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Swept-Source OCT Angiography of Serpiginous Choroiditis

Open AccessPublished:December 29, 2017DOI:https://doi.org/10.1016/j.oret.2017.11.001

      Purpose

      To examine and quantify choriocapillaris lesions in active and quiescent serpiginous choroiditis (SC) using swept-source (SS) OCT angiography (OCTA) and en face image analysis.

      Design

      Prospective, observational case series.

      Participants

      Patients with a clinical diagnosis of SC.

      Methods

      A SS-OCTA prototype was used to image active and quiescent serpiginous lesions longitudinally before and after anti-inflammatory treatment. En face slabs of choriocapillaris flow or outer nuclear layer structure were generated from OCTA and OCT data, respectively.

      Main Outcome Measures

      Qualitative and quantitative analyses on lesion boundary and area using a semiautomated MATLAB algorithm. Lesions also were compared with traditional multimodal imaging.

      Results

      Six eyes of 3 patients were imaged. Choroidal lesions were identified and analyzed in 4 of 6 eyes. Lesions with well-defined boundaries were identified in the choriocapillaris slab in areas of both active and inactive choroiditis. The choriocapillaris slab lesion size and shape showed good correlation with lesions identified on indocyanine green angiography. The choriocapillaris slab lesion area increased with disease activity and decreased with corticosteroid treatment. During active disease, the choriocapillaris slab lesion area was larger than both the outer nuclear layer (ONL) slab and fundus autofluorescence lesion areas. Active choriocapillaris slab lesions not associated with corresponding abnormal autofluorescence resolved without clinical scarring after treatment. In inactive scars, the areas of retinal and choriocapillaris lesions were similar and did not change over time.

      Conclusions

      En face analysis of SS-OCTA choriocapillaris flow voids provide a noninvasive method for the detection of lesions in patients with SC. The presence of lesions in the choriocapillaris in the absence of retinal pigment epithelium and outer retinal abnormalities supports the hypothesis that choriocapillaris is the primary site of pathologic features in SC and may be a sensitive early sign of disease activity. We propose a simple grading system of SC lesions based on SS-OCTA and fundus autofluorescence findings. Swept-source OCTA is a promising noninvasive method for monitoring patients with SC.

      Abbreviations and Acronyms:

