. The FAF isincreased (hyperautofluorescence) in the presence of increased metabolic activity of the RPE and decreased(hypoautofluorescence) when there is loss of the RPE.We observed that the structural changes on OCT scansoccurring during the course of SLC followed a stepwiseorderly sequence, similar to those as seen on the FAFimages. Increased autofluorescence in the acute lesions seenas diffuse, subtle, feeble hyperautofluorescent probablyreflects retinal edema which was structurally evident ashyperreflectivity spreading into the outer retinal layers inthe OCT scans of our patients. This possibly suggestscellular infiltration or extracellular fluid accumulation in
J Ophthal Inflamm Infect (2011) 1:157–163Fig. 2 Combined fundus autofluorescence (FAF) and spectral domainoptical coherence tomography (SD-OCT) images through the activelesion(s). The green frame (left panel) indicates the borders of thescanned area. The position marker corresponds to the retinal locationthrough which the displayed OCT scan is obtained. In the right eye (a–c), in acute stage (a), there is an ill-defined area of increasedautofluorescence (left panel) with fuzzy area of hyperreflectivity inouter retinal layers (white arrows) involving the retinal pigmentepithelium (RPE), photoreceptor outer segment tips (POST), photoreceptor inner segment–outer segment (IS–OS) junction, external limitingmembrane (ELM), and outer nuclear layer (ONL) (right panel). Theinner retinal layers showed mild distortion. There was absence of anybackscattering from the inner choroid (red arrows). About 2 weeks later161(b), as the lesions started healing, they became well defined with a thinhypoautofluorescent border and predominantly hyperautofluorescencecentrally in the right eye (left panel). The SD-OCT showed irregularknobby elevations (white arrows) of the outer retinal layers (rightpanel). The RPE, POST, IS–OS junction, and ELM could not bedistinguished. There was an increased reflectance from the choroidallayers (red arrows) due to disappearing RPE–photoreceptor complex.Three months later (c), as the lesions healed further, they appearedstippled with predominantly hypoautofluorescence (left panel). The SDOCT scan showed loss of RPE, POST, IS–OS junction, and ELM (whitearrows) (right panel). The increased backscattering of the choroidpersisted (red arrows). d–f Similar changes were seen in the left eye inacute (d), healing (e), and healed (f) stages of active lesions of SLC
162these layers due to inflammation. As the lesions startedhealing, hyperautofluorescence decreased and hypoautofluorescence increased due to loss of RPE. The outer retinallayers on OCT scans of our patients showed attenuation andprogressive loss in the affected areas as the lesions healed.The FAF becomes increasingly hypoautofluorescent whichindicates severe damage to RPE and photoreceptors. Thiswas seen as an irreversible, collective loss of the outerretinal layers involving the RPE, photoreceptor outer andinner segments, and the ELM in OCT scans.Acute inflammatory lesions involving the RPE oftencause a thickening at the level of RPE. It is believed that thelesions in SC arise deep in the retina, and the overlyingretina appears edematous. The edema subsides as thelesions heal, and the RPE–choriocapillaries undergo atrophy. There is loss of photoreceptor–RPE complex withvariable degrees of RPE hyperplasia. Yeh et al. havehypothesized that RPE may be the site of primary insultand hence, more severely damaged in presumedtuberculosis-associated serpiginouslike choroidopathy .Increased autofluorescence in acute phase may be due to anumber of factors. The size, number, or content of thefluorophores in the RPE cells may be altered by inflammation which increases the fluorophores content by inducingcertain prooxidative pathways. Increased autofluorescencein other inflammatory conditions also such as White DotSyndromes has been correlated with areas of RPE elevationon OCT image during active disease . Once healed, thehypoautofluorescent areas showed resolution of RPEabnormalities on OCT scan.The FAF abnormalities (hyperautofluorescent in activestage progressively becoming hypoautofluorescent inhealed stage) have been well recognized (unpublisheddata). We observed that in the very initial stages of diseaseoccurrence, when there was feeble hyperautofluorescencein the areas of new lesions, the OCT showed hyperreflectivity in the outer retinal layers that was fuzzy andill defined. The choroid did not show any reflectance. Thisis an important OCT finding during the acute stage of SLCthat may reflect the site of primary insult in SLC. However,SD-OCT technology is not yet able to image the choroidsimilarly to the retina, and hence, the absence of choroidchanges on SD-OCT is not enough to definitely exclude itsprimary involvement in SLC.Hyperreflectivity in the outer retinal layers in an active SClesion is believed to be suggestive of acute inflammationinvolving deeper retinal and choroidal structures. From theOCT findings of our patients, we speculate that in an acutelesion of SLC, there is an increased metabolic activity causedby primary inflammation of the RPE cells. Release ofinflammatory mediators into the retinal layers adjacent to theRPE causes a fuzzy, hyperreflective appearance on SD-OCT.J Ophthal Inflamm Infect (2011) 1:157–163Following an acute inflammatory episode, the RPE cellsundergo hyperplasia and hypertrophy which is evident ashyperautofluorescence on FAF due to increased collection oflipofuscin. This corresponds to the localized, knobbly elevations of the outer retinal layers which represents clumping ofthe inflamed RPE cells. Once these damaged RPE cellsundergo atrophy, there is an irreversible loss of photoreceptorsgiving rise to the loss of the outer retinal layers on OCT. Thesimultaneous increased hypoautofluorescence depicts theatrophied RPE cells. The late pigmentation of the retinal scarassociated with RPE hypertrophy or hyperplasia also leads to adecreased FAF signal (especially when photoreceptors aredisrupted), as can also be seen in Figs. 1 and 2. The baring ofchoroidal vessels in healed lesions of SC in contrast to theirmasking by hyperpigmentary changes of the RPE in SLCmay also be due to entirely different entities affecting theinner choroid and the RPE cells, respectively.The limitations of our study include a small number ofcases and lack of clinicopathologic correlation. The outerretinal bands on SD-OCT, particularly IS/OS junction andPOST, have not been so far correlated to the histologicalstructures, and such correlation is still mostly presumed.However, the sequential ultrastructural changes in the outerretinal morphology on SD-OCT scans as seen in ourpatients provide important information that may add anew dimension in understanding the primary site ofpathology in inflammatory conditions affecting the choroidand the RPE–photoreceptor complex.Conflict of interestinterest.None of the authors have any proprietaryOpen Access This article is distributed under the terms of theCreative Commons Attribution License which permits any use,distribution and reproduction in any medium, provided the originalauthor(s) and source are credited.References1. Schatz H, Maumenee AE, Patz A (1974) Geographic helicoidperipapillary choroidopathy: clinical presentation and fluoresceinangiographic findings. Trans Am Acad Ophthalmol Otolaryngol78:747–7612. 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Spectralis HRA OCT (Heidelberg Engineering, Heidelberg, Summary statement Simultaneous spectral domain optical coherence tomography and fundus autofluorescence findings correlated well during the course of acute tubercular serpiginouslike choroiditis an