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The Epidemiology of Acanthamoeba Keratitis in the United States
The Epidemiology of Acanthamoeba Keratitis in the United States Jeanette K. Stehr-Green, M.D., Theodore M. Bailey, M.D., and Govinda S. Visvesvara, Ph.D. We surveyed members of the Ocular Microbiology and Immunology.Croup and reviewed laboratory requests at the Centers for Disease Control to determine better the epidemiology of Acanthamoeba keratitis in the United States. A total of 208 cases of Acanthamoeba keratitis were identified. The number of cases increased gradually between 1981 and 1984, with a dramatic increase beginning in 1985. Males and females were equally affected. Of the 208 patients, 85 (41 %) resided in California, Texas, Florida, or Pennsylvania. Of 189 patients, 160 (85%) wore contact lenses, predominantly daily-wear or extended-wear soft lenses. Of the 138 patients who wore contact lenses and for whom information was available, 88 (64%) used saline prepared by dissolving salt tablets in distilled water. Patients aged 50 years and older were more likely to have had a history of trauma than younger patients, and males were more likely to have a history of trauma than females. ACANTHAMOEBA KERATITIS is a chronic infection of the cornea caused by members of the genus Acanihamoeba, The disease is not nationally reportable; therefore, its incidence is unknown. However, published reports suggest that although relatively rare, Acanthamoeba keratitis is being diagnosed with increased frequency. Since the first case of Acanthamoeba keratitis was diagnosed in 1973,1 over 25 additional reports have been published on patients
Accepted for publication Jan. 12, 1989. From the Divisions of Host Factors (Dr. Stehr-Green) and Parasitic Diseases (Drs. Bailey and Visvesvara), Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U. S. Department of Health and Human Services, Atlanta, Georgia. Reprint requests to Govinda S. Visvesvara, Ph.D., Division of Parasitic Diseases, Centers for Disease Control, Atlanta, GA 30333.
©AMERICAN JOURNAL OF OPHTHALMOLOGY
107:331-336,
in the United States.v" Nineteen of the reports, describing 60 patients, have been published since 1985, and 12 reports, describing 37 patients, have been published since 1987. However, because case reports are only a sample of all diagnosed cases, estimates of the incidence of the disease are still lacking. Historically, Acanthamoeba keratitis has been associated with penetrating corneal trauma and exposure to contaminated water. I •3•8 ,9 More recently, an association with contact lens wear has become apparent.vv'"" In a case-control study of soft contact lens wearers, using homemade saline, disinfecting lenses less frequently than recommended by the manufacturer, and wearing lenses while swimming were associated with Acanthamoeba keratitis." However, this study involved only soft contact lens wearers and, therefore, was not designed to look at risk factors among patients who did not wear contact lenses, nor to estimate the proportion of Acanthamoeba keratitis cases attributable to corneal trauma, exposure to contaminated water, or contact lens wear. To estimate better the number of cases of Acanthamoeba keratitis in the United States and the proportion of cases associated with the three major risk factors (corneal trauma, exposure to polluted water, or contact lens wear), we surveyed members of the Ocular Microbiology and Immunology Group (a society of corneal specialists) for reports of cases of Acanthamoeba keratitis. Charaeteristics of cases reported through group members, combined with those cases reported through requests for laboratory services at the Division of Parasitic Diseases, Centers for Disease Control, are presented herein.
Material and Methods In August 1986, all members of the Ocular Microbiology and Immunology Group living in APRIL,
1989
331
332
AMERICAN JOURNAL OF OPHTHALMOLOGY
the United States were contacted by mail. They were asked whether or not they had ever diagnosed, treated, or been consulted about a patient with Acanthamoeba keratitis. If yes, they were asked to provide demographic information (sex, age, state of residence, date of onset of keratitis, and associated risk factors) for each case; to maintain patient confidentiality, names and personal identifiers were not requested. Members were given preaddressed, postagepaid postcards on which to reply. * Members were encouraged to continue reporting cases by this method as they were diagnosed. Between May and July 1988, we contacted all physicians by phone who had reported cases to determine the method of diagnosis and to identify patients reported from multiple sources. Patients residing outside the United States at the onset of keratitis and patients whose infections were not confirmed by culture, histology, or immunofluorescence studies were excluded from the analyses. To identify additional cases of Acanthamoeba keratitis not reported through the survey, we reviewed specimen log books for Acanthamoeba laboratory requests maintained by the Division of Parasitic Diseases through July 1988. Information on all patients with corneal specimens found to be positive for Acanthamoeba on culture, histology, or immunofluorescence studies was abstracted from specimen data sheets. We attempted to contact by phone all physicians submitting samples found to be positive to obtain additional demographic information. Statistical tests used in the comparisons were Fisher's two-tailed exact test and Wilcoxon rank-sum test where appropriate.
Results As of August 1986, the Ocular Microbiology and Immunology Group had 287 members living in the United States. Of these, 20 could not be reached. Of the remaining 267, 175 (66%) responded by returning the provided postcard. Fifty eight (33%) reported diagnosing, treating, or being consulted about at least one confirmed case of Acanthamoeba keratitis, and 11 (6%) reported diagnosing, treating, or being consulted
'Because of changes in postage labels used by the Centers for Disease Control, postcards originally distributed for this study are no longer valid.
