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    Subconjunctival corticosteroidsfor benign lymphoid hyperplasia

    Appropriate treatment of subconjunctival

    benign lymphoid hyperplasia (BLH) has beenunclear. Most have noted poor response tooral or topical corticosteroids. Many recom-mend observation. Radiotherapy has beenused, but there are risks of vision loss.

    In this case, we found dramatic response tolocal subconjunctival injection of long actingcorticosteroids, which may represent a ther-apeutic option for subconjunctival benignlymphoid hyperplasia.

    Case reportA 72 year old woman noticed an enlargingmass on the nasal conjunctiva over the

    previous year. She denied any discomfort,diplopia, or visual changes. She was pseudo-phakic in both eyes, and did not have anypast ocular trauma, infection, or eye disease.She had a history of hypothyroidism, multi-ple myeloma, tuberculosis, and pulmonarysarcoidosis. Two months before presentationshe was found to have colon carcinomatreated with colectomy and chemotherapy.She was reportedly free of any tumourmetastasis.

    Her visual acuity was 20/30 in the right eyeand 20/40 in the left, and extraocular motility

    was full in both eyes. Examination revealed asalmon coloured, raised, and moderately firmpatch on the nasal conjunctiva of the righteye without significant neovascularisation(fig 1A). Dilated fundus examination wasunremarkable. A head MRI scan showedmoderate enlargement of the medial rectusmuscle without involvement of the muscletendon. A simple biopsy (2 mm62 mm61 mm) of the lesion was performed.

    Pathological examination revealed benignlymphohistiocytic infiltrates (fig 2). Thelymphoid reaction showed a predominanceof T cells (CD3+), numerous histiocytes, anda smaller number of B cells (CD20+). There

    was no evidence of neoplastic plasma cells,metastatic carcinoma, or well defined sarcoidgranulomas.

    The patient elected to have surgical treat-ment over other options including observa-tion. The patient received a 20 mg/0.5 mlsubconjunctival injection of triamcinolone(in 0.5 ml in the nasal bulbar conjunctiva)

    just superior to the mass. On follow upexamination 2 months later, the patientcontinued to deny any discomfort or visualchanges and was very pleased about herresponse to the treatment. Remarkably, thelesion completely resolved being no longer

    visible or palpable (fig 1B). This patientunfortunately died 9 months later fromcomplications secondary to a fall, but duringthis time there was no recurrence of theconjunctival lesion.

    CommentA patient presenting with a slow growingsalmon coloured subconjunctival massshould always raise suspicion of neoplastic

    causes. Patients with ocular BLH and lym-phoma will often have the similar presentingsymptoms and demographic profiles. Inaddition they appear very similar radiologi-cally,1 and thus definitive diagnosis requirestissue biopsy. A pathological diagnosis of BLHtraditionally requires reactive follicles, poly-clonality, and the absence of cytologicalatypia.2 Lymphoproliferative lesions canoccur throughout the ocular adnexa, andsome studies suggest a more benign coursefor conjunctival BLH compared to those inthe orbit.3 Coupland et al found that of 112cases, 32 (29%) were in the conjunctiva, 52(46%) in the orbit and the remainder in theeyelid, lacrimal gland, and caruncle.4 Theoptimal treatment for BLH is uncertain.Many recommend frequent observation.Others have tried focal radiotherapy withsome success,5 but there is a significant riskof vision loss.6 In a recent review of 117 casesof conjunctival lymphoproliferative lesions,17% were BLH, 22% were atypical lymphoidhyperplasia, and 56% were lymphoma.7 In

    these cases 9% were observed, 42% hadcomplete excisional biopsy, 4% had biopsyand cryotherapy, 44% had biopsy and exter-nal beam irradiation, and 6% had biopsy andchemotherapy. 7

    In this case report, we found a dramaticresponse to local subconjunctival injection ofa long acting corticosteroid. The corticoster-oid near the reactive follicle must have beensufficient to suppress lymphocyte prolifera-tion. This response may represent a thera-peutic option for BLH.

    D G Telander, T Z Lee, S E Pambuccian,A J W Huang

    Department of Ophthalmology, University ofMinnesota, Minneapolis, MN, USA

    S E PambuccianDepartment of Pathology, University of Minnesota,Minneapolis, MN, USA

    D G TelanderUCLA/Jules Stein Eye Institute, Los Angeles, CA, USA

    T Z LeeApple Hill Eye Center, 25 Monument Road, Suite 297,

    York, PA 17403, USA

    Correspondence to: Andrew J W Huang, MD,Department of Ophthalmology, University of

    Minnesota, 516 Delaware Street SE, 9th Floor,Minneapolis, MN 55455, USA; [email protected]

    doi: 10.1136/bjo.2004.051342

    References

    1 Knowles DM, Jakobeic FA. Malignant lymphomaand lymphoid hyperplasia occurring in the ocularadnexa. In: Knowles DA, ed. Neoplastichematology. Baltimore: Williams & Wilkins,1992:100946.

    2 Cockerham GC, Jakobiek FA.Lymphoproliferative disorders of the ocularadnexa. Int Ophthalmol Clin 1997;37:3959.

    3 Knowles DM, Jakobiek FA, McNally L,et al.Lymphoid lyperplasia and malignant lymphomaoccurring in the ocular adnexa (orbit, conjunctiva,and eyelids): a prospective multiparametricanalysis of 108 cases during 1977 to 1987. HumPathol1990;21:95973.

    Figure 1 (A) Slit lamp photograph of thepatients right eye on initial presentation. Notethe size, salmon colour and raised appearanceof the lesion. (B) Slit lamp photograph of thesame lesion 2 months later followingsubconjunctival injection of triamcinolone. Thesubconjunctival lesion appeared to havecompletely resolved with no obvious remnantsseen on the sclera or conjunctiva. (Reproduced

    with permission.)

    Figure 2 Haematoxylin and eosin staining,106magnification of the lesion biopsied infigure 1A. Note the abundance of lymphocytesseen more clearly in the magnified section in thelower right part of the figure. Also note thepredominance of T cells (CD 3+) with a lessnumerous population of B cells (CD20+) typicalof benign lymphoid hyperplasia.

    LETTERS

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    Log onto our website (www.bjophthalmol.com), find the paper that interests you, andsend your response via email by clicking onthe eLetters option in the box at the topright hand corner.

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    Accepted for publication 1 October 2004

    770 Br J Ophthalmol2005;89:770787

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    4 Coupland SE, Krause L, Delecluse H-J, et al.Lymphoproliferative lesions of the ocularadenexa. Analysis of 112 cases.Ophthalmology1998;105:143041.

    5 Keleti D, Flickinger JC, Hobson SR,et al.Radiotherapy of lymphoproliferative diseases ofthe orbit. Surveillance of 65 cases.Am J ClinOncol1992;15:4227.

    6 Bessel EM, Henk JM, Whitelocke RAF,et al.Ocular morbidity after radiotherapy of orbitaland conjunctival lymphoma. Eye1987;1:9096.

    7 Shields CL, Shields JA, Carvalho C, et al.Conjunctival lymphoid tumors. clinical analysis of117 cases and relationship to systemiclymphoma.Ophthalmology2001;108:97984.

    Congenital upper eyelid eversioncomplicated by cornealperforationCongenital upper eyelid eversion is a rarecondition more frequently seen in blackinfants and in Downs syndrome. If recog-nised early, the condition can be managedconservatively without recourse to surgery.We highlight a case that presented late withsevere sight threatening complications.Surgical intervention was consequently theonly appropriate way to manage the patient.

    Case reportA 7 month old black female was referred tothe emergency room of the King Khaled EyeSpecialist Hospital in Riyadh, Saudi Arabia.She had a history of a white spot in the rightcornea, and a right upper lid that had flippedup since birth.

    She was born by breech delivery and wassubsequently diagnosed as having Downssyndrome. On examination she had completeeversion of the right upper lid with mildconjunctival chemosis. The lid could berepositioned with ease but when the childcried it reverted. There was a corneal opacity

    with a central descematocele and iris adhe-sion to the endothelium. The child wasadmitted and started on intensive topicalantibiotics. In spite of manual inversion of

    the upper lid as well as a moist chamber, thelid continued to re-evert. A lateral tarsor-rhaphy and penetrating keratoplasty wereperformed under general anesthesia but,postoperatively, the eyelid continued to evert(fig 1). Because of the risk of exposure to thetransplanted cornea, a full thickness skingraft to the right upper lid was performed(fig 2). Subsequently, the lid retained itsnormal position and the child could fix andfollow adequately with the eye. The trans-planted cornea was clear at the 10 weekpostoperative visit after which the patient

    was lost to follow up.

    CommentCongenital eversion of the upper eyelid wasfirst described in 1896 by Adams1 who calledthe condition double congenital ectropion.The exact incidence of this condition is notknown. Sellar2 reviewed the literature in 1992and found 51 reported cases. Since then onlytwo more case reports could be found in theliterature.3 4 The eversion is usually present atbirth, but late onset of total eversion of theupper eyelids has been described in infancy,5

    and as late as 11 years of age. 2

    The condition typically is bilateral andasymmetrical but unilateral cases have beendescribed. The underlying pathophysiology isobscure and several possible mechanismshave been proposed and associations recog-nised. The incidence appears to be higher inblack infants,6 infants with trisomy 21,2 andin infants born with collodion skin disease.7

    Abnormalities such as orbicularis hypotonia,8

    birth trauma, vertical shortening of theanterior lamellar or vertical elongation ofthe posterior lamellar of the eyelid and failureof the orbital septum to fuse with the levatoraponeurosis (with adipose tissue interposi-tion),9 absence of effective lateral canthalligament, and lateral elongation of the eyelidhave all been implicated as possible patho-

    physiological factors. Once everted, orbicu-laris spasm10 may act as a sphincter that leadsto a vicious cycle of conjunctival strangula-tion and oedema secondary to venous stasis.This chemotic conjunctiva usually protectsthe cornea from exposure and, hence, cornealcomplications have thus far not beenreported in infants. To our knowledge thisis the first reported case of congenital eyelideversion complicated by corneal exposure,descematocele, and perforation.

