Brit. J. Ophthal. (I976) 6o, I 63 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Scleritis and

PETER G. WATSON* AND SOHAN SINGH HAYREHt From Moorfields Hospital, City Road, London*, and Addenbrooke's Hospital, Cambridge*, and the Department of , University of Iowa Hospitals and Clinics, Iowa City, USAt

From the earliest available descriptions of episcleritis Leigh, I965), subconjunctival phlegma or simple (Slade, 1838; Rognetta, i844; Desmarres, 1847) or phlegmatous by Mackenzie (I830), a confusion has existed between and and episcleritis periodica fugax by Fuchs (I895). episcleritis. This has led to contradictory views Duke-Elder and Leigh (I965) distinguished be- on the relative severity and prognosis of these tween nodular episcleritis and rheumatic episcleritis, conditions, and the erroneous belief that episcleritis but such a differentiation appears to be unjustified is accompanied by serious complications (Viswaling- as can be associated with ham, 1936; Wood, 1936; Mann and Markson, I950; either condition. We have classified episcleritis Clavel and Teulieres, 1958). While Slade (I838), into two types: Rognetta (i844), and Desmarres (I847), thought i. Simple episcleritis that episcleritis was both common and severe, 2. Nodular episcleritis. Mackenzie (i830) considered it to be neither and gave copyright. at the same time a vivid and accurate description SCLERITIS of scleritis. This confusion still persists today. In an attempt to clarify the position we have Many classifications of scleral have been been studying patients with scleritis and episcleritis proposed (Holthouse, I893; van der Hoeve, in a special clinic at Moorfields Eye Hospital 1934; Franceschetti and Bischler, I950; Duke- during the past io years. Of these, 207 patients Elder and Leigh, I965; Sevel, I967) which have (30I ) with episcleritis and 159 patients (2I7 been based on a mixture of clinical and pathological eyes) with scleritis were analysed in depth.§ The observations. Although we tried to adopt these, http://bjo.bmj.com/ results reported below have led us to conclude from the clinical point of view they have all been that scleritis and episcleritis are clinically distinct, unsatisfactory. We eventually adopted the following with a different symptomatology and prognosis classification because, although there is some slight and requiring different management. overlap between the groups, clinically we have The incidence of these conditions is not known, observed several distinct patterns. This classifica- but Williamson (1974) suggested that it was about tion has proved to be satisfactory and has enabled us to assign almost all the patients to a particular o-o8 per cent of hospital new patient referrals. Our on September 26, 2021 by guest. Protected series is from highly selected patients, all being category at the initial examination. referred from elsewhere, often where there was (a) Anterior scleritis difficulty in diagnosis, and with unusual problems. i. Diffuse scleritis This is reflected in the fact that go per cent of the 2. Nodular scleritis patients who had rheumatoid arthritis were seen 3. Necrotizing scleritis within a year of the start of the special clinic. a. with b. without inflammation (scleromalacia per- forans) Classification (b) Posterior scleritis. EPISCLERITIS Episcleritis has been recognized for over a century, Material although-,called by many different names, such as Using the above classification, patients were subconj4ctivitis by von Graefe (Duke-Elder and distributed as in Table I. §Mr B. Augier and Mrs B. Phillips of the Institute of Ophthal- mology. London, used the University of London computer to analyse the findings Normal anatomy Before Address for reprints: 22 Parkside, Cambridge, England*, or considering the criteria by which the University of Iowa, Iowa City, Iowa 52242, USAt is reached it is necessary to. 164 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

understand the normal vascular anatomy of the 3. Scleral (deep episcleral) plexus (Fig. I) outer coats of the eye. The blood vessels of the This plexus consists of a rete (criss-cross) of episclera are not easily seen in the uninflamed eye, vessels lying within the visceral layer of Tenon's but as soon as the eye becomes congested three capsule, closely applied to the . At the limbus quite separate vascular plexuses become readily the superficial and deep episcleral plexuses merge visible. into one another and terminate in the superficial marginal plexuses of the . When congested i. Bulbar conjunctival plexus (Fig. i) this layer looks bluish- in colour and is immobile. This is the most superficial plexus of fine hair-like interlacing vessels freely moveable over the under- Clinical examination lying structures. Overlying the episclera the Careful examination will determine the depth of conjunctival arteries are derived from two sources the inflammation, so that it is almost always possible the anterior ciliary arteries at the limbus, and the to decide when the patient is first seen whether palpebral branches of the ophthalmic and lacrimal scleritis or episcleritis is present. This depends on arteries. When they are inflamed the colour is accurate observation of the relationship of one bright red. layer of vessels to the other and to the underlying sclera. 2. Episcleral plexus (Fig. i) HISTORY The vessels, which are straight and radially arranged, lie in the superficial episclera (parietal A detailed clinical history is taken of the patient's layer of Tenon's capsule) at a depth of about one- ocular and systemic disorders, including family quarter to one-third of the distance between the history. Any contact with chemical irritants and surface of the and sclera (Graves, solvents is noted, as is any history of allergic 1937). The visible vessels are mainly veins, accept- conditions, rheumatic, connective-tissue or skincopyright. ing the aqueous veins at intervals around the . disease, , venereal disease, , or These vessels are moveable over the deep layers, . The site, distribution, and nature of although not so easily as the conjunctival vessels. any ocular and disturbances of vision are In the anterior episcleral plexus (anterior to the important in deciding the type of inflammation equator and over the muscle) the vessels belong to present. the anterior ciliary system; while in the posterior EXAMINATION OF THE EYE episcleral arterial plexus (posterior to the equator) http://bjo.bmj.com/ they are derived from the arteries of the oblique After the has been recorded, the muscles, the posterior ciliary arteries, and the vessels following routine of examination is used: of the sheaths (Hayreh and Baines, 1972). When inflamed, these radially arranged vessels I. External examination of the eye in daylight can easily be seen, giving the eye a salmon pink It is essential to examine a case of episcleritis in colour. daylight as this is often the only way of distin- on September 26, 2021 by guest. Protected

FIG. i Normal vascular networks of episclera. There are three layers- the-deepest is almost invisible in the uninflamed eye Scleritis and episcleritis I65 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

guishing episcleritis from the much more serious dary , and optic . Prop- scleral disease. In episcleritis the colour is salmon tosis and limitation of movement of the extraocular pink; in deep scleral disease the colour has a muscles are also looked for as evidence of an much deeper purple hue. These colour changes involvement of posterior sclera. are difficult to distinguish in tungsten or fluorescent light. After recurrent attacks of scleral inflammation SYSTEMIC EXAMINATION the sclera may become more transparent and is sometimes thinner, and as a consequence the grey As scleritis is frequently a manifestation, and may be seen through the sclera. Some- sometimes the first manifestation, of systemic times these areas are black and well defined, but disease, a thorough is impera- more often they give a faint grey tinge to the sclera. tive, special attention being paid to the joints and This is a particularly important observation in the cardiovascular system to eliminate a .* scleromalacia perforans, in which there is no sur- rounding inflammation. Time and again it is Special investigations possible to see areas of scleral thinning in daylight which were invisible with the slit-lamp or by ROUTINE STUDIES CARRIED OUT IN ALL PATIENTS illumination with tungsten or fluorescent light. i. Full blood count This included haemoglobin estimation, white blood examination cell count and differential white cell count, and 2. Slit-lamp microscopic erythrocyte sedimentation rate. Of the greatest assistance in distinguishing epi- scleritis from scleritis is the relationship of one 2. Rheumatoid arthritis latex agglutination test vascular network with another and the changes within them. The of this examination is to The Rose-Waaler sheep-cell agglutination test was object copyright. confirm the macroscopic findings. In scleritis, the used as a confirmatory test for rheumatoid factor. examination is directed to detecting scleral oedema and the involvement of scleral vessels, ignoring 3. Serum uric acid estimation the fact that the overlying episclera will be con- gested and oedematous. In episcleritis there will be no oedema of the sclera. In addition avascular 4. Serological tests for patches must be diligently searched for, as these A patient who had a positive Wassermann reaction indicate a vasculitis and carry a poor prognosis. also had the fluorescent treponemal antibody http://bjo.bmj.com/ absorption (FTA (ABS)) test, Reiter's comple- Diffuse illumination confirms the macroscopic ment-fixation test, the Venereal Disease Refer- impression that only episcleral tissue is involved, ence Laboratory (VDRL) test, and the Treponema and in addition reveals any corneal changes. pallidum immobilization (TPI) test to confirm the diagnosis of syphilis. It was recognized that some Slit-lamp examination detects the depth of maxi- cases of syphilis might have been missed as only the mum vascular involvement, infiltration, and oedema Wassermann and Kahn tests were performed as a on September 26, 2021 by guest. Protected of the episclera. Any corneal changes can be routine. In the case of any abnormal result the categorized and the anterior segment and vitreous test was repeated. scrutinized for evidence of . Red-free light examination should never be omitted; 5. X-rays of the chest and sacro-iliac joints it is the ideal method of examining the vascular These were taken changes because the vessels become more easily whether the patient had any visible. Infiltration of the episclera also shows relevant complaints or not. up as a yellow patch. Adrenaline i: IOOO or io per cent can be instilled into the con- ADDITIONAL STUDIES CARRIED OUT IN CERTAIN junctival sac. This constricts the conjunctival and PATIENTS superficial episcleral vessels more than the deep i. A full immunological survey for tissue anti- scleral plexus, thus revealing any underlying bodies, soluble immune complexes, complement, scleral disease. erythematosus cells, and antinuclear factor (ANF) were undertaken. 3. General eye examination 2. Mantoux test. 3. Electroretinograms and electro-oculograms were is to exclude as It essential complications such *r his was carried out in our clinic by the rheumatologists Dr , uveitis, pars planitis, choroiditis, secon- Fawler, Dr Hazleman, and Dr Lachmann I66 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

performed initially in all patients but later in the Within one year of the onset of this condition 92 series these were confined to patients with severe per cent had sought advice. disease and to all those with posterior scleritis. AGE AND SEX DISTRIBUTION Results Scleritis was more than I times as common in PATIENTS women as in men. This contrasted with episcleritis, which was equally common in both sexes. The data were derived from 207 patients (30I eyes) with scleritis and 159 patients (2I7 eyes) with episcleritis (Table I). i. Scieritis Analysis of the age and sex distribution for the different types of scleritis revealed distinct pat- FAMILY HISTORY terns for each type of scleritis. The diffuse and A family history was elicited in 14 patients (four nodular varieties were most prevalent. In men of these patients had simple episcleritis, three the peak incidence occurred in the fourth decade nodular episcleritis, six nodular scleritis, and (P= < o05); women showed two separate peak one diffuse anterior scleritis). In the case of the incidences, one in the third decade and another three patients with nodular scleritis the condition in the sixth decade (P=

