visual loss despite anticoagulation in radiation-induced optic neuropathy

Clinical and Experimental Ophthalmology

2004;

32

: 325–340

Letters to the Editor

_______________________________

Letters to the Editor

Clinical Case Notes

In vivo

confocal microscopy of Thygeson’s

superficial punctate keratitis

A

BSTRACT

A 56-year-old Chinese man diagnosed with Thygeson’s keratitis byclinical biomicroscopy was examined using a tandem scanning con-focal microscope. Among normal superficial epithelial cells, clumps ofmarkedly enlarged epithelial cells were identified. Multiple highlyreflective filamentary structures were observed in the deeper layers.Most of these lesions were linear; some demonstrated curled endsand others demonstrated branching lesions with ‘sprouts’. Noinflammatory cells were evident in the areas of corneal stromasampled.

In vivo

confocal microscopy may be helpful in the diagnosisof Thygeson’s superficial keratitis. To the best of our knowledge, wereport the first

in vivo

confocal images of focal desquamation ofepithelium and intraepithelial hyper-reflective linear lesions inEnglish literature.

Key words:

confocal microscopy, Thygeson’s superficial punc-tate keratitis.

I

NTRODUCTION

Thygeson’s superficial punctate keratitis is a disease entity firstdescribed by Phillips Thygeson in 1950.

1

The typical clinicalfeatures include bilateral greyish-white elevated conglomeratedintraepithelial dots, which are centrally located on the cornea. Theonset is insidious with periods of remission and exacerbation.

2

Thelongest course reported was up to 40 years.

3

The exact aetiology ofThygeson’s superficial punctate keratitis remains unknown. Associ-ation with viral infections such as adenovirus, herpes simplex andvaricella zoster virus have been suggested.

4,5

Topical steroid therapy has been the mainstay of treatment forthis condition. However, recurrences are common if steroids arewithdrawn and steroids may prolong the course of the diseaseprocess. Other treatment options include patching, therapeuticsoft contact lenses,

6

topical antivirals,

7,8

topical 2% cyclosporinA

9,10

and photorefractive keratectomy

11

have all been demon-strated to be beneficial. However, there is no consensus as to theoptimal treatment strategy for this disease.

Some of the histological features described include intracellularand intercellular oedema at different epithelial levels and exudatesunder the epithelium. In cases with acute inflammation, poly-morphonuclear leucocytes were seen in moderate amounts.

12

Inusing

in vivo

confocal microscopy, one can examine the histologicaldetails of this condition

in vivo

.

C

ASE

REPORT

A 56-year-old Chinese man developed intermittent grittiness inboth eyes, associated with photophobia and tearing, for 3 years.Slit-lamp microscopy revealed the typical features of Thygeson’ssuperficial punctate keratitis including fine elevated, conglomer-ated greyish white dots distributed over the central cornea (Fig. 1).The corneal lesions were bilateral without conjunctival inflamma-tion. The corneal sensation measured with cotton wool testing wasnormal in both eyes. The best-corrected visual acuity was 6/7.5 foreach eye. He was initially treated with topical lubricants with nosignificant improvement. We examined the patient during an acuteepisode of Thygeson’s keratitis with a tandem scanning confocalmicroscope (ASL-1000 Confocal Microscope OS-1, AdvanceScanning Ltd). The images were captured and analysed using theASL Image Analyser software and directly saved to the hard drive.

The superficial epithelial cells were normal in morphology,tightly adherent to neighbouring cells (Fig. 2a). The epithelial celllayer was first noted at the reading of 68

µ

m (counter set as zeroat the level of tear film) where the cell density was 1219

±

276cells/mm

2

(cell density was assessed using the automated counterOptimate 6.5 for Windows on 10 frames taken from the epitheliallayer). Amongst the normal cells, clumps of enlarged epithelialcells were identified (Fig. 2b). These were approximately twice thesize of the cells in Fig. 2a. The cell margins were hyper-reflective,which typically represents desquamating epithelial cells.

13

As the scanning motor advanced 20

µ

m deeper than the super-ficial epithelial layer, multiple highly reflective filamentary struc-tures were observed. The linear lesions were located within theepithelium and anterior stroma. Most of them had curled ends.Some were demonstrating two to three branched lesions that

Figure 1.

Clinical photo of left cornea demonstrating the elevatedgreyish-white conglomerated intraepithelial dots.

326 Letters to the Editor

resembled ‘sprouts’. In the background of these hyper-reflectivefilamentary lesions, multiple closely packed nuclei of basal epithe-lial cells were identified (Fig. 3a). These filamentous lesions werealso present in the anterior stromal layer (Fig. 3b) where nuclei ofkeratocytes were identified. Subepithelial nerve plexi were notclearly identified. No inflammatory cells were evident in theareas of corneal stroma sampled. The endothelium of the patientdemonstrated normal cell morphology and density (2852

±

156cells/mm

2

).The patient was subsequently prescribed conventional topical

steroid (Gutt 0.1% fluorometholone q.i.d.; FML, Allergan, Irvine, CA,USA) for 4 weeks. The patient was monitored by biomicroscopy at2-weekly intervals. The corneal lesions partially resolved over time.The intraocular pressures remained normal in both eyes throughoutthe treatment period. Unfortunately, the patient defaulted at 4 weeksfor further

in vivo

confocal microscopic examination.

D

ISCUSSION

According to the description of

in vivo

confocal microscopy onnormal corneal structures, the epithelial cells could either be

hyper-reflective or hypo-reflective.

12

The epithelial cells werenormally tightly adhering to the neighbouring cells. Previousconfocal images on normal cornea reported the epithelial thick-ness to be 50

µ

m.

14

In our patient, the superficial epithelial cellsdemonstrated the loss of intercellular adhesion, enlargement ofcell size and hyper-reflectivity. All of these features were believedto be signs of epithelial oedema and desquamation.

13

Theseclumps of desquamating epithelium may be responsible for theconglomerated whitish dots that one could see on slit-lampexamination.

The highly reflective linear lesions were identified at a level of110–130

µ

m deep. This position corresponded to the intraepithe-lial and subepithelial layers. We postulate that these lesions couldrepresent columns of linearly orientated columns of devitalizedepithelial cells, which were pushed upwards from the basal epithe-lial cell layer as in patients with filamentary keratitis. The locationand morphology were both consistent to our hypothesis. However,the typical filaments of filamentous keratitis are usually linearhyper-reflective lesions protruding into the tear film.

13

Intraepithe-lial filamentary lesions would make the diagnosis of filamentarykeratitis unlikely.

Figure 2.

(a)

Normal epithelial cells tightly adherent to neighbours.(b)

The presence of large epithelial cells with hyper-reflectivemargins.

Figure 3.

(a)

The presence of hyper-reflective ‘squiggly’ lesionsin the subepithelial layers (arrow indicates basal epithelial cells).(b)

The presence of hyper-reflective ‘sprout-like’ lesions in theBowman’s or anterior stromal layer of the cornea.

Letters to the Editor 327

In conclusion,

in vivo

confocal microscopy may be helpful in thediagnosis of Thygeson’s superficial keratitis. We report the firstimages of focal desquamation of epithelium and intraepithelialhyper-reflective linear filaments in English literature. The monitor-ing of confocal features invisible to conventional biomicroscopymay be helpful in determining treatment response.

A

CKNOWLEDGEMENT

Financially supported in part by the Action For Vision Eye Foun-dation, Hong Kong.

Lulu L Cheng

BMedSc FCOphthHK

,Alvin L Young

MMedSc FRCSI

, Angus KK Wong

FRCS

,Ricky WK Law

FRCS

and Dennis SC Lam

FRCS FRCOphth

Department of Ophthalmology and Visual Sciences, The ChineseUniversity of Hong Kong, Prince of Wales Hospital, Hong Kong

R

EFERENCES

1. Thygeson P. Superficial punctate keratitis.

JAMA

1950;

144

:1544–8.

2. Thygeson P. Clinical and laboratory observations of super-ficial punctate keratitis.

Am J Ophthalmol

1966;

61

: 1345.3. Tanzer DJ, Smith RE. Superficial punctate keratitis of Thyge-

son: the longest course on record?

