Recrudescent Acanthamoeba Recrudescent Acanthamoeba Keratitis Related to Persistent Keratitis Related to Persistent Contact Lens WearContact Lens Wear

Elmer Y TuElmer Y Tu1A1A, Charlotte E Joslin, Charlotte E Joslin11, Megan E Shoff, Megan E Shoff22, Janet A. Lee, Janet A. Lee11, , Ali DjalilianAli Djalilian11

11Department of Ophthalmology and Visual SciencesDepartment of Ophthalmology and Visual SciencesUniversity of Illinois Eye and Ear InfirmaryUniversity of Illinois Eye and Ear InfirmaryChicago, IllinoisChicago, Illinois22Department of Molecular GeneticsDepartment of Molecular GeneticsThe Ohio State UniversityThe Ohio State UniversityColumbus, OhioColumbus, Ohio

1A Allergan – travel honoraria

No conflicts of interest pertaining to this presentation.

Off-label use will be discussed

Purpose:Purpose: To report patients with a To report patients with a second diagnosis of Acanthamoeba second diagnosis of Acanthamoeba keratitis after continuing contact lens keratitis after continuing contact lens wearwear

Methods:Methods: Acanthamoeba keratitis Acanthamoeba keratitis patients diagnosed between 06/2003 – patients diagnosed between 06/2003 – 09/200709/2007 University of Illinois Eye and Ear InfirmaryUniversity of Illinois Eye and Ear Infirmary Cases reviewed for involvement of multiple Cases reviewed for involvement of multiple

eyeseyes

ResultsResults

88 total patients identified with 88 total patients identified with Acanthamoeba keratitisAcanthamoeba keratitis

9 patients diagnosed with multiple 9 patients diagnosed with multiple infectionsinfections 7 presenting with bilateral disease7 presenting with bilateral disease 1 patient had the contralateral eye involved 1 patient had the contralateral eye involved

3 months later3 months later 1 patient presented with re-involvement of 1 patient presented with re-involvement of

the same eye 17 months laterthe same eye 17 months later

Case 1Case 1

17 year old white male presented 6/1/07 with a 17 year old white male presented 6/1/07 with a severe, painful recurrent keratitis OS severe, painful recurrent keratitis OS Failed treatment topical antibiotics, antivirals and Failed treatment topical antibiotics, antivirals and

corticosteroidcorticosteroid Confocal microscopy c/w Confocal microscopy c/w AcanthamoebaAcanthamoeba

Cultures negativeCultures negative Resolution over three months with propamidine and Resolution over three months with propamidine and

chlorhexidine with small residual scar (figure above)chlorhexidine with small residual scar (figure above)

Patient continued contact lens wear OD, despite Patient continued contact lens wear OD, despite warnings to discontinuewarnings to discontinue

Resolved scar

Partial immune ring

Epithelium

Stroma

Acanthamoeba CystsCase 1Case 1

Patient presented with necrotic ulcer OD Patient presented with necrotic ulcer OD 9/7/079/7/07 Partially treated ulcer was culture negativePartially treated ulcer was culture negative

Fortified cefazolin and gentamicinFortified cefazolin and gentamicin Good response clinically and symptomaticallyGood response clinically and symptomatically

9/18/20079/18/2007 Reports increasing discomfort and forms an Reports increasing discomfort and forms an

immune ring (figure below)immune ring (figure below) Confocal positive (see above)Confocal positive (see above)

Case 2Case 2

16 year old African-American male 2/13/0616 year old African-American male 2/13/06 SCL wearer treated for 2 weeks with Viroptic and SCL wearer treated for 2 weeks with Viroptic and

AcyclovirAcyclovir Referred for keratitis with radial neuritis ODReferred for keratitis with radial neuritis OD Confocal/ Diff-Quick Smear/ Culture positiveConfocal/ Diff-Quick Smear/ Culture positive 20/20 vision after 3 months of therapy20/20 vision after 3 months of therapy

