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to describe the course and outcome of treatment of advanced acanthamoeba sclerokeratitis with intravenous pentamidine .
a case of advanced acanthamoeba sclerokeratitis was resistant to conventional therapy and was treated with intravenous pentamidine .
the eye showed acanthamoeba organisms within the cornea and evidence of acute and chronic inflammation throughout the remainder of the eye .
acanthamoebal sclerokeratitis is an uncommon and severe complication of advanced acanthamoeba keratitis ( ak).13 despite intensive medical and surgical treatment , enucleation may be required to manage this disease .
pentamidine has shown effectiveness against acanthamoeba with synergistic effects when used in combination with polyhexamethylene biguanide ( phmb).410 in vitro testing may not always be associated with in vivo effectiveness.11
a 59-year - old female presented for a second opinion with previously diagnosed ak of her right eye .
the contact lens type and solution were unknown , but she did wash her contact lens case out with tap water on a regular basis . she first noted pain and decreased vision in the right eye approximately 2 years earlier and saw an ophthalmologist . a ring stromal opacity was seen and she was treated for herpetic keratitis .
several months later she was diagnosed with acute retinal necrosis and was hospitalized and treated with foscarnet .
the patient underwent penetrating keratoplasty in the right eye 9 months after initial treatment for presumed corneal opacity secondary to herpes simplex keratitis .
treatment was continued for 1 year when the patient presented at our institution for a second opinion .
her ocular medications on presentation were : topical phmb every 23 hours , topical propamidine ( brolene ) three times per day , topical moxifloxacin ( vigamox ) three times per day , prednisolone actetate 1% every 23 hours , and dorzolamide - timolol ( cosopt ) three times per day .
she had apparently had multiple ( 1012 ) subtenons injections of triancinolone ( kenalog ) over the past year .
on examination , visual acuity in the right eye was hand motion at 1 foot with light projection in all quadrants .
the sclera showed moderate injection , and there was a white plaque consistent with triancinolone present beneath tenons capsule superiorly .
the retina of the right eye could not be visualized , but ultrasound b scan showed a clear vitreous cavity and intact retina .
confocal microscopy ( confoscan 3  nidek ) of the corneal graft showed cystic structures consistent with acanthamoeba throughout the depth of the cornea ( figure 2 ) .
famcyclovir was discontinued , and topical propamidine , clotrimazole 1% and chlorhexidine 0.02% were added every hour for the first week and then decreased to every 2 hours .
prednisolone actetate 1% was reduced to four times per day , and dorzolamide - timolol was reduced to twice per day .
the patient was admitted to the hospital under the infectious disease service for a course of intravenous pentamidine .
the treatment was associated with nausea , but no episodes of hypotension or hypoglycemia occurred .
eleven days into this course of treatment a combined penetrating keratoplasty , cataract removal with lens implant was performed .
orbital and brain computed tomography ( ct ) scan and magnetic resonance imaging ( mri ) were performed during the hospitalization and did not demonstrate any orbital or intracranial extension .
one month following her eye surgery her cornea was found to be clear with a quiet anterior chamber and posterior chamber lens implant .
her topical medications were moxifloxacin , neosporin , phmb , clotrimazole 1% , chlorhexidine 0.02% , and prednisolone actetate 1% , all four times per day .
she was also using atropine 1% and dorzolamide - timolol , each twice per day .
the eye remained stable , and the patient continued her medications for 6 months when she presented with a 1 week history of pain .
examination noted a 2 mm cream - colored loculated mass in the superior anterior chamber ( figure 4 ) .
the mass was removed in the operating room and sent for bacterial , fungal , and acanthamoebal cultures .
cultures grew one colony of coagulase negative staphylococcus , which was felt to be a contaminant .
the intraocular inflammation progressed over the next 3 weeks and a trans pars plana vitrectomy was performed with intravitreal injection of vancomycin 1.0 mg and ceftazidine 2.25 mg . at the time of this surgery
the patient was again admitted and given a 4-day course of intravenous pentamidine 200 mg per day .
the postoperative medications were phmb , clotrimazole , chlorhexidine , neosporin , propamidine , and prednisolone actetate , all every hour for the first week and then tapered to 4 times per day .
the eye remained inflamed and painful with vision of light perception but no accurate projection .
confocal microscopy demonstrated structures within the corneal stroma consistent with acanthamoeba ( figure 5 ) .
the pathology of the enucleated globe demonstrated acanthamoebal cysts within the cornea ( figure 6 ) and evidence of acute and chronic inflammation throughout the globe but no evidence of active organisms ( figure 7 ) .
the treatment of advanced acanthamoeba sclerokeratitis is a challenge.13 it is diagnostically difficult to distinguish between secondary inflammatory reaction and actual acanthamoebal infection of the sclera.3 topical treatment of the cornea may not achieve therapeutic levels in the sclera.12 systemic treatment with ketaconazole and fluconazole has been used in the treatment of acanthamoeba keratitis and sclerokeratitis.12 pentamidine has been shown to have effectiveness against acanthamoeba and has synergism with the biguanide compounds.410 the presence of chorioretinal inflammation in this eye does not necessarily indicate presence of acanthamoeba in the posterior segment .
chorioretinal inflammation has been seen with the presence of acanthamoeba13 and also as a sterile inflammation.14 the sudden development of intense ocular inflammation in this patient after apparent successful treatment of the infection led to the concern that active infection had recurred .
the failure of a prolonged therapeutic response to intravenous pentamidine could indicate that the treatment was of insufficient duration , that therapeutic levels were not attained and/or maintained , or that the acanthamoeba was resistant to pentamidine .
if the scleritis was an immune - mediated response,3 then aggressive systemic immunosuppression may have changed the course of this case .
this was not used in this case because of the concern that the acanthamoeba was active .
it is clear that the use of systemic pentamidine in this case did not effectively alter the progression of the disease and eventual loss of the eye .
perhaps earlier intervention or combined systemic antiamebial therapy and immunosuppression would achieve a better outcome .
miltefosine and voriconazole have shown strong inhibitory effects on acanthamoeba trophozoites in vitro and might be candidates for in vivo testing.15
purposeto describe the course and outcome of treatment of advanced acanthamoeba sclerokeratitis with intravenous pentamidine.methodsa case of advanced acanthamoeba sclerokeratitis was resistant to conventional therapy and was treated with intravenous pentamidine . 
 the eye was later removed due to incapacitating pain.resultsthe eye showed acanthamoeba organisms within the cornea and evidence of acute and chronic inflammation throughout the remainder of the eye . 
 the patient has survived without orbital recurrence for 2 years.conclusionsthis case demonstrates late inflammation with active acanthameoba keratitis following systemic pentamidine therapy .