Annals of the Rheumatic Diseases, 1977, 36, 152-156

Involvement of the eye in SLE and sclerodermaA study using fluorescein angiography in addition to clinical ophthalmicassessment

DAVID M. GRENNAN AND JOHN FORRESTER

From the Centrefor Rheumatic Diseases and University Department ofMedicine, Glasgow Royal Infirmary,and University Department ofOphthalmology, Western Infirmary, Glasgow

SUMMARY General examination of the eye was carried out in 22 patients with systemic lupuserythematosus (SLE) and in 10 with scleroderma. 3 of the SLE and 2 of the scleroderma patients hadkeratoconjunctivitis sicca. Fluorescein angiography showed abnormalities of the retinal vasculaturein one of a subgroup of 12 SLE patients and one of 10 scleroderma patients. None of the 12 SLEpatients had abnormalities of the choroidal vasculature, while 5 of the 10 scleroderma patients hadpatchy areas ofnonperfusion of the choroidal capillary bed.

Eye involvement was studied in patients withscleroderma and systemic lupus erythematosus (SLE)seen in a connective tissue disease clinic. In additionto routine clinical methods we used fluoresceinangiography to study the choroidal and retinalvasculatures (Wessing, 1969).There have been few reports on the use of this

technique in connective tissue disease (Hammanisand Streiff, 1973). A recent review suggested thatin SLE retinal microvascular abnormalities could beshown using fluorescein angiography in the absenceof visible fundal lesions (Lachman and Hazelmann,1975). It has also been suggested that this techniquemay be important in assessing disease activity inpatients with suspected cerebral lupus (Edmonds etal., 1975). Therefore we considered it important toinvestigate the ocular circulation by this techniquein our patients with SLE.

Post-mortem studies in patients with sclerodermahave shown abnormalities of the choroidal vascula-ture (Maclean and Guthrie, 1969; Farkas et al.,1972) as well as exudates in the retina (Maclean andGuthrie, 1969). These abnormalities were associatedwith advanced disease, often in hypertensive patients.In addition, other fundal abnormalities have beendescribed in scleroderma including retinal oedema,haemorrhages, and exudates (Dolfus, 1958), venousthrombosis (Josten, 1958), and cotton wool spots

Accepted for publication June 14, 1976Correspondence to Dr. D. M. Grennan, Rheumatic DiseasesUnit, Wellcome Medical Research Institute, Department ofMedicine, University of Otago Medical School, Dunedin,New Zealand.

(Pollack and Becker 1962). The pathology of theselesions was described by Manschot (1965) and theyare generally regarded as being secondary to latehypertensive disease. We investigated the choroidaland retinal vasculatures in a group of patients withearly as well as advanced manifestations of sclero-derma and believe this to be the first report of asystematic study of such patients by fluoresceinangiography.

Patients

SLETwenty-two patients with SLE had a generalophthalmic examination and were screened forkeratoconjunctivitis sicca (KCS). All patientssatisfied the preliminary criteria of the ARA for adiagnosis of SLE (Cohen et al., 1971). Fluoresceinangiography was carried out on 12 of these patients.9 were being treated with steroids and the diseaseprocess was considered to be under reasonablecontrol in all except one patient. 8 patients, however,had some clinical evidence of disease activity. 7 hadrenal disease but none had evidence of cerebralinvolvement at the time the test was carried out.9 patients had antibodies to native DNA as shownby the Farr test (Hughes, 1971) at the time offluorescein angiography, 4 had diminished levels ofcomplement C4, and 2 of these also had loweredcomplement C3 levels at this time.

SCLERODERMAThe clinical features of the 10 patients investigatedare shown in the Table. 3 patients had florid, rapidly

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Involvement of the eye in SLE and scleroderma 153

progressive generalized cutaneous disease which wasassociated with Raynaud's phenomenon and poly-arthralgia in the first, oesophageal involvement inthe second, and oesophageal and pulmonary involve-ment, Raynaud's phenomenon, and telangiectasiain the third. The disease in the other 7 patients hasbeen less aggressive and, unlike Cases 2 and 3 whoreceived penicillamine, their untreated prognosis wasjudged not to justify any potentially hazardous drugtherapy. Case 10 had sclerodactyly, Raynaud'sphenomenon, and polyarthritis, while Cases 4-9 allhad some internal organ involvement in addition tocutaneous changes.

Methods

OPHTHALMIC ASSESSMENTIn addition to general ophthalmological examination,including binocular indirect ophthalmoscopy, allpatients had tear flow measurements taken byaugmented Schirmer tear testing, plus slit-lampbiomicroscopy of the anterior segment of the eyeafter the instillation of Rose bengal dye for thediagnosis of KCS. Fundal photographs were takenin all cases.

