Lymphatic microvessel density as a predictive marker for the recurrence time of pterygium: A three-year follow-up study

Purpose To investigate whether lymphatic microvessel density (LMVD) could be used as a predictive marker for the recurrence time of pterygia. Methods This was a prospective case series study. Ninety-six patients with unilateral eye primary nasal pterygia were included. The patients were clinically evaluated to grade the severity of their pterygia (32 were Grade 1, 29 were Grade 2, and 35 were Grade 3) before they underwent bare sclera resection with the use of mitomycin C. Excised tissues from the 96 patients and the ten normal nasal conjunctiva obtained from age-matched donor eyeballs (controls) were immunostained with LYVE-1 and CD31 monoclonal antibodies to evaluate LMVD and blood microvessel density (BMVD). The patients were followed up for three years or until pterygium recurrence was identified, which was defined as fibrovascular regrowth past the limbus in a previously compromised area. The recurrence time (RT) for a pterygium was calculated, and its relationship with LMVD and/or BMVD was statistically analyzed. Results In total, there were 24 cases of pterygium recurrence. The recurrence rate of Grade 1 was 28.1% (9/32), Grade 2 was 24.1% (7/29), and Grade 3 was 22.9% (8/35), as classified in the primary pterygium (p>0.05); the overall recurrence rate was 25% (24/96) for all patients during the three-year follow-up. In the tissue analysis, there were a small number of CD31 (+), LYVE-1(-) BMVD and only a few CD31 (weak), LYVE-1(+) LMVD in the ten normal nasal conjunctiva tissues. BMVD and LMVD increased significantly in the pterygium tissue compared to the control tissue and were significantly correlated with the width and area of pterygium in Grades 1–3 (all p values <0.05). RT was not correlated with BMVD or pterygium grade, but LMVD was significantly and negatively correlated with RT within each group and in the total patient cohort. Furthermore, we determined that an LMVD greater than 20 in the surgical specimens predicted pterygium recurrence. Conclusions The LMVD of surgical specimens is an independent risk factor and a valuable predictive factor for the recurrence time of pterygia.

[1]  Haotian Lin,et al.  Increasing lymphatic microvessel density in primary pterygia. , 2012, Archives of ophthalmology.

[2]  Sameh S Mandour,et al.  Preoperative subpterygial mitomycin C injection versus limbal conjunctival autograft transplantation for prevention of pterygium recurrence. , 2011, Journal of Ocular Pharmacology and Therapeutics.

[3]  Haotian Lin,et al.  Clinicopathological correlation analysis of (lymph) angiogenesis and corneal graft rejection , 2011, Molecular vision.

[4]  Yuanlian Zeng,et al.  Immunological study of lymphangiogenesis in pterygium pathogenesis , 2011 .

[5]  Boban Džunić,et al.  Analysis of pathohistological characteristics of pterygium. , 2010, Bosnian journal of basic medical sciences.

[6]  Liang Xu,et al.  Epidemiology of pterygium in aged rural population of Beijing, China. , 2010, Chinese medical journal.

[7]  Shiqi Ling,et al.  Crucial role of corneal lymphangiogenesis for allograft rejection in alkali‐burned cornea bed , 2009, Clinical & experimental ophthalmology.

[8]  Haotian Lin,et al.  Development of new lymphatic vessels in alkali‐burned corneas , 2009, Acta ophthalmologica.

[9]  R. Dana,et al.  Regulation of blood vessel versus lymphatic vessel growth in the cornea. , 2009, Investigative ophthalmology & visual science.

[10]  D. Spandidos,et al.  Pathogenetic mechanisms and treatment options for ophthalmic pterygium: trends and perspectives (Review). , 2009, International journal of molecular medicine.

[11]  Haotian Lin,et al.  [Exploration of lymphangiogenesis in alkali burned human cornea]. , 2009, [Zhonghua yan ke za zhi] Chinese journal of ophthalmology.

[12]  Haotian Lin,et al.  Clinical and Experimental Research of Corneal Lymphangiogenesis after Keratoplasty , 2008, Ophthalmologica.