TIME BETWEEN ONSET AND FIRST ATTENDANCE in the third to sixth decades, with a distinct peakcopyright. In contrast to episcleritis, patients with scleritis during the fourth. The condition was rare in the attended much sooner after the onset of the disease, young and the old. but even so (presumably because the onset was often insidious) many patients did not seek advice Scleritis-nodular anterior scleritis until the pain had become severe, which might The nodular disease in both sexes was most pre- not have been for several weeks. Of the patients valent from the fourth to sixth decades, but in with episcleritis I3 per cent reported in the first women there was a very marked peak during the http://bjo.bmj.com/ month and 64 per cent within two months. Of sixth decade. those with scleritis the results were very similar, 37 per cent being seen within the first month and 68 per cent before the end of the second month. Scleritis-necrotizing type with inflammation Of the patients who presented with this severe variety of scleritis the majority were women, but Table I Patients with episcleritis and scleritis whose of those who presented during the fourth decade records were analysed by computer all but one were men. on September 26, 2021 by guest. Protected Further Diagnosis Patients Eyes subdivisions Eyes Scleritis-necrotizing type without inflammation (scleromalacia perforans) Episcleritis I 59 217 Simple 170 All these patients were women. The age range Nodular 47 was 35 to 75 years, most cases occurring in the Scleritis 207 30I Diffuse anterior II9 fifth decade. Nodular anterior I34 *Necrotizing with Scleritis-posterior scleritis inflammation 29 Posterior scleritis was usually associated with a without 42 diffuse anterior inflammation I3 J scleritis, occurring most frequently Posterior 6 in women in their sixth decade, but one woman of 35 years was seen with this condition. *The incidence of necrotizing anterior scleritis is open to question because, although sometimes obvious when the patient first presents, the disease more often starts as a diffuse or nodular anterior scleritis. 2. Episcleritis Active treatment has certainly prevented some patients from de- veloping necrotic lesions. Only those patients whose diagnosis was Altogether 88 men and 71 women suffered from absolutely certain have been included in this category episcleritis. There was a significant variation in the Scleritis and episcleritis i67 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

sex distribution at different ages. The condition symptoms; in nodular episcleritis, scleritis, and was not seen in childhood. Episcleritis in men diffuse anterior scleritis the onset was much more occurred maximally from the third to the sixth gradual, the intensity of the inflammation increasing decade, with a peak in the fourth decade. In over a period of several days. The redness was women, however, although there was a peak sectorial, ranging in intensity from the barely incidence in the fourth and fifth decades, the distri- noticeable to the fiery red; the degree of inflam- bution did not show a predilection for any parti- mation bearing no relationship with the seriousness cular age group. The difference between the of the condition. Indeed, in scleromalacia perforans peak incidence in the different series was highly (necrotizing scleritis without surrounding inflam- significant (P= < o005). There was no significant mation) there might be no redness of the eye at all. difference in the sexes between the time of onset of simple and nodular episcleritis, but nodular epi- scleritis had a peak incidence in the fifth decade LACRIMATION, , AND CONJUNCTIVAL whereas simple episcleritis was most common in DISCHARGE the fourth decade (P=

Patients with nodular disease did not have more on September 26, 2021 by guest. Protected 2. Episcleritis severe symptoms than those with simple episcleritis. Of patients with episcleritis, 36-5 per cent developed Photophobia and lacrimation showed some cor- the condition in both eyes. When only one eye relation with corneal changes, but these symptoms was affected there was no significant difference in were not always due to changes within the cornea. the distribution between right and left eyes. Nodular disease occurred more commonly uni- PAIN laterally than bilaterally. The fellow eye was affected either between one and three months or after six Scleritis years. There were no exceptions to this in this This is one of the very few severely painful eye series. conditions and severe pain was complained of in 6o per cent of these patients (Table II). The pain, Symptoms which was boring in character, was either localized to the eye or generalized, in which case it radiated REDNESS from the orbital margin to the temple or the jaw Almost all patients naturally presented with in the distribution of the trigeminal nerve. Some redness of the eyes. In simple episcleritis the patients had been erroneously diagnosed as having onset was often extremely rapid, the eye becoming or sinusitis, and one patient was thought flushed within a few minutes of the onset of to have a cerebral tumour. Many other patients I68 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table II Types of pain experienced in different types of scleritis (percentage) Localized Generalized Both localized Total no. Type of scleritis only only and generalized of eyes Diffuse anterior 14 I5 30 II9 Nodular anterior 25 I6 20 134 Necrotizing anterior With inflammation 0 I5 46 29 Without inflarnmation (scleromalacia perforans) 0 13 I9 I3 Posterior 0 5 33 6 suffered mild discomfort, but as this did not the various types from their typical clinical appear- constitute one of their complaints these patients ances although, as already stated, while necrotizing are not included in the table. Pain is rarely com- scleral disease sometimes started as a nodular plained of in scleromalacia perforans, in which scleritis, its presence could usually be suspected there is no surrounding inflammation; this is in because of the severity of the symptoms. marked contrast to the pain of necrotizing scleritis, The essential diagnostic feature in scleritis was which is the severest of all, often preventing sleep the involvement of scleral tissue in the inflam- and causing severe loss of weight, and described by matory process. This usually took the form of Mackenzie (I830) more than I40 years ago scleral oedema which could be detected by observ- ['the pain . . . is pulsative and deep seated, the chief ing the outward displacement of the deep vascular pain, however, is not so much in the eyeball, as round network of the episclera (Fig. 2).

the , under the eyebrow, and in the temple, cheek Because the episclera was always swollen and copyright. and side of the nose, and is severely aggravated from congested in scleritis, scleral oedema was the sign sunset to sunrise']. which had to be looked for. The deep episcleral The pain could indeed be so severe that the eye vascular plexus was more congested than the had to be removed. superficial network, giving rise to the typical bluish-red colour. The conjunctival vessels were Episcleritis rarely involved. Severe pain is not a feature of episcleral involve- http://bjo.bmj.com/ ment. Discomfort, rarely described as pain, oc- SCLERITIS-NODULAR ANTERIOR SCLERITIS (Fig. 3) curred in 51 per cent of patients and was almost Although these patients resembled those with equally common in simple and nodular types. The nodular episcleritis on cursory examination, de- sensation in the eye was described as hot, sharp, tailed examination revealed marked differences a slight ache, or irritable. Equally the pain around and rarely presented any difficulty in diagnosis. the eye was described as an ache and, although it The nodule was deep red in colour, totally immo- sometimes radiated to the temple or jaw, it was bile and quite separate from the overlying con- never described as boring. However, very occa- gested episcleral tissues. All the vessels were lifted on September 26, 2021 by guest. Protected sionally a patient will present with severe swelling by the nodule. There was, of course, some secon- of the lids, extreme discomfort, and even dary overlying episcleritis and conjunctival con- and temporary . gestion which involved the whole anterior episclera The pain or discomfort was localized to the eye in 20 per cent (Fig. 3). Multiple nodules were seen in 25 per cent of those patients with simple epi- in 42 per cent, sometimes reaching an enormous scleritis and 33 per cent of those with nodular size; in 50 per cent they were tender. episcleritis, and was felt around the eye but not in the eye itself in only 9 per cent of those with simple episcleritis and 14 per cent with nodular SCLERITIS-DIFFUSE ANTERIOR SCLERITIS (Fig. 4) episcleritis. Both localized and generalized pain This was the most benign form of scleritis and it was experienced in i9 per cent in simple episcleritis was associated with the least severe of the associated and in io per cent in the nodular variety. general conditions. The patients might present with an eye in which the sclera was obscured by a diffuse redness and swollen episclera, which Physical signs might be accompanied in severe cases by conjunc- SCLERITIS tival oedema so severe as to obscure the cornea In the classification of scleritis which we have and protrude from between the . In these adopted it has been possible to distinguish each of patients adrenaline i :iooo had to be applied to Scieritis and episcleritis 169 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

FIG. zSlit-lamp appearances in scleritis. Sclera is swollen so that deep plexus of vessels is displacedforwards. Accompanying episcleritis causes slight separation of superficial networks

~. complications other than scieral thinning and 40 per cent suffered a deterioration of visual acuity. who were firstseen at the onset of P ~~~~~~~~~Thosepatients the disease presented with a localized patch of scleritis which was associated with acute congestion, copyright. sometimes so severe as to merit the term 'brawny' scleritis, but there was nothing in the physical -~ appearances, the aetiology or prognosis, to justify including them as a separate category. Another physical sign which must alert one to the presence of severe necrotizing scleral disease

is the avascularity of a patch of episcleral tissue http://bjo.bmj.com/ overlying or adjacent to an area of scleral oedema FIG. 3 Nodular anterior scleritis. A discrete scleral (Fig. 6). This sign was found in 27-5 per cent of nodule, displacement of deep vessels over nodule and surrounding inflammation overlying unaffected sclera are characteristic of this condition

4 the conjunctival sac so that the deep scleral on September 26, 2021 by guest. Protected network and the scleral tissue itself could be visualized, and any degree of scleral oedema deter- mined. In the less severe cases the area of redness might be confined to a small area of the globe with very little overlying congestion. The inflam- mation was more widespread than in the nodular disease, and the extent of the involvement varied from a small area (61 per cent) to the whole anterior segment (39 per cent). The vascular pattern was I occasionally grossly distorted and the normal radial pattern lost, with replacement of these vessels with abnormal tortuous new channels (Fig. 5). The eye was tender in 54 per cent of patients.

