Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

British Journal of Ophthalmology, 1988, 72, 646-659

Birdshot chorioretinopathy: clinical characteristics and evolution*

HILDE A PRIEM'2 AND JENDO A OOSTERHUIS2 From the 'Eye Clinic, University ofGent, Belgium, and the 2Eye Clinic, University ofLeiden, The Netherlands

SUMMARY During the period 1980-6 102 patients from 14 European eye clinics were diagnosed as having birdshot chorioretinopathy (BSCR). All were Caucasian, and the series consisted of 47 men and 55 women, with a mean age of 52*5 years. The major findings in this rare disorder concern the ocular fundus. Most marked are the patterned distribution of depigmented spots without hyperpigmentation, radiation from the optic disc in association with vitritis, retinal vasculopathy with frequent cystoid macular oedema, and involvement of the optic nerve head. The distribution and appearance of the lesions suggest that they are related to the major choroidal veins. Complications of the disease were epiretinal membranes, retinal neovascularisation, recurrent vitreous haemorrhage, subretinal neovascular membranes occurring both in the juxtapapillary and macular regions, and optic atrophy. The medical history was not contributory. HLA testing showed very strong disease association with HLA A29 (95.8%). The evidence suggests that it is a single disease a entity rather than group of disorders because of the remarkable similarity in the copyright. ophthalmological appearance and the clinical course, combined with the exceptionally high association with HLA A29.

In 1980 a rare ocular disease was described by Ryan and Maumenee.' In the absence of a known aetiology, they chose the descriptive name 'birdshot http://bjo.bmj.com/ retinochoroidopathy' inspired by the unusual picture, which showed multiple small, cream coloured lesions, scattered mainly around the optic disc and radiating towards the equator, without hyperpigmentation at the level of the retinal pigment _ * epithelium. Because of the presence of vitritis, : retinal vasculitis, and cystoid macular oedema they <7i on September 29, 2021 by guest. Protected likened the disease to pars planitis, but emphasised the absence of snowbanking over the pars plana. Other descriptive names have been used for this *This paper is the result of a collaboration by the following members of the European Fluorescein Angiography Club: P Amalric (Albi, France); M Spitznas (Bonn, FRG); C Orsini Dupont (Caen, France); G Coscas, A Gaudric, G Soubrane (Creteil, France); JJ de Laey, H A Priem (Gent, Belgium); J Hooymans, Z Timmerman (Groningen, The Netherlands); J A Oosterhuis, A H Renger-van _ Louvain,LoviBlim;ABrRBahaitnDijk(Leiden,Belgium);The ANetherlands);Bird, R Blach,AZ Leys.Gregor,rgnB ASnyersM Hamilton, D \. _ Sharp, J Shilling (London, England); A F Deutman (Leuven-UThe (Nijmegen, Netherlands); J A Bernard, G Quentel (Paris, France); G S Fig. 1 PatientofFranceschettiand Babel with systemic Baarsma, P T V M de Jong, B C P Polak (Rotterdam, The sarcoidosis. Whitefleckspredominantly in nasalperiphery Netherlands). and round optic disc with radialpattern and tendency toform Correspondence to Dr H A Priem, Dienst Oogheelkunde, lines towardsperiphery. (Bypermission ofthe Fondation Academisch Ziekenhuis, De Pintelaan 185, 9000 Gent, Belgium. ProfessorA Franceschetti.) 646 Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

