Original Article

Prediction of response to treatment in patients with scleritis using a standardised scoring system

Peter McCluskey, MB BS, FRACO, FRACS* Denis Wakefield, MD, FRACP, FRCPA?

Abstract

Scleritis is a severe chronic inflammation of the eye wall. High-dose corticosteroids and other immunosuppressive drugs are often required to control the inflammatory process. With the development of new and potentially more effective treatment modalities for scleritis has emerged the need for an accurate and reproducible system for quantifying the severity of scleritis and evaluating the response of individual patients to treatment.

We have developed a quantitative scoring system, based on common clinical signs of scleritis, and evaluated it in 24 patients with scleritis. Our results indicate that this system is simple, rapid, reprodu- cible and useful in grading the severity of scleritis and in predicting the response of patients to systemic immunosuppressive therapy.

Key words: Quantitation, scleritis, scoring system, treatment.

Scleritis is an uncommon, severely destructive, chronic inflammatory disorder affecting the eye wall. It presents a difficult management problem,

~~

*Laboratory of Ocular Immunology, School of Pathology, University of N S W; Ophthalmology Department, St Vincent's Hospital; Ophthalmology Department, Royal Prince Aljred Hospital, Sydney, Australia. TLaboratoly of Ocular Immunology, School of Pathology, University of NSW; Department of Immunology, Prince of Wales Hospital; Uveiris Research Clinic, Sydney Eye Hospital, Sydney, Australia.

often requiring high-dose systemic corticosteroid therapy or other immunosuppressive regimens to control the inflammatory response. Recent studies by ourselves, and others, have demonstrated the effectiveness of pulse therapy with intravenous methylprednisolone and cytotoxic drugs in the treatment of scleriti~.'-~ With the advent of more effective therapy for this disease has emerged the need to develop a more efficient, reproducible system to record accurately the response of the disease to treatment. Scleritis has been classified using an anatomical system for the site of the pathology and dividing the severity of the inflam- matory response into diffuse, nodular and necrotising forms.' This system divides patients with scleritis into several different clinical groups. However, this system is not quantifiable and may lead to difficulty in assessing the progress of the disease and its response to treatment.

In our clinic we have found this anatomical system useful for classifying scleritis but of little use in accurately predicting the patient's response to treatment, particularly over relatively short periods of time. To address this problem we developed a standardised system for scoring the extent and severity of scleritis, based on common clinical signs, which can be readily quantified and recorded at each patient visit.6 The scoring system described in this paper was designed for use in all types of scleritis, except scleromalacia perforans.

We have previously reported the use of a scleritis scoring system to assess the response of scleritis to therapy.'.6 Based on our previous experience with such a system, we have made several modifications

Reprint requests: Dr P. J. McCluskey, School of Pathology, University of New South Wales, PO Box 1, Kensington, NSW 2033, Australia.

Prediction of response to treatment in patients with scleritis using a standardised scoring system 21 1

to the parameters previously used and evaluated this scleritis scoring system in 24 patients with scleritis.

The aim of this study was to determine whether our scleritis scoring system was of use in the management of patients with scleritis by predicting the risk of visual loss and the need for, and response to, systemic immunosuppressive therapy.

The scoring system The scleritis scoring system is based on eight common, easily determined clinical signs seen in patients with scleritis that we and others have recog- nised to be frequently associated with scleral inflammation

The scleritis score is calculated by the sum of the value assigned to each clinical sign (Table 1). The maximum possible score is 25. In bilateral disease, each eye is scored separately. Disease resolution is defined as a total score of 0 points. Improvement is defined as a decrease in the score by four or more points over a period of two weeks. This change in the total score is the minimum change which is able to be readily clinically detected.

The individual signs are described below.