SCLERITIS-NECROTIZING SCLERITIS WITH SIGNS OF ADJACENTINFLAMMATION (Fig. 6) ~FIG. 4 Diffuse anterior scleritis. Underlying scleral This was found to be the most destructive formn of oedema could be detected only by first blanching the disease. Of these patients 6o per cent developed swollen congested episclera with i :1000o adrenaline 170 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

FIG Abnormal, tortuous vascular N'iiU. ~~~~~~~~~~~~~~channelswhich develop after recurrent attacks of diffuse anterior scieritis copyright.

had become involved (Fig. mation subsided, or was suppressed by treatment, transparent sclera remained. Complications did not -- ~~~~~~~~supervene until the inflammatory process had pro- gressed through almOst 360 degrees. Rarely the whole anterior became inflamed at one segment and http://bjo.bmj.com/ the same time, and in some of these eyes areas of occurred which, if they had not been l illtreatedurgently, would have become sequestrated, exposing the underlying . It was not, however, our experience that staphyloma (bulging of the on September 26, 2021 by guest. Protected

FIG. 6 Necrotizingr anterior scleritis. Superficially this- patient appears to be similar to those shown in Figs 4 and 5, but there is an avascular area adjacent to the limbus. If this is not treated, ulceration rapidly occurs similar to that in Fig. 7 patients with necrotizing scleritis with inflammationv and in 23 per cent of those without inflammation (scleromalacia perforans). Several types of response were noted. In some K eyes the inflammation remained localized to one small area, arid, if not checked by treatment, FIG. 7 Necrotizing anterior scleritis. Late stage of necrotizing scleritis. Inflammation is progressing resulted in almostaMost total lossls of scleral tissue from the globe, leaving an area of avascular necrotic scleraaround thatresultedreiarea. More frequentlytoequental theonfsleraminflammationtionssu startedtedf behind. Almost always these areas are crossed, as here, in one area and spread in both directions around by a large vein which drains the limbal area on a thin the globe until the whole of the anterior segment bridge of normal sclera Scleritis and episcleritis I7I Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

uvea into the scleral defect) occurred unless the circular crack, and the area inside this would take became raised above 30 mmHg on a yellowish or greyish appearance and after a and had remained high for a prolonged period. variable period would separate as a sequestrum Avascularity of a patch of overlying sclera oc- together with the overlying episciera. Large curred in 27-5 per cent of the patients. These patches abnormal vessels surrounded and crossed the area, often occurred very early in the disease, and the and where they crossed it near the limbus they condition must be treated vigorously if further left an area of about o 5 mm on either side of a necrosis is to be prevented. The eye was tender in relatively normal sclera. The resulting defect was 40 per cent of these patients. covered by a very thin layer of connective tissue which appeared to be derived from the conjunctiva. Unless the intraocular pressure rose, no staphy- SCLERITIS-NECROTIZING SCLERITIS WITHOUT loma was seen. In no case was the eve tender to ADJACENT INFLAMMATION (SCLEROMALACIA the PERFORANS) (Fig. 8) touch. This condition was associated with long-standing rheumatoid arthritis in 46 per cent of patients. SCLERITIS-POSTERIOR SCLERITIS They presented without any subjective symptoms, We were certain of the diagnosis in six cases the doctor or the patient having noticed either a (2z9 per cent), but it was suspected in several greyish or yellowish patch on the sclera or, in cases, and it was likely that others escaped our more severe cases, areas of complete loss of tissue. notice. Since there are no apparent external signs Any inflammatory change was minimal. There of posterior scleritis unless there is also an asso- was no reactive oedema because it appeared that ciated anterior scleritis, the presence of proptosis, the episcleral tissue overlying the defect had disap- exudative detachment and other fundus changes, peared, and elsewhere it was so thin as to be almost including papilloedema, may mislead the ophthal-

invisible. The number of vessels in the remaining mologist to such an extent that the correct diag- copyright. episcleral tissue also appeared to be much dimin- nosis is never made. In view of this it is possible ished, giving a porcelain-like appearance to the that the incidence of posterior scleritis may not be white of the eye when viewed from a distance. as low as indicated by the present series, as our Altogether 40 per cent of the patients had more patients were all referred from elsewhere. The con- than one necrotic patch. We had the opportunity dition was unilateral in four of the six cases. of watching some of these develop and the pattern seemed to be the same. The conjunctiva and remaining episclera might become suffused over a PRESENTING FEATURES IN POSTERIOR SCLERITIS http://bjo.bmj.com/ wide area or might remain unaltered. A demar- Symptoms. In all the patients there was extreme cation line would develop in the sclera, like a pain and tenderness. on September 26, 2021 by guest. Protected

FIG. 8 Necrotizing scleritis without inflammation (scleromalacia perforans). Almost complete dissolution of scleral collagen occurring with little if any surrounding inflammation in woman of 6o years with long-standing rheumatoid arthritis 172 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

FIG. 9 Appearance offundus after resolution of extensive serous detachment in patient with posterior scleritis who presented with diminution of vision, anterior scleritis, slight proptosis, and a diffuse leak early in dye transit on fluorescein angiography copyright.

Visual acuity. All eyes except one showed some In the early stages there was a diffuse leak early reduction in visual acuity. in the dye transit on fluorescein angiography. http://bjo.bmj.com/ Fundus changes. In four of these patients there Proptosis. Two patients presented with proptosis, was an exudative retinal detachment associated a diffuse anterior scleritis, limitation of ocular with swelling of the and an anterior movements, especially upwards, and retraction of diffuse scleritis. The anterior scleral involvement the lower lid (Fig. io) when attempting to look was minimal and had to be looked for carefully, upwards. This physical sign seemed to be specific but the retinal changes were typical. Areas of for this condition and was presumably caused by on September 26, 2021 by guest. Protected exudation occurred beneath the , giving the infiltration of both the tendons and the muscle appearance of pale greyish-white spots with a cone in the region of the posterior scleritis. surrounding dark greyish line that could be seen was also a presenting feature of posterior scleritis through the overlying serous detachment (Fig. 9). because of involvement of the muscles and tissues

FIG. IO Posterior scleritis. Retraction of left lower lid in patient with posterior scleritis who also had severe _ limitation of ocular movements. Ocular ' movements became normal with - treatment but the lid sign remained Scleritis and episcleritis 173 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

within the muscle cone by the inflammatory process. All these features returned to normal after treatment. The exudative detachment in one patient disappeared within five hours of starting treatment. The site of inflammation remained pale and white after the inflammation had disappeared, leaving some areas of pigment migration at the edges, giving the appearance of a high-water mark.

EPISCLERITIS Simple and nodular episcleritis differed in their clinical signs, but in both, the oedema or infiltration were entirely within the episcleral tissue; the sclera itself was not involved. The episcleral vascular network was maximally congested, with some FIG. 12 Nodular episcleritis. Swelling and oedema congestion of the conjunctival vessels and minimal confined to episcleral tissue and vessels retain their congestion of the scleral vessels (Fig. iI). normal architecture EPISCLERITIS-NODULAR EPISCLERITIS EPISCLERITIS-SIMPLE EPISCLERITIS In contrast with simple episcleritis the oedema and The redness of the episclera was often very intense infiltration of nodular episcleritis were localized to and was localized to one sector in 69 per cent of one part of the globe, except in seven eyes in patients and generalized in 3I per cent. The epi- which the redness was widespread. A nodule from scleral vessels, although engorged, retained their within the episcleral tissue, which was surrounded copyright. normal radial position and architecture. The by some congestion, was mobile on the underlying colour varied from fiery red to a mild red flush sclera and there was no involvement of the sclera but did not have the bluish hue so typically seen in in the oedema. The scleral plexus of vessels could scleritis. be distinguished deep to the nodule lying flat on the In simple episcleritis there was a diffuse oedema sclera, which retained its normal contour (Figs iI of the episcleral tissue which was sometimes and I2). The nodules were usually single but were infiltrated by greyish deposits which appeared sometimes multiple, reaching the size of a large pea. yellowish in red-free light. The depth of the The eye was tender to the touch in 40 per cent. http://bjo.bmj.com/ oedema and its effect on the vascular plexus was best recognized by slit-lamp examination, using a Vascular changes in the episclera narrow beam. The eye was tender to the touch in Although vascular changes were most unusual in 33 per cent of cases. episcleritis, vessels that appeared to be abnormal on September 26, 2021 by guest. Protected

FIG. i iEpiscleritis. Although deep vascular network is congested there is no scleral swelling, oedema and infiltration being confined to episclera 174 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

either in course or type were noted in i 9 eyes Table IV Fall of visual acuity in scleritis due with simple episcleritis and iO eyes with nodular to keratitis episcieritis. All these patients had had recurrent attacks at the same site for many years. One patient No. of eyes with fall in visual acuity showed avascularity of the episcleral nodule which Keratitis during follow-up to be due to the of the was thought intensity oedema, Superficial 2 as the vessels returned to normal as soon as treat- Midstromal 3 ment was given. Deep o Guttering 3 Complications Others 5 Complications of some sort were found in only I5 per cent of patients with episcleritis but ocular Keratitis complications, other than simple increased scleral SCLERITIS transparency or thinning, occurred in 57 per cent of all patients with scleritis. The complications Corneal changes of a type characteristically seen looked for and analysed were: in scleritis were observed in 29 per cent of patients. i. Fall in visual acuity This keratitis can be serious, leading to permanent 2. Keratitis changes in the cornea; these are so characteristic 3. that when certain types of sclerosing keratitis and 4. Uveitis lipid changes are seen in an eye which is otherwise 5. Glaucoma normal, it can be inferred that the patient has had 6. Scleral thinning (and scleral defects) scleritis at some time in the past. Characteristic corneal changes were seen in each type of anterior scleritis and could be classifiedcopyright. Fall in visual acuity as follows: SCLERITIS A total of 42 eyes (14 per cent) in patients with Nodular scleritis scleritis lost a significant amount of vision after i. Localized stromal keratitis the disease had been present for one year. This fall ii. Localized keratitis in visual acuity was attributed to cataract (five eyes), sclerosing anterior uveitis (two eyes), and posterior uveitis http://bjo.bmj.com/ (two eyes). The commonest reason for the fall in Diffuse scleritis visual acuity was the association with keratitis i. Acute stromal keratitis (Table IV), particularly if this was accompanied ii. Sclerosing keratitis by a uveitis. iii. Corneal guttering

