Letters to the Editor

Choroidal and optic disc

metastases in a man with

metachronous and

metastatic breast

carcinoma

Minu Singh, Ajay Kumar Kotagiri and

Masoud Teimory

Worthing and Southlands Hospital NHSTrust, Worthing, UK

doi: 10.1111/j.1600-0420.2007.00957.x

Editor,

W e read with interest the articleby Wickremasinghe et al. (2007)

on ocular presentations of breast can-cer. We agree with the authors thatmale breast carcinoma is a rare dis-ease accounting for 1% of all breastcancer diagnosis and less than 1.5%of all malignant tumours in men(Fowble 1991). We report an unusualand interesting case of bilateral simul-taneous choroidal metastases andunilateral optic disc metastasis frommetachronous breast cancer in a man.

A 65-year-old man presented with ahistory of gradual painless blurring ofvision in his left eye. There was noth-ing notable in his past ophthalmic his-tory. His best corrected visual acuitywas 6 ⁄ 6 in the right eye and handmovements in the left eye. A left relat-ive afferent pupillary defect was notedon examination.

Fundus examination of the righteye revealed two flat choroidal lesionsof one disc diameter size inferotempo-rally within the vascular arcade (Fig.1A). In the left eye, multiple ill-defined elevated creamy white lesionswere noted in the posterior pole withserous retinal detachment. There wasalso diffuse yellowish thickening ofthe optic disc with surroundingvenous congestion and juxtapapillarychoroidal metastasis at the temporaland inferior margins in the left eye(Fig. 1B). Standardized B-scan ultra-sonography of the left eye demonstra-ted mild elevation of optic disc withhigh internal reflectivity, and echogenicsubretinal mass with overlying serous

retinal detachment (Fig. 2A, B). Ocu-lar metastasis was diagnosed and thepatient was referred for radiotherapy(Fig. 1C).

His past medical history was signifi-cant: breast carcinoma was diagnosed6 years ago. He presented with inciden-tal finding of a swelling in his left breastand nipple inversion. He was treatedby mastectomy and axillary clearance.The surgerywas followedby chemother-apy, radiotherapy and a 5 year courseof tamoxifen. Histological examinationshowed invasive ductal carcinoma. Thetumour was highly positive for oestro-gen and progesterone receptors. He

was monitored in clinic by periodicalmammography for recurrence.

The patient failed chemotherapyand tamoxifen treatment; 6 years afterhis initial presentation, he developedrecurrence on the other side. He sub-sequently underwent right mastectomywith axillary clearance. The surgerywas again followed by chemotherapyand radiotherapy. The histology dem-onstrated multifocal ductal carcinomawith extensive vascular invasion. Bythis time, the breast carcinoma alsodisseminated to liver and bone.

Uveal metastasis is the most com-mon malignancy of adult eyes (Shields

(A)

(B)

(C)

Fig. 1. Fundus photographs. (A) Right eye showing flat multifocal choroidal metastasis infero-

temporally within the vascular arcade. (B) Left eye showing optic disc metastasis, juxtapapillary

choroidal metastasis and inferior serous retinal detachment. (C) Left eye after radiotherapy

showing diffuse enlargement of optic disc and mottling of retinal pigment epithelium.

Acta Ophthalmologica Scandinavica 2007

688

& Shields 1992). Among uveal metas-tases, choroid is the most frequentsite. The most common primarysource is breast carcinoma in femalesand lung cancer in males. Metastasisto the optic disc is very uncommonand accounts for 4.5% of all intraocu-lar metastases. The systemic prognosisfor patients with optic disc metastasisis generally poor (Shields et al. 2000).

Carcinoma of the breast is rare inmen. Physicians and patients have alow index of suspicion for the disease;in addition, it tends to be diagnosedlate in men leading to increased mor-bidity and mortality. Bilateral breastcarcinoma is more common in womenthan in men. In a large case series, theprevalence of bilaterality was found tobe only 1.4% in men (Crichlow 1972).Men are also more likely to develop asecond type of cancer than to havea recurrence of the same type inthe opposite breast as compared towomen.

This patient developed recurrenceof the same type of carcinoma in thecontralateral breast with widespreadsystemic and ocular metastases 6 yearsafter his initial presentation despiteadequate treatment. This case high-lights the increased risk of ocular meta-stases and the presence of advanceddisease at the time of presentation inmale patients with breast carcinoma.

ReferencesCrichlow RW (1972): Carcinoma of the male

breast. Surg Gynecol Obstet 134: 1011–

1019.