Birdshotchorioretinopathy: clinical characteristics and evolution 647 entity, such as 'vitiliginous chorioretinitis' by Gass,2 (average 54*4 years). All were Caucasian. They were who stressed the similarity of the fundus patches to examined both clinically and by colour photography cutaneous vitiligo, 'salmon-patch choroidopathy' by and fluorescein angiography (Table 1). The clinical Aaberg,3 and 'chorioretinopathie en grains de riz' by files and the photographic documentation were Amalric and Cuq,4 who saw a similarity to the rice studied by one of us (HAP). grain pattern. The first set of data included the general history, Probably the first description of birdshot chorio- with specific reference to skin disease, allergy, and retinopathy (BSCR) in the early literature occurred hearing loss; and the ocular history, which covered in 1949 in a case report by Franceschetti and Babel.' previous eye disease, surgery, and family history. They described a 63-year-old woman with a condition The second set of data concerned the clinical examin- they named 'chorioretinopathie en taches de bougie' ation, including visual acuity, findings on slit-lamp (candlewax spots), who had systemic features of examination, tonometry, and ophthalmoscopy. The sarcoidosis. On ocular examination she had minimal third described the fluorescein angiographic findings. involvement of the anterior segment with only The fourth dealt with additional investigations such minute keratic precipitates (KP) but had dense as colour vision tests, perimetry, dark adaptation, vitreous opacity. The authors described a pale optic electro-oculogram (EOG), electroretinogram disc, very narrow retinal vessels, and multiple white (ERG), visually evoked potentials (VEP), and HLA 'retinal and chorioretinal' spots, and stressed the typing. Finally, long term behaviour and the absence of pigmentation of the spots (Fig. 1). Later influence of treatment were assessed. they saw areas of choroidal atrophy appear in the inferonasal quadrant. All these features are characteristic of BSCR. Table 1 Clinicalandfunctional investigations Other authors have highlighted special character- NumberofBSCRpatients istics of BSCR such as distinctive electrophysiologi- involved cal abnormalities,6 its association with the HLA A29 copyright. gene,7 and the occurrence of complications such as Total number in study 102 Fundus pictures 102 subretinal neovascular membranes'9 and optic Fluorescein angiography 102 atrophy.'2 The association with a rhegmatogenous Medical history 71 retinal detachment has also been reported.'6""' Ocular history 79 More case reports followed""'7 dealing with small Slit-lamp 68 Tonometry 60 numbers of patients only, giving the overall impres- Visual acuity 94 sion that BSCR is a rare disease. Colourvision tests 31

In this study we analyse in a large series of patients Perimetry 43 http://bjo.bmj.com/ the entity known as birdshot chorioretinopathy Dark adaptation tests 24 (BSCR) as defined by the EOG and ERG 42 accepted clinical picture. In VEP 30 particular, we sought to determine whether or not HLA typing 48 (in 5 patients A29 only) this is a single clinical entity or simply a collection of exotic cases with similar appearance. Table 2 Medicalhistory in 71 BSCRpatients Subjects and methods No. ofpatients on September 29, 2021 by guest. Protected The patients were collected from 14 ophthalmologi- Arterial hypertension 16 cal in Cardiac disease 5 departments five European countries. The Cerebrovascular accident 2 minimum criteria used for patient selection were Rheumatic disease, arthritis 6 based on the clinical manifestations as described by Low backache 2 Ryan and Maumenee.' Each patient was required to Gout I have the cream spots a Allergy (penicillin, fluorescein) 6 typical coloured birdshot with Eczema, psoriasis 4 symmetrical appearance in both eyes (if asymmetri- Hirsutism I cal, then one eye should at least be very characteristic Vitiligo (only in summer season) 1 of BSCR in number, size, and distribution of the Hearing loss 3 lesions), together with one of the following features: Meniere's disease 1 Migraine I evidence of retinal vasculopathy, evidence of disc Infectious disease: oedema or optic atrophy, or presence of vitreous tuberculosis 2 cells. viral hepatitis 2 The patients consisted of 47 men aged 23-79 years pericarditis I sarcoidosis 1 (average 50-7 years) and 55 women aged 32-74 years Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

