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Ann Anat 191 (2009) 563—567

0940-9602/$ - sdoi:10.1016/j.

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CASE REPORT

Cataracta ossea – Ultrastructural andspecimen analysis

Stefan Koinzera,�, Pia Scharpenacka, Hannelore Katzkeb,Ivo Leuschnerc, Johann Roidera

aDepartment of Ophthalmology, University hospital of Schleswig-Holstein, Campus Kiel, Haus 25, Arnold-Heller-Str. 3,D-24105 Kiel, GermanybInstitute of Geosciences, Crystallography, Christian-Albrechts-Universitat, Olshausenstr. 40, D-24098 Kiel, GermanycDepartment of Pathology, University hospital of Schleswig-Holstein, Campus Kiel, Michaelisstr. 11,D-24105 Kiel, Germany

Received 5 June 2009; received in revised form 30 August 2009; accepted 30 August 2009

KEYWORDSCataract;Cataracta ossea;Osseous cataract;Heterotopicossification;Penetrating eyetrauma

ee front matter & 2009aanat.2009.08.003

g author. Tel.: +49 4317 2428.esses: koinzer@auge.unauge.uni-kiel.de (P. Schi-kiel.de (H. Katzke), ileroider@auge.uni-kiel.d

SummaryBackground: Although intraocular osseous metaplasia is a well-known phenomenon,ossification of the lens is a rare phenomenon nowadays.Material and Methods: An enucleated phthisical eye showed a rock-hard intraocularparticle. Lens status after a trauma 36 years ago had been unclear. Differentialdiagnosis included an intraocular foreign body or ossification of the lens. X-raydiffraction analysis showed microcrystalline apatite indicating a mineralizedstructure. Histologic specimens revealed a mineralized lens that underwentsecondary osseous metaplasia.Conclusions: Due to the small number of cases, the mechanisms and preconditionsof osseous metaplasia of the lens are not understood in detail, but injury to the lenscapsule and availability of blood supply are being discussed. Both were present inthis case, in which the luxated lens ended up in the ciliary body region. Themechanism resembled enchondral ossification rather than intramembranousossification, which is seen in osseous metaplasia of other intraocular structures.& 2009 Elsevier GmbH. All rights reserved.

Elsevier GmbH. All rights rese

597 2366;

i-kiel.de (S. Koinzer)arpenack)uschner@path.uni-kiel.dee (J. Roider)

Introduction

Heterotopic ossification is a well-known phenom-enon and occurs in all areas of the body, includingthe eye. Intraocular ossification has been reportedin a number of larger case series and predominantlyaffects the choroid, but also the ciliary body and

rved.

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Figure 1. Macroscopic photograph of the opened eyeballshowing PVR-membranes encapsulating the rock-hardintraocular particle.

S. Koinzer et al.564

the retina (Fledelius, 1975; Monselise et al., 1985;Rohrbach et al., 1990) It occurs in chronic andsevere diseases of the eye like chronic retinaldetachment, chronic inflammation or tumorgrowth, but also congenital like in osseous chori-stoma. Ossification of the lens is a rare phenomen-on, which was first described by Gluge (1843) andWagner (1851). It took until the early 20th century,that the idea of true ossification of the lens becamewidely accepted (Graefe and Saemisch, 1905;Lubarsch and Henke, 1937). Two larger series foundcataracta ossea in 7 out of 81 (Samuels, 1938) or 7out of 16 (Betsch, 1927) globes showing boneformation. To our knowledge, only four case reportshave been published after World War II. One reportsabout a 5-year-old Danish boy who showed osseousmetaplasia of the lens 3 years after rubellainfection (Fledelius, 1975). The others report aboutpost-traumatic ossification of the lens in adults(Rohrbach et al., 1990; Leita and Nitta, 1971;Naumann, 1980). We report another case in anadult, using X-ray analysis and histopathologicalexamination.

Figure 2. Macroscopic view of the intraocular particle,size 8 mm.

Material and methods

The left eye of a 64-year-old male patient wasenucleated because of a painful amaurosis. Thiseyeball had suffered a penentrating scleral traumaat the nasal inferior quadrant, which was treatedconservatively, after the patient had been involvedin a traffic accident 36 years ago. No severeintraocular inflammation has been recorded. Thetrauma had caused vitreous hemorrhage, and thelens had been dislocated to an unknown locus.Visual acuity had been light perception andintraocular pressure 5 mm Hg. The fellow eye hadfull visual acuity and has not shown signs ofsympathetic ophthalmia at any time.