Cornea

1999;

18

: 729–30.4. Braley AE, Alexander RC. Superficial punctate keratitis. Isola-

tion of a virus.

Arch Ophthalmol

1953;

50

: 147–54.5. Lemp MA, Chambers RW, Lundy J. Viral isolate in superficial

punctate keratitis.

Arch Ophthalmol

1974;

91

: 8–10.6. Goldberg DB, Schanzlin DJ, Brown SI. Management of

Thygeson’s superficial punctate keratitis.

Am J Ophthalmol

1980;

89

: 22–4.7. Tabbara KF, Ostler HB, Dawson C, Oh J. Thygeson’s super-

ficial punctate keratitis.

Ophthalmology

1981;

88

: 75–7.8. Nesburn AB, Lowe GH, Lepoff NJ

et al.

Effect of topicaltrifluridine on Thygeson’s superficial punctate keratitis.

Ophthalmology

1984;

91

: 1188–92.9. Holsclaw DS, Wong IG, Sherman M. Masked trial of topical

ciclosporin A in the treatment of refractory Thygeson’s punc-tate keratitis.

Invest Ophthalmol Vis Sci

1994;

35

: 1302.10. Reinhard T, Sundmacher R. Topical cyclosporin A in Thyge-

son’s superficial punctate keratitis.

Grafe’s Arch Clin Exp Ophthal-mol

1999;

237

: 109–12.11. Fite SW, Chodosh J. Photorefractive keratectomy for myopia

in the setting of Thygeson’s superficial punctate keratitis.

Cornea

2001;

20

: 425–6.12. Hogan MJ, Zimmerman LE.

Ophthalmic Pathology. An Atlas andTextbook.

Philadelphia: WB Saunders, 1962; 295–6.13. Böhnke M, Masters BR. Confocal microscopy of the cornea.

Prog Retinal Eye Res

1999;

18

: 553–628.14. Patel SV, McLaren JW, Hodge DO, Bourne WM. Normal

human keratocyte density and corneal thickness measurementby using confocal microscopy

in vivo

.

Invest Ophthalmol Vis Sci

2001;

42

: 333–9.

Tapioca melanoma of the iris mimicking a vascular tumour: a clinicopathological correlation

A

BSTRACT

Although vascular iris processes are usually benign, they may be aclinical manifestation of iris melanoma, and this should be consideredin the differential diagnosis. The case is reported of a 20-year-oldman with a highly vascularized tapioca melanoma of the left iriswithout involvement of the anterior chamber angle or ciliary body,but with observed growth tendency. Sector iridectomy was per-formed 2 months after first examination. In addition, two separatefloating tumour nodules were observed in the anterior chamberangle at 6 o’clock and were removed by aspiration. After 1 yearfollow up, no recurrence of melanoma cells was observed. In tapiocairis melanomas, diagnostic differentiation from congenital, inflamma-tory, vascular and neoplastic iris processes is required. Carefulbiomicroscopic examination of the iris in patients with vascular iristumours may help the ophthalmologist to identify malignant irismelanomas (tapioca type) and plan appropriate surgical treatment.

Key words:

histopathology, iris, malignant melanoma, tapiocamelanoma, tumour.

I

NTRODUCTION

Differentiation of vascular iris tumours with a tapioca-like mor-phology is important as they may represent malignant melanomaof the iris.

1,2

In such cases early diagnosis and surgical interventionoffer the best chance of avoiding severe threat to visual function.

1,2

C

ASE

REPORT

A 20-year-old man with red hair and blue irides was referredbecause of a vascularized iris tumour left with growth tendency.The lesion, which had been observed for the past 8 years, wasthought to be an iris papilloma (Fig. 1a). The unaided visual acuity(VA) was 6/6 bilaterally, and intraocular pressure was 13 mmHgbilaterally.

Slit-lamp biomicroscopy revealed a pale, highly vasculartumour with nasal extension from 8 to 10 o’clock. The tumourshowed a yellow-rose colour with a prominent tapioca-like surfacecomponent (Fig. 1b). Gonioscopy (Fig. 1c) and ultrasound biomi-croscopy (Fig. 2) revealed an unaffected anterior chamber anglebut two minute roundish tumour nodules in the chamber angle atthe 6 o’clock position. The anterior and posterior segments wereotherwise unremarkable. Blood–aqueous barrier was intact (laserflare photometry, 2.5 photon counts/ms; FC-1000, Kowa, Tokyo,Japan). Iris fluorescein angiography demonstrated prominentcorkscrew-like vascularization of the tumour with leakage (Fig. 3).

Because of continuing growth, the tumour was excised througha corneal incision from 6 to 10.30 o’clock via a basal sectoriridectomy. Intraoperatively, the two roundish tumour nodules inthe inferior chamber angle were aspirated with Charleux’s cannula.Postoperative best spectacle corrected VA was 6/6 left (+0.50 D).The 1-year follow-up examination found no residual tumour orrecurrence (Fig. 4).


Histopathology

The iris tissue measured 6

×

5

×

10 mm. The entire iris stroma wasreplaced by a non-pigmented tumour that showed plaque-likegrowth on the anterior iris surface and extended into the anteriorchamber. The tumour consisted of spindle-shaped cells with low-grade nuclear pleomorphisms and prominent nucleoli. Poor tumourcell cohesion was noted, especially near the iris surface. No mitoseswere observed (Fig. 5). Staining for S-100 and HMB-45 confirmeda melanocytic origin. Many large blood vessels were visiblebetween tumour cells. The histological diagnosis was malignantnon-pigmented spindle cell melanoma of the iris (tapiocamelanoma).

D

ISCUSSION

The term ‘tapioca’ melanoma is derived from an indigenous Brazil-ian language and refers to the pale granular starch material derivedfrom manioc tubers. Lorenz E Zimmerman classified this lesion

Figure 1.

(a)

Yellow-rose coloured tumour of the left iris withpapillomatous superficial structure. (b)

Slit-lamp photograph ofthe tapioca melanoma with dilated corkscrew vessels (arrows).(c) Gonioscopy showing a prominent multinodular tumourcomplex with no tumour spreading into the anterior chamber angle(arrowhead).

Figure 2.

Ultrasound biomicroscopy showing a solid lesioninvolving iris stroma (arrows). The ciliary body is free of tumour.

Figure 3.

Iris fluorescein angiography demonstrating the markedtumour vascularization.

Figure 4.

Left eye 3 months postoperatively showing large sectoriridectomy and clear lens.


histopathologically in 1959 as an atypical iris melanoma.

3

The term‘tapioca melanoma’ was introduced by Algernon Reese in 1972,because of the similarity of the pale tumour nodules to tapiocapudding.

3–5

Only a few case reports have been published since1972.

1,3–8

The diagnosis of tapioca melanoma is based on biomicroscopyand histopathology. It is typically found in younger patients (meanage 30 years) and presents as a pale pigmented or amelanotic iristumour with single or multiple prominent iris surface nodules.

1,5

Histopathologically, these tumours consist of poorly pigmentedspindle or epitheloid like malignant melanoma cells with a diffusegrowth pattern on the iris. Diverse clinical behaviour, prognosisand histopathology suggest that tapioca melanomas do not appearto be different from other iris melanomas. Indeed, they probablydo not represent a single entity, but rather are distinguished clini-cally due to their distinctive clinical picture in contrast to normaliris melanomas.

In our patient, a pronounced papillomatous surface with visibleblood vessels was observed (pseudopapilloma of the iris). Tapiocamelanoma may also be poorly adhesive. It is noteworthy that two

small tumour nodules separated from the tumour surface during a2-month period of observation and settled in the 6 o’clock positionof the anterior chamber angle, from where they could easily beaspirated and removed from the anterior chamber.

Iris melanomas still carry an excellent prognosis and metastaticdisease is extremely rare (3–5%).

9,10

The differential diagnosis includes juvenile xanthogranuloma,Lisch and Koeppe nodules, infectious granulomas, vascular tumours,leiomyoma, metastases, iris naevus syndrome, and varix nodules ofthe iris.

