PURPOSE To identify prognostic factors affecting visual outcome in Acanthamoeba keratitis (AK) treated with topical chlorhexidine gluconate (CHG). METHODS A total of 35 eyes in 34 patients with AK were treated with 0.02% topical CHG. Patients were divided into two groups according to the final visual outcome: Group 1, final visual acuity (VA) of 20/25 or greater (22 eyes); Group 2, less than 20/25 (13 eyes). We compared these groups and evaluated the effectiveness of topical CHG compared with outcomes in previous reports. RESULTS Ring infiltrate was observed more often in Group 2 (4.5% vs 61.5%, OR 33.6, 95% confidence interval (CI) 3.4-333.9, P<0.01). The duration between onset and diagnosis of AK was significantly longer (24.9 days vs 48.4 days, OR 1.03, 95% CI 1.00-1.06, P = 0.04) and VA at initial examination (log MAR) significantly lower (0.47 vs 1.59, OR 25.5, 95% CI 3.4-186.7, P<0.01) in Group 2 (visual outcome <20/25). Multivariate analysis revealed that only VA at initial examination was independently associated with worse visual outcome (adjusted OR 24.5, 95% CI 1.9-312.6, P=0.01). Seventeen (85.0%) of the 20 eyes diagnosed within 1 month and 24 (82.8%) of 29 eyes diagnosed within 2 months achieved a VA of 20/40 or greater. CONCLUSION VA at initial examination was the most predictive factors for final visual outcome in AK. Topical CHG was comparably effective to other treatments, including polyhexamethyl biguanide and propamidine isethionate.

Polyhexamethylene biguanide (PHMB) is a polymeric biguanide disinfectant that has not previously been used in the treatment of infection. Six patients with confirmed Acanthamoeba keratitis were treated with PHMB 0.02%. All patients had uncontrolled keratitis refractory to therapy with multiple conventional antiamebic agents. The rationale for use and the dose of PHMB was determined by in vitro sensitivity testing of the Acanthamoeba corneal isolates to the drugs available for use. Trophozoite forms were sensitive to most agents. Only PHMB was cysticidal at low concentrations in all cases. Sensitivity to the other drugs, including propamidine, showed wide variation. In 5 of 6 cases, complete resolution of inflammation followed the introduction of PHMB. Toxicity to the ocular surface was not evident with PHMB, unlike propamidine or neomycin. The reasons for the treatment failure in one case, despite cyst sensitivity to both PHMB and propamidine, are not clear. PHMB is a promising new treatment for this infection.

AIM To determine the incidence, regional variation in frequency, outcome, and risk factors for acanthamoeba keratitis (AK) in England and Wales. METHODS AK cases presenting from 1 October 1997 to 30 September 1999 were identified by the British Ophthalmic Surveillance Unit active reporting system. Clinical and patient postal questionnaire data were analysed. RESULTS 106 reported cases met study criteria. The annual incidence for the 2 years was 1.26 and 1.13 per million adults and, for contact lens (CL) wearers, 21.14 and 17.53 per million. There was marked regional variation in incidence (0 to 85.13 per million adult CL wearers), with CL wearers in the south having a ninefold increased risk of AK compared with those resident in the north (95% confidence limits: 2.2-38.9, p<0.0001), and a threefold increased risk with hard as opposed to soft domestic water (95% confidence limits: 1.73 to 6.58, p<0.001). Treatment and outcome data were similar to those previously reported. 93/106 (88%) patients were CL wearers. Among these, 46/77 (60%) were disinfecting irregularly, and 20/63 (32%) had been swimming in CLs. One step hydrogen peroxide and chlorine release soft CL (SCL) disinfection systems were significantly over-represented among the cases. Among SCL users, one or more previously established risk factors for AK were identified in 50/55 (91%) patients. CONCLUSIONS The incidence was considerably higher than most previous estimates, and was static. The geographical variation in incidence may be partly related to the increase in risk associated with hard water. The fact that water quality can have such an effect on the risk of AK suggests that many CL wearers must be letting tapwater come into contact with their lenses or storage cases. Improved education for CL wearers and practitioners about hygiene practice and the variable efficacy of contact lens systems could be expected to reduce the incidence of this disease.

PURPOSE A sharp increase of Acanthamoeba keratitis from two cases per year to 30 cases per year at our institution prompted this study to determine whether there was a change in the clinical characteristics, basic epidemiology, and outcome of this disease. METHODS We reviewed all cases of Acanthamoeba keratitis diagnosed at the University of Iowa Hospitals and Clinics from mid-1993 through 1994. RESULTS We screened 217 patients with keratitis by tandem scanning confocal microscopy and suspected Acanthamoeba in 51 patients. Diagnosis was confirmed by cytology in 43 patients (48 eyes). There were no positive cultures. Patients examined within four weeks of onset of symptoms were younger (mean age, 32.6 +/- 15.4 years) and wore contact lenses (11 of 18 patients), and infrequently herpes simplex keratitis (four of 18 patients) was diagnosed. Patients examined after four weeks were older (mean age, 54.0 +/- 19.5 years), infrequently wore contact lenses (six of 25 patients), and often had herpes simplex keratitis (12 of 25 patients). CONCLUSIONS Corneal examination with tandem scanning confocal microscopy was associated with a marked increase in the detection of Acanthamoeba, strongly suggesting that the disease is more prevalent than suspected. Acanthamoeba may account for many cases of clinically presumed herpes simplex keratitis, the leading cause of corneal blindness in the United States. Acanthamoeba should be considered in the differential diagnosis of any unexplained keratitis, even those of short duration.

