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Multimodal Fundus Imaging in Choroidal Osteoma

EDUARDO V. NAVAJAS, ROGERIO A. COSTA, DANIELA CALUCCI, DENA S. HAMMOUDI,

E. RAND SIMPSON, AND FILIBERTO ALTOMARE

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● PURPOSE: To describe the morphologic features ofcalcified and decalcified choroidal osteomas using multi-modal imaging and correlate these findings with a previ-ous histopathologic study.● DESIGN: Retrospective observational case series.● METHODS: Three patients with choroidal osteomaunderwent complete ophthalmologic examination, fun-dus photography, and multimodal fundus imaging,including Fourier-domain optical coherence tomogra-phy (FD-OCT) and blue-light fundus autofluorescence(bAF).● RESULTS: FD-OCT imaging of calcified tumors re-vealed a distinctive latticework pattern of reflectivityresembling the spongy bone structure seen histopatho-logically. On bAF the fluorescence was relatively wellpreserved overlying calcified tumors. In decalcifiedareas 2 patterns of reflectivity were identified: the firstconsisted of areas of relative hyperreflectivity with alamellar appearance while the second was character-ized by heterogeneous, hyperreflective, mound-likeirregular areas associated with some posterior opticalshadowing. Decalcified tumor areas had reduced over-all fluorescence on bAF.● CONCLUSION: FD-OCT demonstrated different reflec-ivity patterns in both calcified and decalcified portions ofhe choroidal osteoma, which may correspond to differ-nt stages of tumor evolution. A distinctive latticeworkattern of reflectivity similar to spongy bone was seen inalcified tumors. These observations improve our knowl-dge of the in vivo structure of choroidal osteomas anday have implications for the diagnosis and managementf this tumor. (Am J Ophthalmol 2012;153:90–895. © 2012 by Elsevier Inc. All rights reserved.)

Supplemental Material available at AJO.com.ccepted for publication Oct 20, 2011.From the Department of Ophthalmology and Vision Sciences, Princessargaret Hospital, University of Toronto, Toronto, Ontario, Canada

E.V.N., D.S.H., E.R.S., F.A.); Macular Imaging and Treatment Division,ospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil (R.A.C.);epartment of Ophthalmology, Faculdade de Medicina de Ribeirãoreto, Universidade de São Paulo, Ribeirão Preto, São Paulo, BrazilR.A.C.); and Division of Macula, Centro Brasileiro de Ciencias Visuais,elo Horizonte, Minas Gerais, Brazil (R.A.C., D.C.).Inquiries to Eduardo V. Navajas, Princess Margaret Hospital, 610niversity Ave, 18th floor Eye Clinic, M5G 2M9 Toronto, ON, Canada;

e-mail: edunavajas@gmail.com

© 2012 BY ELSEVIER INC. A90

C HOROIDAL OSTEOMA IS A BENIGN OSSEOUS TU-

mor of the choroid that, unlike other intraocularossifications, usually affects healthy eyes.1 It is

unilateral in approximately 80% of cases and more oftenaffects young female subjects.2 Clinically it appears asellow-white to orange-red lesions, depending on theegree of thinning and depigmentation of the overlyingetinal pigment epithelium (RPE). Because of the cal-ific composition, choroidal osteomas present with higheflectivity and acoustic shadowing on ultrasonography,nd appear as hyperdense plaques at the level of thehoroid on computed tomography. On time-domainptical coherence tomography (TD-OCT) irregularlate-like high-signal-intensity areas as well as photore-eptor loss were observed over decalcified regions of theumor.3–5 Limitations of TD-OCT technology, however,

precluded adequate imaging of the choroidal vascularcompartment.

Recent advances in OCT technology, such as thedevelopment of new light sources and a novel high-speedOCT technique called spectral OCT, which is based on“Fourier-domain” (FD) detection, have allowed higheraxial resolution imaging with improved sensitivity andincreased measurement speed to more than 50 timescompared with TD-OCT instruments.6 Moreover, thentegration of FD-OCT findings with data from relativelyew imaging modalities, such as blue-light fundus auto-uorescence (bAF), carries the potential for an expandednterpretation of fundus imaging findings. Herein, weescribe the morphologic features in patients with choroi-al osteoma undergoing multimodal fundus imaging, witharticular interest in findings obtained on FD-OCT imag-ng and bAF.