648 Hilde A Priem andJendo A Oosterhuis

Results Table 3 Ocular history in 79patients with BSCR The study comprised 203 eyes of 102 BSCR patients; Eyes one eye with an extensive corneal leucoma since Open angle glaucoma 16 (1 eye Scheie operation) childhood preventing fundus examination was not Secondary glaucoma 2 (2 trabeculectomies) included. Full information on the clinical and Cataract extraction 5 (3 ECCE with IOL, 2 ICCE) Rhegmatogenous retinal 2 functional investigations were not always available at detachment the time of collection of the material (Table 1). Aphakic retinal detachment 1 Peripheral retinal breaks 1 MEDICAL AND OCULAR HISTORY Central retinal vein occlusion 1 Branch vein occlusion 2 A full medical history was recorded for 71 patients, Chloroquine keratopathy 1 but in most cases no relevant general disorder was Corneal leucoma (unknown 1 identified (Table 2). In one patient with hilar aetiology) lymphadenopathy the diagnosis of sarcoidosis was confirmed by biopsy and a positive Kveim test. Table 4 Oculat Sarcoidosis was specifically sought in 38 other patients symptoms at onset (81 BSCRpatients) but was negative in all. The incidence of arterial No. ofpatients hypertension in 16 patients, coronary artery disease in Blurred vision 58 5, cerebrovascular accident in 2, and retinal vein Floaters 30 obstruction in 3 was higher than one would expect in Night blindness 8 a similar age group. Distorted vision 4 With the exception of a rather high incidence of Photopsia 4 open angle glaucoma there were no apparent ocular Irritation 4 disorders associated with BSCR (Table 3). Pain 2 A variety of ocular conditions were identified in family members but none of them showed evidence Table 5 Visual acuity at initial ascertainment ofBSCR copyright. of BSCR. The dizygotic twin sister of a 52-year-old female patient was extensively examined; one sister Eyes had blood group AB+ and the other one A+, No. % although both were identical HLA types. The twin sister had normal 6/7 5 or more (0-8 or more) 73 39 visual acuity in both eyes and no 6/18-6/9 (0-4-0-7) 64 34 ocular complaints. Funduscopy revealed marked 6/60-6/24(0-1-0-3) 35 19 arteriosclerosis and two small perivascular haemorr- <6/60 (<0-1) 15 8 Total 187 eyes* 100% hages but no signs of BSCR. http://bjo.bmj.com/ On assessment of the diagnosis BSCR, many patients already had a long history of visual *One eye not in study. symptoms (Table 4). Blurred vision and floaters were the most common complaints. patients. Only two of them showed redness of one or both eyes and signs of acute inflammation of the CLINICAL EXAMINATION anterior segment. Eight patients had bilateral fine pigmented KP, and eight had very mild flare and cells Visual acuity in the anterior chamber of both eyes. In 13 eyes lens on September 29, 2021 by guest. Protected There was a wide range of visual acuity on assessment opacities were present but did not prevent adequate of the diagnosis BSCR. However, most eyes (73%) had a visual acuity of 6/18 or better (Table 5). Fig. 2 Clinical manifestations ofbirdshot In many patients the diagnosis BSCR was not chorioretinopathy. A and B: Patients aged56 years (Gent). made initially, since the clinical picture did not Typicalsymmetricalfundus pictures ofBSCR. Small become well known until 1980. The significance of neovascular tuft at inferior margin ofoptic disc (arrow in B). the good visual acuity at the time of diagnosis is C: Samefundus as in B. Radial linearstructures in nasal therefore greater when evaluated in relation to the periphery. Large choroidal vessels run over the lesions duration of ocular symptoms (Table 6). Out of 84 (arrow). D: Patient aged37years (Leiden). Large area of eyes 33 had a visual acuity of 6/26 or less when ocular juxtapapillary atrophy with increased visibility ofmajor complaints had been choroidal vessels. E: Patientaged 51 years (Leiden). present for more than one year. Sheathing ofretinal vessel (arrow). F: Patent aged 64years (Gent). Leftfundus ofBSCRpatient with ocular history ofIO Anterior segment and vitreous years' duration. The optic disc ispale, the retinal vessels are Details of the anterior segment were obtained in 68 irregular and narrow, small haemorrhages arepresent. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

Fig. 2A Fig. 2B copyright. http://bjo.bmj.com/

rIg2. 2 on September 29, 2021 by guest. Protected

Fig. 2E Fig. 2F Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

650 HildeA Priem andJendo A Oosterhuis fundus examination. In 80 patients (159 eyes) exami- 11 patients the condition was markedly asymmetri- nation ofthe vitreous was recorded: cells were seen in cal. The following aspects of the lesions were 121 eyes (76.1%) and opacities in 73 eyes (45-9%). In considered: appearance, distribution, and fluoro- total, signs of vitreous involvement were present in angiographic behaviour. 83% of the eyes examined. In most eyes the lesions were remarkably uniform in colour, shape, and size (158 eyes, 77 8%). Most Ophthalmoscopic andfluoroangiographicfindings frequently they were oval, with the longest diameter Choroidal lesions. In 91 patients both eyes were directed towards the optic disc and a diameter of less symmetrically involved (colour plate 2A, B) whilst in than 1/4 disc diameter (DD); they had a cream copyright. http://bjo.bmj.com/ on September 29, 2021 by guest. Protected

FI-g. .. Fig. 3D Fig. 3 Evolution ofbirdshotchorioretinopathy. A: Patientaged 44years (Gent). Righteye in 1975, diagnosed as bilateral papillouveitis. Note disc oedema, retinal haemorrhage (arrow). BSCRflecks are hardly visible. B: Samefundus asA in 1985: pale optic disc, narrow vessels, markedjuxtapapillary lesions; the birdshotflecks have become more clearly visible. C: Patient aged34years (Gent). Righteye in 1972 showingswollen optic disc; diagnosis: bilateralpapillouveitis. D: Samefundus as C in 1985 (courtesy ofB Snyers, Louvain), clearly showing birdshotflecks, narrowed arteries, small darkish dots aspossiblesign ofredistribution ofpigment. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

