En Face Enhanced-Depth Swept-SourceOptical Coherence Tomography Features ofChronic Central Serous Chorioretinopathy

Daniela Ferrara MD PhD1 Kathrin J Mohler BS23 Nadia Waheed MD MPH1 Mehreen Adhi MBBS1

Jonathan J Liu MS2 Ireneusz Grulkowski PhD2 Martin F Kraus Dipl24 Caroline Baumal MD1

Joachim Hornegger PhD4 James G Fujimoto PhD2 Jay S Duker MD1

Objective To characterize en face features of the retinal pigment epithelium (RPE) and choroid in eyes withchronic central serous chorioretinopathy (CSCR) using a high-speed enhanced-depth swept-source opticalcoherence tomography (SS-OCT) prototype

Design Consecutive patients with chronic CSCR were prospectively examined with SS-OCTParticipants Fifteen eyes of 13 patientsMethods Three-dimensional 66 mm macular cube raster scans were obtained with SS-OCT operating at

1050 nm wavelength and 100 000 A-linessec with 6 mm axial resolution Segmentation of the RPE generated areference surface en face SS-OCT images of the RPE and choroid were extracted at varying depths every 35 mm(1 pixel) Abnormal features were characterized by systematic analysis of multimodal fundus imaging includingcolor photographs fundus autofluorescence fluorescein angiography and indocyanine-green angiography(ICGA)

Main Outcome Measures En face SS-OCT morphology of the RPE and individual choroidal layersResults En face SS-OCT imaging at the RPE level revealed absence of signal corresponding to RPE

detachment or RPE loss in 15 of 15 (100) eyes En face SS-OCT imaging at the choriocapillaris level showedfocally enlarged vessels in 8 of 15 eyes (53) At the level of Sattlerrsquos layer en face SS-OCT documented focalchoroidal dilation in 8 of 15 eyes (53) and diffuse choroidal dilation in 7 of 15 eyes (47) At the level of Hallerrsquoslayer these same features were observed in 3 of 15 eyes (20) and 12 of 15 eyes (80) respectively In allaffected eyes these choroidal vascular abnormalities were seen just below areas of RPE abnormalities In 2 eyeswith secondary choroidal neovascularization (CNV) distinct en face SS-OCT features corresponded to theneovascular lesions

Conclusions High-speed enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization ofpathologic features of the RPE and choroid in eyes with chronic CSCR not usually appreciated with standardspectral domain (SD) OCT En face SS-OCT imaging seems to be a useful tool in the identification of CNV withoutthe use of angiography This in vivo documentation of the RPE and choroidal vasculature at variable depths mayhelp elucidate the pathophysiology of disease and can contribute to the diagnosis and management of chronicCSCR

Financial Disclosure(s) Proprietary or commercial disclosure may be found after the referencesOphthalmology 2013-1e8 ordf 2013 by the American Academy of Ophthalmology

Central serous chorioretinopathy (CSCR) is characterizedby 1 or more serous detachments of the neurosensory retinacommonly associated with retinal pigment epithelium (RPE)detachments There is a broad spectrum of clinical pre-sentations1e6 Central serous chorioretinopathy tends toaffect the retina primarily in the macular area but multifocalor extensive retinal involvement also can occur as well asinferior serous retinal detachment37 Symptoms are self-limited in most of the cases but the disease can be recur-rent or bilateral in approximately one-third of cases89

Although the visual prognosis is usually good in acutemanifestations RPE loss geographic atrophy chronic

2013 by the American Academy of OphthalmologyPublished by Elsevier Inc

cystic retinal changes subretinal fibrinous accumulationsubretinal fibrosis and secondary choroidal neo-vascularization (CNV) are known late complications thatcan be associated with permanent visual loss10 Clinical andepidemiologic evidence points to a relationship betweenCSCR and elevated levels of circulating catecholaminesand corticosteroids from exogenous or endogenoussources Of note local injections of corticosteroids do notseem to induce the disease often311e21 The pathophysi-ology of this intriguing condition remains unknown Func-tional and morphologic features on indocyanine-greenangiography (ICGA) and optical coherence tomography

1ISSN 0161-642013$ - see front matterhttpdxdoiorg101016jophtha201310014

Ophthalmology Volume - Number - Month 2013

(OCT) strongly suggest that the choroid is primarilyinvolved Choroidal hyperpermeability vascular conges-tion and increased choroidal thickness were found to behallmarks of the entity2223

Three-dimensional OCT is a useful tool in the investi-gation of chorioretinal disorders2425 However the detailedassessment of the choroid is fundamentally limited incommercially available spectral-domain (SD)-OCT deviceseven when applying the enhanced depth imaging strategyfor imaging acquisition2226 Swept-source (SS)-OCT is aFourier domain depth-resolved method that uses awavelength-tunable laser and a dual-balanced photo detectorinstead of a broadband super-luminescent diode spectro-meter and high-speed line-scan camera that are used inSD-OCT Swept-source OCT technology offers severalpotential advantages in comparison with SD-OCTincluding higher imaging speeds higher detection effi-ciencies improved imaging range reduced sensitivity rolloff with imaging depth and adaptability to longer imagingwavelengths2728 This study characterized 3-dimensional enface features of the RPE and choroid in eyes with chronicCSCR using a novel high-speed high-resolutionenhanced-depth SS-OCT prototype with improved tissuepenetration at 1050 nm wavelength

