scientific report intermittent exotropia increasing with ...intermittent exotropia who had a...

SCIENTIFIC REPORT

Intermittent exotropia increasing with near fixation: a ‘‘soft’’sign of neurological diseaseP H Phillips, K J Fray, M C Brodsky. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Br J Ophthalmol 2005;89:1120–1122. doi: 10.1136/bjo.2004.063123

Aim: To examine the association of distance-near disparitywith neurological disease in children with intermittentexotropia.Methods: A retrospective analysis was performed of themedical records of all children with intermittent exotropiaexamined at the Arkansas Children’s Hospital between 1989and 2002. The study group consisted of children withintermittent exotropia who had a near deviation thatexceeded the deviation at distance by at least 10 prismdioptres. The control group consisted of children withintermittent exotropia who had a distance deviation greaterthan or equal to the deviation at near. The main outcomemeasure was the prevalence of neurological abnormalities inthe study and control groups.Results: Among the 29 patients in the study group, 19 (66%)had a history of concurrent neurological abnormalities.Associated neurological conditions included developmentaldelay (10 patients), attention deficit disorder (four patients),cerebral palsy (four patients), history of intracranial hae-morrhage (four patients), periventricular leucomalacia (threepatients), seizures (two patients), cortical visual impairment(two patients), hydrocephalus (one patient), history of anoxicbrain damage (one patient), history of encephalitis (onepatient), and autism (one patient). Among the 37 patients inthe control group, seven (19%) had a history of concurrentneurological abnormalities. The difference in the prevalenceof neurological disease between the study group and thecontrol group was significant (p = 0.0002).Conclusion: Intermittent exotropia increasing with nearfixation is associated with neurological disease in children.

Children with intermittent exotropia often have anexodeviation that increases with distance fixation.1 2

However, some children exhibit an exodeviation thatincreases during near fixation. It has been our impressionthat the latter group frequently has associated neurological orneurodevelopmental disorders. To test this hypothesis, weretrospectively reviewed the medical records of our patientswith intermittent exotropia.

METHODSRetrospective analysis of the medical records of all childrenwith intermittent exotropia examined at the ArkansasChildren’s Hospital between 1989 and 2002. The study groupconsisted of children with intermittent exotropia whose neardeviation was at least 10 prism dioptres greater than theirdistance deviation. The control group consisted of childrenwith intermittent exotropia who had a distance deviationgreater than or equal to the deviation at near. Children whohad strabismus surgery were categorised by ocular motilitymeasurements obtained before their strabismus surgery.

Children who had undergone strabismus surgery beforeexamination by one of the investigators were excluded fromthe analysis. In addition, children who had a near deviationthat was less than 10 prism dioptres greater than the distancedeviation, who had an inconsistent distance/near disparity, orwho were uncooperative for distance and near measurementswere excluded from the analysis. None of the patients hadamblyopia, ptosis, anisocoria, nystagmus, limited ductions orany other associated ocular disease. The absence of amblyo-pia was confirmed in preverbal children by the ability tomaintain central steady fixation with each eye and amongliterate children, by the presence of visual acuity equal to orgreater than 20/30 in each eye and equal visual acuity in botheyes.All patients were examined by at least two investigators.

Cover/uncover testing was used to diagnosis intermittentexotropia. Prism and alternate cover testing was performedwith distance (6 metres) and near (33 cm) fixation targets inorder to determine the magnitude of the exodeviation.Accurate fixation and accommodation were assured byhaving the patient identify different fixation targets asmeasurements were being obtained. Depending on the ageand development of the patient, Snellen letters or Allensymbols were used as fixation targets. Ocular occlusion wasnot performed before obtaining the measurements notedabove. When possible, confrontation visual field testing wasperformed to rule out hemianopic visual field deficits.The charts were reviewed for the presence of associated

ocular, neurological and systemic diseases. All patients andparents in the study and control groups were routinelyquestioned at each visit regarding the presence of neurolo-gical diseases including developmental delay, attentiondeficit disorder, and seizures. Most of the patients diagnosedwith neurological disease were evaluated by a paediatricneurologist or a child development specialist before theirophthalmological evaluation.

Statistical analysisThe prevalence of neurological disease and the sex distribu-tion in the study and control groups were compared with atwo tailed x2 test. The age distribution in each group wascompared with a two sample t test.

RESULTSA total of 94 children had intermittent exotropia. Twentyeight children were excluded from the analysis. Reasons forexclusion included insufficient cooperation for accuratedistance measurements (18 patients), an exodeviation atnear that exceeded the deviation at distance by less than10 prism dioptres (eight patients), strabismus surgery thatwas performed before evaluation by one of the investigators(one patient), and ocular motility measurements that wereinconsistent (one patient).The characteristics of the study and control groups are

shown in table 1. The study and control groups did not differ

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significantly with respect to sex and age at evaluation. The 29patients in the study group had intermittent exotropia thatincreased with near fixation with a mean deviation of19 prism dioptres at distance and 35 prism dioptres at near.Seventeen of these 29 patients had an intermittent neardeviation greater than or equal to 35 prism dioptres indicat-ing robust fusional convergence amplitudes; 19 of these 29patients (66%) had a history of concurrent neurologicalabnormalities as listed in table 2.The control group consisted of 37 patients with a mean

exodeviation of 30 prism dioptres at distance and 13 prismdioptres at near. Seven of these 37 patients (19%) had ahistory of concurrent neurological abnormalities as listed intable 2. The prevalence of neurological abnormalities wassignificantly higher in the patients who had an intermittentexotropia that increased with near fixation compared withthe control group (p=0.0002). Despite the significantdifference in prevalence, the spectrum of neurologicalabnormalities was qualitatively similar between both groups.

DISCUSSIONWe found a high prevalence of neurological disease inchildren with intermittent exotropia increasing at nearfixation. Convergence insufficiency has been associated withseveral neurological disorders including head trauma, dys-lexia, Parkinson’s disease, congenital central hypoventilationsyndrome, subdural haematoma, and stroke.3–14 The term‘‘convergence insufficiency’’ has been loosely applied to thisheterogeneous group of patients with exodeviations thatbecome problematic during near fixation. In this context,apparent convergence insufficiency may arise from multiplemechanisms ranging from decreased fusional convergenceamplitudes, a low accommodative convergence/accommoda-tion ratio, accommodative insufficiency, poor convergenceeffort, poor accommodative effort, poor concentration, andpharmacological effects of medications.3–14 We are unable toassign a specific neurophysiological substrate to our studypatients with intermittent exotropia that increases with near

fixation. However, many of our study patients were ableintermittently to fuse large exodeviation, demonstrating thattheir convergence amplitudes were greater than normal.The magnitude of exodeviations at near is affected by

accommodative and convergence effort. We encouragedaccommodative and convergence effort by requiring ourchildren to identify fixation targets as measurements werebeing obtained. However, we cannot exclude the possibilitythat reduced accommodative or convergence effort may havecontributed to the high prevalence of exodeviations thatincrease with near fixation in children with neurologicaldisease.This study should be viewed in light of its inherent

limitations. Firstly, because our cohort was gleaned from achildren’s hospital population, our findings do not necessa-rily reflect the prevalence of neurological dysfunction in thegeneral population. However, the increased prevalence ofneurological disease in our children with intermittentexotropia that increases with near fixation compared withour control group of patients suggests that this association isreal. Secondly, the prevalence of neurological disease wasdetermined from a retrospective chart review. Not everypatient was examined by a paediatric neurologist. However,patients and parents were routinely questioned regarding thepresence of neurological disease at each visit. It is unlikelythat a more detailed paediatric neurological evaluation wouldhave disclosed clinically significant undiagnosed neurologicaldisease in a significant number of our apparently healthypatients. Finally, we did not formally measure accommoda-tive or convergence amplitudes in most of our patients withintermittent exotropia that increases with near fixation.Our study confirms a high prevalence of neurological

disease in children who have intermittent exotropia thatincreases with near fixation. However, no patient wassubsequently found to have a serious treatable neurologicallesion. As such, neuroimaging is not warranted, and furtherdiagnostic evaluation can be guided by the clinical history.Although the determinants of increased near disparity in

Table 1 Characteristics of the study and control groups

Sex (no of females)(mean)

Age (years)(mean (SD))

Distance deviation(prism dioptres)(mean (SD))

Near deviation(prism dioptres)

Study group (n = 29) 13 6.7 (8.3) 19 (10) 35 (11)range 3–17 range 0–40 range 10–55

Control group(n = 37)

17 4.4 (9.0)range 3–14

30 (11)range 14–60

13 (11)range 0–45

p Value 0.87 0.24

Table 2 Neurological diseases in study and control patients

Neurological diseases

Study group (n = 29) Control group (n = 37)

No of patients* No of patients*

Developmental delay 10 4Cerebral palsy 4 2Attention deficit disorder 4 1History of intracranial haemorrhage 4 0Periventricular leucomalacia 3 1Seizure disorder 2 4Cortical visual impairment 2 0History of hydrocephalus 1 0History of anoxic brain damage 1 0History of encephalitis 1 0Autism 1 1

*Most patients had more than one neurological abnormality

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intermittent exotropia have yet to be defined, this form ofstrabismus appears to be a ‘‘soft’’ sign of neurological diseasein children should prompt a search for other signs ofneurological disease.

ACKNOWLEDGEMENTSupported in part by unrestricted grant from Research to PreventBlindness and the Pat & Willard Walker Eye Research Center, JonesEye Institute, University of Arkansas for Medical Sciences.

Authors’ affiliations. . . . . . . . . . . . . . . . . . . . .

P H Phillips, K J Fray, M C Brodsky, Department of Ophthalmology,University of Arkansas for Medical Sciences, Little Rock, AR, USAM C Brodsky, Department of Pediatrics, University of Arkansas forMedical Sciences, Little Rock, AR, USA

Correspondence to: Paul H Phillips, MD, Arkansas Children’s Hospital,800 Marshall Street, Little Rock, AR 72202, USA; [email protected]

Accepted for publication 1 March 2005

REFERENCES1 Kushner BJ, Morton GV. Distance/near differences in intermittent exotropia.