April, 1989
about at least one patient with suspected but unconfirmed Acanthamoeba keratitis. Using follow-up calls to physicians, we identified 149 patients with confirmed Acanthamoeba keratitis (excluding duplicates and unconfirmed cases). Review of specimen log books from the Division of Parasitic Diseases identified 144 patients with specimens positive for Acanthamoeba. Fifty nine had not been reported through the survey. These 59 were combined with the 149 cases reported through the survey for the following analyses. The first case of Acanthamoeba keratitis was diagnosed in 1973 in a man from southern Texas with a history of ocular trauma and exposure to contaminated water' (Fig. 1). Between 1973 and 1981, only five additional cases were diagnosed. The number of cases increased gradually from 1981 through 1984, with a dramatic increase in 1985 through 1987. The number again fell in the second quarter of 1988. Of the 208 patients, 101 (49%) were male and 107 (51%) were female. The median age at the onset of keratitis was 29 years, but ranged from 13 to 82 years. Age distribution did not vary by sex. Age and sex distribution did not vary over time. Patients resided in 34 states and the District of Columbia at the onset of their symptoms (Fig. 2). Most cases (41 %) were reported from California (29), Texas (29), Florida (IS), and Pennsylvania (12). Complete risk factor information was not available for each patient. Of the 189 patients for whom at least partial information on risk factors was available, 179 (95%) had at least one risk factor for Acanthamoeba keratitis (history of corneal trauma, exposure to contaminated water, or contact lens wear). Patients aged 50 years and older were less likely to have had a risk factor identified (18 of 21 [86%] vs 156 of 159 [98%], P = .02) than younger patients. Of the 189 patients for whom information was available, 160 (85%) wore contact lenses, most of which were daily-wear or extended-wear soft lenses (Table). Of 154 patients, 26 (17%) had a history of corneal trauma and 37 of 150 (25%) had a history of exposure to contaminated water. Of the 138 patients who wore contact lenses for whom information was available, 88 (64%) had a history of using saline prepared using distilled water and salt tablets. Patients aged 50 years and older were more likely to have had a history of trauma (seven of 18 [39%] vs 18 of 133 [14%], P = .01) and were less likely to have worn contact lenses (11 of 23 [48%] vs 145 of 160 [91%], P < .0001) than younger
16 15 14 13 12 11 10 (f)
9
(f)
8
w
-c
U
7
6 5 4 3 2
'~
0
R
=
RR~
~
1973 1974 1975 1976 1977 1978'1979 1980 1981 1982 1983 1984 1985 1986 1987 1988
QUARTER OF ONSET Fig. 1 (Stehr-Green, Bailey, and Visvesvara). United States Acanthamoeba keratitis cases by date of onset of symptoms, 1973 through June 1988.
~ NO CASES . . . . 10-19 CASES
I2ZZl 1-4 CASES _ >=20 CASES
B8SB!lI 5-9 CASES
Fig. 2 (Stehr-Green, Bailey, and Visvesvara). United States Acanthamoeba keratitis cases by state of residence, 1973 through June 1988.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
TABLE ACANTHAMOEBA KERATITIS LENSTYPE
BY CONTACT LENS
TYPE NO.
Daily-wear, soft Extended-wear, soft Soft, type unknown Saturn lens Rigid gas-permeable Hard lens Unknown
(%)
89
(56)
31
(19)
9
(6)
12
(8)
11
(7)
3
(2)
5
(3)
patients. Males were more likely to have had a history of trauma (19 of 74 [26%] vs seven of 80 [9%], P = .009) and were less likely to have had a history of contact lens wear (73 of 91 [80%] vs 87 of 98 [89%], P = .02) than females.
