856 Br J Ophthalmol 2000;84:856–859 Incidence of ocular side eVects of topical â Br J Ophthalmol: first published as 10.1136/bjo.84.8.856 on 1 August 2000. Downloaded from blockers in the Netherlands Luc M van Beek, RobJWdeKeizer, BettineCPPolak, Paul R Elzenaar, Nicolaas J van Haeringen, Aize Kijlstra Abstract literature. These side eVects include pseudo- Background—Several ocular side eVects ocular cicatricial pemphigoid,5 conjunctival including uveitis, have been reported keratinisation,6 and anterior uveitis.7 Although following topical â blocker treatment for anterior uveitis has been described after glaucoma and ocular hypertension. The timolol8 and betaxolol use,9 its occurrence is incidence of these side eVects was investi- best documented after metipranolol use.7 10–13 gated in the Netherlands. In three diVerent retrospective studies the Methods—A prospective observational reported incidence of metipranolol associated design was used whereby monthly ques- uveitis varied from 6/1000 patients7 to less than tionnaires were sent to all practising oph- 1.87/1000 patient years.14 15 thalmologists in the Netherlands during 3 To our knowledge, except for uveitis, no consecutive months. Questionnaires were incidence figures of ocular side eVects of topi- returned at the end of each month. Any cal â blockers are available for the general patient whose topical â blocker therapy patient population. Therefore, we undertook a was altered because of an ocular reaction observational, nationwide study to determine was noted on this questionnaire. Ophthal- the incidence of ocular side eVects, including mologists who did not return their ques- uveitis, of topical â blockers in the Nether- tionnaires were interviewed by telephone lands. This study shows that 1.5 cases of ocular at the end of the study period. The number side eVects of topical â blockers per 1000 of patients using topical â blockers was patient years can be expected. derived from drug sales figures. Results—70% (328/467) of the ophthal- mologists in the Netherlands participated Methods Department of in the study. During the 3 month study During three consecutive months (April, May, Ophthalmology, period 34 cases were reported: 15 patients June 1997) all practising ophthalmologists in Leiden University had periorbital dermatitis, in eight pa- the Netherlands received a monthly question- Medical Center, naire. Addresses of ophthalmologists were Netherlands tients eyelids and conjunctiva were af- L M van Beek fected, in seven patients the conjunctiva obtained from the Dutch Ophthalmological http://bjo.bmj.com/ RJWdeKeizer was aVected, and four patients had punc- Society (NOG) of which virtually all ophthal- tate keratitis. The calculated incidence of mologists are member in the Netherlands. At Department of ocular side eVects during topical â blocker the end of each month the questionnaires were Ophthalmology, Free therapy was 1.51 cases/1000 patient years. returned. All patients who were diagnosed as University Hospital, having ocular side eVects associated with topi- Amsterdam, Conclusion—Topical â blocker therapy is Netherlands associated with few clinically important cal â blocker use in that month, were noted on BCPPolak this questionnaire. Information about systemic ocular side eVects. No cases of uveitis were on September 26, 2021 by guest. Protected copyright. reported. diseases, patient characteristics (age, sex), â Tramedico BV, (Br J Ophthalmol 2000;84:856–859) blocker used, period of time that the â blocker Medical Department, had been used, co-medication, type of ocular Weesp, Netherlands reaction, and improvement after discontinua- P R Elzenaar Topically applied â adrenergic antagonists (â tion of the drug was reported on this question- Netherlands blockers) are the first line of treatment in naire. Ophthalmic Research primary open angle glaucoma and ocular To achieve a high response rate to our ques- Institute hypertension. Safety of topical â blockers is tionnaire, we needed a simple and unambigu- L M van Beek mainly determined by their systemic â block- ous definition of ocular side eVects of topical â N J van Haeringen ing eVects. The bronchoconstriction and car- blockers. Ocular side eVects were defined as A Kijlstra diac arrhythmias caused by topical â blockers any alteration of topical â blocker medication 1 Institute for Animal may be life threatening. However, ocular side because of an ocular reaction. Alterations that Science and Health, eVects may also necessitate discontinuation or were made because of ineYcacy of â blocker Lelystad, Netherlands changing of topical â blocker therapy. therapy were not included in this study. In the A Kijlstra Various ocular side eVects have been re- Netherlands â blockers are available only on ported after