|Year : 2019 | Volume
| Issue : 4 | Page : 279-284
Preoperative subconjunctival injection of mitomycin C versus conjunctival autografting with fibrin glue fixation in the management of primary pterygium
Asma Ayub Ansari1, Veerendra Bhimashankar Atnoor2, Kailas Chavan3, Ahmed Hussain Syed4
1 Department of Ophthalmology, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Kancheepuram, Tamil Nadu, India
2 Department of Ophthalmology, Dr. VM Government Medical College, Solapur, Maharashtra, India
3 Department of Ophthalmology, Swami Netralaya, Aurangabad, Maharashtra, India
4 Department of Pathology, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Kancheepuram, Tamil Nadu, India
|Date of Submission||29-Sep-2019|
|Date of Decision||24-Oct-2019|
|Date of Acceptance||28-Oct-2019|
|Date of Web Publication||26-Dec-2019|
Dr. Asma Ayub Ansari
Department of Ophthalmology, Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Ammapettai Village, Thiruporur - Nellikuppam Road, Kancheepuram - 603 108, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aims: To measure the outcome of preoperative subconjunctival mitomycin C 1 month before bare sclera and conjunctival autografting using fibrin glue in terms of recurrence rate and complications. Settings and Design: This was a prospective, randomized, interventional, hospital-based comparative study. Materials and Methods: Sixty eyes of 58 consecutive patients with primary, progressive pterygium were randomly allocated into two equal Groups (A and B) of 30 each. In Group A, subconjunctival injection of mitomycin C (MMC) (0.1 ml of 0.1 mg/ml) 1 month before bare sclera technique and in Group B pterygium excision with conjunctival autografting using fibrin glue were performed. The study period was from December 2010 to October 2012, and patients were followed up for 18 months. The outcome measures were significant corneoscleral complications and recurrence. Results: The mean age of patients in the study was 38.6 ± 12.6 years with females slightly outnumbering males. Majority (58.6%) of patients were pursuing outdoor occupations. The mean follow-up period of MMC group was 10.2 ± 4.49 months, whereas that of conjunctival autograft with glue group was 10.8 ± 3.66 months. The average surgery time was more for conjunctival autografting with fibrin glue than subconjunctival mitomycin before bare sclera. One (3.33%) patient in the MMC group and 2 (6.67%) patients in the fibrin glue group had recurrence within the study period. Both the surgical techniques were not found to be associated with any serious vision-threatening complications. Conclusions: Subconjunctival MMC 1 month before bare sclera is simple, safe, economical, less time-consuming, technically less demanding, and as effective as conjunctival autografting with fibrin glue fixation.
Keywords: Bare sclera, conjunctival autograft, fibrin glue, mitomycin C, pterygium
|How to cite this article:|
Ansari AA, Atnoor VB, Chavan K, Syed AH. Preoperative subconjunctival injection of mitomycin C versus conjunctival autografting with fibrin glue fixation in the management of primary pterygium. TNOA J Ophthalmic Sci Res 2019;57:279-84
|How to cite this URL:|
Ansari AA, Atnoor VB, Chavan K, Syed AH. Preoperative subconjunctival injection of mitomycin C versus conjunctival autografting with fibrin glue fixation in the management of primary pterygium. TNOA J Ophthalmic Sci Res [serial online] 2019 [cited 2020 Jul 15];57:279-84. Available from: http://www.tnoajosr.com/text.asp?2019/57/4/279/273987
| Introduction|| |
Pterygium is a subconjunctival elastotic degenerative fibrovascular tissue proliferation which invades from the limbus onto the cornea. It is commonly seen in dry, hot climate and ultraviolet radiation exposure., Surgical intervention is indicated if there is chronic irritation, recurrent inflammation, obstruction of visual axis, induced astigmatism, motility restriction, and cosmetic blemish. Due to a very high recurrence rate (30%–70%) after simple excision, adjunctive treatments, including radiation, antimetabolites, conjunctival grafts, and limbal grafts, are used to decrease the rate of recurrence after surgical excision., The best available option to prevent recurrence after pterygium excision is conjunctival autografting, wherein the graft can be fixed with the help of sutures, fibrin glue, and autologous blood.
