Cytogenetic analysis in ocular lymphoma

LETTERS TOTHE EDITOR

Waardenburg syndrome type 2 in aTurkish family: implications for theimportance of the pattern of funduspigmentation

EDITOR,—Waardenburg syndrome (WS) is atypical auditory pigmentary syndrome withaVected individuals showing varying combi-nations of sensorineural hearing loss, patchyabnormal pigmentation of the eyes, hair andskin, and various defects of neural crestderived tissues.1–3

This syndrome is both clinically and geneti-cally heterogeneous and is clinically classifiedinto four types.3 Mutations of the PAX3 genehave been identified in WS type 1 and 3, whilethose of either the endothelin B receptor gene,the endothelin-3 gene or the soxio gene havebeen identified in WS type 4.4–6 WS type 2 is aheterogeneous group, with about 10% of casescaused by mutations in MITF. But MITFmutations are obviously not the major causeof WS type 2 and for most cases the geneticbasis is as yet unknown.

The diagnostic criteria for WS type 2proposed by Liu et al1 include, in addition tocongenital sensorineural hearing loss andpigmentary disturbances of the hair, pigmen-tary disturbances of the iris but not of thefundus.

In the two aVected boys of the Turkish fam-ily presented here, the pattern of funduspigmentation was one of the most strikingclinical features, with dense hyperpigmentedareas next to hypopigmented areas. We wantto emphasise the importance of a thoroughobservation of the clinical phenotype andespecially of the pattern of fundus pigmenta-tion in WS type 2.

CASE REPORT

A Turkish family presented with two of threesons showing clinical symptoms of WS type 2.Firstly, the 5 year old boy, the youngest ofthree children of a non-consanguineous cou-ple, was referred for ophthalmological evalua-tion because of constant esotropia in the lefteye. The child has worn hearing aids since theage of 16 months; the first reliable audiogramat age 3 years showed profound sensorineuralhearing loss which had not changed over thepast years. Best corrected visual acuity wasright eye 20/20 and left eye 20/400. Cyclople-gic refraction showed anisohypermetropia(right eye +2.5D and left eye +4.5D). He hadbilateral dark brown irides and strabismusconvergens in the left eye (Fig 1, top). Thepattern of fundus pigmentation was of adistinctly abnormal type in both eyes. Areas ofhypopigmentation on the posterior pole aswell as nasally passed over to areas withpigmentary mottling and spots of hyperpig-mentation temporally in the right eye. In theleft eye, these areas of hyperpigmentation weremore extensive in the peripapillary region,nasally, and in the whole fundus periphery,respectively (Fig 1, centre). Audiometryshowed profound bilateral sensorineural hear-ing loss (Fig 1, bottom).

As the parents also reported congenitaldeafness in the second son with “two diVerent

coloured eyes,” we asked them to bring theother family members for examination. Thesecond son, a 7 year old boy, showedcomplete iris heterochromia with a darkbrown iris right and a brilliant blue iris left(Fig 2, top). Cycloplegic refraction revealedan anisohypermetropia (right eye +0.5D andleft eye +5.5D), best corrected visual acuitywas 20/20 right eye and 20/200 left eye.Severe fundus pigmentary disturbances werefound in the left (blue) eye, with extensivealbinoid areas nasally and on the posteriorpole, whereas the temporal region showed ahomogeneous area of dense hyperpigmenta-tion. In the right (dark brown) eye, thepigmentary disturbances were less extensivewith a hyperpigmented peripapillary ring andpigmentary mottling especially in the nasal

region (Fig 2, centre). Conventional audio-logical examinations showed bilateral senori-neural hearing loss with moderate impair-ment on the right and total deafness on theleft side (Fig 2, bottom).

Ophthalmological and audiological evalua-tions made of the father, the eldest brother,and a son of the father‘s first marriage werewithin normal limits. The mother showed pig-mentary mottling in the periphery of the fun-dus only. No other associated abnormalities(such as hair or skin hypopigmentation,medial eyebrow flare, broad and high nasalroot, hypoplasia of alae nasi, or prematuregreying of hair) were found among the familymembers. To calculate the W index, a biomet-ric index for dystopia canthorum, we useddystopia indices for WS as reported by Arias,7

Figure 1 (Top) The 5 year old boy (III-5) with bilateral dark brown irides; corneal reflexesdemonstrate left esotropia; there is no evidence of dystopia canthorum. (Centre) Left: right funduswith an area of hypopigmentation on the posterior pole as well as nasally; pigmentary mottling andspots of hyperpigmentation in the temporal periphery (arrow); (right) left fundus, albinoid in typewith spots of hyperpigmentation nasally and around the whole fundus periphery (arrows). (Bottom)Audiogram: profound bilateral sensorineural hearing loss.

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based upon the inner canthal, interpupillary,and outer canthal distances. The W index forthis family was 1.45, indicating that none ofthe individuals had dystopia canthorum. Thiswas consistent with the clinical picture of WStype 2.

The genomic DNA samples, tested formutations in the PAX3 and MITF genes asdescribed elsewhere,4 showed no abnormallymigrating bands.

COMMENT

Given the classic symptoms of WS type 2expressed in this Turkish family, we had theopportunity to make some interesting obser-vations on the clinical findings in thissyndrome.

In the genomic DNA samples of this familyno abnormally migrating bands in the MITFgene or the PAX 3 gene were seen. Only about

10% of patients who fulfil the diagnostic crite-ria for WS type 2 have an MITF mutation andfor most cases the genetic basis is as yetunknown.4–6 8 Dominantly inherited examplesof auditory pigmentary syndromes withpatchy depigmentation of the skin, hair, eyesor the stria vascularis of the cochlea areusually labelled as Waardenburg syndromes.1 3

Expression of clinical findings is extremelyvariable1 2 and the evaluation of a correcthistory of pedigree was diYcult in this familybecause of the fact that most of the other fam-ily members were living in the Turkey.However, the fundal pigmentary changes ofthe mother were distinct enough to mark heras aVected.

Complete heterochromia irides and espe-cially the brilliant sapphire-blue eye colourhave been noted rarely in non-Waardenburgpeople.2 Slit lamp examination of the left iris

of the second son showed a thick iris of a bril-liant blue colour without any hypoplasticstructures or transillumination defects. It isgenerally assumed that in WS type 2 only themesodermal component of the iris is involvedowing to a lack of melanocytes in themesodermal part of the iris.

Congenital deafness is clinically the mostserious symptom. WS type 2 individuals werefound to have a greater incidence of deafness,more severe and more often bilateral forms ofdeafness.2 Hearing impairment can be ex-plained by a lack of melanocytes in the striavascularis of the cochleae. These two aVectedboys showed bilateral sensorineural hearingloss. Interestingly, we found that the audio-logical results are paralleled by the pattern offundus pigmentation. While the youngest boywith bilateral brown irides and markedbilateral pigmentary abnormalities of the fun-dus had profound bilateral hearing loss (Fig1), the 7 year old boy with heterochromiairides showed diVerent degrees in the severityof fundus anomalies and hearing loss: themoderate degree of hearing loss of the rightear correlated with mild irregularities ofpigmentation of the homolateral fundus, totaldeafness left correlated with severe homola-teral fundus pigmentary disturbances and thebrilliant blue iris (Fig 2).

The pattern of fundus pigmentation is notconsidered as part of diagnostic criteria forWS type 2.1 However, in our family, abnor-malities in fundus pigmentation seem to con-stitute an integral part of this syndrome.Fundi in patients with WS were described as“patchy hypopigmentation,” “pigmentarymottling,” or “albinoid in type” in mostcases.9 10 Only Goldberg9 reported “blond nextto hyperpigmented areas” in a black boy. Inthe two aVected boys, dense hyperpigmentedareas next to marked hypopigmented areaswere one of the most impressive clinical find-ings. This picture seems to be the result of alocalised accumulation of pigmented melano-cytes which were handicapped in their deter-mined homogeneous distribution.

In conclusion, we have presented a TurkishWS type 2 family in which no mutations of theMITF gene could be found. The aVected fam-ily members showed a conspicuous funduspicture with ipsilateral connections betweeniris, fundus, and perhaps, inner ear pigmenta-tion. Therefore, one might suggest, that theclinical signs in WS type 2 could be aconsequence of a failure in distribution of pig-mented melanocytes in their final location.The genetic basis, as yet unknown for mostcases of WS type 2, might be found in a verylate step of the pigmentation pathway.