Arch Ophthalmol 1998;116:478–86.

2 Kushner BJ. Exotropic deviations: a functional classification and approach totreatment. Am Orthopt J 1998;38:81–93.

3 Krohel GB, Kristan RW, Simon JW, et al. Posttraumatic convergenceinsufficiency. Ann Ophthalmol 1986;18:101–4.

4 Lepore FE. Disorders of ocular motility following head trauma. Arch Neurol1995;52:924–6.

5 Cohen M, Groswasser Z, Barchadski R, et al. Convergence insufficiency inbrain-injured patients. Brain Injury 1989;3:187–91.

6 Kowal L. Ophthalmic manifestations of head injury. Aust N Z J Ophthalmol1992;20:35–40.

7 Al-Qurainy IA. Convergence insufficiency and failure of accommodationfollowing midfacial trauma. Br J Oral Maxillofac Surg 1995;32:71–5.

8 Latvala M-L, Korhonen TT, Penttinen M, et al. Ophthalmic findings in dyslexicschool children. Br J Ophthalmol 1994;78:339–43.

9 Racette BA, Gokden M, Tychsen L, et al. Convergence insufficiency inidiopathic Parkinson’s disease responsive to levodopa. Strabismus1999;7:169–74.

10 Repka MX, Claro MC, Loupe DN, et al. Ocular motility in Parkinson’s disease.J Pediatr Ophthalmol Strabismus 1996;33:144–7.

11 Goldberg DS, Ludwig IH. Congenital central hypoventilation syndrome:Ocular findings in 37 children. J Pediatr Ophthalmol Strabismus1996;33:175–80.

12 Spierer A, Huna R, Rechtman C, et al. Convergence insufficiency secondary tosubdural hematoma. Am J Ophthalmol 1995;120:258–60.

13 Ohtsuka K, Maekawa H, Takeda M, et al. Accommodation and convergenceinsufficiency with left middle cerebral artery occlusion. Am J Ophthalmol1988;106:60–4.

14 Stavis M, Murray M, Jenkins P, et al. Objective improvement from base-inprisms for reading discomfort associated with mini-convergenceinsufficiency type exophoria in school children. Binoc Vis Strabismus Q2002;17:135–42.

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Ultrahigh resolution opticalcoherence tomography ofbirdshot retinochoroidopathyBirdshot retinochoroidopathy is a rareinflammatory eye disease with typical clinicalpresentation and strong association with theHLA-A29 allele. Characteristic appearanceson fluorescein angiogram (FA), indocyaninegreen (ICG) angiography, and electroretino-gram (ERG) have been described.1 However,histopathology of the disease has been rare.2 3

The following case is an example of birdshotretinochoroidopathy imaged with ultrahighresolution optical coherence tomography(UHR-OCT), capable of 3 mm axial resolu-tion.4 UHR-OCT is able to clearly delineateindividual intraretinal layers (fig 1).

Case reportA 64 year old man presented to the NewEngland Eye Center (NEEC) for progressivevisual deterioration despite cataract surgeryin the left eye 2 years earlier. The patient’smajor complaints were difficulty seeing atnight and difficulty driving. Best correctedvisual acuity (BCVA) was 20/50 right eye and20/60 left eye. Anterior eye examinationrevealed mild cells and flare in both eyes, amoderate cataract in the right eye, and aposterior chamber intraocular lens in the left.Dilated fundus examination revealed mild

vitritis bilaterally. The optic discs appearedslightly pale and the retinal vasculature wasnarrowed. Fundus appearance was consistentwith the diagnosis of birdshot retinochoroi-dopathy (fig 2A). FA and ICG angiographywere also consistent with this diagnosis(fig 2B). Six mm radial macular OCT3 scansshowed bilateral epiretinal membranes(ERM), with mild thickening in the left eye.The patient subsequently tested positive forthe HLA-A29 antigen. Over the next6 months, the patient was treated for macu-lar oedema with intravitreal Kenalog injec-tions in both eyes, and the macular oedemasubsided.UHR-OCT images were obtained 6 months

later (fig 3), at which time BCVA remainedstable. Repeat fundus examination and OCT3imaging revealed an ERM with no macularoedema and normal retinal thickness in botheyes. UHR-OCT images additionally showedphotoreceptor atrophy in several areas ofboth eyes. RPE degeneration was presentunderneath areas of photoreceptor involve-ment. The inner retinal layers were difficultto delineate, probably because of anatomicaldisorganisation of these layers.

CommentThis case represents a fairly severe case ofbirdshot retinochoroidopathy. In a review byGasch et al, epiretinal membrane was thesecond most common complication of bird-shot retinochoroidopathy next to macularoedema,1 which our patient also had oninitial presentation. ERG findings have

shown Mueller and bipolar cell involvementearly in the disease, while photoreceptors areaffected later.1 The UHR-OCT images pre-sented here show disorganisation of innerretinal layers as well as photoreceptor andRPE atrophy. Choroidal ischaemia, suggestedby ICG angiography, may be the cause of RPEand photoreceptor degeneration.We found two histolopathological reports

of birdshot retinochoroidopathy. One casewas a blind phthisical patient.2 The other wasa more typical yet mild case, which showedlymphocytic infiltration around the choroidaland retinal vasculature with minimal retinaldisturbance.3 Serial UHR-OCT imaging ofpatients could help in understanding andfollowing progression of macular involve-ment in this disease.

A J Witkin, J S DukerNew England Eye Center, Tufts-New England Medical

Center, Tufts University, Boston, MA, USA

T H Ko, J G FujimotoDepartment of Electrical Engineering and Computer

Science and Research Laboratory of Electronics,Massachusetts Institute of Technology, Cambridge,

MA, USA

J S SchumanUPMC Eye Center, Department of Ophthalmology,

University of Pittsburgh School of Medicine,Pittsburgh, PA, USA

Correspondence to: Jay S Duker, MD,Ophthalmology Department, Tufts-New England

Medical Center, 750 Washington Street, Boston, MA02111, USA; [email protected]

doi: 10.1136/bjo.2005.076570

References

1 Gasch AT, Smith JA, Whitcup SM. Birdshotretinochoroidopathy. Br J Ophthalmol1999;83:241–9.

Figure 1 Ultrahigh resolution optical coherence tomography image from a normal eye. Theintraretinal layers are labelled: NFL, nerve fibre layer, GCL, ganglion cell layer, IPL, inner plexiformlayer, INL, inner nuclear layer, OPL, outer plexiform layer, ONL, outer nuclear layer, IS/OS,photoreceptor inner/outer segment junction, RPE, retinal pigment epithelium.

Figure 2 (A) Colour photograph of the left eye. (B) Fluorescein angiogram of the left eye,2 minutes after injection. The image shows two small haemorrhages originating from the superiorarcade, multiple hyperfluorescent spots, and central cystoid macular oedema.

LETTERS

PostScript . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Accepted for publication 29 July 2005

Supported in part by NIH contracts RO1-EY11289-16, R01-EY13178, and P30-EY13078, NSF contractECS-0119452, Air Force Office of Scientific Researchcontract F49620-98-1-0139, Medical Free ElectronLaser Program contract F49620-01-1-0186 and byCarl Zeiss Meditec.

JGF and JSS receive royalties from intellectualproperty licensed by MIT to Carl Zeiss Meditec. JGFand JSS receive research support from Carl ZeissMeditec.

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2 Nussenblatt RB, Mittal KK, Ryan S, et al. Birdshotretinochoroidopathy associated with HLA-A29antigen and immune responsiveness to retinal S-antigen. Am J Ophthalmol 1982;94:147–58.

3 Gaudio PA, Kaye DB, Crawford JB.Histopathology of birdshot retinochoroidopathy.Br J Ophthalmol 2002;86:1439–41.

4 Drexler W, Morgner U, Ghanta RK, et al.Ultrahigh-resolution ophthalmic optical coherencetomography. Nat Med 2001;7:502–7.

Unilateral necrotisingtoxoplasmic retinochoroiditis asthe main clinical manifestation ofa peptide transporter (TAP)deficiencyCongenital HLA class I deficiency is a raredisease frequently resulting in chronic inflam-mation of the respiratory tract, and/or skingranulomas.1 2 The deficiency may be unno-ticed for decades, so pathological outcome isrelatively unpredictable.3 We here describe a14 year old patient with a severe oculartoxoplasmosis who is HLA class I deficient, asa result of a homozygous mutation in the geneencoding one of the two subunits of thepeptide transporter associated with antigenprocessing (TAP). We propose that such adefect should be investigated in patients withsevere ocular toxoplasmosis without acquiredimmunodeficiency.

Case reportAt the time of referral, the patient did nothave any particular medical history except anexaggerated reaction to an intradermal tuber-culin test 1 year earlier. His right eye dis-played a strong reduction of acuity withanterior and posterior inflammatory lesions

and pain. There was corneal inflammationwith flare in the anterior chamber, anterioruveitis with cellular deposits on the cornealendothelium (keratic precipitates) but with-out posterior synechiae and grade B3 vitritis.A focus of chorioretinitis was just visiblein the macular area. The blood neutrophilcount was high (14.49 white cells/6106/l

with 13.48 neutrophils/6106/l), while sero-logy showed high levels of anti-toxoplasmaIgG (543 IU/ml) with an IgM index of 53.73.Anti-toxoplasma therapy was attempted byadministration of sulfadiazine, pyrimetha-mine, and folinic acid for 2 days, followedby prednisone. Despite this treatment, theocular inflammation worsened and led to lossof vision and ocular divergence. A clinicalexamination revealed posterior synechiae andaggravation of the vitritis and B echographyshowed retinal detachment (fig 1A).Surgery was performed, which comprised

pars plana vitrectomy after phacoemulsifica-tion, with ablation of the incompletelydetached posterior hyaloid. The retina wasreattached with silicone oil. The inferiorretina appeared necrotic with a focus ofinflammatory chorioretinitis in the maculararea. Twelve months after surgery, the eyewas no longer painful but vision was limitedto perception of hand movements with oculardivergence (fig 1B). A fundus of the right eyerevealed retraction of the inferior retina andextended gliosis of the macula (fig 1C).The severity of the clinical manifestations

prompted an evaluation of the patient’simmunocompetence, which appear to benormal, except that the amount of HLA classI molecules expressed on the plasma mem-brane of the lymphocytes was reduced 20-fold (figs 2 and 3). The parents wereunrelated, but shared an identical HLAhaplotype, so the patient and his brotherwere HLA homozygous (HLA-A*24; B*14;Cw*08; DRB1*13; DQB1*06). TAP genes,located in the HLA genetic region, werecharacterised, and a stop mutation in theTAP1 was identified at codon 522 (sequenceAAS55412.1 in GenBank), because of a C to Tsubstitution.The patient did not display pulmonary

involvement, contrary to his elder brotherwho displayed a bronchial obstruction unre-sponsive to inhaled bronchodilators, a bacterialcolonisation of the lower airways associated toasthma-like symptoms, but no bronchiectasies.