Birdshot chorioretinopathy: clinical characteristics and evolution 651

Table 6 Initial visual acuity and length ofocular history

Length ofhistory at Visualacuity (numberofeyes) initial ascertainment 617-5+ 619-6118 6124-6160 <6160 4weeks or less 15 4 1 1-5 months 15 7 6-11 months 14 10 6 1 1-4 years 7 25 14 6 Syears and more 11 8 8 5 History not mentioned 11 10 6 3 Total 73 64 35 15 coloured appearance and ill defined margins. In a small number of patients the birdshot lesions were larger than 1/4 DD, were more round than oval, Fig. 4A Patientaged5l years (courtesy ofUniversity Eye and did not show a radial distribution; however, their Clinic, Creteil). BSCRpatient withpetaloidaspectofoptic appearance was symmetrical. disc due to lesions atthe margin, sheathing ofalllarge retinal More exceptionally, a few sharply defined white vessels, cellophane maculopathy. atrophic spots were seen among the typical birdshot lesions, mostly in the posterior pole (Fig. 3B). Distribution. The densest concentration of lesions fluorescent during the dye transit (Fig. 4E). The was seen around the optic disc and in the nasal lesions adjacent to the optic nerve head and occasion- periphery. In many eyes lesions were adjacent to the ally those in the posterior pole were hypofluorescent optic nerve head, giving the disc a typical petaloid (Fig. 4D). In a few eyes sharply circumscribed copyright. appearance (Fig. 4). Sometimes the macular area was atrophic white lesions showed an early and bright involved, but in most patients no flecks were present hyperfluorescence. within the vascular arcades, apart from peripapillary Retinal vessels. There was marked narrowing ofthe lesions. In some eyes, with only a few or less retinal arteries in 124 eyes (61%). In most cases this prominent flecks, they were nearly always located in was associated with an irregularity in the calibre of the inferonasal fundus. the veins (Fig. 2F). In addition, small flame shaped In the majority of cases the lesions showed a well haemorrhages (Figs. 2F, 3A) were present in 27 of defined pattern radiating from the optic disc towards these eyes, mostly in the posterior pole along the http://bjo.bmj.com/ the periphery. There they often became confluent large temporal vessels or near the optic disc. and formed long yellow-white streaks, following the Retinal vascular leakage was a very common large choroidal vessels (Fig. 2C). finding on fluorescein angiography (Fig. 4E). A Another common feature was the tendency of the lesions to progress into large geographic areas of choroidal depigmentation. These areas were most frequently found in the nasal periphery and around on September 29, 2021 by guest. Protected the optic disc. In these zones the large choroidal vessels were easily visible and appeared to be enlarged (Fig. 2). In most eyes depigmentation of the lesions and of the atrophic areas was total and not associated with either pigment migration or hyperpigmentation. In some eyes there were tiny round, dark brown, sharply defined dots scattered over the fundus, unrelated to the lesions or depigmented areas (Fig. 4C). Fluorescein angiography. In the majority of cases the birdshot spots were not evident in the early stage of angiography, becoming apparent in the venous phase as faint hyperfluorescent flecks which did not rIg. 413 Sameyunaus as in A. riuoroangiograpny snowing increase in intensity in the late phase (Fig. 4B). In fainthyperfluorescence ofthe birdshot lesions; slightcentral fresh cases, however, the spots remained hypo- macularoedema. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

652 Hilde A Priem andJendo A Oosterhuis

*gy? X At

Fig. 4C Patient aged55years (courtesy ofA Leys, Leuven). BSCRpatient with lesions adjacent to the optic disc (petaloid aspect) and tiny dark dotsscattered over the fundus. copyright. http://bjo.bmj.com/ on September 29, 2021 by guest. Protected

Fig. 4D Samefundus as C. Fluoroangiogram shows hypofluorescence ofatrophic lesions adjacent to the optic discand ofthe dark dots. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

Birdshot chorioretinopathy: clinical characteristics and evolution 653

Fig. 4E Fluoroangiogram ofa recently diagnosed case (Gent) of BSCR, showing localised hypofluorescence corresponding with BSCR lesions, capillary dye leakage at the optic disc and in nasal periphery.

localised staining of the wall of the large retinal veins was seen in 81 eyes (40%). Profuse leakage from the tested, borderline in 5, and pathological in 34 eyes retinal capillaries was the most constant finding, and (70.8%). cystoid macular oedema was present in 127 eyes Visually evoked cortical responses were recorded (62-6%) (Fig. SA). In none of the patients was retinal in 60 eyes, 32 of which had abnormal amplitudes copyright. capillary closure identified. (53%), while in another 13 eyes there was an Optic disc. Apart from apparent blurred margins. increased latency. due to lesions adjacent to the optic disc, 77 eyes The ERG was normal in 18 out of 84 eyes, in 4 eyes (38%) showed disc swelling. On fluorescein angio- the absence of oscillatory potentials was the only graphy there was evidence of capillary leakage at the abnormal finding, 14 eyes were borderline, and 46 optic nerve head in 38% of all eyes. eyes (54.7%) had an abnormally low ERG. The EOG in 84 eyes showed a subnormal L/D ratio in 60