Trophozoites and cysts of 20 isolates of Acanthamoeba from the cornea and five from related samples were tested in vitro for sensitivity to ten drugs (three aromatic diamidines, two aminoglycosides, two macrolides, a polyene macrolide antibiotic, an organoarsenical and an antimetabolite) and two cationic antiseptics (chlorhexidine and polyhexamethylene biguanide, PHMB). Only chlorhexidine and PHMB showed uniform amoebacidal activity. Aromatic diamidines (pentamidine isethionate, propamidine isethionate and diminazene aceturate) generally proved effective against both forms of the amoeba; only pentamidine gave synergy with the biguanide while propamidine gave an additive effect. Other drugs tested proved erratic or ineffective against different isolates. Chlorhexidine alone, or together with propamidine, was subsequently used in two patients with proven Acanthamoeba keratitis; the causative isolates were sensitive to the individual compounds and to the combination in vitro. The treatment provided resolution of the clinical disease; amoebae were shown to be nonviable by histology and culture. The combination of chlorhexidine and propamidine is recommended for treatment of proven Acanthamoeba keratitis.

OBJECTIVE This study investigates the clinical outcome of Acanthamoeba keratitis treated with polyhexamethyl biguanide (PHMB) and propamidine isethionate (Brolene). DESIGN A retrospective review of all patients treated for Acanthamoeba keratitis between September 1992 and February 1995 was carried out. All patients were treated with PHMB 0.02% and propamidine 0.1% hourly for 3 days, the frequency reduced to four to six times daily according to clinical response. MAIN OUTCOME MEASURES Age, gender, result of laboratory investigation, duration of disease before diagnosis, visual acuity (VA) pretreatment and post-treatment, need for keratoplasty, and presence of adverse reaction were measured. RESULTS One hundred eleven cases were identified in 105 patients (60 male, 45 female; mean age, 32). Ninety-two percent of infections were in contact lens wearers. The clinical diagnosis was confirmed by corneal culture or histopathology in 64 cases (57.7%). The diagnosis was made "early"(within 28 days) in 65 cases (58.6%). Twenty-one (18.9%) were "intermediate"(28 days-2 months) and 20 (18%) were "late"(> 2 months) diagnoses. Overall post-treatment VA was 6/12 or better in the majority (88/111, 79.3%) of cases, and 18 (16.2%) had VA of 6/36 or worse. The VA of > or = 6/12 was achieved by 90.8% of the early, 71.4% of the intermediate, and 65% of the late groups. Clinical relapses occurred in 19 patients on reducing the therapy. Treatment toxicity was never serious and consisted only of stinging or superficial punctate keratopathy. Keratoplasty was indicated in only ten patients, and disease activity was controlled adequately in all patients before grafting. CONCLUSIONS Combined treatment with PHMB and propamidine is well tolerated, nontoxic, and effective. Typically, visual outcome is favorable and the requirement for keratoplasty reduced markedly.

Following the diagnosis of Acanthamoeba keratitis in a contact lens wearer, the antimicrobial susceptibility of the clinical isolate and the environmental source of the infection were investigated. Contrary to previous reports, in vitro antimicrobial testing showed that the infecting strain was inherently resistant to propamidine isethionate. Restriction endonuclease digestion analysis of Acanthamoeba whole-cell DNA of strains isolated from the patient's cornea, contact lens storage container, saline rinsing solution, and kitchen cold-water tap showed that the isolates were identical. This implicates, for the first time, domestic tap water as the source of Acanthamoeba sp. in this infection. It is therefore recommended that the use of homemade saline solutions and the rinsing of contact lenses in tap water be strongly discouraged.

Charts of 320 patients with corneal ulcers seen on the Cornea Service of Wills Eye Hospital from July 1, 1992, to June 30, 1995, were reviewed retrospectively. Of these cases, 96 (30%) were associated with contact lens use. Ulcers in contact lens users accounted for 36% of cases in the last 6 months of 1992 and all of 1993, 20% of cases in 1994, and 29% in the first 6 months of 1995. The contact lenses most commonly associated with ulcers were disposable extended-wear lenses. They were used in 33% of contact lens-associated ulcers in 1992, 27% in 1993, 39% in 1994, and 44% in 1995. Pseudomonas was the predominant organism prior to 1993 (1-4). From 1993 to 1995, however, the number of Pseudomonas ulcers steadily decreased. Two or three Acanthamoeba infections continue to be treated each year. There has been a significant decrease in the number of contact lens-related ulcers treated at our institution compared with previous years (p < 0.01)(3, 4).