Adjunctive mitomycin C (MMC) in pterygium surgery was first described in Japan by Kunitomo and Mori in 1963. Since then, several modalities of usage have been described including preoperative injection and intraoperative application. Long-term use of topical MMC eye drops after pterygium surgery can cause serious complications such as secondary glaucoma, corneal edema, scleral necrosis, and sudden-onset mature cataract. Hence, MMC use has been limited to use as a single intraoperative application with high success rates and fewer complications. Subconjunctival injection of MMC can be used as adjunctive therapy before pterygium excision as it allows exact titration of MMC delivery to the activated fibroblasts and minimizes epithelial toxicity. Donnenfeld et al. reported a success rate of 94% with subconjunctival injection of MMC, 1 month before pterygium excision with the bare sclera technique.
The purpose of the study was to find out whether (1) a simpler technique such as subconjunctival MMC before pterygium excision by bare sclera technique gives results comparable to conjunctival autograft in terms of recurrence and other complications and (2) subconjunctival MMC with pterygium excision by bare sclera technique is associated with complications such as ocular surface toxicity seen with intraoperative application of MMC.
| Materials and Methods|| |
A prospective, randomized, interventional, hospital-based, comparative study was carried out from December 2010 to October 2012. The surgeries were performed from December 2010 to February 2012. Patients were followed up from 6 to 18 months. Sixty eyes of 58 consecutive patients who presented to our hospital with primary, progressive pterygium with age <50 years were included in the study. Of these, 12 patients had bilateral pterygia, 2 of them were willing to get both their eyes operated, so one eye was allotted to Group A and the other was allotted to Group B. In the remaining ten patients, only one eye was included in the study. Approval for conducting the study was obtained from the institutional ethics committee, and written informed consent was obtained from all the included patients. A detailed preoperative comprehensive ophthalmic examination was carried out for each patient.
All patients <50 years of age having primary progressive pterygium, who signed consent form, were included in the study.
Patients having atrophic pterygium; recurrent pterygium; dry eye syndrome; collagen vascular disease; coexistent conjunctival diseases such as previous alkali burns and Mooren's ulcer which predispose to pseudopterygium; history of uveitis, scleritis, and glaucoma; and follow-up <6 months were excluded from the study.
Recurrence was defined as fibrovascular re-encroachment extending beyond the surgical limbus.
The patients were randomized into two Groups (Group A and B) based on computer-generated random number table.
Group A: Subconjunctival injection of MMC (0.1 ml of 0.1 mg/ml) 1 month before bare sclera technique.
Group B: Pterygium excision with conjunctival autografting using fibrin glue. Here, groups of 5–6 patients were made and each group was operated with fibrin glue on single day to reduce the cost. A clinical photograph of every patient was taken pre- and postoperatively on each follow-up visit.
With a 30-G needle on a tuberculin syringe, 0.1 ml of 0.1 mg/ml of MMC was injected into the body of pterygium after instilling a drop of 0.5% proparacaine under aseptic condition approximately 1.5 mm away from the limbus under an operating microscope. A cotton bud was kept for few seconds on injection site to prevent egress of MMC. After injection, the conjunctival sac was irrigated with saline to wash out excess MMC and the patient received one drop of ofloxacin 0.3%, which was continued four times daily for 4 days. Patients were seen 1 day, 1 week, and 1 month after the subconjunctival injection of MMC. A complete slit-lamp examination including fluorescein staining was done on every follow-up.
One month after MMC injection, the patients underwent bare sclera excision of the pterygium. Eye was prepared and draped in usual sterile fashion. All patients were operated under peribulbar block using 5cc of 2% Xylocaine +1:200,000 adrenaline. Eye speculum was applied. The neck of pterygium was grasped with Saint Martin's forceps and its head was dissected off cornea by conjunctival scissors and blunt dissection using a cotton bud. Scleral portion of pterygium was then excised using scissors. A thorough removal of subconjunctival fibrous tissue was then performed. The scleral bed and the cornea were then polished with a No. 15 surgical blade. Antibiotic steroid ointment (polymyxin B sulfate 10,000 units + chloramphenicol 10 mg + dexamethasone sodium phosphate 1 mg/g of ointment) was instilled, and a sterile eye pad was applied. Duration of surgery was noted from the insertion of speculum to its removal at the end of surgery.
