Hrev_master [Eye Reports 2011; 1:e1] [page 1] Bilateral pterygium in the two siblings Suleyman Ciftci,1 Leyla Ciftci2 1Department of Ophthalmology, Diyarbakir Training and Research Hospital; 2Department of Cardiology, Faculty of Medicine, Dicle University, Diyarbakir, Turkey Abstract Pterygia are fibrovascular connective tissue overgrowths of bulbar conjunctiva onto the cornea. There is a worldwide distribution of pterygium, but it occurs more commonly in warm, dry climates. Patients younger than the age of 15 rarely acquire a pterygium. We report a case of bilateral nasal pterygium in two sib- lings. A 10-year-old boy and a 12-year-old girl who are siblings presented with bilateral nasal pterygium. While pterygium is a common dis- order, its bilaterality in young people is not a common condition. This report is the first known report in the peer-reviewed medical lit- erature of patients with bilateral nasal ptery- gium in siblings younger than the age of 15. Introduction Pterygia are fibrovascular connective tissue overgrowths of bulbar conjunctiva onto the cornea. They are horizontally located in the interpalpebral fissure on either the nasal or temporal side of the cornea. Histopathologic examination reveals that the subepithelial tis- sue exhibits elastotic degeneration of colla- gen, resulting from breakdown of the collagen and destruction of Bowman’s membrane. Patients younger than the age of 15 rarely acquire a pterygium.1 Case Report A 10-year-old boy and a 12-year-old girl who are siblings presented with bilateral nasal pterygium. On examination, the anterior seg- ments in both eyes of both patients were oth- erwise normal, as were the posterior segments as well as the intraocular pressures (Figures 1 and 2). The visual acuity of the boy was 8/10 in the right eye and 9/10 in the left eye without correction. The visual acuity of the girl was 9/10 in each eye without correction. There was no evidence of other functional impairments in either of the two siblings. None of their par- ents or their first-degree relatives, who live under the same environmental and geographi- cal conditions, had any pterygia. Discussion There is a worldwide distribution of ptery- gium, but it is more common in warm, dry cli- mates. The association between ultraviolet radiation and formation of pterygia is strong. In addition, local drying of the cornea and con- junctiva in the interpalpebral fissure from tear film abnormalities may lead to fibroblastic growth.1 There is also some evidence that hereditary factors play a role in the develop- ment of pterygium. Several case reports sug- gest a possible autosomal dominant pattern of occurrence.2-4 Our knowledge of the pathogen- esis of pterygium has increased in recent years. Recently, Jaworski et al.5 studied some of the genes that play a role in cell migration. These gene products include spermidine/sper- mine N1-acetyltransferase 1, clusterin, S100 protein, and keratins. Among migration-relat- ed genes present in pterygia is the gene SAT1, which encodes for the enzyme spermidine/ spermine N1-acetyltransferase 1. SAT1 is abundant particularly at the body of the ptery- gium. One polyamine analogue, IPENSpm, a potential inhibitor of SAT1, significantly reduces migration in primary cultures of ptery- gium.5 Another of the more abundantly expressed gene products in pterygia is clus- terin. Clusterin has many functions and is known by several synonyms: apolipoprotein J, testosterone-repressed prostate message 2, sulfated glycoprotein 2, and complement-asso- ciated protein SP-40. Clusterin is abundant particularly at the fibrovascular body of the pterygium.5 S100 proteins comprise a multitude of low molecular weight, calcium-binding proteins that interact with other proteins to modulate biological processes.6,7 S100A8 and S100A9 are present at higher levels in pterygia than in uninvolved conjunctiva, and present in tear fluids of patients with pterygia. S100A9 (also known as calgranulin B) is abundant particu- larly at the leading edge of the pterygium body. S100A9 may be a pterygium and/or conjunctiva