    Congenital eyelid eversion either resolvesspontaneously with conservative treatment or

    with surgical intervention such as a subcon-junctival injection of hyaluronic acid, tarsor-rhaphy with excision of redundantconjunctiva, fornix sutures, and full thick-ness skingraft to the upperlid. In this patient

    because of failure of all conservative mea-sures, the chronicity (7 months) and severity(corneal ulcer/perforation), we elected to doanterior lamellar lengthening by means of afull thickness upper lid skin graft. Cornealperforation necessitating penetrating kerato-plasty is a rare complication of congenitaleyelid eversion, but in this case it wasessential to maintain the integrity of theglobe and to, hopefully, retain vision andprevent deep amblyopia.

    The condition in this reported case ofcongenital eyelid eversion complicated by acorneal ulcer, large descematocele and per-foration, is rare. Congenital upper lid eversion

    may present once in a lifetime to theophthalmologist or newborn nursery paedia-trician. It is nevertheless important to createawareness among healthcare professionals inobstetric and neonatal care of the existence ofthis potentially sight threatening congenitalanomaly, as the condition is very amenable toearly treatment.

    H Al-Hussain, A A Al-Rajhi, S Al-Qahtani,D Meyer

    University of Stellenbosch/King Khaled Eye SpecialistHospital, Faculty of Health Sciences, PO Box 19059,

    Tygerberg, South Africa

    Correspondence to: Professor David Meyer, Universityof Stellenbosch, Faculty of Health Sciences, PO Box

    19059, Tygerberg, South Africa; [email protected]

    doi: 10.1136/bjo.2004.053348

    References

    1 Adams AL. A case of double congenitalectropion. Med Fortnightly1896;9:1378.

    2 Sellar PW, Bryars JH, Archer DB. Latepresentation of congenital ectropion of the eyelidsin a child with Downs syndrome: a case reportand review of the literature. J Pediatr OphthalmolStrabismus1992;29:647.

    3 Watts MT, Dapling RB. Congenital eversion of theupper eyelid: a case report.Ophthal PlastReconstr Surg1995;11:2935.

    4 Dawodu OA. Total eversion of the upper eyelidsin a newborn. Niger Postgrad Med J2001;8:1457.

    5 Siverstone B, Hirsch I, Sternberg MD,et al.Lateonset of total eversion of upper eyelids. AnnOphthalmol1982;14:4778.

    6 Lu LW, Bansal RK, Katzman B. Primary congenitaleversion of the upper lids.J Pediatr OphthalmolStrabismus1979;16:14951.

    7 Shapiro RD, Soentgen ML. Collodion skin diseaseand everted eyelids.Postgrad Med1969;45:21619.

    8 Loeffler M, Hornblass A. Surgical management ofcongenital upper-eyelid eversion.OphthalmicSurg1990;21:736.

    9 Blechman B, Isenberg S. An anatomical etiologyof congenital eyelid eversion. Ophthalmic Surg1984;15:11113.

    10 Raab EL, Saphir RL. Congenital eyelid eversionwith orbicularis spasm.J Pediatr OphthalStrabismus1985;22:1258.

    Homozygous mutation (L527R) ofTGFBIin an individual with latticecorneal dystrophyLattice corneal dystrophy (LCD), an inheritedform of amyloidosis, is characterised by thedevelopment of lattice lines and opacity inthe cornea. LCD is classified clinically intofour subtypes: I, II, III, and IIIA. Severaldistinct mutations of TGFBI have beenassociated with LCDIIIA: P501T,1 L527R,2

    N544S,3 A546T,4 N622K (T1913G andT1913A), and V627S.5 All cases of LCD

    characterised at the molecular genetic levelto date have been attributed to heterozygouspoint mutations of TGFBI. We now presentthe first example of a homozygous pointmutation ofTGFBIin an individual with LCD,a diagnosis supported by clinical, histological,and molecular genetic findings.

    Case reportA 52 year old Japanese man visited ourcorneal clinic in July 1997 with a maincomplaint of gradual impairment of vision.His parents, who were related, were no longeralive and he had no children. He had twobrothers and four sisters. His reporting

    Figure 2 Full thickness skin graft to the upperlid successfully expanded the anterior lamella topermanently solve the problem.

    Figure 1 After the tectonic penetratingkeratoplasty was performed, the lateraltemporal tarsorrhaphy failed to retain the lid inan inverted position.

    Accepted for publication 20 October 2004

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    suggested that his father had had LCD andthat his younger sister had also developedthis condition.

    Slit lamp examination revealed a largeregion of opacity and thick lattice lines inthe middle to deep portion of the cornealstroma in both eyes (fig 1A and B). Given

    that his visual acuity in both eyes decreasedto 20/40, we performed penetrating kerato-plasty on his left eye in December 2000 andon his right eye in May 2002. After thesurgeries, his visual acuity improved to 20/25in each eye and no recurrence has beenobserved to date.

    Histological analysis revealed that theamorphous component of the middle to deepregion of the stroma of both corneas stained

    with eosin (fig 1C) and with Congo red(fig 1D). The detection of apple greendichroism by polarised light microscopy wasalso consistent with amyloid deposition inthe middle to deep region of the corneal

    stroma (fig 1E). Although most of theepithelial cell layer, basement membrane,and hemidesmosomes of the right corneaappeared normal by transmission electronmicroscopy (TEM) (fig 1F), a region wasdetected that seemed to be devoid of basalcells, basement membrane, and hemidesmo-

    somes. TEM also revealed amyloid deposits inthe middle to deep corneal stroma (fig 1G),although Descemets membrane andendothelial cells appeared normal.

    After obtaining informed consent, wepurified DNA from the white blood cellsisolated from 10 ml of the patients blood.With appropriate primers,6 we amplifiedexons 4 and 12 ofTGFBI by the polymerasechain reaction (PCR) and directly sequencedthe products. We detected a homozygouspoint mutation, CTGRCGG (L527R), incodon 527 of TGFBI in the proband (fig 2).Point mutations were not detected in codons124, 518, 544, 546, or 555, mutations in

    which have been associated with cornealdystrophies.

    CommentFujiki et al2 reported that LCDIIIA in L527Rheterozygotes is characterised by a late onset

    and mild clinical findings. Hirano et al7

    reported that the condition caused by L527Rheterozygosity was associated with amyloiddeposition in the deep corneal stroma but not

    with corneal erosion. In contrast, LCD in ourpatient with a homozygous L527R mutation

    was characterised by onset in middle age,recurrent corneal erosion, and amyloiddeposition in the middle to deep region ofthe stroma. The deposits in the probandshowed right eye-left eye asymmetry in sizeand shape, as previously described for someL527R heterozygotes.2 7

    In general, corneal dystrophies caused byhomozygous point mutations in TGFBI arecharacterised by an earlier onset, more severesymptoms, and a higher frequency of recur-rence after keratoplasty compared with those

    attributable to the corresponding heterozy-gous mutations.812 Our study and the twoprevious studies2 7 of this mutation suggestthat this is also the case for L527R. However,the difference in the findings of slit lampexamination between L527R heterozygotesand homozygotes with LCD appears to be lessmarked than that observed between R124Hheterozygotes and homozygotes with

    Avellino corneal dystrophy. The reason forthis discrepancy remains unclear at present.

    Acknowledge mentsThis research was supported by grants from theJapan Society for the Promotion of Science (JSPS)

    and the Ministry of Education, Culture, Sports,

    Science, and Technology of Japan (to MI and TN).

    N Yamada, T-i Chikama, N Morishige,R Yanai, T Nishida

    Department of Biomolecular Recognition andOphthalmology, Yamaguchi University School of

    Medicine, Ube City, Yamaguchi 755-8505, Japan

    N Yamada, R Yanai, M InuiDepartment of Pharmacology, Yamaguchi University

    School of Medicine, Ube City, Yamaguchi 755-8505,Japan

    K SekiDepartment of Ocular Pathophysiology, Yamaguchi

    University School of Medicine, Ube City, Yamaguchi755-8505, Japan

    Figure 1 (A and B) Slit lamp photographs of the right and left eyes, respectively, of the patient.Light microscopic (CE) and transmission electron microscopy (TEM) (F and G) analysis of thesurgically removed corneal specimens of the patient. (C) Haematoxylin and eosin staining of the leftcornea. (D) Congo red staining of the left cornea. (E) Polarised light microscopy of the left cornea.(F) TEM of the epithelial cell layer of the right cornea. (G) TEM of the stromal and endothelial celllayers of the right cornea. Scale bars: 250 mm (CE) or 10 mm (F and G).

    Figure 2 Molecular genetic analysis ofTGFBIof the patient. Direct sequencing of PCRproducts corresponding to exon 12 ofTGFBI. Ahomozygous TRG mutation (arrow) wasdetected at codon 527.

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    Correspondence to: Naoyuki Yamada, MD, PhD,Department of Biomolecular Recognition and

    Ophthalmology, Yamaguchi University School ofMedicine, 1-1-1 Minami Kogushi, Ube City,

    Yamaguchi 755-8505, Japan ;[email protected]

    doi: 10.1136/bjo.2004.056168

    References

    1 Yamamoto S, Okada M, Tsujikawa M, et al. Akerato-epithelin (betaig-h3) mutation in latticecorneal dystrophy type IIIA. Am J Hum Genet1998;62:71922.

    2 Fujiki K, Hotta Y, Nakayasu K,et al.A new L527Rmutation of the betaIGH3 gene in patients withlattice corneal dystrophy with deep stromalopacities.Hum Genet1998;103:2869.

    3 Mashima Y, Yamamoto S, Inoue Y, et al.Association of autosomal dominantly inheritedcorneal dystrophies with BIGH3 gene mutations inJapan.Am J Ophthalmol2000;130:51617.

    4 Dighiero P, Drunat S, Ellies P, et al.A newmutation (A546T) of the betaig-h3 generesponsible for a French lattice corneal dystrophytype IIIA.Am J Ophthalmol2000;129:24851.

    5 Munier FL, Frueh BE, Othenin-Girard P,et al.BIGH3 mutation spectrum in corneal dystrophies.Invest Ophthalmol Vis Sci2002;43:94954.

    6 Munier FL, Korvatska E, Djemai A, et al. Kerato-

    epithelin mutations in four 5q31-linked cornealdystrophies.Nat Genet1997;15:24751.7 Hirano K, Hotta Y, Nakamura M,et al.Late-onset

    form of lattice corneal dystrophy caused byLeu527Arg mutation of the TGFBI gene. Cornea2001;20:5259.