EPISCLERITIS

Necrotizing scleritis on September 26, 2021 by guest. Protected No patient with episcleritis had a fall in visual i. Sclerosing keratitis acuity during the period of follow-up. ii. Keratolysis The incidence of keratitis in different types of Table III Fall of visual acuity in scleritis scleritis is given in Table V. Fall in visual acuity Total 2 lines or more during Acute stromal keratitis (Fig. I3) Type of scleritis no. of period offollow-up eyes (per cent) In the severe necrotizing scleritis of acute onset the cornea became oedematous and dense white Diffuse anterior II9 15 infiltrates appeared within the stroma (Fig. I3). Nodular anterior I34 7 These were sometimes central and sometimes Necrotizing anterior peripheral and might coalesce as the disease pro- With inflammation 29 27 gressed. If, in addition, there was anterior chamber Without inflammation activity, keratic precipitates adhered to the pos- (scleromalacia terior corneal surface. The opacity was sometimes perforans) 1I3 31 Posterior 6 50 surrounded by a 'precipitin' ring. If the scleritis was treated vigorously with full doses of steroids Scleritis and episcleritis 175 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table V Keratitis and vascularization of the cornea in scleritis Keratitis Corneal vascularization Total Type of scleritis no. of Super- Mid- Gutter- Super- Mid- eyes ficial stromal Deep ing Other ficial stromal Deep Other Diffuse anterior iI9 8 I0 2 4 4 3 2 3 2 Nodular anterior 134 6 I4 4 5 6 5 0 I 0 Necrotizing anterior With inflammation 29 4 4 2 4 3 2 I 3 0 Without inflammation (scleromalacia perforans) I3 0 3 I 3 0 I 3 2 I Posterior 6 0 0 I 0 0 0 0 0 0 Total 30I i8 3I Io i6 13 I I 6 9 3 these opacities could disappear without trace. More of the keratitis which might be complete or, more usually, however, linear opacities within the usually, the lamellae of the cornea were altered to stroma remained and, if central, these impaired leave thin linear opacities which looked exactly vision. like the sugar crystals of 'candy floss' (Fig. I4). Crystalline (candy-floss) opacities were seen in 23 patients with diffuse and another 23 patients Sclerosing keratitis (Fig. 14) with nodular scleritis, and five patients with necro- The corneal opacities associated with scleral disease tizing scleral disease. This type of corneal change copyright. usually appeared less dramatically; the cornea could not be correlated with vascularization or any adjacent to the swollen sclera became oedematous particular aetiological agent. Keratolysis was ob- and vessels grew into this oedematous area. Vascu- served in four patients, all of whom had severe larization never seemed to precede the oedema. necrotizing anterior scleritis. These opacities, once Although these opacities usually occurred close to formed, never disappear. In very severe cases the the limbus they could appear in the superficial and opacification of the cornea progressed circum- midstroma centrally in the cornea, having no ferentially until only a central clear area in the http://bjo.bmj.com/ obvious connexion with the site of the scleral cornea remained, and even this area might disap- disease. pear, resulting in a 'scleralized cornea'. Corneat Whatever the type or site of the corneal lesion, grafting was very successful in restoring the visual treatment of the scleritis brought about resolution acuity in these patients. on September 26, 2021 by guest. Protected

'FIG. 13 Acute stromal keratitis in scleritis. Dene white infiltration in cornea in same patient as in Fig. 9. Immune rings similar to those seen in Fig. 14 appeared round these lesions. AAll corneal signs, etc. disappeared after treatment 176 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

FIG. 14 Sclerosing keratitis in scleritis. A 66-year-old woman with a I3-year history of recurrent bilateral diffuse sclero-keratitis with crystalline (candy-floss)deposits in the deep stroma and a 'precipitin ring' around the infiltration at 12.0 o'clock. The vascularization is passive. Vessels enter the cornea only at site of advancing edge of corneal change and at late stage in disease. Acute stromal keratitis will progress to this if left untreated copyright.

Limbal guttering these metabolites to the limbus and it was not a product of the corneal inflammation. Guttering of the peripheral cornea was not infre- quently seen, particularly in patients who had severe long-standing rheumatoid arthritis. These Posterior corneal changes more 2 mm from the gutters never extend than http://bjo.bmj.com/ and Although we have not analysed this series for it, we limbus, but may become circumferential very have recently come to recognize another pattern thin, requiring grafting. Erosion of the deep stroma and of corneal change in scleritis (Holt-Wilson and resembling Terrien's disease may also occur, Watson, I974), which presented as an interstitial in one case this led to an expansion of the eye to i8 keratitis indistinguishable from that seen in con- dioptres of in that axis, necessitating genital syphilis but which occurred in patients over the affected region corneo-scleral grafting who had a mild scleritis and in whom the serological (Fig. I5). investigations were entirely negative (Fig. 17). on September 26, 2021 by guest. Protected Keratitis could be considered the sole reason for a Keratolysis severe fall in visual acuity in I3 eyes (4 per cent). The most severe corneal disease of all is keratolysis. was seen in four all of whom This only patients, EPISCLERITIS had very severe necrotizing scleritis, usually, but not invariably, accompanied by loss of scleral Minimal corneal changes were seen in i5 per cent tissue. In this terrifying situation the whole of the patients with simple episcleritis and in 15 stroma of the cornea disappeared with alarming per cent of those with nodular disease, but these rapidity (Fig. i6). The progress could have been were never severe. The oedema of the cornea stopped by full steroid therapy but only after very occurred when the episcleral inflammation was prolonged treatment would any corneal tissue have close to the limbus and seemed to be a consequence been re-formed. It was usual therefore to graft of this adjacent inflammation. Keratitis was most these eyes when the scleritis had become well common in the superficial and midstromal layers controlled or if rupture appeared imminent. of the cornea in both varieties. Some localized Lipid deposition occurred in areas where the corneal guttering occurred in six eyes after recur- cornea had been damaged and at the inner edge of rent attacks in the same area for many months. a long-standing corneal gutter. This was presum- Vascularization of the cornea occurred in six eyes, ably because of interference with the usual flow of the vessels being deep in three, midstromal in one, Scleritis and episcleritis I77 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

......

FIG. 15 Limbal guttering in

scleritis. A 24-year-old man with a \10\Vio-yearhistory of unilateral scleritis localized to area of sclera between 12.0 and 2.0 o'clock. Cornea in area

has become guttered and produced a

c..>f.'Terrien'-like change. This area required grafting (Fig. I9) because X. of rapidly increasing expansion of globe in this axis copyright.

worse during the course of the disease. All these

patients were between the ages of 55 and 8o years http://bjo.bmj.com/ and all had serious scleral disease. In only three patients (five eyes) with an associated long- standing anterior uveitis was it felt certain that the sclero-uveitis was responsible for the . In two of these patients it was particularly notice- able that the cataract had developed rapidly once the scleritis had involved the sclera through 360°. on September 26, 2021 by guest. Protected Three of these cataracts have required extraction. The sclero-corneal wound has healed normally after cataract extraction in spite of continuing active scleritis in the area of the wound. One FIG. I6 Keratolysis. Severe necrotizing changes in eye developed a steroid-induced cataract after both cornea and sclera which occurred in a period of five weeks in a 74-year-old woman. Systemic steroids suppressed inflammation and both cornea and sclera were grafted successfullv Table VI Keratitis in episcleritis Type of keratitis and superficial in two. No serious complications Episcleritis were found in any of the patients studied. Mid- Superficial stromal Deep Guttering Cataract Simple 7 14 3 5 SCLERITIS Nodular 2 4 I I Comeal Cataracts were detected in only 22 eyes, cent. 7 per vascularization 2 I These were bilateral and senile in type in 15 eyes. 3 o In 12 eyes the cataract was noted to have become NB Some eyes showed more than one type of keratitis I78 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

FIG. 17 Deep stromal corneal changes as seen in group of young patients with diffuse anterior scleritis. When vessels enter cornea they do so adjacent to Descemet's membrane, giving the appearance of a syphilitic interstitial keratitis copyright.

prolonged local steroid treatment. Five eyes in an anterior uveitis did occur it tended to be long- http://bjo.bmj.com/ which cataract developed also showed a severe standing and intractable. long-standing anterior uveitis. The distribution was evenly divided between unilaterally and bilaterally affected eyes. Only two patients developed a uveitis in the other, apparently EPISCLERITIS unaffected, eye. Eight patients, six of whom were over 6o years old, were found to have cataracts. However, in none of Posterior uveitis on September 26, 2021 by guest. Protected these patients did the cataract progress during the period of follow-up, nor were the cataracts worse in All the patients with posterior scleritis had posterior the eyes with episcleritis. One patient had developed uveitis, but posterior uveitis was also found in those a typical steroid cataract from prolonged local steroid who had an anterior scleritis (Table VIII). treatment before we saw him. No correlation was In two of the patients with nodular anterior found between episcleritis, uveitis, or cataract. scleritis, and in three of those with necrotizing disease, discrete areas of subretinal exudation Uveitis Table VII Anterior uveitis in scleritis SCLERITIS Anterior uveitis Anterior uveitis Type of scleritis Eyes (per cent) There was evidence of anterior uveitis in 30 per cent of all the eyes with scleritis. It was found univer- Anterior sally in those patients with scleromalacia perforans Diffuse II9 35 (Table VII). However, it did not always occur in Nodular '34 17 those with necrotizing scleritis, nor was there any Necrotizing 29 37 Scleromalacia perforans 13 100 correlation between the an particular presence of Posterior 6 66 anterior uveitis with any particular disease. When Scleritis and episcleritis I79 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table VIII Posterior uveitis in scleritis uveitis with secondary glaucoma, required other for control of the intraocular pressure. Posterior uveitis None of these patients has yet required surgery. Type of scleritis Eyes (per cent) No patient with posterior scleritis had glaucoma. One patient developed a steroid glaucoma which Anterior has required continuous medication for its control. Diffuse II9 13 Nodular I34 3 Necrotizing 29 17 EPISCLERITIS Scleromalacia perforans 13 23 Glaucoma was detected in nine eyes (4 per cent). Posterior 6 100 Two patients were known to have chronic open- angle glaucoma before the onset of the episcleritis. Five eyes had developed a steroid glaucoma from could be seen at the periphery of the fundus with a prolonged administration of local steroids. In no 'high-water mark' of retinal and subretinal oedema instance could the glaucoma be attributed to the around the patches of exudation. One patient episcleral inflammation, although there was corneal developed an annular choroidal detachment at involvement in one eye. the height of the scleritis. Scleral thinning EPISCLERITIS When the sclera looked blue in the daylight when contrasted with surrounding white sclera this was No severe uveitis occurred in this series. Mild regarded in our analysis as scleral thinning. The uveitis, detectable on the slit-lamp by an increase in the number of cells in the anterior chamber and sclera in many of these patients had become

