J.ophthalmol.(Ukraine).2019;1:3-8.
http://doi.org/10.31288/oftalmolzh2019138
Received: 14 November 2018; Published on-line: 27 February 2019
Relationship of the recurrence after pterygium surgery with the presence of HSV, EBV, CMV, HPV, and BRAFV600E mutation
S.O. Rykov1, Dr Sc (Med), Prof.; K.O Usenko1, MD; S.Iu. Mogilevskyy1, Dr Sc (Med), Prof.; S.V. Ziablitsev2, Dr Sc (Med), Prof.; L.I. Denisiuk1, Cand Sc (Med)
1 Shupik National Medical Academy of Postgraduate Education, Kyiv; Kyiv (Ukraine)
2 Bogomolets National Medical University; Kyiv (Ukraine)
E-mail: sergey.mogilevskyy@gmail.com
TO CITE THIS ARTICLE: RykovSO, UsenkoKO, MogilevskyySIu, ZiablitsevSV, DenisiukLI. Relationship of the recurrence after pterygium surgery with the presence of HSV, EBV, CMV, HPV, and BRAFV600E mutation. J.ophthalmol.(Ukraine).2019;1:3-8. http://doi.org/10.31288/oftalmolzh2019138
Background: Previously, we have reported on associations of pterygium with the presence of herpes simplex virus (HSV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human papillomavirus (HPV), and the BRAFV600E somatic point. The current study attempted to examine the relationship between the recurrence during 1 year after pterygium surgery and the presence of these factors.
Purpose: To identify the relationship between (a) recurrence rates after various surgical techniques for pterygium and (b) the presence of herpes viruses (HSV, EBV, and CMV), HPV 6, 11, 16 and 18 and BRAFV600E mutation.
Materials and Methods: Two hundred and three patients (232 eyes) with a history of pterygium surgery underwent examination. They were divided into five groups based on the method of surgical treatment: Group 1 (the McReynolds transplantation only) of 49 eyes; Group 2 (the McReynolds transplantation, with adjuvant MMC 0.02% applied to the cornea for 30 sec) of 41 eyes; Group 3 (the technique of Arlt) of 49 eyes; Group 4 (the technique of Arlt, with adjuvant MMC 0.02% applied to the cornea for 30 sec) of 46 eyes; Group 5 of 47 eyes that were treated with our technique of pterygium excision involving the growth plate, with conjunctival autoplasty and adjuvant MMC 0.02%. Real-time PCR with PCR kits from DNK Tekhnologiya (Russia) were used to identify HSV, EBV, CMV, and HPV. PCR amplification was performed in a DT-lite real-time PCR system (DNK Tekhnologiya). Mutation detection was performed using TaqMan Mutation Detection Assays (Thermo Fisher Scientific) in a Real-Time PCR System 7500 (Applied Biosystems, USA).
Results: Changing from traditional surgical methods (the McReynolds or Arlt method, alone or with adjunctive mitomycin C) to our methodology for pterygium decreased the recurrence rate at 1 year after pterygium surgery by 17.0% (or 2.1-fold), from 31.9% to 14.9% (χ2 = 5.32; р = 0.021). There was a common trend regarding the relationship between the presence of BRAFV600 mutation and pterygium recurrence in the groups: in the groups with traditional surgical methods, the recurrence rate in BRAFV600 mutation-positive patients varied from 73.3% to 81.2%, whereas the recurrence rate in BRAFV600 mutation-negative patients varied from 4.2% to 10.7% (p < 0.001). The mutation increased the risk of a recurrence within a year after pterygium surgery approximately 35.7-fold (OR=35.72; 95% CI, 15.71-81.24). Changing from traditional surgical methods to our methodology for pterygium decreased the recurrence rate at 1 year after pterygium surgery in BRAFV600 mutation-positive patients by 39.8% (or 2.1-fold), from 77.3% to 37.5% (χ2 = 116.92; р < 0.01). Statistical analysis found no relationship between the distribution of recurrences among the groups, and presence of either individual viruses or their combinations (p > 0.1 for all cases).
Conclusion: The presence of HSV, EBV, CMV, HPV, and/or BRAFV600 mutation in pterygium tissue is a risk factor for recurrence after surgical treatment.