    8 Mashima Y, Konishi M, Nakamura Y, et al.Severe form of juvenile corneal stromal dystrophywith h omozygous R124H mutation in thekeratoepithelin gene in five Japanese patients.Br J Ophthalmol1998;82:12804.

    9 Okada M, Yamamoto S, Watanabe H, et al.Granular corneal dystrophy with homozygousmutations in the kerato-epithelin gene.Am J Ophthalmol1998;126:16976.

    10 Okada M, Yamamoto S, Inoue Y, et al. Severecorneal dystrophy phenotype caused byhomozygous R124H keratoepithelin mutations.Invest Ophthalmol Vis Sci1998;39:194753.

    11 Fujiki K, Hotta Y, Nakayasu K,et al.Homozygotic

    patient with betaig-h3 gene mutation in granulardystrophy. Cornea1998;17:28892.

    12 Inoue T, Watanabe H, Yamamoto S, et al.Different recurrence patterns afterphototherapeutic keratectomy in the cornealdystrophy resulting from homozygous andheterozygous R124H BIG-H3 mutation.Am J Ophthalmol2001;132:2557.

    Vitreous amyloidosis in alanine71 transthyretin mutationFamilial amyloid polyneuropathy (FAP) asso-ciated with mutations in the transthyretin(TTR) gene is the commonest form ofhereditary amyloidosis. The incidence of

    vitreous opacities in FAP varies from 5.4%to 35%,1 2 but vitreous opacities as part of

    systemic amyloidosis are virtually pathogno-monic of FAP. Hereditary non-neuropathicsystemic amyloidosis is associated withmutations in the genes for lysosyme, apoli-poprotein A-I, or fibrinogen Aa-chain. Thereare some 80 known mutations in TTR gene of

    which the methionine 30 variant is the mostcommon.3 The rare alanine 71 (Ala 71)

    variant with vitreous opacities has beendescribed in one family from France andanother from Spain.4 5 We report a case ofFAP Ala 71 without a family history of thedisease who presented with a monocularinferior visual field defect and a correspond-ing vitreous opacity. Amyloid deposition was

    subsequently diagnosed on vitreous and suralnerve biopsy.

    Case reportA 46 year old woman presented with aninferior visual defect in her left eye. Ocularand systemic evaluation was normal includ-ing brain computed tomography scan.Eighteen months later, the patient developedbilateral floaters and visual loss in the left eyereducing her vision to 20/15 right and 20/30left. Deposits of white fluffy material werenoted on the posterior capsule of the left eye(fig 1A) as well as bilateral branching

    vitreous opacities, peripheral retinal haemor-rhages and perivascular sheathing (fig 1B).The left eye had a partial posterior vitreousdetachment (PVD), a large vitreous floaterand old inferior vitreous haemorrhage (VH).

    Vitreous opacification progressed andvisual acuity was reduced to hand movement1 year later. A full blood count, coagulationscreen, and biochemical profile were normal.Creatinine clearance demonstrated a mildreduction in renal function and plasma celldyscrasia was ruled out. Pars plana vitrect-

    omy successfully cleared the vitreous debris,restoring vision to 20/20 in the left eye.Eighteen months later the patient developeda right foot drop, progressive lower limbnumbness, and numbness in both hands. Asural nerve biopsy established the diagnosisof amyloidosis and immunohistochemistryconfirmed that TTR was the major proteinconstituent of the deposits. Cardiac involve-ment was demonstrated on echocardiographyand renal involvement was confirmed byserum amyloid P (SAP) scintigraphy.Sequencing of her TTR gene confirmed thatshe was heterozygous for the amyloidogenic

    Ala 71 variant.

    The patients right visual acuity deterio-rated to 20/120 because of increasing white

    vitreous opacities and nodular opacities onthe anterior vitreous face. Right vitrectomyresulted in a return of visual acuity to 20/20.

    An undiluted right vitreous biopsy confirmedlarge amounts of amyloid of the TTR type(fig 2). The patient currently awaits orthopticliver transplantation (OLT).

    CommentVitreous opacification was initially attributedto old VH secondary to idiopathic retinal

    vasculitis. Vitreous biopsy subsequently con-firmed amyloid in the fellow eye. VH mayoccur secondary to vascular adventitial amy-loid deposition or vitreous separation leadingto a retinal tear, although vitreous opacitiesmay be misinterpreted as Kantarjian and deJong first reported vitreous amyloid in FAP.6

    Amyloid of the vitreous body has beendescribed as glass wool, sheet-like veils orstring of pearls white opacities, whichdiffers from localised ocular amyloid in theorbit, lacrimal gland, conjunctiva, eyelids,sclera, and more specific forms in the cornea.Previous studies have reported abnormalconjunctival vessels, pupillary abnormalities,keratoconjunctivitis sicca, glaucoma, and

    vitreous opacities.Almost all of the circulating TTR is

    produced in the liver and OLT can halt theprogression of this disease and lead to clinicalimprovement. 7 SAP scintigraphy is a methodfor identifying and quantitatively monitoringamyloid deposits in vivo,7 but this techniqueis not sensitive enough to monitor vitreousamyloid. Surprisingly, progressive vitreousamyloid deposition has been reported follow-ing OLT, suggesting the TTR that forms

    vitreous amyloid may be produced locally.8

    Previous reports have established that TTRhas a widespread distribution in the eye butTTR mRNA has exclusively been located inthe retinal pigment epithelium (RPE).9 Giventhat plasma TTR does not cross Bruchsmembrane, it appears that ocular TTR issynthesised at least in part in the RPE, butthe exact factors determining amyloiddeposition are not understood.

    Bilateral branching vitreous deposits ofunknown aetiology should always raise thepossibility of systemic amyloidosis. A relevantfamily history should be sought, but even inits absence, mutations of the TTR gene shouldbe looked for.

    H J Zambarakji, D G CharterisMoorfields Eye Hospital, Vitreoretinal Service,

    London, UK

    Figure 2 Apple-green birefringence withCongo red stain viewed with polarisedmicroscopy of a vitreous biopsy confirming thepresence of amyloid deposits.

    Figure 1 Dense nodular white deposits on the posterior capsule of the left eye were presumed tobe of amyloid origin (A), and fundus periphery demonstrates intraretinal haemorrhages andperivascular white deposits (B).

    Accepted for publication 1 November 2004

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    W AyliffeMayday University Hospital, Ophthalmology

    Department, London, UK

    P J LuthertInstitute of Ophthalmology, Pathology Department,

    London, UK

    F SchonMayday University Hospital, Neurology Department,

    London, UK

    P N Hawkins

    National Amyloidosis Centre, Department ofMedicine, Royal Free and University College Medical

    School, London, UK

    Correspondence to: Dr H Zambarakji, Angiogenesis,Massachusetts Eye and Ear Infirmary, 325 Cambridge

    Street, Boston, MA 02114, USA;[email protected] or

    [email protected]

    doi: 10.1136/bjo.2004.057554

    References

    1 Ando E, Ando Y, Okamura R,et al.Ocularmanifestations of familial amyloidoticpolyneuropathy type I: long term follow up.Br J Ophthalmol1997;81:2958.

    2 Koga T, Ando E, Hirata A, et al.Vitreousopacities and outcome of vitreous surgery inpatients with familial amyloidotic polyneuropathy.Am J Ophthalmol2003;135:18893.

    3 Connors LH, Richardson AM, Theberge R, et al.Tabulation of transthyretin (TTR) variants as of 1/1/2000.Amyloid2000;7:5469.

    4 Benson MD, Turpin JC, Lucotte G, et al. Atransthyretin variant (alanine 71) associated withfamilial amyloidotic polyneuropathy in a Frenchfamily.J Med Genet1993;30:1202.

    5 Almeida MR, Lopez-Andreu F, Munar-Ques M,etal.Transthyretin ALA 71: a new transthyretinvariant in a Spanish family with f amilialamyloidotic polyneuropathy.Hum Mutat1993;2:4201.

    6 Kantarjian AD, de Jong RN. Familial primaryamyloidosis with nervous system involvement.Neurology1953;3:399409.

    7 Rydh A, Suhr O, Hietala SO,et al. Serumamyloid P component scintigraphy in familialamyloid polyneuropathy: regression of visceralamyloid following liver transplantation.Eur J NuclMed1998;25:70913.

    8 Munar-Ques M, Salva-Ladaria L, Mulet-Perera P,et al.Vitreous amyloidosis after livertransplantation in patients with familial amyloidpolyneuropathy: ocular synthesis of mutanttransthyretin. Amyloid2000;7:2669.

    9 Cavallaro T, Martone RL, Dwork AJ, et al. Theretinal pigment epithelium is the unique site oftransthyretin synthesis in the rat eye.InvestOphthalmol Vis Sci1990;31:497501.

    Multifocal electroretinogramdemonstrated macular toxicityassociated with ethambutol

    related optic neuropathyEthambutol is an effective drug in the firstline treatment for tuberculosis but its usemay be associated with ocular toxicity.1 Toxicoptic neuropathy is the most importantocular side effect and is related to the doseand duration of treatment.2 It is usuallybilateral and both central and peripheraltypes of optic neuropathy have beendescribed. The central type involves thepapillomacular bundle and results indecreased visual acuity, caecocentral sco-toma, and blue-yellow colour vision loss,

    whereas the peripheral type causes peripheralvisual field loss, especially bitemporal defects

    with sparing of visual acuity and red-greencolour vision impairment.3 In additional tothe optic nerve toxicity, studies have alsodemonstrated that ethambutol may also betoxic at the retinal level.46 We report apatient with ethambutol related toxic opticneuropathy associated with bilateral maculartoxicity as demonstrated by multifocal elec-troretinogram (mfERG). To our knowledge,evaluation of ethambutol related maculartoxicity with mfERG has not been previouslyreported.

