Radial keratoneuritis as a presenting sign in acanthamoeba keratitis.

The visual outcomes of Acanthamoeba keratitis, a rare cause of corneal infection, can be devastating. This paper reports two contact lens wearers with severe pain and photophobia who presented to the emergency room. Biomicroscopy revealed radial keratoneuritis in both individuals. Tissue culture on a nonnutrient agar plate with Escherichia coli overlay resulted in a heavy growth of Acanthamoeba. The inpatient treatment included 0.02% polyhexamethylene biguanide, chlorhexidine, neomycin/polymyxin B/bacitracin (Neosporin), and oral fluconazole, which successfully controlled the corneal infection and improvement in the best corrected visual acuity in both patients. Infection did not recur during the 12-month follow-up period. Acanthamoeba keratitis can present as radial keratoneuritis, mimicking other common corneal infections resulting in diagnostic and treatment delays. Early diagnosis and prudent treatment of Acanthamoeba keratitis are the keys to restoring vision and avoiding the subsequent need for penetrating keratoplasty.

INTRODUCTION

Acanthamoeba is one of the most common free-living amoebae found in the environment.1 Acanthamoeba keratitis, a painful, progressive, sight-threatening corneal disease, was first reported by Naginton et al.,2 in the United Kingdom in 1974 and shortly thereafter by Jones et al.,3 in the United States in 1975. This often misdiagnosed disease is associated with trauma, exposure to contaminated water, and, more commonly, contact lens use.4

The presence of an infiltrate along the corneal nerves in suppurative keratitis is known as radial keratoneuritis, which has been characterized as a sign of Pseudomonas aeruginosa ulcerative keratitis and Acanthamoeba keratitis.1 Radial keratoneuritis is an important sign in the early phase of Acanthamoeba keratitis; however, it can be easily missed by the routine slit lamp examination. This report investigates two patients with Acanthamoeba keratitis in whom radial keratoneuritis was a presenting sign.

CASE REPORTS

Case 1

A 28-year-old female soft contact lens wearer with a 10-day history of pain, redness, and blurred vision in her left eye presented to the emergency clinic. Prior to the presentation, she had started treatment with antiviral and antibacterial topical medications elsewhere (at a dispensary clinic) without any improvement. Three days before presentation, she had started treatment with 1% topical prednisolone acetate.

At presentation, there was marked photophobia, irritation, and substantial discomfort, but the patient reported symptomatic improvement after the initiation of the topical steroid. The best corrected visual acuity (BCVA) in the right eye was 20/20 and in the left eye, 20/160; the intraocular pressure was 16 mmHg in both eyes. Slit lamp biomicroscopy of the left eye showed intense bulbar conjunctival congestion and multiple radial, linear, and branching anterior stromal infiltrates starting in the paracentral cornea with edematous intervening stroma [Figure 1a]. The overlying epithelium was intact. There was +1 anterior chamber reaction without keratic precipitates. Clinical examination of the right eye was unremarkable. Fundus examination showed a healthy posterior pole in both eyes. The clinical picture was consistent with herpes simplex or Acanthamoeba stromal keratitis. Corneal scraping was performed, and samples underwent Gram, Giemsa, and potassium hydroxide with calcofluor white (KOH + CFW) staining. Culture experiments were conducted using blood agar, chocolate agar, brain heart infusion broth, thioglycollate broth, Sabouraud dextrose agar, and nonnutrient agar with Escherichia coli overlay, allowing for the growth of Acanthamoeba. Both contact lenses and the solution underwent culturing. During the interim of laboratory testing, the patient continued empirical treatment, which included topical prednisolone acetate four times daily, acyclovir ointment five times daily, 1% cyclopentolate drops three times daily, and topical ofloxacin four times daily. The patient was requested to return for follow-up after 1 day.

Figure 1

Slit lamp photograph of the cornea of case 1, showing (a) radial keratoneuritis at presentation, (b) relapse after stopping topical steroid treatment, and (c) complete resolution of the corneal infiltrate after finishing a 6-month treatment for Acanthamoeba keratitis

Laboratory results from the contact lens solution indicated Acanthamoeba cysts. The corticosteroid drops were discontinued, and full anti-Acanthamoeba treatment was initiated, which included 0.02% polyhexamethylene biguanide (Baquacil, ICI America, USA) hourly around the clock, chlorhexidine eye drops hourly around the clock, neomycin/polymyxin B/bacitracin (Neosporin) drops every 2 h around the clock, and oral dose (200 mg) fluconazole two times daily, as well as cycloplegic drops. The patient was requested to return for follow-up after 3 days. A slight improvement was initially observed, followed by extensive spread of stromal infiltrates and increased corneal edema on the seventh day after the initiation of the treatment [Figure 1b].