      FA (fluorescein angiography), FAF (fundus autofluorescence), ICGA (indocyanine green angiography), OCT (optical coherence tomography), OCTA (OCT angiography), ONL (outer nuclear layer), RPE (retinal pigment epithelium), SC (serpiginous choroiditis), SD (spectral-domain), SS (swept-source)
      Serpiginous choroiditis (SC) is a rare form of bilateral, chronic, or recurrent posterior uveitis that is thought to involve primarily the choriocapillaris, with subsequent involvement of the retinal pigment epithelium (RPE) and outer retina.
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Laatikainen L.
      • Erkkilä H.
      A follow-up study on serpiginous choroiditis.
      • Gass J.D.M.
      Stereoscopic atlas of macular diseases: diagnosis and treatment.
      It causes severe permanent vision loss when involving the fovea and parafovea. This has led to a practice pattern of initiating aggressive immunosuppressive treatment on diagnosis, with evidence of progressive expansion of old lesions or with identification of new lesions.
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Christmas N.J.
      • Oh K.T.
      • Oh D.M.
      • Folk J.C.
      Long-term follow-up of patients with serpinginous choroiditis.
      • Hooper P.L.
      • Kaplan H.J.
      Triple agent immunosuppression in serpiginous choroiditis.
      The identification of disease activity before permanent structural damage would provide the opportunity to prevent vision loss.
      Currently, SC is diagnosed based on clinical appearance and characteristic changes of active lesions using fluorescein angiography (FA),
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Nazari Khanamiri H.
      • Rao N.A.
      Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis.
      with indocyanine green angiography (ICGA) as an adjunct that can identify subclinical lesions.
      • Giovannini A.
      • Ripa E.
      • Scassellati-Sforzolini B.
      • et al.
      Indocyanine green angiography in serpiginous choroidopathy.
      • Bouchenaki N.
      • Cimino L.
      • Auer C.
      • et al.
      Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography.
      Both these studies suggest primary inflammatory pathologic features at the level of the choriocapillaris. More recently, fundus autofluorescence (FAF) has been reported to highlight active lesions with foci of hyperautofluorescence, presumably reflecting acute RPE injury overlying the choriocapillaris inflammation.
      • Yeh S.
      • Forooghian F.
      • Wong W.T.
      • et al.
      Fundus autofluorescence imaging of the white dot syndromes.
      However, inactive scars become hypoautofluorescent.
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Nazari Khanamiri H.
      • Rao N.A.
      Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis.
      • Bouchenaki N.
      • Cimino L.
      • Auer C.
      • et al.
      Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography.
      Nevertheless, none of these methods provide high-resolution imaging of the choriocapillaris, which seems to be fundamentally affected in SC.
      OCT angiography (OCTA) has emerged as a noninvasive imaging method to detect the presence or absence of blood flow signal in the retina.
      • Spaide R.F.
      • Klancnik J.M.
      • Cooney M.J.
      Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography.
      Unlike dye-based angiography methods, OCTA allows vascular analyses to be stratified by retinal layer. OCT angiography has provided insights into pathogenic mechanisms of retinal disease, including uveitic conditions.
      • Kim A.Y.
      • Rodger D.C.
      • Shahidzadeh A.
      • et al.
      Quantifying retinal microvascular changes in uveitis using spectral-domain optical coherence tomography angiography.
      Compared with dye angiography, OCTA also has the benefit of providing high-resolution digital images that are amenable to reproducible quantification.
      Most currently available OCTA devices use spectral-domain (SD) OCT technology. Unfortunately, diseases of the choroid and choriocapillaris are difficult to study with SD technology because of RPE attenuation of the 840-nm central wavelength used in this imaging method.
      • Miller A.R.
      • Roisman L.
      • Zhang Q.
      • et al.
      Comparison between spectral-domain and swept-source optical coherence tomography angiographic imaging of choroidal neovascularization.
      Despite this limitation, SD-OCTA has identified flow voids in the choroid of patients with placoid chorioretinal diseases such as acute posterior multifocal placoid pigment epitheliopathy.
      • Klufas M.A.
      • Phasukkijwatana N.
      • Iafe N.A.
      • et al.
      Optical coherence tomography angiography reveals choriocapillaris flow reduction in placoid chorioretinitis.
      Swept-source (SS) OCT and OCTA use a longer central wavelength (1050 nm) that provides improved signal penetration through the RPE and produces high-resolution images of the choriocapillaris and choroidal vessels.
      • Moult E.M.
      • Waheed N.K.
      • Novais E.A.
      • et al.
      Swept-source optical coherence tomography angiography reveals choriocapillaris alterations in eyes with nascent geographic atrophy and drusen-associated geographic atrophy.
      • Mrejen S.
      • Spaide R.F.
      Optical coherence tomography: imaging of the choroid and beyond.
      Swept-source OCTA has the potential to provide the benefits of noninvasive vascular imaging to identify and monitor diseases that are believed to originate in the choriocapillaris.
      In this study, we sought to examine the usefulness of SS-OCTA to detect choriocapillaris involvement in patients with SC. Furthermore, we compared SS-OCTA with other standard imaging methods including FA, ICGA, SD-OCT, and FAF to determine their relative usefulness in characterization of active and quiescent SC.

