Letters

reached as most of the mutations reported todate have only been found in one family.

Although ND is believed to be rare, it islikely that many cases remain undiagnosed.The predominant ocular feature of ND -retrolental mass - is not necessarily patho-gnomonic, and it is clinically difficult toexclude other diseases of undefined aetiology,particularly in sporadic and non-syndromiccases. The ongoing molecular assessment ofthe ND gene will enable us to make definitivediagnoses in cases in which mutations aredetected and will also provide useful informa-tion for genetic counselling. From the mole-cular studies to date, we are aware of themarked heterogeneity of pathogenic muta-tions in the ND gene and, hence, directsequencing of the gene has to be performed totest for unknown mutations.

This study was supported by a grant in aid for scien-tific research (No 05807165, 06454499) from theMinistry ofEducation, Science and Culture ofJapanand a grant for Retinochoroidal Atrophy Researchfrom the Ministry of Health and Welfare of Japan.

YASUSHI ISASHIKIDivision ofMolecular Pathology and Genetic

Epidemiology,Centerfor Chronic Viral Diseases,

Kagoshima University Faculty ofMedicine,Kagoshima-shi, Japan

NORIO OHBATOYOKO YANAGITA

NAOKO HOKITADepartment of Ophthalmology,

Kagoshima University Faculty ofMedicine,Kagoshima-shi, Japan

YOSHIHIRO HOTTAMUTSUKO HAYAKAWA

KEIKO FUJIKIUTAKO TANABE

Department of Ophthalmology,J7untendo University School ofMedicine,

Tokyo, Japan

Correspondence to: Norio Ohba, MD, Departmentof Ophthalmology, Kagoshima University Facultyof Medicine, Sakuragaoka 8-35-1, Kagoshima-shi890, Japan.Accepted for publication 2 March 1995

1 Warburg M. Nonre's disease. A congenitalprogressive oculo-acoustico-cerebral degeneration.Copenhagen: Ejnar Munkszaard, 1966.

2 Berger W, Meindl A, Pol TJR van de, CremersFPM, Ropers HH, Dorner D, et al. Isolation ofa candidate gene for Norrie disease bypositional cloning. Nature Genet 1992; 1:199-203.

3 Chen Z-Y, Hendricks RW, Jobling MA, PowellJF, Breakefield XO, Sims KB, et al. Isolationand characterization of a candidate genefor Norrie disease. Nature Genet 1992; 1:204-8.

4 Meindl A, Berger W, Meitinger T, Pol D van de,Achatz H, D6rner C, et al. Norrie disease iscaused by mutations in an extracellular proteinresembling C-terminal globular domain ofmucins. Nature Genet 1992; 2: 139-43.

5 Berger W, Pol D van de, Warburg M, Gal A,Bleeker-Wagemakers L, Silva H de, et al.Mutations in the candidate gene for Norriedisease. Hum Mol Genet 1992; 1: 461-5.

6 Fuentes ni, Volpini V, Fernindez-Toral F, CotoE, Estivill X. Identification of two new mis-sense mutations (K58N and R121Q) in theNorrie disease (ND) gene in two Spanishfamilies. Hum Mol Genet 1993; 2: 1953-5.

7 Wong F, Goldberg MF, Hao Y. Identification ofa nonsense mutation at codon 128 of theNorrie's disease gene in a male infant. ArchOphthalmol 1993; 111: 1553-7.

8 Fuchs S, Xu SY, Caballero M, Salcedo M, LaOA, Wedemann H, et al. A missense pointmutation (Leul3Arg) of the Norrie diseasegene in a large Cuban kindred with Norriedisease. Hum Mol Genet 1994; 3: 655-6.

9 Isashili Y, Ohba N, Yanagita T, Hokita N, DoiN, Nakagawa M, et al. Novel mutation at theinitiation codon in the Norrie disease gene intwo Japanese families. Hum Genet 1995; 95:105-8.

10 Chen Z-Y, Battinelli EM, Fielder A, Bundey S,Sims K, Breakefield XO, et al. A mutation inthe Norrie disease gene (NDP) with X-linkedfamilial exudative vitreoretinopathy. NatureGenet 1993; 5: 180-3.

Choroidal ischaemic plaques insarcoidosis

EDIToR,-Sarcoidosis is a multisystem granu-lomatous disorder of unknown aetiology. Itmay present with a variety of ocular inflam-matory signs, including anterior or posterioruveitis, vitritis, periphlebitis, and chorioretini-tis; choroidal lesions may manifest as hypo- orhyperpigmentation.1We present a patient manifesting multiple

placoid choroidal lesions with a previoushistory of sarcoidosis.