Propamidine and chlorhexidinePropamidine and chlorhexidine

Patient resumed contact lens wear 3 months Patient resumed contact lens wear 3 months laterlater Sports scholarship to collegeSports scholarship to college

Bright-centered Acanthamoeba cysts

Case 2Case 2

Presented 7/26/07 with pain and Presented 7/26/07 with pain and decreased vision (20/40) OD x 2 weeksdecreased vision (20/40) OD x 2 weeks SCL wear/ AMO Complete Moisture PlusSCL wear/ AMO Complete Moisture Plus Swimming in lenses 3 weeks prior Swimming in lenses 3 weeks prior in another in another

statestate where he was in school for the past 9 where he was in school for the past 9 monthsmonths

Confocal/ Diff-Quick Smear/ Culture positiveConfocal/ Diff-Quick Smear/ Culture positive Genotype distinct from first isolateGenotype distinct from first isolate

Diff-Quik Stain (Original magnifiction 100x oil)

Genotyping resultsGenotyping results

Sequence comparison of the two isolates obtained from Case 2 for a 135 Sequence comparison of the two isolates obtained from Case 2 for a 135 nucleotide base region within one of the highly informative diagnostic fragments nucleotide base region within one of the highly informative diagnostic fragments of the of the AcanthamoebaAcanthamoeba 18S rRNA gene.  The two isolates, 06-005 and 07-072, 18S rRNA gene.  The two isolates, 06-005 and 07-072, clearly differ from each other, with 13/135 base differences.  However, as clearly differ from each other, with 13/135 base differences.  However, as shown, each isolate separately closely resembles different previously reported shown, each isolate separately closely resembles different previously reported AcanthamoebaAcanthamoeba sequences found in the DNA database GenBank. sequences found in the DNA database GenBank.

DiscussionDiscussion

A common question from patients successfully treated for A common question from patients successfully treated for Acanthamoeba Acanthamoeba keratitis (AK) is the safety of subsequent contact lens wear. Since AK is a keratitis (AK) is the safety of subsequent contact lens wear. Since AK is a rare disease estimated to affect approximately 2-20 wearers per million rare disease estimated to affect approximately 2-20 wearers per million contact lens wearers per year, by chance alone, the likelihood of a second contact lens wearers per year, by chance alone, the likelihood of a second infection is remote. The understanding of the risk factors and mechanisms infection is remote. The understanding of the risk factors and mechanisms for the development of AK remain, however, incomplete.for the development of AK remain, however, incomplete.

While the sequential nature of bilateral AK has been previously described, While the sequential nature of bilateral AK has been previously described, as seen in case 1, it does not distinguish the roles of environment and as seen in case 1, it does not distinguish the roles of environment and individual susceptibility since these patients usually have little change in individual susceptibility since these patients usually have little change in their environment during the short time between occurrences.their environment during the short time between occurrences.

Re-occurrence in the same eye 17 months apart, as illustrated in Case 2, Re-occurrence in the same eye 17 months apart, as illustrated in Case 2, may still represent either a reactivation of the original infection or a may still represent either a reactivation of the original infection or a second, new infection. second, new infection. The interval lack of symptoms and signs of The interval lack of symptoms and signs of infection and the identification of two genetically distinct pathogenic infection and the identification of two genetically distinct pathogenic AcanthamoebaAcanthamoeba isolates make it strongly likely that patient 2 contracted a isolates make it strongly likely that patient 2 contracted a new infection after persisting with soft contact lens wear.new infection after persisting with soft contact lens wear.