      Methods

      This single-institution prospective, observational case series was approved by the institutional review board at the University of Washington. Patients with a diagnosis of peripapillary SC, macular SC, or multifocal or ampiginous choroidopathy were recruited for OCTA imaging as part of this study between September 2016 and March 2017. Informed consent was obtained, and the tenets of the Declaration of Helsinki and the regulations of the Health Insurance Portability and Accountability Act of 1996 were followed.
      Swept-source OCTA and SS-OCT images were obtained using a PLEX Elite 9000 (Carl Zeiss AG, Dublin, CA). This device uses a central wavelength of 1050 nm with a 100-kHz A-scan rate and a spectral bandwidth of 100 nm. The axial and lateral resolutions are approximately 5 μm and approximately 14 μm, respectively. An optical microangiography (OMAG) algorithm was used to construct images demonstrating surrogate markers of vascular flow, the technical aspects of which are detailed elsewhere.
      • Zhang A.
      • Zhang Q.
      • Chen C.-L.
      • Wang R.K.
      Methods and algorithms for optical coherence tomography-based angiography: a review and comparison.
      Fields of view sizes included 3 × 3-mm, 6 × 6-mm, 9 × 9-mm, and 12 × 12-mm imaging windows. A 3 × 3-mm cube contains 300 A-scans per B-scan, and a total of 1200 B-scans, 4 repeats each, whereas the 6 × 6-mm, 9 × 9-mm, and 12 × 12-mm cubes hold 500 A-lines per B-scan, with a total of 1000 B-scans, 2 repeats, centered at the fovea or the optic disc. Pixel spacing and the number of repeated B-scans were compromised in larger scans to maintain similar scanning time as 3 × 3-mm cube. The specific scanning window size chosen for analysis was selected based on the size and location of the region containing pathologic features. OCT angiography images of the choriocapillaris slab (measured from 15 to 35 μm below the RPE best-fit line), OCT images of the RPE slab (from 0 to 10 μm anterior to the RPE best-fit line), and OCT images of the outer nuclear layer (ONL) slab (from 55 to 105 μm anterior to the RPE best-fit line) then were generated for en face analysis for the same field of view. A semiautomated MATLAB algorithm (MathWorks, Natick, MA) was used to identify and measure lesion area on the en face slabs. Lesion area was determined manually by one expert grader with fellowship training in both medical retina and uveitis (K.P.-V.), area was calculated, and the lesions in the various slabs then were overlaid for comparison.
      Clinical images were collected for comparison with OCT and OCTA research images. Clinical images were ordered at the discretion of the treating physician and included color fundus photography (FF450Plus; Carl Zeiss AG), spectral-domain OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany), FAF (FF450Plus [Carl Zeiss AG] or Spectralis HRA+OCT [Heidelberg Engineering]), FA (FF450Plus; or P200DTx [Optos PLC, Dunfermline, United Kingdom]), and ICGA (Spectralis HRA+OCT). Indocyanine green angiography and FAF images for patient 1 were exported as TIFF image files and analyzed using the semiautomated MATLAB algorithm to determine lesion size.
      Patients were diagnosed with SC after an evaluation for other infectious and inflammatory causes that included a careful uveitis review of systems and laboratory testing with a complete blood count, comprehensive metabolic panel, Treponema pallidum immunoglobulin (Ig) G and M for syphilis, an interferon-γ release assay for tuberculosis (QuantiFERON-TB Gold, Qiagen, Hilden, Germany), and a chest radiograph. A complete ophthalmic examination was performed, and uveitis was categorized according to Standardization of Uveitis Nomenclature criteria.
      • Jabs D.A.
      • Nussenblatt R.B.
      • Rosenbaum J.T.
      Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.
      Initial treatment consisted of an oral tapering course of corticosteroid with concomitant immunosuppressive treatment, consistent with expert consensus recommendations.
      • Jabs D.A.
      • Rosenbaum J.T.
      • Foster C.S.
      • et al.
      Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel.