Discussion
The results of our survey suggest that the incidence of Acanthamoeba keratitis in the United States is much higher than anticipated from published case reports, and that contact lens wear is the predominant risk factor. Our survey probably did not identify all patients with Acanthamoeba keratitis diagnosed between 1973 and June 1988 in the United States. We only contacted members of the Ocular Microbiology and Immunology Group and ophthalmologists who had submitted specimens to the Division of Parasitic Diseases, Centers for Disease Control, for Acanthamoeba studies. However, Acan" thamoeba keratitis is often difficult to diagnose and virtually always difficult to treat; therefore, most cases are referred to a specialist, at least in consultation, during the course of the disease. Because the Ocular Microbiology and Immunology Group is a group of corneal specialists, we thought they would know about most cases in the United States. However, not all corneal specialists are members of this group and, therefore, would not have been contacted unless they submitted specimens directly to the Centers for Disease Control. As a result, some cases may have been missed and our estimate of disease incidence (although much higher than expected) must be considered a minimal estimate. Although expected from case reports, the dramatic increase in cases beginning in 1985 is
April, 1989
puzzling and cannot be explained through findings from our survey. Two potential explanations exist. First, as more reports on Acanthamoeba have been published, ophthalmologists have become more familiar with the diagnosis and may diagnose the disease more accurately. Review of histologic specimens from Wills Eye Hospital suggest that some early cases of Acanthamoeba may have been missed." Of eight cases of active corneal ulceration undiagnosed before 1983, two were found to have had Acanthamoeba present on review after this organism became better known. Second, the increase in cases could indicate a true increase in incidence of the disease. This could result from increased prevalence of the organism, increased virulence of the organism, or increased number of persons at risk. The first two possibilities seem unlikely. However, the increase of Acanthamoeba keratitis in the United States has been paralleled by an increase in the number of persons wearing contact lenses from an estimated 14.5 million in 1980 to 23.1 million in 1985. 29 This increase has occurred primarily in the number of soft contact lens wearers, who use saline as an integral part of contact lens care. As contact lens wear has become more common, contact lens wearers may have also become less meticulous in handling their lenses or ophthalmologists/optometrists may have become less diligent in instructing patients about the proper care of their lenses. This increase in the number of contact lens wearers and an increase in the number of persons caring improperly for their lenses could increase the number of persons at risk for Acanthamoeba keratitis. The decrease in cases in late 1987 and early 1988 may not be an indication of decreased incidence in Acanthamoeba keratitis. Many months had passed since the original request for cases to be reported by members of the Ocular Microbiology and Immunology Group to the Centers for Disease Control. Without an intervening reminder, many physicians could have forgotten about the survey and, therefore, did not report new cases. Outside laboratories have also become more proficient in culturing and identifying Acanthamoeba. As a result, the Division of Parasitic Diseases may receive a smaller proportion of the requests for Acanthamoeba laboratory services and, therefore, fewer cases may be identified through this source. The nearly equal distribution of Acanthamoeba keratitis cases between males and females is
Acanthamoeba Keratitis
Vol. 107, No.4
unexpected. Marketing data suggest that only 28% of soft contact lens wearers in the United States are male (Catherine 1. McGuire, B.A., written communication, July 10, 1986). If contact lens wear is the predominant risk factor for Acanthamoeba keratitis, the sex distribution of cases should be similar to the sex distribution of contact lens wearers, unless gender plays a role in the infection. We have no reason to suspect men are biologically at an increased risk for Acanthamoeba infection. Perhaps they are more likely to disregard recommended hygienic practices or are involved in activities that increase their risk of corneal trauma or exposure to polluted water. Future prospective studies should address sex-related behavioral differences and the development of corneal infection. The large number of cases reported from California, Texas, Florida, and Pennsylvania is difficult to explain. Careful examination of cases from these states suggests no temporal clustering indicative of a common source of infection (such as through a contaminated lot of contact lens solution). The geographic distribution of Acanthamoeba, although thought to be ubiquitous, is not known. Soil and water sources in these areas may be more highly contaminated with Acanthamoeba, allowing more frequent exposure among persons living in those areas. On the other hand, each of the high incidence areas has an active eye research center. Perhaps ophthalmologists from these states were more familiar with the diagnosis of Acanthamoeba keratitis at an earlier time and diagnosed the disease sooner. Although Acanthamoeba keratitis continues to be a relatively rare disease, its incidence is much higher than expected from published case reports and case series. Contact lens wear and use of homemade saline solutions persist as important risk factors associated with the disease. Persons wearing contact lenses should adhere closely to the contact lens wear and care procedures recommended by manufacturers and health care professionals. Ophthalmologists and optometrists should carefully explain these procedures to their patients who wear contact lenses and review these recommendations periodically. ACKNOWLEDGMENTS
We thank members of the Ocular Microbiology and Immunology Group and other participating ophthalmologists and pathologists for
335
responding to the survey. Dennis Juranek, D.V.M., helped develop this study, and Jennifer Dickerson, B.A., Floy Brandt, B.S., and Marianna Wilson, M.S. assisted in preparing the survey packets.
References 1. Visvesvara, G. 5.: Free-living pathogenic amoeba. In Lennette, E. H., Balows, A., and Hausler, W. J., Jr. (eds.): Manual of Clinical Microbiology, ed. 3. Washington, D.C., American Society for Microbiology, 1980, pp. 704-708. 2. Key, S. N., Green, W. R., WiIlaert, E., Stevens, A. R., Key, S. N.: Keratitis due to Acanthamoeba castellani. Arch. OphthalmoI. 98:475, 1980. 3. Ma, P., WiIlaert, E., [uechter, K. B., and Stevens, A. R.: A case of keratitis due to Acanthamoeba in New York, New York, and features of 10 cases. J. Infect. Dis. 143:662, 1981. 4. Samples, J. R., Binder, P. 5., Luibel, F. J., Font, R. L., Visvesvara, G. 5., and Peter, C. R.: Acanthamoeba keratitis possibly acquired from a hot tub. Arch. OphthalmoI. 102:707, 1984. 5. Hirst, L. W., Green, W. R., Merz, W., Kaufmann, C., Visvesvara, G. 5., Jensen, A., and Howard, M.: Management of Acanthamoeba keratitis. A case report and review of the literature. Ophthalmology 91:1105, 1984. 6. Blackman, H. J., Rao, N. A., Lemp, M. A., and Visvesvara, G. 5.: Acanthamoeba keratitis successfully treated with penetrating keratoplasty. Suggested immunogenic mechanism of action. Cornea 3:125, 1984.
