Multimodal Imaging in Sympathetic Ophthalmia

Ocular Immunology and Inflammation

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

Sarakshi Mahajan MBBS, Alessandro Invernizzi MD, Rupesh Agrawal MD, Jyotirmay Biswas MD, Narsing A. Rao MD & Vishali Gupta MD

To cite this article: Sarakshi Mahajan MBBS, Alessandro Invernizzi MD, Rupesh Agrawal MD, Jyotirmay Biswas MD, Narsing A. Rao MD & Vishali Gupta MD (2016): Multimodal Imaging in Sympathetic Ophthalmia, Ocular Immunology and Inflammation, DOI: 10.1080/09273948.2016.1255339

To link to this article: http://dx.doi.org/10.1080/09273948.2016.1255339

Published online: 14 Dec 2016.

Submit your article to this journal

Article views: 29

View related articles

View Crossmark data

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

Download by: [The UC San Diego Library] Date: 01 January 2017, At: 05:42 Ocular Immunology & Inﬂammation, 2016; 00(00): 1–8 © Taylor & Francis Group, LLC ISSN: 0927-3948 print / 1744-5078 online DOI: 10.1080/09273948.2016.1255339

REVIEW ARTICLE

Multimodal Imaging in Sympathetic Ophthalmia

1 2,3 4 Sarakshi Mahajan, MBBS , Alessandro Invernizzi, MD , Rupesh Agrawal, MD , Jyotirmay Biswas, 5 6 1 MD , Narsing A. Rao, MD , and Vishali Gupta, MD

1Advanced Eye Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India, 2Uveitis and Ocular Infectious Diseases Service – Eye Clinic, Department of Biomedical and Clinical Science, “Luigi Sacco” Liuigi Sacco Hospital, University of Milan, Milan, Italy, 3Department of Clinical Sciences and Community Health, University of Milan, Ophthalmological Unit, IRCCS-Cà Granda Foundation – Ospedale Maggiore Policlinico, Milan, Italy, 4National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, 5Uveitis and Ocular Pathology Department, Sankara Nethralya, Chennai, India, and 6USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

ABSTRACT Purpose: To show the current status of multimodal imaging and its role in supporting an early diagnosis of sympathetic ophthalmia. Methods: The diagnosis is mainly clinical supported with ancillary investigations; mainly ﬂuorescein angiography and others, including indocyanine angiography optical coherence tomography (OCT), OCT enhanced depth imaging, autoﬂuorescence imaging, and ultrasonography.

Results: Various imaging modalities such as OCT, autofluorescence imaging and angiography are critical in the diagnosis and management of sympathetic ophthalmia. The clinician must make adequate use of such ancillary investigations in the management of the patients. Conclusions: Sympathetic ophthalmia is a rare, bilateral inflammation of the uveal tract following penetrating trauma or surgery in one eye. The intraocular inflammation requires a prompt diagnosis so that the treatment can be initiated as early as possible. Keywords: Autofluorescence, fluorescein angiography, indocyanine green angiography, OCT-enhanced depth imaging, sympathetic ophthalmia

Sympathetic ophthalmia (SO) is a rare, bilateral dif- posterior segment manifestations, including optic fuse granulomatous uveitis that usually occurs fol- disc edema, exudative retinal detachment, vitritis lowing penetrating ocular trauma or surgery and Dalen-Fuchs nodules, and has characteristic find- involving the uvea in one eye. The inflammation pri- ings seen during the acute phase.4 Since the inflam- marily involves the choroid to begin with presenting mation primarily involves the choroid, indocyanine – as posterior uveitis that may evolve to panuveitis.1 4 green angiography (ICG) too offers useful informa- Rarely, the inflammation may involve iris and ciliary tion and may be used during follow-up to monitor body initially, followed by panuveitis. The diagnosis response to therapy. The improved imaging modal- of SO is usually based on the history and clinical ities to visualize the choroid with the enhanced depth signs of intraocular inflammation. The ancillary imaging (EDI) OCT, is being used frequently for mea- investigations are useful adjuncts to support the diag- suring changes in the choroidal thickness from the nosis, determine the severity and extent, as well as to inflammatory process. However, the ultrasound B evaluate the response to treatment during follow-up. scan can still be used to demonstrate diffuse choroi- Fundus fluorescein angiography (FFA) has been used dal thickening in the posterior pole with or without most commonly in patients who present early with exudative retinal detachment, in case EDI OCT is

Received 13 May 2016; revised 18 October 2016; accepted 27 October 2016; published online 13 December 2016 Correspondence: Vishali Gupta, MD, Professor, Advanced Eye Center, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012, India. E-mail: [email protected] Color versions of one or more of the ﬁgures in the article can be found online at www.tandfonline.com/ioii.

