Contact lens-related microbial keratitis affects approximately 1 in 500 soft contact lens wearers annually in the United States. Most infections are bacterial in origin and can be managed empirically, often resolving without significant visual sequelae. In some cases, unusual organisms infect the cornea that are resistant to standard broad spectrum antibiotics. One such genus of protozoa, Acanthamoeba, is a rare but important cause of infectious keratitis. Infections caused by Acanthamoeba sp. are often misdiagnosed, initially resulting in a delay in definitive treatment.
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Case 1 – second opinion for chronic eye pain
A 37-year-old female presented to Jeffrey Goshe, MD, for a second opinion regarding chronic right eye pain and photophobia after being treated nine months earlier for an acute corneal ulcer with hypopyon in the setting of contact lens wear. Routine bacterial and fungal cultures were obtained and topical fortified antibiotics were started hourly. Initial cultures were positive for Pseudomonas aeruginosa and the antibiotics were adjusted accordingly. Over the next three months, the ulcer gradually healed and topical steroids were added to reduce the inflammatory response.
After four months, topical steroids were discontinued and the patient reported that her symptoms had resolved. Three weeks later, she experienced recurrent photophobia and eye pain. Steroids were restarted due to a presumed post-inflammatory reaction to initial infection. Over the subsequent four months, multiple attempts were made to taper topical steroids, but the patient was unable to do so due to worsening photophobia and eye pain.
At the time she presented for a second opinion, she was using loteprednol 0.5% (Lotemax®) drops twice daily. She had not worn contact lenses since the initial infection was diagnosed. She complained of 8/10 pain and extreme photophobia OD. Her vision was 20/200. Slit lamp examination (Figure 1) revealed mild diffuse limbal injection, with an area of increased hyperemia superiorly. Her cornea exam was remarkable for a central oval-shaped scar in the area of her original corneal ulcer. Multiple subepithelial infiltrates were present in a ring pattern circumferentially around the peripheral cornea. There was no epithelial defect.
Confocal microscopy reveals infection
Based on the clinical appearance and symptoms, Acanthamoeba infection was suspected. Culture was deferred as there was no epithelial defect. Confocal microscopy was performed revealing multiple double-walled reflective structures consistent with Acanthamoeba cysts (Figure 2)
Treatment with topical chlorhexidine gluconate 0.02% was started hourly and the loteprednol was decreased to once daily. One week later, the patient reported significant reduction in her pain and photophobia. One month later, her symptoms had completely resolved with near resolution of the ring infiltrate noted previously (Figure 3). Steroids were tapered off over the next two months and she was maintained on topical chlorhexidine four times daily. As of her most recent visit, vision was improved to 20/40 with correction.
Case 2 – acute onset of worsening eye pain
A 20-year-old college student returned to Jeffery Goshe, MD, with acute onset of worsening left eye pain, vision and photophobia over the previous three days. Her history was remarkable for culture-positive Acanthamoeba keratitis diagnosed two years prior at the Cole Eye Institute. She completed a 12-month course of topical treatment with chlorhexidine gluconate 0.02%, polyhexamethylene biguanide (PH MB) 0.02% and propamide isethionate 0.1% (Brolene®), after which time her symptoms had resolved and there were no signs of active inflammation. Treatment was discontinued and she was monitored without signs of recurrence for the subsequent three months.
At the time of her second presentation, she had been off all treatment for nine months. She had not worn contact lenses for the past two years. Her best-corrected vision was 20/20 OD and 20/60 OS (previously 20/40 OS at the time of her last appointment six months earlier).
Her right eye examination was normal. Her left eye was remarkable for mild to moderate diffuse limbal injection. Superficial corneal neovascularization was present superiorly. Of note, focal mid-stromal neovascularization was visible, extending into the area of temporal corneal infiltration (Figure 4). The epithelium was intact. The anterior chamber examination revealed a faint cellular reaction without hypopyon.
Anti-microbial treatment re-initiated
In light of her clinical history, the constellation of symptoms and signs was suggestive of recurrent Acanthamoeba keratitis and treatment was re-initiated with chlorhexidine and Brolene OS. Oral ketoconazole 100mg daily was added to provide additional Acanthamoeba coverage. During the first two weeks after restarting treatment, there was an increase in corneal edema causing her vision to decrease to 20/200 (Figure 5). Anterior segment optical coherence tomography demonstrates the depth of infiltration and surrounding edema (Figure 6).
After six weeks of treatment, prednisolone acetate was started once daily. Within one week, the edema was nearly resolved with her best-corrected vision returning to 20/60. As of her most recent follow-up, her vision has improved to 20/50 and her pain and photophobia have completely resolved.
Diagnostic and Therapeutic Tips
- Confocal microscopy is a useful diagnostic tool in the diagnosis of Acanthamoeba keratitis, especially in the setting of an intact corneal epithelium when culture yield may be low.
- Concurrent bacteria and Acanthamoeba infection is relatively uncommon, but a high index of suspicion must be kept for ulcers which do not respond appropriately to conventional treatment or manifest unusual clinical features (e.g. delayed-onset corneal ring infiltrate, difficulty weaning steroids, pain out of proportion to exam findings).
- Recurrent Acanthamoeba infection should be suspected in any patient with a history of Acanthamoeba keratitis who manifests new signs or symptoms following completion of appropriate treatment. A minimum of six months of additional multi-agent treatment should be considered for these patients.
- First-line treatment should consist of hourly biguanides. For advanced or poorly responsive cases, Dr. Goshe recommends combination therapy with multiple agents, including a diamidine. Oral triazoles (e.g. fluconazole, itraconazole) may be used as an adjunct to topical treatment in recalcitrant cases, but are not adequate for as primary therapy. Liver enzymes must be monitored if systemic triazole therapy is instituted.
Cautious use of topical corticosteroids may be beneficial after completing one to two months of anti-infective treatment to reduce symptoms and corneal scarring. Topical steroids must be used with caution and for the shortest possible duration as they may inhibit some innate immune mechanisms necessary to eradicate Acanthamoeba organisms.