1,11,12

In contrast to naevi, iris melanomas show an irregular,loose surface. Iris melanomas are characterized by a pronouncedtumour vascularization with tendency of leakage as a sign ofdisturbed blood–aqueous barrier.

10

The clinical suspicion of tapioca melanoma depends on athorough biomicroscopic examination with special attention togonioscopy. Management involves careful clinical control withphotodocumentation. In cases where objective growth is demon-strated, total surgical removal may be indicated. A sector iridec-tomy, as in our patient, can be recommended only in cases wherethe anterior chamber angle is uninvolved. Otherwise, if the angleis involved, an

en-bloc

excision of the tumour and the adjacent tissueis the therapy of first choice.

1,2

Because of the poor adhesive pattern of iris tapioca melanomacells, a careful intraoperative examination of the anterior chamberis recommended to detect free-floating tumour nodules after thesector iridectomy. The simultaneous aspiration of separate tapiocamelanoma nodules can be one curative option to avoid tumourrecurrence.

A

CKNOWLEDGEMENTS

This study was supported in part by the Alexander von HumboldtFoundation, Bonn, Germany, and the Royal Australian and NewZealand College of Ophthalmologists (RMC).

Arne Viestenz

MD FICO

,

1

Robert M Conway

MD PhD FRANZCO

1,2

and Michael Küchle

MD FEBO

1

1

Department of Ophthalmology, University Erlangen-Nürnberg,Erlangen, Germany and

2

Save Sight Institute, University of Sydney,Sydney, New South Wales, Australia

REFERENCES

1. Hassenstein A, Bialasiewicz AA, von Domarus D, Schäfer H,Richard G. Tapioca melanomas of the iris: immunohisto-chemistry and report on two cases. Graefe’s Arch Clin Exp Oph-thalmol 1999; 237: 424–8.

2. Naumann GOH. Blockexzision intraokularer Prozesse. I.Tumoren der vorderen Uvea. Klin Monatsbl Augenheilkd 1975;166: 436–48.

3. Reese AB, Mund ML, Iwamoto T. Tapioca melanoma of theiris. Part 1. Clinical and light microscopy studies. Am J Ophthal-mol 1972; 74: 840–50.

4. Iwamoto T, Reese AB, Mund ML. Tapioca melanoma of theiris. Part 2. Electron microscopy of the melanoma cells com-pared with normal iris melanocytes. Am J Ophthalmol 1972; 74:851–61.

Figure 5. Histopathology. (a) Tumour plaque (arrows). (b) Melanomacells with loose cell-to-cell contacts (arrows).


5. Zakka KA, Foos RY, Sulit H. Metastatic tapioca irismelanoma. Br J Ophthalmol 1979; 63: 744–9.

6. Haddad R, Konrad K, Stur M. Fine structure of tapiocamelanoma of the iris. Doc Ophthalmol 1985; 61: 157–65.

7. Vittone P, Traverso C, Zingirian M, Bertagno R. Tapiocamelanoma of the iris: a contribution to the structure and itssignificance. Ophthalmologica 1983; 186: 125–35.

8. Wilson RS, Fraunfelder FT, Hanna C. Recurrent tapiocamelanoma of the iris and ciliary body treated with the argonlaser. Am J Ophthalmol 1976; 82: 213–17.

9. Shields JA, Shields CL. Hepatic metastases of diffuse irismelanoma 17 years after enucleation. Am J Ophthalmol 1988;106: 749–50.

10. Rummelt V, Naumann GOH, Naumann GOH, ed. Pathology ofthe Eye. Berlin: Springer, 1997; 743–8.

11. Küchle M, Naumann GOH. [Varix of the iris with spon-taneous regression.] Klin Monatsbl Augenheilkd 1992; 200: 233–6(in German).

12. Viestenz A, Berger T, Küchle M. Cutaneous melanoma metas-tasizing to the iris and choroid: a case report. Graefe’s Arch ClinExp Ophthalmol 2002; 240: 1036–8.

Optic neuropathy secondary to radio-therapy for nasal melanoma

ABSTRACT

Optic neuropathy is a rare but important complication of radiother-apy used in the treatment of cancers of the head and neck, usuallyresulting in rapidly progressive blindness in one or both eyes. Thecase is presented of a 77-year-old woman with bilateral opticneuropathy resulting in blindness, secondary to radiotherapy for amelanoma of the nasal cavity. The onset of optic neuropathyoccurred 9 months post-radiotherapy, at a cumulative dose of 6000rad. The left eye was first involved, with the right eye becominginvolved within 2 weeks. Despite treatment with oral anticoagulationand high dose intravenous methylprednisolone, there was progres-sive deterioration resulting in bilateral optic atrophy, with final visualacuities of perception of light in the right eye and no perception oflight in the left eye. This case demonstrates that oral anticoagulationwas ineffective in the treatment of progressive radiation-inducedoptic neuropathy.

Key words: anticoagulation, head and neck, neoplasms, opticneuropathy, radiotherapy.

INTRODUCTION

Radiation-induced optic neuropathy is a visually devastating com-plication of irradiation to neoplasms of the head and neck forwhich there is no known effective treatment. There are multiplereports in the literature of cases involving tumours in the nasalcavities or paranasal sinuses.1–4 A case is described of bilateralrapidly progressive optic neuropathy, with failure of treatmentwith anticoagulation and high dose intravenous corticosteroids,9 months post-radiotherapy.

CASE REPORT

A 77-year-old woman presented with a 2-week history of rapidlyprogressive visual loss, first in the left eye and then in the right,9 months after radiotherapy for a biopsy-proven melanoma of thenasal cavity. Due to the extensive field of origin and relatively poorprognosis with surgery, radiation therapy was administered withcurative intent at a cumulative dose of 60 Gy in 30 fractions.Radiotherapy was administered using 6-MV X-rays to the right andleft lateral face in addition to the anterior right face. The radiationfield included the right eye, the inner canthus of the left eye, theoptic chiasm, and the distal parts of the optic nerves. Shielding wasprovided over the right eye. There was a past history of hyper-tension, and excision of a localized breast carcinoma 5 yearsearlier.

Her ophthalmic examination showed a left relative afferentpupillary defect and intraocular pressures were normal in botheyes. There was left disc pallor and bilateral posterior vitreousdetachments (Fig. 1). Kinetic perimetry showed a small infero-temporal field remaining in her right eye and fields were unobtain-able in the left eye (Fig. 2). Visual acuity progressed from 6/6 to noperception of light (NPL) in the left eye over a period of 2 weeks,while the vision in the right eye progressed from 6/12 to 6/24 over1 week.

Magnetic resonance imaging (MRI) revealed contrast enhance-ment of both optic nerves from the optic foramina to the opticchiasm bilaterally (Fig. 3). These findings were concluded to beconsistent with radiation necrosis. In order to exclude otherpathology, including a paraneoplastic process, tumour infiltrationof the optic nerves, and other causes of vasculitis, a lumbar punc-ture was performed that demonstrated normal protein, glucose andcytology. In addition, an evaluation for vasculitis including rheu-matoid factor, erythrocyte sedimentation rate (ESR), anti-nuclearantigen (ANA) and extractable nuclear antigen (ENA), was nega-tive. Serum protein electrophoresis, syphilis serology, and carcino-embryonic antigen (CEA) were negative. A temporal artery biopsyshowed no evidence of temporal arteritis. Visual evoked responsesshowed a delayed but well defined response from the right eye,while no reproducible response was obtainable from the left eye.

The patient was treated with intravenous methylprednisolone(500 mg i.v. daily for 5 days) and anticoagulation with warfarin;however, the visual acuity on the right deteriorated to perceptionof light over the next 4 weeks. Subsequently, the patient wasplaced on prednisolone 20 mg orally daily, slowly tapered over2 months. Anticoagulation with warfarin, maintaining an inter-national normalized ratio (INR) of between 2.0 and 3.0 was contin-ued for the same period. After several months the pupils were fixedand dilated, and there was bilateral optic atrophy. MRI of the brain6 months after initial presentation again demonstrated enhance-ment of the proximal ends of both optic nerves as they join theoptic chiasm, and showed a decrease in the size of the optic nervesin this region from 3 mm to 2 mm diameter.