marker5,6 and may also serve as an especially useful indicator for predicting recurrent ptery- gium.8 Kerkhoff et al. have showed that S100A8 and S100A9 are released from neutrophils by a Eye Reports 2011; volume 1:e1 Correspondence: Suleyman Ciftci, Diyarbakir Eğitim ve Araştirma Hastanesi Göz Hastalikları Polikliniği, 21000 Diyarbakir, Turkey. Tel: +90.412.2570206 - Fax: +90.0412.2245267. E-mail: ciftci1977@hotmail.com Key words: bilaterality, pterygium, sibling, young patients. Conflict of interest: the authors report no con- flicts of interest. Received for publication: 6 April 2011. Accepted for publication: 30 May 2011. This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY- NC 3.0). ©Copyright S. Ciftci and L. Ciftci, 2011 Licensee PAGEPress, Italy Eye Reports 2011; 1:e1 doi:10.4081/eye.2011.e1 Figure 2. Nasal pterygia (arrows) in the right and left eyes of the 12-year-old girl. Figure 1. Nasal pterygia (arrows) in the right and left eyes of the 10-year-old boy. Non -co mmerc ial us e o nly [page 2] [Eye Reports 2011; 1:e1] microtubule-dependent mechanism and may induce inflammation by influencing leukocyte trafficking.9 Jaworski et al. suggested the hypothesis that a pterygium may spread across the corneal surface by migration of cells bearing conjunc- tival and limbal markers into the corneal epithelium.5 They observed migration-related transcripts of the following proteins: keratin 19, found in limbal stem cells; keratins 4 and 13, found in conjunctiva and limbal cells; and aldehyde dehydrogenase, found in corneal epithelial cells.5 Matrix metalloproteinases (MMPs) also play a role in the development of pterygium. The pterygial cells which invade over Bowman’s layer were found to have produced increased matrix metalloproteinases. MMP-1, MMP-2, and MMP-9 are likely the main MMPs respon- sible for dissolution of Bowman’s layer, by acti- vating fibroblasts at the head of the pterygium, nearest to intact Bowman’s layer.10 The finding of increased MMPs at the leading edge of a pterygium led to a more recent study on the effect of doxycycline, an MMP inhibitor on pterygium growth. Doxycycline was shown to reduce migration of pterygial epithelial cells in culture.11 Tong et al. concluded that aberrant wound healing processes play a role in pterygium pathogenesis. They compared expression of primary pterygia, recurrent pterygia, and unin- volved conjunctiva, and observed increased expression of adhesion molecules and extra- cellular matrix and structural proteins (fibronectin; collagen and keratin family mem- bers). Expression of epithelial-mesenchymal transition (EMT), with down-regulation of E- cadherin and up-regulation of β-catenin and lymphoid-enhancer-factor-1, has also been pro- posed as a mechanism for the origin of ptery- gial fibroblasts.16 Vascular endothelial growth factor (VEGF) plays an important role in fibrovascular compo- nent of pterygia. Recently Tsai et al. evaluated potential associations between pterygium for- mation and the VEGF gene-460 polymorphism. They observed no significant differences seen between pterygium and control groups in age and sex, but found that VEGF-460C polymor- phism is associated with pterygium formation in young female patients.17 Dushku and Reid found that there is increased expression of p53 in all pterygia they studied. The increased amount of p53 protein in pterygial cells does not cause apoptosis or block cell proliferation, suggesting that the normal p53 functions are inactivated in ptery- gia.10 Despite the increased amount of p53 pro- tein in pterygial cells, pterygium has been described by some as a benign neoplastic lesion.13-15 Conversely, the small leucine-rich proteogly- can (SLRP) family is highly expressed in the cornea and is believed to contribute to corneal transparency. Members of this family include decorin, keratocan, lumican, and mimecan (also called osteoglycin). SLRPs are collective- ly down-regulated in pterygium. Furthermore, there are no transcripts for any of these SLRPs in the pterygium library.5,12 Conclusions Pterygium is a common disorder; however, it is