Figure 3 (A) Horizontal ultrahigh resolution OCT (UHR-OCT) image through the right macula.Notable are an epiretinal membrane (ERM) (yellow arrows), and an area of thinning of the outernuclear layer (ONL) with underlying absence of the photoreceptor inner/outer segment junction(IS/OS) (red asterisk). Retinal pigment epithelium (RPE) disruption is also seen as an increase inchoroidal signal backscattering. Other retinal layers are also labelled as in figure 1. (B) HorizontalUHR-OCT image through the left macula. ERM is present (yellow arrows). Thinning of the ONL anddisruption of the photoreceptor IS/OS junction is present outside of the fovea (red asterisks). RPEdisruption is also present in these areas. The inner retinal layers are not clearly delineated.

Figure 1 Analysis of lesions before and after surgery. (A) B echography before operationdemonstrates total retinal detachment wit a grade D vitreoretinal proliferation. (B) 12 months aftersurgery, circumferential synechiae are noted with capsule opacification and corneal opacities. (C)Posterior pole is not easily recognisable. Nevertheless, a white scar is distinguishable.

PostScript 1661


CommentThe presence of anti-toxoplasma IgM sug-gests that the infection was recent and iscompatible with a primary ocular infection.The particular titre of anti-toxoplasma IgGsuggests that these antibodies might havehad a role in the immunological defence, ashas been observed for viral infections.4

Remarkably, during the pathology, morethan 40% of the T cells of the patient were cd,which can be explained by the infection,known to induce the expansion of this T cellsubset.5 6 After recovery, this numberdecreased twofold.These observations suggest that TAP defi-

ciency should now be considered as a potentialcause of unexplained exacerbated pathology inresponse to intracellular parasites, notably Tgondii. In our patient, special follow up includ-ing prophylactic antibiotherapy is required, inorder to avoid infection of the other eye.

AcknowledgementsWe thank Jose Sahel and Claude Benichou forcritical reading of the manuscript. This work wassupported by ARMESA, INSERM, and theEtablissement Francais du Sang-Alsace.

A Parissiadis, A DormoyLaboratoire d’Histocompatibilite, EFS-Alsace,

Strasbourg, France

D Fricker, D Hanau, H de la SalleINSERM U. 725, EFS-Alsace, Strasbourg, France

J-P CazenaveINSERM U. 311, EFS-Alsace, Strasbourg, France

P LenobleService d’Ophtalmologie, Centre Hospitalier de

Mulhouse, Mulhouse, France

L DonatoPneumologie Pediatrique, Hopital Universitaire de

Strasbourg, Strasbourg, France

Correspondence to: Henri de la Salle, PhD, INSERMU.725, EFS-Alsace, 10, rue Spielmann, 67065

Strasbourg Cedex, France;[email protected]

doi: 10.1136/bjo.2005.078097

References

1 Gadola SD, Moins-Teisserenc HT, Trowsdale J, etal. TAP deficiency syndrome. Clin Exp Immunol2000;121:173–8.

2 De la Salle H, Donato L, Hanau D, et al. PeptideTransporter Defects in HLA Class I Deficiency. In:Ochs HD, Smith CIE, Puck JM, eds. Primaryimmunodeficiency diseases. 2nd ed. New York:Oxford University Press, 2005.

3 De la Salle H, Saulquin X, Mansour I, et al.Asymptomatic deficiency in the peptidetransporter associated to antigen processing(TAP). Clin Exp Immunol 2002;128:525–31.

4 Donato L, de la Salle H, Hanau D, et al.Association of HLA class I antigen deficiencyrelated to a TAP2 gene mutation with familialbronchiectasis. J Pediatr 1995;127:895–900.

5 De Paoli P, Basaglia G, Gennari D, et al.Phenotypic profile and functional characteristicsof human gamma and delta T cells during acutetoxoplasmosis. J Clin Microbiol1992;30:729–31.

6 Scalise F, Gerli R, Castellucci G, et al.Lymphocytes bearing the gamma delta T-cellreceptor in acute toxoplasmosis. Immunology1992;76:668–70.

Scleral contact lenses are notoptically inferior to corneallensesIn the 1950s, chronic corneal hypoxia and itsattendant complications were associated withscleral contact lenses (ScCLs) compared tocorneal contact lenses (CCLs).1 Changes inmechanical design to improve transfer ofoxygenated tears between the corneal-tearfilm interface were partially successful, butaccompanied by increased complexity of lensfitting and design.2 These included fenestra-tions, slots, truncations, and channels. Apartfrom being time consuming and technicallydifficult to manufacture, these modificationswere almost invariably associated with trap-ping of air bubbles behind the ScCL, resultingin reduced vision and localised cornealdesiccation. Without a sealed tear film, theScCL rested progressively more on the cornealapex and limbus—that is, settling back,which caused corneal erosions, scarring, andhypoxia.

The advent of fluorocarbon silicone/acrylateco-polymer ScCLs resulted in greater utilitybecause of high gas permeability.3 One majorcriticism of ScCLs has been the suboptimalvisual acuity achieved when compared toCCLs.3 In this study we compared the bestcorrected visual acuity (BCVA) in patients withRGP ScCLs who failed a trial of CCLs.

Method and resultsThe case notes of 15 patients prescribedScCLs were reviewed over an 18 monthperiod. The reasons for discontinuing CCLuse included discomfort, excessive mobility,poor fit, short wearing times, and subjectivelens intolerance. There were 18 eyes in 15patients whose average age was 37 years (18–80). There were eight males and sevenfemales.The BCVA varied according to the pre-

existing pathology. These were post-penetrat-ing keratoplasty (seven); keratoconus (six),and herpetic scarring (two). Mean astigma-tism was 9.7D (3.5–18D). CCL average BCVAwas 6/18, but with ScCLs was 6/9, of whicheight (44%) achieved 6/5, p=0.1; x2 test.The greatest improvement occurred in the

keratoconus group (BCVA 6/18 with CCLs; to6/9–6/5 with ScCLs); followed by the kerato-plasty group (with ScCL 6/9 in five cases and6/18 in two cases from pre-existing cornealscarring). In all cases the scleral lenses werewell tolerated. No complications were noted.

CommentThe relatively close apposition of the corneato a CCL provides a stable refractive interface.In a normal cornea, the centre is assumed tobe spherical and regular so that a singly curvedCCL can be made based on keratometryreadings. In corneas with highly abnormaltopography such as high astigmatism, severeflattening, apical protrusion, thinning, andscarring, the nature of the refractive interfacebetween the cornea, precorneal tear film, andcontact lens is altered because the aboveassumptions no longer hold true.ScCLs vault the cornea, which eliminates

the need for close alignment to the cornea.This compensates for very abnormal corneasgiving good BCVA that can be difficult toachieve with CCLs.4 As the power of CCLsincreases, positional stability and accuracy offit decreases. High power CCLs tend to bebulkier, thicker, and with a larger diameterthat alters the centre of gravity. These CCLstend to sag or droop with axis mislocation sovision is through the peripheral lens and notthe optic zone. Induced prismatic effectscause reduced vision, lens intolerance, anddiscomfort. This is exacerbated by edgesensation from high edge lift. Lens instabilitywith excessive frictional mobility on thecornea also increases the potential for ero-sions, scarring, and intolerance. ScCLs retainpositional stability and tend not to beassociated with the aforementioned pro-blems.Based on the findings of this study, we

think the use of ScCLs should not beprejudiced because of the perception thatthey are optically inferior to CCLs. The opticaland therapeutic benefit of ScCLs should notbe underestimated. They can have an impor-tant role in management of patients wheresurgery is undesirable or high risk.

A Salam, B MeliaHull and East Yorkshire Eye Hospital, Fountain Street,

Anlaby Road, Hull HU3 2JZ, UK

10 000

1000

100

10

1

IgG

S1 S2 M F

Bw6W6/32

Figure 2 HLA class I deficiency of the patientand his brother. Expression of HLA class Imolecules on the plasma membrane oflymphocytes. Peripheral blood mononuclearcells were isolated from the patient and hisbrother (S1, S2) and their parents (M, F) andstained with the mAb W6/32 (pan-anti-HLAclass I), or 126.39 (anti-HLA-Bw6), or a controlIgG1 mAb. Mean fluorescence intensities of thestaining were quantified in the gatedlymphocyte subpopulations.

Figure 3 HLA class I deficiency of the patientand his brother. Identification of a mutation inthe TAP1 gene. Genomic DNA from S1 and Fwas amplified using the polymerase chainreaction technique and the amplified fragmentswere sequenced. The sequence was read on thereverse complementary non-coding strand andshowed the presence of an A in thehomozygous mutated genome, at the positionwhere the superposition of an A and a G,depicted as an N on the electropherogram, wasobserved in the hemizygous genome of F.

Accepted for publication 1 August 2005

1662 PostScript


A J SinghDepartment of Ophthalmology, Leeds General

Infirmary, Clarendon Wing, Belmont Grove, Leeds,UK

Correspondence to: A J Singh, Department ofOphthalmology, Leeds General Infirmary, Clarendon

Wing, Belmont Grove, Leeds LS2 9NS, UK;[email protected]

doi: 10.1136/bjo.2005.074377

References

1 Tan DT, Pullum KW, Buckley RJ. Medicalapplications of scleral contact lenses: 1. Aretrospective analysis of 343 cases. Cornea1995;14:121–9.

