Comparison between three different high fluence UVA levels in corneal collagen cross-linking for treatment of experimentally induced fungal keratitis in rabbits

Abstract

Introduction The aim of this study was to compare the efficacy of Photo-Activated Chromophore for Keratitis – Corneal Collagen Cross-linking (PACK-CXL) of three different total UVA fluence levels and topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits. Methods This is an interventional experimental study including both eyes of 16 rabbits (32 eyes). Fungal keratitis was induced by intrastromal injection of Fusarium Solani into the cornea. The rabbits were then divided into four groups (8 eyes for each) from which group A received Voriconazole eye drops and considered as control group. Group B, C, D received single PACK-CXL session with total fluence levels of 7.2, 10.0 and 15.0 J/cm2 for each respectively. Daily clinical examination was recorded and all corneas were removed for microbiology and histopathology on day ten. Results The mean clinical signs score eyes treated with high fluence PACK-CXL showed evident clinical improvement from fourth to tenth day of treatment. This improvement was equivalent to that of Voriconazole treatment. The results showed better improvement with increasing the UVA total fluence levels but this difference was not statistically significant (P < 0.05). Similarly, the median CFU/ml declined on increasing UVA fluence but with no statistically significant values. Histopathological examination revealed better improvement of inflammatory signs on higher fluence levels compared to lower ones. Conclusions High intensity PACK-CXL (30 mW/cm2) was as effective as Voriconazole in the treatment of fungal keratitis in rabbits. Increasing the fluence of UVA was associated with slightly better clinical outcomes with no added risks. More clinical studies are needed to confirm these results.

Accelerated high fluence photoactivated chromophore for infectious keratitis—corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study

“…Awad et al used rabbit models to test the efficiency of different PACK-CXL protocols on fungal keratitis, vs. Voriconazole as control. They found all protocols including the standard Voriconazole treatment to be effective with no statistically significant difference between them ( Awad et al, 2022 ). Hafezi et al compared antimicrobial therapy and PACK-CXL using of fluences of either 5.4 J/cm 2 or 7.2 J/cm 2 in a phase 3 trial that involved patients with infectious keratitis ( Hafezi et al, 2022a ).…”

“…More in vitro studies support this result ( Lu et al, 2023 ). In vivo studies examining high fluences on infectious keratitis, however, are scarce ( Nateghi Pettersson et al, 2019 ; Knyazer et al, 2021 ; Hafezi et al, 2022a ; Awad et al, 2022 ; Hafezi et al, 2022b ; Marrie et al, 2023 ), mostly on animal models or human case reports. Our first aim is to show the therapeutic benefit of high fluence PACK-CXL in a case series.…”

Fungal Keratitis: Diagnosis, Management, and Recent Advances

“…Hafezi et al 136 recently used UVA of 9 mW/cm 2 for either 10 min, 13 min, or 20 s with a total fluence of either 5.4 J/cm 2 or 7.2 J/cm 2 . Higher fluences of UVA (up to 15 J/cm 2 ) were tested by Awad et al 137,138 and gave better clinical, microbiological, and pathological outcomes on rabbit eyes. Repeated high fluence PACK-CXL was reported by Hafezi et al 134 Four out of 9 eyes showed good response and infection was completely halted and scared down.…”