Comparative Study of 0.1% Olopatadine Hydrochloride and 0.5% Ketorolac Tromethamine in the Treatment of Seasonal Allergic Conjunctivitis
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View metadata, citation and similar papers at core.ac.uk brought to you by CORE ACTA OPHTHALMOLOGICA SCANDINAVICA 2003 Comparative study of 0.1% olopatadine hydrochloride and 0.5% ketorolac tromethamine in the treatment of seasonal allergic conjunctivitis Volkan Yaylali, Ibrahim Demirlenk, Sinan Tatlipinar, Davut O¨zbay, Arif Esme, Cem Yildirim and Serap O¨zden Pamukkale University School of Medicine, Department of Ophthalmology, Denizli, Turkey ABSTRACT. Purpose: To compare the therapeutic effects of two ophthalmic solutions (0.1% Introduction olopatadine hydrochloride and 0.5% ketorolac tromethamine) with different Seasonal allergic conjunctivitis (SAC) pharmacological mechanisms on the clinical signs and Symptoms of seasonal or hay fever is a common allergic dis- allergic conjunctivitis (SAC). ease typically elicited by airborne aller- Methods: Forty patients with the signs and symptoms of SAC (i.e. hyperaemia, gens such as pollen, grass, weeds and itching, mucus discharge, tearing) were included in this placebo-controlled, ran- animal dander (Abelson & Schaefer domized, parallel group, single centre study. In group 1 (20 patients) one eye of 1993). It is a type 1 hypersensitivity each patient was treated with olopatadine and the other with placebo. In group 2 reaction mediated by IgE in response (20 patients) one eye of each patient was treated with ketorolac solution and the to these environmental antigens. The other with placebo. The principal signs and symptoms of SAC (hyperaemia and principal symptom of SAC is ocular itching) were evaluated at 30 mins and at 2, 7 and 15 days. itching (Abelson & Schaefer 1993). Results: In group 1, both parameters improved significantly in eyes treated with Other signs and symptoms include con- olopatadine compared with those receiving placebo at all control examinations junctival hyperaemia, tearing, mucus (all p < 0.05). Similarly, eyes treated with ketorolac showed significant reductions discharge, chemosis and lid oedema. in signs and symptoms compared with those receiving placebo (all p < 0.05). When Mast cells play an important role in the clinical parameters of eyes treated with olopatadine were compared with the pathophysiology of this condition. those treated with ketorolac, the mean score of hyperaemia was found to be When specific allergens bind to sensi- tized mast cells in the conjunctiva, lower in the olopatadine group, but the difference was not statistically significant degranulation of mast cells, and release (all p > 0.05). However, the itching score was significantly lower in the olopata- of preformed (histamine, eosinophil dine group from the second day through to the end of the study (p < 0.05). chemotactic factor, tryptase) and Conclusions: Both olopatadine and ketorolac ophthalmic solutions were found to newly synthesized mediators (prosta- be effective in alleviating the clinical signs and symptoms of SAC compared to glandins, leukotrines) occur. Hence, placebo. However, olopatadine reduces ocular itching significantly more than typical signs and symptoms of SAC ketorolac. appear. Histamine, which is a pre- formed agent, is accepted as the predom- Key words: ocular allergy – seasonal allergic conjunctivitis – olopatadine – ketorolac inant mediator (Berdy et al. 1991). On the other hand, prostaglandin D2 Acta Ophthalmol. Scand. 2003: 81: 378–382 is produced by the arachidonic acid Copyright # Acta Ophthalmol Scand 2003. ISSN 1395-3907 pathway, and has a role in the patho- genesis of SAC (Woodward et al. 1995). Prostaglandin D2 has been shown to induce conjunctival hyperaemia, oedema and mucus discharge; prostaglandins, 378 ACTA OPHTHALMOLOGICA SCANDINAVICA 2003 particularly D2 and E2, have a hyperaemia, mucus discharge and tear- Results pruritogenic effect on the conjunctiva ing) were involved in this placebo- (Woodward et al. 1995). controlled, randomized, parallel group, Of the 40 subjects, 21 were male and 19 Topically applied ophthalmic agents single centre study. All subjects had a were female. Their average age was are the principal treatment method for history of SAC over the previous 19 years (range 15–25 years). All SAC. Currently available topical drugs 2 years and showed the same classical patients completed the study. Overall include H1 antihistamines such as signs and symptoms of SAC during the topical drop application compliance levocobastine, H1 antihistamine- study period. None of the patients had was 100% in the olopatadine group vasoconstrictor combinations such as a systemic or ocular (dry eye, uveitis, and 90% in the ketorolac group (i.e. antazoline-naphazoline, mast cell stabi- viral-bacterial infection) illness, and two patients missed three applications). lizors such as cromolyn sodium and none had received systemic or topical The mean scores of the clinical para- lodoxamide, and non-steroidal anti- ocular medication during