Skip to main content Skip to main navigation menu Skip to site footer

Fibrin glue: an anti-fibrotic agent for contracted socket

  • Ivon Bremmy Wydha Saputro ,
  • Yulia Primitasari ,
  • Susy Fatmariyanti ,
  • Dyah Fauziah ,
  • Budi Utomo ,


Background: The contracted socket is caused by fibrosis leading to the shortening of the orbital tissue. Vascular endothelial growth factor (VEGF) is a profibrotic factor in postoperative wound healing. The novel option to prevent fibrosis is the use of fibrin glue. This study aims to evaluate the role of fibrin glue in reducing the VEGF expression in cells that cause post-socket surgery scar.

Methods: An in vivo experimental study using an animal model was conducted. We used twenty eyes of white rabbit species as the study sample. The evisceration was carried out and distributed to the animals in four experimental groups consisting of the control group, the MMC group (0.1 ml of mitomycin-C (MMC) 0.4 mg/ml), the triamcinolone acetonide (TCA) group (0.1 ml of TCA 40 mg/ml), and the fibrin glue group (0,1 ml of fibrin glue). The treatment was performed through injection of the subconjunctival. After 14 days, rabbits were euthanized, and conjunctiva samples were cut. Immunoreactivity scores (IRS) were used to analyze the expression of VEGF in epithelia conjunctiva with a significant level of p <0.05. Data were analyzed using SPSS version 26 for Windows.

Results: All groups showed a statistically significant difference in VEGF expression with a p-value 0,000 (p<0,05). The VEGF level was significantly lower in the three treatment groups compared with the control group. The VEGF expression was highest for the control group, followed by fibrin glue, TCA and MMC group. We found significant differences between the control group and the three treatment groups; the MMC group (p=0.001), the TCA group (p=0.002), and the fibrin glue group (p=0.005). While differences in VEGF expression between the three treatment groups could not be proven statistically.

Conclusion: Fibrin glue is proven to reduce VEGF expression as a marker of fibrosis; thus, fibrin glue can be an alternative anti-fibrotic agent.


