Pterygium can cause a range of symptoms in patients, including redness, irritation, and blurry vision. (See Pterygium: An Overview.) It also induces clinical signs, such as inflammation and astigmatism, and can physically block the visual axis, if large enough. Additionally, the cosmetic appearance of the pterygium may be bothersome to patients. What’s more, it can recur after removal.

Given these facts, the purpose of this article is to provide a look at the risk factors for pterygium development, the risk factors for recurrence, including those associated with surgical technique, and the available adjuvant therapies that can reduce recurrence.

Risk Factors for Development

These include prolonged ultraviolet (UV) exposure, male sex, advanced age, alcohol consumption and outdoor occupation¹. Additionally, pterygium is associated with other ocular surface disorders, such as dry eye disease (DED)² It remains unclear whether pterygium contributes to the development of DED or whether the inverse is true. Further, a recent systematic review indicated a relationship between pterygium and pinguecula and abnormal tear function, and symptoms of DED.²

Risk Factors for Recurrence

Determining which patients are at highest risk for recurrence is not fully understood, however many papers have revealed the risk of recurrence is multi-factorial, and related to patient-related factors, the physical appearance/histopathology of the pterygium itself, and the surgical technique employed to remove it.

• Patient-related factors. These include environmental exposures, such as prolonged exposure to UV light, genetics, and race, with Hispanic and darker-skinned individuals at higher risk of recurrence.^3,4
• Physical appearance/histopathology of the pterygium itself. Multiple grading systems have been proposed to help standardize the reporting of pterygium severity and disease recurrence. In 1997, Tan et al proposed a grading system that evaluated episcleral vessels in relationship to the pterygium body: Pterygium that completely obscured the episcleral vessels were graded as fleshy or T3, and were associated with higher risk of recurrence.⁵ In 2012 and 2017, Liu et al and Miyata et al proposed grading systems based on a single parameter of the pterygium morphology of the caruncle or on corneal higher-order irregularity, respectively.^6,7 While the grading system proposed by Liu et al did address rate of recurrence, it had potential for high inter and intra-rater variability, as it was based on the rater’s judgement on the appearance of the caruncle.⁶ The grading system proposed by Miyata et al used topographic data to objectively evaluate pterygium severity, but did not address recurrence rate.⁷ In 2020, Ting et al proposed a grading system that grades the total dimension of the pterygium, as this is directly related to the operative plan, which impacts recurrence rates. It also uses Stocker’s line in its grading scheme (iron line on the cornea at the leading edge of the pterygium), which may serve as a proxy for the chronicity and risk of potential progression of the pterygium.⁸ The purpose of this new grading system was to develop an objective system to standardize reporting of disease severity and risk of recurrence for use in clinical and research applications.
• Surgical technique. There are multiple options for removal, each with their own level of recurrence rates. In the conjunctival autograft technique, typically, the pterygium head is gently avulsed from the corneal surface. Next, the pterygium body is excised from the bulbar conjunctiva, taking care to excise the Tenon fascia down to the bare sclera with special attention on the free edges of the conjunctiva, as this is a source of fibroblastic proliferation, which may lead to recurrence. A diamond burr or sharp blade can then be used to remove any residual attachments to ensure a smooth surface for the application of the graft and re-epithelialization of the cornea. The resulting defect is measured, and a graft is harvested from the inferior or superior bulbar conjunctiva. The graft can be sutured or glued into place. Koranyi et al found that fibrin glue was associated with an 8% recurrence rate, while suture-assisted fixation was associated with a 20% recurrence rate.⁹ Fibrin glue also shortens operative time, and minimizes post-operative discomfort, making it an effective method for graft fixation. Recurrence rates with the conjunctival autograft technique range from 3.3% to 13.5%. In cases of a repeat excision, recurrence rates have been documented up to 33.3%.¹⁰ A drawback of this technique is that a large graft may be required to close a large defect, thereby limiting healthy conjunctiva available for potential future conjunctival surgeries (such as glaucoma filtration surgeries). Harvesting the graft can cause conjunctival scarring at the donor site. It is, therefore, preferred to obtain the graft tissue from the inferior bulbar conjunctiva. Additionally, Al Fayez et al found that limbal epithelial transplant was more effective than free conjunctival autograft at preventing recurrence after excision of recurrent pterygium.¹¹

The Pterygium Extended Removal Followed by Extended Conjunctival Transplant (P.E.R.F.E.C.T.) Technique, a variation on the conjunctival autograft technique, involves a much larger dissection of Tenon’s followed by the placement of a very large, 8 mm by 15 mm and thin, virtually transparent with minimal Tenon’s, autograft. The pterygium is first transected, and the corneal portion of the pterygium is carefully dissected off. Tenon’s layer is then carefully dissected away from the overlying conjunctiva and sclera beneath it. The dissection area is wide, nearly reaching the superior and inferior rectus muscles, and over the medial rectus muscle back to the caruncle. After Tenon’s is removed, extensive bare sclera should be visible above and below the medial rectus muscle. The area of donor graft is also approximately 8 mm by 15 mm. It should extend from near the superior fornix and 1 mm to 2 mm short of the limbus. Nasally, the graft area should nearly reach the pterygium site, leaving a 5 mm to 7 mm bridge of conjunctiva and Tenon’s. The autograft must be nearly transparent, indicating that no Tenon’s is being carried over with the graft. This is to ensure minimal scarring of the donor site. The graft is then transferred to the site of the former pterygium and is sutured into place. Rates of recurrence can be as low as 0.1%.¹² While this technique has an impressively low recurrence rate, it is time consuming and technically challenging, perhaps explaining why it has yet to become the most common procedure for primary pterygium excision.