1 2 S. Mahajan et al. unavailable or media is hazy.3,4 Autoﬂuorescence imaging changes seen from the pathologic changes of retinal pigment epithelium, mostly take place during the chronic phase.

FLUORESCEIN ANGIOGRAPHY

At the onset of intraocular inflammation in sympathetic ophthalmia, the FFA features of retina and choroid differ from those observed during chronic or chronic-recurrent phases of this granulomatous inflammation.Initially,the clinical presentation of SO may be restricted to the ocular fundus in the form of posterior uveitis (Figure 1)with diffuse thickening of the choroid and or multifocal nod- – fi ular changes in the choroid.1 4 The nodular changes may FIGURE 2. Wide- eld fundus image of the left eye in a patient with chronic sympathetic ophthalmia, showing a depigmented be from either Dalen-Fuchs nodules or foci of epithelioid choroid, juxta-papillary choroidal atrophy, and numerous histiocytic cell collections in the inner choroid. nummular chorioretinal scars at the periphery. Subsequently, as the inflammation progresses, the posterior uveitis evolves into panuveitis. However, some patients with SO may present initially with posterior leaks, which gradually increase in size and coalesce under uveitis or anterior granulomatous uveitis that may evolve focal retinal detachments (Figure 3) resulting in multilob- fl ular pooling of the dye with staining of the subretinal into panuveitis. The intraocular in ammation is known 5 to be similar in the exciting eye and in the sympathizing exudates. The focal leaks may represent disruption in eye. In the chronic phase of the inflammation, most RPE cell junctions or damage to RPE. However, there is fi patients present with panuveitis or anterior uveitis with no histopathologic con rmation of such RPE changes fi 4 extensive chorioretinal damage, including depigmenta- correlating with this angiographic nding. The choroid tion of choroid in pigmented individuals and display of perfusion may be delayed focally or as patchy areas. Usually, the optic disc shows leaking of disc vessels or multiple nummular chorioretinal scars predominantly in the periphery of the fundus (Figure 2). staining of the nerve head. Two distinct types of abnormal angiographic features The second type of the angiographic features is similar to that observed in patients with acute posterior multi- are known to occur in SO during initial presentation; 4 initial pinpoint hyperfluorescent leaks or multiple hypo- focal placoid pigment epitheliopathy (APMPPE). These fl fluorescent spots with dye pooling in the late phase. The changes are less common and consist of hypo uorescent pattern with initial pinpoint hyperfluorescent leaks is seen foci during the early phase of angiography and these foci fl more frequently and is virtually identical to that seen in become hyper uorescent subsequently. Unlike APMPPE, – – these focal lesions are slightly elevated and may reveal a the acute phase of Vogt Koyanagi Harada (VKH) dis- 3 ease. Typically, hyperfluorescent multifocal leaks of the mild mottled appearance. It is postulated that the hypo- fl dye at the level of retinal pigment epithelium (RPE) are uorescence could be from the obscuration of choroidal fl present. These leaks are commonly described as pinpoints uorescence by Dalen-Fuchs nodules or from focal

FIGURE 1. A 15-year-old female with repaired full thickness anterior scleral laceration presented about 8 weeks later, with bilateral decreased vision. Fundus examination revealed bilateral hyperemic optic disc with multifocal serous detachments of retina seen in the posterior pole.

Ocular Immunology & Inﬂammation Imaging in Sympathetic Ophthalmia 3

FIGURE 3. The patient with fundus changes depicted in Figure 1 showed multiple hyper- and hypoﬂuorescent spots (A) during early phase of the angiography. The hyperﬂuorescent spots gradually increased in size and coalesced at the sites of retinal detachment (B,C).