ANDREA MÜLLNER-EIDENBÖCKELISABETH MOSER

Department of Ophthalmology, University Hospital ofVienna, Austria

HERWIG FRISCHDepartment of Paedriatrics, University Hospital of

Vienna, Austria

ANDREW P READUniversity Department of Medical Genetics, St Mary‘s

Hospital, Manchester M 13 0JH, UK

Correspondence to: Andrea Müllner-Eidenböck,MD, Department of Ophthalmology, University ofVienna Medical School, Allgemeines Krankenhaus,A-1090 Vienna, Waehringer Guertel 18–20, Austria

[email protected] for publication 20 April 2001

1 Liu XZ, Newton VE, Read AP. Waardenburgsyndrome type 2: phenotypic features and diag-nostic aspects. Am J Med Genet 1995;55:95–100.

Figure 2 (Top) The 7 year old boy (III-4) with heterochromia irides (note the brilliant blue iriscolour left); there is no evidence of dystopia canthorum. (Centre) Left: right fundus with pigmentarymottling especially nasally (arrow); right: left fundus albinoid in type nasally and between optic discand macula; in the temporal region there is a homogeneous dense hyperpigmentation (arrow).(Bottom) Audiogram: bilateral sensorineural hearing loss with moderate impairment in the right earand total deafness in the left ear.

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2 Reynolds JE, Meyer JM, Landa B, et al. Analysisof variability of clinical manifestations in WS.Am J Med Genet 1995;57:540–7.

3 Read AP, Newton VE. Waardenburg syndrome. JMed Genet 1997;34:656–65.

4 Tassabehji M, Newton VE, Liu XZ, et al. Themutational spectrum in Waardenburg syn-drome. Hum Mol Genet 1995;4:2131–7.

5 Tachibana M. A cascade of genes related toWaardenburg syndrome. J Invest Dermatol SympProc 1999;4:126–9.

6 Lalwani A, Attaie A, Randolph F, et al. Mutationin the MITF gene causing WS type II in athree-generation Indian familiy. Am J Med Genet1998;80:406–9.

7 Arias S, Mota M. Apparent non-penetrance fordystopia in WS type I, with some hints on thediagnosis of dystopia canthorum. J Genet Hum1978;26:103–31.

8 Tassabehji M, Newton VE, Read AP. Waarden-burg syndrome type 2 caused by mutations inthe human microphthalmia (MITF) gene. NatGenet 1994;8:251–5.

9 Goldberg MF. Waardenburg’s syndrome withfundus and other anomalies. Arch Ophthalmol1966;76:797–810.

10 Delleman JW, Hageman MJ. Ophthalmologicalfindings in 34 patients with Waardenburgsyndrome. J Pediatr Ophthalmol Strabismus1978;15:341–5.

Trichotillomania

EDITOR,—Trichotillomania is the inability toresist the urge to pull out body hair. Wepresent a case of this rare condition.

CASE REPORT

A 12 year old boy was referred to the eye clinicwith complaints of dropping of eyelashes ofboth upper eyelids. He was seen by hisoptician before the referral. Lid hygiene,propamidine isethionate eye ointment 0.15%(Brolene), and sodium cromoglycate eyedrops 2% (Opticrom) were tried but with nobenefit. The mother reports that his eyelashesgrew while they were abroad on a holiday for afortnight and then fell oV once they returnedfrom their holiday!

When seen in the eye clinic his visual acui-ties were 6/5 bilaterally. He had no significantocular history, was generally fit and well, andwas taking no regular medications. Hisparents did not express any concerns regard-ing his health or his behaviour. On examina-tion, the eyelashes of both upper eyelids werescarce centrally. The few lashes, which wereseen, had pointed and not cut ends. On eitherside the lashes were normal. There was no evi-dence of inflammation or disease of the lidmargins and the rest of the ocular examinationwas normal. There was no evidence of loss ofeyebrow or scalp hair. He is being consideredfor psychiatric evaluation.

COMMENT

Trichotillomania is characterised by an irresist-ible urge to pull one’s hair. Any body hair maybe targeted. Scalp and eyelashes are most com-monly aVected. Onset is generally in childhoodor adolescence, and a chronic course is typical.Depression and anxiety frequently accompany

this disorder. An increased incidence of co-morbid obsessive-compulsive disorder (OCD)has been noted.1 The estimated lifetime preva-lence is 1.5% for male and 3.4% for female col-lege students.2 In very young patients, a moreequal sex ratio is observed. On the whole,women show 5–10 times higher prevalencerates than men.2 The majority of the suVerersdisguise their hair loss very well. Because of thesecrecy and shame about their behaviour, manyremain silent suVerers and treatment is oftendelayed. It is a chronic mental illness thatimposes severe limitations on the patient’ssocial, emotional, and occupational adjust-ment. The pathophysiology of trichotillomaniais not well understood. Treatment optionsinclude: medications such as serotonin re-uptake inhibitors with or without haloperidol,1

paroxetine,3 clomipramine,4 pimozide,2 risperi-done in serotonin reuptake inhibitor refractorytrichotillomania,5 venlafaxine6; behaviour ther-apy habit reversal training1 2 4 and hypno-therapy.1

Trichotillomania has been infrequently re-ported in the ophthalmic literature. Manage-ment can be diYcult. Many of these patientsare aware of their behaviour, but are unable tocurtail it. Others may conceal or deny theirhabit. Psychiatric counselling may be ofbenefit if patients are willing to undergo it.

B B PATILT C DOWD

North Riding Infirmary, Newport Road, MiddlesbroughTS1 5JE, UK

Correspondence to: B B [email protected]

Accepted for publication 5 February 2001

1 Christenson GA, Crow SJ. The characterizationof treatment of trichotillomania. J Clin Psychia-try 1996;57(suppl 8):42–7; discussions 48–9.

2 Ko SM. Under diagnosed psychiatric syndrome:trichotillomania. Ann Acad Med Singapore 1999;28:279–81.

3 Block C, West SA, Baharoglu B. Paroxetinetreatment of trichotillomania in an adolescent. JChild Adol Psychopharmacol 1998;8:69–71.

4 Tynes LL, Winstead DK. Behavioural aspects oftrichotillomania. J La State Soc 1992;144:459–63.

5 Epperson CN, Fasula D, Wasylink S, et al. Risp-eridone addition in serotonin reuptakeinhibitor-resistant trichotillomania: three cases.J Child Adol Psychopharmacol 1999;9:43–9.

6 Ninan PT, Knight B, Kirk L, et al. A controlledtrial of venlafaxine in trichotillomania: interimphase I results. Psychopharmacol Bull 1994;34:221–4.

Gold induced interstitial keratitis

EDITOR,—A 60 year old woman presentedwith intense, bilateral ocular irritation andphotophobia. She had a history of rheumatoidarthritis and was under treatment with pred-nisone, azathioprine, sulindac, plaquenil, andintramuscular injections of gold sodium thi-omaleate (50 mg once weekly). She hadreceived a total of 7.4 g of gold over the past 3years. Examination revealed an extremelyphotophobic patient with a visual acuity of20/20 in both eyes. The conjunctivas weremildly injected, with bilateral perilimbalchemosis. The peripheral cornea showed 360°stromal oedema. Mid-stromal vessels wereseen entering the oedematous stroma from thelimbus (Fig 1 (left)). The rest of the examina-tion was unremarkable. The patient was diag-nosed with rheumatoid marginal keratitis, andtherapy was started with hourly application oftopical prednisolone acetate. Over the next 2months her symptoms gradually resolved, asdid most of her inflammatory findings.However, granular, golden brown pigmenteddeposits appeared in the corneal stroma in thesame peripheral, ring-like distribution as thenow resolved stromal keratitis (Fig 1 (right)).A diagnosis of gold keratopathy was made,and the patient was referred for rheumatologi-cal consultation. A systemic evaluation did notreveal signs of gold toxicity. Gold therapy wasdiscontinued. Over the next 6 months, thestromal deposits partially cleared, and topicalprednisolone was gradually tapered oV. Amilder episode of photophobia and irritation

Figure 1 Scarce central eyelashes on both upper eyelids.

Figure 1 (Left) Slit lamp photograph of the right cornea. Stromal oedema with brush-like stromalvascularisation (arrows). (Right) Slit lamp photograph of the right cornea, using a narrow slit beam.Dense deposition of golden brown granules is seen in the inferior corneal stroma superior to the limbus.Arrows indicate epithelium (long arrow) and endothelium (short arrow).

