628 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / April 1986 Vol. 27 but only delayed excystation of A. polyphaga organ- 5. Hirst LW, Green WR, Merz W, Kaufman C, Visvesvara GS, isms. The reason for the apparent greater effectiveness Jensen A, and Howard M: Management of Acanthamoeba ker- of this system over the other two chemical disinfection atitis. A case report and review of the literature. Ophthalmology 91:1105, 1984. systems is not clear. It is also unclear whether different 6. Samples JR, Binder PS, Luibel FJ, Font RL, Visvervara GS, and strains of Acanthamoeba species would be variably Peter CR: Acanthamoeba keratitis possibly acquired from a hot susceptible to these disinfection systems. However, re- tub. Arch Ophthalmol 102:707, 1984. sults of this study indicate that heat disinfection was 7. Sculley RE, Mark EJ, and McNeely BU: Case records of the more effective overall in killing Acanthamoeba tro- Massachusetts General Hospital. N Engl J Med 312:634, 1985. 8. Blackman HJ, Rao NA, Lemp MA, and Visvesvara GS: Acanth- phozoites and cysts as compared to cold disinfection amoeba keratitis successfully treated with penetrating kerato- systems. plasty: suggested immunogenic mechanisms of action. Cornea Key words: Acanthamoeba, keratitis, soft contact lens, dis- 3:125, 1984. infection 9. Cohen EJ, Buchanan HW, Laughrea PA, Adams CP, Galentine PG, Visvesvara GS, Folberg R, Arentsen JJ, and Laibson PR: From the National Eye Institute,* Bethesda, Maryland, and De- Diagnosis and management of Acanthamoeba keratitis. Am J partments of Ophthalmology! and Microbiology,^ Cleveland Clinic Ophthalmol 100:389, 1985. Foundation, Cleveland, Ohio, and the Centers for Disease Control,§ 10. Moore MB, McCulley JP, Luckenbach M, Gelender H, Newton Atlanta, Georgia. Submitted for publication: August 14, 1985. Reprint C, McDonald MB, and Visvervara GS: Acanthamoeba keratitis requests: David Meisler, MD, Department of Ophthalmology, associated with soft contact lenses. Am J Ophthalmol 100:396, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 1985. 44106. 11. Krachmer JH and Purcell JJ Jr: Bacterial corneal ulcers in cos- metic soft contact lens wearers. Arch Ophthalmol 96:57, 1978. References 12. Yamamoto GK, Pavan-Langston D, Stowe GC, and Albert DM: 1. Visvesvara GS: Free-living pathogenic amoebae. In Manual of Fungal invasion of a therapeutic soft contact lens and cornea. Clinical Microbiology, 3rd ed, Lennette EH, Balows A, Hausler Ann Ophthalmol 11:1731, 1979. WJ, and Truant JP, editors, Washington, DC, American Society 13. Wilson LA, Schlitzer RL, and Ahearn DG: Pseudomonas corneal for Microbiology, 1980, pp. 704-708. ulcers associated with soft contact lens wear. Am J Ophthalmol 2. Culbertson CG: Pathogenic Acanthamoeba (Hartmannella). Am 92:546, 1981. JClinPathol 35:195, 1961. 14. Myrowitz E, Pearlman P, and Goldberg HK: A case of Pseu- 3. Page FC: Re-definition of the genus Acanthamoeba with descrip- domonas keratitis in a soft contact lens wearer using contami- tions of three species. J Protozool 14(4):709, 1967. nated chemical disinfection solution. Contact Intraocul Lens Med 4. Nagington J and Richards JE: Chemotherapeutic compounds J7(4):337, 1981. and Acanthamoebae from eye infections. J Clin Pathol 29:648, 15. Freedman H and Sugar J: Pseudomonas keratitis following cos- 1976. metic soft lens wear. Contact Lens Journal 10:21, 1976. Bioavailability and Corneal Anti-Inflammatory Effect of Topical Suprofen Howard M. Leibowirz,* William J. Ryan,* Allan Kupferman,*f and Louis DeSanrisJ The bioavailability in rabbit cornea and aqueous humor of an centrations of suprofen when administered according to this ophthalmic formulation of suprofen, a nonsteroidal anti-in- regimen. Invest Ophthalmol Vis Sci 27:628-631, 1986 flammatory drug, was evaluated following topical adminis- tration of a single dose to the eye. The drug penetrated rapidly into the uninflamed cornea with intact epithelium; highest Locally administered corticosteroids effectively sup- levels occurred during the first 30 to 45 min after instillation press corneal inflammation, but their use carries the and decreased thereafter. The bioavailability of suprofen in risk of several ocular complications, including cataract, cornea and aqueous humor following administration of a 1.0% glaucoma, and the enhancement of actively replicating concentration was twice that produced by a 0.5% concentration herpes simplex virus. This has prompted the search for of the drug. Topical application of multiple doses of suprofen other effective but potentially less toxic compounds. failed to suppress polymorphonuclear leukocyte invasion of We have studied suprofen, a nonsteroidal anti-inflam- the cornea if treatment was started after the induction of in- matory agent, and report here our data on its bioavail- flammation. Suprofen therapy initiated prior to the induction of corneal inflammation and maintained