Several options available for recurrent pterygium

Preoperative and postoperative measures to control ocular surface inflammation can help prevent pterygium recurrence.

Thomas John

Management of pterygium can be a challenging problem, especially with recurrence of the lesion after surgical excision. The underlying multifactorial processes that appear to play a role in pterygium include cellular proliferation, tissue expansion, connective tissue remodeling, overexpression of VEGF, angiogenesis, stem cell damage from ultraviolet exposure and inflammation.

Various treatment approaches have been advocated, including pterygium excision combined with chemotherapeutic agents such as mitomycin C, thiotepa, intralesional bevacizumab or the use of beta radiation, most of which may be associated with potentially serious ocular complications. The current recommended practice is not to leave the sclera exposed but to cover the region with a graft such as amniotic membrane transplantation or conjunctival autograft. The newer surgical strategies have focused on reducing pterygium recurrence, and this surgical arena still continues to evolve and improve.

In this column, Drs. Sheha and Tseng review various newer surgical techniques to curb pterygium recurrence.

Thomas John, MD
OSN Surgical Maneuvers Editor

by Hosam Sheha, MD, PhD, and Scheffer C.G. Tseng, MD, PhD

Pterygium is a common ocular surface disease characterized by cellular proliferation, neovascularization and inflammation. It indicates conjunctivalization of the cornea due to localized ultraviolet-induced damage to the limbal stem cells. Aggressive fibroblasts in the head of the pterygium are found to be responsible for corneal invasiveness. The indications for surgery include reduced vision due to encroachment on the visual axis, irregular astigmatism, chronic irritation, recurrent inflammation, restrictive ocular motility and cosmetic purposes. Numerous surgical techniques have been described, including bare sclera excision with or without the use of adjuncts such as beta irradiation, thiotepa or mitomycin C; transplantation of amniotic membrane; and conjunctival autograft. The main complication of pterygium treatment is the unpredictable rate and timing of recurrences.

Reducing the risk of pterygium recurrence

Ocular surface inflammation plays an important role in pterygium recurrence. It may activate the transformation of the remaining pterygial body fibroblasts into an invasive phenotype, identical to that of the pterygium head fibroblasts, thus increasing the risk of pterygium recurrence. Therefore, control of inflammation before and after surgery is important for reducing recurrence.

Review of published literature suggests that the surgical technique could probably be the single most important factor influencing recurrence. Due to the inflammatory nature of pterygium tissue, the surgically induced inflammation is usually more intense after pterygium excision. Therefore, minimal surgical manipulation during dissection of pterygium is crucial in reducing recurrence. The use of fibrin glue in lieu of sutures in pterygium surgery has significantly reduced postoperative conjunctival inflammation by reducing the surgical trauma.

Intraoperative application of MMC significantly reduces pterygium recurrence by inhibiting fibroblast proliferation and migration. MMC application on the exposed sclera has the potential risk of sight-threatening complications such as necrotizing scleritis, scleral melt, corneal edema and uveitis. Alternative use of MMC directly over the truncated fibrovascular tissue, in the gap between the conjunctival edge and the underlying Tenon’s capsule (Figure 1), may reduce these complications. Advantages of this technique include decreased MMC dosage and direct application to the area of pathology rather than the entire ocular surface. Moreover, for recurrent pterygium, using running sutures to seal the gap between the conjunctiva and Tenon’s capsule has recently been reported to restore caruncle morphology and ocular motility, prevent granuloma pyogenicum, and create a stronger barrier against further recurrence. Hence, it is likely that the same technique can also be used for primary pterygium to improve the outcome and reduce recurrence.

Figure 1. After bare scleral excision of pterygium, a gap is invariably created between the conjunctiva and Tenon’s capsule (white arrow). This gap allows herniation of the fibrovascular tissue (gray arrow) sandwiched in between to cause recurrence. Images: Sheha H, Tseng SCG

Figure 2. Grading of postoperative host conjunctival inflammation. According to the degree of blood vessel injection, inflammation is graded as grade 0 (no inflammation, A), grade 1 (mild, B), grade 2 (moderate, C) and grade 3 (severe, D).

Figure 3. Different approach for primary and recurrent pterygia. For primary pterygium, incision starts anterior to the semilunar fold (A) to resect the fibrovascular tissue, including the Tenon, from the cornea (B, arrow). For recurrent pterygium, incision starts from the head by lifting the remaining conjunctiva from the cornea (C) and being recessed to the fornix without resection (D, arrow).

Uncontrolled postoperative inflammation is also a leading cause of pterygium recurrence. Host conjunctival inflammation with various intensities (Figure 2) was reported adjacent to the transplanted cryopreserved amniotic membrane after pterygium excision despite intraoperative application of MMC. Nevertheless, its incidence may be higher if pterygium excision is not accompanied by transplantation of cryopreserved amniotic membrane, which is known to exert anti-inflammatory, anti-scarring and anti-angiogenic actions. Postoperative injections of long-acting steroids or 5-fluorouracil have been advocated to halt the progression of recurrence by aborting host tissue inflammation. Further prospective, controlled studies focused on early control of host conjunctival inflammation may not only clarify the pathogenesis of recurrent pterygium but also lead to a better treatment strategy.