    Case reportA 45 year old man with pulmonary tubercu-losis presented with a 3 week history ofgradual bilateral visual loss. He has been onantituberculosis therapy with ethambutol900 mg (15 mg/kg/day), rifampicin 600 mg,isoniazid 300 mg, and pyrazinamide 2 g for4 months. The baseline best corrected visualacuity (BCVA) before antituberculosis ther-apy was 20/30 in the right eye and 20/20 inthe left eye. On presentation, the BCVA was20/200 bilaterally without afferent pupillarydefect. Colour vision testing showed redgreen dyschromatopsia. Dilated fundusexamination revealed bilateral small splinterhaemorrhages adjacent to the optic discs with

    mild left optic disc swelling (fig 1A). Visualfield examination showed bilateral centralscotoma (fig 1B). Magnetic resonance images(MRI) of the brain and orbits were normal. Adiagnosis of toxic optic neuropathy due toethambutol was made.

    Since the optic discs and fundus changeswere relatively subtle compared with thereduction in visual acuity and the central

    visual field defects and red-green dyschro-matopsia were atypical, further investigations

    were performed to evaluate potential asso-ciated retinal toxicity. These included electro-oculogram (EOG), flash electroretinogram(ERG), pattern visual evoked potential(VEP), and mfERG. EOG and flash ERG ofboth eyes were normal. Pattern VEP showedno response for smaller checkers, with weakand delayed response for large checkers of1.8 . MfERG demonstrated bilateral general-ised reduction in N1 and P1 retinal responseamplitudes suggestive of toxic maculopathy(fig 2A).

    In view of the optic neuropathy andmaculopathy, all antituberculosis drugs werestopped after discussion with the physicians.The patients BCVA gradually improved and3 months later, his BCVA improved to 20/30bilaterally. No abnormality was seen onfundus examination. Repeat mfERG record-ing showed recovery of the retinal responsesin both eyes (fig 2B).

    CommentThe exact mechanism of ethambutol inducedtoxic optic neuropathy is unclear but it maybe due to retinal ganglion cells or bipolar cellstoxicity at the retinal level.47 mfERG is atechnique that allows objective assessment ofmacular function in retinal diseases.8 9 In

    contrast with conventional full field flashERG which stimulates and measures theresponse of the entire retina, mfERG stimu-lates individual macular areas and measuresresponses from different retinal locations. Itis useful in differentiating macular and opticnerve diseases as the mfERG in patients withoptic nerve disease should be normal.9 10 Withthe use of mfERG, we demonstrated thatthere was generalised reduction in mfERGresponses at the macula and the areas of

    Accepted for publication 20 October 2004

    Figure 1 (A) Fundus photograph of the right (left) and left (right) eyes on presentationdemonstrating bilateral splinter haemorrhages (arrows) with mild left optic disc swelling. (B)

    Automated visual field test showed central scotoma in the left (left) and right (right) eyes.

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    abnormality were more extensive than theapparent localised visual field defectsdetected by automated perimetry. The abnor-mal mfERG suggests that in addition to toxicoptic neuropathy, ethambutol may also causemacular toxicity at the neurosensory retinallevel. The improvement in the patients BCVAparalleled the improvement in mfERGresponses and therefore mfERG may be auseful tool not only in diagnosis but in the

    serial assessments of ethambutol relatedocular toxicity, particularly in patients withcentral visual loss.

    T Y Y Lai, W-M Chan, D S C LamDepartment of Ophthalmology and Visual Sciences,

    The Chinese University of Hong Kong, Hong Kong EyeHospital, Hong Kong, Peoples Republic of China

    E LimDepartment of Ophthalmology and Visual Sciences,

    The Chinese University of Hong Kong, Prince of WalesHospital, Hong Kong, Peoples Republic of China

    Correspondence to: Dr Wai-Man Chan, Departmentof Ophthalmology and Visual Sciences, The Chinese

    University of Hong Kong, 3/F, Hong Kong EyeHospital, 147K Argyle Street, Kowloon, Hong Kong;

    [email protected]

    doi: 10.1136/bjo.2004.058099

    References

    1 Carr RE, Henkind P. Ocular manifestations ofethambutol. Toxic amblyopia after administrationof an experimental antituberculous drug. ArchOphthalmol1962;67:56671.

    2 Leibold JE. The ocular toxicity of ethambutol andits relation to dose. Ann NY Acad Sci1966;135:9049.

    3 Schild H Fox. Raipd-onset reversible oculartoxicity from ethambutol therapy.Am J Med1991;90:4046.

    4 Van Dijk BW, Spekreijse H. Ethambutol changesthe color coding of carp retinal ganglion cellsreversibly. Invest Ophthalmol Vis Sci1983;24:12833.

    5 Kakisu Y, Adachi-Usami E, Mizota A. Patternelectroretinogram and visual evoked corticalpotential in ethambutol optic neuropathy.DocOphthalmol1987;67:32734.

    6 Nasemann J, Zrenner E, Riedel KG. Recoveryafter severe ethambutol intoxication:psychophysical and electrophysiologicalcorrelations. Doc Ophthalmol1989;71:27992.

    7 Heng JE, Vorwerk CK, Lessell E,et al.Ethambutolis toxic to retinal ganglion cells via an excitotoxicpathway. Invest Ophthalmol Vis Sci1999;40:1906.

    8 Sutter EE, Tran D. The field topography of ERGcomponents in man: I. The photopic luminanceresponse. Vis Res1992;32:43346.

    9 Hood DC. Assessing retinal function with themultifocal technique.Prog Retin Eye Res2000;19:60746.

    10 Kretschmann U, Bock M, Gockeln R,et al.Clinicalapplications of multifocal electroretinography.Doc Ophthalmol2000;100:99113.

    Eye involvement mimickingscleritis in a patient with chroniclymphocytic leukaemia

    Acute leukaemia is known to affect the eye ina wide variety of ways and detailed post-mortem examination will often reveal sub-clinical involvement. Ocular involvement bychronic leukaemia is much less common.1 Wedescribe the clinical presentation, evaluation,and response to therapy of what is to ourknowledge the first case of clinically signifi-cant scleral infiltration by chronic lymphocy-tic leukaemia mimicking scleritis.

    Case reportAn 87 year old man presented with a 2 weekhistory of right eye redness, pain, anddecreased vision. He complained of horizon-tal diplopia for 2 years, which had beencorrected with prisms, but never investigated.Past medical history was notable only forchronic lymphocytic leukaemia (CLL), which

    was first diagnosed 17 years before presenta-tion. He was treated intermittently withchlorambucil, but this was stopped as his

    white cell count had been stable at 306

    109/l with minimal cervical and axillarylymphadenopathy. Vision was 6/18 right eyeand 6/9 left eye. Intraocular pressure (IOP)

    was 18 mm Hg in each eye. His vision wasreduced by bilateral early cataracts and hisright eye showed inferior scleral injection(fig 1A), a fibrinous anterior uveitis, andscattered posterior synechiae.

    The patient was treated with topicalcorticosteroids and cycloplegics, but over the3 weeks following presentation his visiondropped to 6/60 right eye because of choroidaleffusions. He had restricted movement of theright eye, proptosis, and shallowing of theanterior chamber with an increase in IOP to26 mm Hg. Ultrasound revealed thickening ofthe inferior sclera. A CT scan of the right orbit

    revealed a mass in the inferior fornix thatwas attached to the sclera (fig 1B). Excisionbiopsy revealed patchy infiltration by foci ofdensely packed small lymphocytic cells,mainly around small blood vessels (fig 2A).Immunostaining showed a predominance of

    weakly stained CD20 positive B lymphocyteswith scattered CD3 positive T cells consistentwith CLL. Haematological analysis revealed atotal white cell count of 49.16109/l. Hereceived orbital radiotherapy 27.5 Gy in 11fractions using 6 MV x rays, completing thecourse 5 months after presentation. Theinflammation, choroidal effusions, and orbi-tal mass regressed completely but he was left

    with thinning of the inferior sclera (fig 2B).He was last seen 2 years after presentation

    with vision of 6/60 right eye but no evidence

    of active ocular involvement from his CLL. Herefused cataract surgery.

    Figure 2 (A) Trace arrays of multifocal electroretinogram (mfERG) of the right (left) and left (right)eyes on presentation showing generalised reduction of retinal responses at the macula. (B) Tracearrays of mfERG of the right (left) and left (right) eyes 3 months after cessation of ethambutoldemonstrating recovery and improvement of the mfERG responses.

    Accepted for publication 20 October 2004

    Financial support: nil.

    Financial interest: nil.

    Figure 1 (A) Right eye showing diffuseinjection of the inferior sclera. (B) Computedtomography (CT) scan of orbit showing a massthat was confluent with the sclera.

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    CommentThis patient presented with what at firstappeared to be a scleritis with a secondaryfibrinous anterior uveitis. He was 87 yearsold, which is an unusual age for a firstpresentation of either scleritis or anterioruveitis. His history of chronic diplopia andpast medical history of CLL suggested apossible aetiology for these findings. It isuncommon for CLL to affect the eye in aclinically significant way2 although postmor-tem examination has shown relatively fre-quent subclinical involvement in between30% and 90% of patients.3 Despite this, CLL

    has been described causing uveitis, glaucoma,iris infiltration,4 retinal detachments, con-

    junctival vascular changes, optic neuropathy,and orbital involvement as well as the moretypical retinal haemorrhagic changes.

    Episcleral and scleral infiltration is recog-nised in acute leukaemia and has been seenat necropsy in chronic leukaemia in 14% ofcases in one series but this is rarely sympto-matic.3

    In our patient the response to radiotherapywas encouraging and although his finalacuity was not improved this was due in partto the progression of his cataracts. Insummary, this is the first case we are awareof in which CLL had infiltrated the sclera ofan eye to a sufficient degree that it simulated

    scleritis. The scleral mass regressed comple-tely following radiotherapy although visiondid not recover.