The amnion technique utilizes amniotic membrane (either frozen or dehydrated), which has anti-inflammatory and anti-fibrotic properties, to help regenerate the ocular surface.¹³ The resecting procedure is similar to the conjunctival autograft procedure. Care must be taken to ensure the basement membrane is facing up and the stroma down on application of the graft (the stroma side is sticky, and provides a scaffold for corneal epithelial cells to grow). Fibrin glue can be used to fixate the graft. The benefits of the amnion technique are short operative time and conjunctival sparing for patients who may require future glaucoma surgery. Drawbacks include recurrence rates, ranging from 6.4% to 42.3%, and increased cost of surgery.¹³

Other surgical techniques for excising pterygium include a conjunctival transpositional flap and pterygium excision with combined conjunctival autograft and amniotic membrane. The rate of recurrence with a transpositional flap is similar to the rate of conjunctival autografting, however the technique is technically more challenging. Overall, the benefits of the flap technique include decreased operative time, decreased risk of graft loss or inversion, and decreased risk of graft necrosis, as the vessel structure remains intact.^14,15 The drawback is that it is more difficult to use for large pterygium, which leave bare sclera defects larger than 7 mm, although it is still possible, as demonstrated by Aslan et al.¹⁶

The combination conjunctival autograft technique with amniotic membrane is typically reserved for large or inflamed pterygium or in cases of recurrence. In this technique, a small strip of amniotic membrane is placed in the subconjunctival space surrounding the pterygium excision site, and the conjunctival autograft is placed on top. The benefits of this procedure are a 1% recurrence rate at 6 month follow up.¹⁷

A total of 50% of recurrences appear in the first 4 months postoperatively with the surgical techniques mentioned above, and 97% occur within the first year.³ There are multiple adjuvant treatments available to help lower the recurrence rate.

Adjuvant Therapies

Adjuvant therapies have been shown to reduce recurrence rates. They are:

• Mitomitomycin C (MMC). Recurrence rates after primary pterygium excision in combination with MMC have been reported as low as 7%, and for excision of recurrent pterygium rates have been reported as low as 9%.¹⁸
• 5-fluorouracil (5-FU). 5-FU does not appear to produce a statistically significant reduction in recurrence rate when used. However, there does seem to be some evidence that 5-FU can play an important adjuvant role for the treatment of recurrent pterygia. Prabhasawat et al reported that the recurrence rate in controls was 31.4% compared to 7.7% in the 5-FU treatment group.¹⁹
• Multimicroporous expanded polytetrafluoroethylene (e-PTFE) intraoperatively. This is used to reduce symblepharon formation, motility restriction, and conjunctival hyperemia in cases of intractable or multi-recurrent pterygia.²⁰

Postoperatively

Recurrent pterygia are far more aggressive than primary, and differ in their histopathology and gene expression.⁴ Clinical signs of recurrence include conjunctival inflammation, hemorrhage, granuloma, and fibrovascular proliferation.²¹ Postoperatively, the risk of recurrence is managed primarily by attempting to decrease inflammation and postoperative discomfort with the use of topical steroids and NSAIDs. Additionally, there is some evidence that injection of triamcinolone postoperatively may be of some benefit to patients who have signs of early recurrence, as triamcinolone appears to significantly lower the proliferation rate of fibroblasts.²² Treatment and recurrence will evolve as we learn more about the complex molecular pathways that govern formation of these pterygium. CP

References:

1. Rezvan F, Khabazkhoob M, Hooshmand E, Yekta A, Saatchi M, Hashemi H. Prevalence and risk factors of pterygium: a systematic review and meta-analysis. Surv Ophthalmol. 2018;63(5):719-735.
2. Linaburg T, Choi D, Bunya VY, Massaro-Giordano M, Briceño CA. Systematic review: effects of pterygium and pingueculum on the ocular surface and efficacy of surgical excision. Cornea. 2021;40(2):258-267.
3. Hovanesian JA, Starr CE, Vroman DT, et al; ASCRS Cornea Clinical Committee. Surgical techniques and adjuvants for the management of primary and recurrent pterygia. J Cataract Refract Surg. 2017;43(3):405-419.
4. Tong L, Chew J, Yang H, Ang LPK, Tan DTH, Beuerman RW. Distinct gene subsets in pterygia formation and recurrence: dissecting complex biological phenomenon using genome wide expression data. BMC Med Genomics. 2009;2:14.
5. Tan DT Chee SP, Dear KB, Lim AS. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival auto grafting with bare sclera excision. Arch Ophthalmol. 1997;115(10):1235-1240.
6. Liu J, Fu Y, Xu Y, Tseng SC. New grading system to improve the surgical outcome of multirecurrent pterygia. Arch Ophthalmol. 2012;130(1):39-49
7. Miyata K, Minami K, Otani A, Tokunaga T, Tokuda S, Amano S. Proposal for a Novel Severity Grading System for Pterygia Based on Corneal Topographic Data. Cornea. 2017 Jul;36(7):834-840.
8. Ting DSJ, Liu YC, Patil M, et al. Proposal and validation of a new grading system for pterygium (SLIT2). Br J Ophthalmol. 2020 Aug 11:bjophthalmol-2020-315831. [Online ahead of print]
9. Koranyi G, Seregard S, Kopp ED. Cut and paste: a no suture, small incision approach to pterygium surgery. Br J Ophthalmol. 2004;88(7):911-914.
10. Nuzzi R, Tridico F. How to minimize pterygium recurrence rates: clinical perspectives. Clin Ophthalmol. 2018;12:2347-2362.
11. Al Fayez MF. Limbal versus conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology. 2002;109(9):1752-1755.
12. Hirst L. Long-term results of P.E.R.F.E.C.T. for PTERYGIUM. Cornea. 2020 Oct 2. [Online head of print]
13. Clearfield E, Hawkins BS, Kuo IC. Conjunctival autograft versus amniotic membrane transplantation for treatment of pterygium: findings from a Cochrane systematic review. Am J Ophthalmol. 2017;182:8-17.
14. Bilge AD. Comparison of conjunctival autograft and conjunctival transposition flap techniques in primary pterygium surgery. Saudi J Ophthalmol. 2018;32(2):110-113.
15. Dadeya S, Malik KPS, Gullian BP. Pterygium surgery: conjunctival rotation autograft versus conjunctival autograft. Ophthalmic Surg Lasers. 2002;33(4):269-274.
16. Aslan L, Aslankurt M, Aksoy A, Ozdemir M, Yüksel E. Comparison of wide conjunctival flap and conjunctival autografting techniques in pterygium surgery. J Ophthalmol. 2013;2013:209401.
17. Shusko A, Hovanesian JA. Pterygium excision with conjunctival autograft and subconjunctival amniotic membrane as antirecurrence agents. Can J Ophthalmol. 2016;51(6):412-416.
18. Hayasaka S, Noda S, Yamamoto Y, Setogawa T. Postoperative instillation of low-dose mitomycin C in the treatment of primary pterygium. Am J Ophthalmol. 1988;106(6):715-718.
19. Prabhasawat P, Nattaporn Leelapatranura K, Phonjan T. Efficacy of Subconjunctival 5-Flourouracil and Triamcinolone Injection in Impending Recurrent Pterygium. Ophthalmology. 2006 Jul;113(7):1102-9.
20. Kim KW, Kim JC, Moon JH, Koo H, Kim TH, Moon NJ. Management of complicated multirecurrent pterygia using multimicroporous expanded polytetrafluoroethylene. Br J Ophthalmol. 2013;97(6):694-700.
21. Paris Fdos S, de Farias CC, Melo GB, Dos Santos MS, Batista JL, Gomes JA. Postoperative subconjunctival corticosteroid injection to prevent pterygium recurrence. Cornea. 2008 May;27(4):406-10.
22. Viveiros MM, Kitakawa D, Carvalho CS, Candeias J, Padovani CR, Schellini SA. Exposição de fibroblastos de pterígios recidivados e da cápsula de Tenon normal à triancinolona [Exposure of recurrent pterygium and normal Tenon’s capsule fibroblasts to triamcinolone]. Arq Bras Oftalmol. 2012 Jul-Aug;75(4):235-8. Portuguese.
23. Wanzeler ACV, Barbosa IAF, Duarte B, Barbosa EB, Borges DA, Alves M. Impact of pterygium on the ocular surface and meibomian glands. PloS One. 2019;14(9):0213956.
24. Gonçalves RB, Coletta RD, Silvério KG, et al. Impact of smoking on inflammation: overview of molecular mechanisms. Inflamm Res. 2011;60(5):409-424.
25. Rong SS, Peng Y, Liang YB, Cao D, Jhanji V. Does cigarette smoking alter the risk of pterygium? A systematic review and meta-analysis. Invest Ophthalmol Vis Sci. 2014;55(10):6235-6243.

DR. COLE is a resident physician at Weill Cornell Medicine and New York Presbyterian Hospital.

DR. BRISSETTE is an assistant professor of Ophthalmology at Weill Cornell Medicine and New York Presbyterian Hospital. She is an expert in corneal diseases, and performs a variety of advanced surgical procedures, including cataract surgery, premium and complex cataract surgery, laser eye surgery and corneal transplantation.