7. Moore, M. B., McCulley, J. P., Luckenbach, M., Gelender, H., Newton, c., McDonald, M. B., and Visvesvara, G. 5.: Acanthamoeba keratitis associated with soft contact lenses. Am. J. OphthalmoI. 100:396, 1985.
8. Cohen, E. J., Buchanan, H. W., Laughrea, P. A., Adams, C. P., Galentine, P. G., Visvesvara, G.S., Folberg, R., Arentsen, J. J., and Laibson, P. R.: Diagnosis and management of Acanthamoeba keratitis. Am. J. OphthalmoI. 100:389, 1985. 9. Theodore, F. H., Iakobiec, F. A., [uechter, K. B., Ma, P., Troutman, R. c.. Pang, P. M., and Iwamoto, T.: The diagnostic value of a ring infiltrate in acanthamoebic keratitis. Ophthalmology 92:1471, 1985. 10. Margo, C. E., Brinser, J. H., and Groden, L.:
Exfoliated cytopathology of Acanthamoeba keratitis. JAMA 255:2216, 1986. 11. Wilhelmus, K. R., Osato, M.S., Font, R. L., Robinson, N. M., and Jones, D. B.: Rapid diagnosis of Acanthamoeba keratitis using calcofluor white. Arch. OphthalmoI. 104:1309, 1986. 12. Mannis, M. J., Tarnaru, R., Roth, A. M., Burns, M., and Thirkill, c.: Acanthamoeba sclerokeratitis.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
Determining diagnostic criteria. Arch. Ophthalmol. 104:1313, 1986. 13. Moore, M. B., McCulley, J. P., Kaufman, H. E., and Robin, J. B.: Radial keratoneuritis as a presenting sign in Acanthamoeba keratitis. Ophthalmology 93:1310, 1986. 14. Epstein, R. J., Wilson, L. A., Visvesvara, G. S., and Plourde, E. G.: Rapid diagnosis of Acanthamoeba keratitis from corneal scrapings using indirect fluorescent antibody staining. Arch. Ophthalmol. 104:1318, 1986. 15. McDonnel, P. J., and Robin, J. B.: Corneal allograft rejection in a pregnant woman. Cornea 6:281, 1987. 16. Moore, M. B., McCulley, J. P., Newton, c.. Cobo, L. M., Foulks, G. N., O'Day, D. M., Johns, K. J., Driebe, W. T., Wilson, L. A., Epstein, R. J., and Doughman, D. J.: Acanthamoeba keratitis. A growing problem in soft and hard contact lens wearers. Ophthalmology 94:1654, 1987. 17. Cohen, E. J., Parlato, C. J., Arentsen, J. J., Genvert, G. 1., Eagle, R. c., Wieland, M. R., and Laibson, P. R.: Medical and surgical treatment of Acanthamoeba keratitis. Am. J. Ophthalmol. 103:615, 1987. 18. Mathers, W., Stevens, G., Rodrigues, M., Chan, C. c.. Gold, J., Visvesvara, G. S., Lemp, M. A., and Zimmerman, L. E.: Immunopathology and electron microscopy of Acanthamoeba keratitis. Am. J. Ophthalmol. 103:626, 1987. 19. Koenig, S. B., Solomon, J. M., Hyndiuk, R. A., Sucher, R. A., and Gradus, M. S.: Acanthamoeba keratitis associated with gas-permeable contact lens wear. Am. J. Ophthalmol. 103:832, 1987. 20. Dornic, D. 1., Wolf, T., Dillon, W. H., Chris-
April, 1989
tensen, B., and Deem, C. D.: Acanthamoeba keratitis in soft contact lens wearers. J. Am. Optom. Assoc. 58:482, 1987. 21. Holland, G. N., and Donzis, P. B.: Rapid resolution of early Acanthamoeba keratitis after epithelial debridement. Am. J. Ophthalmol. 104:87, 1987. 22. Margo, C. E.: Acanthamoeba keratitis. Arch. Pathol. Lab. Med. 111:759, 1987. 23. Silvany, R. E., Luckenbach, M. W., and Moore, M. B.: The rapid detection of Acanthamoeba in paraffin-embedded sections of corneal tissue with calcofluor white. Arch. Ophthalmol. 105:1366, 1987. 24. Solomon, J. M., Hyndiuk, R. A., Koenig, S. B., and Gradus, M. S.: Acanthamoeba keratitis masquerading as corneal homograft rejection. Arch. Ophthalmol. 105:1326, 1987. 25. Davis, R. M., Schroeder, R. P., Rowsey, J. J., Jensen, H. G., and Tripathi, R. c.: Acanthamoeba keratitis and infectious crystalline keratopathy. Arch. Ophthalmol. 105:1524, 1987. 26. Lindquist, T. D., Sher, N. A., and Doughman, D. J.: Clinical signs and medical therapy of early Acanthamoeba keratitis. Arch. Ophthalmol. 106:73, 1988. 27. Johns, K. J., Head, W. S., and O'Day, D. M.: Corneal toxicity of propamidine. Arch. Ophthalmol. 106:68, 1988. 28. Stehr-Green, J. K., Bailey, T. M., Brandt, F. H., Carr, J. H., Bond, W. W., and Visvesvara, G. S.: Acanthamoeba keratitis in soft contact lens wearers. A case control study. JAMA 257:57, 1987. 29. Ormerod, L. D., and Smith, R. E.: Contact lens-associated microbial keratitis. Arch. Ophthalmol. 104:79, 1986.
