LETTERS TOTHE EDITOR

Congenital toxoplasma chorioretinitistransmitted by preconceptionallyimmune women

EDITOR,—During pregnancy primary toxo-plasmic infection of the mother is a wellknown cause of congenital chorioretinitis dueto fetal contamination by Toxoplasma gondii. Itis generally thought that women infectedbefore conception have no risk of transmittingthe disease to the fetus unless they are severelyimmunocompromised.1 We report two chil-dren with severe ocular lesions due tocongenital toxoplasmosis transmitted by pre-conceptionally immune mothers.

CASE 1A 1 year old girl presented with a convergentsquint as a consequence of bilateral largemacular scars. She was the first child of ahealthy immunocompetent mother. Threemonths before conception, the systematicFrench prenuptial serological screening of themother showed a recent toxoplasmic infectiondiagnosed by a high titre of specific immu-noglobulin M (IgM) (IgM 5200, BiotrolMerck (normal <200), IgG= 40 IU/ml)(Table 1). She was treated with spiramycin 3MIU per day for a month. At the time ofreferral, the mother’s titre of IgM had signifi-cantly decreased (IgM 200) and showed aslightly higher rate of IgG (140 IU/ml). Herdaughter’s serological status showed a hightitre of specific IgG (624 IU/ml), the presenceof specific IgA (6 /12 index ISAGA; immuno-sorbent agglutination assay, Biomérieux,index 0–12) and specific IgM (11/12 indexELISA) confirming a fetal infection. Intracer-ebral calcifications, suggestive of congenitaltoxoplasmosis, were found on the computedtomogram (Fig 1). The child was otherwisehealthy and was not treated.

CASE 2A 1 month old boy was referred because of acongenital cataract in the right eye and amacular atrophic lesion surrounded by anactive whitish ring. He was the third child ofan immunocompetent woman, a native ofSaint-Domingue (Haïti).1 She had long stand-ing toxoplasmic immunity, confirmed by theabsence of specific IgM and stable IgG rates atthe fourth and the 10th weeks of herpregnancy (ELISA, IgG 49 and 54 IU/mlrespectively) providing proof of an anteriortoxoplasmic infection (Table 1). The serologyof the neonate showed evidence of active Tgondii infection with a high IgG titre (ELISA>1200 IU/ml), a positive specific IgM (10/12index ISAGA) as well as a positive specific IgA(6/12 specific ISAGA). The serological studyof the mother, after the birth, showed a

dramatically increased level of IgG (ELISAIgG > 1200 IU/ml) with specific IgA (12/12index ISAGA); however, no specific IgM wasdetected. The child was operated on for hiscataract and was treated orally with pyrimeth-amine and sulphadiazine.

COMMENT

Congenital chorioretinitis may be a challeng-ing clinical situation for which fetal infectionsmust be considered, in particular, congenitaltoxoplasmosis.

Because of the concept that the oVspring ofan immune woman is protected, the diagnosisof infection by T gondii may be overlooked inrare cases especially when there are only ocu-lar manifestations.

In our two cases, the mothers were consid-ered to be immune to T gondii; nevertheless,they transmitted the disease to their childrenwho presented with sight threatening manifes-tations and no systemic symptoms. The moth-ers were not immunocompromised, thusexcluding toxoplasmosis reactivation due toimmunodeficiency.2 DiVerent pathophysio-logical mechanisms may be suggested andmay be illustrated by our two cases.

Regarding our first patient, it has beenreported recently that, exceptionally, congeni-tal toxoplasmosis may be a consequence ofprimary maternal toxoplasmosis infectionpreceding conception.3 4 Despite medicaltreatment, the parasitaemia may remain activeeven months after the onset of the disease andcould be responsible for fetal contamination.An emerging immune response as well as themother’s treatment, reducing the parasitaemiaof the child, may explain the attenuated clini-cal manifestation5 leading to ocular manifesta-tions without other clinical systemic involve-ment and without miscarriage.

The development of toxoplasmosis in thesecond case may be explained by reinfection ofthe mother.5 The mother’s positive specific IgAsuggested that there was reinfection of themother by the parasite, as these immunoglobu-lins are produced during the digestive phase ofthe acute infection.1 5 Strains of diVerentvirulence have been described, and reinfectionby a particularly virulent strain could explainthe inability of the mother’s immune system toprotect the fetus.6 The absence of IgM in themother after the birth of the child is strikingand the origin remains unclear although a simi-lar serological status has already been describedin a case of spontaneous abortion due topresumed reinfection of a preconceptionallyimmune mother.5

The possibility of the rupture of endome-trial toxoplasmic cysts, contaminating thefetus during pregnancy or at birth, can beraised according to Langer7 but this theory hasbeen considered with reservation by otherauthors.8 Nevertheless, because of the IgAlevel in the mother of our second patient, weassume that there is reinfection and not reac-tivation.

