A 12 year history of Chronic, Culture-confirmed Acanthamoeba Keratitis Elmer Y. Tu, MD Joel Sugar, MD Charlotte E. Joslin, PhD Lisa M. Nijm, JD, MD The authors have no financial interest in the subject matter of this poster

Purpose To report a case of chronic, recalcitrant Acanthamoeba keratitis (AK) persisting for over 12+ yrs.

Clinical Presentation (12/27/1995) 32 y.o female physician contact lens wearer seen in consultation at the University of Illinois Eye and Ear Infirmary (IEEI) for chronic keratitis of the right eye of 2 years duration. Herpetic keratitis 1989 OD Recurrent dendritic disease 1994 Dendritic disease resolved with topical trifluridine alone Development of persistent stromal edema, subsequent immune ring June 1995 – Recurrence tx with topical corticosteroids, trifluridine. Persistent inflammation required continued medications as above. Oral acyclovir was added 200 mg q.i.d.

Clinical Presentation (12/27/1995) OS Normal OD VA 20/40-2 Slit lamp examination Mild central stromal edema Fine KP over the central corneal endothelium AC quiet Partial, superficial anterior stromal immune crescent extending between 3 and 7 o’clock paracentrally.

Clinical course Waxing and waning course of corneal inflammation Visual acuity fluctuates between 20/20 and 20/50. Chronic very low dose topical corticosteroids and occasional trifluridine Referred to the University of Iowa Confocal microscopy and epithelial biopsy performed Acanthamoebae identified

Clinical course Initial anti-acanthamoebal treatment Chlorhexidine 0.02% Q2h for 3 weeks Continued for 11 months Q2-qid dosing. Discontinued because of pregnancy Maintained on topical steroids Subsequent 8 years Extended treatment with topical chlorhexidine, polyhexamethyl biguanide (PHMB), desmodine, oral itraconazole without significant change in inflammatory recurrences or activity. Visual acuity largely maintained 20/20-20/25 BSCVA Intact endothelium Stromal haze, scarring No organisms appreciated 2001 Nidek Confoscan 2

Clinical Course Follow up at an outside facility without change in therapy November, 2006 Increasing severity and frequency of episodes of inflammation Prednisolone acetate 1% Q1h Decreasing vision – 20/60 Corneal thickness – 576 OD, 618 OS IOP normal Slit lamp examination – Large KP, moderate corneal haze

Intervention Vision declined to 20/200 despite hourly topical corticosteroids, topical chlorhexidine, oral voriconazole Full thickness Penetrating keratoplasty 1.9.2007 Pathology – endothelial cell attenuation, stromal infiltration No organisms seen Culture – Positive for acanthamoeba Microcystic epithelial edema Acanthamoeba cysts in deep stroma – bright centered thick walled structures (arrow) 2006 Nidek Confoscan 3

Follow-up August, 2009 Visual acuity BSCVA 20/30 Topical loteprednol QD No adjunctive anti-acanthamoebal therapy No further episodes of inflammation

Discussion To our knowledge, our patient represents the longest sustained corneal infestation with recoverable Acanthamoebae reported to date. The stromal inflammation seen in our patient is not uncommon in AK, but usually subsides with preferred therapy which our patient received for years often at high sustained frequencies. Indicates that this organism was clinically resistant Persistence of inflammation has been suggested to represent either persistent infection, reported lasting a year or more, or a sterile reaction to persistent amoebic antigens.

Discussion Persistence of infection is not surprising. Acanthamoebal cysts may survive in harsh environments, remaining viable for decades. Host immune response is likely ineffective in aiding clearance of Acanthamoebae The use of corticosteroids has not been associated with poorer outcomes in AK, and it is unclear what role it may have had here, but was successful in maintaining ~ 20/25 vision for over a decade

Conclusion Clinicians need to be aware that AK may manifest as a chronic recurrent stromal keratitis lasting >10 years Chronic, persistent inflammation should not be interpreted as sterile until otherwise proven Course further mimics HSV keratitis May also coexist with HSV keratitis Should be suspected in any at-risk individuals with this clinical picture Contact lens wearers Confocal microscopy has adjunctive utility in deep AK Identified both at epithelial and deep stromal stage Surgical intervention may be necessary and curative when medical therapy fails Oral voriconazole was added late, earlier, more aggressive medical therapy may be indicated