infection
Fusarium Keratitis:A Case Report and Discussion
ERNEST L. BOWLING, O.D., M.S., F.A.A.O., DIPL. & DEEPAK GUPTA, O.D., F.A.A.O.

Case History

A 32-year old female presented for an emergency visit with complaints of a red and irritated right eye. She said that one day prior, a tree branch hit her in the eye while she was working in her garden. Her ocular history was notable only for soft, planned replacement contact lens wear. Her medical history and family history were both unremarkable.

Findings

Best-corrected vision in the involved eye was 20/40 O.D. and 20/20 O.S. in the fellow eye. Slit lamp examination revealed an epithelial defect, which stained positive with fluorescein. The conjunctiva demonstrated 2+ injection and 1 to 2+ edema. The anterior chamber was deep and quiet, with no signs of iritis. The corneal specialist and I were uncertain whether the epithelial defect was a corneal abrasion or corneal ulcer. Now, the question seemed more nomenclature because treatment for either changed only in terms of dosing. Thus, I started her on moxifloxacin 0.5% (Vigamox, Alcon) O.D. every 30 minutes for q6h and then every hour thereafter. We also prescribed cyclopentolate 2% (cyclogyl, Alcon) O.D. t.i.d. I instructed the patient to discontinue lens wear until resolution of the abrasion and return for a 24-hour follow-up.

On the next day, instead of demonstrating signs of improvement, her eye was worse. Her best-corrected vision had dropped to 20/70 O.D., and slit lamp examination now demonstrated a dense, grayish infiltrate along with the corneal ulceration. Knowing that moxifloxacin provides an excellent spectrum of bacterial coverage and has demonstrated very high tissue concentrations, it was quite apparent that this infection was not primarily bacterial. I referred the patient back to the corneal specialist who ordered cultures. Specifically, he plated some deep scrapings of the lesion on blood agar and Sabouraud agar media. In addition, the corneal specialist was able to obtain a small tissue sample, which was sent for microscopic analysis. Ultimately, these tests confirmed our definitive diagnosis.

Treatment

Rather than wait for laboratory findings to confirm the diagnosis, we decided to change the clinical diagnosis to fungal keratitis and alter the treatment accordingly. We prescribed nata- mycin 5% every 30 minutes and continued with the moxifloxacin every q3h and asked the patient to return for daily follow-ups.

Slit lamp examination finally demonstrated mild improvement on her third day of natamycin therapy. Now, we prescribed both the natamycin and moxifloxacin every three hours until complete resolution of the abrasion, which took almost two months of intense therapy. When the cornea was healthy in terms of the fungal infection, the patient demonstrated significant corneal scarring down to Descemet's membrane near the visual axis. This scarring left her best-corrected visual acuity at 20/50 O.D., which was unacceptable for the patient.

The corneal specialist discussed several surgical options to improve her vision. Ultimately, the patient underwent a penetrating keratoplasty four months later. The surgery was a success in terms of obtaining a clear cornea, but she was left with 5.00D O.D. of corneal astigmatism. She was then fit with a specialty GP, which provides her 20/25 O.D. vision. We continue to monitor her at regular visits.

Discussion

The recent Fusarium keratitis outbreak, first reported in Southeast Asia in early 2006 and here in the United States in March 2006, has refocused attention on fungal infections in eyecare practices. While Fusarium has an

incidence of less than 5% in contact lens wearers, fungal infections have garnered renewed in- terest with these recent reports.¹

Fungal infections are similar in etiology to bacterial ocular infections. They may be transmitted by traumatic events associated with plant or vegetable matter, by ocular and/or systemic disease, through poor contact lens wear and care habits or by decreased resistance secondary to the application of topical or oral corticosteroids.

The diagnosis of fungal keratitis often occurs late, as many cases are initially mistaken for bacterial keratitis or other ocular surface disorders. In clinical practice, if the patient's history is negative for contact with an organic source, many clinicians assume the existence of a bacterial keratitis and treat empirically with a fourth-generation fluoroquinolone, such as moxifloxacin in conjunction with an aminoglycoside, such as tobramycin.

