Comparative Study on the Use of Conjunctival Autograft With or Without Mitomycin-C in Pterygium Surgery
Archimedes L.D. Agahan, MD, Pamela P. Astudillo, MD, Romeo C. Dela Cruz, OD, MD
A pterygium is an elastotic degeneration of the conjunctival tissue and hyalination of the subepithelial tissue resulting in a triangular fibrovascular outgrowth from the conjunctiva encroaching on the cornea.1 The worldwide incidence of pterygia appears to be increased in areas within 36 degrees north and south of the equator, popularly known as the pterygium belt, where the Philippines is located.2,3 The most common cause of pterygium is the exposure to ultraviolet B or UVB rays. Other possible causes include hereditary factors such as the p53 oncogene, a marker for the pterygium gene seen among families, and dry eyes due to abnormalities in the tear film causing proliferation of cells for new growth.
Pterygia are graded according to translucency.5 Atrophic pterygium (T1) is defined as a fleshy conjunctival mass where episcleral vessels are unobscured. Intermediate pterygium (T2) is where episcleral vessels are partially obscured. Fleshy pterygium (T3) is where episcleral vessels are completely obscured by the conjunctival mass. When the lesion progresses to involve the central cornea, it causes significant astigmatism, obstruction of the visual axis, and corneal scarring.
Indications for excision are vision loss secondary to proximity to the visual axis or astigmatism, eye movement restriction, atypical appearance, progressive growth, and cosmetic concerns.4 As early as 1800’s, several techniques have been formulated to remove pterygia. Recurrence has always been a primary concern. Most ophthalmologists define pterygium recurrence as regrowth of fibrovascular pterygium-like tissue crossing the limbus onto the cornea with the fibrovascular recurrence attaining the same degree of corneal encroachment as the original lesion or regrowth exceeding 1 mm onto the cornea.
In the hope of preventing recurrence among patients who underwent simple pterygium excision, adjunctive therapies were introduced such as beta-irradiation and thiotepa application, which are no longer used because of serious complications.6 Mitomycin-C (MMC) is an antibiotic-antineoplastic drug that alkylates DNA and produces crosslinks, inhibiting DNA synthesis. In 1994, MMC was introduced as an adjunct therapy in treating recurrent pterygium.
To our knowledge, there have been limited Ophthalmologyreports comparing the efficacy of conjunctival autograft (CA) alone versus CA with intraoperative MMC as an alternative pterygium treatment. This study determined the recurrence rate of CA with and without MMC in the treatment of primary and recurrent pterygium.
The following demographics were gathered: age, gender, address, occupation, history of any systemic disease, history of previous ocular surgery, best-corrected visual acuity, tonometry, refraction, Schirmer’s I and tear break-up time measurements, and slit lamp examination. An image of the patient’s cornea was recorded for baseline comparison prior to surgery. The size of the pterygium was also recorded. Pterygia with at least 2.0 mm size were included in the study.
Patients who fulfilled the inclusion criteria were divided into two groups: primary and recurrent pterygium. Those with primary pterygium were randomly assigned to two groups: group 1 underwent simple excision with CA and group 2 underwent simple excision with CA and intraoperative low-dose MMC. The recurrent pterygium group was also randomized into either group 3 representing simple excision with CA and group 4 for simple excision with CA and intraoperative low-dose MMC. Randomization was done using sealed envelope type.
Three surgeons performed the surgeries following the same method. In the surgical technique, retrobulbar anesthesia was administered using an equal mixture of 3 mL of 1% lidocaine HCl and 3 mL of 4% bupivacaine HCl. Partial thickness of the 12 o’clock limbal area was bridled using spatulated vicryl 6-0 suture. The pterygium head was carefully dissected from the cornea using a blade 15, and the body was dissected from the conjunctiva using Wescott tenotomy scissors. During the process, the rectus muscle was identified and not disturbed. The conjunctival edge was trimmed using tenotomy scissors. The defect was measured (in mm) with a caliper at primary gaze. The superior bulbar conjunctiva was exposed and marked with gentian violet with a measurement 1mm greater than the conjunctival defect. Lidocaine-epinephrine was injected subconjunctivally to the donor conjunctiva using a gauge 30 needle. Careful dissection and excision of the conjunctiva from the Tenon’s was done. The free graft was placed over the scleral bed, epithelium side up, and anchoring sutures were placed on the four corners of the graft using nylon 10-0. Additional sutures were evenly placed to secure the donor conjunctiva. Tobramycin-dexamethasone eye ointment was applied over the sutured area, and pressure eye patch was placed and retained for 24 hours.
The operative technique for conjunctival autograft with MMC application was essentially the same except for the application of 0.02% MMC in the bare sclera and head of the pterygium for 3 minutes and then washed off with 30 mL of normal saline solution after excision of the pterygium.