When the corneal smears were performed again, they were positive for both Acanthamoeba and P. aeruginosa. The patient was admitted to the hospital, and fortified ceftazidime (50 mg/ml eye drops administered hourly around the clock) was added to the regimen; ofloxacin was discontinued. The patient stabilized first followed by slow improvement. After 2 weeks of intensive treatment, fortified ceftazidime was tapered and was then replaced with ofloxacin (four times daily) as prophylaxis. After 1 month of anti-Acanthamoeba treatment, topical drops were reduced to every 2 h for 2 weeks. The patient was then discharged from the hospital and was kept on the same medications (topical drops every 4 hours) with the exception of neomycin/polymyxin B/bacitracin (Neosporin) eye drops, which were discontinued.

One week after discharge, the hypopyon recurred, and the right eye showed an epithelial defect, approximately 2 × 3 mm, with a prominent ring infiltrate surrounding the epithelial defect. A corneal biopsy showed Acanthamoeba. Full anti-Acanthamoeba treatment – hourly polyhexamethylene biguanide and chlorhexidine eye drops, neomycin/polymyxin B/bacitracin (Neosporin) drops every hour round the clock, and oral dose (200 mg) fluconazole two times daily – was restarted. Within 48 h, the hypopyon had completely resolved, and during the next 3 weeks, the stromal infiltrate showed slight improvement. The intensive treatment was continued for 2 months, followed by a taper over 6 months. At 6 months’ follow-up, patient's BCVA was 20/30. The eye showed no signs of inflammation but did have faint corneal scarring and a mild superficial corneal neovascularization superonasally [Figure 1c]. At the most recent follow-up (14 months after initial presentation), the neovascularization had resolved.

Case 2

A 24-year-old female, complaining of redness, pain, and photophobia in the left eye for 1-week duration, presented to the emergency room. She had a history of periodic contact lens wear for cosmesis 2 weeks before presenting to the emergency room. She had no other ocular or systemic complaints. Her visual acuity was 20/20 in the right eye and 20/40 in the left eye; the intraocular pressure was normal in both eyes. Slit lamp examination of the right eye was normal. The left eye had lid swelling, conjunctival injection, redness, with radial, linear, and branching corneal stromal infiltrates, starting in the paracentral cornea and extending toward the limbus [Figure 2a]. No corneal epithelial defects or any anterior chamber reactions were detected in the left eye. The rest of the eye examination, including the dilated fundus examination, was normal.

Figure 2

Slit lamp photograph of the cornea of case 2, showing (a) radial keratoneuritis at presentation, (b) resolution of the corneal infi ltrate caused by Acanthamoeba keratitis at 6 months, and (c) faint corneal scarring and no clear corneal vascularization at 18 months

Corneal scraping was carried out, and samples underwent Gram and Giemsa staining and culturing. Culture experiments were performed with various types of media, including blood agar, chocolate agar, brain heart infusion broth, thioglycollate broth, Sabouraud dextrose agar, and nonnutrient agar with E. coli overlay. Results obtained from both staining and culturing were suggestive of Acanthamoeba keratitis. Confocal microscopy showed enlarged corneal nerves, but no cysts were observed. Anti-Acanthamoeba treatment was initiated, which included 0.02% polyhexamethylene biguanide and chlorhexidine eye drops hourly around the clock, neomycin/polymyxin B/bacitracin (Neosporin) drops every 2 h around the clock, and oral dose (200 mg) fluconazole two times daily, as well as cycloplegic drops. The patient was admitted to the hospital and was kept on this regimen for 3 weeks. The patient was then discharged with instructions to instill topical chlorhexidine every 6 h for 3 months, topical neomycin/polymyxin B/bacitracin (Neosporin) every 6 h for 3 months, and oral (200 mg) fluconazole two times daily for 1 month only. The patient was regularly followed up in the clinic. A complete resolution of the infiltrate was achieved within 3 months, and no recurrence was detected in the first year of follow-up [Figure 2b]. The patient achieved a final visual acuity of 20/20. At the most recent follow-up visit (18 months after initial presentation), corneal vascularization and recurrence of infiltrate were not detected [Figure 2c].