Fowble B (1991): Breast cancer treatment: a

comprehensive guide to management. St

Louis: Mosby.

Shields JA & Shields CL (1992): Intraocular

tumours: a text and atlas. Philadelphia:

WB Saunders.

Shields JA, Shields CL & Singh AD (2000):

Metastatic neoplasms in the optic disc.

Arch Ophthalmol 118: 217–224.

Wickremasinghe S, Dansingani KK, Tranos

P, Liyanage S, Jones A & Davey C (2007):

Ocular presentations of breast cancer. Acta

Ophthalmol Scand 85: 133–142.

Correspondence:

Ajay Kumar Kotagiri

41 Park Avenue

Worthing

West Sussex BN11 2HX

UK

Tel: +44 1903 536 975

Fax: +44 1903 286 783

Email: ajay.kotagiri@gmail.com

Acute retinal pigment

epithelial tear in the

untreated fellow eye

following repeated

bevacizumab (AvastinTM)

injections

Stefan Mennel,1 Josep Callizo,1 Jorg C.

Schmidt1 and Carsten H. Meyer1,2

1Department of Ophthalmology,Philipps-University Marburg, Germany2Department of Ophthalmology,University of Bonn, Germany

doi: 10.1111/j.1600-0420.2007.00926.x

Editor,

R etinal pigment epithelium (RPE)tears are well recognized

complications of pigment epithelialdetachments (PED) in age-relatedmacular degeneration (AMD). RPEtears may arise spontaneously or aftertrauma, photocoagulation or photody-namic therapy (Mennel et al. 2006;Meyer et al. 2006b). An RPE tear hasrecently been reported as a possiblecomplication after intravitreal injec-tion of anti-VEGF (vascular endo-thelial growth factor) bevacizumab(AvastinTM) (Meyer et al. 2006a).

In this article, we report a patientwith exudative AMD treated with fiveinjections of bevacizumab within aperiod of 4 months. During this timewe observed in the untreated felloweye a rapid progression from a smallage-related maculopathy (ARM) to anextensive exudative AMD with a hugeRPE tear.

(A)

(B)

Fig. 2. Ultrasonography of the left eye, showing (A) echogenic choroidal metastasis and

(B) elevation of optic disc with high internal reflectivity.

Acta Ophthalmologica Scandinavica 2007

689

An 84-year-old female patientnoticed a decrease in visual acuity(VA) right eye (OD) for 2 weeks. Ourexamination disclosed a subfovealchoriodal neovascularization (CNV),fibrovascular PED and subretinalbleeding secondary to AMD OD. Thefellow eye presented the unremarkablepicture of an early stage ARM (Fig.1). The patient’s VA was 20 ⁄ 60 ODand 20 ⁄ 30 left eye (OS). Over a periodof 4 months the patient underwentfive uneventful intravitreal injectionsof 1.25 mg bevacizumab OD. Controlfollowed 1 day, 1 week and 4 weeksafter each injection.

One week after the fourth injection,the patient’s VA decreased to 20 ⁄ 60 in

the untreated fellow eye. Fluoresceinangiography (FA) disclosed a smallextrafoveal hyperfluorescence, a poss-ible sign of an early occult CNV. Bythe fifth injection OD, VA ODimproved up to 20 ⁄ 40, leakage on FAwas reduced and central retinal thick-

ness decreased by 135 lm. However,VA decreased significantly to 20 ⁄400in the left eye. Funduscopy andfluorescein angiography showed anacute giant RPE tear (Fig. 2).

RPE tears develop more frequentlywithin a month of an anti-VEGFapplication. In a study of 2035 injec-tions in 906 patients, Chan et al.(unpublished) found an incidence ofRPE tears of 0.89% among all AMDeyes and 17.5% among eyes with pre-vious PED. The rupture of the PEDmay be triggered by the surgical mani-pulation, induced vitreous traction,changed fluid kinetics, weakened inter-cellular adhesion at the PED or adirect influence of the drug (Geliskenet al. 2006).

