Episcleritis and scleritis Astudy their clinical ... · episcleritis is in fact a scleritis; the...

Brit. Y. Ophthal. (1976) 6o, I92

Episcleritis and scleritisA study of their clinical manifestations and association with rheumatoid arthritis

D. D. M. McGAVIN, J. WILLIAMSON, J. V. FORRESTER, AND W. S. FOULDSTennent Institute of Ophthalmology and Southern General Hospital, GlasgowW. W. BUCHANAN, W. C. DICK, P. LEE, R. N. M. MACSWEEN, AND K. WHALEYCentre for Rheumatic Diseases, Glasgow

Sir William Read, Royal Ophthalmologist duringthe reign of Queen Anne (1702-17I4), who inci-dentally was unable to read or write (Guthrie,1958), gave a choice description of the dangers ofperforation in deep scleritis: 'For it is most certainthat this horny membrane . . . by how muchdeeper the blister is hidden in the membrane . . .

in danger to make an ulceration by breakingthrough the membrane, whereupon may ensue an

utter loss and decay of all the humours'. Furtherdocumentation of the sequelae of scleral inflamma-tion awaited a further century for the description ofstaphylomata by Scarpa (i8i8), who described twocases of posterior staphylomata found at necropsy.

Mackenzie (I830) attributed scleritis to atmosphericconditions and suggested the term 'sclerotitis atmos-pherica' or 'rheumatic ophthalmia'. Later Macken-zie (I854) was to suggest the name 'sclerotitis idio-pathica'. Wolfe (I882), lecturing to the studentsof Anderson College, Glasgow, used the currentlyaccepted nomenclature of episcleritis and scleritis.The later terminology has been excellently recordedby Sevel (I967).

Earlier authors often associated inflammation ofthe sclera with rheumatic disease (Mackenzie,I830; Littell, I840; Wolfe, I882; von Arlt, i885).Besides 'rheumatism', scleritis was attributed togout (Cleobury, i826; Walton, I875), mercury

poisoning (Morgan, I839), venereal disease, parti-cularly syphilis (Morgan, I839; von Arlt, I885);scrofula (Mackenzie, I854); excessive exposure tovarying atmospheric conditions (Mackenzie, I830;de Schweinitz, I899), and menstrual derangement(de Schweinitz, I899).The most consistent systemic disorder associated

with episcleritis and scleritis, particularly the latter,is rheumatoid arthritis (Van der Hoeve, 1934;

Verhoeff and King, 1938; Smoleroff, 1943; Edstromand Osterlind, I948; Mundy, Howard, Stillman,and Bevans, 1951; Hollenhorst and Henderson,I951; Watson and Lobascher, I965; Watson,I966; Lyne and Pitkeathly, I968; Fowler, 1970;

Address for reprints: J. Williamson, Tennent Institute of Ophthal-mology, Glasgow

Jayson and Jones, 197I), and with this in mind thepresent study differentiates rheumatoid episcieritisand scleritis from non-rheumatoid episcleritis andscleritis according to the criteria for 'classical' or'definite' rheumatoid arthritis (Ropes, Bennett,Cobb, Jacox, and Jessar, I959).

Material and methodsExamination of patients was carried out at two centres:the Centre for Rheumatic Diseases, Glasgow, and theTennent Institute of Ophthalmology, Western Infir-mary, Glasgow.

During the years I965 to 1973 any patient seen atthe Centre for Rheumatic Diseases with rheumatoidarthritis who had any eye complaint was referred to anophthalmologist and any case of episcleritis or scleritiswas examined in detail. Those patients examined beforeI97I who were still alive were recalled to hospital orvisited in their homes. It was at the beginning of 1971that a scleritis clinic was instituted at the TennentInstitute, and a pro forma outlined the investigations tobe documented for patients at both centres. In allpatients these investigations included examination byan ophthalmologist and by a rheumatologist; this wassupplemented by laboratory investigations appropriateto ocular inflammation and rheumatoid disease.The purpose of the study was to compare patients

who presented with rheumatoid disease, who subse-quently developed episcleritis and scleritis, with patientswho presented with episcleritis or scleritis in whomrheumatoid disease was incidental to their referral.

CENTRE FOR RHEUMATIC DISEASES

Between I965 and 1973, 42Io patients with rheumatoidarthritis were examined at the Centre for RheumaticDiseases. These patients satisfied the diagnostic criteriaof the American Rheumatism Association (Ropes andothers, 1959). Seven of these patients had episcleritisand 28 had scleritis.

TENNENT INSTITUTE OF OPHTHALMOLOGY

During 197I and 1972, 62 patients were examined atthe scleritis clinic: 35 of these patients had episcleritisand 27 had scleritis. Two of the patients with episcleritisand nine of the patients with scleritis had rheumatoid

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Episcleritis and scleritis 193

arthritis according to the criteria already cited (Ropesand others, 1959).The presentation of results initially gives the incidence

of episcleritis and scleritis in rheumatoid arthritis, andalso the incidence of rheumatoid arthritis in episcleritisand scleritis. Thereafter, unless it is otherwise indicated,the patients are divided into those with rheumatoiddisease and those without rheumatoid disease. Thisresults in four groups of patients with:

i. Rheumatoid episcleritis (nine cases)2. Rheumatoid scleritis (37 cases)3. Non-rheumatoid episcleritis (33 cases)4. Non-rheumatoid scleritis (i8 cases)Comparisons are made between these four groups of

patients. In the section dealing with the systemicmanifestations of rheumatoid disease and also in someof the laboratory investigations a further comparison ismade, that is, between the combined groups of rheu-matoid episcleritis and scleritis and a group of rheuma-toid controls, patients with rheumatoid arthritis matchedfor age and sex with the rheumatoid episcleritis/scleritisgroups but without episcleral or scleral inflammation.This gives two further groups:

5. Rheumatoid episcleritis/scleritis (46 cases)6. Rheumatoid controls (46 cases)Statistical analysis is presented throughout the study.

However, the numbers, in what is a relatively uncommontype of ocular inflammation, are often very limited. Thebiological meaning of statistical evidence thereforerequires critical appraisal.

OPHTHALMIC EXAMINATION

Complaints of eye symptoms were elicited with as littleprompting as possible. The duration of the conditionwas estimated from the first episode of inflammation.Accurate documentation of duration is difficult as it isnot always certain that a condition which may persistintermittently during a period of some years has trulysettled. Visual acuity was assessed by Snellen's testchart at the Tennent Institute with or without glassesas appropriate. Refraction was not done routinely.The anterior segment of each eye was examined in

diffuse light, often in ordinary daylight, and by detailedexamination with a slit-lamp microscope. Patients seenin their homes were examined with a single loupe andfocal light. Slit-lamp examination served to reveal thedepth of inflammation, determining which network ofvessels was predominantly affected. It is occasionallydifficult to be certain whether an apparently nodularepiscleritis is in fact a scleritis; the diagnosis is oftenmore readily apparent in retrospect when, for example,an area of scleral translucency will indicate a scleritis.The greyish-blue colour of deep scleritis is due to thedark uvea becoming evident through translucent sclera.In contrast, episcleritis is usually bright red in colour.A careful slit-lamp examination after observation indiffuse light, with a conclusive diagnosis made only afterobserving the inflammation for varying periods of time,is sufficient in most cases to provide a diagnosis. Never-theless, there remain a few cases in which it is impossibleto differentiate with certainty an episcleritis from asuperficial scleritis. The figures that are given, therefore,are not absolute, but the features associated with

predominantly superficial inflammation affecting pri-marily the episclera will be contrasted with features ofdeeper involvement affecting primarily the sclera.

Ophthalmic examination took note of any cornealcomplications, anterior uveitis and cataract, particularlyposterior subcapsular cataract. The fundi were examinedafter instillation of cyclopentolate hydrochloride BPI per cent. A Haag-Streit applanation tonometer re-corded the intraocular pressure in patients seen inhospital, and a Perkins hand-held applanation tono-meter was used for those patients who were visited intheir homes.Any suggestion of limitation of extraocular muscle

movement or history of diplopia prompted referral tothe orthoptist for a more exact record.

All patients were screened for evidence of kerato-conjunctivitis sicca (KCS) by Schirmer's tear test(Schirmer I) using standardized filter-paper strips*.The length of wetting of the filter paper at the end of5 minutes was measured. A normal tear secretion wasaccepted as I5 mm wetting or more for patients underthe age of 40 years, and io mm wetting for patientsover the age of 40 years, as standardized by Halbergand Berens (I967). All patients with reduced tear flowhad a drop of rose bengal i per cent instilled into theeye, and punctate staining indicated the presence ofdead or dying cells and excess mucus. Confirmation ofKCS was given by Schirmer's test (Schirmer II) inwhich a io per cent ammonia solution is held approxi-mately 15-2 cm below the nose to stimulate tear produc-tion, which is recorded as in Schirmer I.

GENERAL EXAMINATION

The following investigations were designed to measurethe severity of any disease of the locomotor system, andcomplications of rheumatoid arthritis and other connec-tive-tissue disorders.

For each patient were recorded four grades of func-tional incapacity (Steinbrocker, Traeger, and Batterman,I949). The articular index, a summation index, esti-mated the number of involved joints and the severity oftheir involvement as judged by tenderness to pressureover the joint margin. Radiological evidence of thedegree of bone involvement was categorized in fourstages of increasing severity (Steinbrocker and others,I949).A number of extra-articular complications of rheu-

matoid disease were noted: subcutaneous granuloma-tous nodules, peripheral neuropathy, vasculitis manifestas skin ulceration or bruising, and tendon rupture.Atrophy of skin was recorded as a recognized side-effect of treatment with systemic corticosteroids(Scarborough and Shuster, 1960; Greenwood, I966).An enlarged spleen suggested the possibility of Felty'ssyndrome (Felty, 1924), and evidence of amyloidosiswas noted, as rheumatoid arthritis is now the com-monest cause of secondary amyloidosis in westerncountries (Boyle and Buchanan, 197I).

Xerostomia and salivary gland enlargement wererecorded as features associated with Sj6gren's syndrome(Sj6gren, 1933).*Developed by Halberg and Berens (Crookes-Barnes Laboratories,Inc., Wayne, NJ, USA)

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194 British Journal of Ophthalmology

An electrocardiogram was used in most patients(unless bedridden and visited at home) to excludecardiac disease, which has been noted as a complicationin patients with scleritis and rheumatoid arthritis(Smoleroff, 1943; Jayson and Jones, I97I). Bloodpressure recordings and cardiac auscultation screenedpatients for aortic incompetence, which has been asso-ciated with scleritis (Pitkeathly, Howitt, and Lyne,I970).

All patients had a chest x-ray examination to excludeevidence of active tuberculosis or sarcoidosis and todemonstrate any pulmonary complication of rheumatoidarthritis.

LABORATORY METHODS

In each patient the haemoglobin concentration, erythro-cyte sedimentation rate, and serum proteins, althoughnonspecific in nature, reflected the severity of disease.Haemoglobin estimation at the Tennent Institute ofOphthalmology was given as a percentage, but in theCentre for Rheumatic Diseases it was given in gramsper ioo ml. For comparison of data each haemoglobinvalue in g/Ioo ml was converted to a percentage reading,taking 14 gIo00 ml as a value of ioo per cent. Alkalinephosphatase, serum glutamic oxaloacetic transaminase,and serum glutamic pyruvic transaminase were recordedto assess any association of liver disease and scleritis.Liver disease has been noted in 6 per cent of patientswith Sjogren's syndrome without rheumatoid arthritisand in I-5 per cent of patients with Sj6gren's syndromeand rheumatoid arthritis (Whaley, Williamson, Dick,Goudie, Nuki, and Buchanan, 1970). Serum uric acidlevels were estimated to exclude gout. In view of therelevance of scleritis in venereal disease, usually syphilis(Cleobury, i826; von Arlt, I885; Holloway and Fry,1931), the Wassermann reaction, Venereal DiseaseReference Laboratory (VDRL) slide test and Reiterprotein complement-fixation test (RPCFT) were per-formed. Further investigations included the antistrepto-lysin-O titre, and tests for evidence of brucellosis andtoxoplasmosis. The antistreptolysin-O titre may beraised in erythema nodosum, a condition associated withepiscleritis (McCarthy, I96I). Brucellosis, a well recog-nized cause of uveitis (Woods and Guyton, I944;Hewson, I964), has been incriminated in a case ofscleritis (Thomas, Helluy, Cordier, and Algan, I953)and to exclude it the complement-fixation, standardagglutination (direct), and antihuman globulin(Coombs') tests were performed. Cat, Marinoni, Giraldi,and Costa (I97I) reported that two of their cases ofjuvenile rheumatoid arthritis had high false positivetitres for toxoplasmosis, and accordingly the toxoplasmadye test (Sabin and Feldman, 1948) was routinelyinvestigated.A multiplicity of autoantibodies may occur in the

connective-tissue (collagen) disorders (Copeman, I964).Scleritis has been called a collagen disorder (Hayrehand Watson, 1970). In view of this, autoantibody screen-

ing tests were undertaken in each case. Tests were

carried out for rheumatoid factor, using the latexagglutination technique (Hyland Laboratories) (Ziff,Brown, Lospalluto, Badin, and McEwan, 1956), the R3latex agglutination test (Denver Laboratories) using

sera giving a positive result in the rheumatoid latex test,and by the tanned red-cell haemagglutination techniquefor thyroglobulin antibody (Fulthorpe, Roitt, Doniach,and Couchman, I96I). All the remaining autoantibodyinvestigations applied the indirect immunofluorescenttechnique. These were tests for thyroid microsomalantibody, antinuclear factor, salivary duct antibody,mitochondrial antibody, gastric parietal-cell antibody,and smooth-muscle antibody (Table I).The assay of complement C3 (ic/ia globulin) used

specific immunodiffusion plates (Hyland Laboratories)and serum concentrations of IgG, IgA, and IgMglobulins were similarly measured by radial immuno-diffusion using commercially-prepared plates (Behring-werke) according to the method of Mancini, Carbonara,and Heremans (I965).

EYE SWABS

Platinum loop scrapings and swabs taken from theconjunctiva of the inflamed eye (the more inflamed inbilateral disease) in each case seen at the TennentInstitute of Ophthalmology were sent for investigationof bacteria, fungi, and viruses. Platinum-loop scrapingswere plated on chocolate agar for bacteriology. Isolationof fungi was effected by platinum-loop scrapings platedon 2 or 3 per cent malt extract agar with chloromycetin0o05 mg/ml. Swabs for virus studies were placedimmediately in Eagle's tryptose phosphate medium withcalf serum io per cent.

TYPE I ALLERGY (ATOPY)

Lyne and Pitkeathly (1968) with J. W. Kerr and J. M.MacLeod noted that, in 25 of 33 cases having singleattacks of episcleritis, the inflammation affected theinterpalpebral area. The findings in this present studyendorse their report and it seemed worth consideringexternal aggravating factors in the category of immediatehypersensitivity. Altogether 23 patients, all of them withnon-rheumatoid inflammation, and all except six casesof episcleritis, were subjected to skin testing for housedust, grass pollen, altemaria, feathers, house dust mite,Aspergillus, Candida albicans; and cat and dog hair, ifone of these pets was in the home.

Table I Autoantibody investigations

Autoantibody Tissue substrate Reference

Thyroid Human toxic Holborow, Brown, Roitt,microsomal thyroid and Doniach (I959)

Antinuclear Rat liver Beck (Ig6I)factor

Salivary duct Human salivary MacSween, Goudie,gland Anderson, Armstrong,

Murray, Mason, Jasani,Boyle, Buchanan, andWilliamson (I967)

Mitochondrial Rat kidney Goudie, MacSween, andGoldberg (1966)

Gastric parietal Human gastric Adams, Glen, Kennedy,mucosa McKenzie, Morrow,

Anderson, Gray, andMiddleton (I964)

Smooth muscle Rat stomach Johnson, Holborow, andsmooth muscle Glynn (I965)

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Episcleritis and scleritis I95

MORTALITY

An initial impression suggested that more of the patientswith rheumatoid episcleritis or scleritis had died sinceexamination as compared with the group of rheumatoidcontrols. The control group was carefully matched forage, sex, and year of presentation at the Centre forRheumatic Diseases. Contact with the general practi-tioner of each patient determined which patients haddied by February 1974. The Registrar of Births,Deaths and Marriages, Glasgow, provided informationas to the cause of death in each case.

ResultsINCIDENCE (Table II)Between I965 and 1973, 4210 patients with rheu-matoid arthritis were examined at the Centre forRheumatic Diseases. Seven of these patients had

Table II Incidence of episcleritis and scleritis inrheumatoid arthritis

No. of patientsClinic Disease Cases with rheumatoid Per-

arthritis centage

Centre for Episcleritis 7 4210 0-17Rheumatic Scleritis 28 4210 o-67Diseases 1965-73

Scleritis Clinic, Episcleritis 35 2 5.7Tennent Scleritis 27 9 33-3Institute ofOphthalmology1970-71

episcleritis (o0 I7 per cent) and 28 patients hadscleritis (o-67 per cent).