Methods

This study was performed under approved institutional reviewboard protocols from the New England Eye Center and Massa-chusetts Institute of Technology The research adhered to the tenetsof the Declaration of Helsinki and complied with the Health In-surance Portability and Accountability Act of 1996 Signedinformed consent was obtained before SS-OCT examinationConsecutive patients examined at the New England Eye Centerbetween October 2012 and April 2013 with the clinical diagnosisof chronic CSCR as defined by idiopathic single or multiple se-rous detachments of the neurosensory retina in the macular areaassociated with RPE changes or RPE leaks on fluorescein angi-ography (FA) and visual symptoms for at least 6 months wereoffered enrollment in the study in a prospective fashion Exclusioncriteria were any associated previous or concomitant ophthal-mological condition that could confound the interpretation ofmultimodal fundus imaging or history of previous treatment forCSCR including thermal laser photocoagulation photodynamictherapy or intravitreal administration of anti-vascular endothelialgrowth factor

Enrolled patients received a complete ophthalmological exam-ination including assessment of best-corrected visual acuity bio-microscopy intraocular pressure and a dilated fundusexamination Patients were examined with an SS-OCT prototypesystem operating at 1050 nm for enhanced choroidal penetrationsimilar to that described by Potsaid et al27 and Unterhuber et al29

The system uses a commercially available 100 kHz wavelength-swept semiconductor laser (Axsun Technologies Inc BillericaMA) with a sweep bandwidth of approximately 100 nm providingan axial resolution of 6 mm in tissue The light incident on the eyewas 19 mW which is consistent with the American NationalStandard Institute standards for safe ocular exposure30 Three-dimensional 66-mm macular cube raster scans with 400400axial scans were obtained each acquired within 17 seconds Foreach patient at least 2 volumetric scans with orthogonal fast scandirections were acquired processed with software for motioncorrection and merged into a single volumetric dataset to increase

2

the signal31 An intensity and gradient-based semiautomatic al-gorithm was used to segment the RPE or Bruchrsquos membrane inregions of RPE detachment to generate a reference surface for enface display32 En face images of the RPE and choroid wereextracted at varying depths every 35 mm (1 pixel correspondingto the digital resolution of OCT images) from the RPEBruchrsquosmembrane reference surface This analysis permitted point-to-point correlation between en face images and cross-sectional b-scan images Atypical features appearing on the en face imageswere characterized by systematic analysis of multimodal fundusimaging records including color fundus picture fundus auto-fluorescence FA and ICGA

Results

Fifteen eyes of 13 patients seen consecutively and diagnosed withchronic CSCR were enrolled in the study Their baseline charac-teristics were as follows 11 male patients 10 Caucasian and 3Asian patients mean age 507 years (standard deviation 95years) and mean best-corrected visual acuity 2050 (range 2020e20800) All enrolled patients had a history of at least 6 monthsof visual symptoms in the affected eye(s) The mean period of timesince initial presentation was 136 months (range 6e60 months)The mean choroidal thickness assessed on SS-OCT b-scans at thecenter of the fovea was 351 mm (standard deviation 84 mm)which is thicker than the mean choroidal thickness determined bySD-OCT previously reported for normal subjects in this age group(287 mm standard deviation 76 mm)33 En face SS-OCT imagesor c-scans were obtained from the 3-dimensional SS-OCT datasets The en face imaging allowed virtual sectioning of the maculararea in consecutive c-scans 35 mm apart from each other from thevitreous cavity to the sclera Representative c-scans of the RPElayer choriocapillaris and choroidal layers with medium-sizedvessels (inner choroid or the so-called Sattlerrsquos layer) and large-sized vessels (outer choroid or the so-called Hallerrsquos layer) wereobtained To completely characterize the en face SS-OCT featuresof retinal pigment epithelium detachments (PEDs) c-scans abovethe RPE layer also were generated

En face SS-OCT images at the RPE level revealed specificchanges in all eyes which correlated with pathologic changes seenon cross-sectional SS-OCT and multimodal imaging includingfundus autofluorescence FA and ICGA Absence of SS-OCTsignal at the RPE level corresponded to RPE detachment or loss(Fig 1) and was observed in all eyes One eye with RPE leakage atthe center of the macula characterized by the classic ldquoink blotrdquoappearance on FA had the exact corresponding point of RPEdisruption visible on en face SS-OCT (Fig 2) Of note en faceOCT images extracted from slightly above the RPE level showedlarge hypoechoic areas of absent signal corresponding to fluidaccumulation associated with neurosensory retinal detachment orRPE detachment Neurosensory detachments present with smoothborders between the fluid and the dome-shaped retina whereasRPE detachments show a characteristic distinct hyperechoic halocorresponding to the dome-shaped RPE (Fig 2) Within the area ofneurosensory retinal detachment heterogeneous SS-OCT signalwith numerous optically dense dots was observed in some casescorresponding to photoreceptors and RPE debris seen on b-scans(Fig 3 available at httpaaojournalorg)