The enucleated eyeball measured 18� 20� 21mm with corneal diameters of 9� 11 mm. Thechoroid was mineralized. Inside the globe fibrousmembranes spanned antero-posteriorly, the retinawas detached, and retropupillarly there was no lenspresent (Figure 1). In the temporal inferiorquadrant lay a white, hard particle with a roughsurface, located in the ciliary body region andencapsulated in fibrous membranes. It measured8 mm (Figure 2). In order to establish the correctdiagnosis, an X-ray analysis of the particle,scanning electron microscopy and a histolgicalworkup were performed including routine (HE)and Goldner-, Giemsa- and Cossa-stainings.Immunohistochemical analysis of the vasculaturein the area surrounding the ossified lens using

antibodies to CD31, CD34 and D2-40 failed todetect any vascular structures, very likely due tothe destruction of these antigens during specimendecalcification.

Results

The X-ray powder diffraction analysis (CuKaradiation) showed microcrystalline apatite(Ca5[PO4]3[OH,F]), but no other mineralic phasesbesides that. Due to the small crystal size (nm-range), this examination was of limited validity. Anadditional EDX-analysis (energy dispersive X-rayspectroscopy) was performed. It showed peaks forcalcium and phosphor at a ratio of 2.17 to 2.57which was close to the expected value for apatite(2.157, Figure 3). Deposits on the particle’s surfacethat had a dark appearance in scanning electron

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Figure 3. EDX-analysis of the white phase of the particle showing calcium and phosphate in a ratio compatible with apatite.

Figure 4. Scanning electron micrograph of the particle’ssurface.

Figure 5. Specimen of the most prominent area ofchoroidal ossification, containing mineralized osteoidand fatty bone marrow, Goldner-staining. � 250.

Cataracta ossea 565

microscopy (Figure 4) consisted of supposedlyorganic material that contained sulphur. The X-rayanalysis indicated an endogenously mineralizedtissue, which was compatible with the electronmicroscopic view. It showed an uneven, roughsurface resembling bony material.

The choroid showed ubiquitous ossificationwith two prominent foci below the optic nervehead (Figure 5, Goldner) and in the ciliary body(Figure 6, Cossa). The ossification process tookplace in a fibrous tissue environment as inintramembranous ossification. It showed lamellaeof mineralized osteoid matrix and osteocytes,partially with fatty bone marrow, but neitherHaversian canals nor Volkmann’s canals. Figure 6

shows the former location of the lens particle,which was situated beneath a very prominent focusof ossification in the ciliary body region. Residuesof the fibrous membranes, which had beenencapsulating the lens particle, could still be seen.

A specimen of the lens particle itself is shown inFigure 7 (� 1000, Giemsa). The particle containedan acellular mineralized substance. Inside thissubstance, small canals had formed, which weresurrounded by layers of osteoid matrix contain-ing osteocytes. The centers of these canals showedblood vessels and predominantly lipocytes(Figure 7, asterisk). Osteoblasts were very rarelyseen and osteoclasts were not found. Theossification process resembled the stage of

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Figure 6. Specimen of ciliary body region where the lenshad been encapsuled by PVR-membranes prior to workup,Cossa-staining. � 250.

Figure 7. Specimen of the ossified lens, showing miner-alized lens material and canals of Havers with circulardeposits of osteoid matrix and vascularized fatty bonemarrow in the center (asterisk), Giemsa-staining.� 1000.

S. Koinzer et al.566

formation of trabecula in enchondral ossificationwhere spongy bone develops.

Discussion

Heterotopic ossification is a ubiquitous phenome-non in the human body (Bosse, 1997). Ossificationof the human lens was first observed in the mid-19th century (Gluge, 1843; Wagner, 1851, as citedby Betsch, 1927), but until the early 20th century,it was questioned whether the osseous material wasderived from the vitreous rather than the lens, andwhether fibrous tissue as a basis for osseousmetaplasia was derived from intracapsular lensepithelia or surounding structures. By 1940s, it waswidely accepted, that cataracta ossea occurred inseverely damaged eyes. A defective lens capsule by