2 Tan DT, Pullum KW, Buckley RJ. Medicalapplications of scleral contact lenses: 2. Gas-permeable scleral contact lenses. Cornea1995;14:130–7.

3 Pullum KW, Buckley RJ. A study of 530 patientsreferred for rigid gas permeable scleral contactlens assessment. Cornea 1997;16:612–22.

4 Schein OD, Rosenthal P, Ducharme C. A gas-permeable scleral contact lens for visualrehabilitation. Am J Ophthalmol1990 15;109:318–22.

Optometric referrals: towards atwo way flow of information?ommunity optometrists in the UnitedKingdom carry out 17.2 million primaryeyecare examinations per annum,1 whichresult in at least 0.5 million referrals to thehospital eye service.2 3 Optometrists onlyinfrequently receive a reply to these refer-rals,4 5 possibly because 69% are handwrittenon GOS18 forms,6 which can lack legibility6

and details.5 Most optometrist initiated refer-rals take place via general practitioners(GPs), who are increasingly likely to forwardthe optometrist’s letter.6 We improved ourreferrals and audited the replies.

MethodsThe Institute of Optometry set minimumcriteria for referrals in 2004 by typing letterson headed notepaper, including the practi-tioner’s name, enclosing a second copy forthe GP to forward to the ophthalmologist,and including text which explicitly requesteda reply.In February–April 2005 we audited refer-

rals from 2004. Handwritten emergencyreferrals, which make up less than 1% ofreferrals, were not included.

ResultsThere were 181 referrals following 7164 eyeexaminations, 51% were female, and thereasons for referral are given in figure 1.The provisional diagnoses for the ‘‘other’’category include a wide range of conditions,all with a prevalence of less than 3%.A reply was requested in 95% of letters, but

was received for only 23 (13%). There was norelation between the likelihood of reply andthe reason for referral (p=0.37).

CommentThe institute’s referral rate (2.5%) is lowerthan previously reported for optometrists.2 3

This might reflect better facilities for mon-itoring (for example, ocular hypertension) ormanaging (for example, dry eye) conditionsand an ethos that encourages managementwhen appropriate.Although our results are only for one centre

it is disappointing that, despite taking steps to

encourage a reply, this is still rarely forth-coming. The proportion of referrals that receivereplies is so low (13%) that we think it unlikelyto be attributable to patients failing to consultthe GP or ophthalmologist after referral. Forthe few ophthalmologists who do reply this isnot an onerous task: they instruct theirsecretary to copy the reply to the GP to theoptometrist. The NHS code of practice onconfidentiality notes that explicit consent isnot usually required for information disclo-sures that support the delivery of the patient’scare.7 Even if it is thought necessary to obtainconsent, there is no good reason why theophthalmologist should not obtain this.4 Theissue of consent does not seem to be the mainreason for lack of replies: a study found thatophthalmologists actually replied to a higherproportion of referrals when the optometristshad not obtained consent thanwhen they had.4

Replying to referrals helps optometristsprovide continuing patient care and avoidspossible errors from the optometrist relying onthe patient’s recollection of the ophthalmolo-gist’s findings. Feedback also contributes tooptometrists’ professional development andhelps to ensure that inappropriate referralsare minimised in the future.8

Now that direct referral from primary careoptometrists to secondary care ophthalmol-ogy units is becoming more commonplace,9

we hope that a two way flow of informationwill become the norm.

B J W Evans, D E Harle, B CoccoInstitute of Optometry, 56–62 Newington Causeway,

London SE1 6DS, UK

Correspondence to: Professor Bruce Evans, Institute ofOptometry, 56–62 Newington Causeway, London

SE1 6DS, UK; [email protected]

doi: 10.1136/bjo.2005.075531

References

1 Department of Health. Sight tests volume andworkforce survey 2003–2004. www.dh.gov.uk/assetRoot/04/08/65/64/04086564.pdf 2004,accessed 11 April 2005.

2 Hobley AJ, Woodward EG, Port MJ.Retrospective study of optometric referrals.Ophthalmic Physiol Opt 1992;12:395–9.

3 Port MJ. Referrals and notifications byoptometrists within the UK: 1988 survey.Ophthalmic Physiol Opt 1989;9:31–5.

4 Whittaker KW, Ikram K, Anderson DF, et al.Non-communication between ophthalmologists andoptometrists. J R Soc Med 1999;92:247–8.

5 Lash SC. Assessment of information included onthe GOS 18 referral form used by optometrists.Ophthalmic Physiol Opt 2003;23:21–3.

6 Pooley JE, Frost EC. Optometrists’ referrals to thehospital eye service. Ophthal Physiol Opt1999;19:S16–S24.

7 Department of Health. Confidentiality: NHS Codeof Practice. www.publications.doh.gov.uk/ipu/confiden/protect/copv3.pdf 2003, accessed 11April 2005.

8 Ingram DV, Culham LE. Ophthalmologists andoptometrists—interesting times? Br J Ophthalmol2001;85:769–70.

9 Department of Health. Delivering quality in primarycare: General ophthalmic service practitioners.www.dh.gov.uk/assetRoot/04/10/60/33/04106033.pdf 2005, accessed 11 April 2005.

Retinal changes in juvenile Xlinked retinoschisis using threedimensional optical coherencetomographyJuvenile X linked retinoschisis is a congenitalX linked recessive retinal disorder, the char-acteristic funduscopic findings of which are asilver-grey retinal reflex, foveal retinoschisis,and peripheral retinoschisis. Electroretino-grams (ERGs) typically record a reduced b-wave amplitude with relative preservation ofthe a-wave amplitude. Visual acuity (VA)usually deteriorates slowly until the patient isabout 20 years of age, stabilises around0.2,0.5, and sometimes deteriorates furtherbecause of macular degeneration.1–4

Podoleanu and associates developed anovel integration of scanning laser ophthal-moscopy (SLO) and optic coherence tomo-graphy (OCT)—three dimensional opticalcoherence tomography (3-D OCT).5 Usingtransverse scanning, typical for SLO, theinstrument simultaneously produces SLOand interferometric OCT images.6 We canobtain both cross sectional scans (B-scans) aswith conventional OCT and transverse scans(C-scans) using 3-D OCT. This is the firstreport of 3-D OCT findings in juvenile Xlinked retinoschisis.

Case reportA 7 year old boy presented with VA of 0.5 and0.6 in the right and left eyes, respectively.Funduscopy showed a silver-grey retinal reflexand cartwheel-like macular degeneration bilat-erally. Peripheral retinoschisis was absent.ERGs were recorded and dark adaptationtesting was performed. Single flash ERGshowed decreased b-wave amplitude, whichwas consistent with the diagnosis. Dark adap-tation revealed a decreased curve overall.The B-scan findings of 3-D OCT (fig 1)

showed the retina split into four distinctplanes. Two wide hyporeflective spaces splitthe retina. Anteroposterior or oblique linearcolumns were seen across the superficialwide hyporeflective space, forming a bridgethat was not found in the fovea. Thesecolumns are considered to be Muller cells byOCT and histological studies.3 7 8

There was a large cystoid space in the foveaconnected to the superficial wide hyporeflec-tive parafoveal space. A deeper wide hypore-flective space was in the parafoveal retina butdisappeared in the fovea. Small cystoidspaces in the superficial parafoveal retinasplit the retina. Retinal cleavage involving thefovea was found in the outer plexiform layer.Superficial retinal cleavage was most likely inthe nerve fibre layer or the ganglion cell layer.The deep retinal cleavage was in or justaround the outer nuclear layer. C-scan find-ings of 3-D OCT showed the extent of thecleavage planes and the hyporeflective spaces(fig 2). Of particular note, the C-scans

Accepted for publication 24 July 2005 Glaucoma22%

Cataract26%

Other37%

Maculopathy8%

Diabetic eyedisease

4%

Strabismus3%

Figure 1 Reasons for referral.


PostScript 1663


showed many columns in a large space(schisis). This is in contrast with the B-scansthat showed the spaces between the columnsto be cystic spaces. The C-scans provided abetter understanding of this pathology.

CommentRecently, conventional OCT findings of fovealschisis were reported1 7 to be in the outerplexiform layer and adjacent nuclear layers.Histopathologically, foveal schisis was reportedto occur in the outer plexiform layer,2 althoughperipheral retinoschisis was found in the nervefibre layer and ganglion cell layer.3

3-D OCT demonstrated that schisis canoccur in any retinal layers in juvenile X linkedretinoschisis. We obtained cross sectional andtransverse images of the retinoschisis withnear histological precision that showed thedetails of the inner retinal structures and theextent of the schisis. 3-D OCT is useful toevaluate, non-invasively, the retinal pathol-ogy and follow patients with juvenile Xlinked retinoschisis.

Y Minami, S Ishiko, Y Takai, Y Kato,H Kagokawa, A Takamiya, T Nagaoka,

R Kinouchi, A YoshidaDepartment of Ophthalmology, Asahikawa Medical

College, Asahikawa, Japan

Correspondence to: Satoshi Ishiko, Department ofOphthalmology, Asahikawa Medical College, 2-1

Midorigaoka Higashi, Asahikawa, 078-8316, Japan;[email protected]

doi: 10.1136/bjo.2005.075648

References

1 Ozdemir H, Karacorlu S, Karacorl K. Opticalcoherence tomography findings in familial fovealretinoschisis. Am J Ophthalmol2004;137:179–81.

2 Ando A, Takahashi K, Sho K, et al.Histopathological findings of X-linked retinoschisiswith neovascular glaucoma. Graefes Arch ClinExp Ophthalmol 2000;238:1–7.

3 Condon GP, Brownstein S, Wang NS, et al.Congenital hereditary (juvenile X-linked)retinoschisis. Arch Ophthalmol1986;104:576–83.