FLUORESCEIN ANGIOGRAPHYFundal fluorescein angiography was carried outusing an intravenous bolus of3 ml sodium fluorescein15% solution in distilled water. Rapid sequencephotographs at intervals of 1-5 seconds were takenusing a Nikon F2 modified fundus camera with ablue excitor filter (Kodisk W27A) and a yellowbarrier filter (Kodisk W12). A wide angle lens wasincorporated into the camera.

Results

SLEThree of the 22 patients had KCS. One patient hadcytoid bodies in both fundi (Fig. 1). When these werefirst seen this patient had florid active disease withcutaneous, renal, and pleural involvement plus aperipheral neuropathy. Her blood pressure was 130systolic/90 diastolic mmHg. Treatment with steroids(60 mg prednisolone daily) had just been startedbefore the fundal photograph in Fig. 1. Her diseaseresponded to treatment and 4 months later when thegeneral disease activity had decreased (though shestill had some skin rash) the cytoid bodies had nearlydisappeared from both fundi.

Table Clinical features of 10 patients with scleroderma

Case no. Sex Clinicalfeatures Blood Fundus KCS Retinal Choroidal vasculature Therapypressure vasculature(mmHg)

1 M Diffuse cutaneous 120/75 Normal No Normal Patches of choroidal Nil(rapidly progressive), underperfusionRaynaud's phenomenon, polyarthralgia

2 M Diffuse cutaneous 160/100 ,, ,, Venular Normal Penicillamine(rapidly progressive), dilatations 600 mgoesophageal involvement

3 F Diffuse cutaneous 130/90 ,, ,, Normal Patches of choroidal Penicillamine(rapidly progressive), underperfusion lgoesophageal involvement, pulmonary,Raynaud's phenomenon, telangiectasia

4 F Acrosclerosis 150/90 ,, ,, ,, Normal Ibuprofen(slowly progressive),Raynaud's phenomenon,pulmonary involvement, polyarthritis

5 M Sclerodactyly 180/100 ,, ,, ,, ,, Nil(slowly progressive),Raynaud's phenomenon,oesophageal involvement

6 F Acrosclerosis 160/100 ,, ,, ,, ,, Salicylates(slowly progressive),Raynaud's phenomenon, polyarthritis,oesophageal involvement, telangiectasia

7 F Sclerodactyly 90/70 ,, Yes - - Nil(slowly progressive),Raynaud's phenomenon, smallintestinal involvement

8 F Sclerodactyly (slowly progressive), 180/80 ,, No Normal Patches of choroidal Nilcalcinosis, Raynaud's phenomenon, underperfusiontelangiectasia, oesophageal involvement

9 F Sclerodactyly (slowly progressive), 160/100 ,, No ,, ,, Nilcalcinosis, oesophageal involvement

10 F Sclerodactyly (slowly progressive), 140/80 ,, YesRaynaud's phenomenon, polyarthritis,telangiectasia

KCS =keratoconjunctivitis sicca.

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154 Grennan, Forrester

Fig. 1 Right fundus ofa patient with active SLEshowing cytoid bodies.

Among the 12 patients who had fluoresceinangiography, abnormalities of dye perfusion in theretinal vessels were seen in only one patient who wasalso the patient with visible fundal lesions shown inFig. 1. Fig. 2 shows the 11-second fluoresceinangiogram of the right fundus in the arteriolar phase

where areas of dye leakage from the retinal capillariesnear the disc are apparent. The areas are adjacent tothe avascular infarcted areas which correspond tothe cytoid bodies of Fig. 1. Similar but less markedareas of leakage were also seen in the left fundus.No abnormalities of choroidal perfusion were seenin these 12 patients with SLE.

SCLERODERMATwo of the 10 scleroderma patients had KCS. Thefundi of all 10 showed no abnormality on ophthal-moscopy. Fluorscein angiography, however, showedabnormalities in the retinal vasculature in onepatient and in the choroidal vasculature in 5 of the 10patients. Case 2 (Table) showed microaneurysmaldilatation of the terminal venules of the supero-temporal retinal veins (macular branch) (Fig. 3).Fluorescein dye stained the wall of the vessel asshown by persistence of staining into the late stagesof dye passage, but there was no leakage of dye fromthe vessel. A similar microvascular abnormality wasseen in the small peripapillary arterioles at 5 o'clockon the disc.

In 5 patients there were patchy areas of non-perfusion of the choroidal capillary bed whichpersisted in all cases for over 5 seconds and in 3 casesfor more than 8 seconds (Fig. 4). Filling of theseareas with dye eventually occurred by diffusion offluorescein from the normally leaking choriocapil-laris of healthy adjacent areas. All 3 patients with

Fig. 2 11-second fluoresceinangiogram of the right fundus in

.Q the early venous phase of a patientwith active SLE and cytoid bodies.

- 1| | (1) Area of capillary leakageadjacent to (2) the cytoid body.