DISCUSSION

Acanthamoeba keratitis is an uncommon but potentially blinding corneal infection. Delayed recognition and inappropriate treatment of Acanthamoeba keratitis may lead to devastating results. Poor hygiene practices, such as the rinsing and storing of lenses in nonsterile saline or tap water and the failure to comply with recommended lens cleaning and disinfection procedures, are recognized risk factors for this infection.5–8

Clinical diagnosis of Acanthamoeba keratitis is based on the presence of keratitis that is accompanied by severe pain and photophobia, stromal infiltrates, pseudodendriform epithelial lesions, and less commonly, radial keratoneuritis. Radial keratoneuritis is not pathognomonic for Acanthamoeba keratitis, and a similar appearance has also been reported in a case of Pseudomonas keratitis.9 Although radial keratoneuritis is a very useful sign, it is not always present, especially late in the course of the disease. For example, a study by Sun et al.10 reported an incidence of radial keratoneuritis in 2 (10%) of the 20 patients with Acanthamoeba keratitis. In another study, Bacon et al.11 reported an incidence at presentation of 57% among 36 eyes diagnosed within 1 month of the onset, declining to 29% among 24 eyes diagnosed after 2 months. The cause of perineural infiltration is unclear; however, it is possible that the amoebae may migrate more easily along the course of corneal nerves than by other routes or that they may preferentially damage the nervous tissue. A careful slit lamp examination is necessary to identify these infiltrates because only one or two corneal nerves may be affected. The patients in this study were initially misdiagnosed as having another type of microbial keratitis. Many patients with Acanthamoeba keratitis are initially misdiagnosed and are treated for more common infections because the clinical characteristics of Acanthamoeba keratitis are very similar to more common forms of microbial keratitis.2 If the response to a topical antibiotic, antiviral, or corticosteroid therapy produces an initial improvement or stabilization, the clinical picture may be modified, which in turn may complicate the diagnosis.

This type of infection is not only rare but also difficult to treat because the causative organism can exist in two interchangeable forms: an infective trophozoite, which is the main target of treatment, and a dormant cyst form, which is resistant to antiprotozoal therapy and can persist for an extended period of time.12 Treating Acanthamoeba keratitis is also difficult because only a few types of appropriate medications exist. To complicate matters further, these medications can become toxic to the cornea – particularly with prolonged use, which is typically the case in patients with Acanthamoeba keratitis.1314 Additionally, some of these medications have poor corneal penetration; hence, the need exists for periodic epithelial debridement in cases with deep infiltrates. Complicated cases may require surgical treatment such as corneal transplantation, which requires prolonged antirejection therapy and can have poor prognosis.1115

However, Kitzmann et al.16 reported that medically unresponsive cases of Acanthamoeba keratitis can be successfully treated with therapeutic keratoplasty. In their study,16 keratoplasty that was performed after the resolution of active keratitis for corneal scarring was associated with good outcomes. Kitzmann et al. pointed out that multiple grafts may be required and that the visual prognosis is guarded.

In our study, patient 1 initially started a topical corticosteroid, which may explain the lengthy and relatively complicated course of her treatment compared with patient 2, who did begin similar initial treatment. In vitro studies have shown that exposure to dexamethasone increases the number of trophozoites through excystment and growth.17 The suggested mechanism by which corticosteroids may prolong the course of the disease is the inhibition of the macrophage function. Macrophages play an important role in fighting corneal infection caused by Acanthamoeba, most likely by acting as a first line of defense and eliminating substantial numbers of Acanthamoeba trophozoites.18 Therefore, effective doses of amoebicidal therapy should be continued for a prolonged period of time prior to initiating concurrent topical steroid therapy. Steroid therapy may be used to control the inflammatory complications of Acanthamoeba keratitis. The favorable outcomes in these two cases may be related to the early intervention that was performed in response to the presence of radial keratoneuritis (an early sign of Acanthamoeba keratitis) and to the intensive inpatient treatment.

In conclusion, Acanthamoeba keratitis should be considered in patients with radial keratoneuritis. In those patients, early and appropriate workup, followed by efficient treatment, is critical to achieving good outcomes.