4 Forsis H, Krause U, Helve J, et al. Visual acuity in183 cases of X-chromosomal retinoschisis.Can J Ophthalmol 1973;8:385–95.

5 Podoleanu AG, Seeger M, Dobre GM, et al.Transversal and longitudinal images from theretina of living eye using low coherencereflectometry. J Biomed Optics 1998;3:12–20.

6 Yannuzzi LA, Ober MD, Slakter JS, et al.Ophthalmic fundus imaging. Today and beyond.Am J Ophthalmol 2004;137:511–24.

7 Ikeda F, Takahashi K, Kishi S. Optical coherencetomographic features of juvenile retinoschisis.Ringan 1998;52:1497–82.

8 Kirsch LS, Brownstein S, de Wolff-Rouendaal D. Ahistopathological, ultrastructural andimmunohistochemical study of congenitalhereditary retinoschisis. Can J Ophthalmol1996;31:301–10.

Linezolid induced toxic opticneuropathyLinezolid is a new oxazolidinone antibioticwith activity against many important patho-gens including methicillin resistantStaphylococcus and penicillin resistantStreptococcus.1 We report a case of toxic opticneuropathy from chronic treatment withlinezolid. Correct diagnosis and discontinua-tion of the drug resulted in significantrecovery of vision.

Case reportA 56 year old man presented with bilateral,progressive decline in visual acuity for 6–8 months. Medical history included chronicdiabetes mellitus, below the knee amputationof the right leg, hypertension, sinusitis withnasal allergies, and asthma. Several years

earlier he had fractured his left ankle anddeveloped osteomyelitis from methicillinresistant Staphylococcus. He had received line-zolid 600 mg by mouth twice a day for12 months, then once daily for 44 months.Other medications included rosiglitazone,metoprolol, rifampin, furosemide, lisinopril,amlodipine, insulin, and vitamin B complex/folic acid for assistance with wound healing.He was a non-smoker and consumed lessthan one unit of alcohol per week.Best corrected visual acuities were 20/400

in both eyes with eccentric fixation. Ishiharacolour plates were 1/8 right eye and 3/8 lefteye. No relative afferent pupillary defect waspresent. Intraocular pressures were16 mmHg in both eyes. 1+ nuclear sclerosiswas present in both eyes. Fundus examina-tion revealed temporal optic nerve pallor witha corresponding temporal nerve fibre layerdefect more evident in the right eye (fig 1)and a normal macula in both eyes. Humphreyvisual field testing (full field 120 pointscreen) revealed central scotomas in botheyes (fig 2). Fluorescein angiography revealeda normal macula without staining of theperipapillary region in both eyes (not shown).Optical coherence tomography (Stratus OCT,Carl Zeiss Ophthalmic Systems Inc,Humphrey Division, Dublin, CA, USA) ofthe fovea revealed a central foveal thicknessof 205 (SD 5) mm right eye and 216 (4) mmleft eye and a normal macular volume(7.28 mm3 right eye; 6.94 mm3 left eye).Retinal nerve fibre layer thickness analysisby OCT revealed a normal 360˚ averagemeasurement (79.55 mm right eye, 80.57 mmleft eye) with no significant change inthickness detected in the temporal quadrant(64 mm right eye and 58 mm left eye). Fullfield scotopic and photopic electroretinogra-phy demonstrated a normal amplitude andlatency in both eyes, as expected given thesmall central scotoma.The patient was diagnosed with bilateral

optic neuropathy; chronic use of linezolidwas suspected as the cause. Linezolid wasdiscontinued and the patient noted subjectivevisual improvement within several weeks.Three months later his vision improved to 20/40 in both eyes with resolution of the centralscotomas (fig 2). There were 8/15 and 13/15central fixation losses in the right and left eyerespectively initially; this improved to 4/15right eye and 2/16 left eye 3 months afterdiscontinuing therapy.

CommentToxic optic neuropathy has been associatedwith numerous compounds, including expo-sure to ethylene glycol, methanol, isoniazid,ethambutol, and fluoroquinolone, and defi-ciency of vitamin B12, folate, and thiamine.2 3

Linezolid was approved by the FDA, based onstudies employing 28 days of administration.1

There have been five cases of optic neuro-pathy associated with prolonged use of line-zolid3–6 and more than 20 cases of peripheralneuropathy including one individual whodeveloped both sequelae.6–9 In previous opticneuropathy cases the duration of treatmentranged from 5–10 months at a dose of600 mg once or twice per day.3–6 All caseswere bilateral with initial vision decreasedfrom 20/60 to counting fingers both eyes.3–6

Discontinuation of therapy resulted inimprovement of the optic neuropathy withsignificant improvement in visual acuitywithin 1–8 months in all patients, although

Line M

Line NLine P

Figure 1 B-scans of 3-D OCT. Two widehyporeflective spaces split the retina.Anteroposterior or oblique linear columns forma bridge across a superficial widehyporeflective space. In the same layer, there isa large cystoid space in the fovea (line N). Thislayer is probably the outer plexiform layer.Deeper cleavage is seen in the parafoveal areabut not in the fovea (line P). This layer isprobably the outer nuclear layer. Small cystoidspaces (arrowhead) are seen in the superficialparafoveal retina that split the retina (line M).This layer is probably the nerve fibre layer orthe ganglion cell layer.

Figure 2 C-scans of 3-D OCT. C-scans M, N, and P correspond to the same depth of the B-scans(fig 1) in lines M, N, and P. *The location of the fovea. (M) A large cystic space is seen in the foveaand the retina, which includes the small cystic spaces. The small spaces found in the B-scan areconfirmed in the C-scan. (N) This space is equivalent to a superficial schisis and shows the space inthe fovea and the columns around it. In B-scan images, the spaces between the columns arehypothesised to be cystic space; however, in C-scan images, these spaces are not cystic, and manycolumns can be seen in a large space (schisis). (P) This is equivalent to the deeper schisis and showsthe hyperreflective area (no schisis) in the fovea and the large space (schisis) around the fovea.


Competing interests: none declared

1664 PostScript


residual deficits in central acuity or visualevoked response may persist.3–6

Oxazolidinones inhibit bacterial proteinsynthesis by binding to the 70S ribosomal

initiation complex.10 In nutritional opticneuropathies, paracentral scotomas developfrom disruption in mitochondrial function inretinal ganglion cells,8 which are more

susceptible to mitochondrial disruption.2

Mitochondrial dysfunction is the cause ofLeber’s hereditary optic neuropathy, chlor-amphenicol induced bone marrow suppres-sion, and optic neuropathy due to ethambutoland a variety of antibiotics.2 11 12 It is likelythat the development of linezolid associatedoptic neuropathy, manifest by the develop-ment of central scotomas and temporal opticnerve pathology, may be the result of asimilar mechanism.It is important for ophthalmologists to

perform a complete review of systems andelicit a history of prescription and non-prescription medication use. Awareness ofthe potential for linezolid induced opticneuropathy is important since drug with-drawal can lead to visual recovery.

K Kulkarni, L V Del PrioreDepartment of Ophthalmology, Columbia University,635 West 165th Street, New York, NY 10032, USA

K KulkarniUniversity of Medicine and Dentistry of New Jersey,Robert Wood Johnson Medical School, 675 Hoes

Lane, Piscataway, NJ 08854, USA

Correspondence to: Lucian V Del Priore, MD, PhD,Robert L Burch III Scholar, Department of

Ophthalmology, Columbia University, 635 West165th Street, New York, NY 10032, USA; ldelpriore@

yahoo.com

doi: 10.1136/bjo.2005.074237

References

1 Birmingham MC, Rayner CR, Meagher AK, et al.Linezolid for the treatment of multidrug-resistant,gram-positive infections: experience from acompassionate-use program. Clin Infect Dis2003;36:159–68.

2 Carelli V, Ross-Cisneros FN, Sadun AA.Mitochondrial dysfunction as a cause of opticneuropathies. Prog Retin Eye Res2004;23:53–89.

3 Lee E, Burger S, Shah J, et al. Linezolid-associatedtoxic optic neuropathy: a report of 2 cases. ClinInfect Dis 2003;37:1389–91.

4 Frippiat F, Bergiers C, Michel C, et al. Severebilateral optic neuritis associated with prolongedlinezolid therapy. J Antimicrob Chemother2004;53:1114–15.

5 Lewis KE, Ebden P, Wooster SL, et al. Multi-system infection with Nocardia farcinica—therapy with linezolid and minocycline. J Infect2003;46:199–202.

6 Corallo CE, Paull AE. Linezolid-inducedneuropathy. Med J Aust 2002;177:332.

7 Bressler AM, Zimmer SM, Gilmore JL, et al.Peripheral neuropathy associated withprolonged use of linezolid. Lancet Infect Dis2004;4:528–31.

8 Rho JP, Sia IG, Crum BA, et al. Linezolid-associated peripheral neuropathy. Mayo ClinProc 2004;79:927–30.

9 Legout L, Senneville E, Gomel JJ, et al. Linezolid-induced neuropathy. Clin Infect Dis2004;38:767–8.

10 Shinabarger DL, Marotti KR, Murray RW, et al.Mechanism of action of oxazolidinones: effectsof linezolid and eperezolid on translationreactions. Antimicrob Agents Chemother1997;41:2132–6.

11 Skinnider LF, Ghadially FN. Chloramphenicol-induced mitochondrial and ultrastructuralchanges in hemopoietic cells. Arch Pathol LabMed 1976;100:601–5.

12 Bernstein WB, Trotta RF, Rector JT, et al.Mechanisms for linezolid-induced anemia andthrombocytopenia. Ann Pharmacother2003;37:517–20.

Figure 1 Top, photograph suggests subtle temporal pallor to the optic nerve in the right eye with anerve fibre layer defect temporally (arrow, upper left); left eye appears normal (arrow, upper right)with no evident nerve fibre layer defect. Bottom, 3 months after discontinuing linezolid there istemporal pallor and nerve fibre layer defects in the right eye (lower left), again with no definitechanges in the left eye (lower right).