      Results

      Three patients were identified with SC: patient 1 with macular SC, patient 2 with classic peripapillary SC, and patient 3 with multifocal SC. Patient 1 was a 55-year-old white man with a 3-month history of central scotoma and photopsias in the left eye. Fundus imaging, FAF, FA, ICGA, and SS-OCTA were performed (Fig 1), and he was diagnosed with macular SC of the left eye after the evaluation for infectious and inflammatory conditions. The right eye had mild peripapillary atrophy (not shown). Late ICGA images were used to outline the region of choriocapillaris defect and to quantify the area involved in the left eye (Fig 1D). The total area of choriocapillaris defect detected by ICGA was determined to be 17.4 mm2 (Table 1). The lesion shape in the choriocapillaris slab approximated the ICGA boundary, and lesion area was similar at 17.5 mm2. The ONL slab boundary fell within the boundary of the choriocapillaris lesion (Fig 1G), and the lesion area was smaller (14.4 mm2). The RPE lesion, as identified by FAF, demonstrated a similar shape as the choriocapillaris lesion (Fig 1H), and the lesion area was similar (17.6 mm2).
      Figure thumbnail gr1
      Figure 1A, Patient 1 at presentation demonstrating an area of macular serpiginous choroidopathy in the left eye with well-defined borders and areas of retinal pigment epithelium atrophy. Fluorescein angiography showed (B) early hypofluorescence and (C) late hyperfluorescence of the central lesion. D, Late frames from indocyanine green angiography (ICGA) revealed hypofluorescence of the lesion. E, The en face projection of the choriocapillaris slab obtained from swept-source (SS) OCT angiography (OCTA) demonstrated absent small vessel flow. The choriocapillaris lesion boundary and major blood vessel outlines were defined and grouped in (D) the SS-OCTA image and were overlaid en bloc on (E) the magnification-matched ICGA image using MatLab software. F, The hyperreflective region seen in the en face outer retinal slab identified the area of retinal damage. G, Overlay of the larger choriocapillaris lesion (red) with the smaller outer retinal lesion (green). H, Fundus autofluorescence with diffuse central hyperautofluorescence and a thin hypoautofluorescent border.
      Table 1Serpiginous Choroiditis Lesion Area (mm2)
      Patient 1Patient 2Patient 3
      Visit 1Visit 2Visit 2Visit 4Visit 5Visit 1Visit 3
      Choriocapillaris
      As imaged by swept-source OCT angiography.
      17.518.80.421.481.173.301.50
      Outer retina
      As imaged by en face structural swept-source OCT.
      14.416.70.360.820.670.6240.154
      Choroid
      As imaged by indocyanine green angiography on Spectralis HRA+OCT (Heidelberg Engineering).
      17.4
      — = not performed.
      As imaged by swept-source OCT angiography.
      As imaged by en face structural swept-source OCT.
      As imaged by indocyanine green angiography on Spectralis HRA+OCT (Heidelberg Engineering).
      Patient 2 was a 41-year-old white man with a 4-month history of scotoma and photopsia in the left eye. He had been diagnosed with probable SC before presentation, but had not received any treatment. On examination, an inactive serpiginous scar extending from the optic nerve into the macula was noted in the right eye (Fig S2A, C, available at www.ophthalmologyretina.org). In the left eye, there was concern for an area of active peripapillary choroiditis that demonstrated late leakage on fluorescein angiography and hyperautofluorescence at the superotemporal optic nerve border (Fig S2, available at www.ophthalmologyretina.org). Treatment with prednisone and mycophenolate mofetil was initiated, but during the prednisone taper at 10 mg daily, he experienced a recurrence in the left eye (Fig 3F). Oral corticosteroids were increased and tacrolimus started, and the flare was controlled (Fig 3K). On the choriocapillaris slab, the area of the lesion nasal to the retinal vessels did not change in boundary or area over the 3 visits (Fig 3C, H, M, red dotted lines). There was also no change in the ONL slab in this region (Fig 3D, I, N, green dotted lines) or the appearance on FAF (Fig 3B, G, L). In this area, the boundary of the lesion as defined by all 3 imaging methods was aligned closely and the total area involved did not change. This area was considered an inactive scar. In contrast, the temporal aspect of the choriocapillaris slab lesion expanded in size (Fig 3H, solid red line). In comparison with the clinical fundus images, the choriocapillaris slab lesion had sharply delineated borders. The area of ONL disruption also expanded during the flare, but involved less area than the choriocapillaris slab lesion (Table 1; Fig 3I, J). The FAF lesion did not demonstrate expansion of significant hyperautofluorescence, but subtle stippled hyperautofluorescence was noted in the area overlying the choriocapillaris slab lesion (Fig 3G). After additional treatment with pulse oral prednisone and tacrolimus dose increase, the lesion became quiescent on clinical examination (Fig 3K) and the choriocapillaris and ONL lesion areas decreased (Fig 3M–O). In contrast, the area of hyperautofluorescence expanded, and a hypoautofluorescent rim developed (Fig 3L).
      Figure thumbnail gr2