    B J L BurtonMedical Retina Service, Moorfields Eye Hospital, City

    Road, London EC1V 2PD, UK

    E T Cunningham JrDepartment of Ophthalmology, New York University

    School of Medicine, New York, NY, USA

    I A CreeInstitute of Ophthalmology 1143 Bath Street, London

    EC1V 9EL, UK

    C E PavesioMedical Retina Service, Moorfields Eye Hospital, City

    Road London EC1V 2PD, UK

    Correspondence to: Mr C Pavesio, Moorfields EyeHospital, City Road, London EC1V 2PD, UK;

    [email protected]

    doi: 10.1136/bjo.2004.060152

    References

    1 Allen RA, Straatsma BR. Ocular involvement inleukemia and allied disorders. Arch Ophthalmol1961;66:490508.

    2 Buchan J, McKibbin M, Burton T. The prevalenceof ocular disease in chronic lymphocyticleukaemia.Eye2003;17:2730.

    3 Kincaid MC, Green WR. Ocular and orbitalinvolvement in leukemia. Surv Ophthalmol1983;27:21132.

    4 Martin B. Infiltration of the iris in chroniclymphatic leukaemia.Br J Ophthalmol1968;52:7815.

    Regression of choroidalmetastases from breastcarcinoma using aromataseinhibitorsBreast cancer has become a leading healthconcern in the United States, accounting for30% of all cancers among women.1 Oestrogenis an important hormone involved in thedevelopment and growth of breast tumours.2

    It has been found that 6070% of breastcancers have oestrogen receptors.2 Followingtumour resection, receptor positive patientsare commonly treated with hormone therapysuch as tamoxifen. Tamoxifen is a competi-tive antagonist of oestrogen at its receptorsite. It is most often used for postmenopausalpatients with oestrogen receptor positivebreast cancers. However, tamoxifen also hasa partial oestrogen agonist effect which couldbe detrimental, because it can lead to

    increased risk for uterine cancer, throm-boembolism, and treatment failure.3

    The third generation aromatase inhibitors,including anostrozole, letrozole, and vorozole,have emerged as a new treatment for post-menopausal women with oestrogen receptorpositive breast cancer. Their mechanismdiffers from that of tamoxifen as theyminimise peripheral conversion of circulatingandrogen to oestrogen.3 We report onepatient with choroidal metastasis from oes-trogen receptor positive breast cancer whoshowed an excellent response to oral aroma-tase inhibitors.

    Case reportA 66 year old woman presented in January

    2003 with a 5 month history of flashinglights in the right eye. Her medical historyrevealed breast cancer, oestrogen receptorpositive, treated with modified radical mas-tectomy and tamoxifen. In 1989, tamoxifen

    was stopped per the standard 5 year protocol.In October 2002, she developed metastases tothe supraclavicular lymph nodes bone and

    was started on anastrozole.On examination, visual acuity was 20/60

    RE and 20/20 LE. Fundus examinationrevealed subretinal fluid overlying a solitaryamelanotic choroidal metastasis measuring12 mm in base and 3 mm in thickness (fig 1).The patient was continued on anastrozole. In

    September 2003, the choroidal metastasiscompletely regressed with resolution of sub-retinal fluid (fig 2). Her visual acuityremained 20/40 RE and 20/20 LE.

    CommentUveal metastases are the most commonintraocular malignancy. They typically affectthe posterior choroids.4 The most commonprimary sites of cancer are from breast (47%),lung (21%), and gastrointestinal tract (4%). 5

    Classically, choroidal metastases are yellow,plateau shaped, with secondary subretinalfluid. The treatment of choroidal metastases

    Figure 2 September 2003. (A) Following9 months of anastrozole treatment, choroidalmetastasis has regressed.(B) Optical coherencetomography following 9 months of anastrozoletreatment showing resolution of subretinal fluid.

    Accepted for publication 16 November 2004

    Figure 2 (A) Histopathology of scleral massshowing foci of densely packed smalllymphocytic cells, mainly around small blood

    vessels (haematoxylin and eosin stain, original

    magnification6200). (B) Right eye followingtherapy showing thinning of the inferior sclera.

    Figure 1 January 2003. (A) Active choroidalmetastasis from breast carcinoma at firstexamination. (B) Optical coherence

    tomography showing subretinal fluid in thefovea.

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    depends on many factors including location,multiplicity, and activity of each tumour.6 7

    Additionally, the projected visual outcomeand underlying systemic control is important.In some cases, therapy is limited to the eye,especially if systemic metastases are absent orin remission. In these instances, externalbeam radiotherapy or plaque radiotherapy areemployed.6 In most instances, however, thepatient has systemically active metastaticdisease so therapy is directed towards treat-ment of both the ocular and systemic disease

    using chemotherapy or hormone therapy.6

    The most commonly employed hormonaltreatment for breast cancer is tamoxifen.2 It isusually employed for postmenopausalpatients with breast cancer who displayoestrogen receptors. The effect of tamoxifenis due to its anti-oestrogenic activity, bycompetitive inhibition of oestrogen bindingto oestrogen receptors.2 Tamoxifen inhibitsthe expression of oestrogen regulated genesincluding growth factors and angiogenicfactors secreted by the tumour. Tamoxifencan also induce programmed cell death.Tamoxifen additionally has partial agonisteffects, which could be beneficial because itprevents bone demineralisation in postmeno-pausal women.3 However, these oestrogeniceffects are also associated with increasedrisks of uterine cancer, thromboembolism,and treatment failure.3

    Tamoxifen is well tolerated by mostpatients with breast cancer and only 5% ofpatients note related menopausal symptoms,such as hot flashes and vaginal discharge.2

    Retinopathy has been reported in womenwith high doses of tamoxifen, but not withconventional doses.

    In postmenopausal women the mainsource of oestrogen is from peripheral con-

    version of adrenal androgen. New thirdgeneration aromatase inhibitors, includinganastrozole (Arimidex, Zeneca) and letrozole(Femara, Novartis), act by preventing thisconversion, thus lowering circulating oestro-gen levels. Studies have shown that they are

    equal or superior to tamoxifen in clinicallyefficacy for metastatic breast carcinoma.3

    They are well tolerated and have been shownto have important benefits over tamoxifen.Comparative trials indicate that anastrozolehas similar adverse effects compared totamoxifen.8 9 Our patient responded drama-tically to aromatase inhibitors after failing torespond to tamoxifen. Based on this case andthree other cases with a favourable response

    we anticipate that aromatase inhibitors couldbe a promising alternative for patients withchoroidal metastases from oestrogen receptorpositive breast carcinoma.

    M E Manquez, C L Shields, E C Karatza,J A Shields

    Oncology Service, Wills Eye Hospital, ThomasJefferson University, Philadelphia, PA, USA

    Correspondence to: Dr Maria Manquez, OncologyService, Wills Eye Hospital, 840 Walnut Street,

    Philadelphia, PA 19107, USA;[email protected]

    doi: 10.1136/bjo.2004.061127

    References

    1 Feig BW, Berger DH, Fuhrman GM. In: Breastcancer. The MD Anderson surgical oncologyhandbook. Philadelphia: Lippincott Williams andWilkins, 2003:14.

    2 Osborne CK. Tamoxifen in the treatment of breastcancer. N Engl J Med1998;339:160918.

    3 Smith IE, Dowsett M. Aromatase inhibitors inbreast cancer.N Engl J Med2003;348:243142.

    4 Shields JA, Shields CL. In:Metastatic tumor to theuvea and retina. Intraocular tumors. A text andatlas. Philadelphia: WB Saunders,1992:278320.

    5 Shields CL, Shields JA, Gross N, et al. Survey of520 eyes with uveal metastases.Ophthalmology1997;104:126576.

    6 Shields CL. Plaque radiotherapy for themanagement of uveal metastasis. Curr OpinOphthalmol1998;9:317.

    7 Demirci H, Shields CL, Chao AN, et al. Uvealmetastasis from breast cancer in 264 patients.Ophthalmology2003;136:26471.

    8 ATAC(Arimidex, Tamoxifen Alone or inCombination) Trialists Group. Anastrozole aloneor in combination with tamoxifen alone foradjuvant treatment of postmenopausal womenwith ear ly breast cancer: first results of the ATACrandomized trial.Lancet2002;359:21319.

    9 Mouridsen H, Gershanovich M, Sun Y, et al.Superior efficacy of letrozole versus tamoxifen asfirst-line therapy for postmenopausal women withadvanced breast cancer: results of a phase IIIstudy of the International Letrozole Breast CancerGroup. J Clin Oncol2001;19:2596606.

    Fingertip cryoprobe assistedorbital tumour extractionCryoprobes are used to grasp, provide trac-tion, and facilitate orbital tumour removal.14

    Standard ophthalmic cryoprobe tips aretypically rounded and offer small surfaceareas for cryo-adhesion. I describe a newspatulated cryotherapy probe with a largeoval and uniform surface area for adhesion

    and subsequent traction. This report usesphotography to document the use of thisprobe and describes its manufacture andeffectiveness during orbital surgery.

    MethodsThree spatulated probes were manufactured(Mira, Inc, Finger-tip probe, Uxbridge, MA,USA) under Good Manufacturing Practice(GMP), International Standards Organiza-tion (ISO), and Food and Drug Administra-tion (FDA) guidelines (fig 1).

    The medium sized probe has an activesurface of 25.2 mm2. Its design allows forpreferential cooling of the active surface ofthe applicator. Mira tested this probe to coolto up to 85 C on nitrous oxide (as governedby the Joule-Thompson principle).

    ResultsA 77 year old patient was found to have asuperonasal orbital tumour (by clinical exam-ination and radiographic imaging). Thetumour was 18 mm in largest diameter andfound to be contiguous with both the orbital

    the Macula Society (Dr CL Shields), the Paul KayserInternational Award of Merit in Retina Research,Houston, TX (Dr JA Shields).

    Figure 1 Top, the 25.2 mm2 surface arealarge Finger-tip cryotherapy probe set toshow its spatulated active surface. Bottom,computed tomography shows a well defined,1.8 cm lobular tumour in the superonasal orbit.

    Figure 2 Top left, the tumour (arrow) can be seen deep within the superonasal orbit. Top right, thecryoprobe is introduced such that the spatulated tip is placed flush with the tumour and not touchingadjacent orbital tissues. Bottom left, the tumour is delivered from the orbit utilising the cryo-adhesion. Bottom right; the tumour is visualised outside the orbit. Note the freeze within the tissue

    with minimal ice formation on the shaft of the probe.

