Estudo comparativo entre agentes reticulantes para possível aplicação no tratamento de ceratocone.

Abstract

The corneal collagen crosslinking (CXL) is a surgical treatment, used to inhibit disease progression in patients with keratoconus, a progressive corneal distrophy associated with thinning and ectasia, which causes low visual acuity due to secondary irregular astigmatism. Such treatment presents a standard protocol, currently well established, which consists of the application of riboflavin and ultraviolet A (UVA) on the epithelium off corneal surface. Riboflavin acts as a photoinducer and, subject to exposure to UVA radiation, generates free radicals that promote crosslinking in the corneal collagen, besides promoting radiation protection to intraocular structures such as lens and retina. However, riboflavin is a large molecule and requires epithelium off to reach the corneal stroma collagen. Many techniques in the promotion of CXL of corneal collagen crosslinking have been studied in order to avoid corneal de-epithelialization, but none demonstrates the same efficacy as the standard technique. With the present study, we aimed to compare the standard technique of CXL with the treatment using genipine as a cross-linker, with and without corneal de-epithelialization. The chemical, mechanical and morphological properties of pig corneas submitted to the crosslinking treatment with riboflavin and genipine were compared and the cytotoxicity of the crosslinking solutions was compared. Thus, the corneas were divided into four groups: riboflavin and UVA according to standard treatment, genipina with corneal epithelium off, genipina with epithelium on and control without crosslinker. In this way, the corneas were submitted to the characterizations and analyzed by the following techniques: Optical Microscopy, Scanning Electron Microscopy, Mechanical Traction Test, Dilatometry and Swelling Degree. Cytotoxicity analysis was performed comparing the standard treatment with genipine. The results demonstrate a greater corneal tensile strength, as well as a greater degree of swelling when genipine was applied to the epithelium off corneal surface; The downward slopes in the dilatometry curve are linear in the UV-CXL and control, and with genipine, the contraction tends to become more pronounced at higher temperatures. Scanning Electron Microscopy was able to demonstrate a demarcation line in the corneal stroma treated with UV-CXL or genipine and Optical Microscopy exhibits different patterns of transmitted light in the different groups, demonstrating greater UV-CXL opacity. In Conclusion, corneal collagen crosslinking induced by 0.1% genipine produces an increase in corneal resistance without causing considerable corneal opacity and may be useful in the treatment of keratoconus. The potential for cytotoxicity to fibroblasts was similar between crosslinking methods.