      Figure 3Patient 2. First row, One month after initiation of prednisone and mycophenolate mofetil: (A) color fundus and (B) autofluorescence images of an active lesion at the superotemporal disc margin. C, En face swept-source (SS) OCT angiography (OCTA) choriocapillaris slab revealing flow voids associated with an inactive scar that did not change with time (dotted red line) and flow voids that changed with disease activity (solid red outline). D, En face outer retinal slab showing an area of bright hyperreflectivity in the area of scar (dotted green line) and less pronounced hyperreflectivity in the area of disease activity (solid green outline). E, Overlay of the choriocapillaris lesion (red) and outer retina lesion (green). Second row, Disease flare. Arrows indicate new lesions by (F) color fundus and (G) autofluorescence imaging. H, En face SS-OCTA choriocapillaris slab with lesion enlargement and well-defined borders (solid red outline). I, En face outer retina slab with a larger and brighter lesion (solid green outline). J, Overlay of the choriocapillaris lesion (red) and outer retinal lesion (green). Third row, After 1 month of tacrolimus and oral prednisone, (K) decreased activity on color fundus photograph and (L) increased autofluorescence. M, Swept-source OCTA choriocapillaris slab demonstrating reduced lesion area compared with (H) (solid red outline). N, Outer retinal slab demonstrating decreased size and hyperreflectivity of the outer retinal lesion (solid green outline). O, Overlay of the choriocapillaris lesion (red) and outer retinal lesion (green).
      Patient 3 was a 21-year-old white woman with 3 weeks of worsening floaters, photopsias, and central scotomata in the right eye. Fundus imaging, FA, and ICGA were performed (Fig S4, available at www.ophthalmologyretina.org), leading to a diagnosis of multifocal SC in the right eye after the evaluation for infectious and inflammatory conditions. The left eye was affected minimally with 1 perifoveal lesion (Fig S4B, available at www.ophthalmologyretina.org). Triple therapy with prednisone, azathioprine, and tacrolimus was initiated. Despite favorable clinical response to therapy, a significant tremor developed that responded to discontinuation of tacrolimus. She returned 3 weeks later with new photopsias, and new macular lesions were noted in the right eye (Fig 5A, arrows). Fundus autofluorescence imaging showed that 1 lesion was hyperautofluorescent (Fig 5B, white arrow), whereas the adjacent lesion showed minimal FAF changes (Fig 5B, black arrow). Swept-source OCTA obtained at this visit demonstrated very well-defined lesions in the choriocapillaris slab associated with the 2 new clinically apparent lesions (Fig 5C). In addition, multiple small lesions along and beyond the superior arcade were identified that otherwise were not appreciated by routine clinical examination or imaging (Fig 5C, circles). Outer retinal layer abnormalities also were identified on the ONL slab that corresponded to the clinically apparent lesions (Fig 5D, E), but no ONL abnormalities were seen in association with the small lesions superior to the vascular arcade noted only on the choriocapillaris slab. Tacrolimus was restarted, as were oral corticosteroids with a burst-and-taper schedule. With treatment, the visible lesions resolved clinically and evolved into early scars with the development of hypoautofluorescence on FAF (Fig 5I, J). On follow-up, 2 patterns of choriocapillaris flow void changes were noted. The larger lesion associated with FAF changes decreased, but persistent flow abnormalities in the choriocapillaris remained (Fig 5K, white and black arrowheads; Fig 5N–P, areas in red). The ONL slab abnormality associated with the clinically visible and hyperautofluorescence lesion also decreased, but did not resolve completely (Fig 5M, white arrowhead; Fig 5N–P, areas in green). In contrast, the small lesions seen only in the choriocapillaris slab outside the superior arcade resolved completely.
      Figure thumbnail gr3
      Figure 5Patient 3. Left, After discontinuation of tacrolimus, (A) new lesions developed (arrows). B, One lesion demonstrated concurrent hyperautofluorescence (white arrow). C, En face swept-source (SS) OCT angiography (OCTA) choriocapillaris slab revealing flow voids in the areas of the clinical lesions (arrows). Additional lesions were identified (circles in C) that were not clearly visible on color or fundus autofluorescence images (B). D, B-scan through the acute lesions. E, Outer retinal en face slab with areas of hyperreflectivity corresponding to the clinically visible lesions. F, Magnified SS-OCTA choriocapillaris slab image highlighting multiple choriocapillaris lesions (red). G, Magnified outer retinal slab with outer retinal lesions (green). H, Overlap of (F) and (G). Right, After treatment with tacrolimus and prednisone, disease activity (I) decreased on color images and (J) became more hypoautofluorescent. K, Macular en face SS-OCTA choriocapillaris slab. L, B-scan showing early recovery of the ellipsoid layer and decreased signal transmission (white arrowhead). M, Outer retinal slab. N, Magnified SS-OCTA choriocapillaris slab and (O) outer retinal slabs showing improvement in lesion size after treatment. P, Overlap of (N) and (O). Prior scar (yellow) did not change (G) before and (O) after treatment.