En face SS-OCT imaging at the level of the choriocapillarisshowed hypoechoic spots suggesting the presence of enlargedvessels at this level in 8 eyes (53) but images were unremarkablein the other 7 eyes It was unclear whether the absence of identi-fiable choriocapillary changes in the unremarkable eyes (47) wasrelated to a limitation in image resolution given the smallervascular lumen and the complex vascular anatomy at this level or

Figure 1 Patient with chronic chronic central serous chorioretinopathy (CSCR) in both eyes and a small pigment epithelium detachment (PED) close tothe fovea in the right eye Red-free image (A) and fluorescein angiography (FA) (B) show a focal change in the retinal pigment epithelium (RPE) whereasindocyanine-green angiography (ICGA) (C) shows an area of focal hyperfluorescence in the topography of the PED and widespread hyperfluorescencesuggesting increased choroidal permeability En face swept-source optical coherence tomography (SS-OCT) image at the level of the RPE layer (D) reveals asmall focal hyporeflective area correspondent to the PED En face SS-OCT imaging at the level of the choriocapillaris 40 mm below the RPE (E) isunremarkable and at the level of large choroidal vessels 190 mm below the RPE (F) reveals diffuse choroidal dilation The white area in the en face OCTimage (F) shows the choroidal-scleral interface

Ferrara et al Chronic CSCR on En Face SS-OCT

the true absence of vascular engorgement In all affected eyes thechoriocapillaris changes were grossly underlying RPE changeseither PED or RPE loss (Fig 2) seen on b-scans and furtherdocumented on fundus autofluorescence and FA Thesechoriocapillary changes corresponded to hyper-fluorescent spotson ICGA

Choroidal en face SS-OCT imaging at the level of Sattlerrsquoslayer revealed dilation of medium-sized choroidal vessels in 2somewhat distinct patterns In 7 eyes (47) relatively homo-geneous dilation of vessels was observed in the entire series of enface images from this layer which was characterized as ldquodiffusechoroidal dilationrdquo (Fig 3I available at httpaaojournalorg) In 8eyes (53) some vascular branches were found to have biggercalibers than the surrounding enlarged choroidal vessels andwere characterized as ldquofocal choroidal dilationrdquo (Fig 4I availableat httpaaojournalorg) Likewise SS-OCT en face imagesrepresentative of Hallerrsquos layer revealed diffuse choroidal dilationin 12 eyes (80) (Fig1F) and focal choroidal dilation in 3 eyes(20) Comparison of different image modalities revealed acorrespondence between focal and diffuse choroidal dilation onen face OCT images and hyperfluorescent areas on ICGAtypically described as choroidal hyperperfusion (Fig 4H Iavailable at httpaaojournalorg) No correlation could beestablished between choroidal changes and patientsrsquo age genderor duration of symptoms

En face SS-OCT images revealed CNV in 2 eyes corre-sponding to the diagnosis of CNV initially determined by clinicalexamination FA and ICGA In 1 case comparison of differentimage modalities showed subretinal fibrosis in the center of themacula with only residual exudation from CNV and shallow sub-retinal fluid accumulation Middle- to late-phase ICGA showed 1

polypoidal-like formation on the topography of the fibrosis Enface SS-OCT imaging at the level of the Bruchrsquos membrane clearlydelineated an abnormal-appearing neovascular network underlyingthe fibrosis one of whose branches was terminating in the topo-graphy of the polypoidal-like lesion seen on ICGA En face SS-OCT imaging at the level of the choriocapillaris showed adistinct round area with a hyporeflective signal connecting to thecenter of the neovascular network Swept-source OCT en faceimages from the medium and large choroidal vessel layers showeddiffuse choroidal dilation (Fig 5) In the other case with secondaryCNV comparison of different imaging modalities showed asubretinal lesion in the center of the macula limited exudationon FA and a hyperfluorescent spot in the middle- to late-phaseICGA In this eye en face SS-OCT imaging throughout thechoroid revealed a distinct round area with a hyporeflective signalunderneath the subretinal lesion This area seemed to be connectedto the CNV through a defect in the RPE and connected to a largechoroidal vessel in the en face images from deeper levels Thesefeatures also were observed in cross-sectional SS-OCT imagesthrough the fovea (Fig 6)

Discussion

Serous detachment of the neurosensory retina is character-istic of the typical presentation of CSCR but the source ofthe subretinal fluid is still not completely agreed upon19

Retinal PEDs have been identified in up to 63 ofaffected eyes when studied with angiography and cross-sectional OCT imaging and may or may not be associated

3

Figure 2 Patient with chronic chronic central serous chorioretinopathy (CSCR) and serous neurosensory retinal detachment evident on red-free fundusimage (A) Fluorescein angiography (B) reveals 2 hyperfluorescent areas the superior one corresponding to pigment epithelium detachments (PEDs) and theinferior one corresponding to dye leakage in the ldquoink dot signrdquo typical of the disease Late-phase indocyanine-green angiography (ICGA) (C) shows ahyperfluorescent spot in this same topography surrounded by multifocal choroidal hyperfluorescence En face swept-source optical coherence tomography(SS-OCT) image 30 mm above the retinal pigment epithelium (RPE) level (D) with dark areas corresponding to subretinal or sub-RPE fluid the large areawith ldquosmoothrdquo borders corresponds to the serous neurosensory retinal detachment whereas the 2 small areas with a distinct white halo correspond to PEDsEn face SS-OCT image at the RPE level (E) revealing RPE defects at the topography of the PEDs and 30 mm below the RPE level (F) with a focal dilation inthe choriocapillaris at the same topography of the central lesion Cross-sectional b-scans from the areas indicated in A respectively showing the PEDsuperior to the fovea (G) the serous neurosensory retinal detachment involving the fovea (H) and the central PED within the retinal detachment (I)