DISCUSSION

Irradiation of tumours in the nasal cavity or paranasal sinuses isknown to be associated with the rare but severe complication ofoptic neuropathy. Even in the absence of orbital invasion, it isoften necessary to include a portion of the contiguous orbit andmedial one-fourth to one-third of the eyeball in the irradiation


field because of the anatomic configuration of the sinuses andbecause of extension of subclinical disease through the thin bonywalls that separate the sinuses from the orbit.5

The initial diagnosis in this case was complicated by a pasthistory of a breast carcinoma 5 years previously. Carcinomatosis ofthe optic nerve was excluded in this case by negative cytology onlumbar puncture. Despite a clinical picture and MRI findingstypical of radiation-induced optic neuropathy, other causes ofneuropathy, in particular vasculitides, were excluded with appro-priate testing.

Radiation-induced optic neuropathy typically presents as visualloss, either as a field defect or loss of visual acuity, in one eyemonths to years after radiation therapy. This may be followedweeks to months later by loss of vision in the contralateral eye.This loss of vision is usually painless, but pain has been reported insome cases.6 In contrast to the swelling of the optic nerve head thatis seen in acute anterior ischaemic optic neuropathy, the ophthal-moscopic appearance of the optic disc is usually initially normal.7,8

The most important differential diagnoses to be excluded are ofrecurrent tumour causing optic nerve compression, or carcinoma-tosis of the optic nerve. In the past, surgery was sometimes requiredto confirm the diagnosis of radiation-induced optic neuropathy,and exclude recurrent tumour.

Gadolinium-DTPA (gadolinium-diethylenetriaminepentaaceticacid) is an intravenous paramagnetic contrast agent that shortens

proton relaxation times to increase the radio frequency signal inareas of breakdown of the blood–brain barrier, resulting in a brightsignal on T1-weighted images.9,10 In radiation-induced opticneuropathy, there is typically discrete enhancement of the intra-cranial optic nerve, but this is not specific and does not distinguishradiation from other causes of optic neuropathy. The MRI findingsin this case were typical, and interestingly contrast enhancementpersisted 6 months after initial presentation, even when the patienthad bilateral optic atrophy. There is a paucity of information in theliterature as to how long the contrast enhancement may persistafter the onset of radiation-induced optic neuropathy, but onepatient had residual enhancement with gadolinium on MRI13 months after the onset of visual loss.11

The exact pathogenesis of radiation-induced optic neuropathyis unclear. Pathological studies indicate a vascular cause, withradiation-induced capillary endothelial damage, ischaemic demy-elination, glial proliferation, microvascular occlusion andvasogenic oedema.8,12 Risk factors for radiation damage includehigh total radiation dose (especially greater than 60 Gy), highfractional dosage (especially greater than 2.6 Gy), overlappingtreatment fields, adjunctive chemotherapy and pre-existing com-promise to the vasculature, including hypertension and diabetesmellitus.5,13–15

Radiation-induced optic neuropathy usually results in profoundblindness, and there are no proven effective treatments. Hyper-

Figure 1. Fundi at time of presentation: (a) left eye; (b) right eye.

Figure 2. Goldmann visual fields of right eye showing smallremaining inferotemporal field: (a) at presentation; (b) at 1 monthafter presentation.


baric oxygen has been proposed, but results are inconsistent andthere are no large double masked prospective trials assessing itsefficacy.16–18 The rationale for its use is based on the probableischaemic pathogenesis of radiation-induced optic neuropathy.Anecdotal evidence suggests that hyperbaric oxygen treatmentmay be more effective if instituted as soon as possible after theonset of visual loss, especially if given within 2 days.16 Systemiccorticosteroids are ineffective in the treatment of radiation-induced

optic neuropathy9,16 and the lack of response to steroids in ourpatient supported this finding. Anticoagulation was used in thiscase, again with little effect. There is evidence to suggest thatanticoagulation may be an effective treatment for radiation-induced injury to the central nervous system, but it is unclearwhether this can be extrapolated to radiation-induced optic neuro-pathy.19

In conclusion, radiation-induced optic neuropathy is a rare butimportant complication of irradiation in the treatment of tumoursof the nasal cavity and paranasal sinuses which can be readilydiagnosed on MRI with gadolinium contrast. No proven effectivetreatment is currently available and optic neuropathy usuallyresults in progressive blindness.

Helen Garrott MB BS1 and Justin O’Day FRANZCO2

1Royal Victorian Eye and Eye Hospital and2St Vincent’s Medical Centre, Melbourne, Victoria, Australia

REFERENCES

1. Singh J, Sushma V. Postirradiation optic neuropathy in antralcarcinoma. J Clin Neuro-Ophthalmol 1984; 4: 103–4.

2. Shukovsky LJ, Fletcher GH. Retinal and optic nerve complica-tions in a high dose irradiation technique of ethmoid sinus andnasal cavity. Radiology 1972; 104: 629–34.

3. Chan RC, Shukovsky LJ. Effects of irradiation on the eye.Radiology 1976; 120: 673–5.

4. Ross HS, Rosenberg S, Friedman AH. Delayed radiationnecrosis of the optic nerve. Am J Ophthalmol 1973; 76: 683–6.

5. Parsons JT, Bova FJ, Mendenhall WM, Million RR,Fitzgerald CR. Response of the normal eye to high dose radio-therapy. Oncology 1996; 10: 837–47.

6. Parsons JT, Bova FJ, Fitzgerald CR, Mendenhall WM,Million RR. Radiation optic neuropathy after megavoltageexternal-beam irradiation: analysis of time-dose factors. Int JRadiat Oncol Biol Phys 1994; 30: 755–63.

7. Guy J, Fitzsimmons J, Ellis EA, Mancuso A. Gadolinium-DTPA-enhanced magnetic resonance imaging in experimentaloptic neuritis. Ophthalmology 1990; 97: 601–7.

8. Kline LB, Kim JY, Ceballos R. Radiation optic neuropathy.Ophthalmology 1985; 92: 1118–26.

9. Zimmerman CF, Schatz NJ, Glaser SG. Magnetic resonanceimaging of radiation optic neuropathy. Am J Ophthalmol 1990;110: 389–94.

10. Guy J, Mancuso A, Quisling RG, Beck R, Moster M. Gadolinium-DTPA-enhanced magnetic resonance imaging in optic neuro-pathies. Ophthalmology 1990; 97: 592–600.

11. McClellan RL, El Gammal T, Kline LB. Early bilateral radiation-induced optic neuropathy with follow-up MRI. Neuroradiology1995; 37: 131–3.

12. Rottenberg DA, Chernick NL, Deck MDF, Ellis F, Posner JB.Cerebral necrosis following radiotherapy of extracranial neo-plasms. Ann Neurol 1977; 1: 339.

13. Jiang GL, Tucker SL, Guttenberger R et al. Radiation-inducedinjury to the visual pathway. Radiother Oncol 1994; 30: 17–25.

14. Di Chiro G, Oldfield E, Wright DC et al. Cerebral necrosisafter radiotherapy and/or intraarterial chemotherapy for braintumours: PET and neuropathologic studies. AJR Am J Roentgenol1988; 150: 189–97.

Figure 3. Magnetic resonance images (MRI) at presentationshowing gadolinium-contrast enhancement of optic nerves(arrows). (a) Axial MRI (non-fat suppressed) through orbits. (b) T1-weighted coronal MRI.


15. Fishman ML, Bean SC, Cogan DG. Optic atrophy followingprophylactic chemotherapy and cranial radiation for acutelymphocytic leukaemia. Am J Ophthalmol 1976; 82: 571–6.

16. Borruat FX, Schatz NJ, Glaser JS, Feun LG, Matos L. Visualrecovery from radiation-induced optic neuropathy: the role ofhyperbaric oxygen therapy. J Clin Neuro-Ophthalmol 1993; 13:98–101.