In Group B, initial steps up to polishing scleral bed and cornea are similar to bare sclera excision. The vertical and horizontal extents of the bare sclera were measured using a Castroviejo's measuring caliper. A free conjunctival limbal graft of the same size was harvested from superotemporal conjunctiva. In cases where there was poor exposure of donor site, a superior rectus bridle suture was taken to rotate and fix eye in downgaze and hence improve exposure. The dissection was started at forniceal end and brought toward limbus. Care was taken to avoid buttonholing of graft and minimal involvement of underlying Tenon's capsule was ensured. Once the dissection reached the limbus, the graft was flipped onto the cornea. Tenon's attachment at the cornea was meticulously dissected. The graft was then cut at limbus and slid over onto the cornea. It was flipped over again over the cornea, so that its Tenon's surface faces the cornea. Fibrin glue (Reliseal) was reconstituted according to the manufacturer's instructions. Using a Duploject, fibrin glue was applied over the bare sclera and the conjunctival autograft was immediately flipped over the conjunctival defect. Proper care was taken to ensure that the spatial orientation was maintained and that the sides of the graft were opposed to the edges of recipient conjunctiva. After drying period of 3 min, the lid speculum was removed. Antibiotic–steroid eye drops (ofloxacin + dexamethasone) were put, and a sterile eye pad was applied. Duration of surgery was noted from the insertion of speculum to its removal at the end of surgery.
The eye pad was removed after 6 h followed by topical instillation of ofloxacin (0.3%) and dexamethasone (0.1%) eye drops 4 times a day for 15 days. Tablet ibuprofen (400 mg) and tablet ranitidine (150 mg) BID were administered for 5 days.
All patients (both Group A and B) were followed up at 1 week, 1 month, 3 months, 6 months, 12 months, and 18 months postoperatively. The major outcome measures were recurrence rate and complications if any.
Statistical analysis was performed using Statistical Package for the Social Sciences version 20.0 for Windows. Mean ± standard deviation was used for description of age, and frequencies and percentages were calculated for gender. The recurrence of pterygium was described as frequency and percentage. The ages of patients, surgical time, and follow-up in Group A and Group B were compared using independent sample t-test. Simple Z-test was used to compare the recurrence and complications between Group A and Group B. P < 0.05 was considered statistically significant.
| Results|| |
Nine (15.51%) patients were in the age group of 21–30 years, 22 (37.93%) patients were in the age group of 31–40 years, and 27 (46.55%) patients were in the age group of 41–50 years. The average age of the patients in the study was 38.6 ± 12.8 years. Out of 58 patients in the study, 26 (44.83%) were male and 32 (55.17%) were female. Out of 58 patients, 24 (41.38%) were pursuing indoor occupations and 34 (58.62%) were pursuing outdoor occupations. Out of 58 patients, 33 (56.90%) were residing in rural areas and 25 (43.10%) were residing in urban areas. Out of 58 patients, 25 (43.10%) patients had pterygium only in their right eyes, 21 (36.21%) had pterygium only in their left eyes, and 12 (20.69%) patients had bilateral pterygia, i.e., pterygium in both right and left eyes. Out of 60 eyes of 58 patients, 55 (91.67%) were nasal pterygia [Figure 1]; 3 (5%) were temporal pterygia and 2 (3.33%) were double pterygia, i.e., pterygium with both nasal and temporal heads [Figure 2]. The average surgical time for bare sclera with preoperative subconjunctival MMC was 16.73 ± 1.64 min, which includes duration both for subconjunctival injection of MMC and for bare sclera technique. The average surgical time for Group B, i.e., conjunctival autografting using fibrin glue, was 22.87 ± 1.46 min. The average duration of surgery was significantly more for conjunctival autografting using fibrin glue (t-test = 15.05, P < 0.001) [Figure 3] and [Figure 4]. The mean follow-up period of Group A was 10.2 ± 4.49 months and that of Group B was 10.8 ± 3.66 months. There was no statistically significant difference between follow-up period of two groups (t-test = 0.55, P > 0.05). In Group A, there was 1 (3.3%) recurrence over the mean follow-up period of 10.2 ± 4.49 months, and in Group B, there were 2 (6.7%) recurrences over the mean follow-up period of 10.8 ± 3.66 months. Statistically there is no significant difference between recurrence rates by above two surgical techniques (Z-test = 0.59, P > 0.05). All 60 eyes had conjunctival congestion postoperatively. Subconjunctival hemorrhage was seen in four eyes of Group A and one eye of Group B. Conjunctival granuloma was seen in two eyes of Group A and one eye of Group B. In Group A, two eyes had graft edema and another two eyes had graft hemorrhage on the 1st postoperative day. One eye in Group B had graft loss on the 1st postoperative day. Statistically there is no significant difference in complications occurred between the two groups (P > 0.05) [Table 1] and [Table 2].