Thirty-five cases of episcleritis and 27 cases ofscleritis presented at the Tennent Institute ofOphthalmology during 197 I and 1972. Two ofthe cases of episcleritis (5 7 per cent) and nine ofthe cases with scleritis (33.3 per cent) had clinicaland radiological evidence of rheumatoid arthritisaccording to the diagnostic criteria of the AmericanRheumatism Association (Ropes and others, 1959).Each of these cases was sero-positive for rheumatoidfactor. One further case of episcleritis and sixfurther cases of scleritis were weakly sero-positivefor rheumatoid factor, but had no clinical or radio-logical evidence of rheumatoid arthritis.

(Unless otherwise indicated in the remainingdata patients from both clinics with rheumatoidarthritis are combined and compared with thefindings of patients without rheumatoid arthritis.)

AGE, SEX, AND BILATERALITY (Tables IIIa-f)The only group of patients with a mean age outsidethe sixth decade was the non-rheumatoid episcleritisgroup which had a mean value of 45 1 years.

All cases with rheumatoid episcleritis werefemale and this was consistent with the higherincidence of rheumatoid arthritis in women.

Scleritis was found in twice as many women asmen (67'6 to 32-4 per cent). It is interesting to notethat of the non-rheumatoid patients, episcleritiswas found equally in women and men (48-5 and5I 5 per cent), but scleritis showed a markedpreponderance in women (83-3 to i6'7 per cent).The 9 patients with rheumatoid episcleritis

Table IIIa Age (rheumatoid episcleritis andrheumatoid scleritis) 46 cases

AgeDisease Cases range Mean SD SEM

(years) (years)

Episcleritis 9 54-69 58-7 ±5-9 ±2-0Scleritis 37 28-77 58 3 ±iI-8 ±t.9

Statistical analysis: t=o-o840; P=NS

Table IIIb Age (non-rheumatoid episcleritis andnon-rheumatoid scleritis) 5I cases

AgeDisease Cases range Mean SD SEM

(years) (years)

Episcleritis 33 20-75 45.1 ±i4-6 ±2 5Scleritis s8 32-75 53 2 ±13-7 ±3-2

Statistical analysis: t = I 8746; P =NSStatistical analysis (rheumatoid versus non-rheumatoid):

Episcleritis: t= 2-7092; P = < ooo5Scleritis: t=s5044; P==NS

Table IIIc Sex ratio (rheumatoid episcleritis andrheumatoid scleritis) 46 cases

Females MalesDisease Cases Ratio

No. Per cent No. Per cent

Episcleritis 9 9 I00 0 - -Scleritis 37 25 67.6 12 32 4 2.I/1

34 73.9 12 26-5 2-8/I

Table Illd Sex ratio (non-rheumatoid episcleritisand non-rheumatoid scleritis) 51 cases

Females MalesDisease Cases Ratio


Episcleritis 33 I6 48-5 17 515 I/I-IScleritis I8 I5 83.3 3 I6-7 5/I

31 6o-8 20 39.2 i-6/i

Statistical analysis (female): X2=59337; P= <0-02Statistical analysis (rheumatoid versus non-rheumatoid (female):

Scleritis: t= 5175; P=NS

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196 British Yournal of Ophthalmology

Table IlIe Bilaterality (rheumatoid episcleritis andrheumatoid scleritis) 46 cases

Eye inflammation

Disease Cases Percentage Unilateral Bilateral


Episcleritis 9 I9-6 5 55-6 4 44-4Scleritis 37 8o-4 12 32-4 25 67-6

inflammation were more often admitted to thewards, or does it indicate that there was moreclinical indication for electrocardiography in theepiscleritis/scleritis groups? Certainly clinical ex-amination of the control group had given littleevidence of severe cardiovascular disease. The

Table IVa Past medical history and associateddisease (rheumatoid episcleritis and scleritis) 46 cases

Table IlIf Bilaterality (non-rheumatoid episcleritisand non-rheumatoid scleritis) 5 I cases

Eye inflammation

Disease Cases Percentage Unilateral Bilateral


Episcleritis 33 64-7 13 39-4 20 6o-6Scieritis i8 35 3 Is 6I-I 7 38 9

showed a similar number of unilateral and bilateralcases (5:4) but rheumatoid scleritis (37 cases) wasmore commonly bilateral (67-6 per cent). Non-rheumatoid episcleritis (33) was more commonlybilateral (39-4 to 6o06 per cent) and non-rheumatoidscleritis (I8) was more often unilateral (6i-i to38-9 per cent).

PAST MEDICAL HISTORY AND ASSOCIATED DISEASE(Tables IVa, b)A breakdown of medical history and associateddisease revealed a high incidence of associatedabnormality of the cardiovascular and respiratorysystems.Of 30 cases with rheumatoid scleritis (6o0o per

cent) in whom electrocardiograms were taken, i8had ischaemic heart disease. Three further patientscomplained of angina pectoris but had normaltracings. Six patients with non-rheumatoid epis-cleritis (21 9 per cent) had electrocardiographicchanges and one further patient had a possiblepericarditis. Three patients with non-rheumatoidscleritis (I6'7 per cent) had ischaemia of themyocardium. There is a significant differencebetween the incidence of ischaemia in rheumatoidscleritis and that in non-rheumatoid scleritis(P=o00005). The combined episcleritis/scleritisgroups showed a total incidence of myocardialischaemia in 21 of 37 known cases (56-7 percent) in comparison with the rheumatoid controlgroup, eight of 20 known cases (40o0 per cent). It isinteresting to note that only seven in the episcleritis/scleritis groups did not have an electrocardiogramcompared with i6 in the matched control group.Does this reflect the fact that the groups with eye

Episcleritis(9 cases)

Ischaemic heartdisease, 7 cases(2 unknown)

Rheumatic feverHypertension,

7 cases(2 unknown)

Aortic stenosisCerebrovascular

accidentRaynaud'sphenomenon

PneumoniaPleural effusionPleurisySinusitisOsteoarthritisChronic renal

diseaseOral pemphigoidGastric ulcerRecurrent colitisHemicolectomyPelvic abscessDiabetesBilateral otitismedia

Scleritis37 (cases)

PerNo. cent

Ischaemic heartdisease, 30 cases

3 42-9 (7 unknown)2 22-2 Hypertension,

32 cases(5 unknown)

I 14-3 Angina pectorisI (electrocardio-

gram normal)I Cerebrovascular

accidentI PericarditisI Mitral stenosisI Aortic stenosisI and incompe-I tenceI1 Rheumatic fever

Pulmonary embolusI1 Deep venousI thrombosisI PneumoniaI Pleural effusionI SinusitisI RheumatoidI nodules of lung

Tuberculosis ofI lung

EmphysemaAsthmaPneumoconiosisGranulomatous

(collagen)disease

OsteoarthritisDupuytren's

contracturePsoriatic arthritisDuodenal ulcerCholecystectomyHysterectomyDiverticulosisAdenocarcinoma

of bowelAppendicectomyProstatectomyProlapsed bowelInguinal herniaHepatitisHerpes zoster

(trunk)PsoriasisRodent ulcerThyrotoxicosisDiabetesTrigeminal

neuralgiaPernicious anaemiaPuerperal feverChronic otitismedia

PerNo. cent

I8 6o-o

8 25-0

8-I

2.7

13-5

Jo-8

3

3II

I

II

I

554

3

22

44

II

433I

I

3

5

I

I

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statistically insignificant difference between thesetwo groups might well be misleading.

Excluding respiratory complaints such as bron-chitis, emphysema and asthma, pleurisy andrheumatoid pneumonia, pleural effusion, pleurisyand rheumatoid nodules of the lung, both rheuma-toid episcleritis and scleritis had a similar incidence

Table IVb Past medical history and associateddisease (non-rheumatoid episcleritis and non-rheumatoid scleritis) 5i cases

Episcleritis Scleritis(33 cases) (i8 cases)

Per PerNo. cent No. cent

of respiratory complications - that is, three of ninecases in episcleritis (33-3 per cent) and I3 of 37cases in scleritis (35.I per cent). The incidence ofrespiratory disease in non-rheumatoid episcleritisand scleritis was much lower; two of 33 cases inepiscleritis (6'i per cent) and one of i8 cases inscleritis (5'6 per cent). The difference in each case isstatistically significant (P=o'05 and P=o0o05,respectively). The combined rheumatoid episcleri-tis/scleritis groups gave a total of i6 with rheuma-toid respiratory complaints out of 46 cases (34'8per cent) as compared with five of 45 rheumatoidcontrols (ii i per cent). The difference is statistic-ally significant (P=o'oi).

Other associated systemic disorders are listed inTables IVa, b.

Hypertension,30 cases

(3 unknown) 8Ischaemic heart

disease, 32 cases(I unknown) 6

Valvular heartdisease 2

Rheumatic fever 2Pericarditis ICerebrovascular

accident ISinusitis 8Pneumonia 2Asthma 2Bronchitis IOsteoarthritis 5'Rheumatism' 5'Back trouble' 2'Fibrositis' 2'Knee synovitis' ICervical

spondylosis IPaget's disease of

spine andischium I

Coccygodynia IPatellar

displacement IGout IPyelitis 2Tuberculosis of

kidneys IHydronephrosis IRenal stone IDuodenal ulcer 4Hiatus hernia 2Cholecystitis IAppendicectomy IPerianal sinus IApical dental

abscess IJaundice IThyroidectomy IErythema nodosa 2Chronic discoid

lupus erythema-tosus I

Psoriasis IPityriasis rosea IUlcer inguinal

region IAcne rosacea IHerpes zoster

ophthalmicus IDiabetes IGlandular fever IPuerperal fever I

Hypertension,I6 cases

26-7 (2 unknown)Ischaemic heart

diseasex8-8 Rheumatic fever

Aortic incompe-6-I tence

Msgraine3-0 Sinusitis

AsthmaTuberculosis of

chestBronchitisPneumoniaOsteoarthritis

I5-2 'Fibrositis''Slipped disc''Rheumatism'GoutMenopausal

haematuriaCholecystectomyAppendicectomyHysterectomyGastritis'Gastrichaemorrhage'

Duodenal ulcerApical dental

abscessSystemic lupus

erythematosusErythema nodosaMultiple rodent

12-I ulcersJaundiceDepression

4

3

I

5

2

32

II

2

22

25-0

Ii67

5.5

27-8I I* I

I6.7

EYE SYMPTOMS (Tables Va, b)Redness and ocular pain are by far the commonestcomplaints in both episcleritis and scleritis. A redeye was referred to only slightly less often in rheu-

Table Va Eye symptoms (rheumatoid episcleritisand rheumatoid scleritis) 44 cases

Symptoms

Red, inflamed, bloodshotOcular painGritty, sandyBurningItchingWateringIrritationPhotophobiaOedema of lidsHeadacheDischarge, matteringDrynessBlurring of vision

Episcleritis Scleritis(35 cases,

(9 cases) 2 unknown)


8 88-9 29 82-9

3 33 3 I6 45-72 22-2 II 3I.4I III 5 54.30 3 8-6I 3I 2 5-70 20 20 2I I 2-9I I

0 I

Table Vb Eye symptoms (non-rheumatoidepiscleritis and non-rheumatoid scleritis) 51 cases

Episcleritis Scleritis(33 cases) (i 8 cases)

SymptomsNo. Per cent No. Per cent

Red, inflamed, bloodshot 31 93-9 I6 88-9Ocular pain i6 48-5 13 72-2Gritty, sandy 8 24-2 3 I6'7Headache 4 s2s- 5 *6Oedema of lids 4 oIrritation 3 9-I 3Discharge, mattering 3 0Burning 2 6-I 2 II*IWatering 2 0Dryness I 3-0 IBlurring of vision I IItching o IPhotophobia o o

II

II

I

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I98 British Journal of Ophthalmology

matoid episcleritis (88-9 per cent) than in non-rheumatoid episcleritis (93-9 per cent), and inrheumatoid scleritis (82z9 per cent) compared withnon-rheumatoid scleritis (88&9 per cent). A greaterdisparity of complaint was notable with regard toocular pain in rheumatoid episcleritis (33-3 per cent)compared with non-rheumatoid episcleritis (48 5per cent), and in rheumatoid scleritis (45-7 per cent)compared with non-rheumatoid scleritis (72-2per cent). The lower incidence of complaint byrheumatoid patients probably reflects the measureof discomfort they experience elsewhere.

LENGTH OF HISTORY OF EYE INFLAMMATION(Tables VIa, b)

Figures giving the duration of ocular inflammationmust be interpreted cautiously, as it is impossibleto know whether the inflammation is truly quiescent.However, in each of the four groups of patientsthe mean duration (with a large standard deviationin each case) showed no significant difference. Itwas interesting to note that the mean duration ofocular inflammation in the rheumatoid patients wasshorter than that in the non-rheumatoid patients;36-2 months (rheumatoid episcleritis) and 35-omonths (rheumatoid scleritis) compared with 42-4months (non-rheumatoid episcleritis) and 48-9months (non-rheumatoid scleritis). There was awide range in each group, from a few days or weeksto 23 years.

Table VIa Length of history of eye inflammation(rheumatoid episcleritis and rheumatoid scleritis)40 cases

MeanDisease Cases Range (months) SD SEM

Episcleritis 8 3 days/ 36-2 ±6o-o ±2I+2(I unknown) I5 years

Scleritis 32 I week/ 35s0 +54-0 +9-6(5 unknown) 20 years

Statistical analysis: t=0o0534; P=NS

Table VIb Length of history of eye inflammation(non-rheumatoid episcleritis and non-rheumatoidscleritis) 49 cases

MeanDisease Cases Range (months) SD SEM

Episcleritis 31 4 weeks/ 42.4 ±74 2 ±I3 3(2 unknown) 23i years

Scleritis I8 7 weeks/ 48-9 ±74-2 ±17-520 years

Statistical analysis: t=0o2938; P=NSStatistical analysis (rheumatoid versus non-rheumatoid):

Episcleritis: t-=OII39; P=NSScleritis: t=o05713; P=NS

VISUAL ACUITY (Table VII)

Visual acuity was recorded in the Tennent Instituteof Ophthalmology but it was not recorded routinelyin patients seen at the Centre for RheumaticDiseases. An arbitrary dividing line of visual acuityof 6/12 (Snellen), or worse, provided a parameter for

Table VII Visual acuity (Tennent Institute ofOphthalmology) 62 cases

No. of eyes withDisease Eyes visual acuity Percentage

(total no.) < 6/9

Episcleritis 56 8 14-3Scleritis 41 I5 36.6

Statistical analysis (episcleritis versus scleritis):x2=6 5070; P= <0 025

the level of visual acuity achieved by each patient.Of the total of 56 eyes with episcleritis, eight eyes(14-3 per cent) had a visual acuity of 6/12 or worse,and of the 4I eyes with scleritis, I5 (36-6 per cent)had a visual acuity of 6/12 or worse. The differencebetween these two groups is statistically significant(P=0o025). It must be emphasized that refractionwas not done as a routine in these cases and thatthe difference is based on the patient's best visualacuity either with distance glasses or without.

TYPE OF INFLAMMATION (Tables VIIIa, b)

All nine cases of rheumatoid episcleritis were ofthe 'simple' variety. Nodular episcleritis was notedin six cases (I8-2 per cent) of the patients with non-rheumatoid inflammation (Fig. I) and simpleepiscleritis was recorded in 27 (818 per cent).Diffuse scleritis (Fig. 2) was more common inrheumatoid scleritis (83 3 per cent) and non-rheumatoid scleritis (6i1i per cent). A nodularscleritis was slightly less common in rheumatoidscleritis (I6-7 per cent) as compared with non-rheumatoid scleritis (33-3 per cent). One case ofnon-rheumatoid necrotizing scleritis (Fig. 3) pre-sented in a patient who had developed gout somemonths earlier, but the area of necrotic sclera was

Table VIlla Type of inflammation (rheumatoidepiscleritis and rheumatoid scleritis) 45 cases

Per PerDisease Cases cent Type cent

Episcleritis 9 Nodular oSimple 9

Scleritis 36 (I unknown) *Nodular 6 I6-7Anterior 36 I00 Diffuse 30 83-3Posterior 8 22-2 Necrotizing o

*Scleral translucency in 29 cases (8o-6 per cent)

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Episcleritis and scleritis I99

Table VIIIb Type of inflammation (non-rheumatoidepiscleritis and non-rheumatoid scleritis) 51 cases

Per PerDisease Cases cent Type cent

Episcleritis 33 Nodular 6 I8-2Simple 27 8I-8

Scleritis i8 Nodular 6 33-3Anterior I8 IoO* Diffuse i I 6I-IPosterior I 5 6 Necrotizing s 5 6

*Scleral translucency in two cases (i I-I per cent)

probably determined by a subconjunctival injectionof methylprednisolone some days previously.Co-existent posterior scleritis was more common inrheumatoid scleritis (22z2 per cent) than in non-rheumatoid scleritis (5-6 per cent). The figure ofeight cases in rheumatoid inflammation was atentative one, based on two cases of choroiditis,one case of retinal detachment, and five cases ofextraocular muscle imbalance, suggesting tendon

epis-

FIG. I Nodular non-rheumatoid episcleritis

FIG. 3 Necrotizing scleritis

or muscle involvement. These figures do not includepatients with macular disturbance which mighthave been due to other causes. The section onposterior segment abnormality will deal with thisin more detail. One of the most interesting findingswas the difference between rheumatoid and non-rheumatoid scleritis in the incidence of scleraltranslucency (Fig. 2). Of 36 cases with rheumatoidscleritis, 29 (8o-6 per cent) showed scleral translu-cency as compared with two of i8 cases with non-rheumatoid scleritis ( II i per cent).