METHODS

THREE PATIENTS WITH CHOROIDAL OSTEOMA WHO HAD

undergone multimodal fundus imaging from July 1, 2009to December 31, 2010 were identified through a reviewof medical records at the Macular Imaging and Treat-ment Division of the Hospital de Olhos de Araraquara(Araraquara, São Paulo, Brazil). The diagnosis was based onthe presence of a yellow-white to orange-red mass deepto the RPE with well-defined margins and bone densityon ultrasonography.2 All participants underwent FD-

CT and bAF imaging on commercially available

quipment (Spectralis HRA�OCT, Heidelberg Engi-

LL RIGHTS RESERVED. 0002-9394/$36.00doi:10.1016/j.ajo.2011.10.025

neering Inc, Heidelberg, Germany). The bAF documen-tation was obtained with an excitation wavelength of488 nm and the emitted light detected above 500 nm,using the high-resolution mode with the ART (auto-matic real time) mean module set at 25 frames and“normalized” function on.

RESULTS

PATIENT CHARACTERISTICS AND TUMOR FEATURES ARE

summarized in the Table and Figure 1. Four eyes of 3patients (2 female and 1 male) were included. One eye ofa patient with bilateral choroidal osteoma was excludedbecause of significant vitreous opacities. Fluorescein an-giography was performed in Patient 1 (Supplemental

TABLE. Characteristics of P

Patient Number, Sex, Age (y)

BCVA

OD OS

1, F, 16 20/125�1 20/20�2 Juxtapapillary/macu

2, F, 61 20/640 20/125 Juxtapapillary/macu

3, M, 36 20/320�1 20/125 Juxtapapillary/macu

BCVA � best-corrected visual acuity; F � female; M � male; NAaExcluded because of significant vitreous opacities.

FIGURE 1. Color fundus photographs and blue-light autofluoosteoma. (Top left) Patient 1: calcified choroidal osteomaneovascularization; note relatively preserved fluorescence on bAchoroidal osteoma with central decalcification and peripheradecalcified tumoral regions while relatively preserved fluorescen2, vascular spiders were observed (arrows). (Bottom left and rfluorescence on bAF was observed in decalcified tumoral regio

Figure, available at AJO.com).

MULTIMODAL IMAGING INVOL. 153, NO. 5

In calcified areas, we identified on FD-OCT areas with alatticework reflective pattern within the choroid (Figure 2,Top) and associated reflective signals corresponding tolarge vessels located mostly between the calcified tumoraltissue and the RPE-Bruch reflective complex (Figure 3,Top). In some regions, an apparent hyperreflective lineseparating the calcified tumoral tissue and adjacent, pre-sumably unaffected, choroid was observed (Figure 2, Mid-dle). The retinal layers overlying calcified tumoral tissuepresented relatively preserved reflectivity on FD-OCT,with the exception of the foveal region of Patient 1, whohad choroidal neovascularization in the past (Figure 2,Bottom). A thin hyporeflective space was frequentlyidentified underneath (ie, external to) the RPE–Bruchreflective complex in calcified tumoral regions (Figure 3,Middle). Given that calcified regions presented pre-

ts With Choroidal Osteoma

Location and Stage of Tumor

OD OS

alcified NA

entrally decalcified, peripherally calcified Juxtapapillary/maculara

ecalcified Juxtapapillary/macular;

decalcified

ot applicable.

nce (bAF) of 3 patients with juxtapapillary/macular choroidalassociated subretinal scar from previous foveal choroidal

corresponding calcified tumoral regions. (Top right) Patient 2:lcification; decreased fluorescence on bAF was observed in

bAF was observed in calcified regions. In both Patients 1 andPatient 3: bilateral decalcified choroidal osteomas; decreased

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CHOROIDAL OSTEOMA 891

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right), this hyporeflective space may correspond toremaining choriocapillaris.

In decalcified areas, we identified 2 different reflectivepatterns on FD-OCT, which were both associated withcomplete disorganization of the adjacent outer retinasignaling. The first consisted of areas of relative hyperre-flectivity with a lamellar appearance (external to theRPE–Bruch reflective complex) (Figures 3 and 4, Bottom),while the second was characterized by heterogeneously,hyperreflective, mound-like irregular areas associated withsome posterior optical shadowing (Figure 4, Top), whichoccasionally were located above (ie, internal to) the Bruchmembrane (Figure 4, Middle). In lamellar-appearing re-gions, with few exceptions, no reflective signals fromchoroidal vessels could be identified (Figures 3 and 4,

ottom). Moreover, an arborescent hyporeflective verticaltructure was identified in the deeper part of the lamellar-ppearing region in Patient 2 (Figure 3, Bottom), and mayorrespond to a posterior ciliary vessel penetrating theclera. On bAF documentation, decalcified tumor areasresented areas of no fluorescence alternating with areas ofild residual fluorescence (Figure 1, Top right and Bottom

