COMPARISON OF PREOPERATIVE AND INTRAOPERATIVE MITOMYCIN C IN PREVENTION OF PTERYGIUM RECURRENCE AND POSTOPERATIVE COMPLICATIONS.
Objective: To compare the frequency of recurrence and corneoscleral complications with pre-operative and intraoperative mitomycin C when used with excision of primary pterygium by bare sclera technique.
Study Design: Quasi experimental study.
Place of Study: Armed Forces Institute of Ophthalmology Rawalpindi
Duration of Study: Ten months (October 2006 to July 2007).
Patients and Methods: A total of 70 cases with primary pterygium were selected and divided equally into group A and B. In cases of group A, 0.1cc of 0.15 mg/ml of MMC was injected sub-conjunctivally and pterygium excision with bare sclera technique was done 4 weeks later. In cases of group B, after removing the pterygium by bare sclera technique, a sponge soaked in 0.04% MMC was applied over the bare sclera for three minutes intraoperatively. The patients were followed up to see recurrence and corneoscleral complications for three months.
Results: A total of 70 cases, 35 in each group were analyzed statistically. Mean age of group A was 40.83+-12.655 years whereas that of group B was 44.57+-13.718 years. Group A had 28 (80%) males and 7 (20%) females. Group B had 23 (65.7%) males and 12 (34.3%) females. Number of patients who presented with recurrence in group A was 1 (2.9%) and group B were 4 (11.4%). In group A no patient presented with corneoscleral complications during the study whereas in group B these complications were seen in 7 (20%). Chi-square test revealed no significant difference in recurrence (P=0.356) whereas it showed significant difference in corneoscleral complications between the groups (P=0.011).
Conclusion: Preoperative MMC is as effective as intraoperative MMC in preventing recurrence but it is much safer than intraoperative MMC causing less corneoscleral complications.
Pterygium is a common fibrovascular proliferative disease affecting the ocular surface, which may result in visual deterioration from encroachment of the visual axis, progressive scarring and irregular astigmatism1. Histologically it is an active, invasive, inflammatory process, a key feature of which is focal limbal failure resulting in "conjunctivalization" of the cornea2. Primary pterygium may be excised using bare sclera technique (BST) but surgical trauma and subsequent postoperative inflammation contributes to pterygium recurrence. To prevent recurrence, two major adjunctive therapies are usually performed: (1) the application of antimetabolites, and (2) conjunctival or limbal autograft3.
Mitomycin C (MMC) prevents pterygium recurrence by its ability to inhibit fibroblast proliferation at the level of the episclera. It is an antineoplastic antibiotic agent isolated from the fermentation filtrate of Streptomyces caespitosus. It alkylates and crosslinks DNA and inhibits DNA, RNA, and protein synthesis4. Intraoperative use of MMC can cause delayed conjunctival healing and serious vision-threatening complications such as scleral necrosis and corneal perforation within 4 weeks4,5.
Preoperative subconjunctival injection of MMC delivers drug directly to subconjunctival fibroblasts responsible for recurrence and also prevents ocular surface toxicity causing less damage to stem cells and less retardation of epithelial healing6.
PATIENTS AND METHODS
This Quasi experimental study was conducted at Eye department of Military Hospital Rawalpindi (now AFIO). The study was carried out from October 2006 to July 2007. It included a total of 70 cases divided into two groups:
Group A (pre-operative MMC) ___ 35 cases
Group B (intra-operative MMC) ___ 35 cases
Ethical committee of the hospital approved the study. All cases of primary pterygium extending for more than 1mm on the cornea were included in the study. Any patient having previous history of conjunctival or squint surgery, ocular cicatricial diseases, keratoconjunctivitis sicca, recurrent corneal conditions like herpetic keratitis or those who were not expected to stay at Rawalpindi for at least one year after surgery were excluded from the study.
