Effects of Mitomycin C on Corneal Endothelial Cell Counts in Pterygium Surgery: Role of Application Location




Purpose


To evaluate changes in corneal endothelial cell counts after pterygium surgery with application of mitomycin C (MMC) either on the perilimbal sclera or in the subconjunctival space.


Design


Prospective, randomized interventional study.


Methods


Fifty-six eyes of 56 patients with primary pterygium underwent excision followed by removal of subconjunctival fibrovascular tissue, 0.02% MMC application, and amniotic membrane transplantation. These were stratified randomly into 2 groups. In 1 group (n = 28), MMC was applied on the perilimbal bare sclera (sclera group), and in other group (n = 28), MMC was applied under conjunctiva, where subconjunctival fibrovascular tissue was removed (subconjunctiva group). Based on severity of pterygium fleshiness, MMC was used for 1, 3, or 5 minutes in 8, 13, and 7 eyes, respectively, in the sclera group and in 9, 13, and 6 eyes, respectively, in the subconjunctiva group. Central corneal endothelial cell counts were evaluated before and during 6 months of follow-up after surgery.


Results


Mean preoperative endothelial cell count was 2810 ± 278 cells/mm 2 in the sclera group and 2857 ± 332 cells/mm 2 in the subconjunctiva group. Mean endothelial cell losses in sclera and subconjunctiva groups were 9.7% and 9.0% at 1 week, 6.5% and 6.5% at 1 month, 4.0% and 5.0% at 3 months, and 3.4% and 4.8% at 6 months, respectively, with no statistically significant difference between the 2 groups. Longer durations of MMC application were associated with significantly greater endothelial losses in both groups.


Conclusions


Regardless of application location, MMC use during pterygium surgery can cause a significant decrease in central endothelial cell count.


The most undesirable outcome after surgical excision of primary pterygium is recurrence. To decrease the recurrence rate after pterygium surgery, the initial bare sclera technique has been replaced by methods to cover the bare sclera such as conjunctival autograft or amniotic membrane transplantation. In addition, various adjunctive methods have been used such as β irradiation and several chemical agents, including mitomycin C (MMC), 5-fluorouracil, and thiotepa. Among these, intraoperative application of MMC, an alkylating agent that inhibits DNA synthesis, is the most common adjunctive method used for pterygium surgery.


Many studies have shown that intraoperative use of MMC significantly reduces the recurrence rate of pterygium after excision. Intraoperative MMC has been used mostly on the exposed sclera after pterygium excision. Moreover, to avoid scleral complications of MMC, it also has been applied under the conjunctiva away from the limbus after extensive excision of the pterygium. However, the major concern of MMC application is its safety.


Several complications have been reported after pterygium excision with adjunctive MMC therapy, including necrotizing scleritis, scleral calcification and ulceration, corneal edema, iritis, glaucoma, and cataract. Although conjunctival epithelium and sclera have been described as the 2 main target tissues for MMC, corneal endothelial cells also may be affected. Adverse effects of MMC on corneal endothelium previously have been demonstrated after photorefractive surgery and after glaucoma surgeries. Few recent studies have reported significant corneal endothelial loss after application of MMC for 2 to 5 minutes on the sclera in pterygium surgery. However, it remains unclear whether application of MMC under conjunctiva away from the limbus, rather than on the sclera, has any effect on corneal endothelial cells.


Because proximity of the application site to the cornea may have an effect on the corneal endothelial cell loss resulting from MMC, we postulated that application of MMC under the conjunctiva away from the limbus, rather than on the perilimbal sclera, may result in less endothelial cell loss. Therefore, in this study, we compared endothelial cell loss in patients with primary pterygium who received intraoperative MMC application either on the perilimbal sclera or under the conjunctiva away from the limbus.


Methods


In this prospective randomized study, 58 eyes of 58 patients with primary pterygium underwent extensive excision followed by MMC application and amniotic membrane transplantation. The patients were randomized to receive MMC either on the perilimbal sclera (28 eyes, sclera group) or under the conjunctiva away from the limbus (28 eyes, subconjunctiva group).