inflammatory toxins or trauma were thought to be aprecondition allowing the invasion of fibrous tissueand blood vessels into the lens capsule (Samuels,1938). This concept of the importance of bloodsupply to the ossifying lens is still accepted nowa-days (Rohrbach et al., 1990; Finkelstein and Boniuk,1969). Larger case series led some to conclude thatcataracta ossea was not unusual, especially Betsch(1927), who found lens ossification in 7 of 16 globeswith intraocular bone formation. However, afterthe 1940s, most examiners report of no more thanone case total even in larger case series ofossification of the globe (e.g. Fledelius, 1975;Monselise et al., 1985; Rohrbach et al., 1990).The decreasing frequency of cataracta ossea maybe due to improved surgical care. Anatomicalreconstruction of severely damaged eyes hasgreatly improved since microsurgical methods havebecome widely available. Therapy regimens incases of severe intraocular inflammation have alsogreatly changed, including vitrectomy, lensectomyand intravitreal drug administration. Because ofthe risk of phacolytic secondary glaucoma, it isstate of the art to remove a lens from an eye withan injured lens capsule. Consequently, lenses donot seem to prevail long enough in eyes fulfillingthe preconditions for osseous metaplasia any more.The patient we describe had suffered a penetratingeye injury in 1969 with injury to the lens capsule,which was not treated surgically. The lens wasluxated to the ciliary body region, where bloodsupply was readily available. To further elucidatethe role of the vasculature in lens ossification weused antibodies to CD31, CD34 and D2-40 to detectblood vessels. Since we were able to detect bloodvessels in control tissues but not in decalcifiedspecimens we postulate that the decalcificationmethods destroyed these antigens, which under-lines the usefulness of alternative modes ofexamination.

In the case described, the origin of the intrao-cular particle was unclear. Histological workuprequired decalcification, which would destroy theparticle’s structural integrity. For this reason, itwas examined by X-ray analyses (X-ray powderdiffraction analysis, EDX-analysis), which providedreliable hints concerning its origin. EDX-resultsvary and are close, but not identical, to theexpected value for apatite. The heterogenouscomposition of the mineralized tissue, displayingcataracta calcarea (containing cholesterol andcalcium carbonates rather than phosphates) be-sides osseous tissue, accounts for that. Histologicalworkup established the diagnosis suspected afterX-ray examination. Eckardt et al. (1993) have usedEDX-analysis to confirm the presence of silicone oil

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in intraocular tissues. Additional information on theX-ray analyses used is provided by Pavicevic andAmthauer (2000).

The pathophysiology of intraocular ossificationand the cytokines involved are matter of debate. Awidely accepted postulate is a pathway of fibrousmetaplasia of the retinal pigment epithelium (RPE)and further transformation into (pre-) osteoblasts(Rohrbach et al., 1990; Toyran et al., 2005). Toyranet al. (2005) suggested a pathway of interleukin-1-(IL 1) or tumor necrosis factor a- (TNF a) release byinflammatory cells, that would stimulate the RPEto release transforming growth factor b1 (TGF b1)and bone morphogenic protein 7 (BMP-7). TGF b1triggers the epithelial–mesenchymal transforma-tion of RPE-cells into fibroblasts. BMP-7 and growthdifferentiation factor 5 (GDF-5) in turn stimulateosseous metaplasia. It is possible, that the adjacentfocus of ossification in the ciliary body was a sourcefor cytokine diffusion into the lens of our casewhich promoted osseous metaplasia.

The importance of inflammation for intraocularossification is supported by Monselise et al. (1985).They found chronic inflammation to cause themajority of spongy bone formation, but trauma tocause the majority of compact bone formation. Thecase above showed compact bone in the choroiddue to previous trauma, but spongy bone in themineralized lens. Possibly, inflammation has pre-vailed for a certain time in this eye, even if ourspecimens do not show inflammatory cells.

Contrary to other heterotopic bone character-ized by high growth rates that are rich in osteocytesand osteoclasts (Bosse, 1997), we found only fewosteocytes and few osteoclasts. Since the timecourse of lens ossification varies widely, from 3 tomore than 20 years, it is not possible to determinefrom our case whether the relative lack ofosteocytes and osteoclasts is a general phenomen-on in cataracta ossea or is dependent on the stageof ossification.

Conclusions

Cataracta ossea rarely develops after seriousinjury of an eye. X-ray analysis of the lens particle

provided valuable clues concerning its origin priorto decalcification for histologic workup.

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