FIGURE 2. Fourier-domain optical coherence tomography evalquiescent subretinal neovascularization. (Top) Note a lattichyperreflective dots surrounding hyporeflective cavernous spaceline (arrows) was observed between the tumoral tissue and adj(curved arrow) appeared to emanate from the center of the tum

eft and right).

AMERICAN JOURNAL OF892

DISCUSSION

A PREVIOUS HISTOPATHOLOGIC STUDY LOCATED THE CHO-

roidal osteoma between the choriocapillaris and outerchoroidal tissue and revealed spongy bone, consisting ofdense bony trabeculae surrounding marrow spaces withloose connective tissue and vessels.7 In the current study

e identified a latticework reflective pattern within thehoroid on FD-OCT in calcified tumoral regions that mayorrespond to spongy bone. Freton and Finger, usingD-OCT, described a similar pattern in patients withhoroidal osteoma.8 The hyperreflective lines between the

tumor and choroid identified in the current study may alsobe explained by histopathologic data available,7 beingrobably related to the displacement of choroidal melano-ytes toward the choriocapillaris and the adjacent innercleral lamella by the intrachoroidal tumoral tissue. Alter-atively, these lines of hyperreflectivity may correspond tohe tumor-choroid interface.

Choroidal osteoma may replace the full thickness ofhe choroid, with spontaneous decalcification occurringn up to 46% of patients in 10 years.2 The combination

n of Patient 1, with calcified choroidal osteoma and associatedk reflective pattern (square box), characterized by multipleterisk), in calcified tumoral regions. (Middle) A hyperreflectivet outer choroid. (Bottom) The neovascular (subretinal) lesion

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of a tumor occupying the full thickness of the choroid

OPHTHALMOLOGY MAY 2012

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with subsequent complete decalcification could makethe overlying retina appose almost directly the sclera.This premise would explain the lamellar reflectivepattern observed in some decalcified tumoral areas inthe current study, indicating that little or no tumoraltissue is left and the areas of lamellar reflective patternwould correspond to posterior scleral tissue. Moreover,the arborescent hyporeflective vertical structure seen inthe deeper part of the lamellar-appearing region inPatient 2 (Figure 3, Bottom), which possibly corre-sponds to a posterior ciliary vessel penetrating thesclera, provides further support of our hypothesis.

The second FD-OCT reflective pattern identified indecalcified regions (hyperreflective mound-like irregularareas associated with some posterior shadowing) maycorrespond to tumoral regions in which spongy organiza-tion was lost secondary to partial decalcification. Thisprocess would leave a tumor that has no definite cavernousspace and significantly blocks FD-OCT signal. This reflec-tivity pattern was occasionally identified above the Bruchmembrane, and may correspond to tumoral tissue in a

FIGURE 3. Fourier-domain optical coherence tomography evcalcified choroidal osteoma. (Top) Note a latticework reflectivesurrounding hyporeflective cavernous spaces (asterisk), in calcibe identified in the inner aspect of the choroidal osteoma. (Midblue-light autofluorescence, a thin hyporeflective space (arrowreflective complex. (Bottom) Note a lamellar reflective patternlikely corresponding to reflective signals from posterior scleral tarrow) that may correspond to a posterior ciliary vessel penetr

sub-RPE location. However, unless the Bruch membrane s

MULTIMODAL IMAGING INVOL. 153, NO. 5

was disrupted by the tumor, it is very unlikely thatchoroidal osteoma grew over it. Alternatively, thehyperreflective material identified above the Bruchmembrane may correspond to extensive fibrous RPEmetaplasia.