1. Area The total area of the sclera involved by scleritis is estimated as the number of quadrants involved. The

Table 1. Scoring system for severity of scleritis Clinical feature Clinical grading Score

1 Area of

2 Tenderness 3 Nodules

4 Scleral

inflammation

Necrosis

5 Corneal Involvement

6 Anterior Chamber Cells*

7 Vitreous Cellst

8 Retinal Detachment

each quadrant (quadrants 1-4)

Absent Present AbsentlQuiescent Present Progressive AbsentlQuiescent Present Progressive no cells I 20 cellslfield >2O cellslfield no vitreous haze grade 1 or 2 haze grade 3 or 4 haze Absent Present

0-4

1

0-4 0 1 0 4 6 0 2 4 0 1 2 0 1 2 0 2

(0-4)

Improvement = a decrease in the scleritis score of 4 or more points. Resolution = a decrease in the scleritis score to zero. *adapted from Hogan er al.' tadapted from Nussenblatt er 01.'

area involved by scleral inflammation is an indicator of the degree of disturbance to the scleral vessels and is a useful parameter to aid assessment of scleritis severity. Total area is scored as one point per quadrant area.

2. Tenderness Scleritis is a painfuk disease associated with charac- teristic tenderness in all cases, except scleromalacia perforans which is excluded from this system. It is relatively difficult to grade tenderness, therefore we have devised an arbitary grading from 0 to 4, on the basis of examination findings (Table 2). Patients with grade 3 or 4 tenderness exhibit reflex withdrawal on attempted palpation, are appre- hensive to palpation and have exquisite tenderness on light palpation. Patients with grade 1 or 2 tenderness exhibit none of the apprehension which characterises the higher grades, but are tender to palpation of the globe with finger pressure suffi- cient to produce blanching of episcleral vessels or indent the sclera.

3. Nodules A common clinical feature of scleritis is the development of tender nodules in the sclera. Nodules are localised areas of scleral oedema and cellu!ar infiltration which may be obvious to gross inspection or require careful slit lamp examination to detect. The presence of one or more nodules is assigned a score of one point.

4. Necrosis Scleral necrosis is characteristic of the most severe forms of scleritis and has been associated with a higher rate of underlying systemic disease in some ~ e r i e s , ~ therefore its presence, and response to treatment, is highly significant. Careful clinical examination is necessary to detect the subtle bluish colour change characteristic of early scleral necrosis.

Table 2. Scleral tenderness ~

Score

0 1 2

3 4

- ~ ~ ~ ~

Clinical signs

no tenderness tenderness to palpation sufficient to indent the globe tenderness to palpation sufficient to blanch episcleral blood vessels exquisite tenderness to light palpation withdrawal and apprehension to attempted palpation plus exquisite tenderness to palpation

21 2 Australian and New Zealand Journal of Ophthalmology 1991; 19(3)

The colour change seen in thinning areas of the sclera is often best appreciated in natural daylight. Meticulous attention must also be paid to exami- nation of the blood vessels in involved areas to identify areas of avascularity which are associated with scleral necrosis.

The presence of scleral necrosis indicates that aggressive antiinflammatory therapy will be necessary and is scored as four points. Progression of the area of necrosis whilst receiving treatment, which is defined as an increase in the size of the area of necrosis or the development of new areas, indicates lack of disease control and is heavily weighted at six points.

Areas of necrosis which have become ‘quiescent’ in that they have begun to revascularise and heal, do not represent uncontrolled inflammation and therefore are scored as zero.

5. Corneal involvement Corneal involvement in scleritis may take several forms including: acute stromal keratitis (keratolysis), sclerosing keratitis and peripheral corneal melting (marginal corneal ulcer^).^ Scleritis which crosses the limbus and is associated with destructive keratitis is almost always associated with systemic vasculitis.’ Keratitis associated with scleritis poses a significant threat to vision and to the structural integrity of the eye. It is therefore scored as two points. Progression of keratitis either by an increase in area or development of new lesions while receiving therapy is heavily weighted at four points.

6. Anterior chamber cells Uveitis may occur in patients with scleritis. A modification of the system devised by Hogan and Kimura’ for grading the severity of anterior chamber activity is used to score the amount of activity from zero to two points according to the number of cells per slit lamp field.

7. Vitreous cells Vitreous cells and debris are scored from zero to two points using a modification of the grading system devised by N~ssenblatt .~ Significant vitreous inflammation is uncommon and usually accom- panies severe scleritis.

8. Retinal detachmenl Non-rhegmatogenous retinal and/or ciliochoroidal detachment indicates involvement of the posterior sclera and choroid. It indicates a significant

potential threat to vision and is therefore weighted at two points.