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Involvement of the eye in SLE and scleroderma 155

aggressive generalized scleroderma had some abnor-mality on fluorescein angiography, 2 showingabnormal choroidal vessels and one showing abnor-mal retinal vessels. The 3 other patients withabnormal choroidal vasculatures had fairly benigndisease. One patient with abnormal choroidal vesselshad a raised blood pressure (160/100 mmHg).Patchy choroidal ischaemia did not interfere with ,a ..either visual acuity or visual fields.

._ Fig. 4 6-second fluorescein angiogram of a patient withscleroderma in the retinal arteriolar phase shows back-ground fluorescence from the normal choroid surroundingareas of nonperfusion ofdye (1,2).

Discussion

Keratoconjunctivitis sicca has been reportedpreviously in both SLE and scleroderma (Steinbergand Talal, 1971; Whaley et al., 1973; Alarcon-Segovia et al., 1974). In the series of Alarcon-

(a) Segovia et al., 6 of 25 patients with sclerodermahad abnormal Schirmer and Rose bengal stainingtests, thus satisfying our criteria for KCS, andthis is roughly equivalent to its incidence in oursmaller series. In addition to showing reduced tearflow plus typical staining of the conjunctival epithe-lium with Rose bengal dye, 3 of our cases (2 SLE,1 scleroderma) had filamentary keratopathy. 2further SLE patients, not included in the KCSgroup, had reduced tear flow but therewas no uptake

- ~~~~ ~ or Rose bengal dy.No blepharophimosis, cataract,; ;@ ~~~~~~~~~~~ordisturbances of ocular mobility was found in anyof the scleroderma patients.The incidence of fundal lesions in SLE has been

variously reported at 5 %~(Lachman and Hazelman,/ " -[ gDs 1975) and 93% (Dubois and Tuffanelli, 1964). In

our series only one of more than 22 patients withSLE had fundal abormalities (Fig. 1) which corre-lated with the fluorescein angiographic appearanceof altered retinal vascular haemodynamics, includingobliteration of the small arterioles (Fig. 2). Thispatient had active systemic disease at the time. None

(b) of our patients had known cerebral lupus, so ourFig. 3 (a) 125-second fluorescein angiogram in the findings do not conflict with those of Edmonds et al.nidvenous phase of the one patient with scleroderma (1975) regarding the potential usefulness of thismnd retinal vascular abnormalities. There is micro- technique in the assessment of patients with sus-mneurysmal dilatation of the superotemporal retinal vein pected cerebral lupus. However, we were unable towhich is not apparent on fundoscopy (b). show fluorescein angiographic abnormalities in any

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156 Grennan, Forrester

case with normal fundi and low disease activity, incontrast to others (Lachman and Hazelman, 1975).We will continue to assess this technique wherepossible in patients with exacerbations of SLE.No choroidal vasculature abnormalities were foundin the SLE patients.

In the scleroderma group no cases of retinopathywere found on ophthalmoscopy, confirming thereport of Kirkham (1969) who studied 10 cases.Previous case reports of retinopathy were associatedwith significant degrees of hypertension (Josten,1958; Pollack and Becker, 1962; Ashton et al.,1968), and a true correlation with sclerodermacould not be made. However, the most signifi-cant finding in our study was of abnormalitiesof choroidal perfusion affecting the choriocapillarisand small choroidal arterioles in 5 out of 10 caseswith scleroderma as shown by fluorescein angio-graphy. Only one of these patients had a diastolicblood pressure over 90 mmHg, suggesting that theabnormalities were not related to systemic hyper-tension. Previous histological studies have shownthickening of the basement membrane of theprecapillary arteriole plus endothelial swelling withobliteration of the lumen of the vessel and areas ofinfarction in the choroid (MacLean and Guthrie,1969; Farkas et al., 1972). Arterioles elsewhere in thebody may also be obliterated in scleroderma(Rodnan, 1963). Although other authors have notedthat a clear distinction could not be made betweenthe choroidopathy of scleroderma and that ofmalignant hypertension since they studied post-mortem eyes, often in previously hypertensivepatients, the pathology seemed sufficiently out ofproportion to the degree of hypertension noted tomerit a tentative correlation with scleroderma. Ourfindings of patchy choroidal ischaemia are in keepingwith this. These findings were noted in 3 patientswith benign variants of scleroderma as well as in the2 with aggressive disease.The significance of the retinal microvascular

abnormality recorded in Case 2 (Fig. 3) is not clear,as it was not found in the other cases of scleroderma,and has not been reported before. Its relevancetherefore is dubious.One characteristic of scleroderma may be a

generalized vascular abnormality which as Nortonand Nardo (1970) have suggested could be a primaryfactor in the pathogenesis of the disease. In view ofthe apparent frequency of choroidal vascular abnor-malities in this preliminary series of patients withscleroderma, we suggest that fluorescein angiographymay prove to be a useful additional method ofcharacterizing patients with early connective tissuedisease, although further study of larger numbers ofpatients is now required.

D.M.G. is a Robins Clinical Research Fellow. Weare grateful to Professor W. S. Foulds for advice andhelpful comments.

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