Ophthalmology Volume - Number - Month 2013

with neurosensory retinal detachments or clinical symp-toms9 Because FA shows focal single or multiple leaksfrom the RPE that are characteristic of the entity focal ordiffuse RPE dysfunction has been hypothesized as theprimary pathologic mechanism in CSCR3435 Howeveradditional morphologic features derived from old and newinvestigative results challenge this hypothesis Retinalchanges may represent a later stage in disease evolution andthe choroid seems to be primarily affected2223 In our groupof patients with chronic CSCR en face SS-OCT imagesdocumented PEDs in all eyes as well as morphologicchanges in the choroid underneath and beyond RPEchanges

It has been proposed that ischemia or impaired auto-regulation of choroidal circulationdpotentially related tohypercortisolism systemic hypertension and sympatheticderegulationdmay play a role in choroidal hyper-permeability on CSCR936e40 Congested and dilatedchoroidal capillaries and veins choroidal staining andleakage into the interstitial space are commonly seen on

4

ICGA These widespread areas of abnormal choroidal cir-culation can occur throughout the posterior pole even fromsites not seen on FA3841 Abnormalities in 1 or more lobulescan be frequently observed in both symptomatic andasymptomatic eyes as well as in unaffected fellow eyes2336

Nonetheless ICGA does not show hyperfluorescence in allcases of chronic CSCR42 Previous studies reportedincreased choroidal thickness observed on cross-sectionalOCT images with no corresponding changes on ICGA23

This incidental inconsistency between the 2 imagingmethods might indicate a relative limitation of ICGA inidentifying particular alterations of the choroidalmorphology in CSCR The interpretation of the angiogramis affected by numerous factors related to some extent tothe nature of the examination and to techniques of imageacquisition Moreover the 2-dimensional nature of theICGA means that all choroidal layers overlap in theangiogram which makes it difficult to identify the individ-ual layers (Fig 3 available at httpaaojournalorg) On thebasis of the visualization of 3-dimensional SS-OCT data we

Figure 5 Patient with chronic chronic central serous chorioretinopathy (CSCR) and subretinal fibrosis due to secondary choroidal neovascularization(CNV) evident on red-free fundus image (A) Fluorescein angiography (B) documents widespread retinal pigment epithelium (RPE) changes around thefibrosis which blocks the background fluorescence Middle-phase indocyanine-green angiography (ICGA) (C) suggests a polypoidal-like neovascular lesionEn face swept-source optical coherence tomography (SS-OCT) image at the level of the RPE (D) reveals the neovascular network extending from thefibrosis En face SS-OCT image 25 mm below the RPE (E) reveals distinct focal choroidal dilation at the level of the choriocapillaris whereas diffusechoroidal dilation was observed on medium and large vessel layers as seen on an en face OCT image at 250 mm below the RPE level (F)

Ferrara et al Chronic CSCR on En Face SS-OCT

were able to characterize individual layers of the retina andchoroid However the focal and diffuse choroidal dilationswe observed on en face SS-OCT images did correspond tohyperfluorescent areas on ICGA (Fig 2 and Fig 4 availableat httpaaojournalorg) Of note these particularmorphologic changes in the choroidal vasculature that weobserved in en face SS-OCT cannot be seen on cross-sectional OCT images Therefore en face imaging is supe-rior to cross-sectional imaging for visualizing these features

The natural course of the disease and the occurrence ofsecondary complications are highly variable and somewhatunpredictable in CSCR The therapeutic response topotentially beneficial interventions ultimately targetschoroidal congestion and hyperpermeability4243 By usingen face SS-OCT images we observed focal and diffusevascular dilation at the level of the choriocapillaris in half(53) of the enrolled eyes and at the level of Sattlerrsquos andHallerrsquos layers in all eyes In the 2 eyes with secondaryCNV a single well-delineated area of hypoechoic SS-OCTsignal was observed at the site of the CNV In the eye withfibrotic CNV this feature was present at the level of theBruchrsquos membrane (Fig 5) whereas in the eye with activeCNV it was present throughout the choroidal depth fromBruchrsquos membrane to the choroidal-scleral interface (Fig6) No definitive conclusions can be made from these 2anecdotal cases Nonetheless multimodal imaging analysisand 3-dimensional OCT visualization of the macular areasuggest that our observation might be related to pronouncedchoroidal vascular dilation or remodeling or to extracellular

fluid accumulation It also raises the question of whether abetter understanding of en face choroidal features couldcontribute to the differential diagnosis between CSCR andpolypoidal choroidal vasculopathy masquerading as CSCRindicate eyes with higher risk of developing secondaryCNV or indicate other predictive markers of diseaseevolution