Consecutive toxoplasmic infection in sib-lings may occur. Indeed, siblings with oculartoxoplasmosis have been reported9–11 and pose

the question of congenital or acquired originof these iterative intrafamilial toxoplasmicinfections. In none of these papers has thecongenital origin of the infection been provedcalling into question congenital reinfection ofthese siblings.

Positive toxoplasmic screening before or atthe beginning of the pregnancy may bewrongfully reassuring and may lead to anunderestimate the toxoplasmic origin of somecongenital chorioretinitis. The presentation ofthese two children with severe ocular manifes-tations of congenital toxoplasmosis showsindeed that this diagnosis cannot be totallyexcluded even if the mother has been infectedby the parasite before conception.

We thank Mr Carlos Pavesio (London), consultantophthalmic surgeon, for interesting comments con-cerning our two cases and Mr Phillip Harris(Edinburgh) for his help.

HÉLÈNE DOLLFUSPASCAL DUREAU

Service d’Ophtalmologie, Hôpital Necker-EnfantsMalades, Université Paris V, Paris, France

CHRISTOPHE HENNEQUINService de Microbiologie, Hôpital Necker-Enfants

Malades, Univeristé Paris V, Paris, France

YVES UTEZAService d’Ophtalmologie, Hôpital Necker-Enfants

Malades, Université Paris V, Paris, France

ALAIN BRONService d’Ophtalmologie, Hôpital Général de Dijon,

Dijon, France

JEAN LOUIS DUFIERService d’Ophtalmologie, Hôpital Necker-Enfants

Malades, Université Paris V, Paris, France

Correspondence to: Dr Hélène Dollfus, 8 Avenuedes Vosges, 67140 Barr, France.Accepted for publication 3 June 1998

1 Hennequin C, Dureau P, N’Guyen L, et al. Con-genital toxoplasmosis acquired from an immunewoman. Pediatr Infect Dis J 1997;16:75–7.

2 Marty P, Bongain A, Thulliez P, et al. Prenataldiagnosis of severe fetal toxoplasmosis as a resultof toxoplasmic reactivation in a HIV-1 seroposit-ive woman. Prenatal Diagn 1994;14:414–15.

3 Pons JC, Sigrand C, Grangeot-Keros L, et al.Toxoplasmose congénitale: transmission au foe-tus d’une infection maternelle antéconception-nelle. Presse Méd 1995;24:3–5.

4 Desmont G, Couvreur J, Thulliez P. Toxoplas-mose congénitale et toxoplasmose ganglionnairematernelle préconceptionnelle. Presse Méd1991;20:387–8.

Table 1 Main serological findings in the two cases

Child Mother before conception Mother after birth

IgM IgG IgA IgM IgG IgA IgM IgG IgA

Case 1 + + + ++ + NA + + NACase 2 + + + − + − − ++ ++

Level of specific antibodies against Toxoplasma gondii: (+ to ++) present, (−) not present, or (NA) not available.

Figure 1 Intracerebral calcifications (arrows)suggestive of congenital toxoplasmosis found onthe computed tomogram.

Br J Ophthalmol 1998;82:1444–14481444

5 Fortier B, Aissa E, Ajana F, et al. Spontaneousabortion and reinfection by Toxoplasma gondii.Lancet 1991;338:444.

6 Howe DK, Sibley LD. Toxoplasma gondiicomprises three clonal lineages: correlation of aparasite genotype with human disease. J InfectDis 1995;172:1561–6.

7 Langer H. Repeated congenital infection withToxoplasma gondii. Obstet Gynecol 1963;21:318–29.

8 Remington JS. Toxoplasmosis. In: Remingtonand Klein, eds, Infectious diseases of the fetus andnewborn infant. 4th ed. Philadelphia: Saunders,1995:89–195.

9 Lou P, Kazdan J, Kumar Basu P. Oculartoxoplasmosis in three consecutive siblings. ArchOphthalmol 1978;96:613–14.

10 Stern G, Romano PE. Congenital ocular toxo-plasmosis. Possible occurence in siblings ArchOphthalmol 1978;96:615–17.

11 Asbell PE, Vermund SH, Hofeldt AJ. Presumedtoxoplasmic retinochoroiditis in four siblings.Am J Ophthalmol 1982;94:656–63.