the 4 weeks meters were computed for each exami- inflammatory drugs (NSAIDs) which prior to the study. All patients started nation (Table 2). The baseline scores inhibit prostaglandin synthesis, such and completed the study within the were found to be similar in both groups as ketorolac tromethamine. Inhibition month of April in order to avoid a (p > 0.05). In group 1, both itching and of prostaglandin synthesis, including major variance in allergen counts. In hyperaemia improved significantly in prostaglandins D2 and E2, may play a our region, April is the period when eyes receiving olopatadine solution role in the treatment of SAC. Ketorolac patients with SAC display maximum compared to placebo eyes at all control is an NSAID approved in the USA for signs and symptoms, indicating a examinations (p < 0.05) (Figs 1 and 2). the relief of ocular itching associated heavy allergen exposure. Similarly, eyes receiving ketorolac solu- with SAC which works by inhibiting Group 1 comprised 20 patients. One tion showed a significant reduction in the prostaglandins’ pruritogenic effects eye of each of these patients received signs and symptoms compared to pla- on the conjunctiva. A new topical drug, olopatadine and the other eye received cebo eyes at all examinations (p < 0.05) olopatadine, has been shown to have a placebo (Tears Naturale II1, Alcon, (Figs 1 and 2). When the mean scores of dual action, in terms of both mast cell Fort Worth, TX, USA), both twice olopatadine treated eyes were com- degranulation inhibition and histamine daily. Group 2 (20 patients) used ketor- pared to the scores of ketorolac treated H1 receptor blockage (Sharif et al. olac solution in one eye and the placebo eyes, the mean scores of hyper- 1996; Yanni et al. 1996; Abelson 1998; (Tears Naturale II1, Alcon) in the fel- aemia were found to be lower in the Abelson & Spitalny 1998; Deschenes low eye, four times daily. Informed olopatadine group, indicating better et al. 1999). This agent has a rapid consent was obtained from all patients. therapeutic effectiveness, although onset due to antihistamine activity and In order to achieve better rates of com- the difference did not reach statistical prolonged duration of action due to pliance, patients were given 15-day significance (p ¼ 0.154, 0.9, 0.65, mast cell stabilization, which allows timetables indicating the control days 0.79, 0.79, for baseline, 30 mins, 2, for a twice daily dosage. and drop instillation times. Patients 7 and 15 days scores, respectively) The aim of the current study was to were asked to mark each medication (Figs 1 and 2). Itching scores, however, compare the therapeutic effectiveness of administration on these schedules and were found to be significantly lower two ophthalmic solutions (0.1% olopata- these lists were checked at each control in the olopatadine group at 2, 7 and dine hydrochloride; Patanol1 (Alcon visit. 15 days (p ¼ 0.339, 0.446, 0.018, 0.007, Laboratories, Fort Worth, TX, USA) Clinical signs and symptoms were evalu- 0.036, for baseline, 30 mins, 2, 7 and and 0.5% ketorolac tromethamine; Acu- ated at baseline, and at 30 mins and 2, 15 days, respectively) (Figs 1 and 2). lar1 (Allergan, Irvine, CA, USA) with 7 and 15 days. The main parameters different pharmacological mechanisms on assessed were ocular itching and hyperae- the clinical signs and symptoms of SAC. mia. The grading of signs and symptoms are shown in Table 1. Discussion Statistical analysis was performed Both olopatadine and ketorolac Material and Methods using the paired t-test. A p-value ophthalmic solutions were found to be < 0.05 was accepted as statistically sig- A total of 40 patients with the signs and effective in the treatment of SAC com- nificant. symptoms of SAC (ocular itching, pared to placebo. These two drugs act Table 1. Scoring of signs and symptoms of allergic conjunctivitis. Score Itching* 0 None 1 Intermittent tickling sensation, involving more than corner of eye 2 Mild, continuous itch without desire to rub 3 Severe itch with desire to rub Hyperaemia 0 None 1 Mild, slightly dilated blood vessels, pink in colour, may be quadrantal 2 Moderate, more apparent vessel dilatation, vessel colour is more intense, involves most of vessel bed 3 Severe, numerous and obvious dilated blood vessels, colour deep red, not quadrantic * Itching was scored by the patients. 379 ACTA OPHTHALMOLOGICA SCANDINAVICA 2003 Table 2. Mean itching and hyperaemia scores (SD). via different pharmacological mechan- isms. Olopatadine is a new topical ocu- Baseline 30 mins 2nd day 7th day 15th day lar dibenzoxepin derivative (Yanni et al. Itching 1996). It inhibits the release of pre- Olopatadine 2.3 (0.9) 0.4 (0.8) 0.05 (0.2) 0 0 formed and newly synthesized inflam- Placebo 2.2 (1.1) 1.3 (1.2) 1.1 (1.2) 1 (1.1) 1 (1.1) matory mediators from mast cells upon p-value 0.76 0.011 0.0001 0.0001 0.0001 allergen challenge, and also has antihis- Ketorolac 2.5 (0.5) 0.6 (0.8) 0.4 (0.6) 0.3 (0.4) 0.2 (0.4) taminic properties towards H1 recep- Placebo 2.6 (0.5) 1.8 (1.1) 1.4 (0.9) 1.4 (1.0) 1.2 (1.0) tors.