The cases were informed in detail about the study and chances of postoperative recurrence and complications due to surgery as well as MMC toxicity. Then informed written consent was obtained.
In cases of group A, 0.1cc of 0.15 mg/ml of MMC was injected sub-conjunctively with an insulin syringe after instillation of topical anaesthesia. These cases were then sent back to report after one month in operation theatre for excision by bare sclera technique under local anesthesia.
In cases of group B, after removing the pterygium by bare sclera technique, a sponge soaked in MMC was applied over the bare sclera and behind the limbus. A single application of 0.1 cc of 0.4 mg/ml (0.04%) of the drug diluted in balanced salt solution was applied for a period of three minutes. The sclera was washed continuously for at least 5 minutes with saline solution to remove excess of MMC solution employed during surgery. The patients were advised to take oral NSAIDs post operatively for 3 days and topical antibiotic-steroid combination for 2 weeks.
Follow up visits to see recurrence and corneoscleral complications were conducted at 2 weeks, 4 weeks, 2 months and 3 months postoperatively. Recurrence and corneoscleral complications were identified and noted down on a follow-up proforma.
Data was analyzed using SPSS 11.0. Descriptive statistics were used to calculate the frequency (percentages) of recurrence and corneoscleral complications in operated cases. Chi-square test was applied to compare the frequency of recurrence and corneoscleral complications between the two groups. Mean and standard deviation for age were calculated.
A total of 70 cases, 35 in each group were analysed statistically. After applying independent sample t test for age distribution in both groups, it was found that mean age in group A was 40.83+-12.655 years while in group B it was 44.57+-13.72 years. Even though average age of group A was less than group B, this difference was found to be insignificant after applying test of significance (P=0.240).
Descriptive statistics were used to calculate gender distribution in each group. Group A had 28 (80%) males and 7 (20%) females. Male to female ratio in this group was 4:1. Group B had 23 (65.7%) males and 12 (34.3%) females. Male to female ratio in this group was 2:1. The total number of males in both the groups was 51 (72.9%) and females were 19 (27.1%). Thus total male to female ratio in both groups was 3:1, males being more than females. Using Chi square test on gender distribution between the two groups the p value was found to be 0.179 which was insignificant.
Number of patients who presented with recurrence in group A was 1 (2.9%) and group B were 4(11.4%) (Table 1).
Table-1 Frequency of recurrence
###GROUP A###GROUP B
In group A no patient presented with corneoscleral complications during the study whereas in group B 7(20%) patients developed complications (Table 2).
Table -2: frequency of corneoscleral complication
###GROUP A###GROUP B
chi square Test for Significant p = 0.011
Out of these 4 patients had thinning of sclera, 2 developed corneal epithelial defects and 1 had dellen. All the patients improved with artificial tear replacement. Chi-square test revealed no significant difference in recurrence (P=0.356) whereas significant difference in corneoscleral complications between the groups (P=0.011) was seen.
Singh et al introduced the use of MMC, as an adjunct to pterygium surgery, to Western ophthalmology in 1988. Although MMC significantly reduced the rate of pterygium recurrence, severe complications such as corneal oedema, corneal perforation, scleral calcification, corectopia, iritis, sudden onset mature cataract, severe secondary glaucoma, incapacitating photophobia, and pain were also reported8. These complications occurred within the first postoperative period and were mostly because of high cumulative doses of MMC or poor selection of patients who either had dry eyes or some immune disorders9.
Our study included patients from different ages and both genders. Patients younger than the age of 15 years rarely acquire pterygium. Although the prevalence of the lesion increases with age, the highest incidence occurs between the ages of 20 and 49 years10. Study of other research papers revealed a mean age varying from 47 to 52 years11,12. It is also suggested that recurrences may be more frequent in young adults than older individuals13. Gender distribution of similar studies was found to have male to female ratio of 2:111,13. It was important to include both the genders because pterygium is more common in males because of their outdoor activities and thus more exposure not only to the ultraviolet light but other irritants a well14,15. A study conducted by Hilgers demonstrated a higher prevalence among men. However, the difference between the sexes was eliminated when only indoor workers were considered which was not possible in our study10.
