Results

DISEASE FREQUENCY

Data were received from 12 of the 14 English RHAs. A total of 243 patients (259 eyes) with a diagnosis of AK were identified among this population of approximately 41 million. The total annualised incidence was 0.14 per 100 000 individuals, but there was considerable variation between the 12 participating RHAs (0.01–0.88 per 100 000) (Table 1). At Moorfields Eye Hospital the increase in frequency of cases presenting in the early 1990s3 10 (1990, n=22; 1991, n=27) has continued, reaching a plateau of approximately 40 cases per year in 1994 and 1995. This has been followed by a dramatic 46% decrease in the number of cases during the final year of the survey. Although small numbers in the majority of the other RHAs prevent detailed analysis, this pattern appears to have occurred throughout the country (Table 1). Seasonal variations in frequency were also identified: a calculation based on Poisson probabilities showed that the observed number of cases was significantly higher than expected for August and September and significantly lower than expected for February and March (Table 2).

DIAGNOSIS

A positive tissue diagnosis of Acanthamoeba was made for 131/243 (54%) patients, and for a further 53 (22%) diagnosis was confirmed by the presence of perineural infiltrates.

There were 59 cases of presumed AK who had atypical keratitis with an array of characteristic signs and symptoms3 such as positive culture from CL paraphernalia accompanying other typical features (n=48), epitheliopathy (n=27), limbitis (n=19), severe or disproportionate pain (n=17), and ring infiltrates (n=6).

The proportion of patients diagnosed early (antiamoebal therapy commenced within 30 days of presentation) was 137/200 (69%) during the first 3 years, significantly rising to 33/37 (89%) in the final year (χ² = 6.591, p<0.02) (Table 3). For six patients insufficient data prevented accurate calculation of diagnostic delay. Among patients who had not been wearing contact lenses only 9/18 (50%) were diagnosed early.

TREATMENT AND OUTCOME

For 197/218 patients (90%) medical therapy included polyhexamethyl biguanide (PHMB) (168/218, 77%)) and/or chlorhexidine (44/218, 20%); the most common treatment combination was propamidine isethionate and PHMB (108/218, 50%) (Table 4). For 25 patients medical therapy details were incomplete. The average duration of medical therapy for patients in the study was 6 months (median 135 days; range 16–886 days), although 26 patients were still on medication or lost to follow up at the time of analysis (6 months after the study period).

Surgery was performed on 40/243 (16%) patients (41/259 eyes), 30/243 (12%) patients (31 eyes) receiving penetrating or lamellar keratoplasty (Table 5). No significant difference existed in the proportions of confirmed and presumed AK cases known to have required surgery (29/181 and 7/58 respectively, χ² = 0.537). Of the 203 patients who had not had any surgery there were 54 who were still under review, 17 of whom still had visual acuities of less than 6/12. Among non-CL wearers (18 unilateral patients) surgery (including two enucleations) was required in 8/18 (44%) of cases.

The final acuities for eyes of patients who had been discharged (n=161, 175 eyes) were 6/6 or better for 113/175 (65%), 6/9 to 6/12 for 53/175 (30%), and 6/18 to 6/60 for 5/175 (3%). Four patients with unilateral infection were left with light perception (n=2) or anophthalmos (n=2). Among patients still under review (n=61, 61 eyes) or lost to follow up (n=21, 23 eyes) acuities had reached 6/6 or better for 25/84 (30%) eyes, 6/9 to 6/12 for 31/84 (37%), 6/18 to 6/60 for 11/84 (13%), and unknown for three eyes. Fourteen of 84 eyes had perception of light only. In all, 25/82 (31%) of these patients were known to be still on medical therapy. When confirmed and presumed AK cases were compared, there was no significant difference in the numbers of patients known to have achieved 6/12 or better (153/182 and 53/58 respectively, χ² = 1.935). Although similar numbers in the early and late diagnosed patients achieved at least 6/12, a significantly greater proportion of the early diagnosed group achieved 6/6 or better (99/170 compared with 25/67, χ²= 8.433, p<0.01). The proportions of patients achieving 6/12 or better among those treated with propamidine and PHMB only (99/107) or propamidine and chlorhexidine only (15/15) were both significantly higher than the proportion of patients with this outcome among those initially treated with propamidine and neomycin sulphate with PHMB added later (21/30) (χ²= 10.936, p<0.001 and 5.625, p<0.02 respectively). Patients who had undergone surgery were significantly less likely to achieve 6/12 or better (23/35) than patients who had received medical therapy only (23/35 compared with 180/202, χ² = 13.287, p<0.001).

The visual outcome among non-CL wearers was markedly worse: at the time of analysis (nine were still under review) only 10/18 (56%) had achieved 6/12 or better, and six (33%) had perception of light or anophthalmos following enucleation.

PATIENT CHARACTERISTICS

Patient ages ranged from 4 to 64 years, with a mean age of 31.5 years; 135 (56%) were male and 108 (44%) were female.