At the late phase, the angiogram shows subretinal pooling of dye in lobular pattern in right and left fundus (C,D). obliteration of the choriocapillaris by the inflammatory imaging modality to evaluate the choroid and to look cells extending from the choroid.6 Thelatehyperfluores- for the presence of choroidal infiltrates.9,10 The common cence represents staining of the lesions.7 findings on ICGA for patients with SO are multiple hypo- ThechronicphaseofSOiscomplicated by chorioret- cyanescent spots, as against hyperfluorescent spots on inal damage, nummular scars, choroidal atrophy, subret- corresponding FFA (Figure 4). These spots are likely to inal fibrosis, and choroidal neovascularization.4,5 These be due to cellular infiltration of the choroid and presence features result in variable angiographic changes reflective of Dalen-Fuchs nodules or overlying edema, based on of the complications. Typically, the nummular scars reveal studies that have correlated these findings histopatholo- – window defects from chorioretinal adhesions and focal gically and found them to be consistent.10 12 The presence RPE and inner choroidal damage. The subretinal fibrotic or absence of these hypocyanescent spots in each phase of changes reveal a gradual increase in hyperfluorescence ICGA may also give a clue to the type of lesion involved. and staining.8 Histologically, the nummular scars may Various studies have reported the pattern observed, how- represent focal absence of RPE and photoreceptors cells, ever there are no consistent reports. Bernasconi et al.10 and as reported in enucleated eyes of Vogt–Koyanagi–Harada Casella et al.12 described lesions in different stages of SO. disease.9 At these sites of RPE damage, retinal glial cells While Casella and colleagues reported a pattern of ICG in are seen in direct contact with Bruch’s membrane. The acute stages of SO, Bernasconi reported two cases, one subretinal fibrosis reflects proliferated and metaplastic case each in the acute and chronic stage. Casella correlated RPE cells devoid of melanin granules and these cells the ICG changes in the acute stage with the histopatholo- morphologically resemble fibrotic tissue localized to sub- gic features of enucleated eye with sympathetic ophthal- retinal space. The choroidal and disc neovascularization is mia. Bernasconi et al. reported persistence of the rare and these new vessels show leaking of the dye. hypocyanescent areas throughout the intermediate and late phases (Figure 4), with corresponding areas of hyperfluorescence on FFA (Figure 4) and yellow atrophic areas INDOCYANINE GREEN ANGIOGRAPHY on fundus examination, interpreted as likely to be due to chorioretinal atrophy. On the other hand, if the spots fade As SO primarily involves inflammation of the choroid, inthelatephase,itwasinterpretedtobeactivechoroidal indocyanine green angiography (ICGA) can be a good space occupying lesions that resulted in late impregnation

FIGURE 4. Fundus fluorescein angiography and indocyanine green angiogram images of the left eye of a 37-year-old male with sympathetic ophthalmia. Parts A–D demonstrate early to late fluorescein angiogram images, showing the presence of early hypofluor- escent (A) with hyperfluorescent spots in mid- (B) and late phases (C,D). Dual angiogram of this patient revealed presence of hypocyanescent spots in early (E), mid- (F) and late (G,H) phases of indocyanine green angiogram. of the dye.10 However, Casella et al.12 reported that, even of AF, hyperautofluorescence represents increased meta- though the ICGA showed hypocyanescent spots that per- bolic activity of the RPE, thus predicting dysfunction of sisted throughout the phases, correlation with histopatho- the RPE, while hyperautofluorescence typically occurs logic findings and FFA revealed that the spots were due to with the loss of RPE cells.16,17 Furthermore, not only can Dalen-Fuchs nodules and not chorioretinal atrophy as AF aid in the early detection of disease activity, it also described by Bernasconi.10 Importantly, these hypocya- allows for the evaluation of the extent of damage, the nescent spots are noted to attenuate or disappear after identification of sequelae such as choroidal neovascular- corticosteroid treatment and are consistent with clinical ization secondary to inflammation, as well as under- improvement.10,11 However, Moshfeghi et al. reported stand the pathophysiology of the disease.18,19 that, even though the hypocyanescent spots disappeared In a study of a patient with clinically diagnosed SO, in the intermediate phase, they reappeared in the late Fleischman et al. reported that a petaloid pattern of hyper- phase of ICGA.13 autofluorescence centered on the optic nerve corresponding to areas of exudative retinal detachment on fundus examination was seen in this patient prior to treatment AUTOFLUORESCENCE IMAGING (Figure 5). Following resolution, speckled areas of hyper- and hypoautofluorescence resembling leopard spots were Autofluorescence (AF) can be a useful non-invasive ima- seen in the previous areas of exudative detachment ging modality in patients with SO. AF is a simple and (Figure 6). This patient underwent enucleation for the non-invasive procedure, based on the detection of fluor- contralateral eye and the histology confirmed the diagno- ophores, which is mainly represented by lipofuscin in the sis of SO.20 However, there are limited studies reporting RPE.14 Lipofuscin is a byproduct of phagocytosis with the application of AF in SO. Nevertheless, various studies accumulation of incompletely degraded products of have been done regarding the use and pattern of AF in photoreceptor outer segments and is therefore indicative posterior uveitis and specifically VKH disease, which is of the metabolic activity of the RPE in relation to its histopathologically similar to SO. Characteristic patterns phagocytic function. It has also been shown to produce of each disease are gradually being observed, however, oxygen radicals that can cause apoptosis of the RPE further studies are required to establish the pattern of AF – cells.15 Thus, the amount of lipofuscin is a likely indicator in posterior uveitis, especially that of SO.19 21 The wide- of the disease activity and viability of the RPE. As the field AF allows for detection of lipofuscin in the periphery amount of lipofuscin is positively related to the intensity that corresponds to RPE health in that area.22