transparent rather than thin; however, the blue copyright. a mild aqueous flare, was found in I2 eyes. In in cases in which there had two unilateral cases, flare and cells were noted in patch appeared only been active disease. The change in transparency the unaffected eye. No correlation between comeal was not apparent during the active stage of involvement and uveitis was detected. usually the disease but it was observed at the site of recur- rent simple or nodular episcleritis in I 9 eyes Glaucoma (8 per cent), and in 36-5 per cent of eyes affected with scleritis, during the period of follow-up. SCLERITIS After repeated attacks of episcleritis, particularly http://bjo.bmj.com/ Glaucoma was present in 35 eyes (iI 6 per cent), if these occurred at the same site, the sclera might of which 20 per cent showed associated keratitis. become transparent but not thin. Similarly in Of the patients with secondary glaucoma nine diffuse and nodular scleritis the sclera might had no abnormality other than scleritis, seven also become transparent with the blue choroid showing had keratitis, and six uveitis. through. This was easily seen in daylight and Secondary glaucoma often accompanies severe could be used as an indication of previous scleral anterior scleritis, the cause apparently being due inflammation. Ectasia and destruction of scleral on September 26, 2021 by guest. Protected to obstruction of the outflow channels by oedema tissue occurred only in necrotizing scleritis. This because the intraocular pressure falls and the out- could take the form of an avascular area appearing flow of aqueous rises as soon as the scleritis comes in the centre of an area of scleritis, which then under control with systemic treatment. Six patients, broke down to form a slough and eventually to who had anterior synechiae and a long-standing leave an area of thinning.

Table IX Glaucoma in scleritis Total with Primary Primary Steroid- Type of scleritis Total glaucoma open-angle closed-angle Secondary induced Diffuse anterior II9 12 6 0 6 0 Nodular anterior I34 II 6 0 5 0 Necrotizing anterior 29 8 2 0 5 I Scleromalacia perforans 13 4 0 0 4 0 Posterior 6 0 0 0 0 0

30I 35 14 0 20 I I8o British _ournal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table X Scleral thinning or transparency in scleritis Eyes with thinning Type of inflammation Total no. Total incidence of eyes Localized Generalized (per cent) Episcleritis Simple 170 I2 3 9 Nodular 47 4 0 9 Scleritis Diffuse anterior II9 23 15 32 Nodular anterior 134 35 2 28 Necrotizing anterior 29 II I0 69 Scleromalacia perforans 13 7 6 I00 Posterior 6 I 0 I6

In the type of necrotizing scleritis which pro- necrotizing disease was associated with inflamma- gressed around the globe, the area behind the tion, the episclera became avascular, overlying the advancing edge could become extremely thin, area which would eventually become sequestrated. and sometimes melted away altogether. In the Treatment at this stage would prevent sequestration. variety of necrotizing scleritis without inflammation In scleromalacia perforans sequestration might take (scleromalacia perforans), the episclera was usually place without any warning. The loss of tissue in extremely thin (Fig. 8), and the underlying sclera either condition might involve only a part of the

would become white, develop a demarcated margin, scleral thickness. copyright. and then become sequestrated. The conjunctiva and Sequestration occurred in 22 eyes (7 per cent). thin episclera overlying this process might be Loss of tissue took place in 41 per cent of eyes with slightly congested but this was by no means always necrotizing disease associated with inflammation, the case. A combination of A- and B-scan ultrasound and in 77 per cent of those without inflammation. could be used to distinguish between thinning and The rest of these eyes developed severe thinning increased transparency-A-scan being used to esti- without sequestration. Of eyes with scleral defects mate the thickness and B to locate the lesion. 59 per cent also had keratitis, although this was accompanied by a loss of corneal tissue (keratolysis) http://bjo.bmj.com/ Scleral defects (Fig. i8) in only three eyes (Fig. i6). No scleral defects developed in patients who had episcleritis or any of Scleral defects, as opposed to scleral thinning or the less severe forms of scleritis. increased scleral transparency, were seen only in the severest forms of necrotizing disease. When the Associated systemic of The incidence the various systemic conditions on September 26, 2021 by guest. Protected detected in this series is summarized in Table XI. In eyes where scleritis and episcleritis co- existed, the area of severe damage occurred where the sclera was involved, and not where the episclera was inflamed without deep involvement. We have observed, however, that the patients with herpes zoster ophthalmicus developed an episcleritis at the time of the vesicular eruption. The episcleritis disappeared as the skin condition subsided. Three patients developed a severe nodular scleritis two or three months later at the site of the original lesion. This does not imply that the episcleritis progressed to the scleritis, because there was a distinct interval between the FIG. I8 Scleral defect. Scleral defect occurring in two episodes during which the eye was apparently patient with severe necrotizing scleritis. is normal. Since making this observation we have exposed but no staphyloma occurs unless intraocular studied a further 20 patients who were not included pressure rises above 40 mmHg in this series presenting with herpes zoster ophthal- Scleritis and episcleritis I8r Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table XI Incidence of associated systemic diseases in episcleritis and scleritis Episcleritis Scleritis Disease Diffuse Nodular Necrotizing Scleromalacia Simple Nodular anterior anterior anterior perforans Posterior

Rheumatoid arthritis 5 2 8 4 3 6 0 o o I 0 0 0 0 o o 0 3 0 0 0 Systemic o 0 0 I 2 0 0 Periarteritis nodosa o 0 0 0 2 0 0 Systemic vasculitis o 0 I 0 I 0 0 Wegener's granulomatosis o 0 0 0 I 0 0 o o 0 0 2 0 0 Rheumatic heart disease 2 I I I 0 0 0 Palindromic rheumatoid o o 0 0 2 0 0 Associated with hypersensitivity disorders Erythema nodosum 0 0 0 2 0 0 0 Severe asthma or hay fever 0 0 2 0 0 0 0 Erythema multiforme I 0 0 0 0 0 0 Henoch-Schonlein purpura 0 0 0 0 0 0 Penicillin sensitivity 2 0 0 0 0 0 0

Contact dermatitis 2 I 0 0 0 0 0 copyright. After desensitization vaccination 2 0 0 0 0 0 0 I 2 0 2 0 0 0 Associated with granulomatous conditions Tuberculosis Active I 0 I 0 3 0 0 http://bjo.bmj.com/ Inactive I 2 0 0 0 0 0 Syphilis O I I 3 2 0 0 Associated with virus infection Herpes zoster 2 I 2 14 0 0 0 o 0 0 2 0 0 0 Associated with metabolic disorders on September 26, 2021 by guest. Protected Gout 6 5 2 3 0 0 0 Other associated conditions* I 0 IO 7 I 0 0 *In simple episcleritis one patient had regional ileitis In diffuse anterior scleritis Io patients had other diseases-orbital (I), essential hypertension (3), postirradiation to other eye (I), fragilitas osseum (I), thyrotoxicosis (I), degenerative osteoarthritis (2), ankylosing spondylitis (I) In nodular anterior scleritis seven patients had other diseases-for example, Cogan's syndrome (3), thyrotoxicosis (2), ophthalmia nodosa (I),. hypertension (I) One patient with necrotizing scleritis had hypertension as the only other systemic disease. There was no other evidence of a generalized systemic vasculitis micus and episcleral disease. This phenomenon of In the latter part of the series plasma protein late appearance of scleral disease was observed in estimations and electrophoresis were performed seven of the 20 patients (35 per cent). routinely in all patients with scleritis, and an im- munological survey performed by the Immunology Laboratory investigations Department of the University of Glasgow. Although these results apply only to those patients who were The various laboratory investigations carried out in seen during the last nine months of the analysis, these patients are mentioned on page i65. they are shown in Table XIII because they showed Journal of Ophthalmology I82 British Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table XII Laboratory investigations: abnormal applied. Other examinations were carried out if findings in patients indicated. Of patients in this series 42 per cent were intensively investigated by Fowler (1970), Episcleritis Scleritis who found sacro-iliac abnormalities in seven, of Test whom three had definite ankylosing spondylitis. No. (percent) No. (percent) Only one patient had symptoms which would have led to this diagnosis without specific examina- Erythrocyte sedimen- tation rate 22 I4 76 37 tion. White blood count 7 4 I4 7 Latex test for Electrodiagnostic investigations rheumatoid factor 12 7 28 I3 5 Wassermann reaction I o-6 6 3 Electro-oculograms (EOG) were performed initially Uric acid I8 II.3 14 7 in all patients; later in the series they were per- formed if the patient had severe disease or posterior scleritis. In 71 consecutive patients with episcleritis that a more sophisticated survey would reveal and scleritis presenting in the scleritis clinic, I3 evidence of immunological abnormality not re- had subnormal EOGs in the affected eye. All but vealed by routine laboratory testing. one of these patients had scleritis but this was not Of the 48 patients with scleritis, 27 (56 per cent) severe in every case. The other patients had re- had some positive result in the immunological test. current episcleritis and glaucoma. Eight patients had more than one positive result. These are presented with a control series of 30 Tissue biopsy patients matched for age and sex, with but with no scleral or uveal involvement. Biopsy of scleral tissue is not recommended unless