Patients and methods Patients The 24 patients with scleritis reported in this study were referred for assessment and treatment of scleritis by other ophthalmologists. Patients were examined by the authors before and during treatment and were followed up at regular intervals.

Fourteen of the patients assessed in this study were included in an earlier study.’ All 24 patients were assessed by an ophthalmologist (P McC) and a physician (DW). A detailed history and physical examination was obtained as well as appropriate investigations to ascertain the presence of an under- lying or associated systemic disease. Prior to treatment, all patients had active ocular disease and were receiving a variety of topical and systemic anti- inflammatory medications. The clinical features of the patient group are detailed in Table 3.

Scleritis score For the purpose of this study the scleritis score at presentation and the scleritis score after 12 weeks of treatment was used. The scores for each patient analysed were determined from the patients’ clinical records by modifying the previously calculated scleritis score to conform with the revised scoring system. The scleritis scores of each patient are detailed in Table 3 .

Results Patients were allocated to two groups - those with an initial scleritis score of less than 11 and those with a score of 11 or greater. The initial scleritis score for each patient was analysed to determine its ability to predict the following: patients’ age, sex, site of ocular involvement, scleral necrosis, poor response to systemic corticosteroids, need for fbrther immunosuppressive therapy, treatment side effects resulting in a change of therapy, visual loss, and the incidence of an associated systemic disease. Statistical analysis was performed using Fisher’s exact test. The patient data and the presence or absence of the clinical parameters are detailed in Table 4.

Interobserver variation in calculating scleritis scores was minimal and in the most complex cases only resulted in a variation of at most 2 points between observers (data not shown).

The results show that patients with scleritis can be divided into two groups based on their initial

Prediction of response to treatment in patients with scleritis using a standardised scoring system 213

Table 3. Clinical features of patients and scleritis Treatment score

at 12 weeks Treatment Type of Systemic Pretreatment Sex scleritis Association score Patient Age

(years)

1 17 M 2 63 M 3 11 F 4 27 M 5 54 F 6 35 F 7 67 F 8 55 F 9 35 M

10 62 M 11 57 F 12 61 M 13 29 M 14 81 F 15 79 F 16 44 M 17 43 M 18 56 F 19 45 F 20 58 F 21 64 M 22 61 F 23 33 F 24 71 F

nod dif dif

nod nod dif dif nod dif nec nod

nec p nec nec dif dif

nec p nec nec

nod p nec p nec

nec p nec p

no RA no no

PAN no RA no no no

WEG no

CROHNS SINS

no no

WEG RA

HSP NXG

SVASC SINS RP no

4 7 5 6 9 7 5 7 9 7

10 18 14 14 5 7

14 10 12 13 14 15 14 16

IVMP, NSAID IVMP, CYCLO

0s IVMP

IVMP, CYCLO 0s

IVMP IVMP IVMP

OS, IVMP IVMP, CYCLO IVMP, CYCLO IVMP, CYCLO

OS, NSAID NSAID

IVMP, CSA IVMP, MTX, CYCLO

IVMP, CYCLO os, CYCLO IVMP, CSA IVMP, CSA

OS, IMU, IVMP, CYCLO IVMP, CSA

IVMP, 6-MP

0 0 0 0 0 0 3 0 0 0 0

16 10 9 0 0

16 1 7 7 2

13 16 7

Abbreviations: dif = diffuse anterior scleritis; nod = nodular anterior scleritis; nec = necrotising anterior scleritis; p = posterior scleritis. RA =rheumatoid arthritis; PAN = polyarteritis nodosa; WEG = Wegener’s granulomatosis; CROHNS = Crohns disease; SINS = surgically induced necrotising scleritis; HSP = Henoch-Schonlein purpura; SVASC =systemic vasculitis; RP = relapsing polychondritis; NXG = necrobiotic xanthogranulomatosis. IVMP = pulsed intravenous doses of methylprednisolone; NSAID = non-steroidal anti-inflammatory drugs; CYCLO = cyclophosphamide; 0 s =oral prednisolone; 6-MP = 6-mercaptopurine; CSA = cyclosporin A; MTX = methotrexate; IMU = azathioprine.

scleritis score. When the initial score is less than 11, there is a low-risk of visual loss, a low risk of an associated systemic disease, a low risk of scleral necrosis, a high rate of response to systemic steroid therapy alone and a relatively lower requirement for other forms of immunosuppressive therapy (I’ < 0.05 for each parameter). The opposite pattern is observed in scleritis patients with an initial scleritis score of 11 or greater.