[13]  Terry Kim,et al.  The presence of T-lymphocyte subpopulations (CD4 and CD8) in pterygia: Evaluation of the inflammatory response , 2008, Advances in therapy.

[14]  D. Wakefield,et al.  The pathogenesis of pterygium: current concepts and their therapeutic implications. , 2008, The ocular surface.

[15]  H. Okano,et al.  Epithelial-mesenchymal transition in the pathogenesis of pterygium , 2008 .

[16]  D. Wakefield,et al.  The role of substance P in the pathogenesis of pterygia. , 2007, Investigative ophthalmology & visual science.

[17]  E. Ioachim,et al.  Angiogenesis in pterygium: study of microvessel density, vascular endothelial growth factor, and thrombospondin-1 , 2007, Eye.

[18]  Björn Bachmann,et al.  Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. , 2007, Investigative ophthalmology & visual science.

[19]  E. Crivellato,et al.  Neovascularization and mast cells with tryptase activity increase simultaneously in human pterygium , 2007, Journal of cellular and molecular medicine.

[20]  H. Okano,et al.  Β-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium , 2007 .

[21]  Shuji Takahashi,et al.  Immunolocalisation of E-cadherin and &bgr;-catenin in human pterygium , 2007, British Journal of Ophthalmology.

[22]  Wei Wang,et al.  Relationship between the morbidity of pterygium and the duration of ultraviolet rays exposure in Sanya, China. , 2006, Chinese Medical Journal.

[23]  D. Wakefield,et al.  UVB-mediated induction of cytokines and growth factors in pterygium epithelial cells involves cell surface receptors and intracellular signaling. , 2006, Investigative ophthalmology & visual science.

[24]  Yihai Cao,et al.  Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[25]  F. Tsai,et al.  p53 Expression in Pterygium by Immunohistochemical Analysis: A Series Report of 127 Cases and Review of the Literature , 2005, Cornea.

[26]  P. Heikkilä,et al.  High LYVE-1–Positive Lymphatic Vessel Numbers Are Associated with Poor Outcome in Breast Cancer , 2004, Clinical Cancer Research.

[27]  Toshio Ohhashi,et al.  PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. , 2004, Cancer cell.

[28]  D. Wakefield,et al.  Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases , 2004, Progress in Retinal and Eye Research.

[29]  Claus Cursiefen,et al.  Corneal Lymphangiogenesis: Evidence, Mechanisms, and Implications for Corneal Transplant Immunology , 2003, Cornea.

[30]  M. Orhan,et al.  The roles of T-lymphocyte subpopulations (CD4 and CD8), intercellular adhesion molecule-1 (ICAM-1), HLA-DR receptor, and mast cells in etiopathogenesis of pterygium , 2003, Ocular immunology and inflammation.

[31]  Y. Bar-dayan,et al.  Angiogenesis in pterygium: Morphometric and immunohistochemical study , 2002, Current eye research.

[32]  I. Chowers,et al.  Proliferative activity and p53 expression in primary and recurrent pterygia. , 2001, Ophthalmology.

[33]  D. Tan,et al.  Pterygium: prevalence, demography and risk factors. , 1999, Ophthalmic epidemiology.

[34]  M. Orhan,et al.  Tear functions in patients with pterygium. , 1998, Acta ophthalmologica Scandinavica.

[35]  M. Coroneo,et al.  A Model for Pterygium Formation , 1994, Cornea.

[36]  F. Doran,et al.  Human papillomavirus in pterygium. , 1994, The Central African journal of medicine.

[37]  P. S. Mahar,et al.  Role of mitomycin C in pterygium surgery. , 1993, The British journal of ophthalmology.

[38]  L. Liu,et al.  Immunological studies on the pathogenesis of pterygium. , 1993, Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih.

[39]  S. Hayasaka,et al.  Postoperative instillation of low-dose mitomycin C in the treatment of primary pterygium. , 1988, American journal of ophthalmology-glaucoma.

[40]  O D Pinkerton,et al.  Immunologic basis for the pathogenesis of pterygium. , 1984, American journal of ophthalmology.