En face imaging is complementary to cross-sectionalimaging and enables visualization of structures that cannotbe easily appreciated in cross-sectional images In our groupof patients en face imaging revealed morphologic changesin the choroidal vasculature that could not be initiallyidentified on cross-sectional images alone in part becauseen face imaging documents the vascular anatomy with anorientation comparable to other imaging modalities such asICGA Thus the topographic analysis allowed by en faceimaging facilitates the comparison between multiple imag-ing modalities and permits a better characterization of themorphology and extent of choroidal changes The topo-graphic documentation on en face OCT also permits adetailed assessment of each individual choroidal layerwhich cannot be performed on cross-sectional OCT Thisadvantage is especially useful in the investigation of thechoriocapillaris because of the reduced thickness of itscomplex vascular network However the en face imagingmodality requires high-speed acquisition because each pixelin the en face image requires an axial scan In this sense thehigher imaging speeds allowed by SS-OCT technology are afundamental advantage in comparison with SD-OCT

5

Figure 6 Patient with chronic chronic central serous chorioretinopathy (CSCR) and subfoveal secondary choroidal neovascularization (CNV) evident onred-free fundus image (A) Fluorescein angiography (B) shows the hyperfluorescent active CNV which appears as a hyperfluorescent spot in the late-phaseindocyanine-green angiography (ICGA) (C) En face swept-source optical coherence tomography (SS-OCT) image 30 mm above the retinal pigmentepithelium (RPE) (D) delineates the area of subretinal fluid appearing dark En face SS-OCT image at the level of the RPE (E) shows a focal RPE loss in thecenter of the neovascular complex appearing dark and an additional dark spot corresponding to a small pigment epithelium detachment (PED) En face SS-OCT image 40 mm below the RPE (F) reveals a distinct area of focal choroidal dilation that extends from the choriocapillaris throughout the choroid alsoevident on en face images at 120 mm (G) 160 mm (H) and 260 mm (I) below the RPE Note in I that this distinct area of focal choroidal dilation seems tohave anatomic connection to a large dilated choroidal vessel Cross-sectional b-scans from the areas indicated in A respectively the small PED (J) and thepoint of RPE rupture confirmed by the en face image in panel E (K) The focal choroidal dilation clearly documented on en face images is not visible on theb-scan through the fovea (L)

Ophthalmology Volume - Number - Month 2013

Higher detection efficiencies improved imaging rangereduced sensitivity roll off with imaging depth and adapt-ability to longer imaging wavelengths are other potentialadvantages of SS-OCT in comparison with SD-OCT whichcontributed to the improved image quality of the choroid weachieved using SS-OCT and facilitated the clinical inter-pretation of the results To our knowledge this is the firsttime that distinct choroidal changes are described in eyes

6

with chronic CSCR based on en face SS-OCT Although thephysiopathologic significance of focal versus diffusechoroidal dilation is still to be determined our original re-sults may lead to new insights related to disease mecha-nisms En face SS-OCT also offers a new approach in theassessment of CNV and might offer an alternative nonin-vasive investigative tool in the diagnosis and managementof CNV This test may be useful to understand alterations in

Ferrara et al Chronic CSCR on En Face SS-OCT

the layers underneath the neurosensory retina in pathologiesother than CSCR without requiring venous injection forangiography

Study Limitations

The small number of enrolled patients is a limitation of thisstudy although strict inclusion and exclusion criteria wereapplied to assure the reproducibility of the results These strictcriteria are a 2-edged sword and could limit generalizabilityFuture studies with a larger number of patients are needed toestablish the frequency of our observations in both chronicand acute presentations of CSCR as well as in asymptomaticfellow eyes The use of a new SS-OCT prototype instrumentor image processing method might introduce unexpectedimaging artifacts that must be taken into consideration in theinterpretation of tomographic findings The same concernapplies to the interpretation of a post-acquisition reconstruc-tion of SS-OCT en face images using a segmentation algo-rithm Themost significant limitation of en faceOCT imagingis that pathologies such as edema or atrophy which causedisplacement of retinal or choroidal structure outside of theirnormal anatomic positions can cause these features to bevisualized at different levels of the en face images En faceimages are extracted from the 3-dimensional OCT data setusing a surface referenced to the RPEBruchrsquos membraneposition rather than by specifically identifying and seg-menting individual layers Therefore care must be used in enface image interpretation To support our interpretation of enface SS-OCT images we used point-to-point correlation withcross-sectional SS-OCT b-scans and systematic comparisonwith other fundus imaging modalities including color fundusphotography fundus autofluorescence FA and ICGA

In conclusion the high-speed high-resolution enhanced-depth SS-OCT prototype operating at 1050 nm wavelengthused in this study allowed the characterization of 3-dimen-sional en face features of the RPE and choroid in eyes withchronic CSCR in a fast secure noninvasive and repro-ducible assessment This new investigative tool revealedmorphologic features implicated in underlying physiopath-ologic mechanisms and in the future may contribute to thediagnosis and management of this complex disorder

References

1 Gass JD Pathogenesis of disciform detachment of the neuro-epithelium Am J Ophthalmol 196763(Suppl)1ndash139

2 Yannuzzi LA Type A behavior and central serous chorio-retinopathy Trans Am Ophthalmol Soc 198684799ndash845

3 Yannuzzi LA Shakin JL Fisher YL Altomonte MA Pe-ripheral retinal detachments and retinal pigment epithelialatrophic tracts secondary to central serous pigment epitheli-opathy Ophthalmology 1984911554ndash72

