PTERYGIUM

Signs and Symptoms

Pterygium (plural: pterygia) is typically discovered upon routine ocular evaluation in asymptomatic individuals, or in patients who present with a cosmetic concern about a tissue “growing over the eye.” In some instances, the vascularized pterygium may become red and inflamed, motivating the patient to seek immediate care. In others, the irregular ocular surface can interfere with the stability of the precorneal tear film, creating a symptomatic dry eye syndrome. Pterygia of significant magnitude can induce irregular tractional forces on the cornea, inducing astigmatism and higher-order aberrations.1 In advanced cases, the visual axis can be obscured, resulting in substantially diminished acuity.2,3

Clinical inspection of pterygia reveals a raised, whitish, triangular-shaped wedge of fibrovascular tissue whose base lies within the interpalpebral conjunctiva and whose apex encroaches on the cornea. The leading edge of this tissue often displays a fine, reddish-brown iron deposition line (Stocker’s line). More than 90% of pterygia occur nasally.4

These lesions are more commonly encountered in warmer climates, or in patients who are otherwise chronically exposed to outdoor elements or smoky/dusty environments. The association between outdoor work, sun exposure and pterygium formation is significant.2,4-9 Use of UV-blocking sunglasses has been seen to reduce the incidence.6 One study showed that pterygia occurred three times more frequently in patients of African descent than Caucasians.9 Men are affected somewhat more frequently than women.8,9

Pathophysiology

Ultraviolet light exposure—UV-A at 315nm to 400nm wavelengths and especially UV-B at 280nm to 315nm—appears to be the most significant contributory factor in the development of pterygia.5-11 This may explain why the incidence is vastly greater in populations near the equator and in persons who spend a great deal of time outdoors.11 Other agents that may contribute to the formation of pterygia include allergens, noxious chemicals and irritants (e.g., wind, dirt, dust, air pollution). Heredity may also be a factor.10

While the etiologies are varied and likely multifactorial, pterygia in all cases represent a degenerative condition of the conjunctival stroma with replacement by thickened, tortuous, elastotic fibers. Activated fibroblasts in the leading edge of the pterygium invade and fragment Bowman’s layer as well as a variable amount of the superficial corneal stroma. It has been suggested that multipotential stem and progenitor cells may be involved in pathogenesis through their differentiation into fibroblasts and vascular endothelial cells.12

The detection of T-lymphocyte infiltration in pterygium epithelium strongly supports the suggestion that cellular immunity plays an important role in pterygium formation.13 Epidermal growth factors have been localized in pterygium tissue, and are significantly induced by UV-B in pterygium-derived epithelial cells. This may be the means by which UV irradiation influences the pathogenesis of pterygium.14

Histologically, pterygia are identical to pingueculae, and their development resembles actinic degeneration of the skin. Surface cells in pterygia exhibit squamous metaplasia with increased goblet cell density. These changes are most pronounced directly over the pterygium surface.15 Stocker’s line represents corneal iron deposition in a linear pattern at the leading edge of the lesion. It is derived from tear film lactoferrin and is presumably due to abnormal iron metabolism. The presence of Stocker’s line along the advancing head of the pterygium may signify a lack of growth potential.15

Pterygia often persist after surgical removal; these lesions appear as a fibrovascular scar arising from the excision site. These “recurrent pterygia” probably have no relationship to ultraviolet radiation, but rather may be likened to keloid development in the skin.16

Management

Before initiating management, the clinician must be certain that the diagnosis is correct. A clear distinction must be made between the potentially progressive pterygium and the less threatening pinguecula. When large, pingueculae may be very difficult to differentiate from pterygia. Typically, pingueculae are more yellow in coloration and lie within the interpalpebral space, but do not encroach beyond the limbus.17 Pingueculae also lack the wing-shaped appearance of pterygia, the former being more oval or amoeboid in appearance. It is also crucial to differentiate pterygia from any potentially malignant ocular surface lesions, such as carcinomatous intraepithelial neoplasia or invasive squamous cell carcinoma. Any question as to the exact diagnosis warrants referral to an experienced ocular oncologist or oculoplastic specialist for evaluation and biopsy.

Because pterygium development and proliferation appears to be linked to environmental exposure, management of asymptomatic or mildly irritating pterygia involves UV-blocking spectacles and liberal ocular lubrication especially if dellen develop. Patients should be advised to avoid smoky or dusty areas as much as possible. More inflamed or irritated pterygia may be treated with topical corticosteroid drops (e.g., prednisolone acetate 1% or loteprednol etabonate 0.5% QID for several days or until symptoms adequately resolve).

Surgical intervention may be indicated for cases of pterygia that present with: (1) unacceptable cosmesis, (2) significant, uncorrectable astigmatism or other aberrations, (3) chronic, peripheral corneal non-wetting or diminished stability, or (4) significant ingrowth to the visual axis, compromising or threatening to compromise visual acuity.