Discussion The scleritis scoring system presented here has been found to be useful in quantitating the activity of

scleritis, in following the courses of the disease and predicting its response to treatment. The use of this scoring system is easy to implement since the signs that form the basis of this system are an integral part of the ocular examination of any patient with scleritis. With practice and experience the scleritis score can be quickly and easily assessed in the clinic.

Several features of this scleritis scoring system require emphasis. Scleral tenderness is a prominent feature of scleritis and is usually the first sign to show improvement in patients treated with corticosteroids or other immunosuppressive agents. Scleral nodules, keratitis and necrosis resolve more

Table 4. Analysis of initial scleritis score and disease parameters Scleritis Number of Associated Scleral Loss of Poor steroid Drug side Need for

score patients disease necrosis vision response effects immuno-suppression

Group I

Group I1

Result of Fisher’s exact test P < 0.05 P < 0.001 P < 0.01 P< 0.001 P> 0.05 P< 0.00 1

<11 14 5 2 1 4 3 4

2-11 10 8 9 6 10 5 10

214 Australian and New Zealand Journal of Ophthalmology 1991; 19(3)

Table 5. Analysis of initial scleritis score and disease parameters Scleritis Number of Female Male Age Age Unilateral Bilateral

score patients sex sex 5 40 > 40 disease disease

< I 1 14 8 6 6 8 12 2

2 1 1 10 6 4 2 8 8 2

Group I

Group I1

Result of Fisher's exact test P>O.O5 for each parameter

slowly, as do uveitis and retinal detachment which follow a similar slower time course to resolution.

The results of this study indicate that this scleritis scoring system provides useful information in the management of patients with scleritis. Patients can be divided into two groups, with different clinical features, different visual prognosis, different responses to systemic corticosteroid treatment and requiring differing degrees of immunosuppressive therapy. Patients with a score below 11 are: unlikely to lose vision from scleritis; have a low risk of developing scleral necrosis; have a relatively low risk of an aetiologically related systemic disease; and are less likely to need systemic therapy, other than corticosteroids. Patients with an initial score of 11 or more have a higher risk of: significant visual loss; developing scleral necrosis; having an associated systemic disease; and usually require additional immunosuppressive treatment, in addition to corticosteroids to maintain disease remission.

Standardisation of clinical observations is one of the fundamental steps necessary to allow the proper scientific evaluation of treatment regimens. This scleritis scoring system allows patients with scleritis to be evaluated in a rapid and reproducible manner which is practical in a clinical setting. This study provides statistical evidence 'that this scleritis

scoring system is useful in the clinical management of patients with scleritis by allowing the clinician to make more informed treatment decisions and a more accurate prediction of response to therapy.

References 1. McCluskey PJ, Wakefield D. Intravenous pulse

methylprednisolone in scleritis. Arch Ophthalmol 1987; 105:793-797.

2. Wakefield D, McCluskey PJ. Cyclosporin therapy in severe scleritis Br J Ophthalmol 1989;73:743-746.

3. Foster CS, Forstot SL, Wilson LA. Mortality rate in rheumatoid arthritis patients developing necrotising scleritis or peripheral ulcertive keratitis. Ophthalmology 1984;91:1253.

4. Meyer AR, Watson PG, Franks W, et al. Pulsed immunosuppressive therapy in the treatment of immunologically induced corneal and scleral disease. Eye

5. Watson PG. The nature and treatment of scleral inflammation. Trans Ophthalmol SOC UK, 1982;102:257-281.

6. McCluskey PJ, Wakefield D. Current concepts in the management of scleritis. Aust N Z J Ophthalmol.

7. Watson PG. Vascular changes in peripheral destructive corneal disease. Eye 1990;4:65-73.

8. Hogan MJ, Kimura SJ, Thygeson P. Signs and symptoms of uveitis: 1 Anterior uveitis. Am J Ophthalmol

9. Nussenblatt RB, Palestine AG, Chan C, er al. Standardization of vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology 1985;92:467-471.

1987;1:487-495.

1988;16: 169-176.

1959;47: 155-170.

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