DISTRIBUTION OF INFLAMMATION (Tables IXa, b)

The distribution of ocular inflammation in episcleri-tis is more commonly in the interpalpebral area,suggesting the possibility of external aggravatingfactors. Scleritis will also affect the superiorquadrants of the eye in particular, although lessmarkedly so in non-rheumatoid scleritis. Rheuma-

FIG. 2 Bilateral diffuse scleritis

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Tables IXa, b Distribution of inflammationDistribution of inflammation (rheumatoid episcleritis & rheumatoid scleritis) 38 cases

Episcieritis9 cases

Right (7eyes)

22 2%/

A 55 60 44 50/o

/22.20/

Left (7 eyes)

00/0

5560/a 33.40/a

1/ 2%/

Scleri tis29 cases (8 unknown)

Right (31 eyes) Left (30 eyes)

68.90/

78.9/ 55 20/a

/58.60/a

72 80/a

655 a58.60/

51.7%\Distribution of inflammation (non-rheumatoidepisceritis &non-rheumatoid scleritis) 51 coses

Episcleritis33 cases

Right (23 eyes)

\3-0°h

B 273/ 48.-50/

/18.20/ao

Left (29 eyes)

18.20/

57.6 5.5o5%

/27 30/a

Scleritis17 cases (one posterior scieritis)Right (14 eyes) Left (12 eyes)

\29.30/

47.j/ 6<4.70/a

/5.9o0/a

29.40/

58. 41.20/

/I1180/a

toid scleritis has a fairly even distribution affectingall quadrants of the anterior sclera.

CORNEAL COMPLICATIONS (Tables Xa, b)

An unexpected finding among the rheumatoidpatients was a higher percentage of corneal compli-cations in episcleritis (69z2per cent) compared withscleritis (43-5 per cent). The small number of I3eyes with episcleritis, however, may have given aninaccurate picture when one considers the anatomyof the structures involved. The difference is notstatistically significant. Non-rheumatoid inflam-mation showed a lower percentage of cornealinvolvement in episcleritis (I8-9 per cent) than inscleritis (28o per cent) although the difference was

not statistically significant. Corneal complicationsshowed a higher incidence in rheumatoid ascompared with non-rheumatoid disease, whichwas statistically significant for episcleritis(P=0ooo5) but not for scleritis.The predominant corneal complication is a

sclerosing keratitis which is usually localized at thesite nearest to the inflamed sclera or episclera.Occasionally, in diffuse inflammation, the conditionis annular (Fig. 4). The scar of sclerosing keratitisis permanent but in itself has little effect on visualacuity. However, of io patients with annular sclero-sing keratitis in whom visual acuity was assessed,six (6o0o per cent) had markedly reduced visionIdue to lens changes.

Limbal guttering occurred in one eye with rheu-

FIG. 4 Annular sclerosingkeratitis in a patient wit/ non-rheumatoid scleritis

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Table Xa Corneal complications (rheumatoidepiscleritis and rheumatoid scleritis) 46 cases

Eye inflammation

Disease Eyes Unilateral Cases(no.) (no.)

Episcleritis 13 Localizedstromal I*

Localizedsclerosing I

Annularsclerosing I

Scleritis 62 Localizedsclerosing 2Annularsclerosing I

Keratolysis I

Bilateral Cases Per-(no.) centage

Localizedsclerosing 3 69-z

Localizedsclerosing 6 43-5

Annularsclerosing 4

Grosslydegenerateblind I

Localizedsclerosing I *

Three eyes with scleritis (4-9 per cent) and one with episcleritis(7-6 per cent) developed a limbal gutter at the site of sclerosingkeratitisStatistical analysis: X2=-8399; P =NSIn all unilateral cases and one bilateral case (marked with asterisk)only one eye was affected

Table Xb Corneal complications (non-rheumatoidepiscleritis and non-rheumatoid scleritis) 5 I cases

Eye inflammation

Disease Eyes Unilateral Cases Bilateral Cases Per-(no.) (no.) (no.) centage

Episcleritis 53 Localizedsclerosing 2* I8-9

Localizedsclerosing 2Annularsclerosing I*Limbalguttering IBand kera-topathy I

Scleritis 25 Localized Annularsclerosing 3 sclerosing 2* 28-o

Statistical analysis: X2=o-83II; P=NSStatistical analysis (rheumatoid versus non-rheumatoid):

Episcleritis: X2 =I2-gi6i; P= <00005Scieritis: X2 =I-8oI; P=NS

*Both eyes were affected

FIG. 5 Limbal guttering in a patient withrheumatoid episcleritis

matoid episcleritis, three eyes with rheumatoidscleritis (Fig. 5), and one eye with non-rheumatoidepiscleritis. Apart from the last case, each occurredat the site of an area of sclerosing keratitis. A loca-lized stromal keratitis occurred deep in the mid-stroma in one patient with rheumatoid episcleritis.One patient with rheumatoid scleritis had a per-forating keratolysis, which is the comeal counter-part of a perforating scleritis.

ANTERIOR UVEITIS (Tables XIa, b)The percentage of eyes with active uveitis orevidence of old uveitis was slightly lower in rheu-matoid episcleritis (23 I per cent) compared withrheumatoid scleritis (28-3 per cent). The differenceis not statistically significant. A similar pictureemerged in non-rheumatoid episcleritis (17.0 percent) and non-rheumatoid scleritis (20o per cent).Posterior synechiae suggesting a more active andplastic type of uveitis were found in seven of I7eyes with rheumatoid scleritis (41I2 per cent) ascompared with one eye with posterior synechiaeassociated with non-rheumatoid scleritis (20z0per cent).

CATARACT (Table XII)The findings as regards the development of cataractin patients with rheumatoid scleritis who had

Table XIa Anterior uveitis (rheumatoid episcleritisand rheumatoid scleritis) 45 cases

Eye inflammation

Disease Eyes Unilateral Bilateral Per-(no.) - centage

Affected Cases Affected Caseseyes (no.) eyes (no.)

Episcleritis I 3 - 2* I 23-15 I

Scleritis 6o I I 2 6 28-3(2 unknown) I 4

Statistical analysis: X'=0'1484; P=NS

Table XIb Anterior uveitis (non-rheumatoidepiscleritis and non-rheumatoid scleritis) 51 cases

Eye inflammation

Disease Eyes Unilateral Bilateral Per-(no.) - centage

Affected Cases Affected Caseseyes (no.) eyes (no.)

Episcleritis 53 I 3 2 2 17.0I 2

Scleritis 25 I 4 I I 20-0

Statistical analysis: x'=o Iosx; P=NSStatistical analysis (rheumatoid versus non-rheumatoid):

Episcleritis: X2=o26o8; P =NSScleritis: X'=o-6388; P=NS

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Table XII Posterior subcapsular cataract (PSC)in patients receiving systemic corticosteroids

Rheumatoid Cases Mean age Sex ratio Per-scieritis (no.) ± SD FIM PSC centage

Patients 25 55-89±12-99 3-5/1 9 36-o'Control' group 148 52-5±11-5 9-6/i I7 II-5

Statistical analysis: X2= Io-0639; P = < 0-005

received treatment with systemic corticosteroids are

of particular interest. The incidence of posteriorsubcapsular cataract in patients with rheumatoidscleritis who had been treated with systemic cortico-steroids was high (36-o per cent). Nine of 25patients who had received treatment with systemiccorticosteroids had developed posterior subcapsularcataract. There were three further patients who hadadvanced cataract, two of whom had bilateralcataract (one had one aphakic eye), but these are notincluded for the purposes of statistical analysis.A previous study involving two of us (JW andDDMM), of the incidence of steroid-inducedcataract in patients with rheumatoid arthritis,found that i7 of 148 patients with rheumatoidarthritis (ii.5 per cent) who had received systemiccorticosteroids had posterior subcapsular cataracts.These patients also attended the Centre for Rheu-matic Diseases, Glasgow. Comparison of theincidence of posterior subcapsular cataract in rheu-matoid scleritis (36-o per cent) with posteriorsubcapsular cataract in patients with rheumatoidarthritis without scleritis (I I5 per cent), bothgroups receiving systemic corticosteroid treatment,is statistically significant (P=o0oo5).

Only three other patients in the study had thecharacteristic form of cataract. One patient withrheumatoid episcleritis had bilateral posteriorsubcapsular cataract and had been treated withsystemic corticosteroids for an uncertain length oftime. It is interesting that of 5I patients with non-

rheumatoid episcleritis or scleritis, two patientsdeveloped posterior subcapsular cataract, and thesewere the only two patients of the non-rheumatoidgroup who were receiving systemic corticosteroidtreatment.

POSTERIOR SEGMENT ABNORMALITY (Tables XIIIa, b)

No patient with rheumatoid episcleritis had abnor-mality of the posterior segment of the eye. However,the percentage of abnormal features in associationwith rheumatoid scleritis was 29-I per cent. Thecommonest abnormality was a macular disturbancein i i eyes (20oo per cent), although three of theseeyes were myopic, and this might have affected theirmacular state. The origin of macular disturbanceis difficult to determine in these cases, and the

results need to be viewed with caution. Many ofthe rheumatoid patients received a number ofdifferent antirheumatic drugs which might havedisturbed the retinal picture. However, maculardisturbance is a recognized complication of scleritis(Watson and Lobascher, I965). Two eyes showedold foci of choroiditis and one eye, in a patient nowdeceased, optic atrophy of obscure origin, althoughthe eye had been grossly inflamed and suffered asubsequent perforating keratolysis. It was interest-ing to find oedema of the optic nerve head in onecase, suggesting a possible ischaemic optic neuro-pathy. One patient had an old detached retina.There was an area of old choroiditis in one case

diagnosed as non-rheumatoid episcleritis (i-9 percent of 52 eyes). Two eyes with non-rheumatoidscleritis had a possibly significant abnormality ofthe posterior pole (8-o per cent of 25 eyes); in bothcases these were areas of macular disturbance.There was a marked difference in the incidence

of abnormality between rheumatoid episcleritisand scleritis. The significant difference betweenposterior segment complications in rheumatoidscleritis and non-rheumatoid scleritis (P=o0o5)may reflect more severe disease in the rheumatoidpatient.

INTRAOCULAR PRESSURE (Tables XIVa, b)

One patient with rheumatoid episcleritis hadbilateral raised intraocular pressure, but this was

Table XIIIa Posterior segment abnormality(rheumatoid episcleritis and rheumatoid scieritis)42 cases

Episcleritis Scieritis Per-9 eyes (4 unknown) 55 eyes (7 unknown)* centage

- Macular disturbance 1I 200otOld choroiditis 2 4-2Optic atrophy I 2-IOedema of optic nerve head IOld detached retina I

29-1

*Two cases were obscured by cataractfThree eyes were myopic

Table XIIIb Posterior segment abnormality(non-rheumatoid episcleritis and non-rheumatoidscleritis) 5I cases

Episcieritis Per- Scieritis Per-52 eyes (I unknown) centage* 25 eyes centage

Old choroiditis I i-9 Macular disturbance 2 8-o

*One case obscured by band keratopathyStatistical analysis: X'=I-665x; P=NSStatistical analysis (rheumatoid versus non-rheumatoid):

Scleritis: X2 =4 3844; P = < 0°05

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Table XIVa Raised intraocular pressure* (rheumatoid episcleritis and rheumatoid scleritis) 37 cases

Eye inflammation

Disease Eyes (no.) Unilateral Bilateral Percentage

Cases Eyes affected IOP mmHg Cases Eyes affected lOP mmHg

Episcleritis 9 (4 unknown) s 2 26 -

+25Scleritis 48 (I4 unknown) I I 22 2 2 29 I8-7

+3226+23

4 I 22Absolute glaucoma 22

32

*The highest reading recorded is given in each casetA c13s of closei-aagla glaucz-n nzt coa;isirsd a3 p3itive as the raised pressure was not due to inflammation

Table XIVb Raised intraocular pressure (non-rheumatoid episcleritis and non-rheumatoid scleritis) 5 I cases

Eye inflammation

Disease Eyes (no.) Unilateral Bilateral Percentage

Cases Eyes affected lOP mmHg Cases Eyes affected IOP mmHg

Episcleritis 53 - I I 22 I-9Scleritis 25 3 I 26 - 2-0

3038

2 2* 30+2830+34

*Both tViese cases, although unilateral cases of scleritis, received topical steroids to both eyes. On withdrawing topical steroids all four eyesreverted to normal intraocular pressures. They are con3idered cases of steroid-induced glaucoma and not primarily due to inflammation.Stati3tical analy3is (rheumatoid versus non-rheumatoid): Scleritis, X'=05453; P=NS

due to closed-angle glaucoma and the conditionsettled with bilateral peripheral iridectomies. Noother patient with rheumatoid episcleritis hadraised intraocular pressure. Nine eyes with rheuma-toid scleritis (I8-7 per cent) had raised intraocularpressure; in two cases there was absolute glaucoma.Four eyes had levels recorded by applanationtonometry at or between 22 and 26 mmHg. Oneeye, with a reading at 22 mmHg, was a case of old'burnt out' absolute glaucoma. One eye had areading at 29 mmHg, one at 30 mmHg, and twoat 32 mmHg.

Only one patient with non-rheumatoid episcleritishad one eye with a tension fractionally above normalat 22 mmHg, a percentage of i 9 per cent. Seveneyes with non-rheumatoid scleritis had raisedlevels but in two cases (four eyes) the level ofpressure fell from 30 mmHg (right) + 28 mmHg(left) and 30 mmHg (right) + 34 nmmHg (left) towithin normal limits on withdrawing topicalsteroid treatment. It is considered that these werecases of steroid-induced glaucoma. The remainingthree cases (I2o per cent) include one patient inwhom the intraocular pressure was 38 mmHg. Ineach case the highest reading recorded is given.

Only one patient, a woman with unilateral rheuma-toid scleritis, required a drainage procedure tocontrol her intraocular pressure. There was noflare-up of her scleritis. One patient with a pressureat 22 mmHg in one eye is still receiving miotictreatment. The intraocular pressure of the remain-ing patients all settled coincident with the quieten-ing of their inflammation, including those patientsin whom pressures were recorded in the 30-38mmHg range.

OCULAR MOVEMENTS (Tables XVa, b)No patient with rheumatoid episcleritis hadevidence of muscle imbalance. Eight eyes withrheumatoid scleritis (12-9 per cent) showed limi-tation of movement of one extraocular muscle ormore. Two cases, however, were based on a historyof transient diplopia, suggesting tendon or muscleinvolvement consistent with the site of scleralinflammation. The limitation of movement in theremaining six cases was substantiated by orthopticexamination.Three cases of non-rheumatoid episcleritis (5 7

per cent) suggested possible tendon and/or muscle

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Table XVa Ocular movements (rheumatoidepiscleritis and rheumatoid scleritis) 46 cases

Disease Eyes (no.) Muscle imbalance Percentage

Episcleritis I3 - -

Scleritis 62 8* 12-9

*Two cases based on history of transient diplopia

Table XVb Ocular movement (non-rheumatoidepiscleritis and non-rheumatoid scleritis) 51 cases

Disease Eyes (no.) Muscle imbalance Percentage

Episcleritis 53 3* 5*7Scleritis 25 6t 24-0

*AI1 three cases tentatively based on history of transient diplopiatOne case based on a history of intermittent diplopiaStatistical analysis (non-rheumatoid episcleritis versus non-rheu-matoid scleritis): X2=5-5976: P= <0'025Statistical analysis (rheumatoid versus non-rheumatoid):

Scleritis: x2 =i-6248; P =NS

inflammation, but the conclusion is tentative. Allthree cases gave a brief history of diplopia whichthey associated with an inflamed eye. Six cases withnon-rheumatoid scleritis (24o0 per cent) gaveevidence of tendon and/or muscle imbalance, onecase based on an account of intermittent diplopiaand the remaining five cases confirmed by anorthoptic assessment. The difference in incidencebetween non-rheumatoid episcleritis and non-rheumatoid scleritis is statistically significant(P=oo25).One patient, a 34-year-old woman who had non-

rheumatoid scleritis presented with a dramaticstrabismus. Examination revealed a paresis of theleft lateral rectus muscle. This was the third time inthree years that she had had an inflamed eye. Onthe first occasion there had been a paresis of theright medial rectus muscle. A biopsy (IX3 mm)of the middle section of tendon and muscle of theleft lateral rectus muscle confirmed the presence ofa tenomyositis. Chemosis was characteristic of eachepisode after a few days of ocular pain, and on eachoccasion was thought to herald the onset of anorbital cellulitis.

KERATOCONJUNCTIVITIS SICCA (Tables XVIa, b)One patient with rheumatoid episcleritis (14-2per cent) had definite KCS, and four patients withrheumatoid scleritis (I2-9 per cent). Of the patientswith non-rheumatoid inflammation, four withepiscleritis (I2zI per cent), and one with scleritis(5-6 per cent) had KCS.There were three further cases of possible KCS.

One case was associated with rheumatoid episcleritisand two cases with rheumatoid scleritis. In each

the Schirmer I tear test was markedly reduced.All three patients had died before complete exami-nation could be carried out and no Schirmer II testor rose bengal staining had been done.