Clinical effects of intravitreal bev-acizumab in untreated fellow eyes havebeen demonstrated by Avery et al.(2006). They observed subtle decreasedleakage and regression of optic discproliferations in untreated fellow eyeswith proliferative diabetic retinopathy,and hypothesized that even unilateralintravitreal injections of 1.25 mg Avas-tinTM may induce contralateral effects.Additionally, Tezel et al. (unpublished)reported similar effects in eyes withAMD. They reported reduced macularthickness in untreated fellow eyes afterunilateral intravitreal injection of Mac-ugenTM and AvastinTM. Bakri et al.(unpublished) were able to determinelow AvastinTM concentrations in theuntreated fellow eyes in animal mod-els. All three groups suspected a biolo-gical effect in the fellow eye to becaused by a systemic absorption of thedrug. The uni- and contralateraleffects of anti-VEGF applicationsremain controversial:

• First, the unilateral occurrence ofRPE tears following intravitreal injec-tions seems to be a more commoncomplication in eyes with a fibrovas-cular PED. However, our treated eyewith an extensive PED did notdevelop an RPE tear.• Second, most RPE tears (90%)develop in eyes with previous PED.However, our contralateral RPE tearoccurred in an eye with only minorRPE changes and some drusen.• Third, most unilateral RPE tearsdevelop soon after the first injection(> 75%). Our contralateral RPE tearoccurred after 4 months and the appli-cation of five consecutive contralateral

(A)

(B)

(C)

Fig. 1. Fellow eye (OS) when the treatment

of anti-VEGF was initiated in the right eye.

(A) Fundus colour image of the fellow eye

(OS): the optic disc is with sharp margin,

physiological excavation, the retinal vessels are

without abnormalities. The macula presents

small drusen secondary to age-related maculo-

pathy (ARM). The arrow indicates the direc-

tion, length and location of the corresponding

OCT scan. (B) Late-phase fluorescein angio-

graphy 5 min after dye injection. There is a

mild hyperfluorescence demonstrating drusen,

but no signs of exudative alterations. (C) Optic

coherent tomography (OCT) represents the

physiological architecture of the central macula.

(A)

(B)

(C)

Fig. 2. Fellow eye (OS) 4 months later follow-

ing five injections of anti-VEGF in the right

eye. (A) Fundus colour image of the fellow

eye (OS): the optic disc is with sharp margin,

physiological excavation, the retinal vessels

are without abnormalities. The macula pre-

sents an elevation in an area of 4.5 disc diam-

eters involving the entire macula representing

a huge RPE tear. A diagonal line from super-

o-temporal to nasal-inferior demarcates a

whitish fibrous-like area of the rolled RPE

nasally to a temoral part without RPE mono-

layer (window defect). The arrow indicates

the direction, length and location of the cor-

responding OCT scan. (B) Late-phase fluo-

rescein angiography 5 min after dye injection.

A totally blocked fluorescence area nasally in

the early phase angiography showed some

hyperfluorescence in the late-phase image,

whereas in the temporal part with missing

RPE layer a homogenous hyperfluorescence

was visible from the early phase to the late-

phase angiogram. The red dots demarcate the

temporal edge of the RPE tear. (C) On OCT,

there is a dome-shaped hyper-reflective band

of the contracted RPE. The hypo-reflective

area corresponds to subretinal fluid.

Acta Ophthalmologica Scandinavica 2007

690

injections. The possible progressiveaccumulation of AvastinTM in the fel-low eye may not have been enough toinhibit AMD progression but mayrelate to a delayed RPE tear in this eye.• Fourth, it remains unknown if thisRPE tear developed because of a con-tralateral intravitreal injection ofAvastinTM or followed the naturalcourse of AMD.

Possible clinical effects in theuntreated fellow eye have beenobserved in numerous groups follow-ing unilateral intravitreal AvastinTM

injections. Although low, subclinicaldosages have been determined in ani-mal experiments, the observed biologi-cal effects remain speculative andneed further observation.

ReferencesAvery RL, Pearlman J & Pieramici DJ,

Rabena MD, Castellarin AA, Nasir MA,

Guist MJ, Wendel R & Patel A (2006):

Intravitreal bevacizumab (Avastin) in the

treatment of proliferative diabetic retino-

pathy. Ophthalmology 113: 1695.

e1–1695.e15.

Gelisken F, Ziemssen F, Voelker M & Bartz-

Schmidt KU (2006): Retinal pigment

epithelial tear following intravitreal bevaci-

zumab injection for neovascular age-related

macular degeneration. Acta Ophthalmol

Scand 84: 833–834.

Mennel S, Peter S, Meyer CH & Thumann G

(2006): Effect of photodynamic therapy on

the function of the outer blood–retinal bar-

rier in an in vitro model. Graefes Arch

Clin Exp Ophthalmol 244: 1015–1021.