DiscussionDiscussion

While uncommonly highlighted, bilateral, contemporaneous While uncommonly highlighted, bilateral, contemporaneous disease may occur in up to 8-10% of patients and is congruent disease may occur in up to 8-10% of patients and is congruent with our own experience during the Chicago with our own experience during the Chicago AcanthamoebaAcanthamoeba outbreak.outbreak. Whether this is more common to environmentally Whether this is more common to environmentally sourced outbreaks is unclear. The odds of contracting two sourced outbreaks is unclear. The odds of contracting two separate infections without significantly common risk factors are separate infections without significantly common risk factors are prohibitively unlikely, but in bilateral disease could be attributed to prohibitively unlikely, but in bilateral disease could be attributed to a common exposure, or load, of organisms either in the a common exposure, or load, of organisms either in the environment, as we have previously hypothesized, or overgrowth environment, as we have previously hypothesized, or overgrowth within an individual’s contact lens care system.within an individual’s contact lens care system.

It is also unknown whether individual patients may be uniquely It is also unknown whether individual patients may be uniquely susceptible to susceptible to AcanthamoebaAcanthamoeba keratitis. Case 2 indicates that, keratitis. Case 2 indicates that, despite its rare incidence, an individual can contract a separate despite its rare incidence, an individual can contract a separate rare infection in a different environment while attending college rare infection in a different environment while attending college 900 miles away. Although hygiene factors may play a role, the 900 miles away. Although hygiene factors may play a role, the relative permissiveness of ocular defense mechanisms including relative permissiveness of ocular defense mechanisms including local and systemic immune defenses may also contribute.local and systemic immune defenses may also contribute.

ConclusionConclusion

These cases indicate an ongoing risk for the These cases indicate an ongoing risk for the development of Acanthamoeba keratitis in development of Acanthamoeba keratitis in patients previously infected.patients previously infected. Acanthamoeba keratitis may require not only the Acanthamoeba keratitis may require not only the

presence of organisms, but also some measure of presence of organisms, but also some measure of individual susceptibility.individual susceptibility.

The understanding of the mechanisms and risk The understanding of the mechanisms and risk factors for human corneal infection with factors for human corneal infection with Acanthamoeba remains incomplete and deserves Acanthamoeba remains incomplete and deserves further study. further study.

AcknowledgmentsAcknowledgments

University of Illinois Eye University of Illinois Eye and Ear Infirmaryand Ear Infirmary

Joel Sugar, MDJoel Sugar, MD Leslie T. Stayner, PhDLeslie T. Stayner, PhD Jamie Brahmbhatt, COMTJamie Brahmbhatt, COMT

The Ohio State University, The Ohio State University, Dept. Molecular GeneticsDept. Molecular Genetics Gregory C. Booton, PhDGregory C. Booton, PhD Paul A. Fuerst, PhDPaul A. Fuerst, PhD

Support:Support: Prevent Blindness AmericaPrevent Blindness America Midwest Eye-BanksMidwest Eye-Banks NIH/NEI K23 15689NIH/NEI K23 15689 UIC Campus Research Board UIC Campus Research Board Gerhard Cless FoundationGerhard Cless Foundation

Selected ReferencesSelected References

Joslin CE, Tu EY, Shoff ME, et al. The Association of Contact Lens Solution Use and Acanthamoeba Keratitis. Am J Ophthalmol 2007.

Joslin CE, Tu EY, McMahon TT, Passaro DJ, Stayner LT, Sugar J. Epidemiological characteristics of a Chicago-area Acanthamoeba keratitis outbreak. Am J Ophthalmol 2006;142:212-7.

Wilhelmus KR, Jones DB, Matoba AY, Hamill MB, Pflugfelder SC, Weikert MP. Bilateral acanthamoeba keratitis. Am J Ophthalmol 2008;145:193-197.

Bernauer W, Duguid GI, Dart JK. [Early clinical diagnosis of acanthamoeba keratitis. A study of 70 eyes]. Klin Monatsbl Augenheilkd 1996;208:282-4.

Ficker L, Seal D, Warhurst D, Wright P. Acanthamoeba keratitis--resistance to medical therapy. Eye 1990;4 ( Pt 6):835-8.

Johnson AM, Fielke R, Christy PE, Robinson B, Baverstock PR. Small subunit ribosomal RNA evolution in the genus Acanthamoeba. J Gen Microbiol 1990;136:1689-98.