SJOGREN'S SYNDROME

Sjogren's syndrome is defined as a triad of features;KCS, xerostomia (with or without salivary glandswelling), and a connective-tissue disease. Thepresence of either KCS or xerostomia with a systemicdisorder is accepted as sufficient (Bloch, Buchanan,Wohl, and Bunim, I965).

Only two of the 37 cases of rheumatoid scleritisexhibited the triad of dry eyes, dry mouth, and aconnective-tissue disorder (in this case rheumatoidarthritis). No case of rheumatoid episcleritis hadthe triad of features of Sj6gren's syndrome. How-ever, two further cases of rheumatoid scleritis andone case of rheumatoid episcleritis had KCSassociated with the systemic disease. Eight furthercases of rheumatoid scleritis and two cases ofrheumatoid episcleritis also had xerostomia withrheumatoid arthritis. This means that the totalincidence of Sj6gren's syndrome, according to thecriteria given, is I 2 of 37 cases of rheumatoidscleritis (32-4 per cent) and three of nine cases ofrheumatoid episcleritis (33-3 per cent).

SICCA SYNDROME

One patient with non-rheumatoid episcleritis(3 o per cent) had dry eyes combined with a dry

Table XVIa Keratoconjunctivitis sicca (rheumatoidepiscleritis and rheumatoid scleritis) 42 cases

Disease Cases (no.) No. of KCS cases Percentage

Episcleritis 8 (I unknown)* I 14-2Scleritis 34 (3 unknown)t 4 12'9

*The 'unknown' case had a markedly reduced Schirmer I testtTwo 'unknown' cases had markedly reduced Schirmer I tests(one case is included as a positive KCS because of a reducedSchirmer I test with widespread rose bengal staining)Statistical analysis: x2 =ooog6; P =NS

Table XVIb Keratoconjunctivitis sicca (non-rheumatoid episcleritis and non-rheumatoidscleritis) 51 cases

Disease Cases (no.) No. of KCS cases Percentage

Episcleritis 33 4 12-Scleritis s8 I5s6Statistical analysis: x =o5678; P=NSStatistical analysis (rheumatoid versus non-rheumatoid):

Episcleritis: X2=00247 P=NSScleritis: x'=o-67b0; P=NS

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Table XVII Articular features of patients with rheumatoid episcleritis and rheumatoid scleritis

Rheumatoid episcleritis/scleritis Rheumatoid controls

Features No. of Range Mean No. of Range Mean P valuecases (years) (years) SD SEM cases (years) (years) SD SEM

Duration ofrheumatoid arthritis 46 0°5-50 14.5 ±12-9 ±1-9 46 O-I7-48 9-2 ±10-2 ±I55 <0-05

Functional class 45 I-4 2-7 ±°-9 ±0 I4 46 1-4 2-28 ±o-78 ±O-oI NSArticular index 43 0-78 23I ±20-0 ±31 4I 0-53 I9-0 ±12-9 ±2-0 NSX-ray stage 36 I-4 2.97 ±o-6i ±05- 38 I-4 2.42 ±1503 ±01-7 <00-

NS =Not significant

mouth, features of the sicca syndrome, in which thedryness of mucous membranes is not associatedwith a connective-tissue disorder.

RHEUMATOLOGY

The following data refer to those patients withrheumatoid episcleritis or rheumatoid scleritis andcompare them with a group of rheumatoid controls,matched for age and sex - that is, patients withrheumatoid arthritis but with no evidence ofepiscleral or scleral inflammation. For the purposes

of this paper, as regards the articular and extra-articular features of rheumatoid disease, the patientswith rheumatoid episcleritis and scleritis are com-

bined as one group and compared with the rheu-matoid control group.

DURATION OF RHEUMATOID ARTHRITIS; FUNCTIONAL

CLASS; ARTICULAR INDEX, AND X-RAY STAGE

(Table XVII)

The range of duration was huge in both rheumatoidepiscleritis/scleritis and in rheumatoid controls,from a few months to 50 years. However, episcleritisand scleritis occurred in patients with longer-standing rheumatoid arthritis (mean values 14-5

years compared with 9-2 years). The differenceis statistically significant (P=o0os).The functional class measures in four grades of

increasing severity the degree of functional inca-pacity due to arthritis. The study of functional

incapacity was the only investigation in which therheumatoid control group showed a more severedegree of abnormality compared with the rheuma-toid episcleritis/scleritis group. The mean valuefor 45 known cases of rheumatoid episcleritis/scleritis was 2 I 7 and for 46 cases in the rheumatoidcontrol group was 2z28.The articular index records the number of

involved joints and the severity of their involvementas judged by tenderness to pressure over the jointmargin. The matched group of rheumatoid controlshad a mean value of i9. The difference between thecontrol group and the combined rheumatoid epi-scleritis/scleritis group (mean value: 231) was notstatistically significant.The x-ray stage indicates radiologically the

degree of bone and joint involvement categorizedin four stages of increasing severity. Comparisonof the rheumatoid episcleritis/scleritis group (meanvalue: 2-97) and the group of rheumatoid controls(mean value: 242) indicated that episcleritis andscleritis occurred in a group with more severeerosive arthritis. The difference is statisticallysignificant (P= OOI).

SUBCUTANEOUS NODULES; PERIPHERAL NEUROPATHY;SKIN ULCERS; SKIN BRUISING; SKIN ATROPHY;AMYLOID; TENDON RUPTURE AND SPLENOMEGALY

(Table XVIII)

Of 46 cases with rheumatoid episcleritis or scleritis23 had subcutaneous granulomatous nodules

Table XVIII Extra-articular features in patients with rheumatoid episcleritis and rheumatoid scleritis

Rheumatoid episcleritislscleritis Rheumatoid controls

Extra-articular features No. of cases No. of cases P valueNo. of cases positive Per cent No. of cases positive Per cent

Subcutaneous nodules 46 23 50-0 46 I I 23.9 <005Peripheral neuropathy 45 3 8-9 46 I 2-2 NSSkin ulcers 45 6 13-3 46 2 4 4 NS

bruising 46 Is 23 9 46 5 IO-9 NSatrophy 46 i6 34-8 46 5 IO-9 < O0OI

Amyloid 46 2 4-4 46 0 - _Splenomegaly 46 5 IO-9 46 I 2-2 NSTendon rupture 46 0 46 0 -

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(S° ° per cent). Comparison with the incidence inthe rheumatoid control group (23-9 per cent)showed a statistically significant difference(P=O OI).Three of 45 known cases of rheumatoid episcleri-

tis or scleritis (8-9 per cent) revealed a high inci-dence of peripheral neuropathy as compared withonly one case in the rheumatoid control group(2-2 per cent). However, the difference is notstatistically significant. Two of the patients withrheumatoid episcleritis/scleritis had received treat-ment with systemic corticosteroids and two hadbeen given gold therapy (one patient had receivedboth). Either of these treatments could have pro-duced neuropathy. The patient in the rheumatoidcontrol group had not received systemic treatmentwith corticosteroids or gold.

Six of 45 known cases with rheumatoid episcleritisor scleritis (I3 3 per cent) had skin ulceration as

compared with two of 46 cases in the rheumatoidcontrol group (4.4 per cent). The difference is notstatistically significant for these numbers. Three ofthe patients with rheumatoid episcleritis or scleritishad received treatment with systemic cortico-steroids and both patients in the rheumatoidcontrol group had received similar medication.

Skin bruising occurred more often in patientswith rheumatoid episcleritis or scleritis (i i cases;

23-9 per cent) as compared with the rheumatoidcontrols (5 cases; IO 9 per cent). The differencefor these numbers is not statistically significant.Ten of the patients in the rheumatoid episcleritis/scleritis group had received treatment with systemiccorticosteroids and four of the five positive cases

in the rheumatoid control group had been similarlytreated.

Skin atrophy was found in i 6 patients in therheumatoid episcleritis/scleritis group (34-8 per

cent) as compared with five patients in the rheuma-toid control group (Io 9 per cent); this is statistic-ally significant (P=o'oi). Ten of the patients in the

rheumatoid episcleritis/scleritis group and five inthe rheumatoid control group had been givensystemic corticosteroid treatment.There were two men considered as having

secondary amyloidosis; both had bilateral rheu-matoid scleritis. One case was confirmed by liverbiopsy. No case of amyloidosis was confirmed inthe group of rheumatoid controls.No patient with rheumatoid episcleritis/scleritis

and none of the rheumatoid control group sufferedtendon rupture.The incidence of splenomegaly in the rheumatoid

episcleritis/scleritis group was five of 46 cases

(IO9 per cent). Only one patient of 46 rheumatoidcontrols (2z2 per cent) had a palpable spleen. Thedifference for these numbers is not statisticallysignificant.

Laboratory investigations

The following data record information found insix groups of patients; patients with rheumatoidepiscleritis and rheumatoid scleritis, non-rheuma-toid episcleritis and non-rheumatoid scleritis, andpatients with rheumatoid episcleritis and scleritiscombined as one group for comparison with therheumatoid control group.

HAEMOGLOBIN; ERYTHROCYTE SEDIMENTATION RATE

(ESR); ALBUMIN/GLOBULIN RATIO; ALKALINEPHOSPHATASE; URIC ACID; SERUM GLUTAMICOXALOACETIC TRANSAMINASE (SGOT), and SERUMGLUTAMIC PYRUVIC TRANSAMINASE (SGPT)(Tables XIXa, b, c)

For the purposes of comparison haemoglobinresults for both men and women are groupedtogether. In patients with rheumatoid episcleritisthe mean value was 87-6 per cent but in those withrheumatoid scleritis it was 83 4 per cent. Themean haemoglobin value for patients with non-

Table XIXa Laboratory investigations in patients with rheumatoid episcleritis and rheumatoid scleritisRheumatoid episleritis Rheumatoid scleritis

Laboratory --

investigation No. of No. of P valuecases Mean SD SEM cases Mean SD SEM

Haemoglobin ESR 9 87-6 per cent +15-4 ±5-I 37 83-4 per cent ±i8-2 ±3-0 NS7 74-4 mm/Ist h ±37-9 ±14-3 30 65-3 mm/ist h ±36-i ±6-6 NS

Alumnglbi(Westergren) (Westergren)

Albumin/globulinratio 9 o-88 ±0 37 ±01-2 37 I.03 ±0-4I ±007 NS

Alkaline phosphatase 9 12-07 KA units ±4-73 ±i-58 37 14-68 KA units ±12-73 ±2-09 NSUric acid 8 4-6 mg/Ioo ml ±x-66 +0-59 35 4-88 mg/xoo ml ±1 47 ±0-25 NSSGOT 8 17-88 lU/i ±8-17 +2-89 30 29-33 IU/i ±43-23 ±7-89 NSSGPT 8 15-88 IU/I ±12-86 ±4-55 30 23-87 IU/I ±36-3 ±6-63 NS

Normal values: haemoglobin 90-125 per cent male, 80oI0o per cent female; ESR 5-12 mm/sat h male, 0-7 mm female; A/G ratio 1-03-2-36 g/Ioo ml; alkaline phosphatase 5-15 KA units; uric acid 22-7-2 mg/soo ml male, 0-5-5-7 mg/ioo ml female; SGOT 11-35 IU/I;SGPT 4-28 IU/I

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Table XIXb Laboratory investigations in patients with non-rheumatoid episcleritis and non-rheumatoid scleritisNon-rheumatoid episcleritis Non-rheumatoid scleritis

Laboratory No. of No. of P valueinvestigations cases Mean SD SEM cases Mean SD SEM

Haemoglobin 31 99-9 per cent ±9-2 ±i-6 8 98-4 per cent 8-o ±1-9 NSESR 27 13-3 mm/ist h ±12-8 ±25 I5 I9-9 mm/Ist h ±13-0 ±3 4 NS

(Wintrobe) (Wintrobe)Albumin/globulin

ratio 33 x-75 ±0-38 ±0 07 x8 I553 ±0°33 o-o8 < 0o05Alkaline phosphatase 33 7-36 KA units ±2-6i ±0'45 x8 8-o6 KA units ±3-33 ±0o79 NSUric acid 33 5-39 mg/0oo ml ±1-90 ±0 33 x8 4 41 mg/0oo ml ±1i-25 ±0 29 NSSGOT 32 20z56 IU/I ±7-9 ±'t-4 x8 22-67 IU/i ±i6-04 +3-78 NSSGPT 32 I9-88 IU/I ±9 13 ±i-6I i8 19-39 IU/i ±12-7 ±2 99 NS

Normal values are given with Table XIXa

Table XIXc Laboratory investigations in patients with rheumatoid episcleritis and rheumatoid scleritis:comparison with rheumatoid controls

Rheumatoid episcleritis/scleritis Rheumatoid controls

Laboratory No. of No. of P valueinvestigations cases Mean SD SEM cases Mean SD SEM

Haemoglobin 46 84-3 per cent ±17-6 ±2-6 45 90-I per cent ±12-3 ±i-83 NSESR 37 67-1 mm/Ist h ±36-I ±5-9 45 48-4 mm/ist h ±34' ±5-I <0-025

(Westergren) (Westergren)Albumin/globulin

ratio 46 1I0 ±0°4 ±o-6 40 PI-2 ±0°39 ±o-o6 NSAlkaline phosphatase 46 14-2 KA units ±ii-6 ±17 4I ii-5 KA units ±3-7 ±o-58 NSUric acid 43 4-8 mg/ioo ml ±I-5 ±0-23 40 4-36 mg/ioo ml ±I.14 ±o-i8 NSSGOT 38 26-9 IU/I ±38-7 ±6-3 27 14-6 IU/1 ±5-I ±I-0 NSSGPT 38 22-2 IU/I ±32-8 ±5 3 23 12-0 IU/l ±5 5 ±I-I NS

Normal values are given with Table XIXa

rheumatoid episcleritis was 99 9 per cent, signifi-cantly higher than in those with rheumatoid epi-scleritis (P=o0oos). A similar significant differencewas found for patients with non-rheumatoid scleritis,in whom the mean value for haemoglobin was 98-4per cent, compared with patients with rheumatoidscleritis (P=o0oo5). Comparison of the rheumatoidepiscleritis/scleritis group with rheumatoid controlssuggested that the anaemia might be more severein patients with eye inflammation (84-3 to 90 I percent) but the difference is not statistically significantfor these numbers.

For the purposes of comparison ESR readingsfor both men and women are grouped together.The ESR in rheumatoid inflammation was verymuch higher than that in patients with non-rheumatoid episcleritis or scleritis. Unfortunatelythe methods differed in the two groups. TheWestergren method was used at the Centre forRheumatic Diseases and the Wintrobe method atthe Tennent Institute. There is, however, anobvious difference in severity which does notrequire exact comparison. The mean value inrheumatoid episcleritis was 74-4 mm/ist hour andin rheumatoid scleritis 65-3 mm/ist hour (Wester-gren). Patients with non-rheumatoid episcleritis

had a mean value of I3-3 mm/Ist hour and thosewith non-rheumatoid scleritis gave a mean value ofI9-9 mm/Ist hour (Wintrobe). The ESR in rheu-matoid episcleritis/scleritis patients was higher thanin the rheumatoid control group; mean values were67 i mm compared with 48-4 mm. The differencein these values is statistically significant (P=0 025).The mean value of the albumin/globulin ratio in

rheumatoid episcleritis was o88 while that forrheumatoid scleritis was I103. There was a highpercentage of reversed ratios in both rheumatoidepiscleritis (66-7 per cent) and scleritis (62-2 percent). Non-rheumatoid patients with episcleritisshowed a mean value of I-75 and those withscleritis a mean value of I-53. The differencebetween these two figures is significant (P=o0o5).Neither of the groups with non-rheumatoid inflam-mation had any patient with a reversed ratio. Therewas a highly significant difference between rheuma-toid and non-rheumatoid episcleritis (P=o-ooi) andrheumatoid and non-rheumatoid scleritis (P= o-oo i).The mean value of the albumin/globulin ratio inthe rheumatoid episcleritis/scleritis group (i -o)was more abnormal than the group of rheumatoidcontrols (I i2), but the difference was not statisti-cally significant. Consistent with these findings, the

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number of patients with a reversed albumin/globulinratio was greater in the combined episcleritis/scleritis group (63-o per cent) than in the rheuma-toid control group (47.5 per cent).None of the mean values in all six groups

studied is outside the normal range for alkalinephosphatase of 5-I5 King Armstrong units,although it is interesting to note that the mean

value for rheumatoid scleritis is at the upper limitof normal, and also that IO of 37 cases with rheuma-toid scleritis (27-o per cent) had raised readings.Further, it is noteworthy that there is a statisticallysignificant difference between the levels for rheu-matoid episcleritis and non-rheumatoid episcleritis(P=O ooi) and between rheumatoid scleritis andnon-rheumatoid scleritis (P= o0o5).As with alkaline phosphatase, none of the mean

values for serum uric acid levels in the six groups ofpatients investigated was outside the normal range.

A similar pattern emerged for SGOT andSGPT, where all mean values recorded were withinnormal limits.

WASSERMANN REACTION; VDRL SLIDE TEST, AND

REITER PROTEIN COMPLEMENT-FIXATION TEST

The following data relate only to those patientswith eye inflammation, both rheumatoid and non-

rheumatoid. Seven of the patients with rheumatoidepiscleritis and 28 of the patients with rheumatoidscleritis had these investigations and no patientgave a positive result. All the patients with non-

rheumatoid episcleritis and with non-rheumatoidscleritis gave similarly negative results.