ASSOCIATED FINDINGS eyes (Table 8). http://bjo.bmj.com/ These findings were related to complications of the disease (Table 7). The most frequent complications HLA typing were epiretinal membranes and cellophane maculo- Data on HLA typing were available in 48 patients. In pathy (Fig. 6A and Fig. 4A), subretinal neovascular 43 the complete HLA A and HLA B loci were membranes (Figs. 6B, D), peripheral retinal and disc screened and in an additional S only the HLA A29 neovascularisation (Fig. SB, Fig. 6E, F), vitreous was sought. Forty-six out of these 48 BSCR patients

haemorrhage, and optic atrophy (Fig. 2F). Prolifera- (95.8%) carried the antigen HLA A29. on September 29, 2021 by guest. Protected tive retinopathy was particularly common and occurred in the absence of retinal capillary non- EVOLUTION AND MANAGEMENT perfusion (Fig. SC, D). There was no uniformity in the management of the disease in this large group of patients, which reflects Functional tests their origin from 14 different eye departments. A Perimetry, colour vision tests, dark adaptation and variety of therapies was used for posterior segment electrophysiology studies were performed on only inflammation, including corticosteroids, non- some of the patients (Table 1). steroidal anti-inflammatory drugs (indomethacin), Perimetry was normal in 15 out of 86 eyes, showed immunosuppressive drugs (azathioprine, cyclo- peripheral constriction in 30, a central or paracentral phosphamide, cyclosporin A), and a variety of scotoma in 28, and an enlarged blind spot in 26 eyes. antibiotics. The results of colour vision tests were normal in 21 In many cases the indication for treatment was not out of 62 eyes, 23 eyes showed only a blue-yellow clear. Owing to different criteria for management of defect in 23, and 12 eyes showed both blue-yellow the disease it was difficult to evaluate the influence of and red-green defects. therapy on the visual outcome. The data on a group Dark adaptation was normal in 9 out of 48 eyes of 27 patients with a follow-up of five years or more Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

654 HildeA Priem andJendo A Oosterhuis

Fig. 5A Patientaged years (Gent). BS with severe 5C Patientaged 55years (Gent). BSCR with irregular cystoid macular oedema. Note also hyperfluorescence ofthe re ofvessels and apreretinalhaemorrhage. venous vessel wall (arrow).

did not clearly indicate whether steroids and other macular oedema (3 eyes), and peripheral retinal copyright. anti-inflammatory and immunosuppressive drugs breaks or peripheral degeneration (3 eyes). were beneficial in BSCR (Table 9). The review period for 62 patients ranged from one Argon laser photocoagulation was applied to 17 month to 13 years. After an evolution of five years or eyes for treatment of subretinal neovascular mem- more half of the eyes have maintained a visual acuity branes (7 eyes), vitreous haemorrhage (4 eyes), of 6/18 or better (Table 10). Loss of visual acuity was http://bjo.bmj.com/ on September 29, 2021 by guest. Protected

vig.5H Samepatientas in fig. 2A, B with relapsing vitreous haemorrhage in right eye. After clearing ofthe Fig. 5D Samefundus as 5C. Fluoroangiogram shows haemorrhage a teleangiectatic lesion is seen in the temporal multiplesites ofretinal neovascularisation and widespread periphery. capillary dilatation, but no evidence ofcapillary closure. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

