42 British rournal of Ophthalmology 1995; 79: 42-45 Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and Br J Ophthalmol: first published as 10.1136/bjo.79.1.42 on 1 January 1995. Downloaded from rosacea D V Seal, P Wright, L Ficker, K Hagan, M Troski, P Menday Abstract topical and systemic anti-staphylococcal A prospective, randomised, double blind, antibiotics in addition to anti-inflammatory partial crossover, placebo controlled trial therapy. has been conducted to compare the Fusidic acid has been in clinical use since performance of topical fusidic acid gel 1962 and is particularly effective against (Fucithalmic) and oral oxytetracycline as staphylococci. It has a steroid structure but no treatment for symptomatic chronic glucocorticoid activity. A new gel preparation blepharitis. Treatment success was containing 1% microcrystalline fusidic acid judged both by a reduction in symptoms (Fucithalmic) has recently been shown to be and clinical examination before and after effective for treating acute bacterial conjunc- therapy. Seventy five per cent of patients tivitis and for reducing the staphylococcal lid with blepharitis and associated rosacea flora before surgery.5-8 were symptomatically improved by Oxytetracycline has been selected for the fusidic acid gel and 500/0 by oxytetra- treatment of patients with chronic blepharitis cycline, but fewer (35%/o) appeared to as it has both anti-inflammatory and anti- benefit from the combination. Patients staphylococcal properties.9 10 It has been with chronic blepharitis of other aetiolo- demonstrated to be effective in a controlled gies did not respond to fusidic acid gel but trial in ocular rosacea for comeal infiltrates and 25% did benefit from oxytetracycline and conjunctival hyperaemiaII and in non-ocular 300/0 from the combination. Our results rosacea for papular disease.12 These beneficial demonstrate the need to investigate effects have also been demonstrated with doxy- patients with blepharitis for concomitant cycline. 13 rosacea as they respond well to targeted We have studied the subjective and objective therapy. responses of patients with chronic blepharitis (Br_J Ophthalmol 1995; 79: 42-45) of various aetiologies treated with fusidic acid and oxytetracycline in a randomised, con- trolled prospective way. http://bjo.bmj.com/ Chronic blepharitis is a common problem but is difficult to manage because various aetiolo- gies are involved. Universal treatment cannot Materials and methods therefore be applied and, until now, specific Patients suffering from chronic blepharitis therapy has not been identified for each sub- were offered the opportunity to participate in group. Symptomatic relief remains the major this trial. The majority had taken part in a therapeutic contribution. previous study, assessing the role of staphylo- on October 2, 2021 by guest. Protected copyright. There is controversy over the role of inflam- coccal CMI in this condition, when their mation as distinct from infection, but in some symptoms and signs were tabulated in detail.2 patients the two may be interrelated. This study was designed as a prospective, Tennent Institute of Ophthalmology, Seborrhoeic disease and meibomian dysfunc- randomised, double blind, placebo controlled, Western Infirmary, tion are considered primarily inflammatory.' partial crossover group comparison trial of the 38 Church Street, Atopic keratoconjunctivitis, characterised by effect of fusidic acid and oxytetracycline to Glasgow GIl 6NT D V Seal heavy Staphylococcus aureus colonisation, give symptomatic relief. A similar protocol appears inflammatory rather than infective. for assessing symptoms and signs was used Institute of Folliculitis and ulcerative blepharitis in as before.2 Informed, written consent was Ophthalmology and 'staphylococcal' lid disease usually represent obtained from all patients with chronic Moorfields Eye Hospital, City Road, infection caused by S aureus which may be blepharitis entering the study. Exclusion London EClV 2PD complicated by cell mediated marginal kera- criteria were known hypersensitivity to fusidic P Wright titis.2 3 acid, oxytetracycline, or benzalkonium L Ficker K Hagan We have demonstrated enhanced cell chloride (preservative in Fucithalmic), simul- M Troski mediated immunity (CMI) to S aureus, but not taneous wearing of contact lenses, female to coagulase negative staphylococci (CNS), patients of child bearing potential or those who Leo Laboratories Ltd, Longwich Road, among patients with symptomatic blepharitis. were pregnant or breast feeding, concurrent Princes Risborough, We have found that coagulase negative staphy- use of prescribed anti-infective drugs, other Aylesbury, Bucks lococci represent normal commensal flora.2 4 ophthalmic