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Contact lens wearer presents with eye pain and decreased vision
In the central cornea of the right eye, there was an elevated white plaque with an overlying epithelial defect, surrounding feathery infiltrate and stromal folds.
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A 50-year-old woman presented to the New England Eye Center with 2 weeks of pain, blurry vision and photophobia in the right eye after sleeping in contact lenses. She initially saw an outside optometrist who diagnosed a corneal ulcer and prescribed hourly ofloxacin as well as tobramycin and dexamethasone drops four times daily. Several days later, she subsequently saw an outside ophthalmologist who switched her therapy to hourly moxifloxacin and trimethoprim/polymyxin B every 2 hours, in addition to tobramycin and dexamethasone four times daily. Initially, she noted improvement in her symptoms, but subsequently, her pain worsened and vision deteriorated, and she was referred to NEEC.
Evaluation
Upon evaluation at NEEC, the patient complained of pain in the right eye and decreased vision. Ocular and systemic review of systems was otherwise negative. Her ocular history was notable for use of weekly contact lenses, which she wore for 15 hours a day. She had good contact lens habits, ordinarily removing her lenses at night and cleaning them in a peroxide-based overnight contact lens solution. She avoided getting tap water in her eyes and never used it to clean her lenses. She had no systemic medical conditions or prior surgeries and took no medications.
Examination
Source: Sarah Adelson, MD, and Michael B. Raizman, MD
Uncorrected visual acuity was 20/400 in the right eye and improved to 20/200 with pinhole. Corrected visual acuity in the left eye was 20/25 (baseline). Pupils were round, symmetric and reactive, without afferent pupillary defect. IOPs were 16 mm Hg and 15 mm Hg in the right and left eye, respectively. Confrontation visual fields, extraocular movements and the ocular adnexa were within normal limits bilaterally.
The conjunctiva of the right eye was diffusely injected. In the central cornea, there was a 2.5 mm × 2.5 mm elevated white plaque with an overlying epithelial defect, surrounding feathery infiltrate and underlying deep stromal folds (Figure 1). There were no iris transillumination defects. The anterior chamber was quiet without a hypopyon. The rest of the complete ocular exam, including dilated fundus exam, was normal.
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Corneal stromal infiltrate
The differential diagnosis for a corneal stromal infiltrate with epithelial defect in a contact lens wearer includes infectious etiologies (fungal, bacterial, Acanthamoeba or herpetic keratitis), as well as inflammatory reactions (sterile infiltrate due to hypoxia, reaction to lens solution or staphylococcal marginal ulcer), sterile corneal thinning or melt (usually secondary to systemic autoimmune disease), retained foreign body or rust ring, neurotrophic ulcer, or topical anesthetic abuse.
In the setting of overnight contact lens wear, infectious etiologies are highest on the differential. Bacterial organisms are the most common cause of infectious keratitis, with Staphylococcus, Streptococcus and Moraxella as the most common species. Moraxella tends to cause keratitis in immune-compromised patients and those with pre-existing ocular surface disorders. In a contact lens wearer, Pseudomonas is an important consideration. Protozoal infection with Acanthamoeba is another important cause of infectious keratitis to recognize in contact lens wearers, classically those with poor hygiene practices, because it can have devastating consequences if not caught early. Fungal keratitis is the most common cause of keratitis after corneal trauma with vegetable matter and presents with an infiltrate with a “feathery” border. Atypical mycobacteria are also associated with trauma with vegetable matter as well as corneal surgery.
Workup and management
Corneal cultures were performed for fungus, bacteria and Acanthamoeba. While awaiting culture results, the patient underwent in vivo confocal microscopy (IVCM), which revealed extensive filamentous hyphae, moderate inflammation, as well as decreased nerve density (Figure 2). This result was felt to be consistent with a diagnosis of fungal keratitis, and the patient was started on 200 mg of oral voriconazole daily and topical voriconazole 1% every hour around the clock. Moxifloxacin was continued four times daily as prophylaxis against bacterial superinfection. All steroid-containing medications were stopped, and the patient was counseled to remain out of contact lenses until the infection had fully cleared.
The patient was followed closely, every other day, and underwent regular debridements to remove necrotic tissue and enhance medication penetration. Early on, the patient was switched from topical voriconazole to natamycin 5% for better coverage of fungal hyphae. Over the next 2 weeks, there was a significant decrease in the size and density of the infiltrate and plaque-like deposit. Corneal cultures ultimately grew viridans group Streptococcus and coagulase-negative Staphylococcus; however, these were felt to be contaminants because confocal results were suggestive of fungal infection and the patient was improving on antifungal therapy. After 4 weeks of treatment, repeat IVCM revealed a reduced yet persistent number of fungal hyphae with inflammatory cells in the deeper stroma (Figure 3). Treatment was continued. At week 5, IVCM showed complete eradication of fungal elements, and treatment was slowly tapered down (Figure 4).
Discussion
Fungal keratitis is an infection of the cornea caused by any of the pathologic fungi capable of invading the cornea. This accounts for 5% to 10% of corneal infections in the United States. These fungi include, but are not limited to, Candida spp., Aspergillus spp., Fusarium spp., Cladosporium spp., Curvularia and Rhizopus. The type of fungi varies by geographic location. Filamentous fungi such as Fusarium or Aspergillus are more common in warmer climates. Trauma to the eye is the leading risk factor for this type of infection. In cooler climates, such as the northern U.S., Candida is more common but tends to present in those with chronic illness or a compromised immune state. However, a recent breakout of Fusarium keratitisassociated with contact lens solution demonstrated fungal infections in non-immunocompromised hosts in northern climates as well.