Birdshotchorioretinopathy: clinical characteristics and evolution 655

Table 7 Complications associated with BSCR Table 9 Visualoutcome in 27 BSCRpatients afterfiveyears or more Total number ofeyes with BSCR 203 Epiretinal membrane 20 Patient Initial Final Cause of Follow- Treatnent Retinal neovascularisation 15 no. VA VA visual loss lup Vitreous haemorrhage 5 (years) Subretinal neovascular membrane Parapapillary 1 6/18 6/24 CME 8 Steroids, laser LE 4 6/24 CF CME Macular 8 2 6/12 6/6 CME It) Steroids Optic atrophy 7 6/12 6/6 CME 3 CF CF Macular scar 5 Laser LE CF CF Subretinal Table 8 EOG in 84 eyes with BSCR ncovasc. 4 6/6 CF CME 8 Steroids, 6/7-5 CF CME cyclophosphamide, LID ratio Number ofeyes cyclosporin A+ 5 6/12 6/60 CME 6 Stcroids 171-200% 22 6/12 6/60 CME 151-170% 11 6 6/18 CF CME 6 Steroids, 131-150% 23 6/6 6/12 CME cyclosporin A 111-130% 15 7 6/12 6/9 Vitreous 9 Stcroids <110% 11 6/6 6/6 opacities 8 6/6 6/60 CM&+pucker 5 Steroids 6/5 6/9 CME+ cellophane 9 619 6/12 CME 5 Indomcthacin due to cystoid macular oedema, epiretinal membrane 6/12 6/9 CME in the macula, macular hole, subretinal neovascular 10 6/12 6/12 CME 5 Stcroids CF CF Cataract + membrane, macular scar, and cataract. Vitreous retinal haemorrhage and vitreous floaters were important detachment causes of visual loss in the initial stages of the disease 11 6/12 6/18 PE alteration 6 Sphiramycin, 6/9 6/60 Subretinal steroids, laser LE copyright. but did not contribute to the final visual outcome in neovasc. the group of patients with a minimum follow-up 12 6/12 6/12 CME 6 CF CF CME period of five years. 13 6/6 6/6 CME II Steroids, laser macula Improvement ofvisual acuity was seen in 13 eyes as 6/60 6/60 CME LE a result of clearing of vitreous haemorrhage (3 eyes), 14 6/9 6/60 CME+ 9 Steroids, vitreous' azathioprine removal of cataract (3 eyes), laser photocoagulation haemorrh. of subretinal new vessels (2 eyes), and regression of 6/9 6/24 CME 15 6/9 HM CME 13 Steroids, inflammatory signs (5 eyes). 6/9 6/60 CME azathioprine A few eyes showed a remarkable evolution in the 16 6/18 6/60 CME+ 5 Steroids, IOL RE http://bjo.bmj.com/ appearance ofthe hypopigmented spots (Fig. 3). Five cataract 6/12 6/36 CME+ patients initially had no clear evidence of birdshot cataract spots in the fundus when they presented with 17 CF CF Optic atrophy 5 None papillitis, retinal vasculitis, and varying degrees of CF LP Optic atrophy 18 6/9 6/9 CME 5 Steroids vitritis in both eyes. The typical fundus picture of 6/6 6/9 CME+ BSCR did not appear until several years later, mostly cellophane 19 6/9 6/9 5 when the signs of acute Secondary Trabeculectomy on September 29, 2021 by guest. Protected inflammation had resolved. glaucoma RE+LE HM HM Secondary Discussion glaucoma 20 6/18 6/5 7 Steroids, systemic+ 6/7-5 6/6 topical MEDICAL AND OCULAR ASSOCIATIONS 21 6/24 6/24 CME 10 Steroids The apparently high prevalence of vascular diseases 6/24 6/18 CME 22 6/6 6/6 1 I Steroids retrobulbar might indicate that BSCR is associated with a general 6/7-5 6/6 vascular disorder. No other systemic diseases seem to 23 6/4 6/4 9 Steroids topical 6/4 6/4 be relevant to the disease. Because Gass2 stressed the 24 6/60 6/60 CME 8 Steroids, association of BSCR with vitiligo, this was especially 6/12 6/12 CME azathioprine, sought; however, only one out of 102 patients was indomethacin 25 6/6 6/6 5 Steroids known to have depigmentation of the skin and only 6/6 6/12 after exposure to the sun. Moreover, Wagoner et 26 6/7-5 6/12 PE alterations 6 Steroids, laser 6/18 bil. 's8 on examination 223 6/18 Subretinal subretinal neovasc. of patients with vitiligo, neovasc. found evidence of BSCR in only one. Since multi- 27 6/36 CF CME 6 Steroids, laser LE focal choroidal disease is known to occur in sarcoido- 6/24 CF CME sis,591 at least 38 patients were fully by investigated CME=cystoid macular oedema. CF=counting fingers. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