Before surgery and at all visits after surgery, each patient underwent a complete ocular examination, including slit-lamp photography, measurement of best-corrected visual acuity, and intraocular pressure. Before surgery, the morphologic features of pterygium were graded according to what was described by Tan and associates. In this grading, pterygia were graded as grade 1 (atrophic pterygium), in which episcleral vessels were unobscured by the body of pterygium, grade 3 (fleshy pterygium) in which episcleral vessels were totally obscured, and grade 2 (those between grades 1 and 3) with partially obscured episcleral vessels.


Before surgery, informed consent was obtained from each patient. All surgeries were performed by one surgeon (A.I.) under retrobulbar anesthesia. For surgery, head and body of the pterygium were removed first by a similar technique in all patients followed by extensive dissection of the subconjunctival fibrovascular tissue, as has been described before. After minimal cauterization of bleeding vessels, 0.02% MMC was applied either on the 3- to 4-mm exposed sclera posterior to the limbus (in sclera group) or under the conjunctiva beneath the supranasal and inferonasal edges, where subconjunctival fibrovascular tissues had been removed (in subconjunctiva group). In the latter group, care was taken to avoid exposure of the bare sclera to MMC. MMC was applied by soaking 1 × 1 × 5-mm pieces of Weck-Cel surgical sponge (Beaver-Visitec International, Inc., Waltham, Massachusetts, USA) in 0.02% solution. Two or 3 pieces of sponge were used for the sclera group; in the subconjunctiva group, 3 or 4 pieces were applied. In both groups, duration of MMC application depended on preoperative grading of pterygium morphologic features, with 1-minute application for grade 1, 3 minutes for grade 2, and 5 minutes for grade 3. Then, the eye surface was washed with 100 ml balanced salt solution followed by amniotic membrane transplantation using 10-0 nylon sutures to cover the sclera. After surgery, all patients received an identical regimen of topical steroids (for 6 weeks) and topical antibiotics (for 2 weeks); sutures were removed at 2 weeks after surgery.


Before surgery and at 1 week, 1 month, 3 months, and 6 months after surgery, mean endothelial cell count were measured at the central cornea using a noncontact specular microscope (SP 2000P; Topcon, Tokyo, Japan) with a photographic area of 0.2 × 0.5 mm. Three endothelial measurements were obtained at each visit, and the average was recorded. All measurements were made by one person.


Statistical analysis was performed using SPSS software version 15 (SPSS, Inc, Chicago, Illinois, USA). The chi-square test was used for comparing qualitative variables; for comparison of continuous quantitative variables within a group or between the groups, an analysis of variance was used. The Student t test was used to compare the results between the sclera and the subconjunctiva groups. P values of .05 or less were considered as statistically significant.




Results


Fifty-six eyes of 56 patients (35 males and 21 females) with a mean age of 41.8 ± 10.9 years (range, 17 to 64 years) were included in the study. Twenty-eight patients in each group completed 6 months of follow-up. Demographic data and preoperative characteristics of the patients in sclera and subconjunctiva groups are shown in Table 1 . There were no statistically significant differences in age, gender, grade of pterygium morphology or preoperative mean endothelial cell count (ECC) between the 2 groups ( Table 1 ). The surgery was uneventful in all eyes, and no intraoperative or postoperative complications, including recurrence, developed in any eyes during the follow-up.



TABLE 1

Preoperative Characteristics of Patients Who Underwent Pterygium Surgery with Application of Mitomycin C Either on the Sclera (Sclera Group) or under the Conjunctiva away from the Limbus (Subconjuctiva Group)









































Sclera Group
(n = 28)
Subconjunctiva Group
(n = 28)
P Value
Age (yrs) 41.1 ± 12.0 42.4 ± 10.1 .88
Gender (male/female) 20/8 15/13 .16
Pterygium morphologic grade .93
1 8 9
2 13 13
3 7 6
Preoperative mean endothelial cell count (cells/mm 2 ) 2810 ± 278 2857 ± 332 .56


