Br J Ophthalmol: first published as 10.1136/bjo.69.10.778 on 1 October 1985. Downloaded from British Journal of Ophthalmology, 1985, 69, 778-782 Acanthamoeba keratitis successfully treated medically PETER WRIGHT,' DAVID WARHURST,2 AND BARRIE R JONES' From 'Moorfields Eye Hospital, City Road, London, and the 2Amoebiasis Unit, Pathology Laboratory, Hospitalfor Tropical Diseases, London SUMMARY The first medical cure of a corneal infection due to an Acanthamoeba species is reported. The 44-year-old patient developed a suppurative keratitis associated with an epithelial defect, hypopyon, and secondary glaucoma. Acanthamoeba was confirmed as the causative agent four months after presentation when positive cultures were obtained from the cornea and from the conjunctiva. Sensitivity studies of the isolated organism were performed, and the infection was successfully controlled by treatment with a combination of dibromopropamidine and propamidine isethionate ointment and drops and neomycin drops. Keratoplasty was performed 22 months after onset, and no viable acanthamoebae were present in the resected tissue, though possible cyst remnants were identified by immunofluorescent techniques. copyright. Infection of the eye with Acanthamoeba species has tival cultures and smears showed no organisms and been reported many times'-7 and has been associated no growth in any media but only pus cells and debris. with a fatal meningoencephalitis.2 These infections A slow improvement in the signs followed subcon- are difficult to recognise and treat,' and acantha- junctival and topical gentamicin, mydriatics, and moeba is usually considered only after failure of topical dilute steroids with acetazolamide to control conventional treatment for more common causes of the intraocular pressure. The improvement was not suppurative keratitis. No medical cure has yet been maintained, and on several occasions the hypopyon http://bjo.bmj.com/ reported, and the outcome of all cases has been very increased for no obvious reason and then regressed poor, with excisional keratoplasty as the most again on continued treatment. This relapsing course successful diagnostic and therapeutic measure. continued for several months and in September the corneal epithelium broke down, with increasing Case report stromal suppuration and hypopyon, producing an appearance similar to that seen in a patient subse- CLINICAL PRESENTATION quently shown to have acanthamoeba infections. The patient was a 44-year-old meat porter, physically Smears continued to show only pus cells and debris on September 23, 2021 by guest. Protected very fit and a marathon runner. In April 1979 he was with no organisms. But special cultures for acantha- splashed in the right eye with blood from a condem- moeba from both cornea and conjunctiva grew ned carcass of meat but did not suffer any direct Acanthamoeba sp. identified morphologically as trauma to the eye. Within a few days the eye became A. polyphaga and continued to be positive for some red and sore and a variety of topical medicaments days (Table 1). Nasal and pharyngeal cultures for were given by the patient's general practitioner and acanthamoeba were also taken frequently and were local ophthalmologist including mydriatics, aureo- all negative, as were cultures from the unaffected mycin, gentamicin, and neomycin with corticosteroid left eye. drops. Because of continuing deterioration the patient was referred to Moorfields Eye Hospital, CULTURE TECHNIQUE where in June the findings were of a suppurative Petri dish plates were prepared with 1-5% Oxoid L28 keratitis, hypopyon, and secondary glaucoma with- agar, allowed to set, and left overnight at room out any distinctive features. Corneal and conjunc- temperature. Aerobacter (Klebsiella) aerogenes was Correspondence to Mr P Wright, FRCS, Moorfields Eye Hospital, grown in trypticase-soy broth or on nutrient agar, and City Road, London ECIV 2PD. the bacteria were washed by centrifugation three 778 Br J Ophthalmol: first published as 10.1136/bjo.69.10.778 on 1 October 1985. Downloaded from Acanthamoeba keratitis successfully treated medically 779 times in phosphate-buffered saline (PBS). The Table 1 Culture results bacterial pellet was resuspended to give a milky suspension in distilled water and stored (up to three Righteye months) at 4°C. Two to three drops were spread on Conjunctiva Cornea the agar plates, allowed to absorb at 37°C, and the patient's samples were inoculated directly on to the 17 Sept. + + 20 Sept. - + surface of the plates. They were incubated at 37°C in 24 Sept. - a moist atmosphere for up to three days, and were 27 Sept examined for growth of amoebae by an inverted 30 Sept. - + microscope. Further identification of the amoebae 4 Oct. - - 8 Oct. - _ was by examination