Rose bengal/green light corneal cross-linking (RGX) is a relatively new development in cross-linking technology. The technique uses green light to activate rose bengal, a well-known diagnostic agent for ocular surface damage, and increase the stiffness of the tissue and its resistance to enzymatic digestion [1,2]. This technology has already proved useful in ocular therapy for sealing corneal lacerations [3-5], bonding amniotic membrane to the cornea [6], attaching IOL haptics to the capsular bag [7], treating Acanthamoeba Trophozoites and cysts [8], and it has been successfully used in many other tissues [9]. In contrast to riboflavin/UVA cross-linking, which causes apoptotic cell death at depths of up to 350 µm, the RGX cross-linking effect is limited to the anterior 100 µm of the tissue and is non-toxic to stromal keratocytes [10,11]. Air puff deformation imaging of rabbit eyes indicate that the overall corneal stiffening effect achieved with RGX does not match that of riboflavin/UVA cross-linking [12]. However, reconstructed bio-mechanical parameters from numerical finite element simulations show that the cross-linked layer of the cornea is actually stiffer after RGX than after riboflavin/UVA cross-linking [13]. Recent studies have shown that iontophoresis may be an effective means of helping rose bengal diffuse deeper into the cornea to increase the depth of RGX cross-linking [14].

Although further research is warranted, current evidence suggests that RGX may be a promising candidate for the treatment of very thin corneas.

[1]  Cherfan D, Verter EE, Melki S, et al. Collagen cross-linking using rose bengal and green light to increase corneal stiffness. Invest Ophthalmol Vis Sci. 2013. 54: 3426-3433.

[2]  Fadlallah A, Zhu H, Arafat S, et al. Corneal Resistance to Keratolysis After Collagen Crosslinking With Rose Bengal and Green Light. Invest Ophthalmol Vis Sci. (2016). 57:6610-6614.

[3]  Wang T, Zhu L, Peng Y, et al. Photochemical Cross-Linking for Penetrating Corneal Wound Closure in Enucleated Porcine Eyes. Curr Eye Res. (2017). 42: 1413-1419.

[4]  Soeken TA, Zhu H, DeMartelaere S, et al. Sealing of Corneal Lacerations Using Photoactivated Rose Bengal Dye and Amniotic Membrane. Cornea. (2018). 37: 211-217.

[5]  Lorenzo-Martin E, Gallego-Munoz P, Ibares-Frias L, et al. Rose Bengal and Green Light Versus Riboflavin-UVA Cross-Linking: Corneal Wound Repair Response. Invest Ophthalmol Vis Sci. (2018). 59: 4821-4830.

[6]  Seiler TG, Engler M, Beck E, et al. Interface Bonding With Corneal Crosslinking (CXL) After LASIK Ex Vivo. Invest Ophthalmol Vis Sci. (2017). 58: 6292-6298.

[7]  Alejandre-Alba N, Gutierrez-Contreras R, Dorronsoro C, et al. Intraocular Photobonding to Enable Accommodating Intraocular Lens Function. Transl Vis Sci Technol. (2018). 7: 27.

[8]  Atalay HT, Dogruman-Al F, Sarzhanov F, et al. Effect of Riboflavin/Rose Bengal-Mediated PACK-CXL on Acanthamoeba Trophozoites and Cysts in Vitro. Curr Eye Res (2018) 43: 1322-1325.

[9]  Redmond RW, Kochevar IE. Medical Applications of Rose Bengal- and Riboflavin-Photosensitized Protein Crosslinking. Photochem Photobiol (2019). 95: 1097-1115.

[10]  Wang T, Zhu L, Zhu J, et al. Subacute effects of rose Bengal/Green light cross linking on rabbit thin corneal stability and safety. Lasers Surg Med (2018). 50: 324-332.

[11]  Zhu H, Alt C, Webb RH, et al. Corneal Crosslinking With Rose Bengal and Green Light: Efficacy and Safety Evaluation. Cornea. (2016). 35: 1234-1241.

[12]  Bekesi N, Kochevar IE, Marcos S. Corneal Biomechanical Response Following Collagen Cross-Linking With Rose Bengal-Green Light and Riboflavin-UVA. Invest Ophthalmol Vis Sci. (2016). 57: 992-1001.

[13]  Bekesi N, Gallego-Munoz P, Ibares-Frias L, et al. Biomechanical Changes After In Vivo Collagen Cross-Linking With Rose Bengal-Green Light and Riboflavin-UVA. Invest Ophthalmol Vis Sci. (2017). 58: 1612-1620.

[14]  Tefon Aribas AB, Sarikaya B, Bilgihan K. Iontophoresis-Assisted Rose Bengal and Green Light Corneal Cross-Linking. Cornea. (2020). 39:1533-1540.


Last updated: April 2021