Surgical pearls for recurrent pterygium

In recurrent pterygium, it is advised to wait for at least 6 months before re-operation to avoid further inflammation. The surgery for recurrent pterygium is different from that for primary pterygium (Figure 3). The first key step in recurrent pterygium is to dissect and recess (but not resect) the conjunctiva back to the fornix to avoid conjunctival shortening or symblepharon. The second key step is to seal the gap between the recessed conjunctival edge and Tenon’s capsule with a running 9-0 nylon suture to prevent recurrence. Furthermore, intraoperative application of MMC is not needed. In recurrent pterygia with binocular diplopia and insufficient remaining conjunctiva in the caruncle due to significant conjunctival scarring, a small conjunctival autograft or oral mucosal graft is needed for better fornix reconstruction.

Because the medial rectus muscle is invariably exposed after conjunctival recession and release of conjunctival cicatrix, it is advised to cover the muscle with one layer of cryopreserved amniotic membrane to recreate the muscle sheath and an anti-adhesion biological barrier. The remaining bare sclera is usually large and thus must be covered by a larger layer of cryopreserved amniotic membrane. As focal and partial limbal stem cell deficiency is invariably present in all pterygia including recurrent ones, restoration of limbal integrity is also important. In this regard, it is important to note that transplantation of cryopreserved amniotic membrane is effective in correcting partial limbal stem cell deficiency in many other diseases by promoting expansion of the remaining limbal epithelial stem cells.

In conclusion, several preoperative and postoperative measures to control ocular surface inflammation have been identified to prevent pterygium recurrence. Additional use of MMC has been associated with reducing postoperative recurrence in primary pterygium. For recurrent pterygium, several key surgical techniques are proposed, including sealing of the gap between the conjunctiva and Tenon’s capsule, that may also be deployed for primary pterygium.

References:

• Anderson DF, Ellies P, Pires RT, Tseng SC. Amniotic membrane transplantation for partial limbal stem cell deficiency. Br J Ophthalmol. 2001;85(5):567-575.
• Bradley JC, Yang W, Bradley RH, Reid TW, Schwab IR. The science of pterygia. Br J Ophthalmol. 2010;94(7):815-820.
• Dushku N, John MK, Schultz GS, Reid TW. Pterygia pathogenesis: corneal invasion by matrix metalloproteinase expressing altered limbal epithelial basal cells. Arch Ophthalmol. 2001;119(5):695-706.
• Hirst LW. The treatment of pterygium. Surv Ophthalmol. 2003;48(2):145-180.
• Hirst LW, Sebban A, Chant D. Pterygium recurrence time. Ophthalmology. 1994;101(4):755-758.
• Kheirkhah A, Casas V, Sheha H, Raju VK, Tseng SC. Role of conjunctival inflammation in surgical outcome after amniotic membrane transplantation with or without fibrin glue for pterygium. Cornea. 2008;27(1):56-63.
• Liu J, Fu Y, Xu Y, Tseng SCG. Caruncle grading and sealing the gap between conjunctiva and Tenon to improve the surgical outcome of multi-recurrent pterygia. Arch Ophthalmol. In press.
• Prabhasawat P, Tesavibul N, Leelapatranura K, Phonjan T. Efficacy of subconjunctival 5-fluorouracil and triamcinolone injection in impending recurrent pterygium. Ophthalmology. 2006;113(7):1102-1109.
• Solomon A, Pires RTF, Tseng SCG. Amniotic membrane transplantation after extensive removal of primary and recurrent pterygia. Ophthalmology. 2001;108(3):449-460.
• Ti SE, Tseng SC. Management of primary and recurrent pterygium using amniotic membrane transplantation. Curr Opin Ophthalmol. 2002;13(4):204-212.
• Tseng SCG, Espana EM, Kawakita T, et al. How does amniotic membrane work? Ocul Surf. 2004;2(3):177-187.

• Hosam Sheha, MD, PhD, can be reached at hsheha@biotissue.com.
• Scheffer C.G. Tseng, MD, PhD, can be reached at stseng@ocularsurface.com.

• Edited by Thomas John, MD, clinical associate professor at Loyola University at Chicago. He is in private practice in Oak Brook, Tinley Park and Oak Lawn, Ill. and can be reached at 708-429-2223; fax: 708-429-2226; email: tjcornea@gmail.com.
• Disclosures: Dr. John has no relevant financial disclosures. Dr. Sheha is an employee of TissueTech Inc. Dr. Tseng is an employee, founder and major shareholder of TissueTech Inc., which holds the patent for processing and clinical uses of cryopreserved amniotic membrane distributed by Bio-Tissue Inc.