  1. Mattout HK, Fouda SM, Al-Nashar HY. Evaluation of Topical Mitomycin-C Eye Drops After Reconstructive Surgery for Anophthalmic Contracted Socket. Clinical Ophthalmology (Auckland, NZ). 2021;15:4621.
  2. Peseyie R, Raut AA. Contracted Socket. InStatPearls [Internet]. 2022 Jan 1. StatPearls Publishing.
  3. Chawla U, Anand N, Gupta R, Chadha G, Khurana AK. Epidemiology of Oculoplastic Surgeries Performed at Tertiary Eye Care Hospital in Northern India. Epidemiology. 2021; 9(4).
  4. O'Neill CJ, Oucharek J, Learoyd D, Sidhu SB. Standard and emerging therapies for metastatic differentiated thyroid cancer. The oncologist. 2010;15(2):146-56.
  5. Wilgus TA. Vascular endothelial growth factor and cutaneous scarring. Advances in Wound Care. 2019;8(12):671-8.
  6. Verma A, DeGrado J, Hittelman AB, Wheeler MA, Kaimakliotis HZ, Weiss RM. Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C. BJU international. 2011;107(7):1154-61.
  7. Tawfik HA, Abdulhafez MH, Fouad YA, Rashed HO, Osman WM. Revisiting the role of the myofibroblast in socket surgery: an immunohistochemical study. Ophthalmic Plastic and Reconstructive surgery. 2016;32(4):292.
  8. Hatta M, Massi MN, Natzir R, Ichsan AM. The effectiveness of triamcinolone injection on risk of postoperative operations with the conjunctiva autograft technique and its association with change of VEGF mRNA expression. Biomedical and Pharmacology Journal. 2020;13(2):543-9.
  9. Panda A, Kumar S, Kumar A, Bansal R, Bhartiya S. Fibrin glue in ophthalmology. Indian journal of ophthalmology. 2009;57(5):371.
  10. Komaratih E, Suhendro G, Prakoeswa CR, Rindiastuti Y, Hendrianto E, Susilowati H, Rantam FA. Fibrin Glue Maintain Limbal Mesenchymal Stem Cells Survival: A Novel Cell-Based Therapy Strategy for Modulating Wound Healing After Trabeculectomy. Saudi Journal of Biomedical Reserach. 2019;4(1):11-7.
  11. Rindiastuti Y, Komaratih E, Susilowati H, Soebagyo HD, Rantam FA. Fibrin Glue (FG) Attenuates Fibrosis on Human Tenon's Fibroblasts 9HTFS) of Glaucomatous Eyes: Comparison with Mitomycin C. Biochemical and Cellular Archives. 2019;19(Supp-2):4713-20.
  12. Ramadhan F, Jamaluddin J, Zuhria I, Indriaswati L, Komaratih E. Matrix Metalloproteinase-3 Down-Regulation and Cell Migration Inhibition in Human Pterygium Fibroblasts by Mitomycin-C, Curcumin and Fibrin Glue. The Indonesian Biomedical Journal. 2022;14(2):172-9.
  13. Abdurrauf M, Ramadhan F, Zuhria I, Tambunan BA, Notobroto HB, Surahman B, Komaratih E. Mitomycin C, curcumin, and fibrin glue inhibit the cell proliferation and expression of TGF-β in human pterygium fibroblast. Bali Medical Journal. 2022;11(1):228-33.
  14. Komaratih E, Rindiastuti Y, Susilowati H, Hendrianto E, Suhendro G, Rantam FA. Fibrin Glue (FG) Encapsulated Limbal Mesenchymal Stem Cells (LMSCS) Decrease Bleb Fibrosis Area After Trabeculectomy Through TGF-β and MMP-9 Modulation. Asian Journal of Microbiology, Biotechnology and Environmental Sciences. 2018; 20: 66-73.
  15. Rangel HM, Rolim HT, Vidigal P, Araújo ID, Cronemberger S. Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimental study. Revista do Colégio Brasileiro de Cirurgiões. 2018;45.
  16. Sakarya Y, Sakarya R, Kara S, Soylu T. Fibrin glue coating of the surgical surfaces may facilitate formation of a successful bleb in trabeculectomy surgery. Medical Hypotheses. 2011;77(2):263-5.
  17. Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. Journal of Surgical Research. 2009;153(2):347-58.
  18. Guo Q, Li X, Cui MN, Liang Y, Li XP, Zhao J, Wei LN, Zhang XL, Quan XH. Low-dose mitomycin C decreases the postoperative recurrence rate of pterygium by perturbing NLRP3 inflammatory signalling pathway and suppressing the expression of inflammatory factors. Journal of Ophthalmology. 2019;2019.
  19. Tong JP, Lam DS, Chan WM, Choy KW, Chan KP, Pang CP. Effects of triamcinolone on the expression of VEGF and PEDF in human retinal pigment epithelial and human umbilical vein endothelial cells. Mol Vis. 2006;12(12):1490-5.
  20. Sungkar A, Widyatmoko D, Yarso KY, Wasita B. The effect of duration of wound skin tissue on MDA, TNF-α, IL-6, Caspase 3, VEGF levels, and granulation tissue thickness in the white rat (Rattus novergicus). Bali Medical Journal. 2020; 9(3): 918-923.
  21. Hsieh JY, Smith TD, Meli VS, Tran TN, Botvinick EL, Liu WF. Differential regulation of macrophage inflammatory activation by fibrin and fibrinogen. Acta biomaterialia. 2017; 47:14-24.

How to Cite

Saputro, I. B. W., Primitasari, Y., Fatmariyanti, S., Fauziah, D., & Utomo, B. (2022). Fibrin glue: an anti-fibrotic agent for contracted socket. Bali Medical Journal, 11(3), 1498–1502.




Search Panel