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then occurred, with stromal oedema in thesame distribution. This was controlled byreinstitution of topical prednisolone therapy.One year after onset, the patient continues touse topical prednisolone once a day and isasymptomatic. There is no stromal inflamma-tion, but fine golden granules are still evident.

COMMENT

Two variants of gold induced keratopathy(corneal chrysiasis) have been described.1 Themore common variant manifests as asympto-matic deposition of fine brown or purplegranules in the central posterior cornealstroma, sparing the periphery. Other patternsinclude peripheral deposition with extensiontowards the central cornea, superficial anddeep axial deposition.2 Corneal stromal gran-ule deposition correlates with duration anddosage of therapy and occurs in most, if not allpatients after a cumulative dose of 1 g hasbeen reached.1 2 Corneal gold deposition byitself is not considered an indication todiscontinue gold therapy.2

The second variant of keratopathy is rare,presenting with inflammatory symptoms andsigns. Examination reveals marginal intersti-tial keratitis that may ulcerate, with white,subepithelial limbal infiltration and deep,brush-like stromal vascularisation.1 3

Crescent-shaped marginal ulcers, 2–3 mm inlength may be present. This variant ispresumed to be an idiosyncratic reaction.1 3 Itmay be unilateral or bilateral, and is consid-ered an indication to stop gold therapy.1 Theunderlying pathogenic mechanism, as well asthe possible associations with other systemicgold toxicity, is unknown. However, it is nota-ble that the keratitis in our case was responsiveto topical corticosteroids and recurred aftertheir withdrawal. A similar response has beenreported in systemic manifestations of goldtoxicity.4 5

The diagnosis of gold keratopathy should beconsidered in patients with rheumatoid arthri-tis who present with marginal keratitis.Assessment of possible systemic toxicity iswarranted and cessation of therapy should beconsidered in such cases. Patients should becontinuously followed, since stromal inflam-mation may recur even after cessation of goldtherapy.

Supported in part by National Institute of Healthcore grant EY03040 and by an unrestricted grantfrom Research to Prevent Blindness, New York,USA. Dr Zamir is the recipient of an American Phy-sician fellowship, Boston, MA. Dr Read is the recipi-ent of an American Ophthalmological Society/Herman Knapp Testimonial Fund fellowship,Cleveland, OH, USA.

EHUD ZAMIRRUSSELL W READJOHN C AFFELDT

Doheny Eye Institute, Keck School of Medicine of theUniversity of Southern California, Los Angeles,

California, USA

DHARMARAJAN RAMASWAMYDepartment of Rheumatology

NARSING A RAODoheny Eye Institute

Correspondence to: Narsing A Rao, MD, DohenyEye Institute, Keck School of Medicine, Universityof Southern California, 1450 San Pablo Street,DVRC 211, Los Angeles, CA 90033, USA

[email protected]

Accepted for publication 18 April 2001

1 ArVa RC. Drugs and metals. In: ArVa RC, ed.Grayson’s diseases of the cornea. 3rd ed. St Louis:Mosby-Year Book, 1991:617–31.

2 McCormick SA, DiBartolomeo AG, Raju VK, etal. Ocular chrysiasis. Ophthalmology 1985;92:1432–5.

3 Smith JL. Ocular complications of rheumaticfever and rheumatoid arthritis. Am J Ophthalmol1957;43:575–82.

4 Schapira D, Nahir M, Scharf Y. Pulmonaryinjury induced by gold salts treatment. MedInterne 1985;23:259–63.

5 Hansen RM, Varma RR, Hanson GA. Goldinduced hepatitis and pure red cell aplasia.Complete recovery after corticosteroid andN-acetylcysteine therapy. J Rheumatol 1991;18:1251–3.

Osteosarcoma with metastasis to orbit

EDITOR,—Osteosarcoma is the most commonprimary malignant tumour of the bone. Morethan 90% of patients with this disease die withpulmonary metastases. Metastatic disease tothe orbit from sarcomas is rare.1 An Englishlanguage computer Medline search (fromJanuary 1966 to December 2000) for osteo-sarcoma metastatic to the orbit did not revealany previous report. We describe perhaps thefirst case of osteosarcoma metastasising to theorbit.

CASE REPORT

An 8 year old boy was referred from a districthospital for a swelling over the proximal rightleg of 5 months’ duration. Lower extremityradiography showed a metaphyseal lesion inthe proximal tibia with bone destruction andnew bone formation. A clinical and radiologi-cal diagnosis of osteosarcoma was made. Aplain chest radiograph did not reveal anyabnormality. Histopathological examinationof the tumour confirmed the diagnosis ofosteosarcoma. An above knee amputation ofthe right leg was performed.

One month later, the child developedprotrusion of the right eye (Fig 1). Anophthalmic examination confirmed proptosis

of the right eye. Vision, fundus, and eye move-ments were normal in both eyes. Ultrasoundexamination of the eye revealed a 12 mm × 18mm lobulated, nodular, hypodense retrobul-bar shadow on the temporal side, displacingthe optic nerve medially. An area of necrosiswas seen in the mass, but no calcification waspresent (Fig 2). Computed tomography of theorbit confirmed the findings of ultrasonogra-phy, demonstrating a soft tissue density massin the right orbit displacing the eyeball. Fineneedle aspiration cytology from the massshowed malignant spindle cells. A diagnosis ofosteosarcoma with metastasis to right orbitwas made. The patient was oVered palliativechemotherapy but refused further treatmentand was discharged from the hospital.

COMMENT

Osteosarcoma is the most common primarymalignant tumour of bone. Most cases occurin children, adolescents, and young adultswith a male predominance. The classic site ofoccurrence is the medulla of the metaphysis ofthe long bones, particularly the distal femur,proximal tibia, and proximal humerus. Metas-tases of osteosarcoma typically involve thelungs. Recent studies indicate, however, thatthe incidence of non-pulmonary metastases isincreasing.2

Orbital metastases from malignant neo-plasms are rare and can originate fromanywhere in the body.3 In adults, the primarytumour is almost always a carcinoma, withbreast and lung accounting for the vast major-ity of orbital metastases, followed in frequencyby genitourinary and gastrointestinal prima-ries. In children with orbital metastases theprimary tumours in descending order offrequency are neuroblastoma, Ewing’s sar-coma, and Wilm’s tumour.4 Jain et al5 foundleukaemia and neuroblastoma as the com-monest tumours producing orbital metas-tases. The two populations studied in thesereports diVered geographically (United Statesand India respectively). These tumours tendto involve the orbits and spare the globes incontradistinction to metastatic disease inadults.4 Metastatic osteosarcoma to the eye isvery rare. Newman and DiLoreto6 reported asingle case metastatic to the eyelids. Spauldingand Woodfin7 and Lees8 have reported singlecases of osteosarcoma metastatic to thechoroid. The lung was not involved as a meta-static site in our patient. The spread of tumourto the orbit, sparing the lung, may have possi-bly been through the Batson’s paravertebralsystem. Physicians should be aware thatnon-pulmonary metastases of osteogenic sar-coma may exist at unusual sites.

A MISRADepartment of Ophthalmology, King George’s Medical

College, Lucknow - 226003, India

S MISRAA CHATURVEDI

Department of Surgical Oncology

P K SRIVASTAVADepartment of Radiotherapy

Correspondence to: Dr Sanjeev Misra, 122, Faiza-bad Road, Lucknow-226007, UP, [email protected] for publication 17 May 2001

1 Peyster RG, Shapiro MD, Haik B. Orbital metas-tasis: role of magnetic resonance imaging andcomputed tomography. Radiol Clin North Am1987;25:647–62.

2 Giuliano AE, Feig S, Eilber FR. Changing meta-static patterns of osteosarcoma. Cancer 1984;54:2160–4.

3 Char DH, Miller T, Kroll S. Orbital metastases:diagnosis and course. Br J Ophthalmol 1997;81:386–90.

Figure 1 Clinical photograph showing proptosisof right eye.

Figure 2 Ultrasound showing retrobulbar mass.

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4 Jakobiec FA, Rootman J, Jones IS. Secondaryand metastatic tumors of the orbit. In: DuaneTD, Jaeger EA, eds. Clinical ophthalmology.Philadelphia: JB Lippincott; 1982:1–67.

5 Jain IS, Dinesh K, Mohan K. Ocular and orbitalmetastasis from systemic malignancies. Indian JOphthalmol 1987;35:437–41.

