FP142 : Management of Acanthamoeba Sclerokeratitis with Intravenous Metronidazole: Case Report

Dr. Shaffie Baidwal, B14600, Dr.Anita Raghavan, Dr. Soly Somapalan

ABSTRACT:

Acanthamoeba keratitis is a painful sight threatening and difficult to treat corneal infection caused by pathogenic acanthamoeba. Associated scleritis has been reported and is a potentially blinding complication. However the scleritis is considered to be inflammatory rather than infectious in origin. It is feasible that there is infectious component to the associated scleritis. Intravenous metronidazole may be considered in such cases. We report the use of intravenous metronidazole to successfully treat a case of culture proven acanthamoeba keratitis and scleritis. To the best of our knowledge this is the first reported use of intravenous metronidazole for the treatment of acanthamoeba sclerokeratitis.

KEY WORDS:

1. ASK : Acanthamoeba Sclerokeratitis
2. NNA : Non Nutrient Agar
3. PHMB : Polyhexamethylene Biguanide

INTRODUCTION:

Acanthamoeba keratitis was first reported by Dr. Dan Jones¹ in 1973 and has been subsequently recognised as an important pathogen. Acanthamoeba sclerokeratitis (ASK) is an uncommon but severe complication that potentially can result in blindness,² management of which is notoriously difficult and challenging. Metronidazole, a 5-nitroimidazole derivative, has been well established as the drug of choice for the treatment of several systemic protozoal diseases such as amoebiasis. However it does not appear to be part of most current treatment regimens for Acanthamoeba keratitis manifestations. We report a case of culture proven acanthamoeba sclerokeratitis successfully treated with the use of intravenous metronidazole

CASE REPORT:

A 50-year-old male, presented with a 4-day history of pain and watering in the right eye. He gave a history of bathing in river water 15 days prior to onset of symptoms, followed by use of some unknown topical drops.  On examination, his uncorrected visual acuity was 1/60 in the right eye. Anterior 2/3^rd of corneal stroma displayed diffuse infiltrates with a prominent ring infiltrate, along with mild anterior chamber reaction and keratic precipitates. Posterior segment was within normal limits. Smear examination of corneal scrapings were done by Grams stain, Giemsa stain and KOH mount, and revealed occasional gram positive bacilli along with lymphocytes. Cultures were obtained on blood agar, potato dextrose agar and non nutrient agar (NNA). Based on the clinical suspicion of acanthamoeba, patient was empirically treated with topical econazole eye drops 1% half hourly, topical PHMB 0.04% half hourly, eye ointment itraconazole and neomycin thrice daily along with oral ketoconazole 200mg administered twice daily. Acanthamoeba was cultured on NNA plate by the end of first week confirming the clinical diagnosis. Inspite of intensive medical (antiamoebic) treatment, the clinical picture worsened with progression of the ring infiltrate to involve the deeper layers of the stroma with a central spread to involve the entire cornea. Patient developed secondary glaucoma which was treated medically with antiglaucoma agents. In the latter half of the second week progressive proptosis with impairment of lid movements, increasing scleral inflammation and resistance to retropulsion was noted. No evidence of posterior scleritis was seen on serial ultrasonography. Topical metronidazole 0.5% was added on the seventeenth day. However no clinical improvement was noted and the patient remained extremely symptomatic. Finally, a trial of intravenous metronidazole 500mg in 100ml was administered twice daily in adjunct with the topical regimen. Decline in the intensity of scleral inflammation with reduction in resistance to retropulsion was seen by fifth day. After a week, intravenous formulation was replaced by oral metronidazole 400mg thrice daily. Within ten days, the peripheral cornea showed signs of healing. There was a considerable decline in the scleral inflammation and intensity of the ring infiltrate by the end of second week. The corneal infiltration continued to decrease and oral metronidazole was discontinued after 2 weeks. Topical medications were tapered according to the healing response. Topical cycloimmune 0.1% eye drops were also added to treatment regimen. Two months after presentation, the peripheral infiltrate had healed completely with a residual central ring of infiltration with peripheral stromal vascularization. Scleral thinning was noted in the superior quadrant. The eye remained quiescent and the patient was maintained only on topical cycloimmune 0.1% twice daily. After 5 months off medications, patient presented with inferonasal episcleral congestion with a raised nodule in the right eye. Cornea showed no sign of re-activity. Connective tissue disease was ruled out with blood investigations. Ultrasonography showed nil posterior segment involvement. Tab Metronidazole 400 mg thrice daily was started but was discontinued after 2 weeks as the scleritis started healing and patient was symptomatically better. Topical cycloimmune was discontinued. Within 2 months, patient again presented with nodular scleritis and was started on systemic metronidazole under close monitoring. There was evidence of diminution in the intensity of scleritis and pain by the end of 1 week with complete resolution noted by the end of 1 month. Oral metronidazole was discontinued by the end of 2 months. After a year of inactivity, patient underwent optical keratoplasty. The graft failed after 6 months but there is no evidence of recurrence in the corneal and extracorneal tissues till date.

DISCUSSION:

Medical therapy of Acanthamoeba sclerokeratitis involves a wide range of medications used as monotherapy as well as combination therapies. Metronidazole has been documented as an topical adjunctive agent in the treatment of Acanthamoeba keratitis,^3,4,5 But efficacy of topical metronidazole is yet to be proven since corneal epithelial layer constitutes the main barrier to the passage of this hydrophilic drug into the aqueous humor, although  diffusion through the  stromal layer occurs much more readily. Invitro studies in rabbit and human corneas  showed  that physicochemical properties and diffusion kinetics of metronidazole with concentrations of up to 1%  of the drug, may be considered for the clinical treatment of Acanthamoeba keratitis infections.⁶ Acanthamoeba scleritis was reported to be a result of an immune reaction to the parasite^7,8 although few studies concluded the fact that nodular form of acanthamoeba scleritis is due to the  direct involvement proven microbiologically from specimens taken from the involved sclera.^9,10 Healing of nodular scleritis with systemic use of metronidazole in our case demonstrates the probability of the presence of the parasite within the scleral tissues although not proven since no surgical intervention was attempted at the time of active infection. Intravenous metronidazole may be used for the treatment of acanthamoeba sclerokeratitis with favourable results.

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