Comparative Analysis of Matrix-Regenerating Agent and Corneal Cross-Linking in an Experimental Alkali Burn Rabbit Model

ABSTRACT

Purpose

This study aimed to investigate the clinical and histopathological effects of corneal cross-linking (CXL) and matrix-regenerating agent (RGTA) treatments after corneal alkali burn.

Materials and Methods

Twenty-four alkali-burned corneas from 24 rabbits were divided into three groups: control, CXL, and RGTA. All animals were investigated for epithelial healing, opacification, ulceration, and neovascularization at days 1, 7, 14, and 21 after the alkali burn. Corneas were excised and sent for histological examination on day 21.

Results

One animal each from the CXL and control groups exhibited moderate ulceration, while no ulceration was observed in the RGTA group. No significant difference was observed among the groups in corneal thickness or corneal opacity measurements at the final visit (p = .058 and p = .544, respectively). Both RGTA and CXL treatments were effective in terms of epithelial healing and neovascularization (p = .023 and p = .03, respectively). On histological examination, the CXL and RGTA groups were more effective in treating epithelial loss, stromal edema, corneal vascularization, and leukocytic infiltration than the control group (p < .05). The immunohistochemical staining scores of the CXL and RGTA groups for caspase-3, vascular endothelial growth factor, and matrix metalloproteinase-9 in the epithelium and stroma were significantly lower than those in the control group (p < .05). In the immunohistochemical examination for inducible nitric oxide synthase, epithelial staining scores were similar among the groups (p > .05). In contrast, the stromal staining scores of the CXL and RGTA groups were lower than those of the control group (p < .05).

Conclusion

Both CXL and RGTA therapies were effective in reducing anatomical and histopathological complications after corneal alkali burn. Further investigation is needed to determine the optimal timing, duration, and dosage of these treatments.

KEYWORDS:

• Corneal alkali burn
• RGTA
• regenerating agent
• CXL
• cross-linking

Acknowledgments

Clinical investigators:

E. K, MD: Concept, design, data collection or processing, analysis or interpretation, literature search, writing, critical review.

D. P, MD: Concept, design, analysis or interpretation, literature search, writing, critical review.

N. Y, MD: Concept, analysis or interpretation, critical review.

G. B, MD: Data collection or processing, literature search.

Participating investigators:

M. Y. Y, PhD: Concept, design, data collection or processing, analysis or interpretation, writing, critical review.

Y. Y, MD, PhD: Analysis or interpretation, literature search, critical review.

S. F. R, MS: Design, literature search, writing.

Animal research ethics approval

All procedures in this study conformed to the Declaration of Helsinki and Institutional Review Board (Medical Ethical Committee, Kocaeli University Medical Faculty, Kocaeli, Turkey) and “Principles of laboratory animal care” guidelines were followed [Kocaeli University Animal Experiments Local Ethics Committee (2/5-2017)].

Availability of data and material

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary material.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Kocaeli University Scientific Research Projects Coordination Unit under Grant number [2017/036].