OPHTHALMIC MINIATURE
Oh, this terrible gift of second-sight that comes to some of us when we begin to look through the silvered rings of the arcus senilis. Oliver Wendell Holmes, The Autocrat of the Breakfast-Table Boston, Nov. 1, 1858
Accepted for publication Jan. 12, 1989. From the Divisions of Host Factors (Dr. Stehr-Green) and Parasitic Diseases (Drs. Bailey and Visvesvara), Center for Infectious Diseases, Centers for Disease Control, Public Health Service, U. S. Department of Health and Human Services, Atlanta, Georgia. Reprint requests to Govinda S. Visvesvara, Ph.D., Division of Parasitic Diseases, Centers for Disease Control, Atlanta, GA 30333.
©AMERICAN JOURNAL OF OPHTHALMOLOGY
107:331-336,
in the United States.v" Nineteen of the reports, describing 60 patients, have been published since 1985, and 12 reports, describing 37 patients, have been published since 1987. However, because case reports are only a sample of all diagnosed cases, estimates of the incidence of the disease are still lacking. Historically, Acanthamoeba keratitis has been associated with penetrating corneal trauma and exposure to contaminated water. I •3•8 ,9 More recently, an association with contact lens wear has become apparent.vv'"" In a case-control study of soft contact lens wearers, using homemade saline, disinfecting lenses less frequently than recommended by the manufacturer, and wearing lenses while swimming were associated with Acanthamoeba keratitis." However, this study involved only soft contact lens wearers and, therefore, was not designed to look at risk factors among patients who did not wear contact lenses, nor to estimate the proportion of Acanthamoeba keratitis cases attributable to corneal trauma, exposure to contaminated water, or contact lens wear. To estimate better the number of cases of Acanthamoeba keratitis in the United States and the proportion of cases associated with the three major risk factors (corneal trauma, exposure to polluted water, or contact lens wear), we surveyed members of the Ocular Microbiology and Immunology Group (a society of corneal specialists) for reports of cases of Acanthamoeba keratitis. Charaeteristics of cases reported through group members, combined with those cases reported through requests for laboratory services at the Division of Parasitic Diseases, Centers for Disease Control, are presented herein.
Material and Methods In August 1986, all members of the Ocular Microbiology and Immunology Group living in APRIL,
1989
331
332
AMERICAN JOURNAL OF OPHTHALMOLOGY
the United States were contacted by mail. They were asked whether or not they had ever diagnosed, treated, or been consulted about a patient with Acanthamoeba keratitis. If yes, they were asked to provide demographic information (sex, age, state of residence, date of onset of keratitis, and associated risk factors) for each case; to maintain patient confidentiality, names and personal identifiers were not requested. Members were given preaddressed, postagepaid postcards on which to reply. * Members were encouraged to continue reporting cases by this method as they were diagnosed. Between May and July 1988, we contacted all physicians by phone who had reported cases to determine the method of diagnosis and to identify patients reported from multiple sources. Patients residing outside the United States at the onset of keratitis and patients whose infections were not confirmed by culture, histology, or immunofluorescence studies were excluded from the analyses. To identify additional cases of Acanthamoeba keratitis not reported through the survey, we reviewed specimen log books for Acanthamoeba laboratory requests maintained by the Division of Parasitic Diseases through July 1988. Information on all patients with corneal specimens found to be positive for Acanthamoeba on culture, histology, or immunofluorescence studies was abstracted from specimen data sheets. We attempted to contact by phone all physicians submitting samples found to be positive to obtain additional demographic information. Statistical tests used in the comparisons were Fisher's two-tailed exact test and Wilcoxon rank-sum test where appropriate.
Results As of August 1986, the Ocular Microbiology and Immunology Group had 287 members living in the United States. Of these, 20 could not be reached. Of the remaining 267, 175 (66%) responded by returning the provided postcard. Fifty eight (33%) reported diagnosing, treating, or being consulted about at least one confirmed case of Acanthamoeba keratitis, and 11 (6%) reported diagnosing, treating, or being consulted
'Because of changes in postage labels used by the Centers for Disease Control, postcards originally distributed for this study are no longer valid.
