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      Topical Nonsteroidal Anti-Inflammatory Therapy in Ophthalmology


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          Topically applied nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management and prevention of ocular inflammation and cystoid macular edema related to cataract surgery and the maintenance of mydriasis during cataract surgery. Other common uses are the reduction of discomfort after refractive surgery or in allergic conjunctivitis. NSAIDs primarily act as cyclooxygenase inhibitors and thus reduce the formation of endogenous PGs. Today, several NSAIDs are commercially available: diclofenac, flurbiprofen, indomethacin, ketorolac and suprofen. At present the ophthalmologist has to make a decision between the use of topical corticosteroids, with their potential adverse effects, or of topical NSAIDs, with their possibly increased benefit, unknown effect on ocular pressure, wound healing and corneal tissue, higher costs and limited track record. However, the improvement of surgical techniques might support an increasing use of NSAIDs in the future. Preoperative anti-inflammatory treatment should be considered in eyes at a higher risk of developing severe postoperative inflammatory reactions. This decision has to be made carefully and has to be guided by the clinical circumstances, the spectrum of diagnosis and the individual benefit-risk ratio of each patient.

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          Most cited references25

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          Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs.

          To report corneal complications associated with topical nonsteroidal anti-inflammatory drugs (NSAIDs). Retrospective, noncomparative interventional case series. Eighteen eyes of 16 patients with adverse corneal events associated with NSAID use. Evaluation of 16 patients referred for management of corneal complications during use of topical NSAIDs (ketorolac tromethamine [Acular], diclofenac sodium [Voltaren], diclofenac sodium [Falcon DSOS]). Type and severity of corneal complications. Of the 16 patients, two experienced severe keratopathy, three experienced ulceration, six experienced corneal or scleral melts, and five experienced perforations. Eleven patients had recent cataract surgery; nine of these were on concurrent topical steroids and antibiotics. Another patient who did not have recent surgery was using concurrent topical steroids without antibiotics for sarcoid uveitis. Systemic associations included two patients with rheumatoid arthritis, one patient with asymptomatic Sjogren's syndrome, and two with rosacea. Topical NSAIDs were associated with corneal complications in 18 eyes of 16 patients. Potential risk factors include conditions that predispose the patient to corneal melting, concurrent topical steroids, and epithelial keratopathy in the early postoperative period.
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            Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema.

            To evaluate the efficacy of ketorolac tromethamine 0.5% ophthalmic solution, prednisolone acetate 1.0% ophthalmic solution, and ketorolac and prednisolone combination therapy in the treatment of acute, visually significant, cystoid macular edema (CME) occurring after cataract extraction surgery. Randomized, double-masked, prospective trial. Twenty-eight patients who had undergone cataract extraction and in whom clinical CME developed within 21 to 90 days after cataract surgery. Patients were randomized to topical therapy with ketorolac (group K), prednisolone (group P), or ketorolac and prednisolone combination therapy (group C) four times daily. Treatment was continued until CME resolved or for 3 months, whichever occurred first. Treatment was then tapered over 3 weeks. Examinations were monthly and included Snellen visual acuity, contrast sensitivity, Amsler grid, slit-lamp examination, dilated fundus examination, and fluorescein angiography. Twenty-six of 28 patients completed the study. Patients were enrolled an average of 48 days after surgery. The average improvements in Snellen visual acuity were as follows: 1.6 lines in group K, 1.1 lines in group P, and 3.8 lines in group C. This reached statistical significance for all visits when group C was compared with group P, and for visits 4 and 5 when group C was compared with group K. Group C reached a mean change of two lines or more by visit 2; at no time did either group K or P reach a mean two-line improvement. At no time was a significant difference detected between group K and P with regard to visual acuity or change from baseline. A two-line or more improvement in Snellen acuity was achieved in 16 of 26 patients (61%). Analysis by group revealed four of eight patients (50%) in group P, six of nine patients (67%) in group K, and eight of nine patients (89%) in group C who had achieved a two-line or more improvement. In patients who did improve two lines or more, improvement occurred an average of 2.75 months after initiating therapy in group P, 1.43 months in group K, and 1.33 months in group C. Improvements in contrast sensitivity and leakage on fluorescein angiography tended to mirror improvements in Snellen acuity. Treatment of acute, visually significant pseudophakic CME with ketorolac and prednisolone combination therapy appears to offer benefits over monotherapy with either agent alone. Patients were more likely to experience recovery of two lines or more of visual acuity. Patients treated with combination therapy or ketorolac monotherapy responded more quickly than did patients treated with prednisolone alone.
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              Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery.

              K. Solomon (2001)
              To compare the efficacy and safety of ketorolac 0.5% ophthalmic solution with its vehicle in the treatment of ocular inflammation after cataract surgery and intraocular lens implantation. Multicenter clinical study. One hundred four patients were prospectively randomized, 52 patients in treatment group, 52 patients in control group. Patients received either ketorolac or vehicle four times daily in the operated eye for 14 days starting the day after surgery in a prospective, double-masked, randomized, parallel group study. Only patients with moderate or greater postoperative inflammation the day after surgery were enrolled. The main outcome measures include inflammation (cell, flare, ciliary flush), intraocular pressure and visual acuity. Ketorolac was significantly more effective than vehicle in reducing the manifestations of postoperative ocular inflammation, including: anterior chamber cells (P: = 0.002) and flare (P: = 0.009), conjunctival erythema (P: = 0.010), ciliary flush (P: = 0.022), photophobia (P: = 0.027), and pain (P: = 0.043). Five times as many patients were dropped from the study for lack of efficacy from the vehicle group (22/52) than from the ketorolac group (4/52; P: = 0.001). Ketorolac was found to be equally as safe as vehicle in terms of adverse events, changes in visual acuity, intraocular pressure, and biomicroscopic and ophthalmoscopic variables. Ketorolac tromethamine 0.5% ophthalmic solution was significantly more effective than vehicle in the treatment of moderate or greater ocular inflammation following routine cataract surgery, while being as safe as vehicle.

                Author and article information

                S. Karger AG
                April 2003
                27 February 2003
                : 217
                : 2
                : 89-98
                University Eye Hospital, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
                68563 Ophthalmologica 2003;217:89–98
                © 2003 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                : 24 October 2002
                : 01 November 2002
                Page count
                Tables: 1, References: 154, Pages: 10

                Vision sciences,Ophthalmology & Optometry,Pathology
                Corticosteroid,Conjunctivitis,Ocular inflammation,Cystoid macular edema,Cataract surgery,Refractive surgery,Blood-aqueous barrier,NSAID


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