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Home , Clobetasone butyrate

Trans. aphtha I. Soc. U.K. (1981) 101,27

Clobetasone butyrate eye drops Effect on ocular inflammation and intraocular pressure

J. WILLIAMSON·, L. A. EILONt, AND S. R. WALKERt:t: From The ·Southern General Hospital. Glasgow. and the tGlaxo Group Research Limited. Greenford. Middlesex

Summary butyrate eye drops comprise a new preparation which has been investigated in two comparable, double-blind, multicentre clinical trials in patients with ocular inflammation. One study compared clobetasone butyrate with phosphate eye drops (205 patients) and the other study compared corresponding preparations containing neomycin (169 patients). There was no difference between the responses to cIobetasone butyrate and betamethasone. An excellent or good response was obtained in 73 per cent of patients treated with c1obetasone butyrate, 75 per cent with betamethasone, 69 per cent with cIobetasone butyrate formulated with neomycin, and 76 per cent with betamethasone formulated with neomycin. Patients who were known to react with a rise of intraocular pressure (lOP) to were treated with clobeta­ sone butyrate eye drops in one eye and either eye drops (6 patients) or eye drops (4 patients) in the other eye. The doses were continued for 6 weeks, or less if the lOP rose more than 10 mm Hg in one eye. All patients experienced a greater intraocular pressure rise in the eye treated with prednisolone or hydro­ . The mean changes in lOP were 9 mm Hg for prednisolone compared to 2 mm Hg for cIobetasone butyrate (P<0.05 Wilcoxon signed ranks test) and 16 mm Hg for hydrocortisone compared to 2 mm Hg for c1obetasone butyrate.

A new steroid eye preparation containing c1obetasone Patients and methods butyrate has been undergoing clinical evaluation. There Anti-inflammatory studies have been several reports of its anti-inflammatory Two multicentre, between-patient studies were carried out; one activity in the treatment of various ocular diseases: to compare eye drops containing clobetasone butyrate (0.1 per anterior uveitis (Dunne and Travers, I979); postopera­ cent) with those containing betamethasone sodium phosphate tive inflammation (Ramsell, Bartholomew, and Walker, (0.1 per cent) and the other to compare the corresponding perparations with added neomycin sulphate (0.5 per cent). 1980); allergic conjunctivitis (Frankland and Walker, in Patients were selected who required steroid (or steroid with press); episcIeritis (Lloyd-Jones, Tokarewicl, and anti-infective) eye drops for inflammatory ocular conditions. Watson, in press). Patients receiving other topical or systemic steroid therapy This paper reports on two large multicentre studies in (except oral contraceptives) were excluded. which the anti-inflammatory efficacy of c1obetasone Patients were randomly allocated to one of the prepara­ butyrate eye drops with and without neomycin has been tions. The usual dosage was two drops instilled four times a compared to that of betamethasone with and without day but this was altered by the ophthalmologist depending on neomycin respectively. The effect of c1obetasone the severity of the disease. At the first visit the inflammation butyrate on intraocular pressure has also been investiga­ was recorded as mild, moderate, or severe, and the intra­ ocular pressure was measured. The return visits were made at ted in patients who are known to react to steroid I or 2-weekly intervals when the ophthalmologist assessed the preparations with a raised intraocular pressure and this response to treatment as excellent, good, satisfactory, or poor, has been compared with the effect of hydrocortisone and and again intraocular pressure was measured. prednisolone eye drops. Intraocular pressure studies Address for reprints: Dr. J. Williamson, MD, FRCS, Two double-blind, within-patient studies were carried out. Department of Ophthalmology, Southern General Hospital, Patients were selected who were known to have elevated lOP Glasgow, GS 1 4TF after 4 to 6 weeks administration of betamethasone eye drops. These patients instilled two drops into the eye four times a :j:Present Address: Centre for Medicines Research, day; clobetasone butyrate (0.1 per cent) into one eye and 12, Whitehall, London, SWIA 2DY prednisolone (0.5 per cent) or hydrocortisone (1.0 per cent) 28 Transactions oj the Ophthalmological Society oj the United Kingdom

into the other eye. They returned to the clinic at I or 2-weekly cent of patients had an excellent or good response to intervals and at each visit lOP was measured by applanation treatment, 75 per cent with betamethasone, 69 per cent tonometry. The treatment was stopped after 6 week\>pr earlier with clobetasone butyrate with neomycin, and 76 per ir the pressure in one or both eyes had risen by more than cent with betamethasone with neomycin (Table III). The 10 mm Hg. responses were similar if the results were analysed after 7 days treatment. Also, no difference between the steroid Results treatments could be detected when the results were A I1ti-inJlammalory studies analysed according to the different diseases. 205 patients took part in the trial comparing cIobeta­ sone butyrate with betamethasone eye drops and 169 Table III A nti-inf/ammatory studies: Assessment at last visit patients in the comparison of the drops containing neomycin. Table I gives details of the patients. The Eye drops groups were well matched with respect to age, sex, and Assessment CB B CB+N B+N initial severity of the inflammation; most patients' inflammation was assessed as mild or moderate. The Per Per Per Per majority of patients had postoperative inflammation No. cent No. cent No. cent No. cent (after cataract surgery) (Table II). The mean'period of --- treatment was 29 and 28 days for cIobetasone butyrate Excellent 52 50 42 41 26 32 40 45 and betamethasone drops respectively, and 25 and 28 Good 24 23 35 34 30 37 27 31 days for clobetasone butyrate with neomycin and beta­ Satisractory 19 18 19 19 16 20 15 17 with neomycin. Poor 8 8 6 6 9 11 6 7 After treatment with cIobetasone butyrate, 73 per Inc[l~ases of more than 6 mm Hg in lOP were Table I Anti-inflammatory studies: Patient details observed in several patients during the course of the studies (Table IV). Only"three patients experienced an Eye drops CB B CB+N B+N intraocular pressure rise of over 6 mm Hg during treat­ ment with clobetasone butyrate (with or without No. o/patients: 103 102 81 88 neomycin) whereas thirteen patients showed such an increase during treatment with betamethasone (with or Sex Male 52 46 30 32 without neomycin). Female 50 55 50 55 Unrecorded I I I I Table IV Anti-inflammatory studies: Intraocular pressure Age (yrs) Average 61 60 63 63 rises Range 6-95 8-91 10-95 18-87 Eye drops Rise in Pressure Initial Mild 45 42 30 28 (mm Hg) CB B CB+N B+N assessment Moderate 39 45 38 41 Severe 16 13 13 16 6 4 0 3 2 Unrecorded 2 2 0 3 7 and over 3 10 0 3

