Intracameral Amphotericin B for Recalcitrant Fungal Keratitis – A new Treatment Paradigm Libing K Dong, BS, David B Krebs, MD

Introduction Discussion Fungal Keratitis is a serious and potentially sight threatening infection Fungal Keratitis remains a significant cause of corneal morbidity due that accounts for up to 45% of all corneal infections1. Risk factors to its ability to penetrate deep into the posterior cornea and anterior include contact lens wear, exposure through trauma, and previously chamber (Figure 2). Although multiple routes of antifungal delivery diseased eyes. What is unique and subsequently problematic about have been proposed and used (topical, systemic, subconjunctival), mycotic keratitis is the ability of fungi to penetrate through the corneal they are all limited by their ability to reach the desired location4,5,6,7. 2 stroma into Descemet’s membrane, where they prefer to reside . While The current approach to treating fungal keratitis starts with topical topical antifungal drops and oral antifungals are the current standard of antifungal drops, followed by oral antifungals for persistent care, their limited ability to reach the inner layers of the cornea have infections, and penetrating keratoplasty for intractable cases. resulted in the prolonged recovery and uncertain prognosis of these Case 2 However, time to recovery with this regimen remains poor, and these infections. Here, we will discuss two cases of intractable fungal keratitis grafts are highly susceptible to failure as the recipient’s eye is often in A 41-year-old Caucasian male, soft contact lens user, presented to us successfully treated with intracameral injections of Amphotericin B. a state of persistent inflammation. with a one-week history of pain, redness, and photophobia in the Case 1 right eye. He had no past ocular history but recalled an incident a few We believe intracameral injections should be introduced to the A 59-year-old Caucasian female with a history of soft contact lens wear days prior in which he fell off his dirt bike into some swampy, muddy treatment sequence as soon as topical drops fail to eradicate the was referred to us with complaints of pain, foreign body sensation, and water. He also frequently slept in his contact lenses and used well infection. The benefit of this delivery is that this route places the drug decreased vision in her right eye. She had no history of ocular trauma or water at home. He had been treated by his referring optometrist with directly where the infection resides and can be done safely in the disease but often slept in her contacts. The referring optometrist had topical antibiotics/steroids for a week without Improvement. office with minimal equipment. Intracameral amphotericin B appears to be very safe with no complications in more than 80% of patients.6 treated her with topical antibiotics and steroids for two days without Upon presentation, vision in the right eye was hand motions. Slit lamp Observational adverse effects of ICAMB were mostly limited to post improvement. exam revealed a white corneal stromal infiltrate at 7’oclock, measuring injection pain and discomfort, which resolved within hours. Vision Initial exam revealed a best corrected visual acuity of 20/400 in the right 2.5mm x 2.5mm, with an overlying epithelial defect. A small hypopyon can decline initially following injection as the amphotericin B kills the eye. Slit lamp exam showed a large, white corneal infiltrate with stromal and moderate white blood cells were present in the anterior chamber, fungus, causing transient inflammation. Other potential edema, thinning, and an overlying epithelial defect located at the but fundus exam showed no evidence of endophthalmitis. Scrapings complications include anterior chamber reaction, secondary infection 7’oclock position, measuring 3mm x 2.5mm (Figure 1). Anterior chamber and cultures revealed Fusarium species. The patient was placed on through the keratolimbal paracentesis, bleeding from mechanical had moderate cell and flare, but no hypopyon was present. Corneal natamycin 5% every hour. However, after two weeks, he continued to trauma to the iris, and formation of anterior subcapsular cataract in scrapings and cultures with repeat showed fungal keratitis caused by have visual decline, pain, and photophobia. the unlikely event that the needle comes in contact with the anterior Bipolaris species. The patient was placed on topical natamycin 5% At this time, the patient received an injection of intracameral lens capsule. hourly, topical voriconazole 1% hourly, and oral voriconazole 100mg amphotericin B 10mcg/0.1mL. By the end of the first week post In conclusion, we believe that intracameral amphotericin B should be twice daily. Over the next few weeks, she developed a persistent injection, evidence of epithelial healing was apparent, vision in the hypopyon and intractable pain with no improvement in vision. given routinely and early on in the management of fungal keratitis, right eye improved to 20/70, and he no longer experienced pain. One right after topical antifungal medications fail to eradicate the Serious considerations was given to performing a therapeutic month after, there was total reepithelialization of the cornea with a infection, even before oral antifungals and penetrating keratoplasty. penetrating keratoplasty. Instead, she was administered a single semi-translucent scar, and best corrected vision was 20/20. 3 injection of intracameral amphotericin B 10mcg/0.1mL . The eye was References prepped with topical anesthetics and antibiotics, a small keratolimbal 1. Niu L, Liu X, Ma Z, et al. Fungal keratitis: Pathogenesis, diagnosis and prevention. Microb paracentesis was made with a sterile superblade, and the amphotericin Pathog. 2019;138:103802. B was injected into the anterior chamber. The incision was self healing 2. Krachmer, Jay H., and David A. Palay. Cornea Color Atlas. Mosby, 1995. 3. Bourcier, T., et al. Fungal Keratitis. Journal Français D'Ophtalmologie. 2017;40(9):307-13 and the patient remained on topical natamycin and voriconazole 4. Yoon KC, Jeong IY, Im SK, Chae HJ, Yang SY. Therapeutic effect of intracameral following the procedure. amphotericin B injection in the treatment of fungal keratitis. Cornea. 2007;26(7):814– 818. Within a few days of the injection, the patient experienced significant 5. Shao Y, Yu Y, Pei CG, et al. Therapeutic efficacy of intracameral amphotericin B injection improvement in vision and comfort. The size of the infiltrate decreased for 60 patients with keratomycosis. Int J Ophthalmol. 2010;3(3):257–260. 6. Sharma B, Kataria P, Anand R, et al. Efficacy Profile of Intracameral Amphotericin B. The and the hypopyon resolved by day four. By one-week post injection, Often Forgotten Step. Asia Pac J Ophthalmol (Phila). 2015;4(6):360–366. vision in the right eye improved to 20/60, the infiltrate had completely 7. Sahay, Pranita, et al. Pharmacologic Therapy for Mycotic Keratitis. Survey of epithelialized, and she was left with a mild stromal scar. Best corrected Ophthalmology, 2019;64(3):380–400. 8. Isipradit S. Efficacy of fluconazole subconjunctival injection as adjunctive therapy for visual acuity was 20/20 one month after treatment. severe recalcitrant fungal corneal ulcer. 2008;91(3):309-315