BOTULINUM TOXIN FOR THE TEMPORARY TREATMENT OF INVOLUTIONAL LOWER LID ENTROPION: A CLINICAL AND MORPHOLOGICAL STUDY 1 3 l D. H. W. STEEL\ H. B. HOH , , R. A. HARRAD and C. R. COLLINS2 Bristol SUMMARY treatment and waiting lists for surgery are the norm. Purpose: A prospective study was designed to evaluate During this waiting period corneal complications may the use of botulinum toxin as a temporary treatment in occur. A variety of temporary conservative measures patients awaiting surgical repair for involutional entro­ such as lid taping and lubricant ointment are used to pion and to compare its use with lid taping. alleviate symptoms and prevent ocular complications Methods: Botulinum toxin was administered to 30 whilst awaiting surgery. A retrospective study of patients with involutional entropion (35 eyelids). senile entropion at our hospital highlighted problems These patients had all previously been using lid taping with the use of taping and an alternative temporary 1 and lubricant ointment as a temporary measure whilst treatment was sought. awaiting lid surgery. Patients' symptoms and signs were The successful use of botulinum toxin in involu­ assessed before and after toxin injection. The date of tional entropion has been reported2,3 but has not entropion recurrence was recorded. Eyelid tissue from been generally accepted as a form of treatment. A 8 patients treated with toxin and 3 control patients who pilot study confirmed that the technique was had not been given toxin was obtained after surgical acceptable to patients and produced encouraging entropion repair and examined histologically to ensure results.1 We designed a prospective study to compare the botulinum toxin had no potential detrimental the use of botulinum toxin in the temporary effects on the results of surgery. treatment of senile entropion with lid taping and Results: The toxin was simple and quick to administer. lubricant ointment. Eyelid tissue was examined after 33 35 Anatomical success was achieved in of the eyelids surgical entropion repair to assess whether there with significant improvements in symptoms and signs. were any detrimental effects on muscle histology The mean duration of action of the toxin was 12.5 which could affect the outcome of entropion surgery. weeks. Lower lid laxity was inversely correlated with duration of toxin action. There were no consistent changes in orbicularis oculi morphology after toxin MATERIALS AND METHODS injection. Thirty consecutive patients were recruited from our Conclusion: Botulinum toxin is a highly effective waiting lists over a 5 month period. This represented temporary treatment for involutional entropion with 35 eyelids with involutional entropion. Cases of few complications and no adverse effects on the results entropion due to other causes were excluded. At of surgical entropion repair. the time of listing for surgery, all these patients had been instructed on the use of lid taping and lubricant Senile or involutional entropion is a common condi­ ointment as a temporary measure whilst awaiting tion and is important both because of its potential their lid surgery. corneal complications and because of the disabling Informed consent was obtained and 20 units of symptoms it causes. Surgical repair is the definitive botulinum toxin in 0.1 ml was injected subdermally using a 27 gauge needle into the lateral part of the From: lBristo\ Eye Hospital; 2Bristol Royal Infirmary, Bristol, preseptal orbicularis so as to raise a skin bleb (Fig. 3 UK; University Malaya, Lembah Pantai, Kuala Lumpur, 1). The lateral portion of the lid was chosen to Malaysia, Correspondence to: Mr D. H. W. Steel, Bristol Eye Hospital, prevent interference with the lacrimal pump asso­ Lower Maudlin Street, Bristol BSl 2LX, UK. ciated with the medial part of the orbicularis. Eye (1997) 11,472-475 © 1997 Royal College of Ophthalmologists BOTULINUM FOR LOWER LID ENTROPION 473 The mean of 400 muscle fibre diameters (as measured along the 'minor axis'S) as well as the percentage of muscle fibre area compared with loose connective tissue was estimated for each specimen. The proportion of type 2 muscle fibres for each specimen was also recorded. RESULTS The mean duration of entropion symptoms prior to entry into the trials-was 11 months with a median of 6 months. Before Botulinum Toxin Injection Watering, foreign body sensation and discomfort were experienced by all patients despite using lid Fig. 1. Technique of botulinum toxin injection. taping and lubricant ointment. Twenty-seven Patients were evaluated for clinical symptoms and patients had inferior punctate epithelial erosions signs associated with the entropion before toxin �nd �onjunctival erythema, and 3 patients had early injection and then again 2 and approximately 10-12 mfenor corneal vascularisation. weeks after injection. �atie�ts were generally dissatisfiedwith lid taping, Symptoms of discomfort, foreign body sensation, gIvmg It a low score for the symptomatic relief watering, photophobia and blurring were graded as obtained and the acceptability of the treatment absent, mild, moderate or severe, and scored 0, 1, 2 or (Table I). 