ANTISTREPTOLYSIN-O TITRE (ASO); BRUCELLOSIS AND

TOXOPLASMOSIS

The following data relate only to those patientswith rheumatoid episcleritis and scleritis, and non-

rheumatoid episcleritis and scleritis.

One patient with rheumatoid episcleritis (I4-3per cent) had a raised ASO titre at 724 units andsix with rheumatoid scleritis (20 7 per cent) hadraised titres at 320 units (2), 400 units (2), 500units, and 640 units. Three patients with non-

rheumatoid episcleritis (9 i per cent) showed raisedASO titres, two readings at 320 units and one at

I280 units. One case of non-rheumatoid scleritis(5-6 per cent) had a raised titre at 320 units. Noneof the patients with a raised ASO titre had erythemanodosum.Only one of 28 patients with rheumatoid scleritis

(3y5 per cent) had a tentative positive result forbrucellosis. The standard agglutination test gave a

titre of i /8o for Brucella abortus, but the Coombs'test was negative. Serum was anti-complementary.One patient with non-rheumatoid episcleritis (3-1per cent) had a positive titre for Brucella abortusat i/i6o in both the standard agglutination andCoombs' test. However, the complement-fixationtest was negative.The only group of patients with a percentage

incidence of positive toxoplasmosis dye test titresoutside the normal adult range, approximately30-40 per cent (Ludlam, 1972), was the very small

group of seven cases with rheumatoid episcleritisin which the percentage was 71I4 per cent (TablesXXa, b). It is interesting to note that 8-6 per centof the patients with rheumatoid episcleritis or

rheumatoid scleritis had a titre of I/256 or more.

The group with non-rheumatoid episcleritis andnon-rheumatoid scleritis showed only one in thesame range (I/1024), 2-0 per cent. It is probablethat in the normal adult population the incidenceof antibodies at a titre of 1/256 is not more than I1Oper cent (Beattie, 1958; Ludlam and Beattie, I963).

AUTOANTIBODIES (Tables XXIa, b)

The following results refer only to those patientswith rheumatoid and non-rheumatoid eye inflam-

Table XXa Toxoplasma dye test titres in 35 cases (rheumatoid episcleritis and rheumatoid scleritis)

Disease Cases < i/8 +I/8 +i/i6 +I/32 +±/64 +I/I28 +1/256 +1/512 +I/I024

Episcleritis 7 (2 unknown) 2 - I 2 - I - - I

Scleritis 28 (9 unknown) I5Total+ 5 (7I-4 per cent)

I 6

Total+ 13 (46-4 per cent)

Table XXb Toxoplasmosis (non-rheumatoid episcleritis and non-rheumatoid scleritis) 5 I cases

Disease Cases < I/8 + I/8 +I/i6 +I/32 + I/64 + I/I28 + I/256 +1/512 + I/I024

Episcleritis 33 17 5 - 8 2 I - - -

Total + i6 (48-5 per cent)Scleritis I8 I2 - I I 3 - - - I

Total+ 5 (27-8 per cent)

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Episcieritis and scleritis zog

Autoantibody

Rheumatoid latexAntinuclear factorThyroglobulin TRCThyroid microsomalSmooth muscleSalivary ductGastric parietal cellMitochondrial


Episcleritis (9 cases)

Cases (no.) Per-+ Weakly + centage

9 9 0 I009 2 0 22'29 0 0 -

9 I 0II-I8 (I unknown) I 12-59 4 0 44-49 3 33-38 (I unknown) o

Scleritis (37 cases)

37 35 I 97.3*37 8 I 24 337 3 0 8-i37 4 2 56-234(3unknown) 2 6 23 5

35(2unknown) 5 5 28-637 5 I 56-234 (3 unknown) o

Episcleritis (33 cases)

+ Weakly +

0 I

I 20 l

3 I0 0

0 0

I 40

Scleritis (i8 cases)0 64 2

0 0

I 0

I I

o o

2 0

o 0

Percentage

3-09-I3-0

12-1

1552

33-333.3

5*6

I I*I

mation. Apart from the relatively high incidence ofsalivary duct antibody in the small group withrheumatoid episcleritis, where a positive result was

given in four of nine cases (44-4 per cent), and an

apparently high incidence of smooth-muscle anti-body in rheumatoid scleritis, where eight of 34

cases were positive (23-5 per cent) (although six of-these were only weakly positive) the positiveautoantibodies listed in Table XXIa in patientswith rheumatoid episcleritis and rheumatoid scleri-tis is generally in the range expected for patientswith rheumatoid arthritis (see Discussion). Thepossibly significant finding in the non-rheumatoidpatients is the high incidence of a weakly positive

rheumatoid factor in patients with non-rheumatoidscleritis, six of i8 cases (33-3 per cent). Also, sixpatients had a positive antinuclear factor (33-3per cent); in two of them this was weakly positive.Three patients had a positive rheumatoid factortogether with a positive antinuclear factor. Theremaining autoantibody investigations in the non-rheumatoid patients were in the range accepted fora general population (see Discussion).

R3 TITRE (Table XXII)

Sixteen of the rheumatoid episcleritis/scleritisgroup (42-I per cent) had titres of 1/5I2 or highercompared with eight of the rheumatoid controls(2I*6 per cent). The difference was just outsidesignificance for these numbers (X2=3-6148).

IC/IA GLOBULIN (HUMAN COMPLEMENT C3);IMMUNOGLOBULIN IgG, IMMUNOGLOBULIN IgA,AND IMMUNOGLOBULIN IgM (Tables XXIIIa, b)

These data also relate only to those patients withrheumatoid and non-rheumatoid eye inflammation.The mean values for rheumatoid episcleritis andrheumatoid scleritis, and non-rheumatoid episcleri-tis and non-rheumatoid scleritis, all fall within thenormal range for each of these investigations.Tables XXIIIa, b record the occasional readingswhich do not fall within the normal range. Thesevariants predominated in the investigation of ic/iaglobulin, where six patients with rheumatoidepiscleritis or rheumatoid scleritis and six patientswith non-rheumatoid episcleritis and non-rheuma-toid scleritis had depressed levels.

BACTERIOLOGY; VIROLOGY, AND MYCOLOGY

Examination of the conjunctiva for bacteria, viruses,and fungi was carried out only in those patientsseen at the Tennent Institute of Ophthalmology.One patient with non-rheumatoid episcleritis

had a coagulase-negative staphylococcus. Onepatient with rheumatoid scleritis and one patient

Table XXII R3 titres

20-Episcleri tis/scleritis Rheumatoid controls38 coses (8 unknown) 37 cases (6 unknown)*

5

v0-9

6 61 n-1z r, I 5 5

Table XXIa Autoantibodies (rheumatoidepiscleritis and rheumatoid scleritis) 46 cases

Autoantibody



*One ca3e is included in which the Rose-Waaler test was used

Table XXIb Autoantibodies (non-rheumatoidepiscleritis and non-rheumatoid scleritis) 5I cases copyright.

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2IO British Journal of Ophthalmology

Table XXIIIa 3lc/[la globulin and immunoglobulins IgG, igA, and IgM in rheumatoid episcleritis andrheumatoid scleritis

Rheumatoid episcleritis Rheumatoid scleritis

Outside normal Outside normal

Globulin or Cases Mean SD SEM Below Above Cases Mean SD SEM Below Aboveimmunoglobulin (no.) (mg/ioo ml) (no.) (mglioo ml) - -

Per Per PerNo. cent No. cent No. cent

3lc/13la globulin 8 I26-5 ±44.I ±i56 2 250- 33 142-3 ±36-7 ±6-4 4 12-1 2 6-iImmunoglobulin igG 7 1365-7 ±546-4 ±2o6-5 - - 33 I717-3 ±790-2 ±137-6 I 3-0 2 6-i

igA 7 3914 ±i52-8 ±57-8 - - 33 488-5 ±259'3 ±452 - 3 9-1IgM 7 141-7 ±57-8 ±21-9 - - 33 193-3 ±112-0 ± 9-5 - -

Normal values: i3lc/,3la globulin Ioo-i9o mg/ioo ml; immunoglobulin igG 560-2800 mg/Ioo ml; immunoglobulin igA I04-845 mg/OO ml;immunoglobulin IgM 54-443 mg/1oo ml

Table XXIIIb Ilc/lla globulin and immunoglobulins igG, igA and IgM in non-rheumatoid episcleritisand non-rheumatoid scieritis

Non-rheumatoid episcleritis Non-rheumatoid scleritis

Outside normal Outside normal

Globulin or Cases Mean SD SEM Below Above Cases Mean SD SEM Below Aboveimmunoglobulin (no.) (mg/loo ml) (no.) (mg/Ioo ml)

Per ~~~~~~Per PerNo. cent No. cent No. cent

,3lc/3la globulin 29 1345 ±319 ±5-9 3 10-4- I6 148-8 ±44-2 ±11-0 3 i8-8 i 6.3Immunoglobulin igG 29 1225-2 ±491-7 ±91-3 - - 17 13341 ±339-4 ±82 3 - -

igA 29 341-5 ±179-7 ±33-4 I 3 4 17 403-2 ±253-6 ±6i-5 I 5-9 I 5.9xgM 29 I69-0 ±86-o i±6-o I 3-4- I7 202-3 i09-8 ±267 - I 59

Normal values are given with Table XXIIIa

with non-rheumatoid scleritis was a carrier ofStayhylococcus albus.No case in the series had any virus cultured from

the conjunctiva.Two patients with non-rheumatoid episcleritis

had fungi isolated from the conjunctiva, in bothcases the Penicillium species. Two patients withrheumatoid scleritis had fungi present, in one casePenicillium and in one Aspergillus. One further casewith non-rheurnatoid scleritis produced a fungusof the Paecilomyces species.

MORTALITY (Tables XXIV and XXV)The following data relate to those patients withrheumatoid episcleritis and rheumatoid scleritis,

Table XXIV Mortality (rheumatoid episcleritis,rheumatoid scleritis and rheumatoid controls) 66 cases

Disease Cases Deceased Percentage

Rheumatoid episcleritis/scleritis 33 (2 unknown)* I5 45-5

Rheumatoid controls 33 (2 unknown)* 6 18-2

Statistical analysis: X2=5-6571; P= <0-025*These four patients could not be traced

Table XXV Cause of death and associated diseaserecorded on death certificates (17 cases)

Rheumatoid episcleritis/scleritis(i I cases; 4 unknown)

Myocardial infarction andcongestive cardiac failure

Peptic ulcerationCerebrovascular accidentBronchopneumoniaPulmonary embolusPulmonary oedemaHypertensionAortic stenosis and

incompetenceHepatitis'Natural causes'Myeloproliferative diseaseRenal failurePerforated diverticulum of

colonDiabetes (maturity onset)

Rheumatoidcontrols(6 cases)

No. Percentage No. Percentage

45.527-39-'

402

0000

000

I1I1

66-7

33-3I6.7

53

0I

00

00

I

comparing them with the rheumatoid controlgroup, matched for age, sex, and year of presenta-tion.By February 1974, 15 of 33 known cases of

rheumatoid episcleritis or rheumatoid scleritis

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Episcleritis and scleritis 2Ir

Table XXVI Type I allergy (atopy) 23 patients

Diagnosis Control

Episcleritis -ScleritisEpiScleritisEpiscleritis -Episcleritis -EpiscleritisScleritis -EpiScleritis -Episcleritis -Episcleritis -ScleritisEpiscleritisScleritis -Episcleritis -EpiscleritisEpiscleritis -EpiscleritisScleritis -

Episcleritis -Episcleritis -EpiscleritisScleritis -

Episcleritis -

Housedust

4-

House dustmite(scratch test)

Grasspollen

Alternaria Feathers Aspergillus Candidaalbicans

2-4--

+- t- -

+

_-

(45-5 per cent) had died since examination. Thecontrol group of patients by February 1974 gave

only six of 33 known cases (i8'2 per cent) whowere deceased. The difference is statisticallysignificant (P=0'025).The details of cause of death, as recorded on the

death certificates of these patients, give the expectedhigh incidence of cardiovascular and respiratorydisease. One unexpected feature was the findingthat three patients of the rheumatoid episcleritis/scleritis groups (27-3 per cent) died after gastro-intestinal haemorrhage.

TYPE I ALLERGY (ATOPY) (Table XXVI)

Skin tests in 23 patients, all with non-rheumatoideye inflammation, and all but six of them cases ofepiscleritis, did not suggest that there is an in-creased incidence of atopic disease in these patients.Of the 23 patients, four had a mild positive reactionto house dust or house dust mite, and five hadpositive skin tests to more than one antigen. Threeof the patients with positive skin tests gave a clearhistory of either hay fever or asthma; the remainingpatients with positive skin tests had no clinicalhistory of type I allergy.

Discussion

OPHTHALMOLOGY

There have been few reports reviewing episcleritisand scleritis; most papers have been on individualcases of interest. Studies by Watson and Lobascher(I965), Sevel (I965), Watson (I966), Sevel (I967),

Lyne and Pitkeathly (I968), Fowler (1970), Jaysonand Jones (I97I), with follow-up studies by Jonesand Jayson (I973), Watson (1974), and Lyne(1974), are the sum total of reviews. The incidenceof scleritis in rheumatoid arthritis in the studypresented has some similarity with the majority ofreports previously documented (Table XXVII).Jayson and Jones (I971) in a group of I42 patientshad a notably dissimilar figure and Sevel's estimateof one case of scleritis in 3000 patients with rheuma-toid arthritis is much lower than our own conclu-sions. As with the review of Jayson and Jones(I971) this present series was a prospective studyfor incidence. The incidence of episcleritis inpatients presenting with rheumatoid arthritis hasnot been documented elsewhere, which is under-standable as the condition is relatively uncommon,at least in so far as presentation is concerned. Onlyseven patients, an average of approximately one foreach year of the study, are included in this group.

Table XXVII Scleritis in rheumatoid arthritis

Patients withAuthors Date Percentage

Rheumatoidarthritis Sdleritis

Smith 1957 465 2 0-4Bywaters I 964 1000 1-2 015Hart I964 900 ±7 o-8Richardson I964 100 ±3 0-3Sevel I965 3000 00-03

(Estimate)Jayson and

Jones 1971 142 9 6.3Present study 1976 4210 28 o-67

Age(years)

3440

3437

so22

76613536

5'

46

4767

40

4021

34

495o70

4350

Sex

FemaleFemaleFemaleFemaleFemaleMaleFemaleFemaleFemaleFemaleFemaleMaleFemaleFemaleMaleMaleMaleFemaleFemaleMaleFemaleMaleMale

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212 British 7ournal of Ophthalmology

Reports giving the incidence of rheumatoidarthritis in episcleritis and scleritis (Table XXVIII)are consistent with the findings of this study. Itwill be interesting to follow up the patients withoutapparent rheumatoid disease some years hence,particularly in view of the finding of one patientwith episcleritis and six with scleritis, each ofwhom had a weakly positive rheumatoid factor.A very interesting question posed by Sevel

(I966) is whether scleritis has been seen more oftenin recent years. A histogram of his 43 cases whichhad presented at the Pathology Department, Insti-tute of Ophthalmology, London, between 1950and I964 suggests an increased incidence of scleritissince I954. Studies in rheumatoid arthritis suggestthat the incidence of rheumatoid vasculitis hasincreased since the advent of treatment with sys-temic corticosteroids (Ferguson and Slocumb,196I; Smyth and Gum, 196I), although this viewdoes not have unquestioned acceptance (Schmid,Cooper, Ziff, and McEwen, I96I). It may be that-the same vasculitis that is possibly related tosystemic corticosteroid treatment, in particular tovariations in dosage (Slocumb, 1953), has been-instrumental in initiating a greater frequency ofscleritis. Systemic corticosteroids were first used inthe treatment of rheumatoid arthritis in I949(Hench, Kendall, Slocumb, and Polly, 1949) andin the treatment of scleritis in 195I (Talkov,Colpoys, Davis, Papper, and Fienberg, 1951).The only reports giving the mean age of patients

with scleritis in rheumatoid arthritis are those ofSevel (I966), and Jayson and Jones (I97i). Thenine patients of Jayson and Jones had a mean ageof 56-5 years, which is similar to the figure givenhere (Table IIIa). Sevel's series of II cases withrheumatoid scleritis had a mean age of 64-I years,