Shinty and ocular trauma in north westScotland

EDITOR,—Sports related eye injuries accountfor up to 42% of ocular trauma requiringhospitalisation1 and 10% of ruptured globes.2

The commonest cause of sports related oculartrauma seen in this department is shinty.

Shinty is a parochial game with a devotedfollowing and a playing area which stretchesfrom Argyll and Bute in the south to Invernessin the east to Skye in the west. It is derivedfrom hurling and is thought to have beenintroduced by St Bridget who travelled toScotland with St Columba to promote christi-anity in the highlands.

The game itself is not unlike hockey withtwo opposing teams who attempt to scoremore goals than the opposition using a curvedstick or “caman”. Two notable diVerencesexist between the two games, however. Thereis no restriction on the height above which thecaman may be raised or above which the ballmay travel.

We report two cases of ocular trauma whichare representative of the cases commonly seenin this department during the shinty season.

CASE 1A 30 year old man was admitted after beingstruck on the face with a shinty stick.

Visual acuity was perception of light only. A10 mm horizontal upper lid laceration wasnoted with a 200 degree superior iridodialysis.The lens was subluxated inferiorly with zonu-lar dehiscence above. Intraocular pressure was15 mm Hg with no orbital fracture.

After initial primary repair of the lid thepatient was treated with topical steroids andantibiotics. The eye settled with visual acuityof counting fingers. One month after theoriginal injury an acute rise in intraocularpressure to 54 mm Hg was lowered medicallybefore lensectomy and anterior vitrectomy.Much of the disinserted iris was also removed.

Six months after the original injury visualacuity was 6/12 with an aphakic correction.

CASE 2A 29 year old man was struck on the left eyeby a shinty ball. Visual acuity was noperception of light. A partial thickness upperlid laceration was present and the globe wasclearly ruptured and disorganised.

Examination under anaesthesia revealed afull thickness laceration of the globe extendingfor a total of 20 mm and involving the wholecorneal diameter. Uveal tissue and vitreouswere seen to be prolapsing through the woundwith no identifiable lens. A primary enuclea-

tion was performed. The patient currently hasvisual acuity of 6/5 in the right eye with noevidence of sympathetic ophthalmia.

COMMENT

Shinty related ocular trauma causes signifi-cant ocular morbidity and occasionally theinjuries are devastating. Patients are exclu-sively male.

Unfortunately, the globe is particularly vul-nerable owing to the nature and dimensions ofthe equipment used in shinty. The diameter ofthe ball (6.03–6.36 cm) and the head of thecaman (no greater than 6 cm wide)3 allowportions of both to traumatise the globe withonly partial protection from the orbital rim.The ball is also very hard, comprising an innercore of dense cork with an outer layer ofleather3 and can reach speeds of up to 80 milesper hour.

The recent spate of shinty related injurieshas reopened the debate as to whether thewearing of faceguards or helmets should becompulsory during formal matches and prac-tice sessions. At present, such protection isoptional, including physical education atschool.

We feel that faceguards and helmets shouldbe worn at all levels of the game and should becompulsory with particular emphasis onenforcement at school and junior levels. Untilthe traditionalists who feel that the game is insome way “spoiled” by protective headgearrelent, this easily preventable sports injury willcontinue to cause serious ocular morbidity inthe highlands of Scotland.

AT PURDIEI F WHYTE

Department of Ophthalmology, Raigmore Hospital,Inverness IV2 3UJ

Correspondence to: Dr Purdie.Accepted for publication 3 June 1998

1 Macewen CJ. Eye injuries: a prospective study of5671 cases. Br J Ophthalmol 1989;73:888–94.

2 Schein OD, Hibberd PL, Shingleton PL, et al.The spectrum and burden of ocular injury. Oph-thalmology 1988;95:300–5.

3 The Cammanachd Association Annual 1997–1998.

Ultrastructural alterations in the stromaadjacent to non-inflammatory cornealperforations associated with longstanding rheumatoid arthritis

EDITOR,—Patients with rheumatoid arthritiscommonly have two types of corneal ulcera-tion. One is a peripheral corneal ulcerationthought to be caused by complex mediatedhypersensitivity.1 The other is a paracentralcorneal ulceration that tends to perforate thecornea rapidly. Its pathogenesis remains un-known, though a key feature is the lack ofinflammation, leading to the suggestion that itis the result of surface disease (drying).