656 HildeA Priem andJendo A Oosterhuis

Table 10 Visualacuity atlastcontrol (numbers ofeyes) by focal depigmentation of the choroidal melano- cytes' and compares the lesions with vitiligo of the Visual acuity Follow-up period skin. We could not establish a relation with vitiligo in I year 2years years 8years our patients. Moreover, the birdshot lesions have a distribution which does not correspond with the 6/75+ 21 17 3 8 diffuse presence of the melanocytes in the choroid. 6/18-6/9 23 25 13 3 6/60-6/24 14 12 6 7 Several findings suggest that the birdshot lesions <6/60 10 3 10 4 are located in the outer choroid and are associated with the large choroidal vessels. On many occasions large choroidal vessels are clearly seen to cross over means of chest x-ray, full blood counts, biochemical the lesions (Fig. 2C). The birdshot lesions show a tests including calcium and angiotensin-converting radial arrangement round the optic disc; this distribu- enzyme, Kveim test, and sometimes biopsy of skin tion corresponds most with the pattern of the large lesions. However, in only one was evidence of choroidal vessels and more specifically the choroidal sarcoidosis found; one other case ofBSCR associated veins. Most eyes showed macular sparing by the with sarcoidosis has been reported in Japan." birdshot lesions, an area which in most people is There was a particularly high incidence of open relatively free of large choroidal veins. However, the angle glaucoma (15 eyes, 19%) not associated with lack of lesions in the central fundus is not a constant pigment dispersion in the anterior chamber and feature, and one case has been reported in which the without evidence of elevated venous episcleral macula was the most affected site.'4 Very often the pressure. more peripheral lesions are confluent and form Two of the 79 patients with available ocular history elongated yellow-white streaks parallel to the had a rhegmatogenous retinal detachment, and choroidal vessels, suggestive of vascular sheathing. another patient had laser treatment for a peripheral Their predominant occurrence nasally inferior to the optic disc and the development of confluent lesions in retinal hole with operculum. The occurrence of copyright. rhegmatogenous retinal detachment in BSCR has the inferior nasal quadrant have also been reported been recorded 6"'11 and is a recognised complication by other authors.84 The large size and high density of of uveitis.20 Rhegmatogenous retinal detachment both choroidal veins and lesions at this site may be may complicate BSCR due to alterations and shrink- significant. The deep location of the lesions would age. The finding of minimal involvement of the explain their indistinct appearance and the lack of anterior segment is consistent with the other clinical secondary retinal pigment-epithelial reaction or dis- reports on BSCR, as is the case with the high turbance even in longstanding cases. The mild late percentage of vitreous opacities. phase hyperfluorescence of the birdshot lesions is in In general, the medical history and examinations accordance with a deep seated inflammatory focus http://bjo.bmj.com/ were not helpful in establishing an aetiological factor which gradually accumulates fluorescein. for BSCR. Retinal vasculopathy was a major feature of BSCR in this group of 203 eyes, manifest as cystoid macular FUNDUS CHANGES oedema in 127 eyes (62.6%) and perivascular leakage The ophthalmoscopic and fluorescein-angiographic in 81 eyes (40%). In several eyes the retinal vasculitis findings of the birdshot lesions, retinal vasculopathy, associated with vitreous cells -and papillitis was the and most of the complications have been previously presenting sign of the disease. on September 29, 2021 by guest. Protected reported. Retinal neovascularisation occurred in 15 eyes in The depigmented choroidal lesions are the most the absence of retinal capillary closure, making prominent feature of BSCR. Several suggestions it unlikely that the growth was in response to have been made regarding the pathogenesis of these lesions, depending on speculations as to their nature Fig. 6 Complications in birdshotchorioretinopathy. and on their level in the eye. According to Ryan and A: Patient aged56 years (Gent). Epiretinal membrane Maumeneel 'the depigmented spots may be related superior to optic disc (arrows). B: Patientaged58years ,to previous accumulation of fluid or to inflammatory (courtesy ofPAmalric, Albi). BSCR withjuxtapapillary foci in the choroid or in the retinal pigment subretinal neovascularisation. C: Patientaged52years epithelium'. Gass,2 however, finds the patches 'unlike (courtesy ofPAmalric, Albi). Left eye in 1981: note white birdshot lesion most other infiltrative or atrophic hypopigmented under the macula. D: Samefundus as C in 1983: subretinal neovascularisation has developed at the site fundus lesions' because they are not elevated as they ofthe birdshot lesion. E: Patient aged 44years (courtesy of are with a nodular inflammatory cellular infiltrate, JShilling, London). BSCR withprepapillary nor are they depressed as in the case of atrophy of the neovascularization (July 1978). F: Samefundus as E. choroid and retina. He suggests that they are 'caused Peripheral retinal neovascularisation. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from copyright. http://bjo.bmj.com/ on September 29, 2021 by guest. Protected