17. Guy J, Schatz NJ. Hyperbaric oxygen in the treatment ofradiation-induced neuropathy. Ophthalmology 1986; 93: 1083–8.

18. Roden D, Bosley TM, Fowble B et al. Delayed radiation injuryto the retrobulbar optic nerves and chiasm: clinical syndromeand treatment with hyperbaric oxygen and corticosteroids.Ophthalmology 1990; 97: 346–51.

19. Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW,Schold SC Jr. Treatment of radiation-induced nervous systeminjury with heparin and warfarin. Neurology 1994; 44: 2020–27.

Visual loss despite anticoagulation in radiation-induced optic neuropathy

ABSTRACT

Radiation therapy to the brain may produce necrosis and loss offunction months after completion of the treatment. The case ispresented of a 62-year-old man who developed radiation-inducedoptic neuropathy 2 years after treatment for a glioma of the lefttemporal lobe, despite being on anticoagulation therapy. Althoughanticoagulation appears to be beneficial in cerebral radiation necro-sis, its usefulness in the treatment of radiation-induced optic neurop-athy is unclear.

Key words: anticoagulation, optic neuropathy, radiation therapy,radiotherapy.

INTRODUCTION

Radiation therapy to the brain may produce necrosis and loss offunction months after completion of the treatment. A variety oftreatments, including systemic corticosteroids and hyperbaricoxygen administration, have failed to consistently halt or reversethe process. Anticoagulant therapy has been suggested as a viabletreatment for radiation damage to the brain.1 We report a patientwho developed radiation optic neuropathy while on coumadin.

CASE REPORT

A 62-year-old man presented complaining of visual loss in the lefteye 5 days before examination. He had been diagnosed with agrade II glioma of the left temporal lobe and underwent a lobec-tomy via left frontotemporal craniotomy in April 1997, 2 yearspreviously. There was no involvement of the extracranial opticnerve by the tumour itself. Chemotherapy with two cycles ofprocarbazine and vincristine was initiated shortly after surgery.During this time the patient developed a pulmonary embolism. AGreenfield filter was placed and he was begun on coumadin. Hisinternational normalized ratio (INR) was maintained between 1.8

and 2.5. In December 1997, after the chemotherapy treatment wascomplete, radiotherapy consisting of the administration of 54 Gyof radiation to the area began. This was delivered through opposedlateral ports to 45 Gy in 25 fractions followed by a cone-downboost weighted 2 : 1 left to right to a total dose of 54 Gy in 30fractions over 51 elapsed days.

Painless visual loss in the left eye began in March 1999. Hisprevious ophthalmological examinations were normal. Neuro-ophthalmologic examination revealed vision of 6/7.5 right and6/120 left. He could identify all the Ishihara colour plates with theright eye but none with the left. There was a left relative afferentpupillary defect. Left kinetic perimetry revealed a central scotomawith a residual island of vision inferiorly (Fig. 1a). A superiortemporal defect was plotted for the right eye (Fig. 1b).

The left optic disc was pale. Except for bilateral pseudophakia,the remainder of the examination was normal. Magnetic resonanceimaging revealed enhancement of the left intracranial optic nerveafter gadolinium administration, consistent with radiation damage(Fig. 2). There was no tumour recurrence. No improvement invision occurred. His INR was maintained between 1.8 and 2.5.

DISCUSSION

Radiation-induced optic neuropathy (RON) is a devastating com-plication that may occur between 3 months to 8 years after radia-tion treatment, with a peak incidence at 1.5 years. The risk of RONincreases significantly with doses over 50 Gy, higher doses perfraction (greater than 1.9 Gy) and increasing age.2,3 Other factorsthought to be important include the presence of optic nerve dys-function at the beginning of radiation treatment (optic nerve com-pression and vascular compromise may lower the optic nervethreshold to radiation damage), concomitant treatment withchemotherapy, and diabetes mellitus.4 The aetiology is endothelialnecrosis.

The use of anticoagulation is controversial and has never beenshown to be effective in RON. The mechanism of action incerebral radiation damage is speculated to be due to the reversal ofor protection against small vessel endothelial damage. Exactly howis not known.

Radiation-induced optic neuropathy typically presents asretrobulbar neuritis with rapid painless visual loss. The diagnosisis made by observing no abnormality on unenhanced T1 and T2-weighted images, but enhancement of the anterior visual pathwayon T1-weighted enhanced images.5 The efficacy of various treat-ment modalities is controversial. Administration of systemiccorticosteroids fails to halt the visual loss in a consistent manner.Hyperbaric oxygen therapy was deemed to be ineffective in thetreatment of 13 patients with radiation induced optic nerve orchiasmal visual loss.6 Treatment earlier in the course of the disorderwith higher doses may be more effective.7

Treatment of radiation-induced nervous system injury withanticoagulation therapy resulted in some recovery of function infive of eight patients with cerebral radionecrosis.1 However, noneof these patients had any visual dysfunction. Barbosa et al. docu-mented no improvement following anticoagulation treatment in apatient with bilateral radiation optic neuropathy.8 Landau andKiller reported a patient who developed visual loss due to radiationnecrosis of the optic nerve despite being on anticoagulation duringradiation treatment as well as when the visual loss occurred.9


Our patient received chemotherapy with radiation, whichincreases the risk of radiation injury. He was not on anticoagula-tion therapy at the time of radiation. However, his visual lossbegan and continued to deteriorate while he was on full anticoag-ulation. Considering the present patient and others with visualloss,4,5 it appears possible that anticoagulation therapy may not bean effective treatment for radiation injury to the anterior visualpathways.

Radiation-induced optic neuropathy is an uncommon but not arare condition. Although anticoagulation appears to be beneficialin cerebral radiation necrosis, its usefulness in the treatment ofRON is unclear. This is the second reported patient who devel-oped the disorder while on anticoagulants and should promptother physicians with similar or contrary experiences to recordtheir observations, so that evidence-based guidelines for treatingthis disorder may be established.

Figure 1. (a) Left kinetic visual field showing a central scotoma and small inferior island of vision. (b) Right static visual field illustrating asuperior temporal defect.

Figure 2. Coronal magnetic resonance images of left optic nerve (arrow): (a) before gadolinium; and (b) after gadolinium, showing enhancement.


Helen V Danesh-Meyer FRANZCO,1,2

Peter J Savino MD2 and Robert C Sergott MD2

1Department of Ophthalmology, University of Auckland, Auckland,New Zealand and 2Wills Eye Hospital, Neuro-ophthalmology Service,

Thomas Jefferson Medical College, Philadelphia, PA, USA

REFERENCES

1. Glantz MJ, Burger PC, Friedman AH et al. Treatment ofradiation-induced nervous system injury with heparin andwarfarin. Neurology 1994; 44: 2020–27.

2. Jiang GL, Tucker SL, Guttenberg R et al. Radiation-inducedinjury to the visual pathway. Radiother Oncol 1994; 30: 17–25.

3. Parsons JT, Bova FJ, Fitzgerald CR et al. Radiation opticneuropathy after megavoltage external-beam irradiation:analysis of time-dose factors. Int J Radiat Oncol Biol Phys 1994;30: 755–63.

4. Peck FC, Ju McGovern ER. Radiation necrosis of the brain inacromegaly. J Neurosurg 1966; 25: 536–42.

5. Hudgins PA, Newman NJ, Dillon WP, Hoffman JC.Radiation-induced optic neuropathy: characteristic appear-ances on gadolinium-enhanced MR. Am J Neuroradiol 1992; 13:235–8.

6. Roden D, Bosley TM, Fowble B et al. Delayed radiation injuryto the retrobulbar optic nerves and chiasm. Ophthalmology1990; 97: 346–35.

7. Guy J, Schatz NJ. Hyperbaric oxygen in treatment ofradiation-induced optic neuropathy. Ophthalmology 1986;93: 1083–8.

8. Barbosa AP, Cavalho D, Marrques L, Monteiro M. Inefficiencyof the anticoagulant therapy in the regression of radiation-induced optic neuropathy in Cushing’s disease. J EndocrinolInvest 1999; 22: 301–5.