CASE REPORTA 45-year-old white man presented in July1994 with a severe bilateral acute anterioruveitis with raised intraocular pressure in theleft eye. He also had bilateral punctate epithe-lial erosions and band keratopathy of his leftcornea. Fundal examination revealedmultiple placoid areas of choroidal pallorwidespread throughout both fundi, but con-centrated around the posterior poles (Fig 1).

Past medical history included pulmonaryconsolidation in 1989 at which pointbronchial biopsy revealed non-caseating gran-ulomata. He had had an episode of left herpeszoster ophthalmicus with corneal involvementin 1991. In April 1994 he presented with arecurring, itchy skin rash of oedematouspapules on the shoulders, back, chest, andproximal limbs; biopsy again revealed non-caseating granulomata.He was admitted for investigation and his

uveitis treated with topical steroids, centralvisual acuity returning to normal as this sub-sided. Intravenous fundal angiography wasperformed with fluorescein (IVF) and indo-cyanine green (ICG); IVF showed no earlymasking (Fig 2A) but areas of late staininghyperfluorescence corresponding to theplacoid lesions (Fig 2B) and ICG revealed amarked, sustained hypofluorescence in thesame areas (Fig 3).

Routine blood testing revealed a markedhypercalcaemia (corrected calcium 3-60mmol/l) and renal impairment (urea 19-2mmol/l, creatinine 334 umol/l). He was alsonoted to have a benign paraproteinaemia(IgG type kappa 7 g/l). He was treated withintravenous hydration, diuretics, and corti-costeroids and improved rapidly.

I ~ ~ -AFigure 1 Fundus photographs showingflat,hypopigmented lesions in both fundi.

F-ig 2A

Fig2vBFigure 2 (A) Fluorescein angiographic pictureof the early arterial phase in the right eyeshowing no masking of the choroid. (B) Latefluorescein angiographic picture illustrating latestaining hyperfluorescence of the lesions.

Figure 3 Indocyanine green angiographicpicture showing hypofluorescent areascorresponding to the areas of late staining in theIVF in the right eye.

Four weeks after presentation his anterioruveitis had cleared and the fundal placoidlesions had begun to show signs of hyperpig-mentation.

COMMENTOcular sarcoidosis may present withchoroidal lesions in 29-50% of cases.1Appearances may vary from patches ofcreamy yellow depigmentation to a serpigi-nous appearance extending out from the peri-papillary regionl 2; and have also mimickedbirdshot choroidopathy.3 The single reportedcase of serpiginous choroiditis associated withsarcoidosis in the literature was marked byearly masking and late staining on IVF.

Lesions mimicking birdshot choroidopathyhave been described as hypopigmented, flatlesions which manifested late staining onIVF.3 However, fundal distribution wasmainly confined to the peripapillary and nasalregions and active investigation of patientswith birdshot choroidopathy has revealed nolink with sarcoidosis.The appearance demonstrated in our

patient is more reminiscent of acute posteriormultifocal placoid pigment epitheliopathy,and indeed this has been linked with areas of

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Letters

non-perfusion in the choroid as demonstratedon ICG.4 The lack of early masking on IVFand the sustained hypofluorescence of thelesions on ICG (which is highly proteinbound and therefore stays in the circulatorysystem4), suggest that the lesions may repre-sent areas of relative choroidal ischaemia.

Previous authors have postulated that focaldepigmented chorioretinal areas in sarcoido-sis may correspond to subpigment epithelialgranulomata similar to Dalen-Fuch's nodules(typically found in sympathetic ophthalmia).5It has been suggested that these lesions maycompress the choroidal vasculature ratherthan invade it. However, ocular postmortemexamination of patients with fundal sarcoido-sis has revealed non-caseating granulomataconsisting mainly of epithelioid cells withinthe choroid, lymphocytic vascular cuffing wasclosely associated with these lesions.6 Thismay indicate a possible mechanism for theapparent vascular insufficiency of the choroidin the angiographic findings in our patient.

RAJIV MAINIGRAEME D M SHARPE

STUART T D ROXBURGHDepartment of Ophthalmology,

Ninewell's Hospital and Medical School,Dundee, Scotland DDI 9SY

Correspondence to: Dr S T D Roxburgh.Accepted for publication 2 March 1995

1 Spalton DJ, Sanders MD. Fundus changes inhistologically confirmed sarcoidosis. Br JfOphthalmol 1981; 65: 348-58.

2 Edelsten C, Stanford MR, Graham EM.Serpiginous choroiditis: an unusual presenta-tion of ocular sarcoidosis. Br Jf Ophthalmol1994; 78: 70-1.

3 Brod RD. Presumed sarcoid choroidopathymimicking birdshot retinochoroidopathy. Am JOChthalmol 1990; 109: 357-8.

4 Dhaliwal RS, Maguire AM, Flower RW, ArribasNP. Acute posterior multifocal placoid pigmentepitheliopathy. An indocyanine green angio-graphic study. Retina 1993; 13: 317-25.

