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ORIGINAL ARTICLE
Year : 2003  |  Volume : 51  |  Issue : 1  |  Page : 59-65
 

Comparison of single-drop mitomycin C regime with other mitomycin C regimes in pterygium surgery.


Department of Ophthalmology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India

Correspondence Address:
Ved P Gupta
Department of Ophthalmology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi
India
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PMID: 12701864

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   Abstract 

Purpose: To evaluate the safety and efficacy of single-drop instillation of mitomycin C (MMC) in pterygium surgery and to compare the results with both postoperative and intraoperative application of MMC. Methods: Eighty eyes of 72 patients with pterygium were randomised into 4 equal groups: group 1 - control - bare scleral excision (BSE); group 2 - BSE with single-drop instillation of mitomycin C (MMC) 0.02% at the end of the surgery; group 3 - BSE with postoperative MMC 0.02% drops twice a day for 5 days; and group 4 - BSE with intraoperative MMC 0.02%. Results: The recurrence of pterygium was observed in 14 (70%), 4 (20%), 4 (20%) and 3 (15%) eyes of group 1, 2, 3, and 4 respectively. The recurrence rate after BSE with single drop MMC regime (group 2) was significantly lower than group 1 recurrence ( P = 0.001) and was statistically comparable to that of group 3 and 4. Scleral defects in the bare area occurred in 4 (20%), 16 (80%) and 16 (80%) eyes of group 2, 3, and 4 respectively. The incidence of scleral defects was significantly lower in group 2 compared to group 3 (P=0.0001) and group 4 (P=0.0001). Compared to group 1 and 2, a significant delay in wound epithelialisation occurred in group 3 ( P=0.003) and 4 ( P=0.004). An ischaemic area in the bare sclera developed in 8 (40%) and 6 (30%) eyes of group 3 and 4 respectively, while ischaemic area did not develop in group 1 and 2. Conclusion: Single-drop instillation of 0.02% mitomycin C following pterygium excision appears both safe and efficacious.


Keywords: Mitomycin C, single drop, pterygium surgery, recurrence, scleral complications


How to cite this article:
Gupta VP, Saxena T. Comparison of single-drop mitomycin C regime with other mitomycin C regimes in pterygium surgery. Indian J Ophthalmol 2003;51:59-65

How to cite this URL:
Gupta VP, Saxena T. Comparison of single-drop mitomycin C regime with other mitomycin C regimes in pterygium surgery. Indian J Ophthalmol [serial online] 2003 [cited 2014 Aug 21];51:59-65. Available from: http://www.ijo.in/text.asp?2003/51/1/59/14736


Pterygium is a common ocular surface disorder of the subconjunctival tissues characterised by fibrovascular growth encroaching upon the cornea. Pterygium creates many problems for the patient including symptoms of irritation, foreign body sensation and lacrimation, cosmetic disfigurement, and functional problems such as reduced visual acuity, diplopia and problems fitting contact lenses. It occurs worldwide, with a higher incidence in tropical and subtropical countries including India. A variety of surgical procedures have been described but the recurrence of pterygium still remains the major complication. Recurrence rates vary from procedure to procedure. Simple excision and excision with bare sclera technique (D'Ombrain's[1]) carry a high recurrence rate of 30% - 100% and 5%[2] - 89%[3] respectively. Even conjunctival autografting to cover the bare sclera is associated with recurrence rates of 2%[4] - 39%.[5] Therefore, various adjuvant therapies have been used to prevent recurrence of pterygium after excision, e.g., irradiation, argon and excimer laser, thiotepa and mitomycin C (MMC) application. Various studies have reported the efficacy of mm0 C in reducing the recurrence rate following pterygium surgery.[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] It has been used in concentrations of 0.02% - 0.1% both postoperatively[6],[7],[8],[9],[10],[11],[12],[13] and intraoperatively.[14],[15],[16],[17] Although the recurrence rate has been reduced after use of MMC, there are reports of serious vision-threatening complications following MMC application.[18],[19],[20] Rubinfeld et al[19] reported severe complications such as scleral thinning, corneal oedema, secondary glaucoma, corneal perforation, iritis and cataract formation after postoperative instillation of 0.04% MMC and urged extreme caution while using this agent for prevention of pterygium recurrence. In view of the severe complications following use of MMC and the high recurrence rate of 38%[5] there is a need to explore a new regime of MMC which could reduce the recurrence rate without causing serious complications. We explored the use of 0.02% MMC as a single-drop instillation at the end of bare scleral pterygium surgery in this study. The objective of the study was to evaluate the safety and efficacy of single-drop instillation of mitomycin C at the end of the surgery, and to compare this with other recommended MMC regimes such as postoperative and intraoperative applications.


