Intrastromal injection of voriconazole as a therapeutic of fungal hypopyon: a case report

Intrastromal injection of voriconazole as a therapeutic of fungal hypopyon: a case report

Nabil Albab^1,&, Mohammed Oujidi², Sarah Belghamaidi¹, Jihane Hakam¹, Ibtissam Hajji¹, Redouane Moutaj², Abdeljalil Moutaouakil¹

¹Department of Ophthalmology, Mohamed VI University Hospital of Marrakech, Marrakech, Morocco, ²Department of Parasitology, Military Hospital Avicenne, Mohamed VI University Hospital of Marrakech, Marrakech, Morocco

^&Corresponding author
Nabil Albab, Department of Ophthalmology, Mohamed VI University Hospital of Marrakech, Marrakech, Morocco

Introduction    

Fungal infections of the cornea or of the anterior chamber are a rare case, challenging to manage, which causes several complications specifically the blindness. In our study we describe a case of a 7 year old child, for whom we used intracameral and intrastromal injections of voriconazole.

Patient and observation     

We describe the case of a 7-year-old child, victim of ocular trauma causing a corneal wound that was sutured urgently. The child has been regularly monitored in our department. Few months later, he consults for a painful red eye evolving within two weeks. Slit lamp examination revealed a visual acuity limited to hand movements and conjunctival hyperemia. The cornea was clear, however we objected the presence of a total hypopyon in the anterior chamber (Figure 1). The lens and the fundus were inaccessible to examination. We performed a puncture of the anterior chamber into the operating room. The puncture liquid was sent to the laboratory. After that, we injected 0,05ml of voriconazole (VFEND, Pfizer Inc, New York, USA) concentrated to 50 micrograms/0.1 ml intracamerally. The puncture fluid being analyzed in the laboratory, revealed the presence of amoebiasis. Post intrastromal injection, the patient underwent a local treatment with topical antifungal therapy. He was examinated every two days and the response to the therapy was recorded. His best corrected visual acuity (BCVA) went from hand movements to 2/10. The hypopyon regressed in two weeks until complete disappearance (Figure 2). The infection was considered resolved when there was complete healing of the hypopyon and of the anterior chamber inflammation. The patient continued using topical antifungal therapy for next two weeks after complete healing.

Discussion     

Fungal infections of the cornea or of the anterior chamber are major cause of blindness in the world [1]. They are usually challenging to manage [2]. In the last few years, broad spectrum antifungal agents such as voriconazole have been tried and also alternate routes of administration such as intracorneal injections have been used to treat deep and/or resistant fungal keratitis [3]. However, the penetration of many antifungal drugs into the cornea being suboptimal, it makes it difficult to treat cases of deep mycotic keratitis. To overcome these problems, investigators have evaluated alternate routes such as the use of intracameral and intrastromal injections of voriconazole [4]. Voriconazole has the best in vitro efficacy against pathogenic fungi compared with other agents and it has low minimum inhibitory concentration (MIC) values against Candida [5]. In our case, Voriconazole 50 microgramm/0.1 mL was injected in the anterior chamber after ponction of the hypopyon. We believe that this technique of injection, has the best chance of achieving MIC of the drug at the tissue level. Only few preliminary clinical studies have reported the effect of intracameral injection of Voriconazole on deep keratomycosis and endophtalmitis and seems to be safe and effective [6]. The experimental use of intracameral voriconazole in humans showed no toxic effects when the aqueous concentration was 10 μg/mL - 1.5 mg/mL, above 1.5 mg/mL there was a dose-dependant reduction in corneal endothelial cells, trabecular meshwork cells, and retinal pigment epithelial cells [7]. This medical therapy was safe, allowing higher drug bioavailability within the anterior chamber thus controlling the intraocular infection compared to topical use. However, clinical trials assessing the safety and efficacy of intracameral Voriconazole should be considered [8].

Conclusion     

The use of voriconazole as an intracameral injection has shown its superiority in treating fungal endophtalmitis. Further studies should be underwent to learn more about better injection strategies and so as to consider better its benefits and side effects.

Competing interests     

The authors declare no competing interests.

Authors’ contributions     

All the authors have read and agreed to the final manuscript.

Figures     

Figure 1: image showing the presence of a total hypopyon in the anterior chamber

Figure 2: image of hypopion regression after 2 weeks of treatment

References     

1. Bharathi MJ, Ramakrishnan R, Vasu S, Meenakshi R, Palaniappan R. Epidemiological characteristics and laboratory diagnosis of fungal keratitis: a three-year study. Indian J Ophthalmol. 2003 Dec;51(4):315-21. PubMed | Google Scholar


2. Yoon KC, Jeong IY, Im SK, Chae HJ, Yang SY. Therapeutic effect of intracameral amphotericin B injection in the treatment of fungal keratitis. Cornea. 2007 Aug;26(7):814-8. PubMed | Google Scholar


3. Solaiman KA, Alkawas AA, Ibrahim BM, Mahdy MM, Shalaby MA. Topical Voriconazole Drops With and Without Intrastromal Voriconazole Injection for Treatment of Deep or Resistant Fungal Keratitis. J Clin Exp Ophthalmol. 2015;6:4. Google Scholar


4. Prakash G, Sharma N, Goel M, Titiyal JS, Vajpayee RB. Evaluation of intrastromal injection of voriconazole as a therapeutic adjunctive for the management of deep recalcitrant fungal keratitis. American journal of ophthalmology. 2008;146(1):56-59. PubMed | Google Scholar


5. Kalaiselvi G, Narayana S, Krishnan T, Sengupta S. Intrastromal voriconazole for deep recalcitrant fungal keratitis: a case series. British Journal of Ophthalmology. 2015;99(2):195-198. PubMed | Google Scholar


6. Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. American journal of ophthalmology. 2010;149(6):916-921. PubMed | Google Scholar


7. Kernt M, Kampik A. Intracameral voriconazole: in vitro safety for human ocular cells. Toxicology. 2009 Apr 28;258(2-3):84-93. PubMed | Google Scholar


8. Haddad RS, El-Mollayess GM. Combination of intracameral and intrastromal voriconazole in the treatment of recalcitrant Acremonium fungal keratitis. Middle East African journal of ophthalmology. 2012;19(2):265-8. PubMed | Google Scholar