| Discussion|| |
The primary concern in pterygium surgery is recurrence. It is believed that surgical trauma and subsequent postoperative inflammation activates subconjunctival fibroblast and the proliferation of fibroblast with a deposition of extracellular matrix protein in turn contributes to pterygium recurrence. The mechanism by which conjunctival autografting reduces recurrence rates are– presence of limbal stem cells which helps to restore the limbal barrier in case of conjunctivo-limbal autografting additionally contact inhibition effect on residual abnormal tissue by conjunctival autograft., However, conjunctival autografting has its drawbacks and limitations, in that it may adversely affect outcome of future glaucoma filtration surgeries if needed and it is of limited use in cases with large double-headed pterygia and scarred conjunctiva as enough donor conjunctival tissue might not be available. The use of fibrin bioadhesive in conjunctivolimbal autograft surgery in primary pterygium simplifies surgical techniques, shortens surgical duration, and produces less postoperative patient discomfort. However, major concern regarding the use of fibrin glue is its cost. The average operation cost decreases with increasing number of patients scheduled for surgery. However, in practice, to operate pterygium patients on the same day in order to reach certain patient number may increase patient's waiting time for the operation. Thus, it is not always possible to reach a desirable patient number to reduce the cost. And also, the concerns regarding donor-site limitations remain unaddressed. Recently, adjunctive MMC has become a more commonly used technique in preventing pterygium recurrence. MMC is an effective intraoperative treatment for preventing recurrence of pterygium. The effect of drug depends on dose and length of application. However, intraoperative use of MMC is sometimes associated with vision-threatening complications such as glaucoma, corneal edema, corneal perforation, scleral melting, and cataract formation. Chen et al. showed that a concentration of 0.1 mg/ml inhibits fibroblast replication and that concentrations of >0.3 mg/ml actually cause death of fibroblast. Hence, we chose concentration of 0.1 mg/ml, which is well below the toxic level associated with cell death. To avoid potential side effects of MMC, minimal concentration of MMC was used in the present study. Subconjunctival route allows exact dose delivery (0.1 ml of 0.1 mg/ml of MMC) rather than the inexact and substantially higher dosing with sponge delivery during intraoperative application. Eyes became less inflamed and quiescent at1 month and there was less bleeding than is normally associated with pterygium excision.