Table XXVIIIa Rheumatoid arthritis in scleritis


RheumatoidScieritis arthritis

Watson I966 Io8 35 32-4Lyne and

Pitkeathly I 968 31 9 29-0Present study 1976 27 9 33-3

Table XXVIIIb Rheumatoid arthritis in episcleritis


RheumatoidEpiscleritis arthritis

Watson i966 I17 4 3 4Lyne and

Pitkeathly I968 55 3 5-5Present study 1976 35 2 5-7

but these were eyes which required enucleation,and so were particularly severe examples. Ninepatients in our study with rheumatoid episcleritisgave an almost exactly similar mean age as thepatients with rheumatoid scleritis (Table IIIa).Non-rheumatoid inflammation presented a lowermean age, particularly for episcleritis (Table IIIb).Lyne and Pitkeathly (I968) reported a similarpicture in 55 cases of episcleritis with men havinga mean age of 45 years and women 48 years, buttheir figures included three cases of rheumatoidarthritis. Their 3I cases of scleritis, including ninecases of rheumatoid arthritis, had a mean age of49 years for men and 50 years for women. It maybe that rheumatoid episcleritis and scleritis tend toaffect a slightly older age-group of patients withrheumatoid disease. Two of us (JW and DDMM)examined a group of 148 patients with rheumatoidarthritis for evidence of steroid-induced cataract,and their mean age was 52-5 years. The controlgroup of 159 patients with rheumatoid arthritis,who had never been treated with systemic cortico-steroids, had a mean age of 49-3 years (William-son, Paterson, McGavin, Jasani, Boyle, and Doig,I969). In the progression of the disease the mostsevere cases affect an even older age-group; thiswas evident in the pathological series of Sevel(I966). The predominance of women with rheu-matoid ocular inflammation (Table IMIc) reflectsthe higher incidence of women with rheumatoidarthritis, a ratio of 2 or 3:1 (Boyle and Buchanan,I97I), and this agrees with previous studies (Sevel,I965; Jayson and Jones, 197I). Non-rheumatoidinflammation presents us with an intriguing prob-lem. The report of Lyne and Pitkeathly (I968),with only three cases of rheumatoid arthritis intheir 55 cases of episcleritis, supports the evidenceof this study that non-rheumatoid episcleritisoccurs equally in the sexes (Table IIId). If episcleri-tis is due to immune-complex disease and has asimilar basis in this respect to scleritis, as suggestedby Jones (197I), why is there such a notable differ-ence in the respective sex ratios? The sex ratio innon-rheumatoid scleritis (Table HId), togetherwith the finding that one-third of these patientshad a weakly positive rheumatoid factor (one was aman), gives some concern for the future of thesepatients.An unusual connective-tissue disorder seen in

the present study, in a 45-year-old man withrheumatoid scleritis, presented with widespreadgranulomas of orbits, nasal septum, sinuses, andlungs, which had occurred intermittently for morethan Io years. The clinical picture was less severethan that of a true Wegener's disease, and lackedthe glomerulonephritis typically present in thisdisease (Godman and Churg, 1954). A chronicdacryocystitis eventually required dacryocystec-

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tomy; histological examination showed no necro-tizing vasculitis but did show that finger-tipvasculitis, subcutaneous nodules, and skin ulcera-tion had occurred. This case may fall into thecategory of a limited form of Wegener's disease, asdescribed by Carrington and Liebow (I966) in i6patients, nine of whom had pulmonary lesions only.Four similar cases have been reported more recently(Cassan, Coles, and Harrison, 1970). Other connec-tive-tissue disorders found in the non-rheumatoidgroups of patients were chronic discoid lupuserythematosus associated with episcleritis, andsystemic lupus erythematosus associated withscleritis (one case of each). There is some doubtwhether these two conditions are separate entities,although systemic manifestations are rare in thechronic discoid form of lupus erythematosus (Boyleand Buchanan, I971). Systemic lupus erythemato-sus has been described previously in two cases ofepiscleritis by Harvey, Shulman, Tumulty, Conley,and Schoenrich (I954) and in isolated reports byLarson (I96I) and Spaeth (I967). Associatedscleritis has been reported in two cases (Sevel, I965;Watson, 1966). No previous paper gives episcleritisas a complication of chronic discoid lupus erythe-matosus.

In the late nineteenth and early twentiethcentury, gout was considered to be an importantcause of ocular inflammation, but the associationin most cases of episcleritis or scleritis is vague andindefinite (Duke-Elder and Leigh, I965). Duringthis century reports of episcleritis have been re-corded by Gilbert (1914), Savin (1938), and Mc-Williams (I952). In recent years only Watson andLobascher (1965) reported one case with an epi-scleritis. Two male patients with gout were seen inthe present study; one with non-rheumatoid epi-scleritis and one with a non-rheumatoid necrotizingscleritis. The necrotizing element developed someweeks after the onset of scleritis, and might havebeen iatrogenic in origin. The patient had a diffusescleritis which progressed to develop widespreadscleral translucency in the upper half of the anteriorsclera. A subconjunctival injection in the upper andlower fornices was followed by an area of necrosisabove (Fig. 3). The eye subsequently settled satis-factorily. Subconjunctival injections of atropinehave been incriminated in the aetiology of scleritis(Tooker, 1931; Swan and Butler, 195I). Three ofthe five cases of Swan and Butler had skin sensi-tivity reactions to atropine.Erythema nodosum, a condition previously

associated with episcleritis (McCarthy, I96I) andreported with scleritis (Watson and Lobascher,1965) was evident in two women with non-rheuma-toid episcleritis, and one woman with non-rheuma-toid scleritis. There are many common disordersassociated with erythema nodosum, including

streptococcal infection, sarcoidosis, tuberculosis,drug reactions (for example, to sulphonamides),rheumatic fever, gonorrhoea, lymphogranulomainguinale, and coccidioidomycosis (Fry, I952).James (I96I) could not give any aetiological factorin only 23 of I70 cases of erythema nodosum. Hefound evidence of sarcoidosis in I26 and infection,usually streptococcal, in 2I. None of the threepatients in this study had a raised ASO titre or anydefinite history of the conditions listed. The epi-scleritis in both cases was 'simple', but the patientwith scleritis had a nodular lesion. An anterioruveitis was present in the case of nodular scleritis,and this has been documented previously (Allan,I90I). Duke-Elder and Leigh stated that scleralkeratitis was a rarity, citing Palich-Szanto (I959).One of the cases of episcleritis, which was bilateral,had associated bilateral sclerosing keratitis.

It is uncertain why many patients with rheuma-toid episcleritis and rheumatoid scleritis had amarked increase in electrocardiographic abnor-malities (Table IVa). It is possible that the changes,which include bundle-branch block myocardialinfarction, and non-specific S-T wave changes,might have been in part, at least, due to rheumatoidinvolvement of the heart, but without necropsyit is impossible to differentiate between rheumatoiddisease, induced ischaemia, and other causes ofischaemic heart disease (Hart, I969). Pitkeathly,Howitt, and Lyne (1970) documented three casesof aortic incompetence in patients with scleritis,one of whom had a history of polyarthritis ofuncertain origin. They presented the scleritis andaortic incompetence as two manifestations ofconnective-tissue disease. Both patients had rightbundle-branch block; this conduction defect wasfound in three patients with rheumatoid scleritis.A further case of aortic incompetence associatedwith rheumatoid scleritis was described by Jonesand Jayson (I973) in their follow-up study (Jaysonand Jones, 1971). In one male patient in this studywith diffuse rheumatoid scleritis aortic stenosis andincompetence were discovered post mortem. Onewith rheumatoid episcleritis had aortic stenosis andone with non-rheumatoid scleritis had aorticincompetence. None of these patients had a historyof rheumatic fever. According to Sokoloff (I972)rheumatoid disease may occasionally cause avalvulitis with incompetence (Van Valkenburgh,Georges, and Irby, I972). Pericarditis has beendescribed in association with rheumatoid arthritisand scleritis (Smoleroff, I943; Edstrom andOsterlind, 1948; Jayson and Jones, 197I). Twopatients in the present study had clinical evidenceof pericarditis; one had rheumatoid scleritis andthe other non-rheumatoid episcleritis. Pericarditisis a recognized complication of rheumatoid disease(Harrold, I968; Bacon and Gibson, 1974) and it

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was noted by Bonfiglio and Atwater (I969) thatpatients with pericarditis more often had severejoint disease. Kirk and Cosh (I969) found that io

of I00 patients with rheumatoid arthritis hadclinical features of pericarditis.A striking increase in pulmonary complications -

such as pleurisy, pneumonitis, pleural effusion,and rheumatoid nodules - was apparent in patientswith rheumatoid episcleritis and rheumatoid scleritis(Table IVa). Pleural effusion is a recognized entityin rheumatoid disease (Carr and Mayne, I962;Walker and Wright, I 967). This complication occursin severe rheumatoid disease as manifested by thepresence of subcutaneous nodules (Boyle andBuchanan, 1971). Pulmonary nodules are themselvesnot uncommon (Noonan, Taylor, and Engleman,I963). This significant finding of pulmonary diseasein patients with rheumatoid eye inflammation as

compared with rheumatoid controls, together withthe possibility of greater cardiac involvement,emphasizes the serious nature of extra-articularrheumatoid disease affecting vital structures withthe probable final seal of significance in the higherincidence of mortality in patients so affected.

There is an increasing appreciation of the asso-

ciation of ocular inflammation and joint disordersin patients with inflammatory bowel disease.Wright, Lumsden, Luntz, Sevel, and Truelove(I965) found that II8 per cent of I44 patients withulcerative colitis had iritis, and 17A4 per centhad sacro-iliac joint abnormalities. Billson, deDombal, Watkinson, and Goligher (1967) substan-tiated the association of eye inflammation andulcerative colitis, and Jayson, Salmon, and Harrison(1970) found that 50 per cent of patients withankylosing spondylitis and colitis had an anterioruveitis. Lyne and Pitkeathly (I968) reported twopatients with ulcerative colitis associated withscleritis, but without any connective-tissue disorder.'Watson (I966) described one case of regionalileitis associated with episcleritis, and Hopkins,Horan, Burton, Clamp, de Dombal, and Goligher(1974) recorded two patients with episcleritisassociated with regional ileitis. One patient in thepresent study with rheumatoid episcleritis hadrecurrent colitis, and one with rheumatoid scleritishad diverticulosis; both were women. The patientwith recurrent colitis had an associated anterioruveitis; the patient with diverticulosis had a

particularly severe bilateral scleritis with sclerosingkeratitis, anterior uveitis, and secondary glaucomain one eye. However, while it is reported thatpatients with ulcerative colitis and uveitis have a

threefold increase in peripheral joint disease(Wright and Watkinson, I965; McEwen, I968)the arthritis is regarded in most instances as distinctfrom rheumatoid arthritis. It has been calledarthritic ulcerative colitis (Ruhl and Sokoloff,

I965) and colitic arthritis or acute toxic arthritis(Fernandez-Herlihy, 1959). Regional ileitis (Crohn'sdisease) exhibits the same type of peripheralarthritis (Ferguson, 1972). This form of arthritiswas first described by Hench (I935). It beginsabruptly and reaches its height of intensity withinthe first day or so, involving the small joints ofhands or feet less often than does rheumatoidarthritis (Wright and Watkinson, I965).

It has been suggested that peptic ulcerationoccurs more commonly in rheumatoid arthritis(Atwater, Mongan, Wieche, and Jacox, I965;Bowen, Mayne, Caine, and Bartholomew, I960;Meltzer, Bockman, Kanenson, and Cohen, 1958),but both are such common diseases that it is unwiseto be dogmatic. Four of our patients with rheuma-toid scleritis had peptic ulceration and three of theI I known to have died since examination hadgastrointestinal haemorrhage recorded on theirdeath certificates. If the association is valid, is itcaused by a vasculitis or is it a therapeutic conse-quence of, for example, salicylates? Certainly allthree patients who died of gastrointestinal haemorr-hage had been receiving salicylates. Against this itis noteworthy that four patients with non-rheuma-toid episcleritis, that is without severe disease,also had a history of peptic ulceration.

Skin diseases reported with episcleritis areeczema (Watson and Lobascher, I965), contactdermatitis and acne rosacea (Watson, I966),psoriasis, lichen planus, and erythema elevatumdiutinum (Lyne and Pitkeathly, I968); and withscleritis, epidermolysis bullosa dystrophica (Mazzaand Panagis, I967). Erythema nodosum, whichhas already been discussed, has been associatedwith both episcleritis and scleritis. Psoriasis wasevident in two women in the study, one withrheumatoid scleritis and one with non-rheumatoidepiscleritis. There were no secondary eye complica-tions in either of the patients with psoriasis. Afurther patient with non-rheumatoid episcleritishad a history of pityriasis rosea.

Reviewing the literature of scleritis in rheuma-toid arthritis, Sevel (I966) found that the conditionwas more often bilateral. The ratio of 2:I agreeswith the findings given here (Table IIIe). In hisown series of II enucleated eyes, the disease wasunilateral in eight, an inconsistency which Sevelwas unable to explain. Extra-articular manifesta-tions of rheumatoid disease are significantlyapparent in this present study and the fact that inmost cases rheumatoid scleritis is bilateral reflectsthe widespread nature of extra-articular involve-ment. Non-rheumatoid scleritis was more oftenunilateral and whether or not these patients willlater develop autoimmune disease, it seems thatthey have a more localized disorder. Non-rheuma-toid episcleritis in contrast was more often bilateral

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(Table IIIf) and characteristically recurrent, withinflammation alternating from one eye to the other.

It is generally recognized that the symptoms ofepiscleritis are less distressing than those of scleritis(Watson and Lobascher, I965; Jayson and Jones,1971). One of the objects of this presentation wasto provide evidence that these accepted differencesdo exist. Ocular pain was more apparent in scleritis.The patients complained of a red eye more oftenin both rheumatoid and non-rheumatoid episcleritisthan did those with scleritis (Tables Va, b). Adistinctive finding was the higher incidence ofcomplaints of redness and pain in non-rheumatoidinflammation. Perhaps the rheumatoid patientsuffers to such a degree elsewhere that the spon-taneous complaint of a red and painful eye is notalways given. However, Jones and Jayson (1973)pointed out that the fewer complaints in patientswith rheumatoid eye inflammation might be due tothe many anti-inflammatory drugs which thesepatients were receiving, or possibly the higherpain threshold which has been described in rheu-matoid arthritis (Huskisson and Hart, 1972). In hisearly description of 'sclerotitis', Mackenzie (I830)reported that a number of patients described theireyes as hot and dry at the onset of an episode ofinflammation. It was interesting to discover a fewpatients in this study who said that a dry, gritty,or burning eye would often precede the flare-up ofinflammation.

It was surprising to find that the history of eyeinflammation was slightly longer in the non-rheumatoid group of patients, both for episcleritisand scleritis (Table VIb). A simple explanationmight be the problem of recollection. Many patientswere examined early in the disease, but not all.With so many physical disabilities in what is gener-ally severe rheumatoid disease, the rheumatoidpatient might simply have misjudged how long theeye trouble had lasted. Lyne and Pitkeathly (I968)gave a mean duration for all forms of episcleritis of20 months and a mean duration for all forms ofscleritis of 6o months. The difficulty is knowingwhen an eye is truly quiet and will remain so.Many patients in this study had quiescent periodsbetween inflammation lasting many months, andin one case seven years. Nevertheless, a ratheruneasy impression given by the rheumatoid patientsis of the disease 'burning out' after two or threeyears.As expected, the deeper inflammation of scleritis

has a more significant effect on visual acuity (TableVII). The study of visual acuity was confined topatients presenting at the Tennent Institute ofOphthalmology as cases of episcleritis or scleritis,and did not include patients presenting withrheumatoid arthritis at the Centre for RheumaticDiseases. Visual acuity in these patients was

affected mainly by anterior segment disease, parti-cularly corneal inflammation and cataract. Thereview of posterior subcapsular cataract/advancedcataract in rheumatoid patients with scleritis whowere receiving systemic corticosteroids also sug-gests, although without supporting figures, a severeeffect on visual acuity (Table XII). Furthermore,the group of patients with rheumatoid scleritis whohad a posterior segment abnormality would havesome disturbance of vision (Table XIIIa). Fortu-nately, a cataract can readily be extracted and thisshould provide some reassurance to the clinicianwho considers that treatment with systemic cortico-steroids is imperative. The male patient whodeveloped gout, and subsequently scleritis, re-corded a visual acuity which dropped from 6/6-2to 6/i8-i in four weeks, due to the development of avariable myopic astigmatism. This eventuallysettled coincident with quiescence of his scleritisas a mixed astigmatism which, on refraction, gavea visual acuity of 6/5, a reminder that reduction invision might have had a very simple solution.The abundance of terms used to describe epi-

scleritis and scleritis requires a new simplicity ofapproach, and this was provided by the classificationof Watson, Hayreh, and Awdry (I968a, b), whichwas used in this study (Tables VIIIa, b). Clearlythe pathological activity in scleritis and nodularepiscleritis has the same basis (Manschot, I96I;Sevel, I967), and it only remains to give a descrip-tion of the appearance of any inflammation. Therehas been much confusion regarding the terms'scleromalacia' and 'scleromalacia perforans' (Vander Hoeve, 1934). 'Scleromalacia' is often used fora diffuse scleritis with scleral translucency, but thisis not the eye which is the most likely to perforate,and so confusion results. According to the literaturethe eye which commonly perforates has a typicallynecrotizing sclera, and the inflammation is necroticand the sclera opaque but not translucent (Fig. 3).Most reports of scleromalacia perforans give adistinct destructive picture to the scleral lesion,describing such features as necrosis, sloughing, orulceration (Van der Hoeve, 1934; Oast, I937;Verhoeff and King, 1938; Harbater, I949; Shaned-ling, 1950; Francois, I951; Talkov and others,I951; Ashton and Hobbs, I952; Renard, Lelievre,and Mazel, 1953; Ellis and Holtz, 1953; Armstrongand McGovern, 1955; Marquard, I956; Boberg-Ans, 1958; Williams and Rosenthal, 1959; Taffetand Carter, I96I; Francois, Victoria-Troncoso,Hanssens, and Bakskulin, I969; Gombos, I967).Blum and Salmoun (I963) and Merz (I964)reported cases where scleral translucency withalarming progressive ectasia necessitated surgicalintervention. In these cases there was no necrosisor ulceration.The importance of these observations is the

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216 British yournal of Ophthalmology

appreciation that areas of scleral translucency onlyrarely give cause for concern. Rheumatoid noduleof the sclera was the term used by Ashton andHobbs (I952) to describe the scleritis found inrheumatoid arthritis. It gives an accurate descrip-tion of the granulomatous reaction, similar to thatfound in the subcutaneous nodule of rheumatoidarthritis. However, a sub-division of the lesions intonodular, diffuse, or necrotizing scleritis provides aclear and simple picture of the scleral reaction withthe premise that the inflammation is granulomatous.The overall descriptive term for scleritis whichsatisfies the pathological uniformity of the conditionis necrogranulomatous scleritis (Sevel, i967). It isinteresting that none of our cases of rheumatoidepiscleritis was nodular in character, whereas innon-rheumatoid episcleritis nearly one-fifth ofcases were nodular (Tables VIIIa, b). Two cases ofrheumatoid inflammation initially diagnosed asnodular episcleritis both progressed to a scleritis.Only one patient in the study presented with anecrotizing scleritis. A 63-year-old man developeda non-rheumatoid gouty scleritis, but the necro-tizing lesion discussed earlier was probably inducedby a subconjunctival steroid injection. Duke-Elder and Leigh (i965) described the possibility ofrecurrent nodular episcleritis causing the circum-comeal region of the sclera eventually to becomeslate-coloured. We submit that any appearance ofthis nature is due to involvement of the sclera andis no longer an episcleritis but a scleritis. The twopatients diagnosed initially as having nodularrheumatoid episcleritis subsequently had a distinctslate-coloured zone at the site of inflammation,and were therefore cases of scleritis.