Of the I2 patients with a positive result in the there is great difficulty in diagnosing the eyecopyright. rheumatoid arthritis latex agglutination test, only condition or the underlying systemic disease. two had clinical rheumatoid arthritis. Episcleral biopsies were performed on three patients to try to elucidate the underlying disease. Two showed infiltration of the tissue with chronic Skin tests inflammatory cells including occasional plasma Intradermal or prick tests-inhalant, mould, fabric, cells, but no changes specific to any other disease. dusts, and pollens-were performed in 30 patients One revealed a lvmphomatous infiltration of the http://bjo.bmj.com/ with episcleritis, particularly those who gave some episclera. history of allergy. Mild reactions were detected to several agents in eight patients, but no overall Treatment (see pages i87 to I89) pattern of allergic response as judged by this response could be detected. Two patients gave a The various medical treatments given for scleritis history of a flare-up of episcleritis when in contact and episcleritis are summarized in Tables XIV with printer's ink. The results of intradermal, patch and XV. Recently oxyphenbutazone (Tanderil) and prick tests were negative, but vapour exposure ophthalmic ointment has been used in episcleritis on September 26, 2021 by guest. Protected produced flushing of the episclera. and has been the subject of a double-blind controlled trial (Watson, McKay, Clemmett, and Wilkinson, X-ray examination 1973), but it was not used in the patients in this series. X-ray examination of the chest and sacro-iliac joints was carried out routinely in all patients with Surgical treatment scleritis unless there was some contraindication. The seven-day rule with regard to ovulation was Three cataracts have required extraction in the

Table XIII Tissue antibody responses Rheumatoid Antinuclear factor Thyroid Tanned Smooth Gastric Raised Patients factor (latex) R3 antibodv RBC muscle parietal y-globulin Scleritis (48) 3 1I2 2 5 2 7 6 4 Control (30) 0 0 0 2 0 I 2 0 Scleritis and episcleritis I83 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

presence of active scleritis. No complications Enucleation followed these operations. Scleritis is a serious condition and even if fully and Four patients have had corneo-scleral grafts for carefully treated can lead to the loss of the eye, as descemetocele formation, expansion of the globe, indeed happened in three of the patients in this increasing corneal guttering, and threatened per- series. Only one of these patients was seen early in foration (Fig. I9). All have done well. the disease and she was not able to tolerate steroid Two patients were given scleral grafts to cover treatment; the eye was removed for intractable thin sclera. The graft remained in place in one; pain after the necrotizing disease had spread in the other patient the graft became involved by inexorably around the globe. The vision was pre- scleritis and eroded away, leaving the choroid served until the last area of undamaged sclera covered by a thin layer of conjunctiva. The course became involved, but then fell rapidly from 6/i8 to of the scleral disease was not influenced by the hand movements within a week. Another eye was grafting. removed because it was blind and extremelypainful. The third patient had severe keratolysis and Table XIV Treatments given in episcleritis necrotizing scleritis with loss of corneal and scleral tissue when first seen. Attempts at covering these Simple Nodular defects by grafting failed and the eye was eventually Treatment episcleritis episcleritis removed.

Not known 2 3 Follow-up Placebo 6 0 Local drops 8o 17 Of the 159 patients with episcleritis and the 207 Systemic prednisolone 2 I patients with scleritis, 146 (9i per cent) and i86 *Systemic sintisone 3 2 (go per cent), respectively, have been followed-up Systemic other steroid 0 0 during a period of between one and eight years copyright. Systemic 0 0 (mean 5-8 years). All the patients who had not Systemic oxyphenbutazone 22 2 Systemic indomethacin 2 2 attended the clinic for six months and had had the Other systemic treatment disease for at least one year were sent a question- for example, aspirin 4 naire in an attempt to determine the recurrence Local steroid with rate. Altogether 332 patients, of 366 who were systemic steroid I0 4 circularized (9I per cent), replied to the question- Local steroid with systemic naire or returned to the clinic for follow-up. oxyphenbutazone 17 9 In cases in which scleritis was seen in the initial http://bjo.bmj.com/ Local steroid with systemic stages and fully treated the recurrence rate was indomethacin 5 0 Other antibiotics 6 only 20 per cent. The recurrence rate was higher in 17 those patients with anterior diffuse scleritis than

Table XV Treatments given in scleritis on September 26, 2021 by guest. Protected Anterior Treatment Posterior Diffuse Nodular Necrotizing Scleromalacia perforans

Not known 2 7 0 0 0

Placebo 0 0 0 0 0 Local steroid 22 34 0 0 Systemic prednisolone I0 7 2 0 Systemic sintisone 7 12 0 0 0

Systemic antibiotics 0 0 0 0

Systemic oxyphenbutazone 7 5I 2 2 0 Systemic indomethacin 4 0 0

Other systemic treatment I I 0 0 0 Local steroid with systemic steroid '9 I4 7 5 2 Other systemic steroid 0 0 0 0 0 Local steroid with systemic oxyphenbutazone '7 21 5 0 2 Local steroid with systemic indomethacin 4 4 0 0 0 Other combinations 26 27 '4 3 I 184 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

FIG. I9 Overlay corneo-scleral lamellar graft on same patient as in Fig. I5 whose astigmatism was reducedfrom I5D to 6D by this procedure. Grafting only adds supporting tissue and does not affect underlying pathology

with any other variety. The recurrences were also patients, six (43 per cent) had had necrotizing more severe in scleritis than episcleritis, 6o per scleral disease, one diffuse anterior scieritis, and cent of them requiring further hospital treatment. five nodular scleritis. None of the patients withcopyright. It is important to follow up those patients with scleromalacia perforans was known to have died necrotizing disease because the disease can continue during this period, although many of these patients to progress when they are symptom-free, and they may require continuous treatment even when the disease is quiescent. Table XVI Duration of disease In episcleritis, however, each attack is self- Months Years limiting and usually clears without treatment. This Disease http://bjo.bmj.com/ has been confirmed in a double-blind controlled 6 i8 3 6 10 15 20 30 trial (Watson and others, 1973) in which each attack varied from a few hours to several days, the Episcleritis 6 35 24 I7 I I 29 0 4 average being about seven days. Episcleritis was Scleritis 10 34 24 I9 6 I 0 6 most common in the interpalpebral region, often changing from one side to the other with each attack. However, some patients always developed the Table XVII Percentage of recurrences inflammation at the same site although recurrences on September 26, 2021 by guest. Protected of both episcleritis and scleritis could occur up to Both eyes 30 years after the onset of the disease (Table XVII). Two-thirds of the patients had recurrences up to Recurrence Total Same Other Simul- At different six years after the onset of the disease, but after eye eye taneously times this the recurrence rate fell. We found that there Episcleritis 64 46 5 27 22 was often a considerable interval between the onset Scleritis 69 48 4 31 15 of the disease and the first attendance of the patient, who often came only because of apprehen- sion caused by the recurrent attacks rather than Table XVIII Severity of recurrences (per cent) the severity of the symptoms. Treatment needed Deaths (Table XIX) Disease Not At By own By self- Of the I4 patients who were known to have died severe hospital doctor medication during the period of follow-up, only two had Episcleritis 3 I 38 26 4 episcleritis. One died as a result of a road accident, Scleritis 27 6o I and the other committed suicide. Of the remaining 13 Scleritis and episcleritis I85 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Table XIX Cause of death in the I4 patients who died during the period offollow-up Patient Sex Type of scleritis General conditions Cause of death I1 Female Necrotizing Rheumatoid arthritis Coronary thrombosis Cardiovascular disease 2 Female Necrotizing Rheumatoid arthritis Bronchopneumonia 3 Male Necrotizing Diffuse connective-tissue disease Cerebral haemorrhage Chronic nephritis Hypertension 4 Female Necrotizing Hypertension Cerebral haemorrhage 5 Female Necrotizing Bronchitis Congestive heart failure Emphysema 6 Male Necrotizing Pulmonary tuberculosis Bronchopneumonia Emphysema Bronchiectasis 7 Male Diffuse anterior Gastrointestinal haemorrhage 8 Male Nodular Rheumatoid arthritis Coronary thrombosis 9 Male Nodular Myocardial infarction I0 Male Nodular Old herpes zoster ophthalmicus Myocardial infarction I I Male Nodular Old herpes zoster ophthalmriicus Myocardial infarction I2 Male Nodular Stabbed to death '3 Male Nodular Suicide I4 Male Simple episcleritis Road accident

had long-standing rheumatoid arthritis and were associated systemic disease was 42 per cent, of copyright. generally unwell at the time of their initial exami- which I5 per cent consisted of connective-tissue nation. Unfortunately three of these patients diseases. were not found for follow-up and might well have It has been suggested in the literature (Duke- died in the interim. Of those who died of natural Elder and Leigh, I965) that rheumatoid arthritis causes, 54 per cent had necrotizing disease, and is the commonest single associated condition, but it 27 per cent of the patients with severe necrotizing was found in only io per cent of our patients. scleritis were dead within eight years of the onset Scleritis also occurs in association with other of the scleritis. connective-tissue diseases-systemic lupus erythe- http://bjo.bmj.com/ Five of the patients who died were known to matosus, polyarteritis nodosa, relapsing polychon- have had diffuse connective-tissue disease; 2I per dritis, Wegener's granulomatosis-thus reflecting cent of all those with connective-tissue disease in the collagenous nature of the tissue of which the this series. Another had hypertension and, it was sclera is composed. Altogether 31 patients (15 per thought, could have had a systemic vasculitis. As no cent) were found to have manifest connective-tissue necropsy was performed this could not be confirmed. disease; in seven of these the scleritis was the presenting feature. In I9 other patients there were on September 26, 2021 by guest. Protected Discussion conditions thought to have been immunologically induced, including two who had erythema nodosum. While scleritis is an uncommon disease, accounting A total of 40 had positive latex agglutination tests for only o-o8 per cent of new referrals to eye for rheumatoid arthritis and a positive antinuclear departments (Williamson, I974), of those with the factor, and if all the immunological tests are in- necrotizing disease 21 per cent died within cluded, 72 patients (35 per cent) in the series tested eight years of the onset. The presence of scleritis had some abnormality of this type. may therefore portend serious systemic disease. It seems that necrotizing scleral disease repre- Early diagnosis may lead to early treatment of the sents a different phase of scleritis in certain patients. general condition, prolonging and probably im- In some patients who have had recurrent scleral proving the quality of life for these patients. disease for many years the scleritis has changed in In our present series 46 per cent of the patients type, coinciding with a change in the character of with scleritis had a known associated systemic the systemic disease-for example, the onset of condition. Of these, I5 per cent had definite vasculitis in rheumatoid arthritis and renal disease connective-tissue disease, confirmed by a rheuma- in systemic lupus erythematosus. In other tologist (Table XI). This incidence has recently patients the onset of disease is 'malignant' wit been confirmed in an analysis of a further 88 progressive and inexorable destruction of scler.. patients with scleritis, in whom the incidence of tissues if treatment is not adequate. The mortality i86 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