In the sclera group, mean ECC decreased from a preoperative value of 2810 ± 278 cells/mm 2 to postoperative values of 2541 ± 296 cells/mm 2 at 1 week, 2627 ± 272 cells/mm 2 at 1 month, 2699 ± 281 cells/mm 2 at 3 months, and 2715 ± 290 at 6 months after surgery. In this group, there were statistically significant reductions in postoperative mean ECC values compared with preoperative value at all time points ( P < .0001). In the subconjunctiva group, mean ECC declined from a preoperative value of 2857 ± 332 cells/mm 2 to postoperative values of 2597 ± 288 cells/mm 2 at 1 week, 2665 ± 270 cells/mm 2 at 1 month, 2708 ± 286 cells/mm 2 at 3 months, and 2713 ± 297 cells/mm 2 at 6 months after surgery. In the subconjunctiva group, there were statistically significant reductions in postoperative mean ECC values compared with preoperative value at all time points ( P < .0001). Comparison of the sclera and the subconjunctiva groups showed no statistically significant differences in mean ECC between them at any postoperative time point.


Postoperative endothelial cell losses for different durations of MMC application have been shown in Table 2 . In both groups, for each specific duration of MMC application, there was a progressive improvement in mean endothelial cell loss over time, with statistically significant decreases in cell losses between 1 week and 1 month and between 1 month and 3 months, but not between 3 months and 6 months after surgery.



TABLE 2

Postoperative Endothelial Cell Loss after Excision of Pterygium with Various Durations of MMC Application Either on the Sclera (Sclera Group) or under the Conjunctiva away from the Limbus (Subconjuctiva Group)

























































Postoperative Endothelial Loss (%) a MMC Application Duration (min): Sclera Group P Value MMC Application Duration (min): Subconjunctiva Group P Value
1 (n = 8) 3 (n = 13) 5 (n = 7) 1 (n = 9) 3 (n = 13) 5 (n = 6)
After 1 wk 5.2 ± 2.1 9.7 ± 1.5 14.6 ± 4.0 <.001 5.6 ± 1.2 9.2 ± 2.9 13.7 ± 1.2 <.001
After 1 mo 2.8 ± 1.6 6.6 ± 2.6 10.5 ± 4.5 <.001 3.8 ± 2.0 6.6 ± 2.3 10.4 ± 4.5 <.001
After 3 mos 1.7 ± 1.1 4.4 ± 2.1 5.8 ± 4.6 .02 2.4 ± 1.8 4.9 ± 3.7 8.9 ± 7.7 .03
After 6 mos 1.5 ± 1.2 4.1 ± 2.7 4.4 ± 5.5 .17 2.7 ± 2.4 4.7 ± 4.4 8.4 ± 7.5 .08

MMC = mitomycin C; mo = month; wk = week.

a Compared with preoperative mean endothelial cell counts.



Longer durations of MMC application were associated with greater endothelial cell losses, with statistically significant differences in cell loss among various application durations at 1 week, 1 month, and 3 months after surgery in both groups. At 6 months after surgery, however, there was no statistically significant difference in mean endothelial loss among various application durations ( Table 2 ).


Comparison of the sclera and the subconjunctiva groups revealed no statistically significant difference between mean postoperative cell losses in these groups at any time point after surgery ( Table 3 ).



TABLE 3

Comparison of Postoperative Endothelial Cell Loss after Excision of Pterygium with Mitomycin C Application Either on the Sclera (Sclera Group) or under the Conjunctiva away from the Limbus (Subconjuctiva Group)





























Postoperative Endothelial Loss (%) a Sclera Group
(n = 28)
Subconjunctiva Group
(n = 28)
P Value
After 1 wk 9.7 ± 4.2 9.0 ± 3.6 .52
After 1 mo 6.5 ± 4.0 6.5 ± 3.6 .97
After 3 mos 4.0 ± 3.0 5.0 ± 4.9 .37
After 6 mos 3.4 ± 3.4 4.8 ± 4.9 .22

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Jan 16, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Effects of Mitomycin C on Corneal Endothelial Cell Counts in Pterygium Surgery: Role of Application Location
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