6 Newman NM, DiLoreto DA. Metastasis ofprimary osteogenic sarcoma to the eyelid. Am JOphthalmol 1987;104:659–60.

7 Spaulding AG, Woodfin MC Jr. Osteogenicsarcoma metastatic to the choroid. Arch Oph-thalmol 1968;80:84–6.

8 Lees V. A case of metastatic osteosarcoma in thechoroid. Br J Ophthalmol 1947;31:713–16.

An unusual cause of oscillopsia

EDITOR,—Chronic maxillary atelectasis(CMA),1 also known as silent sinus syndrome(SSS)2 describes the same condition. Typi-cally, the patient presents with acute enoph-thalmos and hypoglobus in the absence ofprevious trauma or surgery. Past sinus diseasemay be present and computed tomograph(CT) scans demonstrate ipsilateral sinus con-traction, orbital floor resorption, and thinningwith inferior prolapse into the maxillary sinus.We present a patient who noted oscillopsiawhile jogging 1 year after being diagnosedwith SSS.

CASE REPORT

A 26 year old woman was referred with a 6month history of painless gradual sinking ofthe left eye (Fig 1). She had suVered two epi-sodes of mild sinusitis, one at the age of 12and one at a year before presentation. Visualacuity was 6/6 in each eye and there was noevidence of optic neuropathy. There was4 mm of left relative enophthalmos, no mani-fest deviation, and full extraocular move-ments. The height of the palpebral aperturewas 1 mm less on the left. Orbital CT scansshowed a unilaterally opaque maxillary an-trum and ethmoid sinus, a collapsed in-fundibulum, an imploding medial wall, and aconcave demineralised orbital floor (Fig 2).Eighteen months after becoming sympto-matic, the patient spontaneously remarkedthat she had vertical oscillopsia while jogging.

COMMENT

Oscillopsia is an illusion that the world is inmotion; we believe that this is the first report

in a patient with SSS. It occurs mostfrequently with disorders of the vestibular sys-tem, cerebellum, or brainstem. Our patienthad no associated neurological signs or symp-toms, and a normal head CT scan. Amechanical cause of oscillopsia caused by aninstability of fixation is a rare but welldocumented finding.3

In our patient we postulate that theoscillopsia during jogging arises from inad-equate globe support caused by demineralisa-tion and downward displacement of theorbital floor and Lockwood’s ligament, whilethe levator palpebrae superioris and Whit-nall’s ligament remain in their normal posi-tion. Patients with SSS may also develop ver-tical diplopia,4 lid retraction,5 lagophthalmos,6

or blurred vision.7

Spontaneous enophthalmos unrelated totrauma, surgery, local malignancy, or systemicdisease is uncommon. The presence of diplo-pia may suggest an underlying neuro-ophthalmic disorder; however, hypoglobusand enophthalmos point to the orbital/maxillary area as the primary site of pathology.

HADI J ZAMBARAKJIGEOFFREY E ROSE

Orbital Clinic, Moorfields Eye Hospital, City Road,London EC1V 2PD, UK

Correspondence to: Mr G E RoseAccepted for publication 6 June 2001

1 Montgomery WW. Mucocele of the maxillarysinus causing enophthalmos. Eye Ear NoseThroat Mon 1964;43:41–3.

2 Soparkar CN, Patrinely JR, Cuaycong MJ, et al.The silent sinus syndrome. A cause of spontane-ous enophthalmos. Ophthalmology 1994;101:772–8.

3 Knight RT SJJ, Nakada T. A case of voluntaryvisual illusions of movement. Arch Neurol 1984;41:95–6.

4 Durig J, Borruat FX, Jaques B. Silent sinussyndrome: an unusual cause of vertical diplopia.Klin Monatsb Augenheilkd 1998;212:397–9.

5 Bartley GB. The diVerential diagnosis and classi-fication of eyelid retraction. Ophthalmology1996;103:168–76.

6 Rubin PAD RS. Functionnal indications forenophthalmos repair. Ophthalmic Plast Recon-struct Surg 1999;14:284–92.

7 Wan MK, Francis IC, Carter PR, et al. The spec-trum of presentation of silent sinus syndrome. JNeuro-Ophthalmol 2000;20:207–12.

Cytogenetic analysis in ocularlymphoma

EDITOR,—A 56 year old man was referred tothe ocular oncology service with complaints ofpain, redness, and blurring of vision in his lefteye for the previous 2 months. He had no sig-nificant past ocular history. He was a knownhypertensive with no known allergies.

On examination his visual acuity was 6/18in the right eye and 6/6 in the left eye. Therewas 2 mm of relative exophthalmos on theright side. A pink subconjunctival patch wasnoticed in the superior quadrant (Fig 1). Hehad a shallow anterior chamber. Gonioscopyshowed that anterior bowing of the iris closed270 degrees of the angle. A YAG iridotomywas performed and pupils dilated for fundusevaluation. Funduscopy showed extensiveperipheral elevation of the ciliary body andpars plana, which appeared to extend subreti-nally to the disc with an overlying retinaldetachment in places (Fig 2) Ultrasoundbiomicroscopy along with B scan of the globeconfirmed diVuse infiltration of the ciliarybody and choroid (Fig 3A). DiVuse extensionof this abnormal tissue behind he globe wasalso evident. The left eye was normal. A work-ing diagnosis of benign reactive lymphoidhyperplasia was made and an incisional biopsy

planned. The patient was subsequently admit-ted for an incisional biopsy and investigationsto rule out systemic disease. No systemic evi-dence of lymphoma was found, however.Histopathology confirmed the diagnosis ofwell diVerentiated B cell lymphoma (diVuselarge cell lymphoma (REAL classification)1)(Fig 4).

A cytogenetic analysis was also performedas detailed previously.2 3 Only a partial analysiswas possible, but from analysis of 12 divisionsthe karyotype was determined to be: 2 cells,46 XY; 10 cells, 43–46 X-Y, add (1) (q?)[10],add (6)(q?)[10], −10[10], −14[10],+2mar[5].

The patient was subsequently started on 30mg of prednisolone and was referred to theradiotherapy department where he received30 Gy in 15 sessions over a 3 week period.Follow up at 4 months and further 3 monthsfollowing the radiotherapy showed resolution

Figure 1 There is left hypoglobus, enophthalmos(indicated by the deeper upper lid sulcus) and anarrower left palpebral aperture.

Figure 2 Unwrapped orbital CT scandemonstrates an opaque left maxillary antrumand inferior bowing of the orbital floor.

Figure 1 Photograph showing the conjunctivallesion at presentation.

Figure 2 (A) Colour fundus photographshowing the posterior extension of the lesion. (B)Fundus fluorescein angiography showing multipleareas of hyperfluorescence.

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of the mass. The patient has since beenasymptomatic.

COMMENT

Characteristic cytogenetic abnormalities areknown to be associated with certain types oflymphoma.4–6 In addition to classic transloca-tion of chromosome 8 and 14 in Burkitt’slymphoma, other chromosome rearrange-ments are related to subsets of lymphoma.5 Toour knowledge this is the first report ofchromosome abnormalities in ocularlymphoma. We observed abnormalities fre-quently associated with non-Hodgkin’slymphoma (NHL), including rearrangementsof chromosome 1 and 6, which are found inboth B and T cell NHL, as is a loss of the Ychromosome.6 Trisomy of chromosome 12was also observed in this ocular lymphoma,and has been linked with small lymphocytic ordiVuse large cell B NHL,5 and from a study ofdiVuse large cell lymphomas of stomach,chromosome 12 was again found to be themost consistent abnormality.4 Although its tooearly to identify which abnormalities arespecifically related to the development of thiseye lymphoma, it is apparent that certainalterations are characteristic of lymphoma in

general, suggesting that similarities exist be-tween development of ocular and otherlymphomas.

S PRASADDepartment of Ophthalmology and Orthoptics,

University of SheYeld, Royal Hallamshire Hospital,SheYeld S10 2JF, UK

P PURIDepartment of Ophthalmology, Royal Hallamshire

Hospital

K SISLEYDepartment of Ophthalmology and Orthoptics,

University of SheYeld

A PARSONSI G RENNIE

Department of Ophthalmology and Orthoptics,University of SheYeld

Correspondence to: Mr S PrasadAccepted for publication 4 February 2001

1 Harris NL, JaVe ES, Stein H, et al. A revisedEuropean-American classification of lymphoidneoplasms: a proposal from the InternationalLymphoma study group. Comment in: Blood1994;84:1359–60; comment in Blood 1995;85:857–60; comment in Blood 1995;85:1972–4.