Surgical excision involves dissection and removal of the fibrous tissue down to the level of Tenon’s capsule. Conjunctival autograft—a technique which involves excision of the pterygium and covering of the resulting bare sclera with a free conjunctival graft harvested from an uninvolved site of the ocular surface—is typically used to prevent recurrence.11,18,19 The use of fibrin glue has advanced the utility of conjunctival autografts by eliminating the need for suturing, thus reducing both operating time and postoperative pain and inflammation.20

An alternative to conjunctival autograft involves the use of cryopreserved amniotic membrane transplantation (e.g., AmnioGraft, BioTissue).21-23 Amniotic transplants typically are reserved for patients with recurrence following conjunctival autograft and those with insufficient viable conjunctival tissue, or those with glaucoma who may need the superior conjunctiva preserved for future trabeculectomy. Unfortunately, amniotic membrane transplantation has been associated with a higher rate of recurrence and generally poorer cosmetic outcome.24

Medical adjuncts in the form of the antimetabolites mitomycin-C and 5-fluorouracil may be used in order to reduce a pterygium’s potential for recurrence.25-27 Unfortunately, these antimetabolites can have attendant complications and are therefore typically reserved for cases of previous surgical failure. Topical cyclosporine (Restasis, Allergan) has also been shown in multiple clinical trials to help diminish the rate of pterygium recurrence after surgery.28-30 Beyond medical adjuncts, single-dose beta-irradiation remains the simplest procedure following bare sclera surgery. It is an effective and safe treatment that reduces the risk of primary pterygium recurrence.31

Recent studies have evaluated the use of anti-VEGF drugs such as bevacizumab in the management of pterygia.5,32 In theory, the ability of these medications to induce regression of abnormal blood vessel growth might help to retard the progression of pterygia; however, the clinical effects seen in these trials has been inconsistent and inconclusive. Despite safety, these studies have shown limited impact on growth and, as in other instances where they are used, a need for repeated injections in order to maintain the therapeutic effect.

Clinical Pearls

The word pterygium is ultimately derived from the Greek word pteryx, meaning “wing” and indicative of the characteristic triangular shape of this lesion. In the Latin-American community where the incidence of pterygium can be quite high, the condition is often referred to as carnosidad, which means “fleshy.” The name actually derives from the Spanish word carne, meaning “meat.”

Pterygia do have the capacity to affect vision if left unchecked. The corneal degradative effects of any pterygium appear to extend approximately three millimeters beyond the leading edge, or head, of the lesion.33 This means that the pterygium need not cover the visual axis to inflict significant visual compromise. In our collective experience, we have witnessed seemingly benign pterygia at least two millimeters off the visual axis that have induced in excess of 10 diopters of irregular corneal astigmatism, and resulted in a best-corrected acuity of 20/80.

It is not wise to wait until a pterygium impacts the visual axis or vision before recommending surgical excision. Since healthy corneal tissue beyond the leading edge of the pterygium must be resected during excision, waiting until the visual axis is affected virtually guarantees permanent visual reduction. Pterygia should not be allowed to progress beyond the midway point between the limbus and the pupil.

Follow-up on medium to large sized pterygia should be performed at least once or twice yearly. It should include a manifest refraction, corneal topography, slit lamp evaluation and photodocumentation with measurement of the pterygium.

1. Zare M, Zarei-Ghanavati S, Ansari-Astaneh MR, et al. Effects of pterygium on ocular aberrations. Cornea. 2010;29(11):1232-5.

2. Al-Bdour M, Al-Latayfeh MM. Risk factors for pterygium in an adult Jordanian population. Acta Ophthalmol Scand. 2004;82(1):64-7.

3. Yaacov-Peña F, Jure D, Ocampos J, et al. Prevalence and causes of blindness in an urban area of Paraguay. Arq Bras Oftalmol. 2012;75(5):341-3.

4. Alqahtani JM. The prevalence of pterygium in Alkhobar: A hospital-based study. J Family Community Med. 2013;20(3):159-61.

5. Mauro J, Foster CS. Pterygia: pathogenesis and the role of subconjunctival bevacizumab in treatment. Semin Ophthalmol. 2009;24(3):130-4.

6. Nemesure B, Wu SY, Hennis A, Leske MC; Barbados Eye Studies Group. Nine-year incidence and risk factors for pterygium in the Barbados eye studies. Ophthalmology. 2008;115(12):2153-8.

7. Vojnikovic B, Njiric S, Coklo M, et al. Sunlight and incidence of pterygium on Croatian Island Rab—epidemiological study. Coll Antropol. 2007;31 Suppl 1:61-2.

8. Liu L, Wu J, Geng J, Yuan Z, Huang D. Geographical prevalence and risk factors for pterygium: a systematic review and meta-analysis. BMJ Open. 2013;3(11):e003787.