4 Spaide RF Campeas L Haas A et al Central serous cho-rioretinopathy in younger adults Ophthalmology 19961032070ndash9

5 Kitzmann AS Pulido JS Diehl NN et al The incidence ofcentral serous chorioretinopathy in Olmsted County Minne-sota 1980-2002 Ophthalmology 2008115169ndash73

6 Ross A Ross AH Mohamed Q Review and update of centralserous chorioretinopathy Curr Opin Ophthalmol 201122166ndash73

7 Piccolino FC de la Longrais RR Ravera G et al The fovealphotoreceptor layer and visual acuity loss in central serouschorioretinopathy Am J Ophthalmol 200513987ndash99

8 Gilbert CM Owens SL Smith PD Fine SL Long-termfollow-up of central serous chorioretinopathy Br J Oph-thalmol 198468815ndash20

9 Liew G Quin G Gillies M Fraser-Bell S Central serouschorioretinopathy a review of epidemiology and pathophysi-ology Clin Experiment Ophthalmol 201341201ndash14

10 Gomolin JE Choroidal neovascularization and central serouschorioretinopathy Can J Ophthalmol 19892420ndash3

11 Bouzas EA Scott MH Mastorakos G et al Central serouschorioretinopathy in endogenous hypercortisolism ArchOphthalmol 19931111229ndash33

12 Bouzas EA Karadimas P Pournaras CJ Central serous cho-rioretinopathy and glucocorticoids Surv Ophthalmol 200247431ndash48

13 Quillen DA Gass DM Brod RD et al Central serous cho-rioretinopathy in women Ophthalmology 199610372ndash9

14 Carvalho-Recchia CA Yannuzzi LA Negrao S et al Corti-costeroids and central serous chorioretinopathy Ophthal-mology 20021091834ndash7

15 Haimovici R Rumelt S Melby J Endocrine abnormalities inpatients with central serous chorioretinopathy Ophthalmology2003110698ndash703

16 Harada T Harada K Six cases of central serous chorioretin-opathy induced by systemic corticosteroid therapy DocOphthalmol 19856037ndash44

17 Tittl M Maar N Polska E et al Choroidal hemodynamicchanges during isometric exercise in patients with inactivecentral serous chorioretinopathy Invest Ophthalmol Vis Sci2005464717ndash21

18 Fawzi AA Holland GN Kreiger AE et al Central serouschorioretinopathy after solid organ transplantation Ophthal-mology 2006113805ndash13

19 Thoelen AM Bernasconi PP Schmid C Messmer EP Centralserous chorioretinopathy associated with a carcinoma of theadrenal cortex Retina 20002098ndash9

20 Fawzi AA Cunningham ET Jr Central serous chorioretinop-athy after bone marrow transplantation Am J Ophthalmol2001131804ndash5

21 Rahbani-Nobar MB Javadzadeh A Ghojazadeh L et al The ef-fect of Helicobacter pylori treatment on remission of idiopathiccentral serous chorioretinopathy Mol Vis [serial online] 20111799ndash103 Available at httpwwwmolvisorgmolvisv17a13Accessed September 29 2013

22 Imamura Y Fujiwara T Margolis R Spaide RF Enhanceddepth imaging optical coherence tomography of the choroid incentral serous chorioretinopathy Retina 2009291469ndash73

23 Kim YT Kang SW Bai KH Choroidal thickness in both eyesof patients with unilateral active central serous chorioretinop-athy Eye (Lond) 2011251635ndash40

24 Drexler W Fujimoto JG State-of-the-art retinal opticalcoherence tomography Prog Retin Eye Res 20082745ndash88

25 Regatieri CV Branchini L Fujimoto JG Duker JS Choroidalimaging using spectral-domain optical coherence tomographyRetina 201232865ndash76

26 Spaide RF Koizumi H Pozzoni MC Enhanced depth imagingspectral-domain optical coherence tomography Am J Oph-thalmol 2008146496ndash500

27 Potsaid B Baumann B Huang D et al Ultrahigh speed 1050nmswept sourceFourier domain OCT retinal and anterior segment

7

Ferrara et al Chronic CSCR on En Face SS-OCT

the layers underneath the neurosensory retina in pathologiesother than CSCR without requiring venous injection forangiography

Study Limitations

The small number of enrolled patients is a limitation of thisstudy although strict inclusion and exclusion criteria wereapplied to assure the reproducibility of the results These strictcriteria are a 2-edged sword and could limit generalizabilityFuture studies with a larger number of patients are needed toestablish the frequency of our observations in both chronicand acute presentations of CSCR as well as in asymptomaticfellow eyes The use of a new SS-OCT prototype instrumentor image processing method might introduce unexpectedimaging artifacts that must be taken into consideration in theinterpretation of tomographic findings The same concernapplies to the interpretation of a post-acquisition reconstruc-tion of SS-OCT en face images using a segmentation algo-rithm Themost significant limitation of en faceOCT imagingis that pathologies such as edema or atrophy which causedisplacement of retinal or choroidal structure outside of theirnormal anatomic positions can cause these features to bevisualized at different levels of the en face images En faceimages are extracted from the 3-dimensional OCT data setusing a surface referenced to the RPEBruchrsquos membraneposition rather than by specifically identifying and seg-menting individual layers Therefore care must be used in enface image interpretation To support our interpretation of enface SS-OCT images we used point-to-point correlation withcross-sectional SS-OCT b-scans and systematic comparisonwith other fundus imaging modalities including color fundusphotography fundus autofluorescence FA and ICGA