2 Sisley K, Rennie IG, Parsons MA, et al.Abnormalities of chromosome 3 and 8 in poste-rior uveal melanoma correlate with prognosis.Genes Chromosom Cancer 1997;19:22–8.

3 Sisley K, Brand C, Parsons MA, et al. Cytogenet-ics of iris melanomas: disparity with other uvealtract melanomas. Cancer Genet Cytogenet 1998;101:128–33.

4 Chan WY, Wong N, Chan ABW, et al. Consistentcopy number gain in chromosome 12 in primarydiVuse large cell lymphomas of the stomach. AmJ Pathol 1998;152:11–16.

5 Donner LR. Cytogenetics of lymphoma: a briefreview of its theoretical and practical signifi-cance. Cancer Genet Cytogenet 1997;94:20–6.

6 Heim S, Mitelman F. Malignant lymphoma. In:Heim, Mitelman, eds. Cancer Cytogenetics. NewYork: Wiley Liss.

Grotesque bilateral eyelid swelling as asymptom of Munchausen’s syndrome

EDITOR,—Eyelid swelling can be diVuse orsolid, acute or chronic, isolated or part of asyndrome. The diVerential diagnosis of solid,chronic, and isolated eyelid swelling com-prises tumours of multiple origin. We report acase of eyelid swelling which was caused byautomutilation as part of Munchausen’s syn-drome.

CASE REPORT

A 44 year old white woman presented withbilateral lower eyelid swelling that had beenpresent for 6 months, which made readingimpossible (Fig 1). In the past she had under-gone several paranasal sinus operations and 3years earlier she had been treated for a presep-tal orbital cellulitis and pansinusitis. For thepast 4 years she had been bedridden becauseof fibromyalgia.

The swellings measured 7 × 5 × 2 cm and feltsolid on palpation. Complete ocular, internal,

otolaryngological, dermatological, parasitologi-cal, and psychological examination revealed noclues for the diagnosis. The swellings were sur-gically removed to the level of the orbitalseptum, the defects being covered with fullthickness skin grafts. Histological examinationshowed chronic lymphoedema with lym-phangiectasia, inflammation, and striking eosi-nophilia, but no conclusive diagnosis could bemade at this time. During uneventful healing ofthe lower lids, the patient developed bilateralupper eyelid swelling. These swellings wereremoved as well and replaced by split skingrafts. Histology of the upper lids showeddensely packed empty spaces, which almostobscured pre-existent structures such as theorbicularis muscle (Fig 2). In between a patchyinfiltrate of lymphocytes, neutrophils, eosi-nophils, and many macrophages was seen. Athigh magnification (Fig 3), the empty spacesrevealed a lining of macrophages as wasdemonstrated by positivity for the CD 68 anti-body, a reaction pattern highly suggestive of afactitial process. The diagnosis of Mun-chausen’s syndrome was made.

COMMENT

The patient was confronted with these resultsand admitted having pin-pricked herself afterputting fatty ointments on her eyelids. Shethought this would help the “blisters” todisappear more rapidly. After an emotionalconversation, she was able to get up and walkfor the first time in 4 years. The repeated psy-chiatric evaluation resulted in a diagnosis of afactitious disorder with physical signs super-imposed on a somatisation disorder. Thecomplaints seemed to have a function in themaintenance of the balance of power in thematrimonial relationship. The patient refusedpsychiatric treatment.

Factitious disorders, such as the Mun-chausen’s syndrome, are under the patient’svoluntary control and are intended to get ormaintain the role of patient.1–3 Self inflictedenucleation and corneal perforation are de-scribed ophthalmological representatives ofthese disorders and easy to recognise.4–6 Theabove described swellings are a less common

Figure 3 (A)Ultrasound biomicroscopy showinginfiltration of the ciliary body and choroid. (B)Ocular B scan ultrasonography showing theposterior extension.

Figure 4 Histological section of the lesionconfirming the lesion to be a well diVerentiated Bcell lymphoma.

Figure 1 The patient presented with bilaterallower eyelid swelling.

Figure 2 Histology of the upper lids showeddensely packed empty spaces.

Figure 3 At high magnification the emptyspaces reveal a lining of macrophages.

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and more diYcult to prove example of an ocu-lar factitious disorder, although the patient’smedical history might make the doctor suspi-cious. In summary, self inflicted disorders mustbe considered as a cause of eyelid swelling.

MAARTEN PH MOURITSINNA V SASIM

Department of Ophthalmology, University MedicalCenter Utrecht, Netherlands

SEBASTIAAN C J VAN DER PUTTEDepartment of Pathology

Correspondence to: Dr Maarten Ph Mourits, OrbitalUnit, Department of Ophthalmology, UniversityMedical Center Utrecht, POBox 85500, 3508 GAUtrecht, NetherlandsM.P.Mourits @oogh.azu.nlAccepted for publication 16 April 2001

1 Shafer N, Shafer R. Factitious disorders includ-ing Munchausen’s syndrome. NY State J Med1980;80:594.

2 Rosenberg PN, Krohel GB, Webb RM, et al.Ocular Munchausen’s syndrome. Ophthalmology1986;93:1120–3.

3 Numata-Watanabe K, Hayasaka S, Kadoi C, etal. Decreased visual acuity and diplopia in apatient with Munchausen syndrome. Ophthal-moliga 1998;212:337–8.

4 Duke-Elder S, MacFaul PA. Self-inflicted inju-ries. In: Duke-Elder S, ed. System of Ophthalmol-ogy. London: Henry Kimpton 1972;14,partI:58.

5 Palmowski A, Heinz G, Ruprecht KW. Self-inflicted injuries of the eye: diVerential diagnosisof self-inflicted lacerating corneal injury. KlinMonatsbl Augenheilkd 1994;204:30–2.

6 Heinz P, Bodanowitz S, Hesse L. Keratitis punc-tata superficialis caused by self-injury. KlinMonatsbl Augenheilkd 1995;207:130–2.

Angle closure glaucoma secondary tohemiretinal vein occlusion

EDITOR,—Central retinal vein occlusion(CRVO) has been reported to cause shallow-ing of the anterior chamber with acute angleclosure glaucoma.1 2 This is due to anteriordisplacement of the lens-iris diaphragmcaused by either the transudation of fluid fromretinal vessels into the vitreous cavity or swell-ing of the ciliary body due to spasm, oedema,or detachment which may cause relaxation oflens zonules with subsequent crowding andclosure of the angle.2 3 We describe a patientwho developed angle closure glaucoma with-out neovascularisation of the angle secondaryto hemiretinal vein occlusion which re-sponded to miotics and iridotomy suggestinga “pupillary block” mechanism. This is thefirst report of angle closure glaucoma follow-ing a hemiretinal vein occlusion.

CASE REPORT

A 63 year old African American man with con-trolled systemic hypertension noted reducedvision in his right eye for 1 month. Bestcorrected visual acuity was 20/200 right eyewith +1.75 −0.75 × 85, and 20/25 left eye with+2.25 −1.00 × 95. Slit lamp examination wasunremarkable, pupils were equally reactivewithout an aVerent pupillary defect. Intraocularpressure (IOP) was 26 mm Hg right eye and 25mm Hg left eye. Gonioscopy revealed grade 3angles in both eyes. The superior half of theretina right eye had dilated tortuous veins andmultiple superficial haemorrhages. The rightoptic nerve was oedematous and hyperaemic.Retinal examination was unremarkable left eyewith a cup to disc ratio of 0.4 horizontally by0.5 vertically. The patient was diagnosed with ahemiretinal vein occlusion right eye, elevatedIOP in both eyes, and treated with betaxolol0.25% twice daily in both eyes.

Two weeks later visual acuity was countingfingers right eye and unchanged left eye. IOP

was 42 mm Hg right eye and 20 mm Hg lefteye, on betaxolol. The patient was referred toour oYce.