9. Landau K, Killer HE. Radiation damage. Neurology 1996; 46:889.

Progressive visual loss in a patient with presumed temporal arteritis despite treatment: how to make the diagnosis

ABSTRACT

Giant cell (temporal) arteritis is a severe potentially fatal systemicvasculitis characterized by focal involvement of the cranial arteriesresulting in ischaemic arterial occlusion. The case is presented ofa 75-year-old woman with presumed giant cell arteritis andnormal bilateral temporal artery biopsies. Despite a seeminglyadequate course of systemic steroid therapy, the patient devel-oped sudden catastrophic vision loss. Cerebral angiography andultrasonography were useful investigations to determine the mostappropriate artery to biopsy to confirm the diagnosis of giant cellarteritis.

Key words: biopsy, giant cell arteritis, steroids.

INTRODUCTION

Giant cell (temporal) arteritis is a severe potentially fatal systemicvasculitis characterized by focal involvement of the cranial arteriesresulting in ischaemic arterial occlusion. The typical ophthalmicpresentation is sudden catastrophic visual loss from ischaemic opticneuropathy or central retinal artery occlusion and is a classicophthalmic emergency. The diagnosis is usually confirmed histo-logically with superficial temporal artery biopsy.

The case is presented here of a 75-year-old woman with pre-sumed giant cell arteritis who presented with normal temporalartery biopsies and who, despite treatment, developed suddencatastrophic vision loss.

CASE REPORT

A 75-year-old woman presented with deterioration of vision, head-aches and generalized malaise. She had previously diagnosedatrophic age-related macular degeneration in each eye with visionof right 6/9 and left 6/12. She was otherwise well. At presentationvisual acuity was reduced to 6/24 in each eye. There was noafferent pupillary defect, intraocular pressures were 14 mmHg andfundoscopy revealed macular degenerative changes and mild bilat-eral disc swelling. Erythrocyte sedimentation rate was 40 mm/h(normal <30 mm/h). C-reactive protein was not recorded.

A clinical diagnosis of giant cell arteritis was made and thepatient was commenced on 80 mg of oral prednisolone. The con-stitutional symptoms resolved and the disc appearance returned tonormal. Left and subsequent right temporal artery biopsies wereboth normal. Prednisolone was then slowly tapered to 20 mg daily.

Six months later, while still on prednisolone 10 mg, the patientdeveloped sudden profound vision loss, accompanied by jaw clau-dication, headache, scalp tenderness and a history of migratinglumps on the scalp. Vision was vague light perception right eye andhand movement only left eye. There was tenderness in the regionof the previous temporal artery biopsies. No nodules were palpableover the scalp. On fundoscopy both discs were pallid and swollen.Erythrocyte sedimentation rate (ESR) was 60 mm/h and C-reactiveprotein was 16 mg/L (normal <8 mg/L).

The patient was admitted to hospital and treated with intrave-nous methylprednisolone within 12 h of the onset of visual loss.Methylprednisolone was given at 1 g daily for 3 days followed byoral prednisolone 80 mg daily for presumed giant cell arteritis.Following neurological consultation a cerebral angiogram wasperformed which showed occlusion of each temporal artery, totalocclusion of the right ophthalmic artery and decreased flow in theleft ophthalmic artery. Each occipital artery showed narrowing andbeading typical of that seen in arteritis.

An ultrasonically guided right occipital artery biopsy was sub-sequently performed by the neurosurgeons, which confirmedhistologically the diagnosis of giant cell arteritis. Vision in the lefteye improved to 6/24 with a central visual field of about 10°,although the right eye was unchanged at perception of light. Thepatient remains on prednisolone 10 mg daily and has been stablefor 12 months of follow up.

DISCUSSION

The typical ophthalmic presentation of giant cell arteritis is suddencatastrophic visual loss from ischaemic optic neuropathy or central


retinal artery occlusion. Giant cell arteritis is commoner in women,occurs more frequently with increasing age and is extremely rarebefore age 50.1

Giant cell arteritis is exquisitely sensitive to corticosteroid treat-ment and progression of visual loss on treatment is rare.2 Patientsrequire many months to years of therapy before the disease burnsout.3 Long-term corticosteroid therapy is hazardous especially inolder patients and it is essential to confirm a clinical diagnosishistologically if possible.4 A negative temporal artery biopsy mayoccur in up to 15% of patients with clinical features of giant cellarteritis and adequate biopsies of each temporal artery should beobtained to confirm a clinical diagnosis.5 A recent retrospective

study of bilateral temporal artery biopsies in 91 patients withtemporal arteritis reported that the histology was identical in eachartery in 90 of the 91 patients,6 suggesting that bilateral biopsiesare not necessary in most patients.

When the diagnosis remains uncertain, as in this patient, adecision needs to made whether to continue steroid therapy orcease steroid therapy and pursue other causes of visual loss. Thispatient is typical of those in whom it is difficult to decide upon thebest management. Despite a seemingly adequate course of systemicsteroid therapy, the patient developed sudden catastrophic visionloss on low-dose steroid therapy. In this patient, cerebral angiogra-phy and ultrasonography were useful investigations to determinethe most appropriate artery to biopsy to confirm the diagnosis ofgiant cell arteritis. This case illustrates the challenges facing theclinician managing patients with temporal arteritis and ability of anoccipital artery biopsy to confirm the diagnosis in atypical giantcell arteritis.

Bogna Zborowska MB BS,1 Jonathan Ell FRACP,4

Martin McGee-Collett FRACS,2 Richard Scolyer FRCPA3

and Peter J McCluskey MD FRANZCO1

Departments of 1Ophthalmology, 2Neurosurgery and3Anatomical Pathology, and 4Institute of Clinical Neuroscience,

Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

REFERENCES

1. Ghanchi FD, Dutton GN. Current concepts in giant cell (tem-poral) arteritis. Surv Ophthalmol 1997; 42: 99–123.

2. Aiello PD, Trautman JC, McPhee TJ et al. Visual prognosis ingiant cell arteritis. Ophthalmol 1993; 100: 550–55.

3. Matteson EL, Gold KN, Bloch DA, Hunder GG. Long-termsurvival of patients with giant cell arteritis in the AmericanCollege of Rheumatology giant cell arteritis criteria cohort.Am J Med 1996; 100: 193–6.

4. Huston KA, Hunder GG. Giant cell (cranial) arteritis: a clinicalreview. Am Heart J 1980; 100: 99–105.

5. Allison MC, Gallagher PJ. Temporal artery biopsy and corticos-teroid treatment. Ann Rheum Dis 1984; 43: 416–17.

6. Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC,Sergott RC. Low diagnostic yield with second biopsies insuspected giant cell arteritis. J Neuro-Ophthalmol 2000; 20:

213–15.

Anterior uveitis in a child with Takayasu’s arteritis

ABSTRACT

Takayasu’s arteritis is a rare idiopathic arteriopathy that producesnarrowing and eventually closure of affected blood vessels. Ocularsymptoms typically occur late in the disease process in thoseindividuals who have severe involvement of the aortic arch and thecarotid arteries. Visual loss typically occurs as a result of eithersystemic hypertension or concomitant ocular hypo-perfusion. We

Figure 1. Left external carotid angiogram showing multiple areasof narrowing of the occipital artery.

Figure 2. Right occipital artery showing luminal narrowing,transmural inflammation and intimal fibromyxoid change (H&E;original magnification ×40).


describe an unusual case of Takayasu’s arteritis presenting in a childwho complained of painful blurred vision. In this individual, nocarotid artery disease was identified on vascular imaging and noevidence of impairment of ocular perfusion was demonstrable.Vision loss in this instance was due to anterior uveitis and cystoidmaculopathy. These are atypical and rarely described features ofTakayasu’s arteritis. The patient responded well to anti-inflammatorytreatment and his symptoms resolved. The clinical significance ofthese findings are discussed and the relevant literature reviewed.

Key words: cystoid maculopathy, Takayasu’s arteritis, uveitis.