Regarding pterygium recurrence, it is believed that surgical trauma and subsequent postoperative inflammation activates subconjunctival fibroblastic activity. The proliferation of fibroblasts with deposition of extracellular matrix proteins in turn contributes to the pterygium recurrence16. Injecting MMC in subconjunctival space allows exact titration of MMC delivery to the activated fibroblasts and it minimizes epithelial toxicity. Why leaving MMC subconjunctively for a month before pterygium excision would reduce complications is based on enormous potential of conjunctiva for healing and combating infection because of its high vasularity, presence of numerous inflammatory and immunocompetent cells and immunoglobulins17-19. In bare sclera technique of pterygium excision this conjunctival advantage was lost.
A study was conducted by Dawood et al in Combined Military Hospital Kharian Pakistan on a total of 91 cases with age and gender distribution similar to our study and included armed forces personnel. Same dose of MMC was injected preoperatively and there was only 1 recurrence13. Another such study was carried out by Donnenfeld in 2003. The rate of recurrence in a group of 36 patients was 6% over a mean follow-up time of 24.4 months. The higher recurrence rate in this study may be because of a much longer follow-up period.6 A study conducted on our local population revealed a recurrence of 17% at an average follow-up of 14.3 months. Total number of patients included was 88 with male to female ratio of 4:1. The concentration of MMC used was 0.04% applied for 3 minutes intraoperatively. The dose of drug used and the method adopted was similar to that of our group B. This study had a longer follow-up period and included males more than females which might have contributed to higher rate of recurrence7.
Young applied 0.02% MMC intraoperatively for five minutes and followed up for 1 year. The rate of recurrence was 15.9%20. Another study showed a recurrence of 33.3% in 60 cases having 0.02% MMC being applied for 3 minutes and 2.7% in 74 cases where same preparation was applied for 5 minutes after 12 months of follow-up. The rate increased to 36.6% and 5.4% in both groups respectively after follow-up of another 3 months only (total 15 months)21. Same dosage of MMC with different recurrence rates highlights the importance of other factors like age and ultraviolet exposure.
Various studies prove that very few, if any, complications occurred with intraoperative MMC7,21,22. Treatable delen were noted in 13 out of 371 patients who had pterygium excision followed by topical MMC 0.02% application for 5 minutes in a follow-up period of 26 months23. Frucht-Pery showed that when conjunctival autografting was combined with MMC, 1 out of 120 patients developed minor melting of the flap24. All these studies support the results of my group A which had no complication but our group B showed corneoscleral complications at a higher rate. In our study, 7 patients developed complications. Out of these 6 had an average age of 62.67 years. This advanced age may have been responsible for the increased number of complications. There are multiple reports where patients with advanced age developed sclera melting and other corneoscleral complications with intraoperative use of MMC4,25.
Moreover, most of the patients with complications belonged to lower socioeconomic class where malnourishment, illiteracy and poor hygiene are prevalent. Fortunately all these patients improved with conservative treatment without any need of surgical intervention.
Our study proves that preoperative MMC is as effective as intraoperative MMC in preventing recurrence but it is much safer than intraoperative MMC causing less corneoscleral complications. This technique can be used with more confidence in high risk patients specially those with advanced ages or who have predisposing conditions and still need excision due to high astigmatism or visual deterioration.
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20.Young AL, Leung GYS, Wong AKK, Cheng LL. A randomised trial comparing 0.02% Mitomycin C and limbal conjunctival autograft after excision of primary pterygium. Br J Ophthalmol 2004; 88: 995-7.
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|Publication:||Pakistan Armed Forces Medical Journal|
|Article Type:||Clinical report|
|Date:||Sep 30, 2011|
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