3 respectively, giving a cumulative maximum score of After Botulinum Toxin Injection 15. Patients were asked about the amount of sympto­ matic relief obtained and how acceptable they found The toxin began to take effect within 24 hours of e�ch treatment to use. These were graded on a sliding administration in all patients. Anatomical success, i.e. VIsual analogue scale from 0 (poor) to a maximum of complete resolution of the entropion, was achieved 10 (excellent). The presence or absence of conjuncti­ in 33 of the 35 eyelids (29 patients). There was a val erythema, punctate corneal staining with fluor­ significant improvement in symptoms with complete escein and corneal vascularisation was noted. resolution of all symptoms in 22 patients (Table I). The eyelid was assessed for horizontal laxity by The toxin injection was generally perceived by the measuring the amount of lateral movement of the patients to provide good symptomatic relief and be central part of the eyelid on horizontal lid traction. In an acceptable form of treatment (Table I). Twenty­ addition downward excursion of the eyelid on one patients were completely satisfied with the toxin downgaze was assessed as a measure of lower lid treatment, i.e. gave it a score of 10/10 for the amount retractor function.4 of symptomatic relief obtained and the acceptability The time at which the entropion recurred follow­ of the treatment. ing botulinum toxin was assessed from the history The mean duration of action of the toxin, i.e. time and confirmed by examination. to entropion recurrence, was 12.5 weeks (range 6-23 Paired t-tests were used to compare measurements weeks). In 3 patients (5 eyelids) in whom surgery was before and after toxin injection. contraindicated, toxin injection was repeated after the initial effect wore off. The mean duration of repeat action in this small group was 27 weeks (range 21-32 weeks). Histological Method .There was no significantchange in lower lid laxity, Lid tissue from 8 patients in the study who under­ WIth mean values of 5.9 mm before toxin injection went a Quickert's repair (transverse lid split, everting and 6.1 mm after (p = 0.21). There was an inverse sutures and horizontal lid shortening) of their entropion, after the effect of the toxin had ceased Table I. Patient scores was obtained for histological analysis. Lid tissue fro� Before After a further group of patients with entropion who had toxin toxin injectiona not been given toxin was also obtained. The blocks of injection lid t�ssue were frozen in liquid nitrogen and cryostat Cumulative symptom score (mean) 7.6 0.97 (p<O.OOl) Amount of symptomatic relief 3.1 9.3 (p<O.OOl) sectIOns were cut perpendicular to the lid margin. obtained (mean) The sections were stained with haematoxylin and Acceptability of treatment (mean) 2.3 8.8 (p<O.OOl) eosin and histochemically with myosin ATPase at pH ayv'hile the patient was being treated with lid taping and lubricant 9.5. omtment. 474 D. H. W. STEEL ET AL. correlation between horizontal lid laxity and the but again no difference could be demonstrated duration of action of the toxin which was statistically between the treated and untreated muscle (Fig. 2). significant (,2 = 0.347, p<O.OOl, Pearson's correlation Histochemical staining demonstrated a random coefficient). distribution of type 1 and type 2 fibres with a Lower lid retractor function was unaffected by the preponderance of the latter, similar to previous toxin (mean 4 mm both before and after toxin), studies of orbicularis oculi6,7 (Fig. 3). There was no except in 1 patient in whom there was a marked difference in fibre type percentages or fibre type reduction in function from 4.5 mm to 1 mm. The distribution between the control and toxin-treated retractor function returned to normal after 12 weeks. lids (Table II). There was no correlation between lower lid retractor function and duration of action of the toxin. Complications that occurred were few. One DISCUSSION patient had increased epiphora after toxin injection Botulinum toxin has been shown to be a highly secondary to bilateral punctal eversion. This effective temporary treatment for involutional entro­ returned to normal as orbicularis function returned. pion with few complications. The toxin was simple One patient experienced diplopia on dextroelevation and relatively painless to administer allowing its secondary to inferior oblique underaction. There was potential use in an outpatient setting by trained non­ no diplopia in the primary position and symptoms medical personnel. resolved in 3 weeks. Lid taping has a low patient acceptability: it is The cost of botulinum toxin is an important cosmetically unsightly, causes skin soreness and, in consideration. The current cost of one 500 unit vial our experience, elderly patients find it difficult to of botulinum toxin (Dysport, Porton Laboratories), apply.