CASE REPORTS

We examined two individuals, a 38 year oldwoman and a 76 year old woman, with unilat-eral corneal epithelial defects and aqueoustear deficiencies. Both patients had beentreated for rheumatoid arthritis for severalyears; however, neither had been on systemiccorticosteroids. The 76 year old had had suc-cessful cataract surgery 1 week previously andwas using 0.1% betamethasone eye drops. Atthe time of presentation both women hadsevere dry eye (possibly secondary Sjögren’ssyndrome, though no biopsies were taken to

confirm this) as assessed by detailed slit lampexamination with fluorescein and rose bengalstaining, and by the Schirmer test. The 38year old was started on 0.1% fluorometholoneand 0.3% norfloxacin and dibekacin eye dropsfour times a day, and the 76 year old wasswitched to the topical application of 0.1%betamethasone and 0.3% ofloxacin ointmentsfour times a day. A few weeks later paracentralcorneal perforations developed suddenly,though without pain (Fig 1). Unlike periph-eral corneal ulceration, little or no inflamma-tion was seen on the ocular surface at anytime. Penetrating keratoplasties were per-formed and a treatment regimen was begunthat included artificial tears (for dry eye) and0.1% betamethasone topically four times aday. In addition, the 76 year old received 2 mgbetamethasone intravenously once a day and1 g flomoxef sodium intravenously twice a dayfor the first 3 days after surgery; this wasfollowed by betamethasone (1 mg) andantibiotic (300 mg cefzinil; 100 mg, threetimes a day) taken internally for 1 week. At thetime of writing, topical steroids (in both cases0.1% betamethasone) continue to be used,and both patients are doing well 7 years (38year old) and 5 years (76 year old) aftersurgery, with no sign of another perforation.

At the time of surgery, corneal tissuedirectly adjacent to the paracentral perfora-tion, as well as tissue in the peripheral cornea,was obtained for histopathological study. Inline with the lack of clinically detectableinflammation (Fig 1), light microscopic exam-ination of both cases revealed only a fewinflammatory cells surrounding the perforationand none in more peripheral areas (data notshown). In both patients’ corneas, electronmicroscopy documented many electron densedeposits in the extracellular stromal matrix (Fig2). These amorphous deposits were intimatelyassociated with collagen, and might representdegraded and/or aggregating collagen fibrilsresulting from the melting process. Also de-tected were numerous atypical, thin fibrils (Fig2; inset). These were fairly widely interspersedwith normal diameter collagen though, onoccasion, they appeared in groups. Interest-ingly, these abnormal electron microscopic fea-tures were observed not only in stroma right atthe edge of the perforation, but in more periph-eral regions of the cornea as well.

COMMENT

The general clinical presentations of boththese individuals, especially the lack of inflam-mation, are similar to previous reports of per-forated paracentral corneas.2 Often, infiltrat-ing macrophages and T cells that areassociated with HLA class II antigens arelocated around corneal ulcers,3 and various

Figure 1 Paracentral corneal perforation (38year old woman). There is little or noinflammation on the ocular surface. Theanterior chamber is maintained by a therapeuticcontact lens.

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cytokines and proteinases secreted from thesecells are thought to trigger a corneal perfora-tion. However, this pathogenesis is unlikely inour cases because little or no inflammatorycell infiltration was detected.

As in all connective tissues, collagen im-parts to stroma by far the majority of its tensilestrength. It follows that ultrastructural colla-gen alterations might cause our patients’corneas to become somewhat fragile, predis-posing them to non-inflammatory cornealperforations. With this in mind, it is notewor-thy that the alterations of the corneal extracel-lular matrix we report here closely resemblethose seen in ruptured hand tendons of rheu-matoid arthritis patients.4 It is possible, there-fore, that a similar structural weakening ofboth these connective tissues occurs and isassociated with collagen abnormalities in longstanding rheumatoid arthritis.