   Materials and Methods Top


This prospective randomised controlled study was conducted at the Department of Ophthalmology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India. Eighty eyes with primary and recurrent pterygia were enrolled between March 1996 and December 1998. Age-and recurrence-matched randomisation of primary and recurrent pterygia was performed in such a way that the primary and recurrent pterygia of identical age groups were equally distributed in the following four groups:

Group 1: Control group (n=20) - Excision of pterygium by the bare sclera technique (BSE).

Group 2 (n=20): BSE + single drop of 0.02% MMC, instilled at the end of the surgery.

Group 3 (n=20): BSE + postoperative instillation of 0.02% MMC eye drops, twice daily for five days.

Group 4 (n=20): BSE + a single intraoperative sponge application of 0.02% MMC to the exposed sclera, cornea and the resected pterygium site.

Patients below 50 years of age, with unilateral or bilateral progressive nasal pterygium were included in the study. The exclusion criteria included history of ocular disease predisposing to ulceration or poor wound healing such as Sjogren's syndrome, rheumatoid arthritis, dry eye, acne rosacea or herpetic keratitis. Patients above 50 years were not included.

Written informed consent was obtained from each patient. A complete ocular examination, including slitlamp biomicroscopy and cycloplegic refraction and photographic documentation of the pterygia was performed for each patient before surgery.

All surgeries were performed on an outpatient basis by the same surgeon using the same technique. No pre-medication was given to any patient. All eyes were locally anaesthetised using 2% xylocaine drops topically, and facial and retrobulbar blocks. The surgical technique was as follows:

After cleaning and draping the eye, the eyelids were retracted by a self-retaining eyelid retractor. Stay sutures were passed at 6 and 12 o'clock limbus, using 6-0 black silk, the eye was rotated in the opposite direction and the apex of the pterygium was dissected from the cornea using a No.11 surgical blade on Bard Parker handle and Tooke's knife. The pterygium tissue was dissected from the overlying conjunctiva, 4-5mm of conjunctiva was also excised. No cautery was applied on the sclera and episcleral or scleral dissection was not undertaken during surgery. The conjunctiva was fixed to the episcleral tissue by passing three sutures with 7-0 polygalactin, leaving behind a bare sclera (5mm x 8mm).

MMC was freshly prepared on the day of the surgery under sterile conditions from the commercially available 2 mg vial by mixing it with 10 ml sterile distilled water. In group 2 patients one drop of pre-prepared 0.02% MMC was instilled at the bare sclera at the end of the surgery. In group 3 patients, instillation of one drop of 0.02% MMC twice a day for five days was started from the first postoperative day. In group 4 patients, after excision of the pterygium tissue, a sterile sponge (5x5mm) soaked in 8-10 drops of 0.02% mitomycin C eye drops was applied over the exposed corneosclera and resected pterygium site for 5 minutes. The conjunctiva and the Tenon's capsule were pulled over the sponge. The sponge was removed after 5 minutes and the eye was irrigated with 20 ml of normal saline. At the end of the surgery, eyes of all patients were patched after applying ciprofloxacin 0.3% eye ointment.