Ocular Immunology & Inﬂammation Imaging in Sympathetic Ophthalmia 5

FIGURE 5. (A) Autofluorescence image of a patient with sympathetic ophthalmia showing the presence of diffuse hyperautofluorescence spots around the peripapillary region (though not in characteristic petaloid pattern). (B) Autofluorescence images of a patient with sympathetic ophthalmia after treatment showing the presence of multiple hypoautofluorescent spots.

FIGURE 6. Ultrasound of sympathizing eye showing shallow retinal detachment at the macula (A), increased choroidal thickness at high gain (B), and at low gain (C), and at the low gain magniﬁed image (D).

ULTRASOUND B SCAN antecedent trauma. The only inciting factor has been some surgical procedure, most commonly B-scan ultrasonography in SO typically shows dif- vitreoretinal surgery.24 B-scan ultrasonography also fuse choroidal thickening (in >60% of cases) and in becomes an essential tool in the management of some cases, serous retinal detachment at the poster- cataract in SO prior to surgery in cases where the ior pole.23 Cases of SO have been reported in the retina cannot be visualized due to posterior syne- literature, where there has been no history of chiae or dense cataract (Figures 7 and 8).

feature only reported in SO and VKH is the presence, in some cases, of hyperreflective septa (likely fibrin made) crossing the detachment and dividing it in pockets (Figure 7A). As a consequence of the photoreceptors’ disconnection from the RPE, the shedding of the outer segments can be interrupted in the area of fluid accumulation resulting in photoreceptors outer segment elongation (Figure 7B). Such alterations can regress and completely disappear if prompt therapy is started.27 On the contrary, longstanding fluid leads to irreversible damage of the overlaying retina, resulting in cystoid macular edema formation and loss of photoreceptors function, similar to that described in chronic central serous chorioretinopathy.27,28 A case of persis- tent subretinal fluid in SO secondary to a RPE tear has been recently described by the use of SD-OCT.29 Although reported just in single cases, choroidal features in the acute phases of SO resemble the widely described alterations found in VKH, including folds, massive thickening and loss of the physiologic archi- tecture of the choroidal layers (Figure 9B).30,31 During the chronic stage of the disease, atrophic changes have FIGURE 7. Spectral domain optical coherence tomography (SD- been reported in the choroidal structure, regardless the OCT) and enhanced depth imaging (EDI-OCT) findings in two inflammatory status of the patient.32 Choroidal thick- different eyes affected by acute sympathetic ophthalmia (SO). ness has been shown to be a good biomarker for During the acute phase of the disease, multiple serous detach- monitoring disease activity in VKH, especially during ments of the neurosensory retina appear on SD-OCT as empty 33 spaces (A). A distinctive feature only reported in SO and VKH is the chronic stage of the disease. Considering the the presence in some patients of hyperreflective septa (white similarities existing between VKH and SO, a possible arrowheads) crossing the detachment and dividing it in pockets role of EDI-OCT-based choroidal thickness assessment (white asterisks). EDI-OCT (B) shows choroidal thickening, sub- in the management of SO patients should hence be retinal choroidal folds (black arrowheads) and loss of the physiologic choroidal vascular pattern (black asterisks). Photoreceptors speculated, although follow-up studies focusing on outer segments appear elongated (white arrows). the correlation between choroidal changes and SO activity have not been reported in the literature so far. SD-OCT can also be used to image and follow the OPTICAL COHERENCE TOMOGRAPHY evolution of Dalen-Fuchs nodules.32,34 These peculiar SO lesions appear as round-shaped hyperreflective Spectral domain optical coherence tomography (SD- areas located at the level of the outer retina and dis- OCT) is a non-invasive imaging technique that allows rupting the RPE, as well as the outer retinal bands collecting tomographic quasi-histologic scans of the (Figure 8A). In response to therapy, the lesions usually 25 retina and RPE. In the last few years, technological regress but RPE disruption can persist (Figure 8B,C).35 improvements in the SD-OCT technology have over- come the limitations of the technique in penetrating