RISK FACTORS AMONG NON-CONTACT LENS WEARERS

Questionnaires were completed by 12/18 (67%) patients who had not been wearing contact lenses. Eleven (61%) of these non-CL wearers had a recent history of trauma (minor in all but three cases) in a garden (n=4), building site (n=3), dairy farming (n=2), fishing (n=1), or nautical (n=1) environment. Four patients had developed the disease following water/snow sporting activities. Data were insufficient for the remaining three patients.

RISK FACTORS AMONG CONTACT LENS WEARERS

A total of 225 of the 243 patients (93%) had been wearing CLs when their symptoms started, and 157/225 (70%) completed a questionnaire; 221/225 (98%) had worn CLs for more than 6 months, and only 5/225 (2%) CL patients had a medical indication for CL wear (three were aphakic, one was keratoconic, and one had a corneal graft). Data on penetrance of different CL types and modalities are not available for each year of the study period. Recent data on currentprescribing habits,13 however (which inevitably overestimate the proportion of the population wearing newer CL modalities) suggest that SCLs were overrepresented, and rigid gas permeable lenses markedly underrepresented among the study patients (Table 6).

In contrast with the non-CL users, a minority of the CL wearers had a recent history of trauma (14/225, 7%), and few (5/225, 2%) had acute concurrent ocular disease (two had acute epithelial necrosis after overnight CL use, an aphakic patient with glaucoma had anterior uveitis, one had conjunctivitis unrelated to CL wear, and one had CL related dry eye).

Adequate CL storage case hygiene (weekly rinsing of the case with sterile saline, boiled water, or disinfection solution followed by drying by leaving it open or by wiping with a clean tissue) was carried out by only seven of the 135 (5%) CL wearers for whom these data were available. Eighty two of 131 storage cases (63%) tested were culture positive for Acanthamoeba.

Among patients with rigid lenses, 11/17 (65%) failed to perform regular disinfection, and for three of the four subjects who had been compliant with correct disinfection routines there was a history of swimming pool bathing with contact lenses in situ.

Among SCL wearers for whom disinfection data were sufficient there were 56/150 (37%) who were disinfecting irregularly and a further 40/150 (27%) who failed to carry out any disinfection. Chlorine release systems were overrepresented among the AK patients using soft lenses (Table 7). Fourteen of 158 (9%) patients (for whom these data were available) were known to have rinsed or soaked their SCL in tap water or other non-sterile water. Forty seven of the 205 (23%) SCL users were known to have swum or engaged in water sports while wearing their lenses before infection. Among questionnaire respondents who had been wearing SCL, one or more established CL related risk factors9 12 were identified for 125/138 (91%) patients (Table 8).

Discussion

DISEASE FREQUENCY

Despite the wide coverage of this multicentre survey the national annualised incidence of acanthamoeba keratitis may be substantially greater than calculated from the results (0.14 per 100 000); regional coordinators could not be found for two of the 14 English RHAs, and within each of the contributing RHAs there were units that declined participation or were unable to identify cases retrospectively. In addition, the likelihood of enhanced case detection by larger specialist referral centres, as strongly suggested by the considerably higher incidence rates for North East Thames, North Western, and South Western, prevents any reliable analysis of the geographical distribution of the disease. This large database of cases does, however, enable detection of changing frequency of disease during the 4 year study period, and can show that these changes appear to have occurred throughout the country.

The continued increase in frequency during the 1992–5 period is likely to be associated with the growing popularity of disposable lenses and the inadequate disinfection routines with which they were associated at the time.12 Growing recognition of the disease may also have increased the number of cases diagnosed.

With SCL associated with 205/243 (84%) of the total number of patients, it is hypothesised that a number of factors improving SCL hygiene practices may have brought about the marked decline in the number of AK cases during the final year (October 1995–September 1996). During 1993 the first “multipurpose” soft lens disinfection systems were introduced, providing a practical alternative to the chlorine release disinfection systems previously advocated for use with disposable lenses. The latter have been shown, when compared with other systems, to be associated with a 15 times greater risk of developing AK.12 The most widely used brands of these new, multipurpose solutions are ineffective againstAcanthamoeba.14 It is possible, however, that they may provide greater protection from AK (compared with chlorine release systems) as a result of their surfactant content and recommended “rub and rinse” step, which may be expected to significantly reduce the microbiological load.15 These systems also eliminate the need for a separate saline rinsing solution, which, if contaminated or substituted by inappropriate rinsing solution, increases the risk of AK.9 The growing popularity of these new solutions, together with the introduction in early 1995 of lenses for disposal after 1 day (thereby obviating the need for lens care solutions), may have contributed to the reduced number of cases in the final year of the study (after autumn 1995). Thesuddenness of the decline in numbers, however, suggests that the predominant factor may be improved CL hygiene and increased use of more effective disinfection systems after widespread media attention in November 1995 to a CL related AK study publication emphasising the risks associated with chlorine release or omitted disinfection.12