the use of topical blockers. medical prescription. Alterations that were Correspondence to: â L M van Beek, MD, Leiden Blepharoconjunctivitis, conjunctivitis, and made because of systemic side eVects of topical University Medical Center, punctate keratitis have been described in clini- â blockers fell beyond the scope of this study. Department of cal trials.2 In these trials, discontinuation of Ocular side eVects can be caused both by the Ophthalmology, PO Box 9600, 2300 RN Leiden, topical â blockers because of ocular side eVects active compound or by one of the auxiliary Netherlands ranged from 0% to 4.3%, independent of dose components in the eye drop. Because the [email protected] or which â blocker was used.34 objective of our study was to determine the Accepted for publication Other ocular side eVects have only become incidence of ocular side eVects of topical â 24 February 2000 apparent through case reports in the medical blockers as they are used in the Dutch patient www.bjophthalmol.com Incidence of ocular side eVects of topical â blockers in the Netherlands 857 population, no distinction was made between Results Br J Ophthalmol: first published as 10.1136/bjo.84.8.856 on 1 August 2000. Downloaded from reactions to the diVerent components. Information was obtained from 365 of the 467 Ophthalmologists who did not return their practising ophthalmologists in the Netherlands questionnaires were interviewed by telephone (78.2%). Of the responding ophthalmologists at the end of the three months’ study period. In 37 (10.1%) did not participate in the study for these interviews we asked whether the ophthal- various reasons. Information obtained from mologist had encountered any ocular side 328 (70.1%) ophthalmologists in the Nether- eVect of topical â blocker therapy during the lands could be used in the study. study period. If the answer was negative then During the study period we received infor- the interview was ended, if the answer was mation on 34 patients who met our definition positive the same information as with the ques- of an ocular side eVect. Mean age of the tionnaire was collected. patients was 71.3 years, there were 12 men and In the Netherlands, all sales of pharmaceuti- 22 women. Patients with ocular side eVects had cal wholesalers and pharmaceutical industries used their topical â blocker for a median time to local pharmacies are recorded. Sales figures of 14 months (range 1–144 months, Fig 1). In during the study months of all â blocking drugs 28 patients clinical improvement occurred for ophthalmic use (including all brands and after alteration or cessation of the â blocker. generics) were used to estimate the number of No follow up was available for the remaining patients using topical â blocker medication six cases. (Pharm inform BV, FI-rom, June 1997). It was No cases of uveitis were reported. Most assumed that one patient uses one vial of oph- often the eyelids were aVected (15 patients, thalmic â blocker in 1 month. 44%), these patients usually had periorbital dermatitis or blepharitis. In eight patients 160 (23%) both conjunctiva and eyelids were aVected; these patients had blepharoconjuncti- 140 vitis or periorbital dermatitis combined with conjunctivitis or conjunctival hyperaemia. Of 120 seven patients (21%) only the conjunctiva was aVected; these patients had conjunctivitis or 100 conjunctival hyperaemia. The cornea was aVected in four patients (12%); all these 80 patients had punctate keratitis. Analysis of the alterations of topical â blocker medication showed the following data 60 Time (months) Time (Fig 2). In 12 patients timolol medication was altered. In the majority of these patients (eight) 40 timolol was replaced by a preservative-free timolol formulation. Levobunolol medication 20 Median was changed in five patients. Both betaxolol http://bjo.bmj.com/ (14 months) and metipranolol medication were changed in 0 Timolol Betaxolol Levobunolol Carteolol Metipranolol four patients. Carteolol medication was β Blocker changed in three patients. In one patient the bufenolol medication was replaced by another Figure 1 Time that patients used the topical â blocker before it was altered because of ocular side eVects. For seven patients this information could not be obtained (n=27). â blocker. From the telephone inquiries it Median time the patients used their topical â blocker was 14 months (range 1–144 appeared that ophthalmologists often hold the months). preservative responsible for the occurrence of ocular side eVects. However, in five patients, on September 26, 2021 by guest. Protected copyright. who already used either preservative-free 12 timolol (four patients) or preservative-free Stopped eye medication metipranolol (one patient), ocular side eVects 10 Switched to different topical