Transparency of the sclera which may accompanyscleritis is often described as scleral thinning. Thisdescription may create apprehension in the mindof the clinician, and a term such as scleral trans-lucency is preferable. In a recent presentationinvolving one of us (DDMM), ultrasonographicassessment of the thickness of areas of post-scleriticscleral translucency showed that these areas werenot invariably associated with thinning. Only threeof eight patients had distinct evidence of thinning ofsclera (Rooney, McGavin, Sutherland, and Railton,1974). The presence of translucency of the sclerareflects the depth and extent of the scleral inflam-mation, which in this study was very much moreevident in rheumatoid scleritis, indicating thatscleritis in rheumatoid disease is generally moresevere (Tables VIlla, b). Posterior scleritis is morecommon in patients with rheumatoid arthritiswhich also suggests a more extensive inflammationin rheumatoid disease. Inflammation of the posteriorsclera is deduced from its secondary effects onneighbouring tissues. Posterior inflammation re-sulted in choroiditis in two patients, retinal detach-

ment in one, and extraocular muscle imbalance infive. In a paper on the clinical manifestations ofscleritis, Watson (I974) found that of 217 eyeswith episcleritis, 170 had the simple variety and 47had nodular episcleritis. Of 30I eyes with scleritis,I I9 had diffuse anterior scleritis, 134 had nodularanterior scleritis, 42 showed necrotizing scleritis,and six revealed features of a posterior scleritis.This series, easily the largest general study ofepiscleritis and scleritis, is particularly significantfor its record of the clinical features of theseconditions.Lyne and Pitkeathly (I968) noted that single

attacks of episcleritis affected the interpalpebralarea in 25 of 33 cases. This distribution of inflam-mation is substantiated by the present study(Tables IXa, b). Lyne and Pitkeathly suggestedthat minor trauma might account for this distribu-tion and found a foreign body in one case. Certainlyexternal factors would seem to play a part, whethertrauma or some other factor or factors. Patientssometimes complain of a dry, gritty, and burningeye and epiphora was seldom a problem. An eyewhich is inflamed primarily deep to the conjunctivamay slightly increase in temperature. Evaporationof tears may ensue more rapidly in consequence andso irritation due to exposure will affect the inter-palpebral area preferentially. However, this couldaccount only for aggravation of an already inflamedarea. It was thought that type I allergy (atopy)might play a part in the external aggravation of anepiscleritis. However, in the present study noincrease in atopic disease could be found in 23patients with non-rheumatoid eye inflammation, I7of whom had episcleritis. Inflammation affectingthe anterior sclera in rheumatoid arthritis affectsthe upper half of the sclera more often than thelower half (Jayson and Jones, 197I), and Sevel'sreview of the literature confirms this view. Sevel(1965) in his iI cases examined histologically,found that i8-o per cent had disease of the posteriorsegment, and his investigation of the literature withregard to eyes enucleated because of scleritis gavea figure of izvo per cent. These figures are notdissimilar to our own for rheumatoid scleritis(Table VIIIa). However, the distribution ofanterior scleritis in this report, although more oftenaffecting the superior aspect of the sclera, does nothave the considerable emphasis of Sevel's cases(Table IXa). Jayson and Jones (I 970I) in theirgroup of 14 patients found a distribution similarto that seen in our study.

Corneal complications in scleral inflammationhave been described for over a century (Mackenzie,I830). The predominant disturbance is a sclerosingkeratitis which, according to Watson, Hayreh, andAwdry (I968a), occurs in nearly half of thosepatients with scleritis but seldom in those with

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episcieritis. In i i cases which were enucleated andcomprised the series of rheumatoid scleritis (Sevel,I965), 36-o per cent had some form of keratitis.However, rheumatoid episcleritis and rheumatoidscleritis in this investigation showed a high incidenceof corneal complications (Table Xa), in particularsclerosing keratitis (Fig. 4), and it was interestingto find that anterior uveitis although less commonhad a similar incidence in rheumatoid episcleritisand rheumatoid scleritis, unexpected findings asregards episcleritis. The anticipated differencebetween episcleritis and scleritis was confirmed inregard to cataract, glaucoma, and posterior segmentdisease, but it will be recalled that only 13 eyeshad rheumatoid episcleritis. Corneal ulcerationoccurred in two forms; limbal guttering (Fig. 5),which has been called marginal furrows (Brownand Grayson, I968), and keratolysis. While limbalguttering may persist for a considerable time, andduring the active phase of scleral inflammationappears to 'creep' around the limbus, keratolysisis a more dramatic 'melting' of the cornea whichmay result in loss of the anterior chamber with irisprolapse. Watson and Holt-Wilson (I974) describeda further corneal complication of scleritis whichthey called deep keratitis, in which a deep sheetopacity with deep vascularization after long-stand-ing recurrent scleritis was evident. We have recentlyseen a young woman with non-rheumatoid scleritis,who is not included in this study, where thisstriking corneal corrplication was present.The main feature of interest in the patients with

anterior uveitis was the higher incidence of posteriorsynechiae in patients with rheumatoid scleritis ascompared with non-rheumatoid scleritis. Thiswould suggest a more active and tenacious form ofuveal inflammation, which is consistent with theimpression of severe ocular disease in rheuma-toid arthritis. However, the presence of anterioruveitis in both rheumatoid and non-rheumatoidinflammation was very nearly as common in epi-scleritis as in scleritis. Anterior uveitis occurred inapproximately one-fifth of patients with episcleritisand it occurred in about one-quarter of those withscleritis (Tables XIa, b). Iridocyclitis has oftenbeen described with scleritis (Wolfe, i882; Kiehle,1946; Duke-Elder and Leigh, I965). Sevel (I965)in his series of i i rheumatoid cases found histologi-cal evidence of cyclitis in 46-o per cent. The figuresgiven in this study are objective in that they indicateevidence of active or old uveitis (for example,posterior synechiae), and so the true figure will behigher. A deep scleritis will invariably be accom-panied by uveitis-whether iritis, cyclitis, orchoroiditis-but a number of cases, particularlyin the anterior segment, may settle without anyresidual evidence of inflammation.

Posterior subcapsular cataracts have been re-

ported in Io05 to 6o per cent of patients withrheumatoid arthritis receiving treatment with long-term oral corticosteroid therapy (Black, Oglesby,von Sallmann, and Bunim, I960; Giles, Mason,Duff, and McLean, I962; Crews, I963; Irby,Toone, Wittkamp, and Wiesinger, I964; Spencerand Andelman, I965; Furst, Smiley, and Ansell,I966). A similar study at the Centre for RheumaticDiseases, Glasgow, provided an incidence ofsteroid-induced cataract of I V5 per cent (William-son and others, I969). The combination of treat-ment with systemic corticosteroids and the presenceof anterior segment inflammation in the form ofscleritis carries a high risk of the development ofcataract; in this study, an incidence of 36-o percent (Table XII). While it is helpful to be aware ofthis possible complication, it is reassuring thatwhere systemic corticosteroid treatment is clearlyindicated, any resulting cataract can be removedby surgery.

Posterior scleritis can provoke various intraocularside-effects including choroiditis with exudativeretinal detachment (Radn6t, 1948; Harper, I960;Hurd, Snyder, and Ziff, 1970), macular oedema(Watson and Lobascher, I965), retinal striations(Sears, I964) and optic disc oedema (Bertelsen,I960). Orbital myositis is an extraocular manifes-tation (Gorduren, I962; Maria, I956). In hispathological series, Sevel (I965) found choroiditis(64-0 per cent), choroidoretinitis (9-0 per cent) andretinal detachment (64-0 per cent). Rheumatoidscleritis provides disturbing indications of deep-seated inflammation, posterior segment abnor-mality affecting nearly one-third of the patients(Table XIIIa). Although macular disturbancecould have other causes, such as drug-inducedmaculopathy, senile degeneration (Bedell, 1950;Favre, I960) and vascular disease (Norn, I96I) itis recognized that it may occur with retinitis(Manschot and Von Winning, I953) or iridocyclitis(Samuels, 1930; Wolff, I93I). It is possible, there-fore, that the large number of rheumatoid patientswith a macular disturbance may be attributed,in part at least, to the consequence of severescleritis, the incidence being higher than in thenon-rheumatoid patients with scleritis, both groupshaving a mean age in the sixth decade. The uveitisaccompanying a scleritis is more often an anterioruveitis, but whether anterior or posterior it isfrom this serious complication that most of theconsequent ocular problems arise, problems whichaffect vision - such as cataract, glaucoma, exudativeretinal detachment, and macular disturbance. Opticnerve disease after scleritis has had little documen-tation. Bertelsen (I960) described I2 patients witha posterior scleritis and two of these had oedemaof the optic nerve head. The cases of Gorduren(I962) and Maria (1956) of sclerotenonitis and

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2I18 British Journal of Ophthalmology

orbital myositis both had optic nerve oedema withassociated retinal oedema. One patient in thepresent series with a rheumatoid scleritis hadoptic disc oedema.Watson (I966) found that seven of io8 cases with

scleritis (6-5 per cent) had raised intraocularpressure, and Sevel (I965) in his study of enucleatedeyes reported that 45-0 per cent of 43 cases had a

history of secondary glaucoma. Watson's cases

settled with the good response of the scleritis tosystemic treatment. He stated that surgery was

avoided because of the dangers of aggravating theinflammation. Apart from one case of non-rheu-matoid episcleritis with an intraocular pressure

fractionally above the upper limit of the normalrange, all cases of secondary glaucoma in this studywere in patients with scleritis (Tables XIVa, b).As in Watson's series (I966), the intraocularpressure settled coincident with quietening of thescleritis in most cases. One patient required surgery

and one patient, with a minimally raised pressure

(22 mmHg), is still receiving medical treatment. Ifthe indications for operative intervention becomecompelling, surgery should be carried out despitethe presence of inflammation. The patient withrheumatoid arthritis and severe scleritis whorequired surgery underwent a drainage procedurewithout any exacerbation of inflammation.The deeper and more extensive inflammation of

scleritis affects ocular movement considerablymore often than episcleritis, and one suspects thatthe latter may affect movement only because of thediscomfort sustained in moving the eye to theaffected side (Tables XVa, b). There is a closeassociation of scleritis, in particular posteriorscleritis, with tenonitis, myositis, and pseudo-tumour formation. (Although orbital myositis hasbeen called a form of pseudotumour the differen-tiation in terms seems more appropriate.) It issometimes difficult to reach the correct diagnosisin these conditions. The patient presents withpain, limitation of ocular movement, chemosis,and sometimes lid oedema. The indirect conse-

quence of inflammation provides the clue todiagnosis, and this appearance will often simulateorbital cellulitis. Bertelsen (I960) confesses to thismistake in six of his 12 patients with sclerotenonitisand orbital myositis. Both Gorduren (I962) andMaria (1956) began treatment with systemicantibiotics in their cases before reaching the true

diagnosis. Coop (I96I) in a series of 47 cases oforbital pseudotumour found nine which presentedwith chemosis as part of the clinical picture. In thewoman with non-rheumatoid scleritis who pre-

sented with strabismus there was the same confusionin diagnosis. A biopsy of the central strip of tendon/muscle of the lateral rectus muscle confirmed thediagnosis. There was no untoward effect on the

inflammation as a result of surgical intervention.The incidence of Sj6gren's syndrome in rheu-

matoid arthritis has been estimated at between9 and 34 per cent, and in the sicca syndrome thereis a 6o to 75 per cent incidence of connective-tissue disease (Henkind and Gold, 1973). Talal(1972) considers that keratoconjunctivitis siccadevelops in I o to I 5 per cent of patients withrheumatoid arthritis and cites the report of Sten-stam (I947). While the incidence of keratocon-junctivitis sicca in the present study in patients withrheumatoid episcleritis and rheumatoid scleritisfalls within the accepted range for rheumatoidarthritis, the incidence of Sjogren's syndrome isconsiderably higher than that found by Williamson(1970) in patients with rheumatoid arthritis, alsoattending the Centre for Rheumatic Diseases. Hefound that between 6 and 7 per cent of patientswith rheumatoid arthritis had Sj6gren's syndrome.The incidence given here in rheumatoid episcleritis(33.3 per cent) and rheumatoid scleritis (32z4per cent) reflects the extent of extra-articular mani-festations in patients with rheumatoid episcleraland scleral inflammation.

RHEUMATOLOGY

It is not the purpose of this paper to discuss therheumatological findings in any detail. However,some of the results of this aspect of our study leadus to suspect that the underlying disease of scleritisin these patients may be a vasculitis.The arthritis in patients with rheumatoid epi-

scleritis and rheumatoid scleritis was of longerduration and revealed more severe erosive changeson x-ray examination as compared with the rheu-matoid controls (Table XVII). On the other hand,the functional capacity and the degree of jointtenderness were similar in the rheumatoid patientswith and without inflammatory eye disease. Sub-cutaneous nodules in rheumatoid arthritis are foundin approximately one-third of patients (Boyle andBuchanan, 1971). Of the patients with rheumatoidepiscleritis and rheumatoid scleritis 50 per centhad subcutaneous nodules, twice the percentagefound in the control group of patients (TableXVIII). Histological studies of early noduleformation by Sikoloff, McCluskey, and Bunim(1953) suggest that the nodule develops around aninflamed blood vessel. It is significant that biopsy ofepiscleral nodules in patients with rheumatoidarthritis has given a pathological picture similar tothat of the subcutaneous nodule of rheumatoidarthritis (Edstrom and Osterlind, 1948; Mundy,Howard, Stillnan, and Bevans, I951; Ferry, I969),and examination of enucleated eyes with scleritishas confirmed a uniform basic pathology (Manschot,I96I; Sevel, I965).

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Approximately 25 per cent of patients withrheumatoid arthritis have vasculitis on post-mortemexamination (Cruickshank, I954). Rheumatoidvasculitis, unlike classical polyarteritis nodosa,spares the kidneys, and hypertension and asthmaare rare (Ferguson and Slocumb, I96I). It is inter-esting that while respiratory disease and possiblycardiac involvement were features notable in thepatients with rheumatoid eye inflammation, renaldisease was not a problem. Rheumatoid vasculitisaffects the peripheral nerves (Hart, Golding, andMcKenzie, 1957; Ferguson and Slocumb, I96I;Wilkinson and Torrance, I967), giving rise to asensory and/or motor neuropathy (Hart andGolding, I960; Schmid and others, I96I) and todermal infarction (Bywaters, 1957; Golding, Hamil-ton, and Gill, I965). In the group of patients withrheumatoid episcleritis and rheumatoid scleritis,8-9 per cent had a peripheral neuropathy, presum-ably due to vasculitis affecting the vasa nervorum,and i3'3 per cent had skin ulcers, both incidencesvery much higher than expected, although forthese numbers there was no statistically significantincrease in the incidence of peripheral neuropathyor skin ulcers as compared with that in rheumatoidcontrols (Table XVIII).Many patients with rheumatoid scleritis also

manifested skin bruising and skin atrophy (TableXVIII), features almost certainly attributable tosystemic corticosteroid treatment, which most ofthe patients were receiving (Boyle and Buchanan,1971). It has been suggested that systemic cortico-steroids produce alteration in the dermal connectivetissue, particularly in collagen (Scarborough andSchuster, I960; Greenwood, I966).