Figure 2 Humphrey full field 120. Top left and right, left eye and right eye, respectively, demonstratingcentral scotomas at presentation. Bottom left and right, left eye and right eye, respectively, showingimprovement in the central scotomas 3 months after discontinuation of linezolid.


PostScript 1665


Delayed progressive visual lossfollowing wrapping of bilateralclinoidal aneurysms: recovery ofvision and improvement inneuroimaging duringcorticosteroid treatmentReinforcement with muscle, cotton, fibringlue, or some other material is an alternativeto clipping in some intracranial aneurysms1;the surgeon must balance the need to createlocal inflammation (to reinforce the arterialwall) with the risk that the inflammation willspread and damage adjacent structures.Wrapping of clinoidal aneurysms, in particular,rarely may produce delayed and severe visualloss or ocular motor dysfunction.2–7 The clinicalcourse and potential outcome of damage to thevisual pathway, ocular motor tracts, or bothremains controversial, as does the optimummanagement when visual loss occurs. Wepresent the case of a patient who developedsevere bilateral visual loss and neuroimagingevidence of inflammation in the paraclinoidand suprasellar regions 2 months after wrap-ping of bilateral clinoidal aneurysms withcotton and fibrin glue, but who recoveredvisual function and whose neuroimagingappearance improved after treatment withsystemic corticosteroids.

Case reportA 61 year old woman underwent magneticresonance imaging (MRI) and angiographyafter experiencing a minor stroke. The studiesrevealed aneurysms of the clinoidal portion ofboth internal carotid arteries. Endovasculartreatment was unsuccessful. Accordingly,craniotomy was performed. As neither aneur-ysm could be clipped, both were wrappedwith cotton gauze saturated with fibrin glue.The patient did well postoperatively until2 months after surgery, when she notedblurred vision in the right eye. An incompleteleft homonymous hemianopia associatedwith a mild right optic neuropathy wasfound, and MRI showed a thickened, nodu-lar, enhancing area in the paraclinoid andsuprasellar regions with involvement of bothoptic nerves and the optic chiasm.Observation was elected, but the patientdeveloped a severe headache with worseningvisual loss over the next 6 weeks. Repeat MRIshowed an increase in the extent of the areaof the enhancing process (fig 1A), and thepatient was admitted to hospital.At admission, visual acuity was 1/400

temporally in the right eye and 20/40 in theleft eye. Colour vision was markedly dimin-ished in both eyes. Kinetic perimetry showedan incomplete, incongruous left homon-ymous hemianopia (fig 2A). There was norelative afferent pupillary defect. Extraocularmotility was normal, as were corneal andfacial sensation. The right optic disc wasminimally pale; the left optic disc appearednormal. Lumbar puncture showed normalcerebrospinal fluid glucose and protein levels;there were 14 mononuclear white blood cells.Complete blood count and serum chemistrieswere normal. An acute infectious aetiologywas determined to be unlikely, and thepatient was treated with intravenous dexa-methasone 10 mg every 4 hours. Within48 hours, visual acuity had improved to 20/200 in the right eye and 20/30 in the left eye,and the visual field of the right eye hadexpanded temporally. Intravenous dexa-methasone was continued at 6 mg every

4 hours for 2 days, and then reduced to4 mg every 4 hours. After 7 days of treat-ment, the patient’s visual acuity hadimproved to 20/40 in the right eye and to20/20 in the left eye, with further expansionof the peripheral visual field of the right eye.Repeat MRI revealed marked reduction in thesize and enhancement of the basal process.

The patient was discharged home on a2 week tapering oral dose of dexamethasone.Four weeks after discharge, the patient had

visual acuity of 20/20 with slightly dimin-ished colour vision in each eye. An incon-gruous, left homonymous hemianopiaremained (fig 2B–C), but as this visual fielddeficit was scotomatous rather than absolute,

Figure 1 T1 weighted coronal MRI of head with gadolinium contrast (A) obtained at the time ofadmission to hospital. An enhancing lesion surrounds the right internal carotid artery (ICA) and isadjacent to a smaller enhancing lesion abutting the left ICA. The process extends into the righttemporal lobe. (B) 2 months after initiation of steroid therapy. Marked reduction in both the sizeand extent of the lesions as well as the degree of contrast enhancement is noted.

Figure 2 Kinetic perimetry with incongruous left homonymous hemianopia (A) at the time ofadmission and (B) performed after 4 weeks of steroid therapy, with marked expansion of theperipheral visual field of each eye. Static perimetry results (Humphrey 24-2, SITA Standard), botheyes, demonstrate the scotomatous nature of the residual visual field defects (C) after 4 weeks ofsteroid therapy and (D) 2 years after steroid treatment for vision loss.

1666 PostScript


the patient had been able to return to drivingand was now able to perform all of theactivities of daily living. MRI 6 weeks afterdischarge showed no evidence of enhance-ment or mass effect in the paraclinoid orsuprasellar region (fig 1B). Two years afterdischarge and without further treatment, thepatient remains well with stable vision andvisual fields (fig 2D).

CommentReinforcement of unclippable intracranialaneurysms with autologous or alloplasticmaterials was proposed over 80 years ago,with subsequent studies showing that only asubset of these materials produce the desiredlocal effect.1 Unfortunately, some patients inwhom this treatment is used develop visualloss, occasionally several months or yearsafter the surgery.6–9 Although both ischaemiaand infection are thought to be incitingfactors in some cases,10 most cases appear toresult from an inflammatory reaction to thematerial used to wrap the aneurysm.6 7 Thereason that the material incites such areaction is unknown.High quality MRI permits recognition of

the inflammatory process that usually isfound in cases of vision loss.3 4 Unlike inrecent reports,2–4 6 our patient presented witha markedly enhancing bilateral process that,after corticosteroid treatment, diminishedgreatly in both size and degree of contrastenhancement, providing an anatomical cor-relate with the functional improvementdemonstrated clinically. In our patient, ther-apy was initiated approximately 2 monthsafter the visual loss ensued, as was treatmentin the other cases where no diminution of theinflammatory mass was seen. Thus, as notedby others,6 it seems clear that some patientsrecover spontaneously, some improve withsteroid treatment, some improve with sur-gery, and some do not improve regardless oftreatment.To date, there has been no reported

demonstration by MRI of size reduction ofthe inflammatory mass after medical therapyalone. We demonstrate here that cottonassociated inflammation may respond dra-matically to anti-inflammatory therapy bothclinically and by neuroimaging. Furthermore,this case suggests that wrapping of intracra-nial aneurysms with cotton or cotton pro-ducts reinforced with fibrin glue is justifiedwhen no suitable alternative exists, and thattreatment with corticosteroids should bepursued aggressively should visual loss andimaging evidence of postoperative inflamma-tion result, as non-surgical treatment mayresult in both anatomical and functionalimprovement. Should this treatment beunsuccessful, a neurosurgeon should beprepared to explore the patient and attemptdebridement of the inflammatory process.

P S Subramanian, N R MillerDepartment of Ophthalmology, The Johns Hopkins

Hospital, 600 N Wolfe Street, Baltimore, MD 21287,USA

V Renard, R J Tamargo, N R MillerDepartment of Neurosurgery, The Johns Hopkins

Hospital, 600 N Wolfe Street, Baltimore, MD 21287,USA

Correspondence to: Prem S Subramanian, MD, PhD,Ophthalmology Service, Walter Reed Army Medical

Center, 6900 Georgia Ave NW, Washington DC20307-5001, USA;

[email protected]

doi: 10.1136/bjo.2005.078626

References

1 Choudhari KA. Wrapping and coating ofcerebral aneurysms: history, evolution andsurgical management after a re-bleed.Br J Neurosurg 2004;18:259–67.

2 Berger C, Hartmann M, Wildemann B.Progressive visual loss due to a muslinoma—report of a case and review of the literature.Eur J Neurol 2003;10:153–8.

3 Brochert A, Reynolds T, Baker R. MRI in a case ofmuslin-induced granuloma. Neuroradiology2003;45:82–4.

4 Bhatti MT, Holder CA, Newman NJ, et al. MRcharacteristics of muslin-induced opticneuropathy: report of two cases and review of theliterature. Am J Neuroradiol 2000;21:346–52.

5 McFadzean RM, Hadley DM, McIlwaine GG.Optochiasmal arachnoiditis following muslinwrapping of ruptured anterior communicatingartery aneurysms. J Neurosurg 1991;75:393–6.

6 Goldsberry DH, Ross IB, Dhillon G, et al. Visualdysfunction caused by gauze wrapping of anintracranial aneurysm. J Neuroophthalmol2004;24:42–5.

7 Repka MX, Miller NR, Penix JO, et al. Opticneuropathy from the use of intracranial muslin.J Clin Neuroophthalmol 1984;4:147–50.

8 Felsberg GJ, Tien RD, Haplea S, et al. Muslin-induced optic arachnoiditis (‘‘gauzoma’’):findings on CT and MR. J Comput Assist Tomogr1993;17:485–7.

9 Prabhu SS, Keogh AJ, Parekh HC, et al.Optochiasmal arachnoiditis induced by muslinwrapping of intracranial aneurysms. A report oftwo cases and a review of the literature.Br J Neurosurg 1994;8:471–6.

10 Kirollos RW, Tyagi AK, Marks PV, et al. Muslininduced granuloma following wrapping ofintracranial aneurysms: the role of infection as anadditional precipitating factor. Report of twocases and review of the literature. Acta Neurochir(Wien) 1997;139:411–15.

Visual loss may be due to siliconeoil tamponade effect rather thansilicone oil removalWe read with great interest the article byCazabon et al.1

In all the three patients it would have beenbetter to compare the visual acuity just beforethe silicone oil removal than immediatevisual acuity after initial vitrectomy, becausecontact of the eye with the silicone oil couldalso be responsible for visual loss as it wasknown to cause optic nerve damage, asdescribed in earlier reports.2

Earlier, Newsom et al also3 reported unex-plained sudden visual loss following siliconeoil removal in seven patients. They alsoobserved only electrophysiological abnormal-ities.Maybe the unexplained visual loss could be

the result of optic nerve damage and diffusegangilion cell dysfuntion caused by a siliconeoil tamponade effect on the eye rather thanthe procedure of silicone oil removal itself.