WAKAKO ADACHIKOHJI NISHIDA

ANDREW J QUANTOCKSHIGERU KINOSHITA

Department of Ophthalmology, Kyoto PrefecturalUniversity of Medicine, Kyoto, Japan

YASUO ISHIIDepartment of Ophthalmology, Shinkawabashi General

Hospital, Tokyo, Japan

Correspondence to: Kohji Nishida, MD, PhD,Department of Ophthalmology, Kyoto PrefecturalUniversity of Medicine, Kawaramachi Hirokoji,Kyoto 602, Japan.Accepted for publication 29 July 1998

1 Mondino BJ. Inflammatory disease of the periph-eral cornea. Ophthalmology 1988;95:463–72.

2 Cohen KL. Sterile corneal perforation after cata-ract surgery in Sjögren’s syndrome. Br JOphthalmol 1982;66:179–82.

3 Kervick GN, Pflugfelder SC, Haimovici R, et al.Paracentral rheumatoid corneal ulceration:clinical features and cyclosporine therapy. Oph-thalmology 1992;99:80–8.

4 Neurath MF, StoVt E. Ultrastructral causes ofrupture of hand tendons in patients withrheumatoid arthritis. Scand J Plast ReconstrHand Surg 1993;27:59–65.

Overt chorioretinitis after patientacquired toxoplasmosis in animmunocompetent subject

EDITOR,—Acquired Toxoplasma gondii infec-tion is usually asymptomatic and uncompli-cated unless it occurs in severely immuno-depressed patients or in particularepidemiological settings.1 2

We report a case of toxoplasmic chorio-retinitis (CR) occurring 15 months afterpatent primary infection with cervical aden-opathies in an immunocompetent woman.

CASE REPORT

VK, a 31 year old woman, presented withblurred vision in the left eye, which hadstarted a few days previously. Visual acuity onthis side was preserved at 16/20. Split lampexamination showed a negative Tyndall in the

anterior chamber. Ocular pressure was 10 mmHg. Retinal examination with the three mirrormethod revealed a fresh and strictly peripheralchorioretinal lesion at 10 o’clock, suggestive oftoxoplasmosis, with no evidence of previousscarring. Peripapillar haemorrhage and amoderate vitreal reaction were also noted. Theright eye was strictly normal. Two small cervi-cal adenopathies could be felt.

Fifteen months previously this nulliparouswoman had developed cervical adenopathies,with serum anti-toxoplasmic antibody kineticstypical of very recent seroconversion (Table1).3 Specific IgA antibodies persisted 8months after seroconversion and the woman,who wished to become pregnant, was referredto the Reims Toxoplasmosis Group to assessthe risk of maternofetal transmission.4 5

Eight days after onset of the visual disordersthe anterior chamber was sampled by punc-ture. Aqueous humour and peripheral bloodwere tested for toxoplasmic DNA by polymer-ase chain reaction (PCR)6 and/or blood circu-lating T gondii research, and for specific IgG,IgM, and IgA antibodies by immunocapturetests; the Witmer–Desmonts coeYcient (C)was calculated.6 7 Serological tests for viral andother parasitic infections were also done, andher immune status was thoroughly investi-gated (Table 2). Anti-toxoplasma chemo-therapy was started immediately, with a com-bination of pyrimethamine-sulphadiazine andcalcium folinate for 1 month. The visualdisorders improved and the chorioretinallesion healed rapidly.

COMMENT

This case is unusual in that a chorioretinaltoxoplasmic lesion occurred 15 months afterseroconversion in a healthy adult.

The precise date of infection was deducedfrom clinical arguments and the results of bio-logical tests. The first battery of serologicaltests, at the onset of cervical adenopathies(T0), was carried out because the patient wasintending to have children. Eight months laterthe persistence of specific IgA antibodiespointed to active toxoplasmosis. As we hadpreviously observed cases of congenital trans-mission after preconceptional seroconversionwith adenopathies, the patient was advised notto become pregnant yet.3–5 This position wasborne out by the onset of chorioretinitis somemonths later. The ocular involvement wasconfirmed by sampling the anterior chamber(positive Witmer–Desmonts coeYcient, andlocal synthesis of specific IgA) less than 8 daysafter the onset of visual disorders.

Ocular lesions were long considered to be asometimes very late complication of congeni-tal toxoplasmosis, except in case of immuno-depression (human immunodeficiency virus,organ transplantation, etc).1 2 8 Our patient’simmune status was strictly normal; she was

Figure 2 Corneal stroma surrounding the perforated area (76 year old woman). Electron densematerial (arrow), possibly aggregated collagen, is located throughout the extracellular matrix. Also(inset), many atypical, thin fibres (arrowheads) are interspersed with collagen. Bar=200 nm (mainfigure) and 100 nm (inset).

