Alternaria keratitis after deep anterior lamellar keratoplasty.

To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to undergo a repeat DALK as the keratitis did not resolve with medical therapy alone. Patient did not have a recurrence for 11 months following the regraft. This case report highlights the importance of considering the Alternaria species as a possibile cause of non-resolving fungal keratitis after DALK.

INTRODUCTION

Fungal keratitis is a frequent cause of microbial keratitis in India.1 Aspergillus and Fusarium are two of the most common pathogenic fungi isolated.2 Alternaria belongs to group of dematiaceous fungi (black pigmented molds due to melanin) and constitutes an uncommon cause of keratitis with challenging management.234 De-Domingo-Barón et al.1 and Zahra et al.3 have reported cases of Alternaria keratitis in two patients who underwent penetrating keratoplasty.

CASE REPORT

A 30-year-old male patient presented with the complaints of decreased vision in both eyes for 25 years. His best corrected visual acuity (BCVA) was 20/60, N6 and 20/80, N10 in the right and left eyes respectively. On examination, he had bilateral central, leucomatous, vascularized corneal opacity, which was larger in the left eye [Figure 1a] as compared with the right eye. The rest of the ocular and systemic examination was normal. Patient was not a diabetic or hypertensive.

Figure 1a

Vascularized corneal opacity of left eye

Patient underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Post-operatively, patient was prescribed topical 0.5% moxifloxacin, 0.3% tobramycin, 0.1% dexamethasone and 2% hydroxypropyl methyl-cellulose 6 times/day and 1% atropine once at night. Patient developed a recurrent epithelial defect over the next 3 months with a BCVA of 20/60. The defect was treated with a bandage contact lens (BCL).5 At the 3 month follow-up visit, patient presented with reduced vision in the left eye (BCVA 20/200) along with redness and pain. Patient was a driver by occupation and resumed his work 2 days prior when he had an episode of dust particles entering into the left eye. On examination, dust particles were present along with an epithelial defect in the graft. Patient was started on topical 0.3% fluconazole, 0.5% moxifloxacin 0.3% tobramycin along with 2% hydroxypropyl methyl-cellulose eye ointment 6 times/day and 1% carboxymethyl-cellulose hourly.

One week later, a large brown pigmented dry lesion was present on the graft [Figure 1b]. With a working diagnosis of keratitis, corneal scrapping was performed, which showed segmented filamentous fungi on 10% potassium hydroxide mount [Figure 2a] as well as on lactophenol blue stain [Figure 2b].

Figure 1b

Graft showing brown lesion

Figure 2a

10% potassium hydroxide mount showing filamentous fungi

Figure 2b

Lactophenol blue stain showing segmented, filamentous fungi

Culture on sabouraud dextrose agar at 30°C yielded colonies of Alternaria species within 7 days of incubation [Figure 2c]. Oral fluconazole (150 mg) twice daily were started in addition to the topical medications. Patient did not respond to medical therapy and had to undergo a repeat DALK. After removal of the old graft button, four drops of amphotericin B (5 μ/0.1 ml) were place on Descemet's membrane. Patient was prescribed oral fluconazole 150 mg twice daily, ofloxacin 200 mg twice daily and acetazolamide 250 mg twice daily along with topical 5% natamycin, 0.5% moxifloxacin, 0.3% tobramycin, 0.1% dexamethasone, in addition to 2% hydroxypropyl methyl-cellulose 6 times/day and 1% carboxymethyl-cellulose CMC 8 times/day. A BCL was placed for the epithelial defect. Patient improved with complete epithelial healing in 2 weeks and topical 5% natamycin was changed to 1% voriconazole. At 1 month follow-up, the left eye BCVA was 20/60 that remained stable at 11 months follow-up [Figure 2d]. The graft remained clear with no signs of recurrence of fungal infection.

Figure 2c

Alternaria colony on sabouraud dextrose

Figure 2d

11 month after repeat deep anterior lamellar keratoplasty, no signs of recurrence in graft

DISCUSSION

Fungal keratitis is a major cause of corneal blindness in developing countries.1 It has been associated with a spectrum of fungal species such as Aspergillus, Funsarium and Candida in addition to rare types such as dematiaceous fungi including Alternaria and Curvularia.1235 The occurrence of fungal keratitis has been associated with many risk factors such as ocular trauma, diabetes, surgery and use of topical corticosteroids and antibiotics.1

In this case report, the factors which may have predisposed to the development of fungal keratitis include corneal microtrauma in the form of exposure to dust particles, use of topical antibiotics and corticosteroids and BCL. The dust particles may have been the source of the fungal spores. In the literature, Alternaria keratitis has been associated with the use of both soft as well as rigid contact lens.67

Clinically, the lesion of Alternaria keratitis resembles that of a classic filamentary keratitis with the presence of feathery, delicate greyish-white or yellowish white material in the stroma surrounded by infiltration and edema along with satellite lesions. The epithelium may be intact or have a granular, irregular surface. Alternaria, a dematiaceous fungus, may demonstrate macroscopic pigmentation in addition to developing a dense, opaque, greyish-white suppuration in the stroma with minimal associated enlargement and inflammation.18

Following repeat DALK, patient was started on oral fluconazole along with topical 0.5% natamycin, which is a broad spectrum anti-fungal agent. One disadvantage of natamycin is its poor penetration through intact epithelium. So, once the epithelium had healed completely in 2 weeks, patient was switched from 5% natamaycin to 1% voriconazole, which has been shown to be highly effective for Alternaria keratitis.9 Voriconazole is a triazole antifungal agent derived from fluconazole. Studies have established voriconazole to be a valuable fungistatic agent against most yeast in addition to many hyaline and dematiaceous filamentous fungi.10 Oral fluconazole and 1% voriconazole eye drops were continued for 2 months following repeat DALK.

The case report illustrates the role of newer antifungal agents such as topical voriconazole in combination with oral fluconazole for management of non-healing fungal keratitis. We recommend a prospective, randomized, comparative long-term study of various antifungal agents to assess their efficacy as well as gauge the risks and benefits associated with each antifungal in addition to formulating a treatment protocol for non-healing fungal keratitis.

In conclusion, this case report underlines the importance of keeping Alternaria species as differential diagnosis in a case of fungal keratitis. It also highlights the importance of establishing the final diagnosis of fungal keratitis with corneal scraping for culture studies along with demonstrating the fungal elements on microscopic examination. Use of newer antifungal agents such as voriconazole and fluconazole should be considered for fungal keratitis unresponsive to standard treatment regimes.