On examination the anterior chambers wereshallow right eye and deep left eye. IOP was45 mm Hg right eye and 21 mm Hg left eye.The angle was closed without neovascularisa-tion right eye and grade 3 left eye. B scanultrasonography revealed an unremarkableposterior segment without choroidal detach-ments right eye. Brimonidine 0.2% andCosopt were administered to the right eye.Thirty minutes later the IOP was 36 mm Hgright eye. Three hours later IOP right eye was28 mm Hg. Mydriacyl 1%, neosynephrine2.5%, and Cyclogyl 2% were administeredand the IOP increased to 37 mm Hg. Thepatient was discharged on acetazolamide 250mg by mouth four times daily, brimonidine0.2% three times daily right eye, Cosopt twicedaily right eye, and pilocarpine 2% four timesdaily right eye.

The following day, the anterior chamberhad deepened and the IOP was 24 mm Hgright eye. Gonioscopy revealed a closed angle(Fig 1). Pilocarpine 2% was instilled and alaser iridotomy performed right eye. Thefollowing day the IOP was 16 mm Hg righteye. Gonioscopy revealed a grade 2 angle.Acetazolamide was discontinued, pilocarpine4% four times daily right eye, brimonidine0.2% three times daily right eye, and Cosopttwice daily right eye were continued.

Two months later, the anterior chamberswere deep and the angles were grade 3 in botheyes. IOP was 14 mm Hg right eye onpilocarpine 4% four times daily and TimopticXE four times daily 0.5% IOP on subsequentvisits remained below 20 mm Hg, and theangle remained open (Fig 2). Visual acuity didnot improve.

COMMENT

Transient angle closure glaucoma, an infre-quent sequela of CRVO, has not beenreported following hemiretinal vein occlusion(HRVO). Angle closure may occur days tomonths following a CRVO. Neovascular glau-coma may develop weeks or months followinga retinal vascular occlusion. Elevated IOP

during an acute attack of primary pupillaryblock angle closure glaucoma can lead to aretinal vascular occlusion. Risk factors forCRVO and HRVO include systemic hyper-tension and diabetes mellitus. A history ofglaucoma has been associated with CRVO,HRVO, and branch retinal vein occlusion(BRVO).1

The patient in this report developed angleclosure glaucoma within a few weeks of theHRVO. He had a history of systemic hyper-tension. Elevated IOP was noted in both eyeson initial examination. Cycloplegic agentsincreased the IOP, suggesting the angleclosure was not due to a ciliary blockmechanism. Pilocarpine and a laser iridotomyreduced the IOP and opened the angle in thispatient, suggesting a secondary pupillaryblock mechanism. At the time of diagnosis ofangle closure glaucoma the contralateral eyehad a deep anterior chamber and a wide openangle, making a diagnosis of primary pupillaryblock angle closure glaucoma unlikely.

Previous reports of angle closure glaucomasecondary to central retinal vein occlusionsuggest treatment with cycloplegic/mydriaticagents is beneficial in some patients.2 Mioticagents have been reported to be of benefit incases of angle closure glaucoma following aCRVO.3

Determining the mechanism of angle clo-sure in an individual patient following a retinalvascular occlusion will guide the ophthal-mologist to the appropriate treatment options,mydriatic or miotic therapy. Ultrasound bi-omicroscopy may be of benefit in diVerentiat-ing between a ciliary block mechanism4 and apupillary block mechanism.5

Supported in part by grant EY01867 from theNational Eye Institute, National Institutes of Health,Bethesda, MD, an unrestricted grant from Researchto Prevent Blindness Inc, New York, and the Louisand Rachel Rudin Foundation, Inc, New York, NY,USA.

DEMETRIOS HALIKIOPOULOSJANET B SERLE

Department of Ophthalmology, Mount Sinai School ofMedicine of New York University, New York, USA

Correspondence to: Janet B Serle, MD, Box 1183,Mount Sinai School of Medicine, One Gustave LLevy Place, New York, NY 10029, [email protected] for publication 17 May 2001

1 Sperduto RD, Hiller R, Chew E, et al. Riskfactors for hemiretinal vein occlusion: compari-son with risk factors or central and branch reti-nal vein occlusion. Ophthalmology1998;105:765–71.

2 Phelps CD. Angle-closure glaucoma secondaryto ciliary body swelling. Arch Ophthalmol 1974;92:287–90.

3 Grant W. Shallowing of the anterior chamber fol-lowing occlusion of the central retinal vein. AmJ Ophthalmol 1973;75:384–9.

4 Trope GE, Pavlin CJ, Bau A, et al. Malignantglaucoma: clinical and ultrasound biomicro-scopic features. Ophthalmology 1994;101:1030–5.

5 Aslanides IM, Libre PE, Silverman RH, et al.High frequency ultrasound imaging in pupillaryblock glaucoma. Br J Ophthalmol 1995;79:972–6.

Varicella zoster virus immune recoverystromal keratitis in a patient with AIDS

EDITOR,—The advent of potent antiretroviraltherapy has resulted in the recognition of thesyndrome of immune recovery uveitis inpatients with AIDS and a history of cytomega-lovirus (CMV) retinitis.1 Although the patho-genesis of this disease is poorly understood, itis hypothesised to be a consequence of animproved immune response to viral antigen

Figure 1 Gonioscopy, no angle structures seenin the right eye.

Figure 2 Gonioscopy, angle open to scleral spurwith lightly pigmented trabecular meshwork, lefteye.

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already present in the eye, with or withoutactive viral replication.2 We describe a case ofimmune recovery varicella zoster virus (VZV)stromal keratitis in a patient with AIDS.

CASE REPORT

A 37 year old man with AIDS (CD4 = 180cells × 106/l) developed right sided ophthalmiczoster and was treated with aciclovir (800 mgby mouth five times a day). Twelve days afteronset of the rash, topical prednisolone acetate(one drop every 2 hours) was prescribed totreat multiple anterior stromal corneal infil-trates. The keratitis promptly resolved, andthe corticosteroid drops were discontinuedwithin 3 weeks. Over the next 5 months hiscornea remained clear, but his HIV diseaseprogressed with the CD4 count dropping to anadir of 88 cells × 106/l. He was started onpotent antiretroviral therapy and prophylacticaciclovir 400 mg by mouth twice daily. Hiscornea remained clear for the next 2 years, butas his CD4 reached 398 cells × 106/l, hepresented with a complaint of redness of hisright eye. On examination he had multipleanterior stromal infiltrates of his right cornea,similar in appearance to the keratitis associ-ated with the previous episode of ophthalmiczoster (Fig 1). The recurrence of stromalkeratitis occurred 21⁄2 years after discontinua-tion of topical steroids and while the patientwas taking aciclovir prophylaxis.

COMMENT

VZV associated anterior stromal keratitis isthough to be due to immune recognition ofresidual viral antigen in the corneal stroma.3

The incidence of recurrent VZV stromal kera-titis has not been well characterised, nor havefactors which might precipitate recurrences.Recurrent keratitis related to immune systemactivation has been recognised followingadenoviral infection.4 In that case, subepithe-lial opacities associated with a previous

adenoviral follicular, keratoconjunctivitis re-curred 9 months following the original infec-tion in association with a severe upper respira-tory infection. In this report, a patient withAIDS and a history of ophthalmic zoster had arecurrence of anterior corneal stromal infil-trates almost 3 years after the initial skin erup-tion. Recurrence of the keratitis was not asso-ciated with skin or corneal epithelial diseaseand occurred despite aciclovir prophylaxis.Although the recurrence of the keratitis withthis patient’s immune recovery may be coinci-dental, the significant delay between his initialzosteriform eruption and the recurrence of hisstromal disease, as well as the close temporalrelation between the recurrence and thepatient’s immune recovery, suggest that this isa case of immune recovery zoster keratitis in apatient with ophthalmic zoster.

Other examples of immune recovery diseasein patients with AIDS receiving potent antiret-roviral therapy are well recognised. Immunerecovery uveitis has been described in patientswith previous CMV retinitis.1 2 In addition,immune recovery inflammation has been seenin association with previously clinically silentsystemic Mycobacterium avium complex infec-tion and in patients with cryptococcal menin-gitis.5 6 In at least one of the cases of meningi-tis, immune recovery inflammation wasthought to be directed against residual crypto-coccal antigen, as opposed to a delayedimmune response to viable organisms. Asadvances in AIDS therapy continue to im-prove the immune status of patients, immunerecovery inflammation may become increas-ingly recognised.

TPM is the recipient of a Research to Prevent Blind-ness (NY, NY) Lew Wasserman Award.