Fig. 6F Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

658 HildeA Priem andJendo A Oosterhuis ischaemia. Recurrent vitreous haemorrhages and the and the choroid, and that after a period of more or presence of small preretinal neovascular tufts have less active inflammation the condition tends to not yet been described in BSCR. Felder and Brock- stabilise. hurst2' reported retinal neovascularisation in patients The disease is rare, as only 102 cases of typical with posterior uveitis in the absence of capillary non- BSCR were collected in 14 major European eye perfusion, and Henkind' considered that inflamma- clinics during the period 1980-6, and it affects people tion locally in the retinal vascular bed is a sufficient in middle life without predilection for sex. stimulus for the growth of new vessels, though he 2. From the various clinical manifestations it is now found these were more readily induced at the disc possible to consider diagnostic criteria. The major than in the retinal vessels. In our BSCR patients only criterion is the characteristic spotted fundus appear- two eyes showed neovascularisation at the edge of ance associated with evidence of posterior segment the optic nerve head and 13 eyes showed peripheral inflammation and/or evidence of known complica- retinal neovascularisation. tions of the disease. The observation of subretinal neovascularisation Ranged according to their frequency, the ophthal- in 12 eyes with BSCR is in accordance with the moscopic signs are vitritis (83%), cystoid macular observation of Soubrane et al.,8 who reported on oedema (62.6%), arteriolar narrowing and irregu- three BSCR patients with juxtapapillary subretinal larity of veins (61%), retinal vasculitis (40%), disc neovascularisation, and Brucker et al.,' who oedema (38%), cellophane-like maculopathy (10%), observed macular subretinal choroidal neovasculari- retinal neovascularisation (7.5%), subretinal neo- sation in four eyes of two patients with BSCR. In two vascularisation and macular scar (6%), optic atrophy eyes of our series there appeared to be a relationship (3.5%). between a birdshot lesion and the development of a The minimal criteria necessary for the diagnosis of subretinal neovascular membrane (Fig. 6C, D). This BSCR could be formulated as bilateral presence of is not surprising, as new vessels may arise from typical birdshot spots in the fundus and two or more atrophic chorioretinal scars, irrespective of their signs from the preceding list. A further important origin. criterion may be the association with the antigen copyright. HLA A29. CONCLUSIONS 3. The aetiology remains speculative. There 1. The fundus appearance of BSCR shows a high appears to be no specific link with any systemic degree of uniformity and is now well defined, as has disease, although arterial hypertension and vascular been demonstrated in a large group of patients. It occlusive disease occurs rather frequently in this shows a characteristic pattern of multiple small group of patients. depigmented flecks, radiating from the margins of The specificity of the ophthalmoscopic appearance the optic nerve head towards the periphery. It is of BSCR, the constancy of its behaviour, and its very http://bjo.bmj.com/ bilateral and in most cases symmetrical. high association with HLA A29 together suggest that The condition is further characterised by the BSCR is a single nosological entity. There is no presence of various inflammatory signs, mainly in the evidence of a single cause, and it is possible that the posterior segment and only very seldom in the disorder represents a specific response to a variety of anterior segment. Some patients may initially present pathogenetic agents. with a mild to severe vitritis associated with disc oedema, retinal vasculitis, and cystoid macular We thank Mr R Blach and Professor A Bird for their valuable oedema before the flecks become apparent; as the criticism and help in reading the manuscript. We also thank Mrs G on September 29, 2021 by guest. Protected choroidal lesions appear the retinal and vitreous Coulier and Mrs I Jeltes for their secretarial assistance. changes often regress. Other patients present at their References first visit with the typical spotted retina with only minimal involvement of the vitreous and the retinal 1 Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J Ophthalmol 1980; 89: 31-45. vessels. In these cases a low grade inflammation may 2 Gass JDM. Vitiliginous chorioretinitis. Arch Ophthalmol 1981; also have been present for some time, giving rise to a 99: 1778-87. long history offloaters or in some patients not causing 3 Aaberg TM. Diffuse inflammatory salmon patch choroidopathy ocular complaints. The sequelae of previous inflam- syndrome. Read before the International Fluorescein Macula mation, such as optic atrophy, chronic cystoid Symposium, Carmel, California, October 1979. 4 Amalric P. Cuq G. Une forme tres particuliere de choriordtino- macular oedema, epiretinal membranes, peripheral pathie en grains de riz. Bull Soc Ophtalmol Fr 1981; 81: 131-4. retinal and disc neovascularisation, and subretinal 5 Franceschetti A, BabelJ. La chorioretinite en taches de bougie, neovascular membranes are common. It would manifestation de la maladie de Besnier-Boeck. Ophthalmologica appear that BSCR may begin with simultaneous 1949; 118: 701-10. 6 Kaplan HJ, Aaberg RM. Birdshot retinochoroidopathy. Am J inflammatory reactions in the vitreous, the retina, Ophthalmol 1980; 90: 773-82. Br J Ophthalmol: first published as 10.1136/bjo.72.9.646 on 1 September 1988. Downloaded from

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