Meyer CH, Mennel S & Schmidt JC (2006b):

Occult vitreo-macular traction may cause

traumatic RPE tears. Acta Ophthalmol

Scand 84: 560.

Meyer CH, Mennel S, Schmidt JC & Kroll P

(2006a): Acute retinal pigment epithelial

tear following intravitreal bevacizumab

(Avastin) injection for occult choroidal

neovascularisation secondary to age related

macular degeneration. Br J Ophthalmol 90:

1207–1208.

Correspondence:

Stefan Mennel

Department of Ophthalmology

Philipps-University Marburg

Robert-Koch-Str. 4

35037 Marburg

Germany

Tel: +49 6421 286 2600

Fax: +49 6421 286 5678

Email: stefan.mennel@lycos.com

History of ophthalmology:

a distinguished or

extinguished field of

scholarly activity?

Andrzej Grzybowski

Department of History of Medicine,Karol Marcinkowski University MedicalSchool, Poznan, Poland

doi: 10.1111/j.1600-0420.2007.00955.x

‘I f I have seen further [than cer-tain other men], it is by standing

upon the shoulders of giants.’(Isaac Newton, letter to Robert Hook,February 5th, 1675)

Acta Ophthalmologica Scandinavicais one of the few international, peer-reviewed ophthalmology journals topublish papers dealing with the his-tory of ophthalmology.

In an analysis of papers on thehistory of ophthalmology publishedin Acta in the years 1998–2006, sixarticles were found, representing lessthan one per year. These were:

(1) ‘Danish Ophthalmology from1950 to 1975’ (Ehlers 2002);

(2) ‘Gustav Østerberg in the foot-steps of Hans Christian Andersen’(Mellemgaard 2002);

(3) ‘The history of the Ophthal-mological Society of Copenhagen’(Andersen 2002);

(4) ‘The Society’s archives’ (Norn2002);

(5) ‘Marius Tscherning (1854)1939):his life and work in optical physiology’(Norn & Jensen 2004), and

(6) ‘Jesus and the eye: New Testa-ment miracles of vision’ (Mansouret al. 2005).

An analysis of presentations at thetwo major European conferences gavesimilar results. The Nordic Congressof Ophthalmology (NOK) 2006 inclu-ded a session on the history of oph-thalmology, at which six papers werepresented:

(1) ‘Horner’s syndrome – eponymicconfusion and conflict of contriver’(Havelius 2006);

(2) ‘The great confusion and theKarolinska Institute in Stockholm1888–1892’ (Tengroth 2006);

(3) ‘A Swedish rural hospital 1886–1903’ (Ehinger 2006);

(4) ‘Evil eyes’ (Mellemgaard 2006);(5) ‘Bjerrum’s glaucoma theory in

1889’ (Norn 2006), and(6) ‘Tobacco amblyopia – historical

overview of 200 years of the subject’(Grzybowski 2006).

Meanwhile, at the 2006 Meeting ofthe European Association of Visionand Eye Research (EVER), only onepaper was presented at the free paperssession: ‘Edmonde Mariotte (1620–1684), pioneer of neurophysiology andneuro-ophthalmology’ (Grzybowski &Aydin 2006). However, the GeneralAssembly of EVER, following myformal proposal, has decided to opena subsection for the history ofophthalmology in the hope that morepapers will be submitted and a fullsection might be established in thefuture.

The reason for such scant interestin the history of ophthalmology mightbe related to the fact that it is per-ceived as a field of science in whichthere is almost no possibility offurther development and in whichnothing of interest can any longerbe discovered. Some even claimthat everything in the history ofophthalmology has already beendescribed.

As an illustration of how presentknowledge has its origins in the pastand of how many erroneous opinionsshould be reconsidered, let us examinethe case of Wilbrand’s knee. As is wellknown, Wilbrand’s knee is part of theoptic nerve. It appears in the majorityof contemporary textbooks of oph-thalmology and neuro-ophthalmology,and damage to it was previouslyassumed to be responsible for junc-tional scotoma. However, 10 yearsago, Horton demonstrated thatWilbrand’s knee is an artefact ofmonocular enucleation and proposedthat anterior chiasmal syndrome hasa limited localizing value (Horton1997).

Why the history of ophthal-mology should undergo continual re-examination is further illustratedby the fact that many papers onophthalmology are published in thenative language of their authorsand are neither translated into otherlanguages nor presented internation-ally. At NOK 2006 this problem wasnicely exemplified by Mogens Norn,in his work on Bjerrum’s glaucomatheory.

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