TABLE 1.
The advantages and limitations of existing CXL agents.
| CXL agent | Advantages | Limitations | Mechanisms | References |
|---|---|---|---|---|
| Riboflavin | Effectiveness and stability | Corneal epithelial removal and subsequent complications | Generating ROS to form covalent bonds between collagen molecules or fibrils | Spoerl et al. (1998), Wollensak et al. (2003), Raiskup et al. (2015), Hersh et al. (2017), Evangelista and Hatch (2018), Agarwal et al. (2022) |
| Hypo-osmolar riboflavin | Suitable for thin corneas less than 400 μm | Corneal epithelial removal and subsequent complications | Thickening corneas to protect corneal endothelium and intraocular tissues | Nassaralla et al. (2013), Koc et al. (2016), Wollensak and Sporl (2019), Akkaya et al. (2020), Singh et al. (2020), Yurttaser Ocak and Mangan (2021), Celik Buyuktepe and Ucakhan (2022), Salimi et al. (2022) |
| Genipin | Rapidness and strong operability | Corneal epithelial removal and subsequent complications | Generating ROS to form covalent bonds between collagen molecules or fibrils | Avila et al. (2012), Dias et al. (2015), Avila et al. (2016), Song et al. (2017), Song et al. (2019), Tang et al. (2019), Song et al. (2021) |
| FARs & BNAs | Intact corneal epithelium, water solubility and good permeability | Potential toxicity and absence of clinical evidence | Generating ROS to promote DNA-DNA and DNA-protein crosslinking | Paik et al. (2009), Paik et al. (2010), Li et al. (2013), Wen et al. (2013), Li et al. (2014), Babar et al. (2015) |
| Rose Bengal | Time-efficient, and suitable for thin corneas less than 400 μm | Absence of clinical evidence | Singlet oxygen and electron transfer | Cherfan et al. (2013), Bekesi et al. (2016), Fadlallah et al. (2016), Zhu et al. (2016), Bekesi et al. (2017), Lorenzo-Martin et al. (2018), Wang et al. (2018), Wertheimer et al. (2019), Gao et al. (2022) |
| WST11 | Capable to treat corneas of any thickness with excellent safety and efficacy | Absence of clinical evidence | Generating ROS to form covalent bonds between collagen molecules or fibrils | Brekelmans et al. (2017a), Brekelmans et al. (2017b), Hayes et al. (2020) |
| Tgases | Effectiveness and safety | Absence of clinical evidence | Inducing new peptide bonds between collagen molecules | Wu et al. (2019), Wu et al. (2020), Wu et al. (2022) |
| NHS, CS, and EDCI | Intact corneal epithelium and low toxicity | Absence of clinical evidence | Activating carboxylate groups to react with primary amine residues on amino acids by forming either O-acylisourea or N-hydroxysuccinimidyl-ester intermediates | Wang et al. (2017), Haneef et al. (2021) |
| Ru | Biocompatibility and superior biomechanical results | Only two studies | Covalently crosslinking free tyrosine, histidine, and lysine groups under visible light (400-450 nm) | Thangavel et al. (2019), Gulzar et al. (2022) |
| Verteporfin | Effectiveness | Only one study | Generating ROS under a non-thermal laser (698 nm) light without the production of heat | Alageel et al. (2018) |