Patients were given tobramycin-dexamethasone drops four times a day postoperatively and tapered slowly during the course of follow up. Sutures were gradually removed after 3 weeks.
A single examiner, who was blinded to the procedure, did the follow up after 1 day, 1 week, 1 month, 2 months, 3 months, and every 6 months thereafter. In this study, the presence of pterygium recurrence was observed during the entire length of the study. Recurrence was defined as any fibrovascular proliferation encroaching onto the cornea coming from the original pterygium site.
Data were encoded and tallied in SPSS version 10 for Windows. Descriptive statistics were generated for all variables. For nominal data, frequencies and percentages were computed. For numerical data, mean, standard deviation, and the median were generated. Comparison of the different variables under study was done using chi-square, t-test, Mann-Whitney U test, and Fisher’s Exact test.
The research ethics board of PGH has reviewed and approved the protocol.
Table 1. Demographic characteristics of study population (N=58).
The recurrent rates of the different groups are shown in Table 2. Two patients had recurrence of the pterygium, both belonging to the recurrent group. In group 3 (without MMC), the pterygium recurred in a 41-year old laundrywoman with the fibrovascular proliferation on the nasal side of the cornea 2.0 mm from the limbus noted 2 months post-surgery. In group 4 (with MMC), the recurrence was noted in one eye of a 30-year old seafarer with bilateral recurrent pterygium 1 month post-surgery. In this study, the rate of recurrence was 3.22% and there was no difference between the use of MMC or not in both the primary & recurrent groups (p=0.53).
Table 2. Recurrence rates of pterygium.
One patient complained of occasional eye discomfort characterized as sensation of “heaviness” in the affected eye 3 weeks after surgery. On slit-lamp examination, there was note of superficial punctate keratitis with good graft uptake. Patient was started on topical lubricant four times a day with resultant relief.
Table 3. Complications.
There was no difference (p = 0.23) in the proportion of patients with postoperative complications among the groups (Table 3). Steroid-induced increase in intraocular pressure (IOP) (25 to 30 mmHg on week 3) was noted in one patient diagnosed with primary pterygium who underwent CA alone. The steroid was tapered and discontinued within 2 weeks and at 8 weeks post-surgery, IOPs returned to normal. No anti-glaucoma medications were given. Tenon’s cyst was observed in one patient who underwent CA alone. There was no associated limitation of movement of the globe and no medications were given. The plan was to observe.
The management of pterygium recurrence has been a challenge for ophthalmologists for centuries. It has been a source of frustration for both surgeons and patients. Bare sclera and primary closure techniques were frequently performed, with high rates of recurrence.
The introduction of intraoperative MMC to bare sclera has been shown to reduce pterygium recurrence with only minimal complications.7-9 The decreased contact time of the drug to the bare sclera is an important factor to minimize complications. In a 5-year follow-up evaluation of post-pterygium surgery in human eyes using intraoperative MMC, it was found that the use of 0.02% MMC intraoperatively for 3 minutes was safe with no serious complications.8 Another recent study using 0.04% MMC intraoperatively for 1.5 minutes reported no serious complications, such as persistent avascular zones, ulcer or thinning of the sclera, corneal edema, corneal perforation, and scleral calcification.
After the safety of the use of low dose MMC in pterygium excision has been established in 1994, studies thereafter have been conducted to prove its efficacy in reducting pterygium recurrence. Recurrence rates ranged from 4.7% to 33% when combining this adjunct drug with simple pterygium excision.10-14 In a study by Lam, the recurrence was greatly reduced by increasing the concentration and length of exposure of the drug to bare sclera, but this also increased the complications. He reported two cases of scleral melt among patients who had exposure to 0.02% MMC for 5 minutes.14 Thereafter, many have concluded that it was safer to use MMC in moderation and combine it with another effective surgical procedure in reducing recurrence. These studies were the basis for choosing the concentration & exposure time of MMC in this study.
Conjunctival autograft (CA), developed in 1985, is a common surgical procedure that was initially performed for treatment of advanced and recurrent pterygium.15 Currently, it is gaining popularity as a treatment for primary pterygium, with recurrence rates ranging from 13.3% to 20.8%.10,13,16,17 For recurrent pterygium, recurrence rates varied from 13.6% to 31.2%.13,16,17 Studies on mitomycin-C as adjunct therapy to CA have reported further decrease in recurrence rates. Wong compared CA alone versus CA with intraoperative MMC in primary pterygium and reported a significant difference (p<0.03) in recurrence rates between the 2 groups. He concluded that in those with pterygium encroaching one-third to one-half of the cornea, the rate of recurrence was more than double in the CA group.16 Most of the recurrence was noted at the 7th to 9th month of follow up. In another study involving primary pterygium, there was a significant reduction in the recurrence rate when combining CA with MMC compared to CA alone.10 In our study, we not only compared the recurrence rates of CA alone versus CA with MMC in primary but also in recurrent pterygium. Our results showed that recurrence occurred only in the recurrent pterygium group, and that treatment effect was not significantly different between the groups (p=0.53).