ocular tissues and nowadays enhanced depth imaging Optical Coherence Tomography Angiography (EDI-OCT) is available for the study of ocular structures deeper than the RPE such as the choroid and the The latest generation of OCT, named angio-OCT 26 sclera. Today, SD-OCT and EDI-OCT are widely (OCTA), allows the visualization of vascular structures used in the diagnosis and the management of several without dye injection. Up to now, there are no reports retinal diseases and uveitis allowing the detection of in the literature describing OCTA findings in SO.36 fl generic in ammatory changes, such as cystoid macu- OCTA cannot visualize retinal barriers (inner/ lar edema or choroidal thickening as well as distinct outer) breakdown, thus it could be less useful than fi features of speci c uveitis entities. fluorescein or indocyanine green angiography for the fi SO shows peculiar ndings on SD-OCT and EDI- detection of inflammatory changes. Nevertheless, the OCT during the whole course of the disease. The acute capability of OCTA in visualizing occlusive and phase is characterized by multiple serous detachments inflammatory alterations of the choriocapillaris has of the neurosensory retina similar to those described in been recently reported in VKH disease.37 This study fl VKH disease. Such uid accumulations appear on SD- has reported 10 eyes of patients with acute VKH dis- OCT as empty spaces between the neurosensory retina ease who underwent multimodal imaging including 25–27 and the underlying RPE (Figure 7). A distinctive OCTA to evaluate retinochoroidal vasculature. They

Ocular Immunology & Inﬂammation Imaging in Sympathetic Ophthalmia 7

FIGURE 8. Spectral domain optical coherence tomography (SD-OCT) scan passing through a large Dalen-Fuchs nodule. A magnified view of the dotted squared area of the scan including the lesions is visible on the right side of the image. At baseline visit (A), the nodule appears as a hyperreflective round-shaped alteration disrupting the retinal pigmented epithelium (RPE) and penetrating the outer retinal layers. At 2 weeks after the therapy onset (B), a partial regression of the lesion is visible in the outer area. At the last follow-up visit (C), about 1 year after presentation, a further regression of the hyperreflective material constituting the nodule can be appreciated, although the RPE still shows atrophic scarring damage. observed multiple foci of choriocapillaris flow-void presentation may be in the form of serous retinal that correlated with ICGA and showed a decrease in detachments with minimal/absent anterior segment size and number on treatment.37 Similar lesions had inflammation. Fluorescein angiography features are been described in SO by invasive imaging techniques characteristic and may help in making the diagnosis. in the past, thus a possible role of OCTA in the identi- Enhanced depth imaging on OCT, showing thickened fication of such alterations could be considered, as SO choroid with overlying serous detachment, substanti- resembles VKH very closely. ates the diagnosis. Both these features can also be seen Besides the areas of capillary flow-void, OCTA is on an ultrasound B scan. In patients with typical pre- also useful in detecting accompanying choroidal neo- sentation, the treatment may be initiated based on vascularization that may occur as a complication during fundoscopy, fluorescein angiography, and OCT. The the chronic stage of the disease. In a recent study, disease may be monitored on repeat fundoscopy and OCTA has been reported to be more sensitive than OCTs that document reduction of serous detachment, conventional imaging techniques including fluorescein as well as choroidal thickening. OCTA is a newer angiography and OCT in detecting choroidal neovascu- modality, which appears promising during the acute larization in patients with punctate inner choroidopathy phase of SO, as well as for monitoring. and multifocal choroiditis.38 Thus, it may also be useful for detection of the choroidal neovascularization in SO. In conclusion, the diagnosis of sympathetic ophthal- DECLARATION OF INTEREST mia is generally based on the clinical impression and supported by multimodal imaging. SO is suspected in The authors report no conflicts of interest. The authors a patient who presents with inflammation in the oppo- alone are responsible for the content and writing of the site eye following ocular trauma or surgery. The initial article.