P K Rani, R Raman, P Bhende, T SharmaVitreoretinal Services, Sankara Nethralaya, 18

College Road, Chennai, 60006, India

Correspondence to: Dr Padmaja Kumari Rani,Vitreoretinal Services, Sankara Nethralaya, 18

College Road, Chennai, 60006, India;[email protected]

doi: 10.1136/bjo.2005.082602

References

1 Cazabon S, Groenewald C, Pearce IA, et al.Visual loss following removal of intraocularsilicone oil. Br J Ophthalmol 2005;89:799–802.

2 Budde M, Cursiefen C, Holbach LM, et al. Siliconeoil-associated optic nerve degeneration.Am J Ophthalmol 2001;131:392–4.

3 Newsom RS, Johnston R, Sullivan PM, et al.Sudden visual loss after removal of silicone oil.Retina 2004;24:871–7.

Visual loss after silicone oilremovalWe read with interest the paper by Cazabon etal1 on the important emerging problem ofsudden visual loss after removal of siliconeoil. We have seen a similar pattern of visual lossin our own patients, typically in the macula ondetachments associated with giant retinaltears. We have identified 12 cases in two units(St Thomas’s, London, and Sunderland EyeInfirmary), but five of these clearly had onset ofvisual loss before oil removal (onset between1 month and 5 months after oil insertion).2

Results of investigations were very similar tothose reported by Cazabon et al. In four of fivepattern ERG was suggestive of macular dys-function. The timing of onset of visual lossobviously alters the potential aetiology, whichas stated is unknown.In their paper, information on acuity for

cases 2 and 3, between 1 week after oilinsertion and oil removal is not provided. Didthese cases have visual loss preceding oilremoval? Developing cataract can obviouslyhinder interpretation of acuity measurements.In our cases the symptoms described did not fitwith cataract (scotoma, red desaturation) andpersisted if any cataract was removed.We have seen a further case since this

report, a 46 year old woman with a giantretinal tear and macula-on retinal detach-ment affecting the right eye. Acuity reducedduring the period of tamponade from 6/6 at2 weeks after oil insertion to 6/36+1, whichdid not recover after oil removal. She reporteda central negative scotoma. Electrophysiologysuggested macular dysfunction.We have speculated that phototoxicity may

have a role, as oil transmits light more in theblue spectrum than aqueous.3 The fat solublemacular pigments, lutein and zeaxanthin, arethought to protect the macula from photo-oxidative damage. Silicone oil has previouslybeen reported to dissolve fat soluble elementsfrom the retina.4

We measured the macular pigment opticaldensity (MPOD) in this case using a modifiedconfocal scanning laser ophthalmoscope andtwo wavelength autofluorescence technique3 weeks after oil removal. The results showeda substantially reduced MPOD in the eye thathad silicone oil compared to the fellow eye.Although the peak MPOD, at the fovealcentre of both eyes was similar (0.47 rightversus 0.52 left), the MPOD at K degree,1 degree, and 2 degrees eccentricity from thefoveal centre was markedly lower in the eyethat had silicone oil (0.12, 0.06, 0.02 respec-tively versus 0.40, 0.22, 0.07).Although MPOD varies greatly between

individuals, there is usually high interocularsymmetry in normal eyes.5 Further work isrequired to determine whether or not thisrelates to the visual loss and whether


Competing interets: none declared

MAILBOX

Accepted for publication 8 September 2005

PostScript 1667


therapeutic supplementation may reduce therisk of visual loss.

E N Herbert, S H M Liew, T H WilliamsonDepartment of Ophthalmology, St Thomas’s Hospital,

Lambeth Palace Road, London SE1 7EH, UK

Correspondence to: Mr Edward N Herbert,Department of Ophthalmology, St Thomas’s Hospital,

Lambeth Palace Road, London SE1 7EH, UK;[email protected]

doi: 10.1136/bjo.2005.082610

References


2 Herbert EN, Habib M, Steel D, et al. Centralscotoma associated with intraocular silicone oiltamponade develops before oil removal. GraefesArch Clin Exp Ophthalmol DOI 10.1007/s00417-005-0076-6.

3 Azzolini C, Docchio F, Brancato R, et al.Interactions between light and vitreous fluidsubstitutes. Arch Ophthalmol1992;110:1468–71.

4 Refojo MF, Leong FL, Chung H, et al. Extraction ofretinol and cholesterol by intraocular silicone oils.Ophthalmology 1998;95:614–18.

5 Bone RA, Sparrock JM. Comparison of macularpigment densities in human eyes. Vis Res1971;11:1057–64.

Visual loss following silicone oilremovalWe congratulate Cazabon et al on their recent,well illustrated, report.1 Their cases reflect asimilar group of seven patients we recentlyobserved at Moorfields Eye Hospital.2 Theywere relatively young, 19–57 years old, hadmacula-on, or ‘‘just off’’ retinal detachments.Five of seven had giant retinal tears and theothers multiple posterior tears with retinaldetachment. Following vitrectomy and oilinsertion, vision was good and then fell whenthe silicone oil was removed. The oil was inplace for between 105–220 days; threepatients had combined cataract surgery withoil removal.One difference between the reports is that

vision in our group fell immediately followingoil removal, whereas in Liverpool patientsreported visual loss at 1 week. Visual losscould be severe, some lost vision to countingfingers with a relative afferent papillarydefect, and all lost vision without macularsigns, optical coherence tomographic, orangiographic changes.The interpretation of electrophysiological

changes is different from that in our paper,where macular dysfunction was associatedwith generalised retinal dysfunction in some

patients and with an optic neuropathy in one.In this paper only the macular function iscommented on, the 30 Hz cone flicker beingpresented, and it is therefore difficult tocompare data without the full ISCEV data.3 4

It is not clear how the pattern visually evokedpotential (VEP) can be ‘‘normal’’ in case 1,with a visual acuity of 6/36 and an abnormalpattern electroretinogram (PERG); even inmacular disease with this level of visualacuity and an abnormal PERG, the patternVEP is invariably abnormal.3

A recent report of optic neuropathyinduced by silicone oil may perhaps explainour findings in one case.5 However, all theother cases reported so far seem to point to anew as yet unexplained phenomenon ofsudden visual loss following silicone oilremoval. Photoreceptor apoptosis, triggeredby rapid change in vitreous potassium con-centrations, is an attractive theory, but morework is required to elucidate this phenom-enon further. In the meantime we advocate acautious approach to silicone oil in patientswith macular-on detachments.

R S B Newsom, R Johnston, P Sullivan,B Aylward, G Holder, Z Gregor

Southampton Eye Unit, UK

Correspondence to: Richard S B Newsom,Southampton Eye Unit, UK;

[email protected]

doi: 10.1136/bjo.2005.082644

References


2 Newsom RS, Johnston R, Sullivan PM, et al.Sudden visual loss after removal of silicone oil.Retina 2004;24:871–7.

3 Fishman GA, Birch DG, Holder GE, et al.Electrophysiologic testing in disorders of theretina, optic nerve, and visual pathway. 2nd ed.Ophthalmology monograph 2. San Francisco:The Foundation of the American Academy ofOphthalmology, 2001.

4 Marmor MF, Hood DC, Keating D, et al.Guidelines for basic multifocalelectroretinography (mfERG). Doc Ophthalmol2003;106:105–15.

5 Eckle D, Kampik A, Hintschich C, et al. Visual fielddefect in association with chiasmal migration ofintraocular silicone oil. Br J Ophthalmol2005;89:918–20.



of neurological disease (Br J Ophthalmol2005:89;1120–2) has been reprinted in thisissue due to an error in the final paragraph,which has now been corrected.

CORRECTION

NOTICES

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doi: 10.1136/bjo.2005.63123corr1

The paper titled, Intermittent extropiaincreasing with near fixation: a ‘‘soft’’ sign

1668 PostScript


SCIENTIFIC REPORT

Intermittent exotropia increasing with near fixation: a ‘‘soft’’sign of neurological diseaseP H Phillips, K J Fray, M C Brodsky. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Br J Ophthalmol 2005;89:1120–1122. doi: 10.1136/bjo.2004.063123

Aim: To examine the association of distance-near disparity withneurological disease in children with intermittent exotropia.Methods: A retrospective analysis was performed of themedical records of all children with intermittent exotropiaexamined at the Arkansas Children’s Hospital between 1989and 2002. The study group consisted of children withintermittent exotropia who had a near deviation thatexceeded the deviation at distance by at least 10 prismdioptres. The control group consisted of children withintermittent exotropia who had a distance deviation greaterthan or equal to the deviation at near. The main outcomemeasures were the prevalence of neurological abnormalitiesin the study and control groups.Results: Among the 29 patients in the study group, 19 (66%)had a history of concurrent neurological abnormalities.Associated neurological conditions included developmentaldelay (10 patients), attention deficit disorder (four patients),cerebral palsy (four patients), history of intracranial hae-morrhage (four patients), periventricular leucomalacia (threepatients), seizures (two patients), cortical visual impairment(two patients), hydrocephalus (one patient), history of anoxicbrain damage (one patient), history of encephalitis (onepatient), and autism (one patient). Among the 37 patients inthe control group, seven (19%) had a history of concurrentneurological abnormalities. The difference in the prevalenceof neurological disease between the study group and thecontrol group was significant (p = 0.0002).Conclusion: Intermittent exotropia increasing with nearfixation is associated with neurological disease in children.

Children with intermittent exotropia often have anexodeviation that increases with distance fixation.1 2

However, some children exhibit an exodeviation thatincreases during near fixation. It has been our impressionthat the latter group frequently has associated neurological orneurodevelopmental disorders. To test this hypothesis, weretrospectively reviewed the medical records of our patientswith intermittent exotropia.

