Owais Tahhan, Diya Baker

Abstract

Fungal keratitis is a challenging ocular infection, particularly in patients with predisposing factors such as diabetes mellitus and prior ocular surgery. We present the case of an elderly man with a history of penetrating keratoplasty and insulin dependent diabetes who developed Candida keratitis in his right eye. Initial treatment with topical natamycin was started following positive fungal scrapings, but due to supply shortages, therapy was transitioned to topical amphotericin B combined with chlorhexidine. Despite the recognised limitations of amphotericin B, including poor corneal penetration and potential toxicity, the patient’s infection resolved successfully with this regimen. This case highlights both the efficacy of natamycin as first-line therapy and the potential of amphotericin B as a valuable second-line option when standard treatment is unavailable. It underscores the importance of early diagnosis, aggressive antifungal therapy, and flexibility in adapting management strategies to resource limitations. Further studies are warranted to optimise antifungal treatment protocols and improve outcomes in fungal keratitis.

Case Presentation

The patient is an elderly man who presented with a history of severe right eye pain, which had a gradual onset and was constant over the past week. He reported progressively worsening vision and noticeable redness (erythema) in the right eye despite using chloramphenicol ointment obtained from a pharmacy. He denied any recent trauma to the eye. His past medical and ophthalmic history included a penetrating keratoplasty in the right eye two years prior, and he was pseudophakic in both eyes. Additionally, he had a history of a triple-heart bypass and long-standing, insulin-controlled diabetes mellitus.

On examination, his visual acuity was measured at 6/60 in the right eye and 6/7.5 in the left eye. Intraocular pressure was within the normal range, recorded at 12 mmHg in the right eye and 16 mmHg in the left eye. Slit-lamp biomicroscopy of the right eye revealed several significant findings: conjunctival injection, three small corneal epithelial defects approximately 1mm x 1mm in size presenting as satellite lesions with stromal infiltrate and feathery edges, anterior chamber cells graded at 2+ and flare graded at +. There was no hypopyon or fibrin in the anterior chamber. The lens was pseudophakic, and the vitreous was clear. Retinal examination of the right eye was challenging but determined to be flat, while the left eye appeared normal.

Initial microbiological evaluation involved corneal scrapings, which identified the presence of fungal hyphae. Culture results subsequently confirmed the organism to be Candida species.

Based on the clinical suspicion of fungal keratitis and the need to prevent secondary bacterial infections, the patient was started on an aggressive regimen of hourly drops of topical natamycin, levofloxacin, and cefuroxime. He was monitored closely with daily examinations for the first week, transitioning to weekly follow-ups.

After two weeks, due to a shortage of natamycin drops in the hospital, a discussion with a clinical pharmacologist led to the initiation of a second-line treatment regimen. This consisted of hourly drops of amphotericin B and chlorhexidine, with a plan to review the patient after 3-4 days to assess the effectiveness of the new treatment approach.

Discussion

Candida fungal keratitis is an opportunistic infection that significantly impacts individuals with predisposing factors such as diabetes mellitus and prior ocular surgery (1). In our case, the elderly patient’s history of diabetes and previous penetrating keratoplasty likely predisposed him to this severe infection.

Topical natamycin 5% is widely regarded as the first-line treatment for fungal keratitis due to its broad-spectrum antifungal activity against various fungal species, including Fusarium, Aspergillus, and Candida (2). However, its efficacy is limited by poor penetration into the corneal stroma, which can lead to treatment failures, especially in deep-seated infections (3). Intrastromal injections of a new soluble form of natamycin (Natasol 0.01%) are being evaluated and have shown promise in recent studies, potentially offering better outcomes in deep fungal infections (4).

Amphotericin B, another polyene antifungal, is effective against a broader spectrum of fungi, including rare species like Lasiodiplodia and Colletotrichum (5). Its use in fungal keratitis, however, is constrained by its limited penetration through the intact cornea and potential toxicity (6). Intracameral injections of amphotericin B have shown efficacy in managing deep fungal corneal ulcers or refractory cases, with some case series reporting high resolution rates (7).

The primary challenge in treating fungal keratitis is the variability in fungal aetiology and the emergence of drug resistance (8). Proper identification using molecular methods and antifungal susceptibility testing is crucial to guide therapy. Combination therapy, such as using topical natamycin with oral or intrastromal voriconazole, has shown better efficacy than monotherapy in some studies (9).

In our patient’s case, it raises important findings such as the effective use of natamycin as a first-line treatment for fungal keratitis, particularly against Candida species, which aligns with existing literature. However, this case also illustrates the practical challenges that can arise due to economic and supply chain factors, such as the unavailability of natamycin. The successful transition to alternative medications— amphotericin B and chlorhexidine – demonstrates that these drugs can serve as reasonable second-line treatments when natamycin is unavailable. This finding is crucial, particularly for healthcare settings with limited resources or those facing medication shortages. Amphotericin B, despite its limitations such as poor corneal penetration and potential toxicity, proved effective when combined with chlorhexidine, which has broad-spectrum antimicrobial properties.

Conclusion

Despite mixed evidence in the literature, our case report demonstrates that combination therapy using natamycin and amphotericin B can be highly effective in treating severe fungal keratitis, particularly in patients with predisposing factors such as diabetes and prior ocular surgery. While natamycin remains the first-line treatment, its limitations necessitate considering alternative or adjunctive therapies like amphotericin B and voriconazole.

Our case report underscores the importance of prompt and accurate diagnosis of fungal keratitis, followed by aggressive antifungal therapy. While natamycin remains the gold standard for initial treatment, the necessity to switch to alternative medications due to supply issues provides valuable insights into the management of such infections. The patient’s full recovery following the use of amphotericin B and chlorhexidine highlights the viability of these alternatives, supporting their use in similar clinical scenarios.

Despite mixed outcomes reported in the literature, our patient’s successful treatment suggests that alternative medications can achieve comparable results when first-line drugs are not available. This case advocates for further research into the efficacy, safety, and accessibility of various antifungal agents and combinations. Future studies should aim to optimise treatment protocols, ensuring effective management of fungal keratitis even in resource-constrained environments.

References

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