Keywords: pterygium, HSV, EBV, CMV, HPV, BRAFV600 mutation
References
1.Fonseca EC, Rocha EM, Arruda GV. Comparison among adjuvant treatments for primary pterygium: a network meta-analysis. Br J Ophthalmol. 2018 Jun;102(6):748-756. Epub 2017 Nov 16.
2.Zhang Q, Bao N, Liang K, Tao L. Adjuvant Use of Cyclosporine A in the Treatment of Primary Pterygium: A Systematic Review and Meta-Analysis. Cornea. 2018 Aug;37(8):1000-7.
3.Zein H, Ismail A, Abdelmongy M, Elsherif S, Hassanen A, Muhammad B, Assaf F, Elsehili A, Negida A, Yamane S, Abdel-Daim MM, Kadonosono K. Autologous blood for conjunctival autograft fixation in primary pterygium surgery: A systematic review and meta-analysis. Curr Pharm Des. 2018 Oct 1.
4.Rykov SO, Mogilevskyy SIu, Usenko EA. [Recurrence after various surgical techniques for pterygium: 1 year follow-up]. Pytannia eksperymentalnoi ta klinichnoi medytsyny. 2014;18(3):98-102. Ukrainian.
5.Gallagher M, Giannoudis A, Herrington C, Hiscott P. Human papillomavirus in pterygium. Br J Ophthalmol. 2001;85(7):782–4.
6.Piecyk-Sidor M, Polz-Dacewicz M, Zagórski Z, Zarnowski T. Occurrence of human papillomavirus in pterygia. Acta Ophthalmol. 2009; 87 (8): 890–5.
7.Chalkia AK, Spandidos DA, Detorakis ET. Viral involvement in the pathogenesis and clinical features of ophthalmic pterygium (Review). Int J Mol Med. 2013 Sep;32(3):539-43.
8.Otlu B, Emre S, Turkcuoglu P, Doganay S, Durmaz R. Investigation of human papillomavirus and Epstein-Barr virus DNAs in pterygium tissue. Eur J Ophthalmol. 2009 Mar-Apr;19(2):175-9.
9.Rykov SO, Mogilevskyy SIu, Usenko EA. [Impact of HPV and HSV on recurrence after pterygium surgery]. In: [Filatov Memorial Lectures 2016]. Odesa; 2016. p.31-2. Russian.
10.Rykov SO, Usenko KO, Ziablitsev SV, Mogilevskyy SIu. [A method for diagnosing a recurrence in pterygium surgery]. In: [One should be able to see his/her own childhood. Proceedings of the 7th Ukrainian Pediatric Ophthalmology Conference]. July 14-15, 2018; Kyiv. p. 124-6. Ukrainian.
11.Liu R, Zhang T, Zhu G, Xing M. Regulation of mutant TERT by BRAF V600E/MAP kinase pathway through FOS/GABP in human cancer. Nat Commun. 2018 Feb 8;9(1):579.
12.Vuong HG, Duong UN, Altibi AM, Ngo HT, Pham TQ, Tran HM, Gandolfi G, Hassell L. A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma. Endocr Connect. 2017 Apr;6(3):R8-R17.
13.Song JY, Sun SR, Dong F, Huang T, Wu B, Zhou J. Predictive Value of BRAFV600E Mutation for Lymph Node Metastasis in Papillary Thyroid Cancer: A Meta-analysis. Curr Med Sci. 2018 Oct;38(5):785-97.
14.Valachis A, Ullenhag GJ. Discrepancy in BRAF status among patients with metastatic malignant melanoma: A meta-analysis. Eur J Cancer. 2017 Aug;81:106-15.
15.Yang Y, Wang D, Jin L, Wu G, Bai Z, Wang J, Yao H, Zhang Z. Prognostic value of the combination of microsatellite instability and BRAF mutation in colorectal cancer. Cancer Manag Res. 2018 Sep 26;10:3911-3929.
16.Detorakis ET, Drakonaki EE, Spandidos DA. Molecular genetic alterations and viral presence in ophthalmic pterygium. Int J Mol Med. 2000 Jul;6(1):35-41.
17.Rykov SO, Mogilevskyy SIu, Usenko KO, Ziablitsev SV. [Modifed surgical treatment for pterygium reduces the postoperative recurrence rate]. In: [Proceedings of Refractive Plein-Air-18 Conference]. October 18-19, 2018; Kyiv. p. 88-90. Ukrainian.