5 Campo RV, Aaberg TM. Choroidal granuloma insarcoidosis. Am J Ophthalmol 1984; 97:419-27.

6 Laval J. Ocular sarcoidosis. Am J Ophthalmol1952; 35: 551-4.

Ossification in choroidal melanoma

EDITOR,-The correct diagnosis of uvealmelanoma has improved in recent years fol-lowing the introduction of superior methodsof fundus examination, combined withmodern ancillary tests such as fluoresceinangiography and ultrasonography (echo-graphy). A percentage of misdiagnosis, how-ever, is to be expected, even in preselectedpatients undergoing a rigorous screening pro-gramme as in the example of theCollaborative Ocular Melanoma Study(COMS) where a misdiagnosis rate of 0-48%has been reported.' The diagnostic criteria ofuveal melanoma with standardised echogra-phy are: (i) solid, dome-shaped or collarstudmass lesion; (ii) low to medium reflectivity;(iii) regular internal structure; and (iv) avariable degree of internal vascularity.2 Otherfeatures include choroidal excavation, associ-ated exudative retinal detachment, extra-scleral/orbital spread, and, less commonly,vitreous haemorrhage.2 3

Calcification/ossification 'within' choroidalmelanoma mass has not been previouslyreported, either echographically or histologi-cally. We present such a case.

Figure 1 Echographic B-scan showing amushroom-shaped melanoma. The calcified areais seen, appearing as a highly reflective plaque(arrow) and giving rise to a linear shadowingeffect.

Figure 2 Standardised A-scan. The tumour isrepresented by the echo spikes between the twoclosed arrows, a single high amplitude echorepresenting the calcified plaque is seen withinthe tumour mass (open arrow).

in the left eye. There was no history of eyedisease apart from myopia. Systemic inquiryindicated that he was hypertensive receivingdiuretic therapy. On examination, the visionwas 6/12 partly in the right eye and handmovements in the left with a large inferiorscotoma. There was a left afferent pupillarydefect. The anterior segments and intraocularpressures were normal. Fundus examinationon the left showed pigmented cells in thevitreous, a dark, raised, collarstud mass in thesuperonasal quadrant, and associated retinaldetachment involving the macula. Apart frommild atrophic macular changes the rightfundus was normal.

B-scan ultrasonography confirmed thecollarstud nature of the lesion (Fig 1). Thetumour measured 13 mmX10 mm at base,and 9 mm in height. Vascularity was notedduring kinetic examination. An unusualfeature was the presence of a highly reflectiveplaque, located within the tumour at the'neck' of the collarstud, where the tumourhad breached Bruch's membrane. The plaquecaused significant acoustic shadowing, indi-cating that it was calcified. No extrascleralspread was detected. Standardised A-scanshowed the characteristic features ofmelanoma, except at the area of calcificationwhere a single, high reflective, thick spike waslocated within the tumour echoes (Fig 2).Marked vascularity was seen appearing as fastshort vertical oscillation of the tumourechoes. Systemic examination, haematologi-cal and biochemical screen, chest radio-graphy, and liver ultrasonography were allnormal. The eye was enucleated.

Pathological examination showed a heavilypigmented mushroom-shaped mass, 10 mmin base diameter and 7 mm in height. Thetumour was predominantly of 'spindle B' typewith a small amount of epithelioid cells. In theregion of the perforated Bruch's membranethere was an area of fibrosis containing bone,which showed calcification and the presenceof osteocytes (Fig 3). This was surrounded bythe tumour mass. Apart from Bruch's mem-brane at the site of perforation, there was nocalcification elsewhere in the eye. The retinawas stretched and thinned in parts at the sum-mit of the tumour but was not breached by it.There was no evidence of tumour necrosis orextraocular spread.One year after surgery, the patient was alive

and well with no evidence of orbital or distantmetastasis.

COMMENTWe believe this case to be the first in the liter-ature demonstrating a choroidal melanomacontaining a large plaque of calcified bone.Byrne and Green2 reported a small area ofcalcification on echography on a melanomasurface, and underlying an area of localisedretinal detachment, but not within themelanoma mass itself. Calcification inchoroidal melanoma has also been reported

RM

CASE REPORTAn 85-year-old white man presented with a 3year history of painless, gradual loss of vision

Figure 3 Histological section showing the area ofcalcification (C) including osteocytes infibroustissue overlying a nodule ofspindle cell melanoma (M) that has ruptured through Bruch 's membrane,which itself is also showing calcification (arrow). Overlying retina (R) is intact. (Magnificationx 84, haematoxylin and eosin.)

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