      Discussion

      This series of patients with SC illustrates the potential usefulness of SS-OCTA as a method for detecting and monitoring choriocapillaris lesions. This noninvasive method mirrored ICGA findings in 1 patient with inactive disease and provided increased sensitivity for detection of new lesions compared with FAF in 2 patients with active disease.
      OCT angiography imaging in patient 1 demonstrated the ability of this technique noninvasively to identify clinically relevant choriocapillaris lesions that were also present on ICGA, with high agreement on lesion size and location. In patient 2, OCTA demonstrated the presence of a well-defined choriocapillaris lesion that increased in area during a disease flare and decreased in area with corticosteroid treatment. Interestingly, hyperautofluorescence of the new lesion on FAF imaging did not develop until after steroid treatment was initiated and after the choriocapillaris slab lesion already had decreased. This suggests that FAF imaging may not be as sensitive of a noninvasive imaging marker of acute disease as OCTA.
      • Nazari Khanamiri H.
      • Rao N.A.
      Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis.
      • Yeh S.
      • Forooghian F.
      • Wong W.T.
      • et al.
      Fundus autofluorescence imaging of the white dot syndromes.
      • Cardillo Piccolino F.
      • Grosso A.
      • Savini E.
      Fundus autofluorescence in serpiginous choroiditis.
      In both patients 2 and 3, several new lesions failed to induce marked FAF changes, despite clearly visible lesions in the choriocapillaris slab and the ONL slab. Furthermore, in both patients, after treatment was initiated, the choriocapillaris slab and ONL slab lesions decreased in size, but the hyperautofluorescent lesion grew or developed hypoautofluorescence and scarring. This suggests that FAF may lag choriocapillaris-level pathologic features, as would be the case if the RPE (source of FAF signal) were injured indirectly after a primary insult to the choriocapillaris. In contrast, in patient 1 (who had delayed diagnosis and treatment for at least 3–4 months after the initial symptoms), the area of the choriocapillaris lesion and FAF lesion were very similar in size. This disparity suggests that prompt and aggressive treatment provides the opportunity to reverse to some extent the damage to the choriocapillaris and to prevent overlying retinal and RPE damage.
      Considered to be one of the placoid chorioretinopathies, SC classically originates and expands from a peripapillary location in a serpiginous fashion from single or multiple initial lesions. However, there are variations that do not have a peripapillary component and are termed macular serpiginous, that are noteworthy for the number of lesions termed multifocal serpiginous, or that initially have a benign appearance similar to acute posterior multifocal placoid pigment epitheliopathy, but develop a relentlessly progressive course, termed ampiginous choroiditis.
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Nazari Khanamiri H.
      • Rao N.A.
      Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis.
      • Bouchenaki N.
      • Cimino L.
      • Auer C.
      • et al.
      Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography.
      • Hardy R.A.
      • Schatz H.
      Macular geographic helicoid choroidopathy.
      • Gupta V.
      • Agarwal A.
      • Gupta A.
      • et al.
      Clinical characteristics of serpiginous choroidopathy in North India.
      Despite autoimmune, infectious, vascular, and degenerative hypotheses proposed, no cause has been determined definitively.
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Pallin S.L.
      Noninfectious posterior chorioretinopathies: curious multifocal and contiguous disorders.
      It is thought that SC originates in the choriocapillaris, with secondary effects on the RPE and retina, leading some to call it a choriocapillaropathy.
      • Bouchenaki N.
      • Cimino L.
      • Auer C.
      • et al.
      Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography.
      Rare histopathologic studies have demonstrated atrophy of all 3 layers, but support the hypothesis that the choriocapillaris is involved primarily.
      • Hardy R.A.
      • Schatz H.
      Macular geographic helicoid choroidopathy.
      • Wu J.S.
      • Lewis H.
      • Fine S.L.
      • et al.
      Clinicopathologic findings in a patient with serpiginous choroiditis and treated choroidal neovascularization.
      Studies with ICGA suggest a flow void in the choriocapillaris, with better delineation of lesions and often a larger area of involvement than seen on FA or clinical examination.