not common in childhood.4 Few cases of pterygia in childhood have been reported. In a series of 95 patients with pterygia, Ajayi and Bekibele18 reported the youngest was a 10- year-old child with a pterygium. Islam and Wagoner2 reported a family with pterygia. One member of the family was a 4-year-old child. Belliveau and Ali19 reported a 3-year-old child with a pterygium due to xeroderma pigmento- sum; pterygia are a common finding in xero- derma pigmentosa. In the cases in children reported, all except one patient, which report- ed by Islam and Wagoner, were unilateral. In none of the cases reported was there a history of a sibling with a pterygium. Our case is unique in that it is a sibling pair with pterygia, that are also bilateral. I have previously report- ed a boy with bilateral nasal pterygium.20 This report is the first known report in the peer- reviewed medical literature of patients with bilateral nasal pterygium in siblings younger than the age of 15. References 1. Stephen G. Waller, Anthony P. Adamis. Pterygium. Chapter 35. In: William Tasman, eds. Duane's Clinical Ophthalmology on CD-ROM. 1st ed. Philadelphia: Lippincott Williams & Wilkins, 2006. 2. Islam SI, Wagoner MD. Pterygium in young members of one family. Cornea 2001;20:708-10. 3. Zhang JD. An investigation of aetiology and heredity of pterygium. Report of 11 cases in a family. Acta Ophthalmol 1987;65:413-6. 4. Saw SM, Tan D. Pterygium: prevalence, demography and risk factors. Ophthalmic Epidemiol 1999;6:219-28. 5. Jaworski CJ, Aryankalayil-John M, Campos MM, et al. Expression analysis of human pterygium shows a predominance of con- junctival and limbal markers and genes associated with cell migration. Mol Vis 2009;15:2421-34. 6. Riau AK, Wong TT, Beuerman RW, Tong L. Calcium-binding S100 protein expression in pterygium. Mol Vis 2009;15:335-42. 7. Tu CL, Chang W, Bikle DD. The extracellu- lar calcium-sensing receptor is required for calcium-induced differentiation in human keratinocytes. J Biol Chem 2001;276:41079-85. 8 Zhou L, Beuerman RW, Ang LP, et al. Elevation of human alpha-defensins and S100 calcium-binding proteins A8 and A9 in tear fluid of patients with pterygium. Invest Ophthalmol Vis Sci 2009;50:2077- 86. 9. Kerkhoff C, Klempt M, Kaever V, Sorg C. The two calcium-binding proteins, S100A8 and S100A9, are involved in the metabo- lism of arachidonic acid in human neu- trophils. J Biol Chem 1999;274:32672-9. 10. Reid TW, Dushku N. What a study of ptery- gia teaches us about the cornea? Molecular mechanisms of formation. Eye Contact Lens 2010;36:290-5. 11. Cox CA, Amaral J, Salloum R, et al. Doxycycline's effect on ocular angiogene- sis: an in vivo analysis. Ophthalmology 2010;117:1782-91. 12. Kao WW, Liu CY. Roles of lumican and ker- atocan on corneal transparency. Glycoconj J 2002;19:275-85. 13. Dushku N, Reid TW. Immunohisto - chemical evidence that human pterygia originate from an invasion of vimentin- expressing altered limbal epithelial basal cells. Curr Eye Res 1994;13:473-81. 14. Weinstein O, Rosenthal G, Zirkin H, et al. Overexpression of p53 tumor suppressor gene in pterygia. Eye 2002;16:619-21. 15. Tan DT, Tang WY, Liu YP, et al. Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium. Br J Ophthalmol 2000;84:212-6. 16. Tong L, Chew J, Yang H, et al. Distinct gene subsets in pterygia formation and recurrence: dissecting complex biological phenomenon using genome wide expres- sion data. BMC Med Genomics 2009;2:14. 17. Tsai YY, Chiang CC, Bau DT, et al. Vascular endothelial growth factor gene 460 poly- morphism is associated with pterygium formation in female patients. Cornea 2008;27:476-9. 18. Ajayi BG, Bekibele CO. Evaluation of the effectiveness of post-operative beta-irradi- ation in the management of pterygium. Afr J Med Med Sci 2002;31:9-11. 19. Belliveau MJ, Ali A. Pterygium resection with conjunctival autograft in a young child with xeroderma pigmentosum. Cornea 2008;27:1174-5. 20. Ciftci S. Bilateral pterygium, symmetrical nodosity of the auricle, and free iris cyst. Can J Ophthalmol 2009;44:713. Case Report Non -co mmerc ial us e o nly