We observed that the retina overlying calcified areasshowed more often a preserved architecture, in accordancewith a previous study using TD-OCT.5 Given that fluo-rescence was relatively preserved in these regions on bAFand thin, well-defined hyporeflective spaces were identifiedunderneath the RPE–Bruch reflective complex, it seemsreasonable to propose that a residual, but still efficient,choriocapillaris flow may exist in these areas. Indeed, in astudy using ultrahigh-resolution optical coherence tomog-raphy for imaging the monkey fovea, Anger and associatesdemonstrated that choriocapillaris appears as a hyporeflec-tive band under (external to) the retinal pigment epithe-lium.9 In decalcified areas, on the other hand, theverlying outer retina was completely disorganized onD-OCT and the overall fluorescence was reduced, with

tion of Patient 2, with centrally decalcified and peripherallyrn (square box), characterized by multiple hyperreflective dotsumoral regions. (Top) Vascular spiders (arrowhead) could alsoIn the calcified area with overlying preserved fluorescence onas observed between the tumoral tissue and the RPE-Bruchecalcified tumoral region (square box and curved arrow), most. Note an arborescent hyporeflective vertical structure (obliquethe sclera.

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CHOROIDAL OSTEOMA 893

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It is known that bone has autofluorescence even whendecalcified, and it seems to be primarily attributable tocollagen itself rather than to incidental substances ad-sorbed onto it.10,11 This may explain the residual areas ofmild fluorescence seen in Figure 1 (Bottom). Anotherpossibility is that these areas correspond to extensivefibrous metaplasia of the RPE, which also has been shownto have autofluorescence,12,13 either because of RPE-associated lipofuscin or related to its collagenous con-tent.14 Following the same rationale, one can explain the

ild residual autofluorescence seen in Figure 1 (Top,ight). These areas probably correspond to posterior scleralissue, a structure with high collagenous content.

In the current study we identified on FD-OCT thevascular spiders,” a characteristic and pathognomoniceature described by Gass and associates15 that consists ofufts of branching vessels on the choroidal osteoma surface.hese trunks were observed on FD-OCT at differentepths of the tumoral tissue, mostly on its inner aspect.inally, in the patient with choroidal neovascularization, it

FIGURE 4. Fourier-domain optical coherence tomography ev(Top) Note heterogeneous, hyperreflective, mound-like irredecalcified tumoral regions (square box), with disorganizatheterogeneous hyperreflective areas were occasionally identreflective pattern was observed in a decalcified tumoral regto reflective signals from posterior scleral tissue; note absereflective signals from the choroid could be still identified undposterior shadowing.

s noteworthy that the neovascular lesion apparently em- b

AMERICAN JOURNAL OF894

nated from the central portion of the choroidal osteomaFigure 2, Bottom). Our observation supports the hypoth-sis from Foster and associates16 that subretinal neovascu-arization in this condition may represent an extension ofhe osteoma based on the identification of osteoclasts in 1urgically removed neovascular tissue.

In conclusion, we demonstrate different reflectivityatterns in both calcified and decalcified portions of thehoroidal osteoma, which may correspond to differenttages of tumor evolution. In addition, a latticeworkeflective pattern on FD-OCT was described for calcifiedegions of the choroidal osteoma that is similar to spongyone seen on histopathology. Treatment of tumors at thistage could induce decalcification and prevent furtherrowth. We believe that our observations, if confirmed inuture studies using multimodal fundus imaging, improveur knowledge of the in vivo structure of choroidalsteoma and may have implications for diagnosis, follow-p, and treatment of patients with this tumor. Futuretudies should investigate the role of bAF as a possible

ion of Patient 3, with bilateral decalcified choroidal osteoma.r areas associated with some posterior optical shadowing inf the overlying outer retina (arrowhead). (Middle) Theseabove the Bruch membrane (arrows). (Bottom) A lamellar(square box and curved arrow), most likely correspondingf choroidal vessels. (Top and middle) On the other hand,ath the heterogeneous mound-like irregular areas with some

aluatgulaion oifiedionnce oerne

iomarker for tumor regression or growth.

OPHTHALMOLOGY MAY 2012

ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OFInterest and none were reported. Involved in conception and design (E.V.N., R.A.C., D.S.H.); analysis and interpretation (E.V.N., R.A.C., D.S.H.,E.R.S., F.A.); writing the article (E.V.N., R.A.C., D.S.H.); critical revision of the article (E.V.N., R.A.C., D.C., D.S.H., E.R.S., F.A.); final approvalof the article (E.V.N., R.A.C., D.C., D.S.H., E.R.S., F.A.); data collection (E.V.N., R.A.C., D.C.); supply of materials, patients, or resources (E.V.N.,R.A.C., D.C., E.R.S.); literature search (E.V.N., R.A.C.); and administrative, technical, or logistical support (E.V.N., R.A.C., D.C., D.S.H., E.R.S.,F.A.). This retrospective study was approved by the Comitê de Ética em Pesquisa do Hospital das Clínicas de Ribeirão Preto – Universidade de São Paulo(USP) e da Faculdade de Medicina de Ribeirão Preto – Universidade de São Paulo.