    Accepted f or publication 31 October 2004

    Supported in part by the Pan American Ophthalmo-logy Foundation and Retina Research Foundation (DrME Manquez), the Eye Tumor Research Foundation,Philadelphia, PA (Dr CL Shields)the Macula Foundation,New York, NY (Dr CL Shields), the Rosenthal Award of

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    portion of the frontal bone and optic nerve.Ultrasonography revealed intrinsic tumour

    vascularity (low flow). Cavernous haeman-gioma was suspected and an anterior orbi-totomy performed. A combination of sharpand blunt dissection was required to exposethe tumour. Then, a medium sized Finger-tip cryoprobe was used to create an adhe-sion to the tumours surface (fig 2). Thisrelatively large cryo-adhesion allowed foreasier handling of the tumour and improvedtraction (fig 2). The tumour remained adher-

    ent to the cryoprobe for 60 seconds after thenitrous oxide was discontinued. Freezinginduced no change in the appearance ofthe tumour on gross examination.Histopathology revealed cavernous haeman-gioma. No clinical side effects (related tocryo-extraction) were noted.

    CommentCryo-extraction works best with tumours andcysts that contain fluids (for example, blood,tears), as opposed to solid tumours and thosecontaining lipid or keratin (for example,dermoid). Thus, cavernous haemangiomasare particularly good candidates becausefreezing occurs on both the tumours surface(capsule) and within the tumour stroma.

    With a well formed fibrous capsule, the outerand inner ice balls provide a strong attach-ment to the probe.

    The fingertip cryoprobes differ from pre-viously available applicators in that they offerrelatively large, spatulated tips. This allowsfor more homogeneous cryo-adhesion over alarger surface area. The larger surface area ofapplication also increases tissue penetration,resulting in a stronger adhesion.

    This study examines a new type of cryop-robe used to assist orbital surgery duringtumour extraction. It was found capable ofadhering to the tumour. Held by the surgeon,tumour traction could be induced with onehand, while the other hand wielded instru-ments used to sever residual tumour attach-ments.5 Fingertip cryoprobes offer an

    alternative to current devices used for cryo-extraction of orbital tumours.

    Correspondence to: P T Finger, MD, The New YorkEye Cancer Center, 115 East 61st Street, New York

    City, NY 10021, USA; [email protected]

    doi: 10.1136/bjo.2004.055426

    References

    1 Maroon JC, Onik G, Quigley MR, et al.Cryosurgery re-visited for the removal anddestruction of brain, spinal and orbital tumours.Neurol Res1992;14:294302.

    2 Henderson JW, Neault RW. The use of thecryoprobe in the removal of posterior orbitaltumors.Ophthalmic Surg1976;7:457.

    3 Loewenstein A, Geyer O, Lazar M. Cavernoushaemangioma of the orbit: treatment bytransconjunctival cryoextraction.Eye1993;7(Pt4):5978.

    4 Gdal-On M, Gelfand YA. Surgical outcome oftransconjunctival cryosurgical extraction of orbitalcavernous hemangioma.Ophthalmic Surg Lasers1998;29:96973.

    5 Finger PT. Finger-tip cryoprobe assistedenucleation.Am J Ophthalmol, (in press).

    Congenital third nerve palsy,moyamoya disease and opticnerve head staphylomaThe association of congenital optic nervehead anomalies, especially of the morningglory disc variety, with moyamoya disease is

    well recognised and has been described in anumber of patients.14 To the best of ourknowledge, the occurrence of a congenitalthird nerve palsy with moyamoya disease anda congenital optic nerve head anomaly has

    not been reported. We describe a patient whodemonstrated the ipsilateral occurrence ofthese three congenital abnormalities,strengthening the association of congenitaloptic nerve and carotid abnormalities andsuggesting a common underlying aetiology.

    Case reportA 3 year old boy was examined because ofleft sided exotropia and blepharoptosis. Hisbirth, developmental, and medical histories

    were unremarkable. Visual acuity was 20/25right eye and 20/200 left eye. There was anear total ptosis of the left upper eyelid. There

    was a large exotropia and a small hypotropiaof the left eye that he was unable to adduct,elevate, or infraduct. His right pupil reacted

    briskly to light, but the left pupil was dilatedand sluggishly reactive to light. A left relativeafferent pupillary defect was present. Fundusexamination disclosed an anomalous leftoptic disc and peripapillary area, with whatappeared to be an enlarged scleral openingand a staphylomatous defect around the opticpapilla (fig 1). The rest of the retina wasnormal. The right fundus was normal.

    A magnetic resonance imaging scan andmagnetic resonance angiogram of the brainrevealed an absence of the left intracranialcarotid artery and its bifurcation into middleand anterior cerebral arteries. The lenticulo-striate arteries were increased in size, con-sistent with moyamoya vessels (fig 2).

    CommentThis patient has an optic nerve head mal-formation that appears to be most compatible

    with a peripapillary staphyloma or a variantof a morning glory disc anomaly (MGDA).MGDA is one of the cavitary optic discmalformations comprising a congenital, fun-nel-shaped excavation of the posterior peri-papillary sclera that incorporates the opticdisc. In addition to the anomalous retinal

    vasculature that distinguishes the MGDAfrom other excavated optic disc anomaliessuch as optic disc coloboma, the associationof morning glory disc with carotid circulationanomalies, especially moyamoya disease hasbeen reported.15 Moyamoya disease is a rarecerebrovascular disorder characterised bystenosis or occlusion of the distal internalcarotid arteries. Progressive brain ischaemia

    triggers formation of a collateral vascularnetwork in the basal ganglia region referredto as moyamoya (Japanese word for cloud ofsmoke) vessels. The most common clinicalfeatures are transient ischaemic attacks andstroke in children, and intracranial haemor-rhage in adults. Our patient appears to havean extreme form of this condition with totalabsence of the left internal carotid artery andcollateral vessel formation typical of moya-moya disease.

    Congenital third nerve palsy was oncethought not to be associated with otherneurological abnormalities. More recent stu-dies have however revealed a high incidenceof associated neurological deficits such ashemiparesis, seizures, hemianopia, andhydrocephalus. 5 An association of congenital

    third nerve palsy with MGDA or peripapillarystaphyloma has not been reported to the bestof our knowledge. The third nerve palsy inthe present case may be due to an ischaemicbrainstem event or a developmental defectaffecting the left third nerve nucleus.

    The constellation of abnormalities in ourpatient confirms the association of moya-moya vessels with optic nerve head malfor-mations such as MGDA or peripapillarystaphyloma, and the possible neurologicalcomplications of this malformation complex,as evidenced by the third nerve palsy in thiscase. It is possible that an intracranial

    vascular dysgenesis may underlie some casesof the morning glory disc anomaly. Westrongly recommend magnetic resonance

    angiography in conjunction with magneticresonance imaging to identify carotid vascu-lar anomalies in patients with MGDA orperipapillary staphylomas, especially in thepresence of other neurological signs such as acongenital third nerve palsy.

    K Sabti, B A HajjAl-Bahar Eye Center and the Department of

    Ophthalmology, University of Kuwait, Kuwait City,Kuwait

    J-M HwangDepartment of Ophthalmology, Seoul Municipal

    Boramae Hospital, College of Medicine SeoulNational University, Seoul, Korea

    Accepted for publication 1 October 2004

    The work is supported by The EyeCare Foundation, Incand Research to Prevent. Blindness, New York, USA.

    Dr Finger has no proprietary interest in the instrumentdescribed in this study.

    Figure 2 Cerebral angiogram shows totalabsence of left internal carotid artery (arrow)

    with increased size of lenticulostriate arteriescompatible with moyamoya disease.

    Figure 1 Enlarged optic nerve head scleralopening with radial exit of retinal blood vessels.Note staphylomatous appearance ofperipapillary area.

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    J-M Hwang, E I TraboulsiThe Center for Genetic Eye Diseases, Cole Eye

    Institute, Cleveland, OH, USA

    J ReidDepartment of Pediatric Radiology, The Cleveland

    Clinic Foundation, Cleveland, OH, USA

    Correspondence to: Elias I Traboulsi, MD, Center forGenetic Eye Disease, Cole Eye Institute, The Cleveland

    Clinic Foundation, i32, 9500 Euclid Avenue,Cleveland, OH 44195, USA; [email protected]

    doi: 10.1136/bjo.2004.059246

    References

    1 Hanson MR, Price RL, Rothner AD, et al.Developmental anomalies of the optic disc andcarotid circulation. A new association. J ClinNeuroophthalmol1985;5:38.

    2 Massaro M, Thorarensen O, Liu GT, et al.Morning glory disc anomaly and moyamoyavessels.Arch Ophthalmol1998;116:2534.

    3 Bakri SJ, Siker D, Masaryk T, et al. Ocularmalformations, moyamoya disease, and midlinecranial defects: a distinct syndrome.Am J Ophthalmol1998;116:2534.

    4 Krishnan C, Roy A, Traboulsi E. Morning glorydisk anomaly, choroidal coloboma, andcongenital constrictive malformations of the

    internal carotid arteries (moyamoya disease).Ophthalmic Genet2000;21:214.

    5 Tsaloumas MD, Willshaw HE. Congenitaloculomotor palsy: associated neurological andophthalmological findings.Eye1997;11(Pt4):5003.

    Radial optic neurotomy for thetreatment of acute functionalimpairment associated with opticnerve drusenRadial optic neurotomy was recently intro-duced as a treatment option in patients withcentral retinal vein occlusion.1 As describedby Opremcak e t a l,1 central retinal vein

    occlusion might be related to increasedpressure on the central retinal artery and

    vein as well as on optic nerve fibres in theconfined space provided by the scleral ring. It

    was therefore suggested that a relaxation ofthe scleral outlet by a radial optic neurotomymight be an effective surgical treatmentoption. In the light of this information we

    hypothesised, that radial optic neurotomymay also be applicable in patients with visualfield defects and deterioration of visual acuityassociated with optic nerve drusen, wherecompression induced damage to optic nervefibres is the underlying pathogenetic princi-ple2

    Case reportA 27 year old female patient presented withextensive bilateraloptic nerve drusen (fig 1A).While visual acuity was light perception onthe right eye over 4 years, she had experi-enced an acute and rapid deterioration of

    visual acuity from 20/32 to 20/500 and aprogressive visual field loss within the past6 weeks before she was seen in our institu-tion (fig 1B). The progressive visual fielddefect had been documented carefully by thereferring ophthalmologist. Besides the opticnerve drusen, there was no other ophthalmicpathology, no history of glaucoma, or anyother relevant disease. With respect to therapid functional deterioration we discussedradial optic neurotomy as a potential treat-ment option. Surgery was performed, after

    written informed consent, by one of theauthors (AK) and consisted of standard threeport pars plana vitrectomy and radial opticneurotomy. The incision was performed atthe nasal edge of the optic disc in a radialfashion avoiding major retinal vessels. There

    were no intraoperative complications except asmall haemorrhage at the incision site. Thepatient was then carefully followed post-operatively at 3 week intervals. Already at thefirst follow up visit a regression of the visualfield defect and slight improvement of visualacuity was noted (fig 2A). At last presenta-tion 10 weeks after surgery, the visual fielddefect was limited to the inferior nasalquadrant and visual acuity had improved to20/32 (fig 2B). Funduscopy revealed a scar atthe incision site, but no other pathologies(fig 2C).