9. Luthra R, Nemesure BB, Wu SY, et al. Barbados Eye Studies Group. Frequency and risk factors for pterygium in the Barbados Eye Study. Arch Ophthalmol. 2001;119(12):1827-32.

10. Di Girolamo N, Chui J, Coroneo MT, et al. Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases. Prog Retin Eye Res. 2004;23(2):195-228.

11. Todani A, Melki SA. Pterygium: current concepts in pathogenesis and treatment. Int Ophthalmol Clin. 2009;49(1):21-30.

12. Ye J, Song YS, Kang SH, et al. Involvement of bone marrow-derived stem and progenitor cells in the pathogenesis of pterygium. Eye. 2004;18(8):839-43.

13. Beden U, Irkec M, Orhan D, 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. Ocul Immunol Inflamm. 2003;11(2):115-22.

14. Nolan TM, DiGirolamo N, Sachdev NH, et al. The role of ultraviolet irradiation and heparin-binding epidermal growth factor-like growth factor in the pathogenesis of pterygium. Am J Pathol. 2003;162(2):567-74.

15. Detorakis ET, Spandidos DA. Pathogenetic mechanisms and treatment options for ophthalmic pterygium: trends and perspectives (Review). Int J Mol Med. 2009;23(4):439-47.

16. Singh H, Thakur AS, Sharma BL. Primary pterygium – comparsion of limbal conjunctival autografting surgery versus intraoperative mitomycin-C (0.02%) after exicision of primary pterygium. Nat J Comm Med. 2011;2(3): 331-4.

17. Dong N, Li W, Lin H, et al. Abnormal epithelial differentiation and tear film alteration in pinguecula. Invest Ophthalmol Vis Sci. 2009;50(6):2710-5.

18. Frau E, Labetoulle M, Lautier-Frau M, et al. Corneo-conjunctival autograft transplantation for pterygium surgery. Acta Ophthalmol Scand. 2004;82(1):59-63.

19. Chaidaroon W, Wattananikorn S. Conjunctival autograft transplantation for primary pterygium. J Med Assoc Thai. 2003;86(2):111-5.

20. Bahar I, Weinberger D, Gaton DD, et al. Fibrin glue versus vicryl sutures for primary conjunctival closure in pterygium surgery: long-term results. Curr Eye Res. 2007;32(5):399-405.

21. Tananuvat N, Martin T. The results of amniotic membrane transplantation for primary pterygium compared with conjunctival autograft. Cornea. 2004;23(5):458-63.

22. Sangwan VS, Murthy SI, Bansal AK, et al. Surgical treatment of chronically recurring pterygium. Cornea. 2003;22(1):63-5.

23. Huang Y, Li H, Huang Z, et al. Application of amnion membrane transplantation combine with mitomycin C in the treatment of pterygium. Yan Ke Xue Bao. 2004;20(2):74-6.

24. Li M, Zhu M, Yu Y, et al. Comparison of conjunctival autograft transplantation and amniotic membrane transplantation for pterygium: a meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2012;250(3):375-81.

25. Segev F, Jaeger-Roshu S, Gefen-Carmi N, et al. Combined mitomycin C application and free flap conjunctival autograft in pterygium surgery. Cornea. 2003;22(7):598-603.

26. Akarsu C, Taner P, Ergin A. 5-Fluorouracil as chemoadjuvant for primary pterygium surgery: preliminary report. Cornea. 2003;22(6):522-6.

27. Nabawi KS, Ghonim MA, Ali MH. Evaluation of limbal conjunctival autograft and low-dose mitomycin C in the treatment of recurrent pterygium. Ophthalmic Surg Lasers Imaging. 2003;34(3):193-6.

28. Yalcin Tok O, Burcu Nurozler A, Ergun G, et al. Topical cyclosporine A in the prevention of pterygium recurrence. Ophthalmologica. 2008;222(6):391-6.

29. Turan-Vural E, Torun-Acar B, Kivanc SA, Acar S. The effect of topical 0.05% cyclosporine on recurrence following pterygium surgery. Clin Ophthalmol. 2011;5:881-5.

30. Özülken K, Koç M, Ayar O, Hasiripi H. Topical cyclosporine A administration after pterygium surgery. Eur J Ophthalmol. 2012;22 Suppl 7:S5-10.

31. Jurgenliemk-Schulz IM, Hartman LJ, Roesink JM, et al. Prevention of pterygium recurrence by postoperative single-dose beta-irradiation: a prospective randomized clinical double-blind trial. Int J Radiat Oncol Biol Phys. 2004;59(4):1138-47.

32. Sarac O, Demirel S, Oltulu R. Efficacy of intralesional bevacizumab administration in primary pterygium: a quantitative analysis. Eye Contact Lens. 2014;40(1):46-50.

33. Bahar I, Loya N, Weinberger D, et al. Effect of pterygium surgery on corneal topography: a prospective study. Cornea. 2004;23(2):113-7.