Patients with rheumatoid ocular inflammationalso had a high incidence of splenomegaly (i0o9per cent) (Table XVIII). All five patients withsplenomegaly had anaemia and two of the patientshad a neutropenia. The syndrome of chronicrheumatoid arthritis, splenomegaly, and neutro-penia, first described by Felty (1924), is said tooccur in fewer than 5 per cent of patients withrheumatoid arthritis (Walker and Wright, I968).The picture that emerges in the patient with

rheumatoid episcleritis and rheumatoid scleritis isthat of long-standing rheumatoid disease andsevere erosive joint changes on x-ray examination,with many extra-articular manifestations of rheu-matoid disease, many of which reflect an underlyingrheumatoid vasculitis. Episcleritis and scleritis inthese patients is further evidence of widespreadand severe disease affecting eyes, peripheral nerves,skin, lungs, and possibly the heart. These findingssubstantiate the reports of Jones and Jayson (I973),who found a significant incidence of rheumatoidsubcutaneous nodules and other features of micro-vasculitis in patients with rheumatoid scleritis.

LABORATORY INVESTIGATIONS

Laboratory data confirm the expected evidence ofwidespread disorder in patients with rheumatoiddisease as compared with patients with non-rheumatoid eye inflammation. A significant differ-ence was noted in the findings comparing rheuma-toid and non-rheumatoid patients as regardshaemoglobin and albumin/globulin ratio. The ery-throcyte sedimentation rate was measured by twodifferent methods but the readings in patients withrheumatoid disease were clearly far higher (TablesXIXa, b). It is interesting to note that the meanvalues for haemoglobin, erythrocyte sedimentationrate, and albumin/globulin ratio were all moreabnormal in the patients with rheumatoid epi-scleritis and rheumatoid scleritis than in therheumatoid control group, although only thefindings for the erythrocyte sedimentation ratewere statistically significant (Table XIXc).The normal adult range for positive titres to

Toxoplasma gondii is in the region of 30 to 40 percent. Only the small group of patients with rheuma-toid episcleritis had a figure that was very muchhigher (Table XXa). Beattie (1958) found 0-2 percent of normal adults with a titre of 1/256 or moreand Ludlam and Beattie (I963) reported only onetitre at I/512 in 478 women (0o2 per cent). In thepatients with rheumatoid eye inflammation three of35 patients (8-6 per cent) had titres of 1/256 ormore. A similar increased incidence of high titres,noted in this paper in patients with rheumatoid eyeinflammation, has been recorded in primarybiliary cirrhosis (MacSween, 1973), reticulosis orafter immunosuppressive or antimetabolite treat-ment (Broughton, 1970), pregnancy (Purtilo,Hallgren, and Yunis, I972) and where a choroido-retinitis due to toxoplasmosis may relapse and toxo-plasma antibody levels rise (Beattie, 1958). Theseare conditions associated with impaired cell-mediated immunity, and there is recent evidence ofdepression of cell-mediated immunity in somepatients with rheumatoid arthritis (Waxman,Lockshin, Schnapp, and Doneson, 1973).The titre of rheumatoid factor reflects the severity

of the disease (Ziff, 1957; Kellgren and Ball, 1959)and the consequent prognosis (Duthie, Brown,Truelove, Barager, and Lawrie, I964). It is notsurprising, therefore, that some patients withrheumatoid episcleral or scleral inflammation hadrelatively high titres (Table XXII). Higher titresof rheumatoid factor are also associated with manyextra-articular manifestations of rheumatoid diseasesuch as subcutaneous nodules (Kellgren and Ball,I959), vasculitis, peripheral neuropathy, and intrac-table skin ulcers (Epstein and Engleman, 1959).Autoantibody investigations in rheumatoid epi-scleritis and rheumatoid scleritis generally show

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results consistent with the expected incidence in ageneral rheumatoid population (Table XXIa). Intests of patients with rheumatoid arthritis, Pollak(I964) found that 24 per cent had positive antinuclearresults, and Weir, Holborow, and Johnson (I96I)found that 14 per cent were similarly positive.Thyroid antibodies in patients with rheumatoideye inflammation showed no striking increase andindeed did not match the incidence of I5 of 62cases (24-2 per cent) of rheumatoid arthritis foundby Anderson, Goudie, Gray, and Buchanan (I96I).The incidence of thyroid microsomal antibody inthe present study of rheumatoid patients witheye inflammation is only slightly lower than that inthe female group reported by Buchanan, Crooks,Alexander, Koutras, Wayne, and Gray (I96I),where 26- i per cent of 46 women had thyroidmicrosomal antibody. Johnson, Holborow, andGlynn (I965) found an incidence of smooth-muscleantibody in 6-4 per cent of 47 patients with rheuma-toid arthritis and Doniach, Roitt, Walker, andSherlock (I966) an incidence of i6 per cent in32 patients with rheumatoid arthritis. The figuregiven here in rheumatoid scleritis (23-5 per cent) isslightly higher than in these two series, but it isdifficult to reach any conclusion at this stageregarding this finding. High incidences of smooth-muscle antibody have been found in liver disease,particularly active chronic hepatitis (67 per cent),primary biliary cirrhosis (50 per cent), and crypto-genic cirrhosis (28 per cent) (Doniach and others,I966). Certainly liver disease has been noted inassociation with rheumatoid arthritis, but the inci-dence was small; o-66 per cent of patients withrheumatoid arthritis alone and I-5 per cent ofpatients with Sjogren's syndrome, in whom theconnective-tissue disorder was rheumatoid arthritis(Whaley and others, 1970). Salivary duct antibodywas found in one-quarter of patients with rheuma-toid arthritis, apparently uncomplicated by Sj6-gren's syndrome (MacSween, Goudie, Anderson,Armstrong, Murray, Mason, Jasani, Boyle, Bucha-nan, and Williamson, I967), and it would appearthat the present findings are consistent with theirobservations without drawing any conclusion fromthe higher percentage of antibodies in the verysmall group with rheumatoid episcleritis. Arm-strong (I967) considered that there was no evidencethat gastric parietal-cell antibodies occurred morecommonly in rheumatoid arthritis. In his investi-gation of patients with rheumatoid arthritis, i6'2per cent of 246 females and 6-3 per cent of 79 maleshad positive results for gastric parietal-cell antibody.The small group of patients with rheumatoidepiscleritis precludes any accurate conclusion andthe group of patients with rheumatoid scleritishad a percentage incidence of gastric parietal-cellantibody of i6'2 per cent.

The results of the autoantibody tests in patientswith episcleritis and scleritis, but with no clinicalor radiological evidence of rheumatoid arthritis,are of particular interest (Table XXIb). One-thirdof the patients with scleritis gave positive results totests for rheumatoid factor, and this might be anearly manifestation of rheumatoid disease. Alter-natively, it is conceivable that plasma cells in thescleral infiltrate could produce rheumatoid factor.It is known that plasma cells in the lymphoidtissues and in lymphoid infiltrates of synoviuminduce rheumatoid factor which then circulates inthe blood stream (Mellors, Nowoslawski, andKorngold, I96I). It is possible, therefore, that thelow titre of rheumatoid factor in the blood of thosepatients with scleritis, but no rheumatoid arthritis,merely reflects local scleral inflammation. However,only careful long-term follow-up studies willanswer this question. The incidence of antinuclearfactor in the serum of patients with non-rheumatoidscleritis could also indicate potential systemicdisorder. Previous studies give a lower figure forthe presence of antinuclear factor in the serum ofpatients with rheumatoid arthritis (I4 per cent:Weir and others, I96I; 24 per cent: Pollak, I964)and it is known that the prevalence and titre of anti-nuclear factor is highest in patients with severearthritis (Hall, Bardawil, Bayles, Mednis, andGalins, I960), vascular and granulomatous compli-cations and Felty's syndrome (Alexander, Bremner,and Duthie, I960; Ward, Johnson, and Holborow,I964). Thyroglobulin antibody in patients withnon-rheumatoid episcleritis and non-rheumatoidscleritis shows no increase beyond figures pre-viously recorded for normal populations (5 percent: Roitt and Doniach, 1958; 6 per cent: Owenand Smart, 1958; 4 per cent: Blizzard, Hamwi,Skillman, and Wheeler, 1959; io per cent: Beutnerand Witebsky, I962). Similarly, the incidence ofthyroid microsomal antibodies is similar to thefigure of 8 per cent given by Beutner and Witebsky(I962) for a normal population. Other autoantibodytests in patients with non-rheumatoid eye inflam-mation show little variation from general populationstudies for smooth-muscle antibody (I3-5 per cent:MacSween, 1973) and gastric parietal-cell antibody,in which a general population study of hospitalinpatients older than 50 years gave a figure of ioper cent with the higher figure of I3 6 per cent inwomen (Anderson, Buchanan, and Goudie, I967).MacSween (I973) in his group of II4 controlpatients in a study of primary biliary cirrhosisfound an incidence of I0 per cent in women and5 per cent in men.The complement system consists of a group of

serum proteins which amplify the effects of someantigen-antibody interactions (Austen, 1972). Inrheumatoid arthritis, serum complement levels

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have been found to be normal or slightly raised(Ellis and Felix-Davies, I959) and also reduced(Mongan, Cass, Jacox, and Vaughan, I969;Weinstein, Peters, Brown, and Bluestone, I972).Six rheumatoid patients in this study show reducedvalues (Table XXIIIa) and it may be that hypo-complementaemia reflects active vasculitis, as hasbeen shown previously in rheumatoid arthritis(Mongan, Cass, Jacox, and Vaughan, I969;Weinstein and others, 1972). Six of the patientswith non-rheumatoid eye inflammation also hadserum complement levels below ioo mg/IOO ml(Table XXIIIb) and it is difficult to suggest causes

of this finding. One of these patients gave a historyof gout and essential hypertension, and another haderythema nodosa. However, it should be notedthat there is some dubiety as to what is the range

of normal for serum complement readings. Thenormal mean value in this study was taken as

145 mg/IOO ml (+22 mg/10o ml) (Shanbrom,Khoo, and Lou, 1967). Thompson (1972) found a

mean value of ii8 mg/ioo ml (+26 mg/ioo ml) in66 healthy individuals.

Immunoglobulins IgG, IgA, and IgM showlittle variation from normal figures in either rheu-matoid or non-rheumatoid eye inflammation.

MORTALITY

The mortality in rheumatoid patients with epi-scleral and scleral inflammation was soberinglyhigh, 45.5 per cent (Table XXIV). Fifteen of 33

known cases of rheumatoid episcleritis or rheu-matoid scleritis had died since examination, com-

pared with six of 33 known rheumatoid controlpatients (i8-2 per cent). A decreased life expec-

tancy has been observed in rheumatoid arthritis(Reah, I963) and the outlook and severity of thecondition is always more grave in sero-positive

disease (Duthie and others, I964). Jones and Jayson(I973) found that five of their original 14 patientswith rheumatoid scleritis had died within threeyears, a mortality of 36 per cent. Only i8-5 per cent

of their 133 control patients had died during thesame period. The figures for mortality suggest thatthe conclusion of Decker (1972) was accurate:

'death due solely to rheumatoid arthritis is rare

indeed. When it occurs it is due to the extra-

articular manifestations'.

TYPE I ALLERGY (ATOPY)

The simplest methods of screening patients for type

I allergy are either to carry out a series of skintests, as has been done here, or to measure theblood levels of IgE. A group of 23 patients, eachpatient with non-rheumatoid eye inflammation,failed to give any indication on skin testing of a

higher incidence of atopy than would have beenexpected in the general population. The incidenceis within the range found in controls during studiesof type I allergy (Johansson, I967). This finding in asmall series suggests that any external factor whichmight predispose to the interpalpebral distributionof inflammation found in many patients withepiscleritis (Lyne and Pitkeathly, I968) (TableIXb) does not have its origin in a susceptibility toatopic disease.

In a recent publication reviewing ocular mani-festations of rheumatic disorders, Henkind andGold (1973) plead for the inclusion of examinationby an ophthalmologist in the protocol for anyprospective study of rheumatic disease. This study,which has anticipated their request by some years,attempts to collate the ocular manifestations ofepiscleritis and scleritis with the rheumatic dis-orders, in particular rheumatoid arthritis.

Conclusions

i. Episcleritis occurred in approximately twopatients per iooo with rheumatoid arthritis(O0I7 per cent). Scleritis occurred in approxi-mately seven patients per IOOO with rheuma-toid arthritis (o-67 per cent). Rheumatoidarthritis is common in patients presentingwith scleritis, in this series occurring in one-third of patients (33.3 per cent), but is lesscommon in patients presenting with episcleri-tis, occurring in approximately one patientin 20 (5 7 per cent).

2. All patients with rheumatoid episcleritis,rheumatoid scleritis, and non-rheumatoidscleritis had a mean age in the sixth decade,and the disease was more prevalent in women;whereas patients with non-rheumatoid epi-scleritis had a mean age in the fifth decadeand the disease occurred equally between thesexes.

3. Rheumatoid episcleritis and rheumatoidscleritis were associated with widespreadsystemic disease, particularly of the cardio-vascular and respiratory systems.

4. The most common complaints in episcleritisand scleritis were of redness and pain. Ocularpain was more evident in scleritis. Eye symp-toms were more readily noted in non-rheu-matoid inflammation.

5. All groups of patients had a very wide rangein the duration of intermittent ocular inflam-mation, from a few days or weeks to I5 yearsor more.

6. Visual acuity is more severely depressed inscleritis than in episcleritis as a result of theassociated ocular complications.

7. In a classification of scleritis as nodular,

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diffuse, and necrotizing, diffuse scleritis wasthe most common form in both rheumatoidand non-rheumatoid scleritic inflammation.Posterior scleritis was more common inrheumatoid scleritis than in non-rheumatoidinflammation. Scleral translucency was foundconsiderably more often in rheumatoid thanin non-rheumatoid scleritis.

8. Ocular inflammation in episcleritis usuallyaffected the interpalpebral area. Rheumatoidscleritis had a fairly even distribution in allfour quadrants of the anterior sclera.

9. Episcleritis and scleritis associated withrheumatoid disease had more associatedocular complications than episcleritis andscleritis unassociated with rheumatoid disease.

I0. Posterior subcapsular cataract was commonin rheumatoid scleritis in cases in which thepatient had been given systemic cortico-steroids, occurring in 36 per cent of thesepatients.

I I. Rheumatoid episcleritis and rheumatoidscleritis generally presented in patients withrheumatoid disease of long duration and inpatients with radiological evidence of moreadvanced joint disease when compared withrheumatoid control patients.

12. Subcutaneous granulomatous nodules andskin atrophy were significantly more commonin patients with rheumatoid episcleritis andrheumatoid scleritis when compared withrheumatoid control patients. Although notstatistically significant, peripheral neuropathy,skin ulceration, skin bruising, and spleno-megaly were all more apparent in patientswith rheumatoid episcleritis and rheumatoidscleritis than in the rheumatoid control group.

13. Sj6gren's syndrome was more evident inpatients with rheumatoid episcleritis andrheumatoid scleritis when compared withgeneral rheumatoid patients also referred tothe Centre for Rheumatic Diseases.

14. The erythrocyte sedimentation rate wassignificantly higher in patients with rheuma-toid episcleritis and rheumatoid scleritis whencompared with the rheumatoid controlpatients.

I 5. Antibodies to Toxoplasma gondii in patientswith rheumatoid episcleritis and rheumatoidscleritis showed a higher percentage of

raised titres compared with studies in normalpatients.

i6. Autoantibody studies in patients with rheu-matoid episcleritis and with rheumatoidscleritis showed little variation from resultsexpected in rheumatoid arthritis. Autoanti-body studies in patients with non-rheumatoidscleritis showed a high incidence of rheuma-toid factor (33-3 per cent) and antinuclearfactor (33-3 per cent).

17. The prognosis for life is poorer in patientswith rheumatoid disease complicated byepiscleritis or scleritis when compared withrheumatoid controls matched for age, sex,and year of presentation; 45.5 per cent ofthose with eye inflammation had died sincethe examination, compared with i8-z per centof the control group.

I 8. There is no clear evidence of any higherincidence of atopic disease in patients withnon-rheumatoid episcleritis and non-rheuma-toid scleritis as compared with the expectedincidence in a general population.

Many colleagues supported our study, and for this weexpress our warmest gratitude. A number of ophthal-mologists in the west of Scotland took interest in thestudy and referred patients to the scleritis clinic. With-out their help the investigation would have been in-complete. Dr G. B. Ludlam kindly provided data forour study of positive titres for Toxoplasma gondii. MrsHazel Hughes, Mrs Catriona Breen, and Mrs MaryMason of the Immunopathology Laboratory, Glasgow,examined sera for autoantibody studies and MissTineke Simmes gave us information regarding immuno-globulin estimations. Miss Nancy Wylie of the library,Royal College of Physicians and Surgeons, Glasgow,has been a constant help in obtaining papers and check-ing references. The illustrations for the paper werefrom the Department of Medical Illustration, SouthernGeneral Hospital (Mr R. Loudon Brown, Mr RobinEwart, and Mr Alastair Irvine), and from the TennentInstitute of Ophthalmology (Mr John Watt and MrsAnne Currie). Mr R. Clelland, Registrar of Births,Deaths and Marriages, Glasgow, obtained details ofdeath certificates for patients who had died sinceexamination.The expenses of the study were supported by two

grants, from B.D.H. Pharmaceuticals (/Jioo) andGeigy Pharmaceuticals (Cio20).

Tables VIII, XII, XVII, XVIII, XXIV, XXVII,XXVIII, are reproduced in whole or in part by kindpermission of Churchill Livingstone, Edinburgh.

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