    Comment

    Drusen of the optic nerve are the result ofaxonal degeneration of retinal ganglioncells and are composed of acellular concentriccalcified laminations.3 While most cases areidiopathic, drusen have been described inassociation with several acquired condi-tions such as hypertensive retinopathy, vas-cular occlusion, optic atrophy, or chronic

    papilloedema. 4 If drusen are located deep inthe optic nerve, progressive enlargement mayresult in pressure induced atrophy of adjacentnerve fibres producing visual field constric-tion and anterior ischaemic optic neuropa-thy.2 Drusen have also been reported to occurpredominantly in eyes with abnormally smalloptic discs.5 It had been previously hypothe-sised,1 that a radial incision at the nasal edgeof the optic disc might result in a decom-pression of the scleral outlet and the asso-ciated neurovascular compression in patients

    with central retinal vein occlusion.Transferring this hypothesis to our patient,radial optic neurotomy seemed a reasonabletherapeutic approach to us, as a relaxation ordecompression of the scleral outlet mightcounteract the relevant pathogenetic princi-ples of progressive visual field defect in opticnerve drusen. To our knowledge, radial opticneurotomy has not been used for the treat-ment of progressive visual field defects inassociation with optic nerve drusen before.We were very aware of the experimentalcharacter of this surgical intervention andcarefully informed the patient before theoperation. However, with respect to the rapiddeterioration of visual acuity and progressionof visual field constriction, there seemed to beno other treatment option available and the

    surgical intervention appeared justified.The validity of the scleral outlet compart-

    ment syndrome concept in central retinalvein occlusion, as well as the effect of theradial neurotomy, has been questioned6 byHayreh and is currently under discussion.However, the excellent functional outcome inthis case may suggest that radial opticneurotomy potentially provides a relaxationand decompression of the optic nerve, allow-ing a recovery in conditions associated withpressure induced nerve fibre damage as in thecase presented. In retinal vein occlusion,other additional mechanisms of action, suchas the formation of chorioretinal shunts as aresult of radial optic neurotomy, weredescribed to contribute to visual recovery.7

    In summary, this case reports indicates

    that radial optic neurotomy might be con-sidered in patients presenting with sudden

    visual loss and constriction of visual field inassociation with optic nerve drusen. Weconsidered the surgical approach in thissingle case, as there was no other treatmentoption we could offer the patient that mightrestore vision.

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    Figure 1 Highly reflective signal seen during B-scan echography at the optic nerve head of the left eye as typical for optic nerve drusen (A). The drusenwere associated with a concentric visual field defect (B), visual acuity was 20/500.

    Accepted for publication 1 No vember 2004

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    C Haritoglou, S G Prieglinger, M Grueterich,

    A KampikDepartment of Ophthalmology, Ludwig-Maximilians-University, Mathildenstrasse 8, 80336 Munich,

    Germany

    G K KriegelsteinDepartment of Ophthalmology, University of Cologne,

    Joseph-Stelzmann-Strasse 9, 50931 Cologne,Germany

    Correspondence to: Christos Haritoglou, MD,Department of Ophthalmology,

    Ludwig-Maximilians-University, Mathildenstrasse 8,80336 Munich, Germany;

    [email protected]

    doi: 10.1136/bjo.2004.060335

    References

    1 Opremcak EM, Bruce RA, Lomeo MD, et al.Radial optic neurotomy for central retinal veinocclusion. A retrospective pilot study of 11consecutive cases.Retina2001;21:40815.

    2 Moody TA, Irvine AR, Cahn PH, et al. Suddenvisual field constriction associated with optic discdrusen. J Clin Neuroophthalmol1993;13:813.

    3 Tso MOM. Pathology and pathogenesis of drusenof the optic nerve head.Ophthalmology1981;88:106680.

    4 Apple DJ, Rabb MF, Walsh PM. Congenitalanomalies of the optic disc. Surv Ophthalmol1982;27:341.

    5 Jonas JB, Gusek G, Guggenmoos-Holzmann I,et al.Optic nerve head drusen associated with

    abnormally small optic discs. Int Ophthalmol1987;11:7982.

    6 Hayreh SS. Radial optic neurotomy for centralretinal vein occlusion. Retina2002;22:3747.

    7 Garcia-Arumi J, Boixadera A, Martinez-Castillo V,et al.Chorioretinal anastomosis afterradial optic neurotomy for central retinal veinocclusion.Arch Ophthalmol2003;121:138591.

    Early chorioretinal anastomosisin non-ischaemic CRVO: arandomised trialIn non-ischaemic central retinal vein occlu-sion (niCRVO), the two principal determi-nants of final visual acuity are visual acuityand the presence of macular oedema at initialpresentation.1 2 Data from the Central Vein

    Occlusion Study Group2 suggested that ofpatients with CRVO with an initial acuitybetter than 6/15, 65% maintain this, whereaspatients with presenting acuities between6/15 and 6/60, 81% remain the same or get

    worse (19% improve to 6/12 or better, 44%remain between 6/15, and 6/60 and 37% are

    worse than 6/60). Up to 34% of niCRVOmay progress to the ischaemic variant

    with its attendant complications within3 years.2 However, in some studies 83% ofindeterminate cases progress to ischaemicCRVO.1 The creation of a chorioretinal venousanastomosis (CRVA) improved visual acuityin some patients, decreased macular oedema,

    and reduced the incidence of progressionto ischaemic CRVO.35 These importantobservations provide the basis for the study

    we carried out.During the study period 11 patients

    (table 1) were enrolled according to the trialprotocol (see appendix). All anastomoses

    were patent (on fluorescein angiographyand if not repeated, see appendix). Meanpatient age and mean pretreatment (T0)

    visual acuities, retinal thickness (by opticalcoherence tomography, OCT), and cyst height(OCT) did not differ between the two groups(table 1, fig 1). Factorial analysis of variance(ANOVA, Genstat) found that all threemeasures (acuity, retinal thickness, and cystheight, fig 1) decreases significantly betweenT0 and 6 months, but only in the case of cystheight was there a significant difference

    between the laser treated and control groups(F(1,9)= 5.85, p,0.05). The changes inretinal thickness and visual acuity were alsogreater in the treatment group but did notachieve significance (F(1,9)= 2.51 and 1.15,respectively, both p.0.1). Larger group sizesmay have shown a significant effect.

    The principal limitation of this trial is thesmall number of patients, because of thelimited numbers of suitable patients withinthe study period. However, patients wererandomised and well matched. The trialshowed a trend towards better vision over6 months in the laser treated group, althoughthis failed to reach statistical significance.

    Accepted for publication 2 November 2004

    Financial interest: none.

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    Figure 2 There was a regression of the visual field defect noted 3 weeks after radial optic neurotomy (A). Ten weeks postoperatively the visual fielddefect was predominantly limited to the lower nasal quadrant (B). Funduscopy revealed a scar at the incision site at the nasal rim of the optic disc (C).

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    It remains possible that a larger groupof randomised patients would have pro-duced statistically significant numbers. Amulticentre trial would be required to achieve

    this. Another question arises regarding thelonger term outcome in these patients. Againthis should probably be considered in furtherstudies. Cyst height might predict later visualacuity as there is evidence that it correlates

    with visual acuity outcome measures.6 7 It istherefore possible that longer follow up mayhave found a significant improvement inacuity. Retinal thickness predicts and pre-cedes changes in visual acuity in diabeticretinopathy.8

    If the size and duration of this trial hadbeen increased, it is conceivable that resultsmay have proved more informative. The factthat there was a significant effect on cystheight on OCT is, nevertheless, importantand suggests that laser CRVA may reducemacular oedema in CRVO. The finding thatimprovements in visual acuity are recordedlater than reduction in macular oedema8 inother studies implies that a significant effecton visual acuity might have been expected inthese patients at a later time. We thereforerecommend that this be taken into account infuture studies.

    Acknowled gem entsWe gratefully acknowledge the help of ProfessorStephen Dunnett (Cardiff University) with statis-tical analysis of the data.

    R J Antcliff, E J Mayer, T H Williamson,J S Shilling

    Department of Ophthalmology, St Thomass Hospital,Lambeth Palace Road, London E1 7EH, UK

    Correspondence to: Eric Mayer, University of Bristol,Clinical Sciences, Bristol Eye Hospital, Lower Maudlin

    Street, Bristol BS1 2LX, UK; [email protected]

    doi: 10.1136/bjo.2004.062539

    App endixThe principal study end point was visualacuity at 6 months and resolution of macularoedema, the secondary end point was theidentification of subgroups on optical coher-

    ence tomography (OCT 2000, HumphreyInstruments, USA) with a more favourableoutcome including reduction of consecu-tive ischaemia. For entry into the studypatients were required to: (1) be within1 month of symptom onset; (2) have visualacuity of 6/24 or worse; (3) have good retinalperfusion (less than 10 disc diameters ofnon-perfusion); (4) have no relative afferentpupillary defect or neovascularisation; (5)have macular oedema confirmed by opticalcoherence tomography and fluorescein

    fundus angiography (FFA). The followingexclusion criteria were applied: diabetes withmacular oedema in the fellow eye; inability togive informed consent; pregnancy; sensitivityto fluorescein; cloudy media sufficient topreclude adequate fundal photography; ageless than 40 years.