In conclusion the high-speed high-resolution enhanced-depth SS-OCT prototype operating at 1050 nm wavelengthused in this study allowed the characterization of 3-dimen-sional en face features of the RPE and choroid in eyes withchronic CSCR in a fast secure noninvasive and repro-ducible assessment This new investigative tool revealedmorphologic features implicated in underlying physiopath-ologic mechanisms and in the future may contribute to thediagnosis and management of this complex disorder

References

1 Gass JD Pathogenesis of disciform detachment of the neuro-epithelium Am J Ophthalmol 196763(Suppl)1ndash139

2 Yannuzzi LA Type A behavior and central serous chorio-retinopathy Trans Am Ophthalmol Soc 198684799ndash845

3 Yannuzzi LA Shakin JL Fisher YL Altomonte MA Pe-ripheral retinal detachments and retinal pigment epithelialatrophic tracts secondary to central serous pigment epitheli-opathy Ophthalmology 1984911554ndash72

4 Spaide RF Campeas L Haas A et al Central serous cho-rioretinopathy in younger adults Ophthalmology 19961032070ndash9

5 Kitzmann AS Pulido JS Diehl NN et al The incidence ofcentral serous chorioretinopathy in Olmsted County Minne-sota 1980-2002 Ophthalmology 2008115169ndash73

6 Ross A Ross AH Mohamed Q Review and update of centralserous chorioretinopathy Curr Opin Ophthalmol 201122166ndash73

7 Piccolino FC de la Longrais RR Ravera G et al The fovealphotoreceptor layer and visual acuity loss in central serouschorioretinopathy Am J Ophthalmol 200513987ndash99

8 Gilbert CM Owens SL Smith PD Fine SL Long-termfollow-up of central serous chorioretinopathy Br J Oph-thalmol 198468815ndash20

9 Liew G Quin G Gillies M Fraser-Bell S Central serouschorioretinopathy a review of epidemiology and pathophysi-ology Clin Experiment Ophthalmol 201341201ndash14

10 Gomolin JE Choroidal neovascularization and central serouschorioretinopathy Can J Ophthalmol 19892420ndash3

11 Bouzas EA Scott MH Mastorakos G et al Central serouschorioretinopathy in endogenous hypercortisolism ArchOphthalmol 19931111229ndash33

12 Bouzas EA Karadimas P Pournaras CJ Central serous cho-rioretinopathy and glucocorticoids Surv Ophthalmol 200247431ndash48

13 Quillen DA Gass DM Brod RD et al Central serous cho-rioretinopathy in women Ophthalmology 199610372ndash9

14 Carvalho-Recchia CA Yannuzzi LA Negrao S et al Corti-costeroids and central serous chorioretinopathy Ophthal-mology 20021091834ndash7

15 Haimovici R Rumelt S Melby J Endocrine abnormalities inpatients with central serous chorioretinopathy Ophthalmology2003110698ndash703

16 Harada T Harada K Six cases of central serous chorioretin-opathy induced by systemic corticosteroid therapy DocOphthalmol 19856037ndash44

17 Tittl M Maar N Polska E et al Choroidal hemodynamicchanges during isometric exercise in patients with inactivecentral serous chorioretinopathy Invest Ophthalmol Vis Sci2005464717ndash21

18 Fawzi AA Holland GN Kreiger AE et al Central serouschorioretinopathy after solid organ transplantation Ophthal-mology 2006113805ndash13

19 Thoelen AM Bernasconi PP Schmid C Messmer EP Centralserous chorioretinopathy associated with a carcinoma of theadrenal cortex Retina 20002098ndash9

20 Fawzi AA Cunningham ET Jr Central serous chorioretinop-athy after bone marrow transplantation Am J Ophthalmol2001131804ndash5

21 Rahbani-Nobar MB Javadzadeh A Ghojazadeh L et al The ef-fect of Helicobacter pylori treatment on remission of idiopathiccentral serous chorioretinopathy Mol Vis [serial online] 20111799ndash103 Available at httpwwwmolvisorgmolvisv17a13Accessed September 29 2013

22 Imamura Y Fujiwara T Margolis R Spaide RF Enhanceddepth imaging optical coherence tomography of the choroid incentral serous chorioretinopathy Retina 2009291469ndash73

23 Kim YT Kang SW Bai KH Choroidal thickness in both eyesof patients with unilateral active central serous chorioretinop-athy Eye (Lond) 2011251635ndash40

24 Drexler W Fujimoto JG State-of-the-art retinal opticalcoherence tomography Prog Retin Eye Res 20082745ndash88

25 Regatieri CV Branchini L Fujimoto JG Duker JS Choroidalimaging using spectral-domain optical coherence tomographyRetina 201232865ndash76

26 Spaide RF Koizumi H Pozzoni MC Enhanced depth imagingspectral-domain optical coherence tomography Am J Oph-thalmol 2008146496ndash500