Postoperatively all the patients were prescribed oral Ibuprofen 400 mg twice a day, Vitamin C and B-Complex, for five days. All the patients were asked to return on the first postoperative day and the eye dressings were opened; thereafter Neomycin 0.5% and Dexamethasone 0.1% eye drops were instilled four times a day for six weeks. All patients were followed up on day 1, 7, 15 and 30 and thereafter biweekly for 3 months. All patients were followed up for a minimum period of 3 months. Patients who did not develop a recurrence during this period were further followed up every 3-6 months. The follow-up period ranged from 3 months to 4 years. All the patients were evaluated postoperatively for ocular pain, foreign body sensation, photophobia, lacrimation, condition of eyelid and cilia, cosmetic blemishes, conjunctiva, sclera, cornea, anterior chamber reaction, granuloma, ocular movements, visual acuity, intraocular tension and recurrence. Recurrence was defined as the postoperative growth of fibrovascular tissue of more than 1 mm on to the cornea at any time during the study. All recurrences were evaluated by one of the authors (TS) at each follow-up visit and subsequently confirmed by chief investigator (VPG). Slitlamp examination after fluorescein staining was done in all the patients to specially look for superficial punctate keratopathy and scleral defects. Scleral thinning was defined as change in colour of sclera/visibility of uveal pigment and depression in the slitlamp beam focussed on the involved bare scleral surface. Scleral ulceration was defined as discontinuity of scleral surface having steep edges, positive fluorescein staining and irregularity and depression in the slitlamp beam. The scleral ulcer with white/grayish-white base was termed as shallow and with blue/bluish black base as deep ulcer.

Statistical analysis was done using the Chi-square test, Fisher exact test, Student's t-test and one-way analysis of variance (Tukey test at 5%).


   Results Top


This study included 80 eyes with pterygia in 72 patients. The age of the patients ranged from 16 to 50 years, (mean 33.09 + 7.82 years). There was no statistical difference in the mean age between the groups (P=0.81). 66.25% patients of this study were below 35 years. Out of eighty eyes, there were 68 primary and 12 recurrent, and 64 unilateral and 8 bilateral pterygia. The follow-up period ranged from 3 months to 4 years (mean 8.7 months). Demographical and surgical data of the patients are given in [Table - 1].

Scleral thinning in the bare area of the sclera was observed in 4 (20%), 16 (80%) and 16 (80%) eyes of groups 2, 3, and 4 respectively, while patients of group 1 had no evidence of scleral thinning. Scleral ulceration of various sizes and shapes was the cause of scleral thinning in the three study groups. The difference was statistically significant when groups 3 and 4 were compared with group 1 (P<0.001). However, there was no statistical significance when group 2 was compared with group 1 (P= 0.05) The difference of group 2 compared with group 3 (P=0.0001) and with group 4 (P=0.0001) was also significant. The difference between group 3 and 4 (P=0.65) was not significant. Four of 20 eyes of group 2 developed shallow scleral ulceration. Sixteen of 20 eyes of group 3 and group 4 each developed scleral ulceration within first two postoperative weeks. In some of the patients scleral defect was preceded by intense ischaemia of the bare scleral area [Figure - 1][Figure - 2][Figure - 3]. The ischaemic area in the bare sclera developed in 8 (40%) and 6 (30%) eyes of group 3 and 4 respectively (P=0.003 and P=0.02 respectively), while no such complication occurred in groups 1 and 2. Shallow scleral ulcers were observed in 13 (81.25%) eyes of group 3 and 4. The shallow ulcers healed without any sequelae, within one week of starting the therapy consisting of frequent local application of Ciprofloxacin 0.3% eye drops and lubricating eye drops and Ciprofloxacin 0.3% eye ointment at night. Three of 16 eyes of group 3 and 4 each developed deep scleral ulcers [Figure - 1][Figure - 3]. This required intensive therapy that included withdrawal of corticosteriods eye drops, daily pad and bandage with Ciprofloxacin 0.3% eye ointment, Atropine 1% eye ointment and oral Norfloxacin (400 mg, twice a day, for seven days), Acetazolamide and Vitamin C. Swab and scrapings from the base of the scleral ulcer did not reveal any microorganisms. In three patients each of group 3 and 4, with scleral defects, we observed that the bluish discoloration of the bare sclera increased markedly on removing the pad and bandage for about 30 minutes - 1 hr. Interestingly, in all these cases this scleral discoloration used to disappear after bandaging the eye. The details of scleral thinning in groups 2, 3 and 4 are shown on [Table - 2].