April, 1989
about at least one patient with suspected but unconfirmed Acanthamoeba keratitis. Using follow-up calls to physicians, we identified 149 patients with confirmed Acanthamoeba keratitis (excluding duplicates and unconfirmed cases). Review of specimen log books from the Division of Parasitic Diseases identified 144 patients with specimens positive for Acanthamoeba. Fifty nine had not been reported through the survey. These 59 were combined with the 149 cases reported through the survey for the following analyses. The first case of Acanthamoeba keratitis was diagnosed in 1973 in a man from southern Texas with a history of ocular trauma and exposure to contaminated water' (Fig. 1). Between 1973 and 1981, only five additional cases were diagnosed. The number of cases increased gradually from 1981 through 1984, with a dramatic increase in 1985 through 1987. The number again fell in the second quarter of 1988. Of the 208 patients, 101 (49%) were male and 107 (51%) were female. The median age at the onset of keratitis was 29 years, but ranged from 13 to 82 years. Age distribution did not vary by sex. Age and sex distribution did not vary over time. Patients resided in 34 states and the District of Columbia at the onset of their symptoms (Fig. 2). Most cases (41 %) were reported from California (29), Texas (29), Florida (IS), and Pennsylvania (12). Complete risk factor information was not available for each patient. Of the 189 patients for whom at least partial information on risk factors was available, 179 (95%) had at least one risk factor for Acanthamoeba keratitis (history of corneal trauma, exposure to contaminated water, or contact lens wear). Patients aged 50 years and older were less likely to have had a risk factor identified (18 of 21 [86%] vs 156 of 159 [98%], P = .02) than younger patients. Of the 189 patients for whom information was available, 160 (85%) wore contact lenses, most of which were daily-wear or extended-wear soft lenses (Table). Of 154 patients, 26 (17%) had a history of corneal trauma and 37 of 150 (25%) had a history of exposure to contaminated water. Of the 138 patients who wore contact lenses for whom information was available, 88 (64%) had a history of using saline prepared using distilled water and salt tablets. Patients aged 50 years and older were more likely to have had a history of trauma (seven of 18 [39%] vs 18 of 133 [14%], P = .01) and were less likely to have worn contact lenses (11 of 23 [48%] vs 145 of 160 [91%], P < .0001) than younger
16 15 14 13 12 11 10 (f)
9
(f)
8
w
-c
U
7
6 5 4 3 2
'~
0
R
=
RR~
~
1973 1974 1975 1976 1977 1978'1979 1980 1981 1982 1983 1984 1985 1986 1987 1988
QUARTER OF ONSET Fig. 1 (Stehr-Green, Bailey, and Visvesvara). United States Acanthamoeba keratitis cases by date of onset of symptoms, 1973 through June 1988.
~ NO CASES . . . . 10-19 CASES
I2ZZl 1-4 CASES _ >=20 CASES
B8SB!lI 5-9 CASES
Fig. 2 (Stehr-Green, Bailey, and Visvesvara). United States Acanthamoeba keratitis cases by state of residence, 1973 through June 1988.
334
AMERICAN JOURNAL OF OPHTHALMOLOGY
TABLE ACANTHAMOEBA KERATITIS LENSTYPE
BY CONTACT LENS
TYPE NO.
Daily-wear, soft Extended-wear, soft Soft, type unknown Saturn lens Rigid gas-permeable Hard lens Unknown
(%)
89
(56)
31
(19)
9
(6)
12
(8)
11
(7)
3
(2)
5
(3)
patients. Males were more likely to have had a history of trauma (19 of 74 [26%] vs seven of 80 [9%], P = .009) and were less likely to have had a history of contact lens wear (73 of 91 [80%] vs 87 of 98 [89%], P = .02) than females.
Discussion
The results of our survey suggest that the incidence of Acanthamoeba keratitis in the United States is much higher than anticipated from published case reports, and that contact lens wear is the predominant risk factor. Our survey probably did not identify all patients with Acanthamoeba keratitis diagnosed between 1973 and June 1988 in the United States. We only contacted members of the Ocular Microbiology and Immunology Group and ophthalmologists who had submitted specimens to the Division of Parasitic Diseases, Centers for Disease Control, for Acanthamoeba studies. However, Acan" thamoeba keratitis is often difficult to diagnose and virtually always difficult to treat; therefore, most cases are referred to a specialist, at least in consultation, during the course of the disease. Because the Ocular Microbiology and Immunology Group is a group of corneal specialists, we thought they would know about most cases in the United States. However, not all corneal specialists are members of this group and, therefore, would not have been contacted unless they submitted specimens directly to the Centers for Disease Control. As a result, some cases may have been missed and our estimate of disease incidence (although much higher than expected) must be considered a minimal estimate. Although expected from case reports, the dramatic increase in cases beginning in 1985 is
April, 1989