INTRODUCTION

Takayasu’s arteritis (TA) is an inflammatory arteriopathy that gen-erally affects the larger vessels of the neck, thorax and abdomen.1

The disease is rare but is seen more frequently now in Australia dueto increased immigration of individuals with Asian or Africanheritage, in whom it is more common.2,3 In advanced disease,chronic ocular ischaemia can result in cataract, optic neuropathy,neovascular glaucoma, vitreous haemorrhage and retinal detach-ment, which can blind affected individuals.4,5

CASE REPORT

A 12-year-old boy of Asian extraction presenting with malaise,vomiting and fever was later found on examination to be hyperten-sive (180/110 mmHg). A complete physical examination at thistime was otherwise found to be normal. Urine and blood biochem-ical analysis identified only mild renal impairment. The hyper-tension improved after medical treatment that included nifedipine,atenolol, prazosin and captopril.

Three weeks later he presented again, this time complaining ofblurred vision in both eyes and photophobia. Ocular examinationshowed a visual acuity of 6/6 in both eyes and bilateral non-granulomatous uveitis. The intraocular pressure was 14 mmHg inboth eyes and dilated examination of the posterior segment wasnoted to be normal. He was treated with q.i.d. topical steroid

(prednisolone acetate 1%) and cycloplegic medication t.d.s.(homatropine 2%). Initially this proved to be successful and theocular symptoms disappeared after a few days. Topical medicationswere discontinued by 3 weeks and no uveitis screening was per-formed at this time.

He presented again with a short history of increasing visual lossand ocular discomfort about 2 months later. Visual acuity nowmeasured only 6/36 in the right eye and 6/24 in the left eye. Ocularexamination identified severe bilateral fibrinous uveitis in theanterior chamber. Fundal examination showed bilateral cystoidmacular oedema without evidence of vitreous activity.

Examination also identified a decrease in the amplitude of thebrachial artery pulsation between the two arms and a bruit overboth subclavian arteries. A full medical and radiological work-upfor arteritis was therefore undertaken.

Magnetic resonance angiography, nuclear medicine scanningand Doppler ultrasound were performed to assess blood flow of allthe major vessels. Bilateral renal, subclavian and vertebral arterynarrowing was identified, which was consistent with TA. However,the aortic arch and the carotids were normal (Fig. 1). Non-specificserological markers (ESR/CRP) were both raised suggesting aninflammatory aetiology. A uveitis screen including chest X-ray,ACE, ANCA, ANA was normal. In addition serology for HLA-B27,rheumatoid factor, Toxocara and toxoplasma was also negative. Allfour antihypertensive agents utilized were searched via Medline forany known association with fibrinous uveitis and none was identi-fied. Audiometry was also performed to exclude subclinical sensori-neural hearing loss (as seen in Cogan’s syndrome) and this was alsofound to be normal. On the basis of the clinical and radiologicalfindings and using the American College of RheumatologyCriteria6 a diagnosis of TA was made.

Fluorescein angiography was also performed and showed nodelay in the arm-to-retina circulation time and normal arteriovenousfilling time (Fig. 2). On the late films mildly dilated juxta-fovealcapillaries showed evidence of leakage confirming the clinicalevidence of cystoid macular oedema (Fig. 3).

The patient was treated with balloon angioplasty to improveblood flow through the renal arteries. The ocular and systemicsymptoms were felt to be primarily inflammatory in nature. The

Figure 1. Normal arteriovenous phase of the fluorescein angio-gram of the left eye. Lamellar flow is observed to occur in veins ofnormal calibre 2 s after complete arterial filling.

Figure 2. Late transit of the fluorescein angiogram of the left eyeshows optic disc leakage and multiple spots of leakage in the macula.


patient was therefore treated with systemic prednisolone 2 mg/kgper day, oral cyclophosphamide 600 mg weekly and 150 mg aspirinon alternate days in conjunction with topical steroid therapy.

Visual acuity showed a gradual return to normal by 3 monthsand repeat vascular imaging has demonstrated greatly improvedblood flow through the renal arteries. It is now 2 years since hisoriginal presentation and he is currently maintained on pred-nisolone 5 mg/day and methotrexate 20 mg/week. Several inter-mittent flare-ups in anterior chamber activity have occurred andeach has responded well to a brief doubling of the prednisolonedose and topical therapy as necessary. His current visual acuity is6/7.5 in both eyes.

DISCUSSION

Takayasu’s arteritis usually produces symptoms in affected individ-uals due to reduced blood flow to end organs such as the kidney,heart, brain and eye. It is a rare vascular disease with an inflamma-tory aetiology and is characterized by segmental stenoses of theaorta and its major branches.1 Involvement of the renal arteries inTA produces hypertension of varying severity and involvement ofthe carotid arteries usually causes ischaemic ocular symptoms. Themajor differential diagnosis is with fibromuscular dysplasia, whichcan also produce thickening and stenosis of large vessels and hassimilar clinical features in advanced cases.2

There are also numerous inflammatory vasculitides that unlikeTA have a tendency to involve small and medium sized vessels andthat also produce ocular symptoms. These include sarcoidosis,Wegener’s granulomatosis and Cogan’s syndrome. A normal vascu-litic screen and audiology, showing no evidence of sensorineuraldeficit, will in most cases exclude these conditions. However,patients with coexistence of TA and vasculitis such as sarcoid havebeen reported.7–9

Takayasu, a Japanese ophthalmologist, was the first to describeTA in 1908. He identified a patient with vision loss secondary toischaemia of the central retinal artery.5 Subsequently this earlydefinition has been broadened to include any full thickness,chronic granulomatous inflammation of unknown aetiology involv-ing the aorta and its major branches.6 The cause still remains

unknown but an autoimmune mechanism that involves both defec-tive T-cell and humoral function at the level of the artery wall hasbeen postulated.7,10

Takayasu’s arteritis occurs throughout the world, but is rela-tively more common in Asian countries. The incidence in countriessuch as Australia is not known, but in a recent review in the USAit was 2.6/106 per year.9 The incidence is thought to be increasingdue to the current migration trends of most western countries.2

Ethnicity also appears to play a significant role in the age of onsetTA, its clinical features and its final outcome.1,7,10 The mostcommon period for symptoms to occur is in young adults betweenthe second and fourth decade. Visual aberrations have been identi-fied in up to 30% of patients with advanced disease.5,7 Systemiccomplications of TA also observed in late disease such as stroke,heart failure and myocardial infarction have a mortality of about10%.2,3

Over 32% of presentations have been found to occur in thepaediatric age group.3 Children with TA usually develop reno-vascular hypertension secondary to renal artery stenosis. Thisoccurs late in the disease process when the early inflammatorysymptoms have subsided. However, they rarely develop the ocular,cerebral and cardiac ischaemia that occur commonly in adults withend-stage TA.3,5,7

Vascular imaging remains the best method to identify theextent of vessel damage and assess the distribution of the disease.1

However, the degree of lumenal patency may not correlate withthe inflammatory status of the vessel wall adding to diagnosticdifficulty in early presentations of TA.1,6,10 Modalities that do notutilize ionizing radiation, such as Doppler ultrasound and magneticresonance angiography, are often preferred in the work-up ofchildren.3,7

Treatment with oral steroids over a prolonged course with agradual taper is necessary in most individuals. In addition, up to40% may require adjunctive treatment with cytotoxic medicationto prevent relapse.3,6,7 These medications can affect the normalgrowth and development of children, hence the necessity to accu-rately differentiate TA from other clinical conditions, such asfibromuscular dysplasia, that do not require immunosuppressivetherapy.3 Renovascular hypertension can be managed medically ormore definitively with percutaneous angioplasty and later bypasssurgery.3

Systemic hypertension and hypoperfusion of the ophthalmicand ciliary vessels may combine to produce retinal, choroidal andoptic nerve dysfunction.4 Fluorescein angiography is the best wayto clinically assess the effects of impaired ocular perfusion in TA.5

Angiographic features of early ocular ischaemia include: a delay inthe arm-to-retina circulation time, venous dilatation, capillary dil-atation and microaneurysm formation.5 The presence of moderateto severe disease is observed with a delay in the arteriovenousfilling time, arteriovenous shunt formation and areas of capillarynon-perfusion.5

Fluorescein angiography in this individual showed none of thetypical features associated usually associated with TA retinopathy.5

Visual loss in our case was due to uveitis and cystoid macularoedema. We were also able to demonstrate almost complete reso-lution of visual symptoms with anti-inflammatory treatment. Theonly other reported cases of individuals with TA and uveitis haveultimately been shown to have TA coexistent with Cogan’ssyndrome8 or sarcoidosis.9

Our patient was unusual as no carotid artery narrowing wasidentified on vascular imaging and fundal fluorescein angiography

Figure 3. Magnetic resonance angiography demonstrating steno-sis of the left subclavian artery. The carotids show no evidence ofimpairment of blood flow.


identified no evidence of reduced ocular perfusion. This casedemonstrates a rare presentation for Takayasu’s arteritis andemphasizes that visual loss in these individuals can have multipleaetiologies.