Table 1 Kinetics of anti-toxoplasmic IgG, IgM and IgA antibodies (months) from the first serological tests at the time of onset of cervical adenopathies(T0). T8 months corresponds to the first immunological study in parasitological laboratory and T15 months to the onset of chorioretinitis. Note that thefirst serological tests (undertaken in another laboratory) were based only on immunoenzymatic methodology (IgG and IgM (MEIA))

MethodsIgG-Ab (MEIA)(IU/ml)

IgG-Ab*(U/HSDA/ml)

IgM-Ab (MEIA)(index)

IgM-Ab (ICT-M)†0–12

IgA-Ab (ICT-A)†0–12

Cut oV 3 10 0.5 9 2T 0 (onset of cervical adenopathies) 71 ND 9.9 ND NDT 0.5 855 ND 8.3 ND NDT 2 4030 ND 3.6 ND NDT 4 4200 ND 1.5 ND NDT 8 (pregnancy contraindicated) 1820 6400 1.4 11 10.5T 12 880 3200 1.0 10.5 10T 15 (onset of chorioretinitis) 680 6400 1.1 11 10

*Detection of IgG antibodies by high sensitivity direct agglutination (HSDA).†Detection of IgM and IgA antibodies by immunocapture test with revelation by a tachyzoite suspension (ICT-M, ICT-A).

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not on immunosuppressive drugs and had nointercurrent infections. The persistence of twosmall cervical adenopathies and specific IgAantibodies 15 months after the primary infec-tion illustrates the long duration of the activephase of infection in this case complicated bysecondary chorioretinitis.1 9 With a well de-fined interval before onset, this case ofchorioretinal involvement (isolated, unilateral,and without pre-existing lesions) diVers fromother reported cases in which the date of sero-conversion was less precise and the chorio-retinitis was often associated with neurologicalmanifestations.1 8 10

This case of secondary toxoplasmic chorio-retinitis in an immunocompetent womansuggests that all patients with persistent adeno-pathies and serological markers of active Tgondii infection should have regular ocularmonitoring.

Financial support was provided by the ProgrammeHospitalier de Recherche Clinique (1994), Directiondes Hôpitaux, Ministère des AVaires Sociales, de laSanté et de la Ville, Paris, France.

C MARX-CHEMLAI VILLENA

F FOUDRINIERJ M PINON

Reims Toxoplasmosis Group, Laboratoire Parasitologie,Hôpital Maison Blanche (UPRESEA 2070, IFR 53),

CHU, Reims Cedex France

A GOTZAMANISF HAMON

A DUCASSEReims Toxoplasmosis Group, Services Ophtalmologie,

Hôpital Robert Debré, CHU, Reims Cedex France

Correspondence to: C Marx-Chemla, Laboratoirede Parasitologie, Hôpital Maison Blanche, 45 rueCognacq Jay, 51092 Reims Cedex France.Accepted for publication 18 June 1998

1 Holland GN, O’Connor GR, Belfort R Jr, et al.Toxoplasmosis. In: Pepose JS, Holland GN,Wilhelmus KR, eds. Ocular infection and immu-nity. 1st ed. St Louis: Mosby Yearbook,1996;1183–223.

2 Cochereau-Massin I, LeHoang P, Lautier-FrauM, et al. Ocular toxoplasmosis in human immu-nodeficiency virus-infected patients. Am J Oph-thalmol 1992;114:130–5.

3 Thulliez P, DaVos F, Forestier F. Diagnosis oftoxoplasma infection in the pregnant womanand the unborn child :current problems. Scand JInfect Dis 1992;Suppl 84:18–22.

4 Villena I, Chemla C, Quereux C, et al. Prenataldiagnosis of congenital toxoplasmosis transmit-ted by an immunocompetent woman infectedbefore conception. Prenatal diagnosis (in press)

5 Desmonts G, Couvreur J, Thulliez P. Congenitaltoxoplasmosis. Five cases with mother-to-childtransmission of pre-pregnancy infection. PresseMed 1990;19:1445–9.

6 Thelliez E, Aubert D, Ducasse A, et al. Patientssans toxoplasmose oculaire, résultat de la PCRet de l’immunocapture. Ophtalmologie 1996;10:207–9.

7 Thelliez E, Ducasse A, Marx C, et al. Etude desimmunoglobulines spécifiques de la toxoplas-mose dans l’humeur aqueuse. Bull Soc Opht1994;1:51–6.

8 Montoya JG, Remington JS. Toxoplasmic chori-oretinitis in the setting of acute acquiredtoxoplasmosis. Clin Infect Dis 1996;23:277–82.