AYMAN NASERITODD P MARGOLIS

The Francis I Proctor Foundation and the Departmentof Ophthalmology, UCSF, Medical Center,

San Francisco, USA

Correspondence to: Dr Todd P Margolis, The Fran-cis I Proctor Foundation, UCSF, Medical Center,San Francisco, CA, 94143-0944, [email protected] for publication 15 June 2001

1 Zegans ME, Walton RC, Holland GN, et al.Transient vitreous inflammatory reactions asso-ciated with combination antiretroviral therapyin patients with AIDS and cytomegalovirusretinitis. Am J Ophthalmol 1998;125:292–300.

2 Holland GN. Immune recovery uveitis. OcularImmunology and Inflammation 1999;7:215–21.

3 Liesgang TJ. Corneal complications from herpeszoster ophthalmicus. Ophthalmology 1985;92:316–24.

4 Hodge W, Wohl T, Whitcher JP, et al. Cornealsubepithelial infiltrate recurrence sine adeno-virus. Cornea 1995;14:324–5.

5 Race EM, Adelson-Mitty J, Kriegel GR, et al.Focal mycobacterial lymphadenitis followinginitiation of protease-inhibitor therapy in pa-tients with advanced HIV-1 disease. Lancet1998;351:252–5.

6 Woods ML, MacGinley R, Eisen DP, et al. HIVcombination therapy: partial immune restitu-tion unmasking latent cryptococcal infection.AIDS 1998;12:1491–4.

Dipetalonema reconditum in the humaneye

EDITOR,—Human ocular invasion by non-human filarial parasites has been reported formore than 200 years.1 2 However, only justover a handful have actually been removed,described and identified in detail.3–6 Further-more, the Dipetalonema species that have beendescribed in three cases were thought to befrom the body cavity of the natural hosts—theporcupine and the beaver.4 5 7 8

This report describes a case of Dipetalonemareconditum (usually associated with caninefilariasis) in the human eye. It is noteworthythat this worm has morphological similaritiesto the canine heartworm Dirofilaria imitis,which in the past has been described in thehuman eye5 9 but not satisfactorily identified.10

CASE REPORT

A 62 year old white resident of suburban Victo-ria, Australia, presented with a red and irritatedright eye of 2 weeks’ duration. This was exacer-bated after a rural walking trip and did notimprove with topical lubrication. He also notedmild diplopia on extreme right gaze. On exam-ination, the visual acuity was 6/6 in the right eyeand 6/4 in the left. There was mild limitation ofright eye abduction. Localised bulbar conjunc-tival erythema and chemosis were noted infero-temporally in the right eye near the insertion ofthe lateral rectus. Slit lamp biomicroscopyrevealed a slithering, clear, thread-like mobilemass in the subconjunctival space of theinflamed area (Fig 1 and video report (see BJOwebsite)). Intraocular pressure and the rest ofthe ocular examination, including anterior andposterior segments, were unremarkable. Previ-ous history included pyrexia of unknown origin(PUO) and lancinating headaches 5 monthspreviously. Investigation results then of noteincluded erythrocyte sedimentation rate (ESR)96 mm in the first hour, C reactive protein(CRP) 411 mg/l, and trace proteinuria. Heimproved on intravenous ceftriaxone, metroni-dazole, and oral roxithromycin. He had alsohad another period of PUO and suVered withchronic Giardia infection.

The worm was removed following localisedperitomy under topical local anaesthesia usinglignocaine 2%, phenylephrine 10%, and phos-pholine iodide 12.5% (in an attempt toparalyse the worm). The specimen wasremoved alive and intact and sent in normalsaline for identification. Laboratory examina-tion revealed a worm measuring 32 mm inlength with morphological features consistentwith an unfertilised adult female D reconditum.

Patient investigations including thick andthin blood film, full blood count, ESR, CRPelectrolytes, liver function tests, and chest xray were all within normal limits. His pet dogswere found to be serologically negative forDipetalonema.

He was treated with oral mebenazole, topicalprednisolone acetate 1%, and chloramphenicolbefore the worm’s identification. Two weeksfollowing removal of the worm the diplopia hadresolved and residual fibrosis of the conjunctivaat the site of removal was noted.

COMMENT

Dipetalonema reconditum is a nematode that iscommonly found to be endemic in dogs’ sub-cutaneous tissues. Worldwide distribution

Figure 1 Slit lamp photograph of the temporalaspect of the patient’s right eye shows stromalinfiltrates with an intact corneal epithelium.

Figure 1 Subconjunctival infestation withD reconditum (arrow).

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includes the United States, Italy, and Africa.Its infestation in dogs, the only definitive host,is not clinically significant, although they maymanifest an elevated eosinophil and leucocytecount. This manifestation may result in falsepositives in test for circulating Dirofilaria imitismicrofilariae, also known as the dog heart-worm. The diVerentiation of these two wormsis important as Dirofilaria is pathogenic tocanines. Knott’s test11 is used to detect thesemicrofilaria serologically. Identification ofthese two adult worms is by their staining pat-terns with acid phosphatase: Dipetalonemastains evenly while Dirofilaria concentrates theacid phosphatase in two regions.

The Dipetalonema reconditum microfilariumaverages about 250–270 µm in length and4–4.5 µm in width with a round curved body,a distinguishing cephalic hook, and a bluntanterior end. Adult males average 13 mm inlength and females 17–32 mm.12

Dipetalonema has an indirect life cycle withdevelopment of infective larvae that arecarried by fleas (genus Ctenocephalides, Pulex),ticks (Rhipicephalus sanguineus), and lice(Linognathus). Dogs are infected when bittenby the fleas. The microfilarium circulates inthe blood as a first stage larva. The larval lifecycle lasts 61–68 days. The adult worm tendsto infect the subcutaneous tissues.12 Other lesscommon sites of infestation include the bodycavities and the kidneys.

Our case represents human subconjunctivalinfestation with an adult unfertilised D recondi-tum; this is, to our knowledge, the first report inthe literature. The literature reveals three otherdocumented cases of Dipetalonema speciesinfestation in the human eye; however, none ofthem was D reconditum. The chronic nature andslow onset of the symptoms implies that thisinfestation excited a slow and limited inflam-matory reaction within the ocular tissues.

There is no documented treatment for thisinfestation; ivermectin and milbemycin arerecommended. Other control measures in-clude flea, louse, and tick control. Hitherto,there has not been any documented publichealth significance. The incidence of D recon-ditum infestation in Australian dogs hassignificantly decreased since the introductionof the heartworm prevention programme asthe treatment for D immitis also eliminates theD reconditum. As the serology in our patient’sdogs was negative for D reconditum, one canpostulate he was infected via a flea bite in hisrural walking; however, we have no confirma-tive history. There is no documentation of theincidence of D reconditum in the Australianwildlife. As it is a self limiting condition, thedefinitive treatment is removal of the worm.

The authors thank Dr Harsha Sheorey, microbiol-ogist at St Vincent’s Hospital, Melbourne, for hishelp in identifying the organism.

T HUYNHJ THEAN

Royal Victorian Eye and Ear Hospital, Melbourne,Australia

R MAINICentre for Eye Research Australia

Correspondence to: Dr T Huynh, Royal VictorianEye and Ear Hospital, 32 Gisborne Street, EastMelbourne, Victoria 3002, AustraliaAccepted for publication 14 August 2001

1 Duke-Elder S, Perkins ES. Diseases of the uvealtract. System of ophthalmology. London: HenryKimpton, 1966:Vol 9.

2 Barkan A. A case of filarial medinensis in theanterior chamber. Arch Ophthalmol Otolaryngol1876;5:151.

3 Vodovozov AM, Jarulin GR, Djakonowa SW.Dirofilaria im Glaskörper des Menschen.Ophthalmologica 1973;166:88–93.

4 Burns RF, Helzerman R, Patrick M, et al.Intraocular filariasis (a motion picture). Trans AmAcad Ophthalmol Otolaryngol 1975;70:785–8.

5 Beaver PC, Meyer EA, Jarroll EL, et al.Dipetalonema from the eye of a man in Oregon,USA. A case report. Am J Trop Med Hyg 1980;29:367–72.

6 Samples JR, Beaver PC, Fraunfelder FT, et al. Atechnique for removal of filariasis of the anteriorchamber. Ophthalmic Surg 1988;19:124–7.

7 Cooke CT. Nematode worm in the anteriorchamber of the eye. Trans Pacific Coast Oto-ophthalmol Soc 1938;23:141–7.

8 Jones LT, Jordan LW, Sullivan NP. Intraocularnematode worms—report of a case and reviewof the literature. Arch Ophthalmol 1938;20:1006–12.

