Nasreen A. Syed, MD F.C. Blodi Eye Pathology Laboratory University of Iowa
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1 Nasreen A. Syed, MD F.C. Blodi Eye Pathology Laboratory University of Iowa
2 No financial interest in any of the material discussed in this presentation There will be discussion of off label use of medications, not unapproved devices
3 31 year old male referred for foreign body sensation and decreased vision in the right eye Got something in his eye 2 months prior Treated by local optometrist with bandage contact lens and artificial tears for a few days Placed on tobramycin/dexamethasone ointment 2 weeks later, developed an infection and was started on the topical antiviral trifluridine for presumed HSV keratitis Superficial keratectomy (corneal epithelial scraping) performed Pain continued to worsen despite treatment
4 Past ocular history Myopia with contact lens wear No prior history of eye surgery or trauma Past medical history Intermittent cold sores on lips Otherwise negative Social history Construction worker Eye medications Trifluridine every 2 hours, right eye Gatifloxacin every 2 hours, right eye Prednisolone 6x daily, right eye Other medications None
5 Visual acuity with correction (glasses) Right eye 20/300, no improvement with pinhole Left eye 20/30-1, pinhole 20/20-1 Intraocular pressure (tonopen) Right eye 17 Left eye 17 Pupils Right eye 8mm > non-reactive, no RAPD Left eye 6mm > 5mm, no RAPD Fundus exam Right eye hazy view but grossly normal Left eye - normal
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8 Corneal cultures Gram stain and bacterial cultures negative Fungal smear and culture negative Viral testing PCR negative for HSV 1 and 2 Direct fluorescent antibody (DFA) positive for HSV 1
9 Patient treated as HSV stromal keratitis with persistent epithelial defect Acyclovir orally His keratitis and symptoms continue to worsen
10 2 weeks later
11 2 weeks later confocal imaging
12 Superficial keratectomy repeated
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15 PAS stain
16 Wright-Giemsa stain
17 Stains for diagnosis of Acanthamoeba H&E most commonly used PAS GMS Wright-Giemsa Calcofluor white fluorescent stain Acridine orange fluorescent stain Molecular testing is only available through CDC in North America and may take weeks to get results Culture must be done with on agar with a layer of E. coli growing on the surface Tracks of amoeba are considered diagnostic
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19 Acanthamoeba is a ubiquitous single-cell free living organism (Protist) Found in fresh water; soil Two stages in life cycle: Cysts (15μ in diameter) Found in stressful environments Most often seen on histology easiest to identify Trophozoite (20-50μ in diameter) Capable of cell division Nucleus has prominent nucleolus 3 diseases in humans Keratitis usually healthy individuals Granulomatous amebic encephalitis usually in immunocompromised Disseminated infection usually in immunocompromised
20 Diagnosed with Acanthamoeba keratitis Start chlorhexidine drops every 1 hour Cationic antiseptic agent Disrupts membrane function (ergosterol) Amoebicidal and cysticidal Continue: Moxifloxacin drops 4x daily Bacterial superinfection may be present Prednisolone drops 4x daily Acyclovir 400mg PO 5x daily HSV and Acanthamoeba infection can coexist
21 Risk factors for Acanthamoeba keratitis Soft contact lens wear Poor contact lens hygiene Type of contact lens solution Swimming in contaminated fresh water (ponds, lakes, etc) Use of hot tub/jacuzzi, especially when wearing soft contact lenses Trauma with vegetable matter, soil contamination Use of contaminated eye wash after chemical injury
22 Follow up: No improvement over the next 4 weeks Repeat in vivo confocal microscopy confirmed persistent Acanthamoeba Plan large diameter penetrating keratoplasty (full thickness corneal transplant)
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24 Post-operative medication regimen Chlorhexidine 4x daily Brolene 4x daily Aromatic diamidine Inhibit DNA (purine) synthesis Effective against trophozoites and cysts, but resistant isolates exist Levofloxacin 4x daily Prednisolone 4x daily Acyclovir 400mg by mouth 3x daily