27 Potsaid B Baumann B Huang D et al Ultrahigh speed 1050nmswept sourceFourier domain OCT retinal and anterior segment

7

Ophthalmology Volume - Number - Month 2013

imaging at 100000 to 400000 axial scans per second Opt Express[serial online] 20101820029ndash48 Available at httpwwwopticsinfobaseorgoeabstractcfmurifrac14oe-18-19-20029AccessedSeptember 29 2013

28 Motaghiannezam R Schwartz DM Fraser SE In vivo humanchoroidal vascular pattern visualization using high-speedswept-source optical coherence tomography at 1060 nmInvest Ophthalmol Vis Sci 2012532337ndash48

29 Unterhuber A Povazay B Hermann B et al In vivo retinaloptical coherence tomography at 1040 nm - enhanced pene-tration into the choroid Opt Express [serial online] 2005133252ndash8 Available at httpwwwopticsinfobaseorgoeab-stractcfmurifrac14oe-13-9-3252 Accessed September 29 2013

30 American National Standard for Safe Use of Lasers OrlandoFL Laser Institute of America 2007 ANSI Z1361-2007Available at httpwwwliaorgPDFZ136_1_spdf AccessedSeptember 29 2013

31 Kraus MF Potsaid B Mayer MA et al Motion correction inoptical coherence tomography volumes on a per A-scan basisusing orthogonal scan patterns Biomed Opt Express [serialonline] 201231182ndash99 Available at httpwwwoptics-infobaseorgboefulltextcfmurifrac14boe-3-6-1182ampidfrac14233031Accessed September 29 2013

32 Gorczynska I Srinivasan VJ Vuong LN et al Projection OCTfundus imaging for visualizing outer retinal pathology in non-exudative age related macular degeneration Br J Ophthalmol200993603ndash9

33 Margolis R Spaide RF A pilot study of enhanced depth im-aging optical coherence tomography of the choroid in normaleyes Am J Ophthalmol 2009147811ndash5

8

34 Spaide R Autofluorescence from the outer retina and sub-retinal space hypothesis and review Retina 2008285ndash35

35 van Velthoven ME Verbraak FD Garcia PM et al Evaluationof central serous retinopathy with en face optical coherencetomography Br J Ophthalmol 2005891483ndash8

36 Prunte C Flammer J Choroidal capillary and venouscongestion in central serous chorioretinopathy Am J Oph-thalmol 199612126ndash34

37 Tewari HK Gadia R Kumar D et al Sympathetic-para-sympathetic activity and reactivity in central serous chorio-retinopathy a case-control study Invest Ophthalmol Vis Sci2006473474ndash8

38 Piccolino FC Borgia L Central serous chorioretinopathy andindocyanine green angiography Retina 199414231ndash42

39 Tittl MK Spaide RF Wong D et al Systemic findingsassociated with central serous chorioretinopathy Am J Oph-thalmol 199912863ndash8

40 Haimovici R Koh S Gagnon DR et al Risk factors for centralserous chorioretinopathy a case-control study Ophthalmology2004111244ndash9

41 Guyer DR Yannuzzi LA Slakter JS et al Digital indocyaninegreen videoangiography of central serous chorioretinopathyArch Ophthalmol 19941121057ndash62

42 Inoue R Sawa M Tsujikawa M Gomi F Association betweenthe efficacy of photodynamic therapy and indocyanine greenangiography findings for central serous chorioretinopathy AmJ Ophthalmol 2010149441ndash6

43 Rouvas A Stavrakas P Theodossiadis PG et al Long-term re-sults of half-fluence photodynamic therapy for chronic centralserous chorioretinopathy Eur J Ophthalmol 201222417ndash22

Footnotes and Financial Disclosures

Originally received July 9 2013Final revision October 3 2013Accepted October 8 2013Available online --- Manuscript no 2013-11061 New England Eye Center Tufts Medical Center Boston Massachusetts2 Department of Electrical Engineering and Computer Science andResearch Laboratory of Electronics Massachusetts Institute of TechnologyCambridge Massachusetts3 Faculty of Physics Ludwig-Maximilians-University Munich MunichGermany4 Pattern Recognition Lab and Graduate School in Advanced OpticalTechnologies University Erlangen-Nuremburg Erlangen-NuremburgGermany

Financial Disclosure(s)The author(s) have made the following disclosure(s) MFK has a patentowned by MIT and licensed to Optovue Inc JGF has personal financial

interest in Optovue Inc and patents owned by MIT and licensed to CarlZeiss Meditech Inc and Optovue Inc JSD receives research supportfrom Carl Zeiss Meditech Inc and Optovue Inc

Support was provided by the National Institutes of Health (R01-EY011289-27 R01-EY013178-12 R01-EY018184-05 R44EY022864-01 R01-CA075289-16 R01-NS057476-05 and R44-EY022864-01) The AirForce Office of Scientific Research (AFOSR) (FA9550-10-1-0551 andFA9550-10-1-0063) Research to Prevent Blindness Massachusetts LionsClub and German Science Foundation DFG (DFG-GSC80-SAOT) Thefunding organizations had no role in the design or conduct of this research

CorrespondenceJay S Duker MD 800 Washington St Box 450 Boston MA 02111E-mail jdukertuftsmedicalcenterorg