REFERENCES 21. Gupta V, Al-Dhibi HA, Arevalo JF. Retinal imaging in uveitis. Saudi J Ophthalmol. 2014;28:95–103. fi 1. Segawa K, Matsuoka N. Sympathetic ophthalmia: a com- 22. Seidensticker F, Neubauer AS, Wasfy T, et al. Wide- eld fl fundus autofluorescence corresponds to visual fields in parative uorographic and electron microscopic study. Jap J – Ophthalmol. 1971;15:81–87. chorioretinitis patients. Clin Ophthalmol. 2011;5:1667 1671. 2. Shimizu K, Yokochi K, Kobayashi Y. Inflammations of the 23. Castiblanco C, Adelman R. Imaging for sympathetic ophthalmia: impact on the diagnosis and management. Int choroid. In: De Laey JJ, ed. Documenta Ophthalmologica – Proceedings, International Symposium on Fluorescein Ophthalmol Clin. 2012;52:173 181. Angiography, vol. 9. The Hague: W. Junk; 1976:385–390. 24. Forster DJ, Cano MR, Green RL, et al. Echographic features 3. Lewis ML, Gass DM, Spencer WH. Sympathetic uveitis of Vogt-Koyanagi-Harada syndrome. Arch Ophthalmol. 1009;108:1421–1426. after trauma and vitrectomy. Arch Ophthalmol. fi 1978;96:263–267. 25. Keane PA, Sadda SR. Retinal imaging in the twenty- rst century: state of the art and future directions. 4. Gupta V, Gupta A, Dogra MR. Posterior sympathetic – ophthalmia: a single centre long-term study of 40 patients Ophthalmology. 2014;121:2489 2500. from North India. Eye (Lond). 2008;22:1459–1464. 26. Mrejen S, Spaide RF. Optical coherence tomography: imaging of the choroid and beyond. Surv Ophthalmol. 5. Burkholder BM, Dunn JP. Multiple serous retinal detach- – ments seen on wide-field imaging in a patient with sympa- 2013;58:387 429. thetic ophthalmia. JAMA Ophthalmol. 2014;132:1220. 27. Gupta V, Gupta A, Dogra MR, et al. Reversible retinal 6. Sharp DC, Bell RA, Patterson E, et al. Sympathetic ophthal- changes in the acute stage of sympathetic ophthalmia seen fl on spectral domain optical coherence tomography. Int mia. histopathologic and uorescein angiographic correla- – tion. Arch Ophthalmol. 1984;102:232–235. Ophthalmol. 2011;31:105 110. 7. Correnti AJ, Read RW, Kimble JA, et al. Imaging of Dalen- 28. Iida T, Yannuzzi LA, Spaide RF, et al. Cystoid macular degeneration in chronic central serous chorioretinopathy. Fuchs nodules in a likely case of sympathetic ophthalmia by – – fluorescein angiography and OCT. Ophthalmic Surg Lasers Retina. 2003;23:1 7, 137 138. – 29. Mahendradas P, Avadhani K, Madhavarao B, et al. High Imaging. 2010;9:1 3. fi 8. Wang RC, Zamir E, Dugel PU, et al. Progressive subretinal de nition spectral domain optical coherence tomography of fi retinal pigment epithelial rip in a case of sympathetic brosis and blindness associated with multifocal granulo- fl matous chorioretinitis: a variant of sympathetic ophthalmia. ophthalmia. J Ophthalmic In amm Infect. 2013;3:19. Ophthalmology. 2002;109:1527–1531. 30. Behdad B, Rahmani S, Montahaei T, et al. Enhanced depth imaging OCT (EDI-OCT) findings in acute phase of sympa- 9. Inomata H, Rao NA. Depigmented atrophic lesions in sun- – set glow fundus of Vogt-Koyanagi-Harada disease. Am J thetic ophthalmia. Int Ophthalmol. 2015;35:433 439. Ophthalmol. 2001;131:607–614. 31. Fleischman D, Say EA, Wright JD, et al. Multimodality diagnostic imaging in a case of sympathetic ophthalmia. 