AIM To review the clinical characteristics, diagnosis, and visual outcome in patients with non-contact lens related Acanthamoeba keratitis and compare the findings with reported series of contact lens associated Acanthamoeba keratitis. METHODS Medical and microbiology records of 39 consecutive patients with a diagnosis of Acanthamoeba keratitis, at a tertiary eyecare centre in India between January 1996 and June 1998, were analysed retrospectively. RESULTS A majority of the patients presented with poor visual acuity and large corneal stromal infiltrates (mean size 38.20 (SD 26. 18) mm). A predisposing factor was elicited in 19/39 (48.7%) patients (trauma 15, dirty water splash three, leaf juice one). None of the patients had worn contact lenses. Most patients (26/39 (66. 6%)) came from a low socioeconomic background. Complaint of severe pain was not a significant feature and radial keratoneuritis was seen in 1/39 (2.5%) patients. A ring infiltrate was present in 41.1% of cases. A clinical diagnosis of fungal keratitis was made in 45% of the patients before they were seen by us. However, all patients were diagnosed microbiologically at our institute based on demonstration of Acanthamoeba cysts in corneal scrapings (34/39) and/or culture of Acanthamoeba (34/39). Treatment with biguanides (PHMB, 15/38 (39.4%), PHMB with CHx, 23/38 (60.5%), one patient did not return for treatment) resulted in healing with scar formation in 27 out of 31(87.0%) followed up patients (mean time to healing 106.9 days). Overall visual outcome was poor with no statistical difference between cases diagnosed within 30 days (early) or 30 days after (late) start of symptoms. The visual outcome in cases requiring tissue adhesive (five) and keratoplasty (three) was also poor. CONCLUSIONS This is thought to be the largest series of cases of Acanthamoeba keratitis in non-contact lens wearers. In such cases, the disease is advanced at presentation in most patients, pathognomonic clinical features are often not seen, disease progression is rapid, and visual outcome is usually poor. Possible existence of Acanthamoeba pathotypes specifically associated with non-contact lens keratitis and unique to certain geographical areas is suggested.

BACKGROUND: The treatment of Acanthamoeba keratitis has been increasingly successful as diagnoses are made earlier. The authors investigated features of the disease and prognosis in a consecutive series of 15 patients who were treated within 1 month of initial symptoms. METHODS: A database of patients with Acanthamoeba infection presenting between March 1984 and March 1992 was analyzed. The recognition, presenting features, culture methods, results, and treatment of the early cases were reviewed to determine the reasons for a good outcome. RESULTS: Recognition depended on perineural infiltrates (11/15), uveitis (10/15), limbitis (14/15), and infiltrated epithelium; 6 of 15 patients had epithelial defects, but only 3 of 15 had ring infiltrates or ulcers. Epithelial biopsy was culture-positive in 12 of 15 patients. Most (11/15) patients needed only two anti-amebal drugs. One patient only required penetrating keratoplasty for uncontrolled disease. The final visual acuity was at least 6/12 in all patients who had been treated within 1 month of first symptoms, whereas only 17 (53%) of 32 eyes of patients who presented after 1 month achieved a visual acuity of 6/12. CONCLUSIONS: Subtle diagnostic signs, supported by comprehensive microbiologic investigation, justify the immediate instigation of specific antiamebal therapy. Treatment within 1 month of onset results in a lower morbidity and a good visual outcome.

INTRODUCTION: Following laboratory studies on new potential chemotherapy for Acanthamoeba keratitis, when chlorhexidine and propamidine provided an additive in vitro effect, a series of 12 patients with culture-proven Acanthamoeba keratitis from three UK centres was monitored during and after therapy. METHODS: In all cases the clinical diagnosis was confirmed by amoebal culture. In some instances identification of the protozoa by direct microscopy of corneal tissue was possible. The medication was provided topically in drop form until the keratitis had resolved. In vitro sensitivity to chlorhexidine and propamidine was performed on all isolates and compared with sensitivity to a range of other drugs used for treatment of the infection. RESULTS: In vitro drug testing confirmed that trophozoites and cysts of all 12 Acanthamoeba isolates were fully sensitive to chlorhexidine and propamidine. Therapy was satisfactory for controlling and eradicating the acanthamoebal infection in all patients. Three patients developed discrete stromal infiltration at the site of infection that resolved 1 week after commencing therapy, with or without use of steroids. Two patients developed a late inflammatory effect in the stromal scar at 6 months, which resolved with steroids. No clinical evidence of chlorhexidine toxicity was found in any patients. CONCLUSIONS: The combination of topical chlorhexidine and propamidine was very effective for treating Acanthamoeba keratitis provided the drugs were continued for a sufficient period. No drug toxicity or resistance of Acanthamoeba isolates was observed in the 12 treated patients.