In light of the recent Fusarium problem, the efficacy of the fourth-generation fluorquino-lones, such as moxifloxacin and gatifloxacin (Zymar, Allergan), have been at the forefront of industry discussions. Neither is indicated for treatment of fungal infection. Both, however, are safe from fungal contamination in the bottle. In fact, the self-preserved moxifloxacin has proven efficacy beyond the U.S. Pharmacopeias standards for Preservative Effectiveness Testing (PET), killing over 50 pathogens, including gross contamination with Fusarium.²

Additionally, researchers from Bascom Palmer Eye Institute dealt with five cases of culture-proven fungal keratitis associated with contact lens wear that resolved or significantly improved without antifungal therapy. The results will be reported at this years Ocular Microbiology and Immunology Group (OMIG) meeting. In this study, they report that three cases — of which two were treated with moxifloxacin 0.5% — completely resolved with topical fluoroquino- lone therapy. One case required changing to a fortified tobramy-cin and cefazolin regimen to achieve resolution. The final case showed marked initial improvement on the fluoroquinolone therapy alone, but was subsequently treated with natamycin 5%. The authors concluded that fungal keratitis associated with soft contact lens wear may occasionally present in a less aggressive form and that fluoroquino- lone therapy may be an adjunct in vivo to the immune response in eliminating less fulminant fungal infections.³

When selecting an agent to eradicate or prevent a bacterial infection, consider the potency and penetration of the drug. The agent must penetrate the ocular structure and achieve concentrations in the target tissue that exceed the levels necessary to kill the pathogens of concern. Moxifloxacin has been shown to deliver higher tissue concentrations in the cornea, conjunctiva and aqueous humor. In one study completed at The Wilmer Eye Institute, researchers concluded moxifloxacin was the only fourth generation fluoroquinolone to penetrate into the aqueous at concentrations that exceeded the agent's Minimum Bactericidal Concentration for the most common endophthalmitis causing susceptible pathogens.⁴ Other comparative studies show greater concentrations of moxifloxacin in the human conjunctiva and the human corneal stroma with a penetrating keratoplasty model.^5,6

While an argument can be made for empirical treatment, and that fourth-generation fluoroquinolone monotherapy will lead to resolution of most cases of bacterial origin, you must be cautious in cases that do not respond after several days of aggressive therapy. Suspect fungal infections in cases that do not resolve, or develop satellite lesions or branching patterns to the initial lesions. If you suspect a fungal ulcer, corneal scrapings and cultures are mandatory. At this point, many optometric clinicians may prefer to refer the patient to a corneal specialist.

Corneal fungal ulcers are tricky to deal with; the response to therapy is often slow, the one topical ocular medication, nata-mycin 5%, does not penetrate the ocular tissues well, and the potential for permanent vision loss from a fungal infection is high. We think it's best to put these cases in the hands of an experienced corneal specialist.

1. Rattanatam T, Heng WJ, Rapuano CJ, et al. Trends in contact lens-related corneal ulcers. Cornea. 2001 Apr;20(3)-4.

2. Schlech BA, Sutton S, Rosenthal RA, Berry R, et al. Antimicrobial Preservative Effectiveness of Vigamox. 2004;45:ARVO E-Abstract 4913.

3. Munir, WM, Rosenfield SI, Udell I, et al. Clinical Response of Contact Lens Associated Fungal Keratitis on Topical Fluoroquinolone Therapy. OMIG abstract 2006.

4. Kim DH, Stark WJ, O'Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% ophthalmic solution in cataract surgery patients. Ophthalmology. 2005 Nov;112 (11):1992-1996.

5. Wagner RS, Abelson MB, Shapiro A, Torkildsen G. Evaluation of moxifloxacin, ciprofloxacin, gatifloxacin, ofloxacin, and levofloxacin concentrations in human conjunctival tissue. Arch Ophthalmol. 2005 Sep;123(9):1282-3.

6. Holland EJ, Lane S, Kim T, et al. Human cornea and aqueous humor concentrations of moxifloxacin and gatifloxacin following topical ocular dosing with Vigamox solution or Zymar. Invest Ophthalmol Vis Sci. 2006;47:ARVO E-abstract 3577/B51.