      • Lim W.-K.
      • Buggage R.R.
      • Nussenblatt R.B.
      Serpiginous choroiditis.
      • Nazari Khanamiri H.
      • Rao N.A.
      Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis.
      • Giovannini A.
      • Ripa E.
      • Scassellati-Sforzolini B.
      • et al.
      Indocyanine green angiography in serpiginous choroidopathy.
      • Salati C.
      • Pantelis V.
      • Lafaut B.A.
      • et al.
      A 8 months indocyanine angiographic follow-up of a patient with serpiginous choroidopathy.
      • Squirrell D.M.
      • Bhola R.M.
      • Talbot J.F.
      Indocyanine green angiographic findings in serpiginous choroidopathy: evidence of a widespread choriocapillaris defect of the peripapillary area and posterior pole.
      Subclinical hypofluorescent lesions on ICGA can be detected before RPE or retinal changes.
      • Giovannini A.
      • Ripa E.
      • Scassellati-Sforzolini B.
      • et al.
      Indocyanine green angiography in serpiginous choroidopathy.
      However, access to these tests, particularly ICGA, may be limited, and their invasive nature combined with the need for repeated imaging presents a risk–benefit–cost profile that may be unacceptable. Noninvasive choriocapillaris imaging in placoid chorioretinopathies both will advance our understanding of disease pathogenesis and will assist in management decisions. Although not including patients with SC, Klufas et al
      • Klufas M.A.
      • Phasukkijwatana N.
      • Iafe N.A.
      • et al.
      Optical coherence tomography angiography reveals choriocapillaris flow reduction in placoid chorioretinitis.
      recently described SD-OCTA findings in patients with acute posterior multifocal placoid pigment epitheliopathy, persistent placoid maculopathy, and relentless placoid chorioretinitis. They showed areas of absent flow signal on OCTA using a split-spectrum amplitude-decorrelation angiography algorithm at the level of the choriocapillaris that typically were larger than corresponding areas on FA and either the same or larger than ICGA lesions. Outer retina structural OCT demonstrated disruption that colocalized with acute choriocapillaris lesions that decreased either spontaneously or with treatment.
      Our findings in SC also implicate the choriocapillaris as the primary site of pathologic features. Our data suggest that lesions seen on the choriocapillaris slab represent flow voids rather than blockage because of the consistent signal penetration to deeper structures in regions with and without clinical lesions and the absence of shadowing on the B-scans used to generate the en face slabs (Fig S6, available at www.ophthalmologyretina.org). These findings, in conjunction with delayed damage identified on FAF to overlying RPE, suggest an ischemic event at the level of the choriocapillaris rather than inflammatory infiltrate, which would block light signal at deeper levels. However, slow blood flow beyond detection limits could not be differentiated from complete lack of flow with current technology used in this study. Despite this, our data also suggest that the most acute lesions appear as flow voids on OCTA and may have the potential for rapid and complete resolution when treatment is instituted promptly. However, when outer retinal changes develop as identified by the ONL slab abnormalities, and particularly when RPE damage causes FAF changes, permanent scars may be more likely to develop.
      Using SS-OCTA together with other noninvasive imaging methods, we suggest SC lesions can be characterized by grades that are based on characteristic multimodal imaging findings (Table 2). Grade 1 lesions are characterized by the presence of abnormalities at the level of the choriocapillaris as seen by choriocapillaris slab lesions without ONL slab abnormalities or FAF changes. Grade 2 lesions have progressed to involve not only the choriocapillaris, but also the overlying outer retina, and can be identified by the presence of abnormalities in both the choriocapillaris slab and ONL slab. In more acute lesions, the choriocapillaris slab area typically will encompass and extend beyond the ONL slab lesion area. However, in the absence of treatment, the areas of the choriocapillaris and ONL lesion overlap will increase, along with increased border alignment. Grade 3 lesions correspond to subacute chronic disease activity that has led to RPE dysfunction and ultimately to scarring. Grade 3 lesions can be identified by the presence of FAF abnormalities (subacute with hyperautofluorescence, chronic with hypoautofluorescence) in addition to choriocapillaris slab and ONL slab lesions. This grading system has potential clinical importance based on our data suggesting that with prompt treatment, grade 1 and to some extent grade 2 lesions may resolve without subsequent RPE damage or permanent scar formation. We propose this preliminary grading system to assist future studies by providing a systematic approach and consistent language to describe the evolution of acute SC lesions. However, because of the limited number of cases presented herein, the grading system will require validation with a larger number of cases.