25 Post-operative month 2 Infiltrates in the cornea at the graft-host junction Corneal cultures Gram stain and bacterial cultures negative Fungal smear and culture negative In vivo confocal microscopy shows possible amoeba Repeat penetrating keratoplasty (#2) Course of intravenous pentamidine prior to surgery 200mg daily for 14 days Acanthamoeba identified in corneal tissue removed
26 Post-operative medications: Chlorhexidine 4x daily Brolene 4x daily Levofloxacin 4x daily Prednisolone 4x daily Acyclovir 400mg PO 3x daily
27 Episodes of elevated intraocular pressure Allograft rejection New ring infiltrate in graft with recurrence of Acanthamoeba confirmed by confocal microscopy Peripheral corneal melt (thinning) Plan repeat penetrating keratoplasty (#3) Postoperatively, 9 weeks later patient develops corneal infiltrates and scleral nodules
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29 Acanthamoeba sclerokeratitis Scleral involvement estimated to occur in ~15% of Acanthamoeba keratitis cases Typically nodular Etiology debated Infective versus inflammatory origin A few published cases report detection of organisms in the sclera A few small series and other cases found inflammation but no organisms Clinically very difficult to tell if infectious or sterile
30 Infectious component Systemic anti-amebic agents What else can be done? Caspofungin Echinocandin antifungal agent Cysticidal activity in vitro Miltefosine (hexadecylophosphocholine) Anti-cancer, recently anti-protozoal agent Protein kinase inhibitor Reported to be effective in vitro and in vivo against Acanthamoeba Only approved for use in South America & Asia Available under experimental protocol through the Centers for Disease Control
31 Immune component Systemic immunosuppression Review of 19 eyes with Acanthamoeba sclerokeratitis treated with systemic immunosuppression in addition to topical anti-amebic agents Controlled the scleritis in 17 of 19 eyes Systemic immunosuppressive therapy unlikely to result in spread outside the cornea Cryotherapy Double freeze-thaw Equivocal success in keratitis Used more frequently for scleral component of sclerokeratitis Effective against trophozoites but not cysts
32 Our patient Caspofungin IV 50mg daily for 14 day course Sclerokeratoplasty (SKP) with cataract extraction, lens implant, cryotherapy to scleral nodules Intraoperative fundus exam was without retinal pathology Corneoscleral button demonstrates presence of Acanthamoeba
33 Postoperative medications Chlorhexidine 4x daily Voriconazole 4x daily Has been shown to have anti-amebic activity in few cases Prednisolone 4x daily Levofloxacin 4x daily Fluconazole 200mg PO daily Has been shown to have anti-amebic activity in few cases Valacyclovir 1g PO daily Prednisone 40mg PO daily
34 New scleral nodules Methylprednisolone 500mg IV x1 Mycophenolate mofetil (CellCept) started orally Oral prednisone tapered
35 Week 12 Enlarging scleral nodule Evaluated by rheumatology Plan to add oral cyclosporine Week 14 New floaters
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38 Chorioretinitis Suspected opportunistic infection Vitreous tap Gram stain and bacterial cultures negative Fungal smear and cultures negative Anterior chamber tap PCR negative for CMV, HSV, VZV, and toxoplasma Intravitreal voriconazole, vancomycin, and Foscarnet Discontinued mycophenolate mofetil Systemic cyclosporine not started
39 Our patient Reinjected Foscarnet every 2 days x 3 Continued to progress with dense vitritis, inferior retinal detachment, and thickened choroid on B- scan echography Brain MRI and lumbar puncture to rule out central nervous system involvement Negative Enucleation performed Treat blind, painful eye Prevent CNS spread of infection Treated with IV pentamidine, sulfadiazine, and fluconazole prior to surgery (per Infectious Disease recommendation)
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49 Diagnosis: Acanthamoeba panophthalmitis with necrotizing retinitis, necrotizing choroiditis, and focal necrotizing scleritis
50 Summary Acanthamoeba can be difficult to identify in biopsy specimens Special stains may be helpful but often routine stains are sufficient Cultures and molecular testing are not readily available in most cases Identification of clinical risk factors may increase index of suspicion Acanthamoeba endophthalmitis/panophthalmitis is a rare complication of keratitis It can be clinically vexing Scleral nodules may contain organisms should assume that they are infectious
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