complications, or severe renal HP17 9RR P Menday The pathogenic role of bacteria isolated from impairment. patients with chronic blepharitis remains con- The drugs used in this study were Correspondence to: Miss L Ficker. troversial and it is not surprising that there is Fucithalmic, a topical preparation of 1% continued debate over its treatment. Thera- in a Accepted for publication fusidic acid carbomer gel made isotonic by 5 September 1994 peutic approaches have included lid hygiene, adding mannitol, buffered to pH 5 5, and Placebo controlled trial offusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea 43 preserved with benzalkonium chloride; eyelash loss, seborrhoea, telangectasia, Fucithalmic placebo with similar gel but lack- meibomianitis, chronic inflammation of the lid ing the fusidic acid; oxytetracycline tablets margin, superficial punctate corneal epitheli- containing 250 mg oxytetracycline and oxy- opathy, and marginal keratitis. In addition, Br J Ophthalmol: first published as 10.1136/bjo.79.1.42 on 1 January 1995. Downloaded from tetracycline placebo - a matching tablet but patients were examined for the presence of lacking the oxytetracycline. Drugs were dis- rosacea with excessive blushing, thickening patched every 2 months to patients by the and vascularisation of facial skin, rhinophyma, pharmacy so that they were unaware whether papular and pustular erythema, conjunctival they were entering a placebo or active treat- hyperaemia and discharge, telangectasia of the ment phase. lid margin, chalazia, and signs of keratitis. Lid The daily dosage for fusidic acid and microbiology was not performed in this study, placebo gel was one application of one drop of as the aim was to determine the symptomatic gel 12 hourly to the inferior fornix and to the response to each of the two antibiotic treat- eyelid margins, and for oxytetracycline and ment regimens. placebo tablets it was one tablet taken 12 Data were analysed for the comparative hourly with 100 ml of water, at least 1 hour efficacy of the three active treatment regimens before meals. (fucidin, oxytetracycline, or the combination) The maximum duration of therapy was 8 relative to the two placebo phases and to one months, broken into four 2 month phases. All another using Friedman's test, followed by the patients entering the study received topical Mann Whitney U test, comparing magnitude placebo gel and placebo tablets for the first 2 of changes. This was based on the patients' month phase. In the following 2 month phase, subjective assessment of symptoms with each a randomised 50% of patients received fusidic change of treatment and the investigators' acid gel and oxytetracycline tablets, while the assessment of signs, before and after treat- other 50% received either fusidic acid gel and ment. The x2 with Yates's correction was used placebo tablets or oxytetracycline tablets and to test differences in proportions (for example, placebo gel. This was followed by a third phase responders/non-responders). All tests were two of 2 months in which all patients received tailed and statistical significance was defined as placebo medication again. In the final 2 month p<0 05. phase, the 50% of patients who had originally received a combination of both fusidic acid and oxytetracycline were randomly selected so Results that equal numbers would receive either Sixty one patients with chronic blepharitis Fucithalmic gel and placebo tablets or oxy- were recruited into this clinical trial of whom tetracycline tablets and placebo gel. The 43 (71%) completed both placebo and an remaining 50% ofpatients received a combina- active treatment phase. Thirty four patients tion ofboth fusidic acid gel and oxytetracycline completed all four phases, seven completed tablets. three phases, and two completed two phases. The trial flow diagram, for each phase, is Of 43 patients included in the analysis, 23 http://bjo.bmj.com/ illustrated below: were male and 20 were female with a mean age Placebo (Phase 1) Placebo of 56; three patients had unilateral blepharitis, Fucithalmic+ Fucithalmic or the remainder being bilateral. Twenty seven oxytetracycline (Phase 2) oxytetracycline patients were recruited from a previous study Placebo (Phase 3) Placebo of chronic blepharitis, when 116 were tested Fucithalmic or Fucithalmic+ for CMI to S of whom 11 had given aureus,2 on October 2, 2021 by guest. Protected copyright. oxytetracycline (Phase 4) oxytetracycline an enhanced CMI response. Sixteen addi- Patient compliance was expected to be high, tional patients were recruited with chronic since blepharitis is a chronic disease and blepharitis but were not tesL%., for enhance- patients are usually well motivated to partici- ment. No serious adverse reactions