      Table 2Serpiginous Choroiditis Lesion Grade Based on Multimodal Imaging
      Anatomic Involvement
      Acute
       Grade 1Choriocapillaris only
      As imaged by swept-source OCT angiography or indocyanine green angiography.
       Grade 2Grade 1, plus outer retina
      As imaged by OCT.
       Grade 3Grade 2, plus retinal pigment epithelium—hyperautofluorescence on fundus autofluorescence imaging
      ChronicHypoautofluorescence on fundus autofluorescence
      As imaged by swept-source OCT angiography or indocyanine green angiography.
      As imaged by OCT.
      Limitations of this study include the small number of patients, limited follow-up, and limited comparison of OCTA imaging with the traditional standard of ICGA imaging. It is likely that ICGA would detect some or all of the lesions found on SS-OCTA
      • Giovannini A.
      • Ripa E.
      • Scassellati-Sforzolini B.
      • et al.
      Indocyanine green angiography in serpiginous choroidopathy.
      • Bouchenaki N.
      • Cimino L.
      • Auer C.
      • et al.
      Assessment and classification of choroidal vasculitis in posterior uveitis using indocyanine green angiography.
      • Salati C.
      • Pantelis V.
      • Lafaut B.A.
      • et al.
      A 8 months indocyanine angiographic follow-up of a patient with serpiginous choroidopathy.
      ; however, because of the risks associated with an invasive test, it was not performed when the treating clinician at our institution believed that management would not change. Future studies should seek to validate SS-OCTA against traditional ICGA with a prospective study design. Artifacts have been identified in previous studies using SD-OCTA
      • Spaide R.F.
      • Fujimoto J.G.
      • Waheed N.K.
      Image artifacts in optical coherence tomography angiography.
      and have the potential to influence imaging and quantitation of the deeper choroidal structures. Shadowing from overlying retinal structures could lead to false attribution of choroidal flow voids. However, this was not identified as a significant factor in a previous study
      • Klufas M.A.
      • Phasukkijwatana N.
      • Iafe N.A.
      • et al.
      Optical coherence tomography angiography reveals choriocapillaris flow reduction in placoid chorioretinitis.
      or in the work presented herein. These and other issues such as motion artifact will become less of a concern for future studies with improved image processing.
      • Camino A.
      • Zhang M.
      • Gao S.S.
      • et al.
      Evaluation of artifact reduction in optical coherence tomography angiography with real-time tracking and motion correction technology.
      • Hwang T.S.
      • Zhang M.
      • Bhavsar K.
      • et al.
      Visualization of 3 distinct retinal plexuses by projection-resolved optical coherence tomography angiography in diabetic retinopathy.
      • Zhang Q.Q.
      • Zhang A.Q.
      • Lee C.
      • et al.
      Projection artifact removal enables accurate presentation and monitoring of choroidal neovascularization imaged by optical coherence tomography angiography.
      This study also benefitted from the increased scanning speeds provided by an SS system because we were able to obtain images over larger areas of the fundus than were possible previously. The ability to image the entire macula will be particularly useful to detect subclinical lesions that may not be noted by patients or other imaging systems because of their extrafoveal location. Ongoing study of the clinical relevance of SS-OCTA images will help to clarify the usefulness of this method.
      The current era of advanced in vivo imaging allows detection of acute and subclinical lesions in diseases like SC. Symptoms, or the lack thereof, may not reflect active pathologic features as demonstrated on sensitive imaging methods. The potential for identification of lesions with rapid, noninvasive imaging may provide clinicians with a window of opportunity to prevent permanent retinal damage.

      Supplementary Data

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