10. Bernasconi O, Auer C, Zografos L, et al. Indocyanine green fl – angiographic findings in sympathetic ophthalmia. Graefes Ocul Immunol In amm. 2012;20:300 302. Arch Clin Exp Ophthalmol. 1998;236:635–638. 32. Tah V, Zarranz-Ventura J, Sim DA, et al. Characterization of 11. Saatci AO, Paşa E, Söylev MF, et al. Sympathetic ophthal- choroidal structure in sympathetic ophthalmia using optical mia and indocyanine green angiography. Arch Ophthalmol. coherence tomography. Invest Ophthalmol Vis Sci. 2004;122:1568–1569. 2012;53:1156. 12. Casella AM, Farah ME, Martins MC, et al. Sympathetic 33. Jap A, Chee SP. The role of enhanced depth imaging optical ophthalmia – histopathological correlation with fluorescein coherence tomography in chronic Vogt-Koyanagi-Harada and indocyanine green angiography: case report. Arq Bras disease. Br J Ophthalmol. 2016 [Epub ahead of print]. DOI: Oftalmol. 2008;71:886–889. 10.1136/bjophthalmol-2015-308091. 13. Moshfeghi AA, Harrison SA, Ferrone PJ. Indocyanine green 34. Correnti AJ, Read RW, Kimble JA, et al. Imaging of Dalen- fi Fuchs nodules in a likely case of sympathetic ophthalmia by angiography ndings in sympathetic ophthalmia. fl Ophthalmic Surg Lasers Imaging. 2005;36:163–166. uorescein angiography and OCT. Ophthalmic Surg Lasers 14. Delori FC, Dorey CK, Staurenghi G, et al. In vivo fluores- Imaging. 2010 [Epub ahead of print]. DOI: 10.3928/ cence of the ocular fundus exhibits retinal pigment epithe- 15428877-20100215-56. lium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 35. Muakkassa NW, Witkin AJ. Spectral-domain optical coher- 1995;36:718–729. ence tomography of sympathetic ophthalmia with Dalen- Fuchs nodules. Ophthalmic Surg Lasers Imaging Retina. 15. Gaillard ER1, Atherton SJ, Eldred G, et al. Photophysical – studies on human retinal lipofuscin. Photochem Photobiol. 2014;45:610 612. – 36. Spaide RF, Klancnik JM, Cooney MJ. Retinal vascular 1995;61:448 453. fl 16. Durrani K, Foster CS. Fundus autofluorescence imaging in layers imaged by uorescein angiography and optical – – coherence tomography angiography. JAMA Ophthalmol. posterior uveitis. Semin Ophthalmol. 2012;27(5 6):228 235. – 17. Yeh S, Faia LJ, Nussenblatt RB. Advances in the diagnosis 2015;133:45 50. and immunotherapy for ocular inflammatory disease. Semin 37. Aggarwal K, Agarwal A, Mahajan S, et al.; OCTA Study Immunopathol. 2008;30:145–164. Group. The role of optical coherence tomography angiography in the diagnosis and management of acute Vogt- 18. Schmitz-Valckenberg S, Holz FG, Bird AC, et al. Fundus fl autofluorescence imaging: review and perspectives. Retina. Koyanagi-Harada disease. Ocul Immunol In amm. 2016 2008;28:385–409. [Epub ahead of print]. DOI: 10.1080/ 19. Samy A, Lightman S, Ismetova F, et al. Role of autofluores- 09273948.2016.1195001. cence in inflammatory/infective diseases of the retina and 38. Levison AL, Baynes KM, Lowder CY, et al. Choroidal neo- choroid. J Ophthalmol. 2014;2014:418193. vascularisation on optical coherence tomography angiogra- 20. Fleischman D, Say EA, Wright JD, et al. Multimodality phy in punctate inner choroidopathy and multifocal diagnostic imaging in a case of sympathetic ophthalmia. choroiditis. Br J Ophthalmol. 2016 [Epub ahead of print]. Ocul Immunol Inflamm. 2012;20:300–302. DOI: 10.1136/bjophthalmol-2016-308806.

Ocular Immunology & Inﬂammation