in this group is very high. Finally, there appears to found to have severe active syphilis with a positive be yet another type of scleral disease, scleromalacia cerebrospinal fluid serological result. The scleritis perforans, which is almost completely confined to disappeared when the syphilis was fully treated. women, half of whom have long-standing rheu- Altogether 14 patients had a positive Wassermann matoid arthritis. In these sequestration of the reaction in this series, seven presented with simple sclera occurs without warning and little, if any, episcleritis and the others with a diffuse anterior inflammation. This type of scleral reaction is neither and nodular scleritis. The scleritis associated with the same as that found in other forms of scleritis syphilis and tuberculosis was in no way different nor does it necessarily have the same pathogenesis. from the other forms. A biopsy is contraindicated in scleral disease The aetiology of episcleritis is even more un- because the sclera does not heal easily-a fact well certain. However, two patterns are apparent. Most known to surgeons performing detachment opera- patients have intermittent bouts of moderate or tions a few years ago when scleral surgery was the severe inflammation at intervals of one to three rule. Large scleral nodules often contain pultaceous months, lasting seven to ten days and occurring material which, if released, exposes the underlying much more commonly during the spring and choroid, but they may heal with fibrosis if left alone autumn than in the summer or winter. Only rarely (Watson, I974). Much of our knowledge of the can any certain precipitating factor be found, the underlying processes has therefore to be derived attacks usually being related to family upsets and from the few biopsy specimens which have become worries at work. Occasionally, however, a clear available, and from those eyes which have been history of exogenous sensitization is given-for enucleated for severe disease (Sevel, I967; Verhoeff example, contact with printer's inks. In one instance and King, 1958; Anderson and Margolis, 1952; the patient had only to be inside the printing works Fransois, 1970; Henkind, I974). This unfortunately for his eyes to flare up; exposure to the vapours means that we can find out little about the disease in of the ink also produced an attack under hospital most of the patients other than what can be deduced conditions, but skin tests gave negative results. i i percopyright. from their clinical examination and serological in- cent of patients with episcleritis had recurrently high vestigations. Biopsy of the episcleral lesions showed serum uric acid values (more than 6 5 mg per cent on oedema, separation ofthe episcleral fibres, infiltration three readings), and 7 per cent had clinical gout. with lymphocytes, and some cuffing of the vessels. 12 per cent also had a history of asthma and hay Henkind and Gold (I973) observed a rheumatoid fever; only one patient related the attacks to nodule in the episcleral tissue but we have not seen menstruation. Two patients developed episcleritis this. It is certain, however, that the changes typical after a desensitization vaccination. of rheumatoid nodules occur in the sclera in certain The second group of patients gave no history of http://bjo.bmj.com/ patients with necrotizing scleritis and rheumatoid periodicity but rather of mild, prolonged attacks arthritis. More typical, however, is a granulomatous of inflammation. Into this category came almost all reaction in the sclera, similar to that found else- those patients who had some other intercurrent where in the body in connective-tissue disease, the disease. Seven patients had a positive Wassermann predominant feature being fibrinoid necrosis. reaction (one with active syphilis), four had mild Similar lesions can be produced in animals with the rheumatoid arthritis with a positive rheumatoid

Schwartzmann reaction. It was probable therefore factor but only a few joint symptoms, and two had on September 26, 2021 by guest. Protected that in many cases the altered immunity in the erythema multiforme; the others had active tuber- patient was the underlying cause of this condition. culosis, Henoch-Schonlein purpura, or rosacea. The sclera is also involved in gout, in which the Herpes simplex virus has been grown from one response is due to inflammation caused by pro- lesion. The appearances of the episcleritis did teolytic enzymes released from polymorphs which not differ in these two groups, and in neither have ingested uric acid crystals. did the episcleritis progress to a scleritis except The chronic granulomatous diseases of bacterial in those patients with herpes zoster who have origin have also been quoted as a cause of scleritis already been discussed. General physical examin- (Duke-Elder and Leigh, I965). We saw only two ation and chest x-ray failed to reveal any evidence patients with active pulmonary tuberculosis and of focal sepsis. scleritis, although ancient photographs and histo- Herpes zoster involves both the cornea and logical sections make it clear that this was a much sclera. As already discussed, an episcleritis may commoner condition when tuberculosis was severe occur in the early vesicular stage of the disease, and less easily treatable. We have not knowingly disappearing completely and then presenting as a seen scleritis in association with sarcoidosis. deep localized scleritis at the site of the original Syphilis, however, can present as a scleritis. lesion some two to three months later. Alternatively Four patients have presented in this way with the the sclera may be involved early in the disease, in eye changes as their only symptom. They were which case a nodular scleritis is the rule. Scleritis and episcleritis I87 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

Clinical gout was found in five patients who be from the tissue involved in order that presented with episcleral and scleral disease, and complexes may be formed elsewhere. In 32 had raised levels of uric acid on more than one general, one would expect the antigen to occasion. The serum uric acid is a notoriously un- be found at the site of the lesion, for instance reliable test and a single positive recording should the thyroid antigen in autoimmune thyroiditis. not be taken as indicative of underlying gout. It was It should be possible to: observed that those patients with clinical gout and 2. Extract the antigen. scleral and episcleral disease had deposits of uric 3. Reproduce the disease in some experimental acid beneath the conjunctiva around the anterior animal. ciliary vessels at the plica. It was hoped that this 4. Demonstrate specific antibodies to the antigen could be used as a diagnostic sign, but deposits or specifically sensitize cells reacting with which look almost identical are frequently seen in antigen. patients whose serum uric acid is normal. We were not able to fulfil these postulates partly It could be suggested that this group of patients because of the undesirability of obtaining biopsy with episcleritis may represent the earlier stages of tissue in our patients, and because of uncertainty that a benign form of scleritis. If this was so, one would the disease produced in animals was of the same expect a significant number of cases to progress nature. However, the circumstantial evidence from from episcleritis to scleritis, but during the eight- the well-proven association with known connective- year period of follow-up we did not see this. We tissue disease is strongly suggestive that this is a did see three patients who had episcleritis in one manifestation of immune complex disease in a part and scleritis in another part of the same large number of cases. In herpes zoster ophthal- eye. However, it is an interesting and definite micus and gout the precipitating cause is known, observation that the episcleritis did not progress but until more is known about the precipitating to scleritis even during a prolonged follow-up. factors of the immune-complex disease we are not

We feel that this suggests that episcleritis and justified in making any further conclusions. copyright. scleritis are two different types of reaction to a Whatever the pathogenesis might be, we found similar antigen within the different tissues. Thus the that by careful differential diagnosis we were able fact that the episclera is involved in the course of to treat the disease appropriately and adequately the disease does not mean that the underlying so as to prevent a serious destructive change sclera would become involved, even after a long taking place in the eye. The differential diagnosis period of time. We have, as yet, no definite evidence of scleritis and episcleritis is summarized in that scleritis is an , and the Table XX. evidence presented in this paper is only circum- http://bjo.bmj.com/ stantial. Equivalents of Koch's postulates which TREATMENT need to be satisfied for auto-immune disease are as follows (Glynn, 1974): Apart from the very few patients in whom a i. There must be a specific antigen. It may not specific bacterial or viral agent could be found to

Table XX Cardinalfeatures in the differentiation of scleritis from episcleritis on September 26, 2021 by guest. Protected Episcleritis Scleritis Anterior Posterior Scleromalacia Simple Nodular Nodular Diffuse Necrotizing perforans Onset Sudden Usually Gradual Gradual Gradual Insidious Gradual sudden Redness Bright red Red Dusky red Bluish red Bluish red Very slight Variable Pain Slight Slight Moderate, Moderate, Severe, Slight, if any Severe, localized localized localized and localized and localized and localized and referred referred referred referred Photophobia and Occasionally Occasionally Occasionally Occasionally Common None Unusual lacrimation Vsacular changes Superficial Superficial Superficial and Superficial and Superficial and Avascular area Superficial episcleral episcleral deep episcleral deep episcleral deep episcleral and deep and occasionally episcleral avascular patch Chemosis Occasionally Rare Rare Common Variable Absent Common Scleral thinning or Rare Rare Common Common Common Always Rare transparency Visual acuity Normal Normal Normal Occasional loss Common loss Common loss Very common loss i88 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

have caused episcleritis or scleritis, the treatment multiple recurrences, we recommend the following is suppression of the inflammation in order to routine: relieve the discomfort and prevent the destructive changes which may accompany the inflammation. Topical medication: Any one of the following Treatment, which must be continued until the may be used: i. Prednisolone eye drops 0o5 per cent hourly disease has followed its natural course, has proved until 24 hours after the inflammation has to be effective and many eyes are being saved or from severe subsided, then reduced to three times a day prevented developing complications. for a Only three eyes (o.6 per cent) were lost-one that further four days. of a patient who could not tolerate the treatment 2. Betamethasone (Betnesol) eye ointment i per than because of the of the disease. cent four times a day during the attack, and for rather severity eye a further week after the attack has subsided. 3. Oxyphenbutazone (Tanderil) eye ointment EPISCLERITIS io per cent four times a day during the attack, and for a further week after the attack As the condition is self-limiting, harmless, and has frequently symptomless, treatment may not be subsided. necessary. Double-blind controlled studies have Systemic therapy: Occasionally patients will not res- been conducted to determine first whether any pond adequately to local therapy, in which case treatment was necessary and secondly which systemic oxyphenbutazone, indomethacin (Indocid), drugs were most effective in suppressing the or may be needed. inflammation. i. Oxyphenbutazone: 6oo mg daily in divided In this trial some patients received placebo, doses is given until there is a response. The others local steroid ointment, and the remainder dose is then reduced to 400 mg until the eye is oxyphenbutazone ointment. All the patients re- quiet and then it is stopped. This treatment covered within I0 days. Both oxyphenbutazone is given in addition to local treatment. copyright. eye ointment and betamethasone ointment ap- 2. Indomethacin: If the patient fails to make a peared to hasten the recovery by about one day, rapid recovery the drug may be changed to but the differences were not significant (Watson indomethacin I00 mg daily in divided doses, and others, 1973) (Fig. 20). and then reduced to 75 mg as soon as there is If it is felt necessary to treat the patient, either a response. A double-blind controlled study because of the symptomatology or because of just completed indicates that oxyphenbuta- zone and indomethacin are equally effective http://bjo.bmj.com/ 100. as anti-inflammatory agents, although some patients respond better to one drug than the 90 other. 80 3. : In the rare case which does .t ..'* not respond to local treatment, or systemic 70 oxyphenbutazone or indomethacin, it is justifiable to give a short, intensive course of E prednisolone or its equivalent. A suppressive on September 26, 2021 by guest. Protected t; 50 dose for this condition is 6o mg prednisolone c0 daily which, as soon as the inflammation starts E 40 to regress, can be reduced rapidly with a view $ 300, Betamethasone to withdrawing the drug entirely within one ...... Oxyphenbutazone month. 20 Placebo A double-blind controlled study was carried out 10 in these patients (Watson, Lobascher, Sabiston, Lewis-Faning, Fowler, and Jones, I966) which 0 revealed that both oxyphenbutazone and predni- 0 7 14 21 Days solone were effective, but that patients receiving systemic prednisolone had a rebound of their FIG. 20 Improvement of conjunctival and episcleral symptoms, while those having oxyphenbutazone injection in patients with episcleritis treated with remained symptom-free. either placebo, oxyphenbutazone ointment or betamethasone i per cent ointment. Although those treated with active substances improved slightly faster, SCLERITIS 8o per cent of those receiving placebo had recovered by Because of the depth and severity of the inflam- 2I days mation local steroid treatment is ineffective. Drops Scleritis and episcleritis I89 Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