9 Foudrinier F, Marx C, Aubert D, et al. Value ofspecific immunoglobulin A detection by twoimmunocapture assays in the diagnosis of toxo-plasmosis. Eur J Clin Microbiol Infect Dis1995;14:585–90.

10 Thulliez P. Acquired toxoplasmosis with ocularor neurologic involvement. Presse Med 1996;25:438–42.

Anterior segment complications ofindirect diode laser in diabetic patients

EDITOR,—We describe two cases of recurrentcorneal epithelial breakdown following indi-rect diode laser panretinal photocoagulation(PRP) in diabetic patients. The particularnature of diode laser burns may have contrib-uted to this event.

CASE 1A 21 year old insulin dependent diabeticwoman underwent bilateral indirect diode laserPRP under general anaesthesia for proliferativediabetic retinopathy (PDR). She presented 4weeks later with a 3 week history of a painfulleft eye. Visual acuity was 6/12 and a 3 mm × 2mm infiltrative corneal ulcer was noted. Therewas total corneal anaesthesia bilaterally andboth pupils were mid dilated and non-reactiveto light and accommodation. Microbiology wasnegative and the ulcer gradually healed withintensive topical antibiotic treatment. Over thenext 3 months corneal anaesthesia persisted inthe left eye, but resolved in the right. She hadtwo further episodes of corneal epithelialbreakdown on the left which were successfullymanaged with topical lubricants. One year afterlaser treatment visual acuity was 6/6 in the righteye and 6/12 in the left, with residual stromalscarring on the left (Fig 1). Both pupilsremained mid dilated and non-reactive.

CASE 2A 26 year old insulin dependent diabeticwoman underwent indirect diode PRP to theleft eye under general anaesthesia for PDR.One week later she presented with a dilatedand non-reactive left pupil, complained of notbeing able to focus, and had an anaestheticcornea. Subsequently she underwent twofurther treatment sessions to both eyes for per-sistent PDR. She then developed a large

epithelial defect of the left cornea, total cornealanaesthesia bilaterally, and semidilated pupilsnon-reactive to light and accommodation. Theepithelial defect was managed with topicalantibiotics and lubricants with slow resolution.She went on to have three further episodes ofepithelial breakdown on the left and two on theright. Topical lubrication and padding provedto be the most eVective treatment. Eighteenmonths after initial laser treatment, cornealsensation had recovered, visual acuity was6/18 in both eyes, and there was mild centralstromal scarring bilaterally.

COMMENT

Corneal sensation and innervation of thepupil and accommodation is supplied by thelong and short posterior ciliary nerves whichpierce the eye posteriorly and run forward inthe suprachoroidal space. Disruption of thisanatomical pathway could therefore lead tothe problems experienced by the patientsdescribed above. Indeed, pupillary abnormali-ties and a temporary reduction in corneal sen-sitivity have been noted following argon,xenon, and krypton laser PRP.1 2 However, toour knowledge, such profound corneal abnor-malities with ulceration and scarring have notbeen described previously.

The histopathological damage inflicted bylaser burns has been studied in both theanimal and human eye.3–5 Clinically burns canbe classified as follows: grade 1 consists of agreyish retinal discoloration only; grade 2shows whitish discoloration surrounded by agreyish periphery; and finally grade 3 burnshave a distinct white centre, representing thehighest intensity burn.

High intensity laser burns have been shownto damage choroidal nerves in humans andanimals.2–6 The thermal damage profile of aretinal burn caused by the diode laser(wavelength 810 nm) extends deeper into thechoroid than that from an argon blue green

Table 2 Results of the diVerent tests performed on serum and aqueous humour

Blood/ serum Aqueous humour Interpretation

Herpesvirus, CMV, EBV, Lyme, Larva migrans Negative ND No viral or other parasitic infectionHIV Negative ND HIV seronegativeImmunological examination and lymphocyte subpopulations Normal ND No immune deficiencyT gondii DNA Negative Positive with one probe Doubtful result on aqueous humourTotal IgG g/l 12.8 0.056 Witmer–Desmonts coeYcient: 4.6 (suggesting local IgG-Ab

synthesis)Anti-toxoplasmic IgG (U/HSDA/ml) 6400 128Specific IgM (ICT-M) 11/12 0/4 Presence of serum IgM-Ab; no intraocular IgM-Ab synthesisSpecific IgA (ICT-A) 10/12 4/4 Presence of serum IgA-Ab ; intraocular IgA-Ab synthesisDetection of circulating parasite by mouse and cell culture

inoculation Negative ND No circulating toxoplasma

ND = not done.