9 Moorehouse DE. Dirofilaria immitis: a cause ofhuman intra-ocular infection. Infection 1978;6:192–3.

10 Dissanaike AS, Ramalingam S, Fong A, et al.Filaria in the vitreous of the eye of man inpeninsula Malaysia. Am J Trop Med Hyg1977;26:1143–7.

11 Garcia LS, Bruckner DA. Procedures for detect-ing blood parasites. In: Diagnostic medical parasi-tology. American Society for Microbiology. 3rd ed.Santa Monica: Lynne Shore Garcia, ASM Press1997:706.

12 Internal parasites of dogs and cats: diagnosticmanual. Ciba-Geigy, p 3.

Immunohistochemical detection of heatshock protein 27 and Ki-67 in humanpterygium

EDITOR,—Pterygium, a disorder of the ocularsurface, consists of atrophic conjunctivalepithelium and a highly vascularised hyper-trophic and elastotic degenerated connectivetissue. Ultraviolet irradiation is considered tobe the principal environmental factor throughan eVect on the basal stem cells on the nasallimbus and activation of the fibroblasts.1–3 Pre-vious studies have detected chromosomalallelic loss in slightly over 50% of pterygia anda low frequency of microsatellite instability.4

However, no diVerences in cellular prolifera-tion between pterygial and normal conjuncti-val tissue have been detected with flowcytometry.5 On the other hand, a recent reportsuggests that pterygium may be the result of afailure of appropriate cellular apoptosis.6 Westudied 17 pterygia and 12 normal conjunc-tiva tissues from the nasal conjunctiva for theexpression of heat shock protein 27 (Hsp27)and cell proliferation associated nuclear anti-gen Ki-67.

Hsp27, a member of the small heat shockproteins family, is overexpressed in responseto many environmental and pathophysiologi-cal stresses including ultraviolet radiation,hormones, growth factors, infection andanoxia, and may be important in surveillanceof cell integrity acting as a “molecular chaper-one.”7 Recently it has been found that Hsp27constitutive overexpression in embryonic stemcells enhances the diVerentiation mediateddecreased rate of cell proliferation and pre-vents these cells from undergoing apoptosis.8

Specimens from 17 patients (seven malesand 10 females) (mean age 73.6) undergoingprimary pterygium excision and 12 healthypeople (three male and nine female) (meanage 77.7) undergoing cataract surgery werestudied. None of these patients had an

ophthalmic or systemic disease or used topicalor systemic medication. Informed consent wasobtained from patients participating in thisstudy. Formalin fixed, paraYn embeddedserial sections were immunostained usingmonoclonal antibodies against Hsp27 (cloneG3.1) and Ki-67 (clone MIB-1). Morphologi-cal assessment of immunostained tissuepreparations and manual cell counting ofimmunolabelled cells were performed. Hsp27and Ki-67 labelled cell fractions were ex-pressed in percentages.

Hsp27 cytoplasmic immunoreactivity wasobserved only in basal and suprabasal layers ofnormal conjunctival epithelium (mean 36.7)(Fig 1A). On the other hand, strong Hsp27immunopositivity in a high percentage of cellsin all layers of epithelium was found in allpterygia examined in this study (mean 88.1)(Fig 1B, Table 1). Ki-67 immunoreactivitywas confined in nuclei of scattered cells,located mostly in the basal layers of epithe-lium, in normal conjunctival epithelium(mean 5.2) as well as in pterygium (mean 9.4)(Table 1). No staining of Hsp27 and/or Ki-67was observed in substantia propria in normalconjunctiva tissues and pterygia but in ptery-gia, Hsp27 strong immunoreactivity wasobserved in endothelial cells and smoothmuscle cells of vessels. There was a statisticallysignificant diVerence of Hsp27 immunoreac-tivity between normal conjunctival epitheliumand pterygia (p<0.001) but no diVerence inKi-67 immunoreactivity (p=0.1) althoughsome pterygia contained large number of pro-liferative cells. There was no correlationbetween Hsp27 and Ki-67 labelling percent-age in pterygia (p=0.7) and normal conjunc-tiva (p=0.9).

Our findings concerning Ki-67 expressionare consistent with previous results suggestingthat pterygium may not be a disorder of cellproliferation.5 Overexpression of Hsp27 in all

Website extraA video report is on the BJO website. Itshows the undulating appearance of the rightbulbar conjunctival surface in a 62 year oldwhite male as the Dipetalonema reconditumremains mobile immediately before removalfollowing localised peritomy


Table 1 Immunohistochemical staining ofepithelial cells for Hsp27 and Ki-67 in pterygiaand normal conjunctiva

Hsp27immunoreactivity(% positive cells)

Ki-67immunoreactivity(% positive cells)

Pterygia1 100 52 100 23 100 204 90 15 100 156 100 17 100 28 70 19 95 210 50 111 50 2012 80 1513 97 1014 100 1515 90 1516 95 1517 80 20

Mean: 88.1(SD 16.84)

Mean: 9.4(SD 7.75)

Normal conjunctiva1 80 12 70 53 15 104 80 105 10 26 0 07 10 58 25 29 30 1010 60 711 50 512 10 5

Mean: 36.7(SD 29.72)

Mean: 5.2(SD 3.54)

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pterygia is interesting because this protein isknown to be related to diVerentiation whenexpressed in other epithelial tissues—forexample, skin,9 and in view of the recentreport that Hsp27 transient expression seemsessential for preventing embryonic stem cellsfrom undergoing apoptosis.8 Furthermore,Tan et al6 recently proposed that pterygiummay be related to faulty apoptosis. The role ofHsp27 in pterygium remains to be elucidatedsince Hsp27 is expressed in basal epithelialcells of normal conjunctiva, where the cells aremainly diVerentiating stem cells and in all lay-ers of epithelium in pterygia. Further studieswould provide valuable information regardingthe possible role of Hsp27, and the involve-ment of heat shock proteins generally in thepathogenesis of pterygium.

NIKOLAOS PHARMAKAKISDepartment of Ophthalmology, School of Medicine,

University of Patras, Patras 26500, Greece

MARTHA ASSIMAKOPOULOUDepartment of Anatomy, School of Medicine,

University of Patras

Correspondence to: Nikolaos Pharmakakis, MD,Department of Ophthalmology, School of Medicine,University of Patras, 26500 [email protected] for publication 14 March 2001

1 Moran DJ, Hollows FC. Pterygium andultraviolet radiation: a positive correlation. Br JOphthalmol 1984;68:343–6.

2 Kwok LS, Coroneo MT. A model for pterygiumformation. Cornea 1994;13:219–24.

3 Dushku N, Reid TW. Immunohistochemical evi-dence that human pterygia originate from aninvasion of vimentin-expressing altered limbalepithelial basal cells. Curr Eye Res 1994;13:473–81.

4 Spandidos DA, Sourvinos G, Kiaris H, et al.Microsatellite instability and loss of heterozy-gosity in human pterygia. Br J Ophthalmol 1997;81:493–6.

5 Karukonda SR, Thompson HW, Beuerman RW,et al. Cell cycle kinetics in pterygium at threelatitudes. Br J Ophthalmol 1995;79:313–17.

6 Tan DTH, Tang WY, Liu YP, et al. Apoptosis andapoptosis related gene expression in normalconjunctiva and pterygium. Br J Ophthalmol2000;84:212–16.

7 Ciocca DR, Oesterreich S, Chamness GC, et al.Biological and clinical implications of heatshock protein 27000 (HSP27): a review. J NatlCancer Inst 1993;85:1558–70.

8 Mehlen P, Mehlen A, Godet J, et al. Hsp27 as aswitch between diVerentiation and apoptosis inmurine embryonic stem cells. J Biol Chem 1997;272:31657–65.

9 Jantschitsch C, Kindas-Mugge I, Metze D, et al.Expression of the smal heat shock proteinHSP27 in developing human skin. Br J Derma-tol 1998;139:247–53.

Figure 1 (A) Normal conjunctiva: Hsp27 cytoplasmic immunoreactivity in basal and subrabasallayers of epithelium (×400). (B) Pterygium: Hsp27 positive cells in all layers of epithelium. Cells ofsubepithelial connective tissue are Hsp27 negative while vessels are Hsp27 positive (arrows) (×400).

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doi: 10.1136/bjo.85.11.1384e 2001 85: 1384Br J Ophthalmol

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