Conjunctiva Necrosis Following Subconjunctival Amphotericin B Injection in Fungal Keratitis

Abstract

A 30-year-old Bangladeshi gentleman presented with history of sand entering his left eye and was diagnosed as having fungal keratitis by private ophthalmologist. He was treated with three doses of conventional subconjunctival amphotericin B injections (1.5 mg of amphotericin B and 1.2 mg of deoxycholate) over the inferior bulbar conjunctiva and topical antibiotics. Subsequently, he developed conjunctival necrosis over the site of injections and there was no clinical improvement of the keratitis. He was then treated with intensive antifungal and antibiotics eye drops. Debridement of epithelial plug was done and he was given intracameral amphotericin B injection. There was gradual improvement observed then with conjunctival epithelialization. The conjunctival tissue was completely healed after three months along with the corneal ulcer.Subconjunctival injection of Amphotericin B (AMB) may be considered as an adjunct therapy in severe fungal keratitis to address the issue of compliance. Close monitoring is needed due to its known complication of scleritis, scleral thinning and conjunctival necrosis. Liposomal AMB which is known to cause less toxicity given via subconjunctival injection in human subjects needs to be further studied.

Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels

“…Therefore, AMB is commonly formulated with a solubilizing agent such as deoxycholate for clinical applications . However, the AMB deoxycholate formulation at 0.15% solution shows nephrotoxicity and some allergic reactions to the corneal system in long-term and high-dose treatments . To overcome the solubility and dose-limited toxicity problems, some lipid formulations such as AMB lipid complex, liposomal AMB, and AMB colloidal dispersion have been designed as a carrier for AMB antifungals .…”

Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels

“…Therefore, AMB is commonly formulated with a solubilizing agent such as deoxycholate for clinical applications . However, the AMB deoxycholate formulation at 0.15% solution shows nephrotoxicity and some allergic reactions to the corneal system in long-term and high-dose treatments . To overcome the solubility and dose-limited toxicity problems, some lipid formulations such as AMB lipid complex, liposomal AMB, and AMB colloidal dispersion have been designed as a carrier for AMB antifungals .…”

Clinical Characteristics, Outcomes, and Cost Associated with Inpatient Intensive Care for Infectious Keratitis

“…Human studies on SCAs have been limited to case reports with several cases demonstrating shortened treatment duration with use of subconjunctival amphotericin B or fluconazole as adjuvants to topical and systemic therapies for treatment of fungal keratitis [ 19 , 20 , 21 ]. SCAs do carry unique risks, including conjunctival necrosis following amphotericin B, hemorrhagic occlusive vasculitis following inadvertent intraocular injection of gentamicin, corneal opacification after injection of soframycin, and globe perforation [ 22 , 23 , 24 ]. The decision to manage IK with SCAs would require consideration of the frequency of the injection and topical drop administration, and close monitoring of the patient given the lack of studies in human subjects.…”

Recent Perspectives in the Management of Fungal Keratitis

“…Subconjunctival injection, the other route, which attempts to increase drug compliance and concentration, is not favoured due to the resulting conjunctival granuloma formation [102], necrosis and scleritis [103]. Successful use of subconjunctival amphotericin B without any complications in combination with topical amphotericin B and other standard anti-fungal agents has also been reported [104,105].…”

Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels

“…Therefore, AMB is commonly formulated with a solubilizing agent such as deoxycholate for clinical applications . However, the AMB deoxycholate formulation at 0.15% solution shows nephrotoxicity and some allergic reactions to the corneal system in long-term and high-dose treatments . To overcome the solubility and dose-limited toxicity problems, some lipid formulations such as AMB lipid complex, liposomal AMB, and AMB colloidal dispersion have been designed as a carrier for AMB antifungals .…”

Clinical Characteristics, Outcomes, and Cost Associated with Inpatient Intensive Care for Infectious Keratitis

“…Human studies on SCAs have been limited to case reports with several cases demonstrating shortened treatment duration with use of subconjunctival amphotericin B or fluconazole as adjuvants to topical and systemic therapies for treatment of fungal keratitis [ 19 , 20 , 21 ]. SCAs do carry unique risks, including conjunctival necrosis following amphotericin B, hemorrhagic occlusive vasculitis following inadvertent intraocular injection of gentamicin, corneal opacification after injection of soframycin, and globe perforation [ 22 , 23 , 24 ]. The decision to manage IK with SCAs would require consideration of the frequency of the injection and topical drop administration, and close monitoring of the patient given the lack of studies in human subjects.…”

Recent Perspectives in the Management of Fungal Keratitis

“…Subconjunctival injection, the other route, which attempts to increase drug compliance and concentration, is not favoured due to the resulting conjunctival granuloma formation [102], necrosis and scleritis [103]. Successful use of subconjunctival amphotericin B without any complications in combination with topical amphotericin B and other standard anti-fungal agents has also been reported [104,105].…”

Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels

“…Therefore, AMB is commonly formulated with a solubilizing agent such as deoxycholate for clinical applications . However, the AMB deoxycholate formulation at 0.15% solution shows nephrotoxicity and some allergic reactions to the corneal system in long-term and high-dose treatments . To overcome the solubility and dose-limited toxicity problems, some lipid formulations such as AMB lipid complex, liposomal AMB, and AMB colloidal dispersion have been designed as a carrier for AMB antifungals .…”

Clinical Characteristics, Outcomes, and Cost Associated with Inpatient Intensive Care for Infectious Keratitis

“…Human studies on SCAs have been limited to case reports with several cases demonstrating shortened treatment duration with use of subconjunctival amphotericin B or fluconazole as adjuvants to topical and systemic therapies for treatment of fungal keratitis [ 19 , 20 , 21 ]. SCAs do carry unique risks, including conjunctival necrosis following amphotericin B, hemorrhagic occlusive vasculitis following inadvertent intraocular injection of gentamicin, corneal opacification after injection of soframycin, and globe perforation [ 22 , 23 , 24 ]. The decision to manage IK with SCAs would require consideration of the frequency of the injection and topical drop administration, and close monitoring of the patient given the lack of studies in human subjects.…”

Recent Perspectives in the Management of Fungal Keratitis

“…Subconjunctival injection, the other route, which attempts to increase drug compliance and concentration, is not favoured due to the resulting conjunctival granuloma formation [102], necrosis and scleritis [103]. Successful use of subconjunctival amphotericin B without any complications in combination with topical amphotericin B and other standard anti-fungal agents has also been reported [104,105].…”