High fluence PACK-CXL is better than low fluence PACK-CXL

Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) has progressed a great deal since it was first developed (1) as a treatment for infectious keratitis and corneal ulcers. At first, PACK-CXL utilised the same the technical settings as the original CXL-for-ectasia method, the “Dresden protocol” (2), delivering 5.4 J/cm² of UV energy to the riboflavin-saturated region of the cornea where the infection was present. But it soon became clear that a number of factors meant that higher fluences needed to be delivered: ulcers are opaque, and this makes the effect of PACK-CXL somewhat superficial. For deeper pathogen killing in infectious keratitis ulcers, higher fluences need to be delivered (3).

A recent study by Awad et al. (4) has shown in in rabbits that high fluence PACK-CXL (30 mW/cm²) is as effective as voriconazole for the treatment of fungal keratitis. Compared with voriconazole therapy, high-fluence PACK-CXL not only decreased corneal inflammatory signs and acceleratehealing, but it also decreased the incidence of corneal perforation and intraocular inflammation. In other words, high (30 mW/cm²UV-A fluence is associated with better outcomes regarding not only clinical improvement measures, but also the pathological features of inflammation.



1.     Said DG, Elalfy MS, Gatzioufas Z, et al. Collagen cross-linking with photoactivated riboflavin (Pack-cxl) for the treatment of advanced infectious keratitis with corneal melting. Ophthalmology. 2014;121(7):1377-1382.

2.     Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620-627.

3.     Kling S, Hufschmid FS, Torres-Netto EA, et al. High fluence increases the antibacterial efficacy of pack cross-linking. Cornea. 2020;39(8):1020-1026.

4.     Awad R, Hafezi F, Ghaith AA, et al. Comparison between three different high fluence UVA levels in corneal collagen cross-linking for treatment of experimentally induced fungal keratitis in rabbits. European Journal of Ophthalmology. Published online April 6, 2022:112067212210922.

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