As in previous reviews of cases in the USA,5 16 a higher frequency of new cases during the summer/early autumn months was identified. This pattern has been attributed to an increased prevalence of Acanthamoeba in the environment during warmer weather.5 16 An additional association with a summertime flooding of the Iowa River (USA) has also been described.16 It is also likely that warmer weather greatly increases the number of individuals engaging in water sports and outdoor activities (either in the UK or in much warmer climates), thereby increasing the number of people at increased risk of developing AK after contact with dust, soil, insect vectors, or environmental water.5

TREATMENT AND OUTCOMES

As in a previous series,3 outcomes as measured by final acuity and need for surgery were similar among confirmed and “presumed” cases, validating the inclusion of the latter in the survey.

When comparisons are made with a review3 of 72 cases presenting to Moorfields Eye Hospital between 1984 and 1992 a marked improvement in diagnosis and outcome is apparent.

The proportion of patients with an early diagnosis, which, as previously,3 is strongly associated with a more successful outcome, increased from 49% (35/72) to 72% (170/237). Possibly mainly as a consequence of this, the percentage of eyes known to receive a corneal graft reduced from 32% (23/73) to 18% (31/175). The percentage of eyes known to have achieved at least 6/12 visual acuity rose from 79% (58/73) to 87% (222/256), even though 84 eyes were still under review (including 26 eyes on medical therapy) at the time of analysis. Increased use of chlorhexidine and (particularly) PHMB, which have been shown to be the most effective agents againstAcanthamoeba both in vitro17 and clinically,1 18 appears to be another contributing factor.

Failure to show a significantly poorer outcome among patients treated with propamidine and one of the biguanides compared with propamidine and neomycin is probably due to the tendency to introduce a biguanide to failures on the latter regime; patients who received propamidine, neomycin, and subsequent PHMB had a significantly poorer visual outcome compared with those who had received propamidine and a biguanide as the first line of treatment, illustrating the effect of delayed appropriate therapy on the final outcome.

The prognosis for patients contracting the disease in the absence of contact lens wear remains poor. This is probably related to the their frequently more delayed diagnosis. Earlier consideration of AK as a diagnosis among non-CL wearing patients with atypical keratitis following a history of (usually minor) trauma in a rural, dusty, or watery environment—as described in this study and previously2 4 5—is advised. It has also been suggested, however, that infection acquired in rural settings may involve a heavier inoculate and/or more virulent organisms,1 perhaps leading to more severe disease.

RISK FACTORS AMONG CONTACT LENS WEARERS

As in previous series,3-5 a very high proportion of patients were CL wearers (93%), and more than 90% of these were experienced CL wearers without any other predisposing factors. Rigid lenses were underrepresented in the survey, and all but one case had a history of irregular disinfection and/or swimming pool bathing while wearing contact lenses. Easier removal of Acanthamoebatrophozoites and cysts from the rigid CL surface19may be contributing to the apparently reduced risk with these lenses. The most likely explanation for the apparent difference in risk, however, is that the number of cases using rigid CL has remained fairly static during the 4 year period, while the number associated with SCL rapidly increased during the first 3 years of the survey.

Among normal CL wearers, storage case hygiene is known to be inadequate among 28–86%20 and storage case contamination byAcanthamoeba occurs in up to 7%.21 Perhaps as a result of these universally poor standards, case hygiene has previously failed to be identified as a significant risk factor.12 The very high proportion of patients (95%) in this study failing to carry out the most basic level of case hygiene, together with the frequency with which lens storage cases tested were found to be positive for Acanthamoeba (63%), however, suggests that increased education regarding this aspect of CL care could further reduce the incidence of AK.

Among SCL wearer questionnaire respondents (n=138) there was a history of at least one previously established risk factor9-12 —swimming in lenses (34%), omitted disinfection (62%), chlorine disinfection (47%), and non-sterile lens rinsing (8%)—in 91% of these patients. These results, together with the high proportion of inadvisable practices among rigid lens wearers, emphasise the highly preventable nature of this disease among contact lens wearers.

Conclusion

An increased likelihood of earlier diagnosis and the widespread use of more effective medical therapy have greatly improved the prognosis for patients with acanthamoeba keratitis, although a successful outcome for the small proportion of patients with no recent history of CL wear remains less assured. The study demonstrates the highly preventable nature of the disease: 91% of the soft lens wearers (and probably 94% of the rigid lens wearers) could have avoided the disease by carrying out more effective disinfection and/or refraining from swimming while wearing lenses, and a dramatic fall in the incidence was seen after intensive media attention prompted widespread discussion and increased education of CL wearers. The gaining penetrance of new CL disinfectants and daily disposable CL may also be contributing factors. There is a continued need to educate CL wearers about these risks, and since the frequency of AK appears to be largely determined by the ever changing trends in contact lens use, continued monitoring is indicated.