Patients with fungal keratitis may present with decreased vision, pain, photophobia, redness, tearing, foreign body sensation and secretions. Risk factors for fungal keratitis include trauma, ocular surface disease, contact lens use and topical steroid use. These patients have fewer inflammatory signs in comparison to bacterial keratitis, including absence of discharge or injection.
Filamentary fungal keratitis has a different appearance on slit lamp examination from keratitis caused by yeast species. Infiltrates in filamentary fungal keratitis appear whitish-gray with feathery borders. As the infection progresses, satellite lesions, conjunctival injection, purulent secretions and even hypopyon may occur. A deep stromal infiltrate may be present in the absence of an epithelial defect. In contrast, yeast displays raised white colonies that tend to be well defined.
Any corneal ulcer that is unresponsive to broad-spectrum antibiotics or has satellite lesions should raise suspicion for fungal keratitis. Early treatment with broad-spectrum antifungal treatment is crucial in ensuring a good outcome.
Fungal culture in Sabouraud agar is the gold standard for diagnosis of fungal keratitis; however, this can take up to 3 weeks to grow. Moreover, while highly specific, sensitivities are in the range of 50% to 60%. Alternatively, smears with special stains such as Gomori, periodic acid-Schiff, acridine orange, calcofluor white or KOH may be used to obtain a diagnosis more quickly, and they have sensitivities and specificities on par with fungal cultures. Another option for noninvasive real-time diagnosis is in IVCM. This allows both direct visualization of the organism as well as the resultant inflammatory and corneal stromal cell response. Studies have shown that IVCM is able to identify fungal filaments with 89.2% sensitivity and 92.7% specificity, although these rates are highly dependent on the skill and experience of the clinician interpreting the results. Additionally, as demonstrated in this case presentation, IVCM provides a method for monitoring the response to treatment.
The management of fungal ulcers consists of topical antifungals, possibly in combination with systemic antifungals and surgical therapy. Medications available for ocular therapy are limited by their ability to penetrate deep into the cornea. While specially compounded antifungal drops are in wide use, only natamycin 5% is FDA approved and commercially available for topical treatment of fungal keratitis. Studies are mixed as to the relative efficacy of various topical antifungals in undifferentiated fungal keratitis; however, natamycin does appear to be especially effective against Fusarium species. Other specially compounded antimycotics are made by diluting intravenous antifungal medications. Amphotericin B has been shown to be efficacious against yeast and can be used either topically or via intrastromal injection. Voriconazole may be used topically (1% dilution of intravenous dosage), orally or intrastromally (50 µg/0.1 mL). Intrastromal voriconazole has shown good activity in fungal keratitis unresponsive to other treatments. Oral posaconazole, a newer antifungal, has been successful in eradicating deep, resistant Fusarium infections because of its good intraocular penetration.
The clinical course for patients with fungal keratitis is often prolonged. All corneal infections should be followed frequently until there is a marked improvement in clinical exam, and the interval between office visits is guided by clinical progress. Complete resolution may take weeks to months. IOP should be closely monitored during the episode if steroids are used to mitigate scarring. It should be noted that epithelialization does not necessarily indicate that the ulcer is healing. In fact, re-epithelialization may hinder penetration of the fungicide, and periodic debridement may be beneficial as it removes necrotic tissue, diminishes the organismal load and enhances the penetration of the drugs. It may be performed every 24 to 48 hours.
If more conservative management fails, a conjunctival flap may help the infection from progressing further. If there is no response to the flap, a corneal transplant may be necessary. In cases of perforation, patch graft or corneal transplant is used. In several reports, penetrating keratoplasty was needed in up to 31% to 38% of cases.
The sequelae of fungal keratitis can be devastating. Severe vision loss occurs in 26% to 63% of patients. Other consequences range from mild to severe corneal scarring, corneal perforation, anterior segment disruption, glaucoma and endophthalmitis. Up to 15% to 20% may require eventual evisceration for blind painful eyes.
Follow-up
After several weeks of antifungal therapy, the fungal ulcer had resolved, leaving behind an anterior stromal scar in the visual axis rendering best corrected visual acuity 20/50 (Figure 5). The patient underwent a slow taper of her antifungal medications by a drop per week and returned for weekly visits to ensure there was no relapse as her medications were tapered. Interestingly, despite clear evidence of fungal elements on IVCM and good response to antifungal therapy, the patient’s fungal cultures were negative. The patient is planned for hard contact lens fitting at a later date to help improve vision due to surface irregularity overlying the area of stromal scarring.
Summary
Fungal keratitis is an important consideration in patients presenting with a corneal infiltrate, as early recognition and treatment are critical for a good outcome. While cultures remain the gold standard for diagnosis of fungal keratitis, they are slow growing and may be difficult to obtain. IVCM has the advantage of noninvasive, real-time diagnosis and, in the hands of an experienced clinician, has high sensitivity and specificity. The treatment of fungal ulcers consists of topical antifungals, possibly in combination with systemic antifungals and surgical therapy, with natamycin 5% being the most effective topical antifungal against Fusarium spp.
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- For more information:
- Sarah Adelson, MD, and Michael B. Raizman, MD, can be reached at New England Eye Center, Tufts University School of Medicine. 800 Washington Street, Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Aubrey R. Tirpack, MD, and Astrid C. Werner, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.