METHODSRetrospective analysis of the medical records of all childrenwith intermittent exotropia examined at the ArkansasChildren’s Hospital between 1989 and 2002. The study groupconsisted of children with intermittent exotropia whose neardeviation was at least 10 prism dioptres greater than theirdistance deviation. The control group consisted of childrenwith intermittent exotropia who had a distance deviationgreater than or equal to the deviation at near. Children who

had strabismus surgery were categorised by ocular motilitymeasurements obtained before their strabismus surgery.Children who had undergone strabismus surgery beforeexamination by one of the investigators were excluded fromthe analysis. In addition, children who had a near deviationthat was less than 10 prism dioptres greater than the distancedeviation, who had an inconsistent distance/near disparity, orwho were uncooperative for distance and near measurementswere excluded from the analysis. None of the patients hadamblyopia, ptosis, anisocoria, nystagmus, limited ductions orany other associated ocular disease. The absence of amblyo-pia was confirmed in preverbal children by the ability tomaintain central steady fixation with each eye and amongliterate children, by the presence of visual acuity equal to orgreater than 20/30 in each eye and equal visual acuity in botheyes.All patients were examined by at least two investigators.

Cover/uncover testing was used to diagnosis intermittentexotropia. Prism and alternate cover testing was performedwith distance (6 metres) and near (33 cm) fixation targets inorder to determine the magnitude of the exodeviation.Accurate fixation and accommodation were assured byhaving the patient identify different fixation targets asmeasurements were being obtained. Depending on the ageand development of the patient, Snellen letters or Allensymbols were used as fixation targets. Ocular occlusion wasnot performed before obtaining the measurements notedabove. When possible, confrontation visual field testing wasperformed to rule out hemianopic visual field deficits.The charts were reviewed for the presence of associated

ocular, neurological and systemic diseases. All patients andparents in the study and control groups were routinelyquestioned at each visit regarding the presence of neurolo-gical diseases including developmental delay, attentiondeficit disorder, and seizures. Most of the patients diagnosedwith neurological disease were evaluated by a paediatricneurologist or a child development specialist before theirophthalmologic evaluation.

Statistical analysisThe prevalence of neurological disease and the sex distribu-tion in the study and control groups were compared with atwo tailed x2 test. The age distribution in each group wascompared with a two sample t test.

RESULTSA total of 94 children had intermittent exotropia. Twentyeight children were excluded from the analysis. Reasons forexclusion included insufficient cooperation for accuratedistance measurements (18 patients), an exodeviation atnear that exceeded the deviation at distance by less than10 prism dioptres (eight patients), strabismus surgery that

REPRINTED FROM SEPTEMBER ISSUE

1120


was performed before evaluation by one of the investigators(one patient), and ocular motility measurements that wereinconsistent (one patient).The characteristics of the study and control groups are

shown in table 1. The study and control groups did not differsignificantly with respect to sex and age at evaluation. The 29patients in the study group had intermittent exotropia thatincreased with near fixation with a mean deviation of19 prism dioptres at distance and 35 prism dioptres at near.Seventeen of these 29 patients had an intermittent neardeviation greater than or equal to 35 prism dioptres indicat-ing robust fusional convergence amplitudes; 19 of these 29patients (66%) had a history of concurrent neurologicalabnormalities as listed in table 2.The control group consisted of 37 patients with a mean

exodeviation of 30 prism dioptres at distance and 13 prismdioptres at near. Seven of these 37 patients (19%) had ahistory of concurrent neurological abnormalities as listed intable 2. The prevalence of neurological abnormalities wassignificantly higher in the patients who had an intermittentexotropia that increased with near fixation compared withthe control group (p=0.0002). Despite the significantdifference in prevalence, the spectrum of neurologicalabnormalities was qualitatively similar between both groups.

DISCUSSIONWe found a high prevalence of neurological disease inchildren with intermittent exotropia increasing at nearfixation. Exodeviations that increase during near fixationhave been associated with several neurological disordersincluding head trauma, dyslexia, Parkinson’s disease, con-genital central hypoventilation syndrome, subdural haema-toma, and stroke.3–14 The term ‘‘convergence insufficiency’’has been loosely applied to this heterogeneous group ofpatients with exodeviations that become problematicduring near fixation. In this context, apparent convergence

insufficiency may arise from multiple mechanisms rangingfrom decreased fusional convergence amplitudes, a lowaccommodative convergence/accommodation ratio, accom-modative insufficiency, poor convergence effort, poor accom-modative effort, poor concentration, and pharmacologicaleffects of medications.3–14 We are unable to assign a specificneurophysiological substrate to our study patients withintermittent exotropia that increases with near fixation.However, many of our study patients were able intermittentlyto fuse large exodeviations, demonstrating that their con-vergence amplitudes were greater than normal.The magnitude of exodeviations at near is affected by

accommodative and convergence effort. We encouragedaccommodative and convergence effort by requiring ourchildren to identify fixation targets as measurements werebeing obtained. However, we cannot exclude the possibilitythat reduced accommodative or convergence effort may havecontributed to the high prevalence of exodeviations thatincrease with near fixation in children with neurologicaldisease.This study should be viewed in light of its inherent

limitations. Firstly, because our cohort was gleaned from achildren’s hospital population, our findings do not necessa-rily reflect the prevalence of neurological dysfunction in thegeneral population. However, the increased prevalence ofneurological disease in our children with intermittentexotropia that increases with near fixation compared withour control group of patients suggests that this association isreal. Secondly, the prevalence of neurological disease wasdetermined from a retrospective chart review. Not everypatient was examined by a paediatric neurologist. However,patients and parents were routinely questioned regarding thepresence of neurological disease at each visit. It is unlikelythat a more detailed paediatric neurological evaluation wouldhave disclosed clinically significant undiagnosed neurologicaldisease in a significant number of our apparently healthypatients. Finally, we did not formally measure accommodative

Table 1 Characteristics of the study and control groups

Sex (no of females)(mean)

Age (years)(mean (SD))

Distance deviation(prism dioptres)(mean (SD))

Near deviation(prism dioptres)

Study group (n = 29) 13 6.7 (8.3) 19 (10) 35 (11)range 3–17 range 0–40 range 10–55

Control group(n = 37)

17 4.4 (9.0) 30 (11) 13 (11)range 3–14 range 14–60 range 0–45

p Value 0.87 0.24

Table 2 Neurological diseases in study and control patients

Neurological diseases

Study group (n = 29) Control group (n = 37)

No of patients* No of patients*

Developmental delay 10 4Cerebral palsy 4 2Attention deficit disorder 4 1History of intracranial haemorrhage 4 0Periventricular leucomalacia 3 1Seizure disorder 2 4Cortical visual impairment 2 0History of hydrocephalus 1 0History of anoxic brain damage 1 0History of encephalitis 1 0Autism 1 1

*Most patients had more than one neurological abnormality

1121 Phillips, Fray, Brodsky


or convergence amplitudes in most of our patients withintermittent exotropia that increases with near fixation.Our study confirms a high prevalence of neurological disease

in children who have intermittent exotropia that increases withnear fixation. However, no patient was subsequently found tohave a serious treatable neurological lesion. As such, neuroima-ging is not warranted, and further diagnostic evaluation can beguided by the clinical history. Although the determinants ofincreased near disparity in intermittent exotropia have yet to bedefined, this form of strabismus appears to be a ‘‘soft’’ sign ofneurological disease in children.

ACKNOWLEDGEMENTSupported in part by unrestricted grant from Research to PreventBlindness and the Pat & Willard Walker Eye Research Center, JonesEye Institute, University of Arkansas for Medical Sciences.

Authors’ affiliations. . . . . . . . . . . . . . . . . . . . .

P H Phillips, K J Fray, M C Brodsky, Department of Ophthalmology,University of Arkansas for Medical Sciences, Little Rock, AR, USAM C Brodsky, Department of Pediatrics, University of Arkansas forMedical Sciences, Little Rock, AR, USA

Correspondence to: Paul H Phillips, MD, Arkansas Children’s Hospital,800 Marshall Street, Little Rock, AR 72202, USA; [email protected]

Accepted for publication 1 March 2005

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Arch Ophthalmol 1998;116:478–86.2 Kushner BJ. Exotropic deviations: a functional classification and approach to

treatment. Am Orthopt J 1998;38:81–93.3 Krohel GB, Kristan RW, Simon JW, et al. Posttraumatic convergence

insufficiency. Ann Ophthalmol 1986;18:101–4.4 Lepore FE. Disorders of ocular motility following head trauma. Arch Neurol

1995;52:924–6.5 Cohen M, Groswasser Z, Barchadski R, et al. Convergence insufficiency in

brain-injured patients. Brain Injury 1989;3:187–91.6 Kowal L. Ophthalmic manifestations of head injury. Aust N Z J Ophthalmol

1992;20:35–40.7 Al-Qurainy IA. Convergence insufficiency and failure of accommodation

following midfacial trauma. Br J Oral Maxillofac Surg 1995;32:71–5.8 Latvala M-L, Korhonen TT, Penttinen M, et al. Ophthalmic findings in dyslexic

school children. Br J Ophthalmol 1994;78:339–43.9 Racette BA, Gokden M, Tychsen L, et al. Convergence insufficiency in

idiopathic Parkinson’s disease responsive to levodopa. Strabismus1999;7:169–74.

10 Repka MX, Claro MC, Loupe DN, et al. Ocular motility in Parkinson’s disease.J Pediatr Ophthalmol Strabismus 1996;33:144–7.

11 Goldberg DS, Ludwig IH. Congenital central hypoventilation syndrome:Ocular findings in 37 children. J Pediatr Ophthalmol Strabismus1996;33:175–80.

12 Spierer A, Huna R, Rechtman C, et al. Convergence insufficiency secondary tosubdural hematoma. Am J Ophthalmol 1995;120:258–60.

13 Ohtsuka K, Maekawa H, Takeda M, et al. Accommodation and convergenceinsufficiency with left middle cerebral artery occlusion. Am J Ophthalmol1988;106:60–4.

14 Stavis M, Murray M, Jenkins P, et al. Objective improvement from base-inprisms for reading discomfort associated with mini-convergence insufficiencytype exophoria in school children. Binoc Vis Strabismus Q 2002;17:135–42.

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