of trophozoites and cysts in 13 Oct. - - suspension in Page's saline9 under normal light and 15 Oct. - - phase-contrast microscopy. On the basis of the 19 Oct. - presence of in the 23 Oct. acanthopodia slowly moving 28 Oct. trophozoite, and a polygonal double walled cyst with Nasal and nasopharyngeal cultures always negative characteristic ostioles, the organisms were assigned to the genus Acanthamoeba. clear at present and vision is 6/24, being reduced by TREATM ENT lens opacities. The intraocular pressure is controlled On the basis of previous sensitivity results from cases with timolol maleate 025% drops twice daily. of acanthamoeba infection at Moorfields (discussed Histological examination of the excised corneal later) treatment was begun with drops of propa- disc showed no special changes and no signs of midine isethionate 0 1% hourly by day and night with acanthamoeba on light or electron microscope dibromopropamidine ointment 0-15% four-hourly. examination. By immunofluorescent techniques After nine days of treatment the eye became much against acanthamoeba specific antigens it was pos- redder with rapidly worsening lid swelling despite sible to see small curved segments which took up the copyright. improvement in corneal signs. These changes were stain and which probably represented portions of attributed to toxicity, and since the sensitivity results broken up cyst wall. for the organism cultured (Table 2) were now available treatment was changed to neomycin drops SEROLOGY four-hourly day and night. By October the Serum was taken at the time of positive corneal and epithelium had healed, and four-hourly prednisolone conjunctival cultures and on four occasions during drops were added, with steady improvement in the the following month. A low level of antibody was corneal inflammatory signs. The treatment was present with a slight rise, but the titres were not http://bjo.bmj.com/ slowly reduced until the patient was using only significantly raised above levels found in 'normal' neomycin drops four times daily. These were con- sera (Table 3). Antibody could not be detected in tinued for one year, at which time limbal follicles serum or aqueous humour at the time of kerato- developed with some increased palpebral conjunc- plasty. tival hyperaemia and cellularity but no sign of any skin irritation. All topical therapy was stopped and Table 2 Relativesensitivities penetrating keratoplasty proposed, but not per- on September 23, 2021 by guest. Protected formed for a further four months at the patient's Minimalinhibitory concentrations request for social reasons. During this period all the (tg perml) limbal and conjunctival signs disappeared, and no topical therapy was given. IT AmC An 8 mm penetrating keratoplasty was carried out Myxin <12 2-4 22 months after initial presentation. The postopera- Paromomycin 4.9 4.9 tive treatment included propamidine isethionate Ziram 4-9 9-8 drops four times daily in addition to the usual topical Bayer 1703 >39-0 >39-0 Azalomycin 9-8 >19 5 steroid and antibiotics employed. The propamidine Venturicidin >312-0 >312-0 drops were continued four times daily for two months Neomycin sulphate 7-5 39-0 without any evidence of adverse effect on the corneal DS 9073 5-0 9-8 graft or the remainder of the eye. After cessation of Propamidine <125 <1*25 therapy the graft remained clear for nine months, Dibromopropamidinc <125 2-5 when a rejection episode developed but was easily IT= inhibition of trophozoite. controlled with topical steroids. The graft remains AmC=Amoebicidal (subculturc negativc). Br J Ophthalmol: first published as 10.1136/bjo.69.10.778 on 1 October 1985. Downloaded from 780 Peter Wright, David Warhurst, and Barrie R Jones Table 3 Serology against acanthamoeba (Ryan strain) typical acanthopodia. Where no apparently viable amoebae were found, the medium was centrifuged at 20 Scpt. 1/16 13 Oct. 1/32 700 g for five minutes, and the sediment was inocu- 27 Sept. 1/16 19 Oct. 1/32 4Oct. 1/16 lated on to non-nutrient agar plates coated with A. aerogenes and incubated further for 72 hours to detect any viable cysts or trophozoites. Each experiment therefore gave two results, a Discussion minimum inhibitory concentration (MIC) for inhibi- tion of trophozoite growth (MIC.I) and MIC for This case differs from others reported in that it was killing of trophozoites and cysts (MIC.AmC). Tests not associated with direct ocular trauma or previous were initially carried out on an isolate of acantha- corneal ulceration, acanthamoebae were recovered moeba from a corneal ulcer which was undergoing directly from the cornea and the conjunctival sac, and treatment at Moorfields Eye Hospital.' Subsequent the infection was subsequently controlled by topical less extensive tests with the most