Risk factors for pterygium occurrence included younger age and frequent sun exposure. For pterygium recurrence, aside from those mentioned earlier, surgeon’s skill and experience in removing the pterygium could affect the recurrence rate. This was supported by the study of Farrah and coworkers who concluded that the surgeon’s experience could influence the success rates and complications of CA for pterygium treatment.18
One limitation of our study was the short follow-up period. Dela Hoz and associates showed that without MMC, recurrence of pterygium after CA peaked at around 3 to 6 months. If MMC was applied, recurrence was observed at 36 months.19 Our results showed recurrence as early as the first month after surgery in the recurrent pterygium group treated with CA and MMC. Surgeon’s experience and the aggressive nature of the pterygium might explain this early recurrence. Moreover, the patient was a seaman who was constantly exposed to the elements of the sun and wind. Longer follow up is recommended for our study sample to ascertain those that would develop recurrence later.
Complications noted were steroid-induced intraocular pressure elevation and Tenon’s cyst formation. These were not considered to be related to the use of MMC.
In summary, our study showed that conjunctival autograft alone could decrease the recurrence rate among primary and recurrent pterygium, with no significant difference seen with the addition of intraoperative low-dose MMC with a 6-month follow up. Further follow up, however, is recommended to observe for late-onset recurrence and complication.
REFERENCES
1. Ayyala RS, Leibowitz HM. Disorders of the corneal limbus. In: Leibowitz HM, Waring GO, ed. Corneal Disorders: Clinical Diagnosis and Management, 2nd ed. Philadelphia, Pennsylvania: WB Saunders Company, 1998; pp 419-20.
2. Saw SM, Tan D. Pterygium: prevalence, demography, and risk factors. Ophthalmic Epidemiol 1999;6:219-28.
3. Cameron ME, ed. Pterygium Throughout the World. Springfield, Illinois: Thomas Press, 1965.
4. Ang LP, Chua JL, Tan DT. Current concepts and techniques in pterygium treatment. Curr Opin Ophthalmol 2007;18:308-13.
5. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997;115:1235-40.
6. Hirst LW. The treatment of pterygium. Surv Ophthalmol 2003;48:145-80.
7. Mastropasqua L, Carpineto P, Ciancaglini M, et al. Effectiveness of intraoperative mitomycin-C in the treatment of recurrent pterygium. Ophthalmologica 1994; 208:247-9.
8. Raiskup F, Solomon A, Landau D, et al. Mitomycin-C for pterygium: long term evaluation. Br J Ophthalmol 2004;88:1425-8.
9. Diaz L, Villegas V, Emmanueli A. Efficacy and safety of intraoperative mitomycin-C as adjunct therapy for pterygium surgery. Cornea 2008;27:1119-21.
10. Fruch-Pery J, Raiskup F, Ilsar M, et al. Conjunctival autografting combined with low-dose mitomycin-C for prevention of primary pterygium recurrence. Am J Ophthalmol 2006;141:1044-50.
11. Akinci A, Zilelioglu O. Comparison of limbal-conjunctival autograft and intraoperative 0.02% mitomycin-C for treatment of primary pterygium. Int Ophthalmol 2007; 27:281-5.
12. Dela Hoz F, Montero JA, Alio JL, et al. Efficacy of mitomycin-C associated with direct conjunctival closure and sliding conjunctival graft for pterygium surgery. Br J Ophthalmol 2008; 92:175-8.
13. Mutlu FM, Sobaci G, Tatar T, Yildirim E. A comparative study of recurrent pterygium surgery: limbal conjunctival autograft transplantation versus mitomycin-C with conjunctival flap. Ophthalmology 1999;106:817-21.
14. Lam DS, Wong AK, Fan DS, et al. Intraoperative mitomycin-C to prevent recurrence of pterygium after excision. Ophthalmology 1998;105:901-5.
15. Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology 1985;92:1461-70.
16. Wong VA, Law FC. Use of mitomycin-C with conjunctival autograft in pterygium surgery in Asian-Canadians. Ophthalmology 1999;106:1512-5.
17. Mohammad-Salih PA, Sharif AF. Analysis of pterygium size and induced corneal astigmatism. Cornea 2008;27:434-8.
18. Farrah JJ, Lee GA, Greenrod E, Vieira J. Outcomes of autoconjunctival grafting for primary pterygia when performed by consultant compared with trainee ophthalmologists. Clin Exp Ophthalmol 2006;34:857-60.
19. Dela Hoz F, Montero J, Alio J, et al. Efficacy of mitomycin-C associated with direct conjunctival closure and sliding conjunctival graft for pterygium surgery. Br J Ophthalmol 2008; 92:175-178.