puzzling and cannot be explained through findings from our survey. Two potential explanations exist. First, as more reports on Acanthamoeba have been published, ophthalmologists have become more familiar with the diagnosis and may diagnose the disease more accurately. Review of histologic specimens from Wills Eye Hospital suggest that some early cases of Acanthamoeba may have been missed." Of eight cases of active corneal ulceration undiagnosed before 1983, two were found to have had Acanthamoeba present on review after this organism became better known. Second, the increase in cases could indicate a true increase in incidence of the disease. This could result from increased prevalence of the organism, increased virulence of the organism, or increased number of persons at risk. The first two possibilities seem unlikely. However, the increase of Acanthamoeba keratitis in the United States has been paralleled by an increase in the number of persons wearing contact lenses from an estimated 14.5 million in 1980 to 23.1 million in 1985. 29 This increase has occurred primarily in the number of soft contact lens wearers, who use saline as an integral part of contact lens care. As contact lens wear has become more common, contact lens wearers may have also become less meticulous in handling their lenses or ophthalmologists/optometrists may have become less diligent in instructing patients about the proper care of their lenses. This increase in the number of contact lens wearers and an increase in the number of persons caring improperly for their lenses could increase the number of persons at risk for Acanthamoeba keratitis. The decrease in cases in late 1987 and early 1988 may not be an indication of decreased incidence in Acanthamoeba keratitis. Many months had passed since the original request for cases to be reported by members of the Ocular Microbiology and Immunology Group to the Centers for Disease Control. Without an intervening reminder, many physicians could have forgotten about the survey and, therefore, did not report new cases. Outside laboratories have also become more proficient in culturing and identifying Acanthamoeba. As a result, the Division of Parasitic Diseases may receive a smaller proportion of the requests for Acanthamoeba laboratory services and, therefore, fewer cases may be identified through this source. The nearly equal distribution of Acanthamoeba keratitis cases between males and females is
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unexpected. Marketing data suggest that only 28% of soft contact lens wearers in the United States are male (Catherine 1. McGuire, B.A., written communication, July 10, 1986). If contact lens wear is the predominant risk factor for Acanthamoeba keratitis, the sex distribution of cases should be similar to the sex distribution of contact lens wearers, unless gender plays a role in the infection. We have no reason to suspect men are biologically at an increased risk for Acanthamoeba infection. Perhaps they are more likely to disregard recommended hygienic practices or are involved in activities that increase their risk of corneal trauma or exposure to polluted water. Future prospective studies should address sex-related behavioral differences and the development of corneal infection. The large number of cases reported from California, Texas, Florida, and Pennsylvania is difficult to explain. Careful examination of cases from these states suggests no temporal clustering indicative of a common source of infection (such as through a contaminated lot of contact lens solution). The geographic distribution of Acanthamoeba, although thought to be ubiquitous, is not known. Soil and water sources in these areas may be more highly contaminated with Acanthamoeba, allowing more frequent exposure among persons living in those areas. On the other hand, each of the high incidence areas has an active eye research center. Perhaps ophthalmologists from these states were more familiar with the diagnosis of Acanthamoeba keratitis at an earlier time and diagnosed the disease sooner. Although Acanthamoeba keratitis continues to be a relatively rare disease, its incidence is much higher than expected from published case reports and case series. Contact lens wear and use of homemade saline solutions persist as important risk factors associated with the disease. Persons wearing contact lenses should adhere closely to the contact lens wear and care procedures recommended by manufacturers and health care professionals. Ophthalmologists and optometrists should carefully explain these procedures to their patients who wear contact lenses and review these recommendations periodically. ACKNOWLEDGMENTS
We thank members of the Ocular Microbiology and Immunology Group and other participating ophthalmologists and pathologists for
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responding to the survey. Dennis Juranek, D.V.M., helped develop this study, and Jennifer Dickerson, B.A., Floy Brandt, B.S., and Marianna Wilson, M.S. assisted in preparing the survey packets.
References 1. Visvesvara, G. 5.: Free-living pathogenic amoeba. In Lennette, E. H., Balows, A., and Hausler, W. J., Jr. (eds.): Manual of Clinical Microbiology, ed. 3. Washington, D.C., American Society for Microbiology, 1980, pp. 704-708. 2. Key, S. N., Green, W. R., WiIlaert, E., Stevens, A. R., Key, S. N.: Keratitis due to Acanthamoeba castellani. Arch. OphthalmoI. 98:475, 1980. 3. Ma, P., WiIlaert, E., [uechter, K. B., and Stevens, A. R.: A case of keratitis due to Acanthamoeba in New York, New York, and features of 10 cases. J. Infect. Dis. 143:662, 1981. 4. Samples, J. R., Binder, P. 5., Luibel, F. J., Font, R. L., Visvesvara, G. 5., and Peter, C. R.: Acanthamoeba keratitis possibly acquired from a hot tub. Arch. OphthalmoI. 102:707, 1984. 5. Hirst, L. W., Green, W. R., Merz, W., Kaufmann, C., Visvesvara, G. 5., Jensen, A., and Howard, M.: Management of Acanthamoeba keratitis. A case report and review of the literature. Ophthalmology 91:1105, 1984. 6. Blackman, H. J., Rao, N. A., Lemp, M. A., and Visvesvara, G. 5.: Acanthamoeba keratitis successfully treated with penetrating keratoplasty. Suggested immunogenic mechanism of action. Cornea 3:125, 1984.
7. Moore, M. B., McCulley, J. P., Luckenbach, M., Gelender, H., Newton, c., McDonald, M. B., and Visvesvara, G. 5.: Acanthamoeba keratitis associated with soft contact lenses. Am. J. OphthalmoI. 100:396, 1985.