or ointment are soothing and reduce the inflam- after which time they rapidly regress. As soon as mation but are not sufficient to control the scleritis. the condition is brought under control the dosage As a result of our experience we have come to can be dropped within a week to a maintenance the conclusion that the following regimen of level which is usually between io and 20 mg treatment is the most likely to be effective: prednisolone daily. Cautious reduction from this As soon as scleritis is diagnosed: level usually enables the patient to be taken off the Systemic oxyphenbutazone 6oo mg daily in drug or to be maintained with another anti-inflam- divided doses for four days, followed by 400 mg matory agent within three to four weeks. In patients daily until the condition is suppressed. This dosage who have been unable to tolerate, or have failed to is continued for one week after all symptoms have respond to, prednisolone, occasionally a response subsided. Or can be obtained with Sintisone (prednisolone Systemic indomethacin I00 mg daily in divided 2I-stearoylglycolate), eight tablets (each tablet doses, reduced to 75 mg daily in divided doses as soon containing o-63 mg) daily in divided doses (Hayreh as there is a response. Treatment is continued until and Watson, I970). Why this preparation is so the condition has been quiescent for seven days. effective is uncertain, but we have several patients These two drugs appear to be more effective who have to be maintained on it rather than on the than any of the other anti-inflammatory agents in conventional steroids. general use-for example aspirin, (Bru- fen), etc. Surgery Surgery is very rarely necessary in scleral disease. Local steroids Provided the condition is seen early and treated Usually prednisolone or betamethasone can be vigorously, scleral necrosis can be largely prevented. given in addition. Comeal grafting has had to be performed in four patients because of threatened perforation, an copyright. Subconjunctival steroids are not recommended in expanding globe, for peripheral corneal guttering, scleritis and for descemetocele. The corneal grafts have taken well and in all cases the scleritis has become We have seen two patients in whom extreme less severe after this was done. thinning has occurred at the site of a subconjunc- Many reports appear in the literature of scleral tival injection of steroid (Watson, I974; Fraun- grafting for scleromalacia perforans (Holthouse, It is not certain whether it felder and Watson, 1976). I893; Ashton and Hobbs, 1952; Torchia, Dunn, http://bjo.bmj.com/ is the vehicle in which the steroid is contained or Pease, I968; Vancea, Vancea, Jalobceastii, Colev, the steroid itself which is the irritating factor. We and Calin, 1971; Sevel and Abramson, 1972; and have from time to time given intraorbital steroid others). This has been necessary in only two patients injections in patients unable to take steroid syste- in this series-neither of whom could tolerate mically. The effect is transient and the injections steroids. In both patients the graft took well. have to be repeated weekly to be effective. Most In one the whole necrotic area was removed and patients will not tolerate this regimen and so it is the residual area of scleral inflammation could be not satisfactory for routine use. controlled with local steroids and oxyphenbutazone on September 26, 2021 by guest. Protected systemically. In the other the necrotizing process Systemic corticosteroids continued from the edge of the scleral overlap and the eye was eventually lost, no other medical If the scleritis is very severe, and does not respond treatment being tolerated. to the oxyphenbutazone or indomethacin within a We consider scleritis to be a medically treatable week, or if any avascular areas appear in the condition, and provided the dosages of the drugs episclera, systemic steroids must be given in heavy are adequate to suppress the inflammatory change, suppressive doses. The sclera is avascular and high the condition will be controlled. In this we disagree concentrations are required to produce a thera- with Sevel and Abramson (1972) and Aronson and peutic effect. Elliott (I974). We feel our results justify our claim.

Systemic prednisolone Summary 8o mg a day in divided doses is usually sufficient The data from I59 patients (217 eyes) with epis- as an initial dose. If it is effective the response is scleritis and 207 patients (30I eyes) with scleritis dramatic; although there is little change in 24 have been investigated in detail and the results hours or even 48 hours, the pain disappears. The analysed with the help of a computer. Of these eye signs may not improve for a further 48 hours, patients, 9I per cent were followed-up during a o90 British Journal of Ophthalmology Br J Ophthalmol: first published as 10.1136/bjo.60.3.163 on 1 March 1976. Downloaded from

period of one to eight years. A new classification 21 per cent of these patients were among those that is presented which is as follows: died. It is probable that necrotizing scleritis Episcleritis (217 eyes) represents the eye changes of the malignant phase of Simple episcleritis (170 eyes) systemic connective-tissue disease. Nodular episcleritis (47 eyes) Treatment is unnecessary in episcleritis but in Scleritis (30I eyes) scleritis systemic treatment with anti-inflammatory Diffuse anterior scleritis (i I9 eyes) agents or corticosteroids is obligatory. Using these Nodular anterior scleritis (134 eyes) routines of treatment only three patients (o-6 Necrotizing scleritis (42 eyes). Of these, 13 were per cent) have lost an eye. regarded as scleromalacia perforans. Apart from ourselves, the following have worked in Posterior scleritis (6 eyes) the Scleritis Clinic during the past io years: A. Atkinson, P. Awdry, P. E. Cleary, R. S. Clemett, P. Fowler, The diagnosis is based on an exact clinical A. Freedman, B. Hazleman, P. Henderson, A. D. examination which is fully described. Holt-Wilson, D. Jones, S. Lachmann, D. Lloyd-Jones, Episcleritis has been shown to be a benign D. Lobascher, A. J. Lyne, and D. A. R. Mackay, and recurring condition, a mild keratitis being the only we would like to thank them all for their help and occasional complication. Episcleritis does not ideas. We are sure many of these ideas are incorporated progress to scleritis, except in the case of herpes in this article but it is impossible to acknowledge them zoster which sometimes starts as an episcleritis properly because we have forgotten where they origi- with the vesicular stage of the eruption, to reappear nated. We should also like to thank all those surgeons three months later as a scleritis in the same site. who have referred patients to us: without them there clear conclusions could would be no clinic. No be drawn as to the The computer analysis was completed at the Institute aetiology of episcleritis. of Ophthalmology and many of the illustrations were Scleritis is always accompanied by episcleral

reproduced there; the rest were done in the Medicalcopyright. inflammation which must be ignored in making Illustration Department of Addenbrooke's Hospital, the diagnosis. Scleritis is a much more severe disease Cambridge. than episcleritis, leading to loss of visual acuity Figs 6 and I4 were reproduced from the Transactions from corneal changes, uveitis, cataract, or retinal of the Ophthalmological Society of the United Kingdom; detachment if not treated. Necrotizing scleritis with Fig. i6 from Connective-tissue disease in the eye, in inflammation is the severest form of the disease Recent Advances in Ophthalmology, ed. P. Trevor-Roper, cent of the published by Blackwell; and Fig. 20 from the British and 2I per patients with this condition Journal of Ophthalmology. died within the eight-year-period of follow-up. Last but not least we should like to thank all those http://bjo.bmj.com/ Connective-tissue disease was the commonest who have at various times typed part or all of this associated general condition; the incidence of manuscript, in particular Mrs J. Field and Mrs J. necrotizing scleritis was higher in this group and McCombie.

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MANN, W. A., and MARKSON, D. E. (1950) Amer. J7. Ophthal., 33, 459 ROGNETTA, A. (I844) 'Traite philosophique et clinique d'ophtalmologie', p. 275. Paris SEVEL, D. (I967) Amer. J3. Ophthal., 64, 1125 , and ABRAMSON, A. (1972) Brit. J. Ophthal., 56, 791 SLADE, j. (I838) 'Ophthalmia', p. 23. London TORCHIA, K. T., DUNN, R. E., and PEASE, P. J. (I968) Amer. J. Ophthal., 66, 705 VANCEA, P., VANCEA, P.-P., JALOBCEASTII, L., COLEV, G., and CALIN, A. (197I) Arch. Ophtal. (Paris), 3I, 687 VAN DER HOEVE, J. (I934) Arch. Ophthal. (Chicago), II, iii VERHOEFF, F. H., and KING, R. J. (1938) Arch. Ophthal., 20, 10I3 VISWALINGHAM, A. (1936) Brit. 7. Ophthal., 20. 449 WATSON, P. G. (I974) Trans. ophthal. Soc. UK, 94, 773 , LOBASCHER, D. J., SABISTON, D. W., LEWIS-FANING, E., FOWLER, P. D., and JONES, B. R. (I966) Brit. Y. Ophthal., 50, 463 , MCKAY, D. A. R., CLEMETT, R. S., and WILKINSON, P. (1973) Ibid., 57, 866 WILLIAMSON, J. (I974) Trans. ophthal. Soc. UK, 94, 742 WOOD, D. J. (1936) Brit. Y. Ophthal., 20, 5IO copyright. http://bjo.bmj.com/ on September 26, 2021 by guest. Protected