Mark A McDonald FRANZCO, Elvis Ojaimi MB BS andIan Favilla FRANZCO

Monash Medical Centre, Melbourne, Victoria, Australia

REFERENCES

1. Ishikawa K. Diagnostic approach and proposed criteria for theclinical diagnosis of Takayasu arteriopathy. J Am Coll Cardiol1988; 12: 964–72.

2. Numano F, Okawara M et al. Takayasu’s arteritis. Lancet 2000;356: 1023–5.

3. D’Souza SJ, Tsai WS, Silver MM et al. Diagnosis and manage-ment of stenotic aorto-arteriopathy in children. J Paediatrics1998; 132: 1016–22.

4. Lewis TR, Glaser JS, Schats NJ et al. Pulseless (Takayasu)disease with ophthalmic manifestations. J Clin Neuro-Ophthalmol1993; 13: 242–9.

5. Chun YS, Park SJ, Park IK et al. The clinical and ocular mani-festations of Takayasu arteritis. Retina 2001; 21: 132–40.

6. Arend WP, Neat A, Bloch D et al. The American College ofRheumatology 1990 Criteria for the classification of Taka-yasu’s Arteritis. Arthritis Rheum 1990; 33: 1129–34.

7. Kerr GS. Takayasu’s arteritis. Rheum Dis Clin North Am 1995; 21:1041–58.

8. Raza K, Karokis D, Kitas D. Cogan’s syndrome with Taka-yasu’s arteritis. Br J Rheum 1998; 37: 369–72.

9. Jain R, Ionides A, Pavesio C, Russell A, Haskard D. Scleritis asa presenting feature of Takayasu’s disease. Br J Ophthalmol2000; 84: 801.

10. Kerr GS, Hallahan CW, Giordano J. Takayasu arteritis. Ann IntMed 1994; 120: 919.

Isolated trochlear nerve palsy as a presenting feature of primary polycythemia rubra vera

ABSTRACT

A case is reported where the onset of vertical diplopia secondary toa trochlear nerve palsy occurred as the presenting feature ofpolycythemia rubra vera. This may be the first report of an isolatedtrochlear nerve palsy secondary to polycythemia rubra vera andinfarction of the fascicle or nerve.

Key words: diplopia, polycythemia rubra vera, trochlear nerve.

INTRODUCTION

Trochlear nerve palsy is the commonest acquired cause of verticalstrabismus.1 Lesions of the trochlear nerve may be considered in

terms of the anatomical pathway of the nerve from the brainstemto the superior oblique muscle.

Polycythemia refers to a pattern of blood cell changes withincreased haemoglobin, haematocrit and red cell count. In poly-cythemia rubra vera (PRV) endogenous myeloproliferation causesincreased red cell volume. Clinical features result from hyper-viscosity, hypervolaemia or hypermetabolism. We report the onsetof vertical diplopia secondary to a trochlear nerve palsy as thepresenting feature of PRV.

CASE REPORT

A 65-year-old man presented with isolated acute, painless verticaldiplopia and generalized pruritis. There was no history of headtrauma. He had no vascular risk factors such as hypertension,diabetes or smoking, and took no regular medication. He hadundergone right cataract extraction 18 months previously.

Examination revealed a right superior oblique palsy demon-strated by the patient preferring to hold his head tilted to the leftwith chin down. Diplopia was worsened with right head tilt. Hehad a right hypertropia that measured 11 ∆ in primary gaze, 4 ∆ onright gaze and 18 ∆ on left gaze (Fig. 1). A left exophoria for nearwas noted incidentally. Plethoric in appearance, there was mildsplenomegaly, left nucleosclerosis and a normally reactive irregularright post-surgical pupil.

Investigations confirmed the diagnosis of PRV with a haemo-globin of 207 g/L (normal range 130–180 g/L), haematocrit of0.63 L/L (normal range 0.40–0.54 L/L), and red cell mass of 51 mL/kg(normal range 25–35 mL/kg). Renal function, urate levels, whiteblood cell and platelet counts, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody screen and pO2 (83 mmHg)were normal. Bone marrow biopsy and cytogenetic analysis diag-nosed a myeloproliferative disorder, consistent with PRV. Cerebralcomputed tomography, magnetic resonance imaging and angio-graphy were normal.

Interval venesection was commenced with minimal improve-ment in the diplopia over the subsequent 18 months.

DISCUSSION

Trochlear nucleus lesions are usually accompanied by other signsof midbrain injury;2 however, it is difficult to differentiate nuclearfrom fascicular lesions as they lie close together. We believe thisto be the first report of an isolated trochlear nerve palsy second-ary to PRV and infarction of the fascicle or nerve. Withoutcomorbid vasculopathic conditions, coincident trochlear nervepalsy and PRV, or an unmasked congenital fourth nerve palsy areunlikely.

There is a high incidence of peripheral neuropathy in PRV.3,4

Up to 70% of patients with PRV have electrophysiological evi-dence of polyneuropathy, which may be asymptomatic. The pro-posed mechanism is nerve ischaemia secondary to increased bloodviscosity and platelet dysfunction.3,4 A correlation between haema-tocrit and degree of neuropathy has not been demonstrated,4

although some patients improve following venesection.3 Ourpatient did not improve, indicating irreversible damage to thetrochlear nerve or fascicle.

Two existing reports of ocular motor deficits antedated by thediagnosis of PRV exist. A 59-year-old woman presented with a left


oculomotor nerve palsy 10 years following the diagnosis of PRV.5

Cerebrospinal fluid examination identified transformation toacute myeloblastic leukaemia. In the other case, a 64-year-old mandeveloped unilateral visual loss, proptosis and complete ophthal-moplegia 2 years after being diagnosed with PRV.6 Magnetic reso-nance imaging demonstrated bony narrowing of the optic canalsecondary to extramedullary haematopoiesis. Both cases demon-strate different pathological processes as part of PRV resulting inocular nerve palsies.

Unique to this case is the acute presentation of an isolatedtrochlear nerve palsy in a patient not previously known to havePRV. It highlights the importance of considering systemic diseasein the differential diagnosis of trochlear nerve palsy.

Michael M Jones MB BS, Colin I Clement MB BS PhD andDominic B Rowe PhD FRACP

Department of Neurology, Royal North Shore Hospital,Sydney, New South Wales,

Australia

REFERENCES

1. Leigh RJ, Zee DS. The Neurology of Eye Movements, 2nd edn.Philadelphia: FA Davis, 1991.

2. Bennet JL, Pelak VS. Palsies of the third, fourth and sixthcranial nerves. Ophthalmol Clinics North Am 2001; 14: 169–85.

3. Yiannikas C, Mcleod JG, Walsh JC. Peripheral neuropathyassociated with polycythemia vera. Neurology 1983; 33:139–43.

4. Poza JJ, Cobo AM, Marti-Masso JF. Peripheral neuropathyassociated with polycythemia vera. Neurologia 1996; 11: 276–9.

5. Garfinkel D, Shoenfeld Y, Gadoth N, Pinkhas J. Oculomotornerve paresis: presenting sign of acute myeloblastic leukemiain a patient with polycythemia vera. Haematologica 1980; 65:769–72.

6. Pless M, Rizzo JF, Shang J. Orbital apex syndrome: a rarepresentation of extramedullary hematopoiesis. J Neuro-Oncology2002; 57: 37–40.

Figure 1. Composite photograph demonstrating a complete right fourth nerve palsy with a right hypertropia that worsened in left lateralgaze.

visual loss despite anticoagulation in radiation-induced optic neuropathy

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