8. Cohen, E. J., Buchanan, H. W., Laughrea, P. A., Adams, C. P., Galentine, P. G., Visvesvara, G.S., Folberg, R., Arentsen, J. J., and Laibson, P. R.: Diagnosis and management of Acanthamoeba keratitis. Am. J. OphthalmoI. 100:389, 1985. 9. Theodore, F. H., Iakobiec, F. A., [uechter, K. B., Ma, P., Troutman, R. c.. Pang, P. M., and Iwamoto, T.: The diagnostic value of a ring infiltrate in acanthamoebic keratitis. Ophthalmology 92:1471, 1985. 10. Margo, C. E., Brinser, J. H., and Groden, L.:
Exfoliated cytopathology of Acanthamoeba keratitis. JAMA 255:2216, 1986. 11. Wilhelmus, K. R., Osato, M.S., Font, R. L., Robinson, N. M., and Jones, D. B.: Rapid diagnosis of Acanthamoeba keratitis using calcofluor white. Arch. OphthalmoI. 104:1309, 1986. 12. Mannis, M. J., Tarnaru, R., Roth, A. M., Burns, M., and Thirkill, c.: Acanthamoeba sclerokeratitis.
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Determining diagnostic criteria. Arch. Ophthalmol. 104:1313, 1986. 13. Moore, M. B., McCulley, J. P., Kaufman, H. E., and Robin, J. B.: Radial keratoneuritis as a presenting sign in Acanthamoeba keratitis. Ophthalmology 93:1310, 1986. 14. Epstein, R. J., Wilson, L. A., Visvesvara, G. S., and Plourde, E. G.: Rapid diagnosis of Acanthamoeba keratitis from corneal scrapings using indirect fluorescent antibody staining. Arch. Ophthalmol. 104:1318, 1986. 15. McDonnel, P. J., and Robin, J. B.: Corneal allograft rejection in a pregnant woman. Cornea 6:281, 1987. 16. Moore, M. B., McCulley, J. P., Newton, c.. Cobo, L. M., Foulks, G. N., O'Day, D. M., Johns, K. J., Driebe, W. T., Wilson, L. A., Epstein, R. J., and Doughman, D. J.: Acanthamoeba keratitis. A growing problem in soft and hard contact lens wearers. Ophthalmology 94:1654, 1987. 17. Cohen, E. J., Parlato, C. J., Arentsen, J. J., Genvert, G. 1., Eagle, R. c., Wieland, M. R., and Laibson, P. R.: Medical and surgical treatment of Acanthamoeba keratitis. Am. J. Ophthalmol. 103:615, 1987. 18. Mathers, W., Stevens, G., Rodrigues, M., Chan, C. c.. Gold, J., Visvesvara, G. S., Lemp, M. A., and Zimmerman, L. E.: Immunopathology and electron microscopy of Acanthamoeba keratitis. Am. J. Ophthalmol. 103:626, 1987. 19. Koenig, S. B., Solomon, J. M., Hyndiuk, R. A., Sucher, R. A., and Gradus, M. S.: Acanthamoeba keratitis associated with gas-permeable contact lens wear. Am. J. Ophthalmol. 103:832, 1987. 20. Dornic, D. 1., Wolf, T., Dillon, W. H., Chris-
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tensen, B., and Deem, C. D.: Acanthamoeba keratitis in soft contact lens wearers. J. Am. Optom. Assoc. 58:482, 1987. 21. Holland, G. N., and Donzis, P. B.: Rapid resolution of early Acanthamoeba keratitis after epithelial debridement. Am. J. Ophthalmol. 104:87, 1987. 22. Margo, C. E.: Acanthamoeba keratitis. Arch. Pathol. Lab. Med. 111:759, 1987. 23. Silvany, R. E., Luckenbach, M. W., and Moore, M. B.: The rapid detection of Acanthamoeba in paraffin-embedded sections of corneal tissue with calcofluor white. Arch. Ophthalmol. 105:1366, 1987. 24. Solomon, J. M., Hyndiuk, R. A., Koenig, S. B., and Gradus, M. S.: Acanthamoeba keratitis masquerading as corneal homograft rejection. Arch. Ophthalmol. 105:1326, 1987. 25. Davis, R. M., Schroeder, R. P., Rowsey, J. J., Jensen, H. G., and Tripathi, R. c.: Acanthamoeba keratitis and infectious crystalline keratopathy. Arch. Ophthalmol. 105:1524, 1987. 26. Lindquist, T. D., Sher, N. A., and Doughman, D. J.: Clinical signs and medical therapy of early Acanthamoeba keratitis. Arch. Ophthalmol. 106:73, 1988. 27. Johns, K. J., Head, W. S., and O'Day, D. M.: Corneal toxicity of propamidine. Arch. Ophthalmol. 106:68, 1988. 28. Stehr-Green, J. K., Bailey, T. M., Brandt, F. H., Carr, J. H., Bond, W. W., and Visvesvara, G. S.: Acanthamoeba keratitis in soft contact lens wearers. A case control study. JAMA 257:57, 1987. 29. Ormerod, L. D., and Smith, R. E.: Contact lens-associated microbial keratitis. Arch. Ophthalmol. 104:79, 1986.
OPHTHALMIC MINIATURE
Oh, this terrible gift of second-sight that comes to some of us when we begin to look through the silvered rings of the arcus senilis. Oliver Wendell Holmes, The Autocrat of the Breakfast-Table Boston, Nov. 1, 1858