into the post-inflam- ability and anti-inflammatory effectiveness in the cor- mation period did produce a significant (P < 0.01) decrease nea following topical administration to the rabbit eye. in the numbers of PMNs that invaded the inflamed cornea. Materials and Methods. Bioavailability studies: So- There was no significant difference (P > 0.05) in the corneal dium thiamylal was administered intravenously to New anti-inflammatory effect achieved by the 0.5% and 1.0% con- Zealand albino rabbits (1.8-2.4 kg), producing light Downloaded from iovs.arvojournals.org on 09/29/2021 No. 4 Reports 629 anesthesia for approximately 10 min and allowing op- Table 1. Mean concentration of suprofen following timal control of the administration of radiolabeled topical application to the normal rabbit cornea* drug. A single 0.05-ml dose of 3H-suprofen 0.5% (17.6 Cornea (fig/gm) Aqueous humor (iig/ml) AtCi/mg) or 1.0% (16.0 /iCi/mg) was placed on the cen- Time tral corneal surface (epithelium intact) of both non- (min) 0.5% 1.0% 0.5% 1.0% inflamed eyes using a microsyringe. The 0.05-ml dose was contained within the conjunctival sac while the 5 17 (±3) 25 (±5) 0.076 (±0.007) 0.192 (±0.031) 15 11 (±3) 18 (±3) 0.120 (±0.015) 0.719 (±0.020) lids were manually blinked three times and taped 30 14(±l)t 22 (±4)f 0.514 (±0.014) 1.342 (±0.271) closed. At fixed times thereafter animals were killed by 45 10 (±2) 16 (±4) 0.673 (±0.018)* 0.863 (±0.250) intracardiac pentobarbital sodium; three saline-soaked, 60 7(±l)t 6 (±2)f 0.508 (±0.047) 1.570 (±0.346)§ 120 4(±1) 10(±l) 0.354 (±0.044) 0.699 (±0.146)§ cotton-tipped applicators, followed by a dry, cotton- 240 4(±D 6(±1) 0.279 (±0.023) 0.430 (±0.038) tipped applicator, were gently rolled over the corneal 360 2(±1) 6(±D 0.151 (±0.019) 0.238 (±0.030) surface to remove radiolabeled surface contaminants. * Table entries are the arithmetic mean (±SEM) of data derived from six This procedure did not disrupt the epithelium, as de- uninflamed eyes with intact epithelium following topical application of a single 0.05-ml dose. Only one eye of an animal was used to obtain data for a given termined by biomicroscopic observation and fluores- time period. cein staining. t 60-minute value is significantly less (P < 0.01) than the 30-min value in the same column. An aqueous humor sample was aspirated from the % Peak value—significantly greater (P < 0.05) than all other values in the anterior chamber with a 27-gauge needle attached to same column. a tuberculin syringe, and an 8-mm full thickness central § The 120-min value is significantly less (P < 0.05) than 60-min value. corneal specimen was obtained by trephination. The corneal samples were weighed and dissolved in 1.5 ml of 0.5N quaternary ammonium hydroxide in toluene PMN invasion of the inflamed cornea was examined (Soluene 100, Packard Instruments; Downers Grove, both when treatment was initiated after induction of IL) at 37 °C over a 24-hr period. Each sample was acid- inflammation and when treatment was initiated prior ified with 0.2 ml concentrated HC1 to eliminate che- to inflammation and continued after induction of the miluminescence produced by the Soluene. Thereafter inflammatory event. Each regimen is outlined in Table the corneal and aqueous samples were handled iden- 4. A control group treated with suprofen vehicle (a tically. Each was diluted with 15 ml of scintillation proprietary buffered ophthalmic vehicle containing counting solution (Ultrafluor, National Diagnostics; preservative and xanthine derivatives) was run with Somerville, NJ) and counted for a minimum of 10 each experimental trial. One hour after completion of min in a Packard 460C scintillation spectrometer. The each treatment protocol a 10-mm full thickness corneal corrected counts per minute were then converted and button was removed by trephination, and the tissue samples were solubilized with a commercially available expressed as micrograms of suprofen per gram of cor- solubilizing agent (Soluene 100, Packard), as described neal tissue or per milliliter of aqueous humor. The final above. The soluble samples were counted for a mini- figure reported for each designated time period is based mum of 10 min, quantitatively measuring the amount on data from six eyes collected in a minimum of two of radioactivity in the cornea. The specific calculations individual experimental trials. The geometric mean was used to determine the data have been reported.1 Sta- plotted as a function of time, a smooth curve was con- tistical evaluation of the data was performed primarily structed, and the area under the curve was determined with analysis of variance using the Scheffe test. This by use of the trapezoid rule. The area thus obtained investigation conformed to the ARVO Resolution on was used to determine the ability of suprofen, with The Use of Animals in Research. time, to concentrate in the cornea and aqueous humor.