Figure 1 Scarring in left cornea, case 1.

Figure 2 Final scarring pattern of panretinalphotocoagulation as seen typically in bothpatients.

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laser (488–514.5 nm).3 5 This is due to thelower absorption within melanin of the longerdiode laser wavelength. Hence there is poten-tially a greater risk of choroidal nerve damagefrom the diode laser, particularly with anexcessively intense burn. The burn sizeassociated with indirect laser tends to be largerthan that achieved with direct laser, particu-larly if the working distance increases duringPRP, thus causing thermal damage to a greaterarea of retina. Indeed, the post PRP fundusphotographs of both patients show large burnstending towards confluence (Fig 2).

Diabetics with and without retinopathy havesignificantly increased epithelial fragility whencompared with normal controls.7 Diabetics alsohave reduced corneal sensitivity when com-pared with normal controls.8 However, beforelaser treatment, neither of our two patients hadever had any symptoms or signs of corneal dis-ease. All the corneal problems started post laserand were associated with a total lack of cornealsensation. As the corneal sensation recoveredover the months the frequency of the epithelialerosions diminished.

The optics of the diode laser beam meanthat it is possible to clip the edges of the iris inthe laser beam during treatment.9 10 It is possi-ble that this could account for some of thepupillary abnormalities post PRP, but takinginto account the corneal anaesthesia and

reduced accommodation, it would seem morelikely to be a result of damage to a commondenominator.

We hypothesise that the large area involvedin performing an indirect PRP, and the depthof the burn achieved with diode laser, damageda large number of choroidal nerves causing thepupillary and corneal abnormalities.

We propose the following measures to avoidchoroidal nerve damage when performingindirect diode laser PRP. Grade 1 to 2 burnsshould be discretely placed so as to preventconfluence certainly avoiding high intensitygrade 3 burns. Under peribulbar and generalanaesthesia, it is particularly important to useless intense burns as the painful feedback fromchoroidal nerve damage is absent. Careshould be taken with the working distance ofthe laser indirect to avoid unduly large burns.Particular caution should be exercised whentreating in the horizontal retinal meridia, thetypical location of the long ciliary nerves.Finally, the patient should be warned of possi-ble eVects on the anterior segment which mayoccur after indirect diode laser PRP.

S A BUCKLEYD N PARMAR

H JACKSONJ D A MCHUGH

P A HUNTERKing’s College Hospital, London

Correspondence to: Miss Buckley.Accepted for publication 18 June 1998

1 Schiodte SN. EVects on choroidal nerves afterpanretinal xenon arc and argon laser photoco-agulation. Acta Ophthalmol 1984;62:244–55.

2 Menchini U, Scialdone A, Pietroni C, et al. Argonvs krypton PRP side eVects on the anterior seg-ment. Ophthalmologica 1990;201:66–70.

3 Wallow IHL, Spousel WE, Stevens TS. Clinico-pathologic correlation of diode laser burns inmonkeys. Arch Ophthalmol 1991;109:648–53.

4 Tso MO, Wallow IHL, Elgin S. Experimentalphotocoagulation of the human retina. ArchOphthalmol 1977;95:1035–50.

5 McHugh JDA, Marshall J, Capon M, et al.Transpupillary retinal photocoagulation in theeyes of rabbit an human using a diode laser.Lasers Light Ophthalmol 1988;2:125–43.

6 Kaufmann PL, Rohen JW, Gabelt BT, et al. Para-sympathetic denervation of the ciliary musclefollowing panretinal photocoagulation. Curr EyeRes 1991;10:437–55.

7 Saini JS, Khandalavla B. Corneal epithelialfragility in diabetes mellitus. Can J Ophthalmol1995;30:142–6.

8 Ruben ST. Corneal sensation in insulin depend-ent and non-insulin dependent diabetics withproliferative retinopathy. Acta Ophthalmol 1994;72:576–80.

9 Woon WH, Vytche TJ, Hamilton AMP, et al. Irisclipping of a diode laser beam when performingretinal photocoagulation. Br J Ophthalmol 1991;75:386–90.

10 Mills M, Schulman JA, Kooragayala LM, et al.Significant ocular complications following diodelaser treatment for retinopathy of prematurity.Invest Ophthalmol Vis Sci 1996;37(suppl):606.

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