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REFERENCES

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3. Ide T, Ohguro N, Hayashi A, et al. Optical coherencetomography patterns of choroidal osteoma. Am J Ophthal-mol 2000;130(1):131–134.

4. Fukasawa A, Iijima H. Optical coherence tomography ofchoroidal osteoma. Am J Ophthalmol 2002;133(3):419–421.

5. Shields CL, Perez B, Materin MA, Mehta S, Shields JA.Optical coherence tomography of choroidal osteoma in 22cases: evidence for photoreceptor atrophy over the decalci-fied portion of the tumor. Ophthalmology 2007;114(12):e53–58.

6. Costa RA, Skaf M, Melo LA Jr, et al. Retinal assessmentusing optical coherence tomography. Prog Retin Eye Res2006;25(3):325–353.

7. Williams AT, Font RL, Van Dyk HJ, Riekhof FT. Osseouschoristoma of the choroid simulating a choroidal melanoma.Association with a positive 32P test. Arch Ophthalmol1978;96(10):1874–1877.

8. Freton A, Finger PT. Spectral domain-optical coherencetomography analysis of choroidal osteoma. Br J Ophthalmol.

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9. Anger EM, Unterhuber A, Hermann B, et al. Ultrahighresolution optical coherence tomography of the monkeyfovea. Identification of retinal sublayers by correlation withsemithin histology sections. Exp Eye Res 2004;78(6):1117–1125.

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2. Lavinsky D, Belfort RN, Navajas E, Torres V, Martins MC,Belfort R. Fundus autofluorescence of choroidal nevus andmelanoma. Br J Ophthalmol 2007;91(10):1299–1302.

3. Gündüz K, Pulido JS, Bakri SJ, Petit-Fond E. Fundus auto-fluorescence in choroidal melanocytic lesions. Retina 2007;27(6):681–687.

4. Gündüz K, Pulido JS, Ezzat K, Salomao D, Hann C. Reviewof fundus autofluorescence in choroidal melanocytic lesions.Eye 2008;23(3):497–503.

5. Gass JD, Guerry RK, Jack RL, Harris G. Choroidal osteoma.Arch Ophthalmol 1978;96(3):428–435.

6. Foster BS, Fernandez-Suntay JP, Dryja TP, Jakobiec FA,D’Amico DJ. Clinicopathologic reports, case reports, andsmall case series: surgical removal and histopathologicfindings of a subfoveal neovascular membrane associatedwith choroidal osteoma. Arch Ophthalmol 2003;121(2):

273–276.

CHOROIDAL OSTEOMA 895

SUPPLEMENTAL FIGURE. Fluorescein angiography in Patient 1, with juxtapapillary/macular choroidal osteoma. Early framesrevealed patchy choroidal filling and the identification of tumoral spider vessels (arrows). Note staining of the central portion of thetumor in the late phase. Late leakage from choroidal neovascularization was observed in the foveolar region (curved arrow).

MULTIMODAL IMAGING IN CHOROIDAL OSTEOMAVOL. 153, NO. 5 895.e1

Biosketch

Eduardo V. Navajas, MD, PhD, completed his residency in ophthalmology and PhD in retinal imaging at FederalUniversity of São Paulo, São Paulo, Brazil. He then received his training in vitreoretinal surgery (2007 to 2009) at StMichael’s Hospital and ocular oncology at Princess Margaret Hospital (2009 to 2010), both affiliated with the Universityof Toronto. Dr Navajas will be joining the ocular oncology team at Princess Margaret Hospital, University of Toronto,Canada.

AMERICAN JOURNAL OF OPHTHALMOLOGY895.e2 MAY 2012

Biosketch

Rogerio A. Costa, MD, PhD, is currently Director of the Division of Macula: Imaging & Treatment at Centro Brasileirode Ciências Visuais, Belo Horizonte, and Professor of the Post-graduation Program of the Department of Ophthalmologyat Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. Dr Costa was awarded theLatin-American Investigator Award and the Brazilian Council of Ophthalmology Award during his vitreoretinalfellowship. He has authored over 70 peer-reviewed articles and 20 book chapters on macular disease.

MULTIMODAL IMAGING IN CHOROIDAL OSTEOMAVOL. 153, NO. 5 895.e3