Comparison of Collagen Cross-Linking and Amniotic Membrane Transplantation in an Experimental Alkali Burn Rabbit Model

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To compare the effects of collagen cross-linking (CXL) and amniotic membrane transplantation (AMT) on acute corneal alkali burns.


After establishment of an alkali burn model, 32 rabbits were divided into 4 groups: control group, AMT group, CXL group, and AMT + CXL (combined) group. Clinical parameters, including epithelial wound, opacity, ulceration, and neovascularization, were evaluated on postinjury days 1, 7, 14, and 18. Histological parameters were examined in hematoxylin/eosin (H&E) and Masson trichrome–stained corneal sections. Immunohistochemical analyses, including a terminal deoxynucleotidyl transferase–mediated biotin–deoxyuridine triphosphate nick-end labeling assay and cluster of differentiation 68 (CD68) labeling, were performed to determine the apoptotic index and macrophage activation.


On postinjury day 18, the epithelial wound of AMT {4.08% [interquartile range (IQR), 0.68%–5.22%]}, CXL [1.84% (IQR, 0.01%–3.89%)], and combined [3.44% (IQR, 0.01%–4.36%)] groups were significantly lower than the control [15.23% (IQR, 9.86%–23.06%)] group (P = 0.003). No significant difference was detected between the groups in terms of opacity (P = 0.303). Neovascularization was the least severe in the CXL group [16.18% (IQR, 8.39%–21.28%)] and the most severe in the AMT [34.47% (IQR, 17.71%–62.77%)] and combined [35.12% (IQR, 31.96%–59.98%)] groups on day 18 (P = 0.033). Significant increases in the apoptotic index and CD68 labeling were detected in the CXL and combined groups compared with those in the control group (P = 0.047 and P = 0.001, respectively).


CXL treatment is an effective adjuvant treatment for promoting reepithelialization, reducing inflammation and neovascularization, and preventing ulceration in acute alkali burns. Providing AMT after suppressing inflammation may be a more effective treatment.

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