    Upon entry into the trial the followingwere performed: best corrected visual acuity(Snellen and ETDRS); fundus photography,and fluorescein angiography; OCT assess-ment of the macula. Patients were then

    randomised (envelope) to laser or observa-tion groups. Laser anastomosis was per-formed with a 50 mm spot size for0.1 second with 1.52.5 W (maximum powerpossible) with an argon laser. The firstshot was fired at the edge of the vein torupture Bruchs membrane and the secondshot at the edge of the vein to rupture the

    vein. A third shot with a YAG laser wasapplied (35 mJ) if required. Anastomoticsites were attempted in the following loca-tions in order of preferenceinferonasal,inferotemporal, or superonasal. All anasto-moses were made at least 3 disc dia-meters from the optic disc. At 34 weeksrepeat FFA was performed to determineanastomotic success: where no anastomosis

    was present this was repeated, until func-tioning.

    Patients were reassessed at 1, 2, 3, 6, and12 months and acuities and OCT recorded.

    It was expected that approximately 40patients would be required to show a 50%benefit.

    Because of laser surgery it was not possibleto mask the patient or observer as to whichtreatment had been carried out.

    No adverse events were reported or notedin this series.

    References

    1 The Central Vein Occlusion Study. Baseline andearly natural history report.Arch Ophthalmol

    1993;111:108795.2 The Central Vein Occlusion Study Group. Natural

    history and clinical management of central retinalvein occlusion. Arch Ophthalmol1997;115:48691.

    3 McAllister IL, Constable IJ. Laser-inducedchorioretinal venous anastomosis fortreatment of nonischemic central retinalvein occlusion. Arch Ophthalmol1995;113:45662.

    4 McAllister IL, Douglas JP, Constable IJ,et al.Laser-induced chorioretinal venous anastomosisfor nonischemic central retinal vein occlusion:evaluation of the complications and theirrisk factors.Am J Ophthalmol1998;126:21929.

    5 McAllister IL, Vijayasekaran S, Yu DY,et al.Chorioretinal venous anastomoses: effect ofdifferent laser methods and energy in humaneyes without vein occlusion. GraefesArch Clin Exp Ophthalmol1998;236:17481.

    6 Antcliff RJ, Spalton DJ, Stanford MR,et al.Intravitreal triamcinolone for uveitic cystoidmacular edema: an optical coherencetomography study.Ophthalmology2001;108:76572.

    7 Beausencourt E, Remky A, Elsner AE,et al.Infrared scanning laser tomography ofmacular cysts.Ophthalmology2000;107:37585.

    8 Terasaki H, Kojima T, Niwa H, et al.Changes infocal macular electroretinograms and fovealthickness after vitrectomy for diabetic macularedema. Invest Ophthalmol Vis Sci2003;44:446572.

    ObservationLaser

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    Figure 1 Data of retinal thickness (A), cyst height (B), and visual acuity (C) for patients randomisedto laser chorioretinal venous anastomosis or observation. Visual acuity is measured on the ETDRSscale. Retinal thickness and cyst height were measured in pixels (1 pixel= 4 mm). Error bars showstandard errors of means, obtained from factorial analysis of variance. Significant effects areidentified as follows: *p,0.05; **p,0.01.

    Table 1 Comparison of randomised groups for early laser chorioretinal venousanastomosis versus observation in non-ischaemic CRVO (patient data areillustrated, visual acuities are given as ETDRS measures)

    Parameter Control Laser ttest

    Number of patients 5 6Female patients 2 2Left eyes 5 3Mean age 76.4 68.8 1.278, p = 0.117, NSMean pretreatment acuity 0.872 0.827 0.216, p = 0 .417, NSMean 6 month acuity 0.664 0.41 1.388, p = 0.099, NSMean change in acuity over 6 months 0.208 0.417 21.074, p=0.155, NSMean change in retinal thickness onOCT over 6 months

    172.8 459.3. 21.583, p=0.074, NS

    Mean change in cyst height onOCT over 6 months

    87.6 302.6. 22.418, p = 0.019*

    OCT, optical coherence tomography.

    Accepted for publication 14 January 2005

    RJA was supported by the Lady Allerton Fund.

    Competing or financial interests: none.

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    Informed consent and medicaldevices: the case of the contactlensIt is estimated that 1.65 million people in theUnited Kingdom wear contact lenses, 97% of

    whom do so for refractive and cosmeticreasons.1 Contact lens wearers are at risk ofsight threatening adverse events such ascorneal ulceration, which may lead to scar-ring and visual loss. The risk of cornealulceration is approximately 1 in 3000, 1 in

    2000, and 1 in 500 patients per year for hard,soft daily wear, and soft continuous wearlenses, respectively.24

    Informing individuals of the risks asso-ciated with contact lens wear, is importantboth for the wearer and person prescribingthe contact lens. For consent to be legally

    valid it must be informed. This means thatpatients need information about the natureof an intervention, possible alternatives and,specifically, its benefits and risks. There is noreason why the principle of informed consentshould not apply to the prescribing of amedical device such as a contact lens. Wesought to determine the degree to whichcontact lens wearers have been informed ofthe risks associated with contact lens wear.

    MethodsFollowing permission from the respectivemedical school deans, students at UK medicalschools were contacted through electronicmail by their respective university facultiesand asked if they wore or had worn contactlenses in the past year, to follow a link to aquestionnaire (fig 1) sited on the world wide

    web.

    ResultsIn all, 560 replies were received (table 1); 21%of students had received some verbal infor-mation regarding the risk of corneal ulcera-tion and 1% had received this in writtenform. Only 2% had been told of all of the four

    stated risks; 1214% of respondents wereaware of the risk of corneal ulcerationassociated with soft daily, continuous, andhard contact lens wear. Of those who knew ofthis risk 41%, 37%, and 58% underestimatedthe respective morbidity. Only 23% of those

    who think that they had been given sufficientadvice knew of the risk of corneal ulceration.Thirteen per cent of students reported thedevelopment of one or more complicationsassociated with their contact lens wear. Eightper cent of students stated that had they beenaware of the risks stated in the questionnairethey would not have chosen to wear contactlenses. 87% of students would still havechosen to wear a contact lens after readingthe associated risks.

    CommentContact lenses are worn by millions of people

    worldwide. Although the risk of a complica-tion is small, it constitutes a significantpublic health problem when applied to alarge population. Individually it is necessaryto balance this risk against the benefitsoffered by contact lens wear. This can onlybe achieved with the provision of appropriateinformation.

    Although there are limitations with thistype of survey, it would appear that themajority of contact lens wearers, approxi-mately 80% (98% for all four of the stated

    risks) of students surveyed, were unaware ofthe risks to which they were exposed.

    It is important that potential contact lenswearers are fully informed to allow the bestchoice of refractive correction for them.Consumer comparison between the potentialadverse effects of various contact lens typesand wear patterns is important in thisdecision. This is emphasised here as 8% ofthose involved in the study would not havechosen to wear contact lenses had theyknown of the associated risks.

    Although there is no legal stipulationregarding the provision of information when

    prescribing a contact lens, providing informa-tion and obtaining informed consent formspart of good clinical practice. Although

    written consent is not evidence that informeddiscussion has taken place, written agree-ments can be used to provide a basis for theprocess.

    We would recommend that informed con-sent be obtained when prescribing contactlenses and that this should be done with theaid of written information. Concern over theassociated risks should not deter people fromthe benefits of contact lens wear but they arean important consideration and consumershave a right to be informed.

    A Roberts, A E Kaye, R A Kaye, K Tu, S B KayeSt Pauls Eye Unit, 8Z Link, Royal Liverpool University

    Hospital, Prescot Street, Liverpool L7 8XP, UK

    Correspondence to: Stephen B Kaye, St Pauls EyeUnit, 8Z Link, Royal Liverpool University Hospital,

    Prescot Street, Liverpool L7 8XP, UK; [email protected]

    doi: 10.1136/bjo.2004.062315

    References

    1 Schein OD, Glynn RJ, Poggio EC,et al. Therelative risk of ulcerative keratitis among users ofdaily wear and extended wear contact lenses.N Engl J Med1989;321:7738.

    2 MacRae S, Herman C, Stulting RD. Corneal ulcerand adverse reaction rates in premarket contactlens studies.Am J Ophthalmol1991;111:45765.

    3 Poggio EC, Glynn RJ, Schien OD, et al. Theincidence of ulcerative keratitis among users ofdaily wear and extended wear soft contact lenses.N Engl J Med1989;321:77983.

    4 Cheng KH, Leung SL, Hoekman HW, et al.Incidence of contact lens associated microbialkeratitis and its related morbidity. Lancet1999;354:1815.

    Q1 For how long have you been wearing contact lenses?15 years

    510 years >10 yearsQ2 Has your contact lens practitioner ever told you of the following risks which are associated with contact lens wear?

    Corneal ulcers with loss of vision Yes/No Blood vessel formation on the cornea Yes/No Corneal scarring with loss of vision Yes/No Drooping of the upper eye lid (ptosis) Yes/No

    Q3 Has your contact lens practitioner ever given you written information on the following risks which are associated with contact lens wear?

    Corneal ulcers with loss of vision Yes/No Blood vessel formation on the cornea Yes/No Corneal scarring with loss of vision Yes/No Drooping of the upper eye lid (ptosis) Yes/NoQ4 Were you offered a choice of contact lens type by your contact lens practitioner?

    Yes/NoQ5 Do you receive your contact lenses from hospital (Yes/No)or high street (Yes/No) contact lens practitioner?Q6 Do you feel that the information given to you by your contact lens practitioner was sufficient? Yes/No/UnsureQ7 On a scale from one to five, with one being very well and five being not at all, how well do you think you understood the information you were given by your contact lens practitioner?

    15Q8 Have you ever developed any of the following problems? Corneal ulcers Yes/No Blood vessel formation on the cornea Yes/No Corneal scarring Yes/No Drooping of the upper eye lid (ptosis) Yes/NoQ9 The estimated risk of corneal ulceration associated with contact lens wear is stated below. Please indicate if you were aware of these given risks. If the answer is yes please select whether you thought the risk was greater than stated, less than stated or the same as stated.

    Q10 If you were not aware of these risks, would you still have worn contact lenses had you be given the above information? Yes/No

    Soft daily wear lensesSoft continuous wear lensesHard lenses

    Risk

    1/20001/5001/3000

    Aware ofrisk?Yes/NoYes