Key: CB : clobetasone butyrate eye drops B : eye drops Intraocular pressure studies CB+N : clobetasone butyrate with neomycin eye drops Six patients (48 to 62 years) received c1obetasone B+ N : betamethasone phosphate with neomycin eye drops butyrate drops in one eye and prednisolone in the other eye. In each patient a greater rise in lOP was observed Table II A nti-injlammatory studies: Type 0/ disease in the eye receiving prednisolone (statistically signifi­ cant; Wilcoxon matched pairs signed ranks test: Eye drops Diagnosis P<0.05). The change in pressure ranged from 5 to CB B , CB+N B+N 11 mm Hg (mean 9 mm Hg) for the eyes treated with prednisolone and from -1 to 6 mm Hg (mean Postoperative inflammation 63 60 53 59 2 mm Hg) for the eyes treated with cIobetasone butyrate Squamous blepharitis 4 7 9 5 (Table V). Anterior uveitis 13 14 2 6 A further four patients (61-74 years) received cIobeta­ Vernal conjunctivitis 4 7 2 I sone butyrate drops in one eye and hydrocortisone in Episcleritis 7 3 0 3 the other. As with prednisolone drops, each patient Other 12 11 15 14 experienced a greater increase of lOP in the eye receiv­ ing hydrocortisone. The change in pressure with hydro­ Total 103 102 81 88 cortisone ranged from 11 to 20 mm Hg (mean Clobetasone butyrate eye drops 29

Table V Intraocular pressure trials: Results methasone with or without neomycin respectively. CB Comparative steroid Significantly more patients in these studies reacted with Duration of Patient an intraocular pressure rise to betamethasone than to treatment No. Rise in lOP Steroid Rise in lOP c1obetasone butyrate. This property of c1obetasone (wks) (mm Hg) (mm Hg) butyrate has been investigated in specifically designed ----- studies with patients who are known to experience a rise I 4 3 Pred. 8 in lOP with ocular steroid treatment. Clobetasone 2 5 3 Pred. II butyrate has been shown to have a lower propensity to 3 2 2 Pred. 10 raise lOP than (Dunne and Travers, Pred. 4 3 0 5 1979) and betamethasone (Ramsell and others. 1980). 5 4 6 Pred. II 6 6 -I Pred. 7 We have shown that c1obetasone butyrate also has less potential to raise lOP than prednisolone or hydrocorti­ I 4 4 Hyd. 20 sone. Thus, c1obetasone butyrate eye drops may be con­ 2 4 -1 Hyd. II sidered to be a safer steroid therapy, being as effective as 3 2 -I Hyd. 19 betamethasone drops with a lower potential to raise 4 6 4 Hyd. 14 intraocular pressure. CB -c1obetasone butyrate eye drops Pred.-prednisolone eye drops We should like to thank the following ophthalmologists who Hyd.-hydrocortisone eye drops took part in the multicentre anti-inflammatory studies and who kindly allowed their results to be presented: Dr. R. S. Bartholomew, Edinburgh; Mr. P. M. Drummond, Lincoln: 16 m m Hg) and with clobetasone butyrate from -1 to Mr. J. Dunne, Manchester; Mr. R. P. Ellis, Plymouth: Mr. H. 4 mm Hg (mean 2 mm Hg). Hardy, Ipswich; Mr. K. Jordan, Cambridge; Mr. J. L. Kennerley Bankes, London; Miss V. Mohan, Birmingham: Mrs. A. Morrison, Liverpool; Mr. A. Rahman, Birmingham; Conclusion Mr. T. G. RamselJ, Birkenhead; Mr. A. Richards, Reading; The anti-inflammatory studies showed that clobetasone Mr. C. J. Tallents, Kidderminster. butyrate eye drops with or without neomycin were as We should also like to thank Miss J. M. Scheidegger for effective in the treatment of ocular inflammation as beta- secretarial assistance.

References DUNNE, J. A., and TRAVERS, J. P. (1979) Brit. J. Ophthal .• 63, 762 FRANKLAND, A. W., and WALKER, S. R. c/in. Allergy. In press LLOYD-JONES, D .. TOKAREWICZ, A.,.and WATSON, P. G. Brit. J. Ophthal. In press RAMSELL, T. G .. BARTHOLOMEW, R. S., and WALKER, S. R. (1980) Ibid.. 64,43