As recurrence of pterygium is common in younger patients, we included patients <50 years of age in our study. In the present study, the youngest patient was 23 years old and the oldest was 48 years old. The average age of the study patient was 38.6 ± 12.8 years. The mean age of Group A patients was 38.57 ± 12.6 years and that of Group B was 38.53 ± 13.14 years. Gazzard et al. in their study found that the prevalence rates of pterygium in subjects over 51 years were 6 times that of 21–30 years old. Luanratanakorn et al. in their study found 56 (33.5%) males and 111 (66.5%) females. Kim et al. found 13 (38.2%) males and 21 (61.8%) females. In the Meiktila Eye Study by Durkin et al., out of 2076 participants, 836 (40.27%) were male and 1240 (59.73%) were female and stated that the more number of females is due to the fact that the Meiktila Eye Study was a population-based, cross-sectional ophthalmic survey of the inhabitants of rural villages where both men and women are involved in outdoor activities, particularly in farming districts such as Meiktila. This holds true in the present study also wherein 60% of patients were living in rural areas, where both males and females do outdoor work in the form of farming. In the present study, 33 (56.9%) patients were residing in rural areas and the remaining 25 (43.10%) patients were from urban area. Singh et al. conducted a study in five randomly selected villages in Wardha district of Maharashtra state and found high prevalence of pinguecula and pterygium. McCarty et al. in their study in Victoria found that the rates of pterygium in rural residents were more than five times as high as in urban residents and concluded that pterygium is a significant public health problem in rural areas, primarily as a result of ocular sun exposure. The average surgical time for bare sclera with preoperative subconjunctival MMC was 16.73 ± 1.64 min, which includes duration both for subconjunctival injection of MMC and for bare sclera technique. The average surgical time for Group B, i.e., conjunctival autografting using fibrin glue, was 22.87 ± 1.46 min, which includes duration both for reconstitution of fibrin glue and for surgery. Surgical time for conjunctival autografting using fibrin glue was significantly more than that of bare sclera with preoperative subconjunctival MMC. However, preoperative subconjunctival MMC before bare sclera excision of pterygium is a two-stage procedure. To obviate this problem, Zaky and Khalifa suggested giving subconjunctival MMC 1 day before bare sclera excision of pterygium, and the results were comparable to that of subconjunctival MMC 1 month before bare sclera excision of pterygium.
In our study, recurrence rate was 3.3% in the Group A at the end of mean follow-up of 10.2 ± 4.49 months. Low recurrence rates in the present study compared to Donnenfeld et al. and others may be due to relatively shorter follow-up period.
In our study, recurrence rate in the Group B was 6.7% at the end of mean follow-up of 10.8 ± 3.66 months. Recurrence rate after conjunctival autografting with fibrin glue in various studies ranges from 4% to 12%. Recurrence rate in the present study is comparable with those found in literature. In GroupA, recurrence appeared 6 months postoperatively, whereas in Group B, recurrence appeared at 6 months in one patient and at 12month followup in another.
All patients had conjunctival congestion postoperatively due to surgical trauma, which decreased with topical antibiotic–steroid eye drops. Four patients in Group A had subconjunctival hemorrhage after the injection of MMC, which cleared in a week. No patients had any sign of conjunctival or corneal staining on any visit after subconjunctival injection of MMC. Two patients had conjunctival granuloma at 1 week and 1 month postoperatively after bare sclera technique, which resolved completely with topical steroid eye drops till the next follow-up. None of the patients had any serious vision-threatening complications within the study period such as glaucoma, corneal edema, corneal perforation, scleral melting, and cataract which are associated with intraoperative application of MMC.
In Group B, i.e., conjunctival autografting using fibrin glue, two patients had graft edema and another two patients had hemorrhage under the graft on the 1st postoperative day which cleared with topical antibiotic–steroid eye drops till the 1st week of follow-up. One patient had donor-site granuloma on the 1st week postoperatively, which resolved with topical steroid and lubricating eye drops on 1-month follow-up. One patient had graft loss on the 1st postoperative day that was followed up without any intervention and had no recurrence within the study period.
| Conclusions|| |
In our study, recurrence rate with subconjunctival MMC before bare sclera excision of pterygium was 3.33% and it is comparable to recurrence rate by other standard techniques such as conjunctival autograft using suture or fibrin glue (6.67%).
Subconjunctival MMC 1 month before bare sclera is simple, safe, economical, less time-consuming, technically less demanding, and as effective as conjunctival autografting. It has a definite role in patients with recurrent pterygium, large double-headed pterygia, patients with glaucoma who may require filtration surgery in future and combined pterygium with cataract patients. In conclusion, subconjunctival MMC 1 month before bare sclera has a potential to replace other methods of management of pterygium because of its simplicity, low recurrence rate, and less complications. However, a longer follow-up period and a larger sample size are needed to further establish the safety and efficacy of preoperative MMC in pterygium surgery.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]