Brownish pigmentation was noticed in the bare area of the sclera of 1 (5%) and 4 (20%) eyes of group 3 and 4 respectively. We observed that patients who had deeper scleral defects in the postoperative period also developed brownish pigmentation in the bare area of the sclera after the defect healed. Postoperative ocular pain was encountered in 10 (50%), 15 (75%) and 15 (75%) patients in the three study groups and 4 (20%) patients in the control group. As compared to group 1, ocular pain was significantly greater in group 2 (P=0.04), group 3 (P=0.0004) and group 4 (P=0.0004) respectively, but the difference was not statistically significant between the three study groups. Foreign body sensation, photophobia and lacrimation were encountered in many patients of the three study groups and the control group. Delayed epithelialisation for 3-4 weeks was noted in group 3 and 4 patients, while in group 1 and 2 epithelialization of the bare sclera occurred within 2 weeks of surgery. As compared to the control group and group 2 there was a significant delay in epithelialisation of the wound in group 3 and 4 (P=0.003 and P=0.004 respectively). A granuloma which appeared at the site of the suture knot and was associated with surrounding congestion, was observed in 3 (15%) and 4 (20%) eyes of groups 3 and 4 respectively. None of the patients developed poliosis, vitiligo, madarosis, depigmentation of the eyelid, conjunctival defects, ulcer, symblepharon and degenerative calcification, uveitis or cataract. A comparative evaluation of postoperative side effects and complications is shown in [Table - 3].

Recurrence of the pterygia was another major postoperative complication noted in our study. It occurred in 14 (70%), 4 (20%), 4 (20%) and 3 (15%) eyes of group 1, 2, 3, and 4 respectively. In group 2, of 4 patients who developed recurrence, 3 had primary pterygia and one had recurrent pterygium. In group 3 and 4 all the recurrences occurred in patients with primary pterygia. All the recurrences in group 2, 3, and 4 were seen in patients below 35 years of age. In the control group 13 of 14 recurrences occurred in patients below 35 years of age, and only one recurrence occurred in a 41-year-old patient. The mean age of all patients with recurrence (29.08 years) was significantly lower than that of the patients without recurrence (35.18 years) (P=0.001). Compared with the control group, incidence of recurrence of pterygium was significantly lower in group 2 (P=0.001), 3 (P=0.001), and 4 (P=0.0004), but this difference was not significant between the three study groups.


   Discussion Top


Bare scleral excision of pterygium is mostly accompanied by unacceptably high recurrence.[3],[5] Mitomycin C is commonly recommended to reduce recurrence. Mitomycin C is an antineoplastic antibiotic with radiomimetic properties, that selectively inhibit DNA, RNA and protein synthesis.[21],[22],[23] Since its introduction by Kunitomo and Mori[24] in 1963, it has been used postoperatively[6],[7],[8],[9],[10],[11],[12],[13] and intraoperatively[14],[15],[16],[17] in different concentrations. Postoperative application of topical MMC in a dose of 1mg/ml four times a day for two weeks to 0.1 mg/ml twice a day for five days decreased the recurrence rates to 0%-11%.[6],[7],[8],[9],[10],[11],[12],[13] Prospective studies have also reported that single intraoperative scleral application of 0.1mg/ml to 0.2mg/ml MMC for 3-5 minutes reduces the recurrence rates to 3.3%-12%.[14],[15],[16],[17]

In the present study, the recurrence rates in the three MMC-treated groups 2, 3, and 4 were 20%, 20% and 15% respectively while a significantly higher recurrence rate of pterygium (70%) occurred in the control group during the mean follow-up period of 8.7 months. Although the intra-operative sponge application of MMC (group 4) caused minimum recurrence, no statistically significant difference in recurrence was observed among the three MMC-treated groups. The high recurrence in groups 3 and 4 in this study compared with the reports in the literature[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] may be due to the following reasons: (1). Our study comprised young patients (mean age 33.09 years) and 66.25 % patients were < 35 years of age. All the recurrences in the study groups occurred in patients < 35 years. (2) Our study was conducted in an area with high prevalence of pterygia because of the dry, dusty and smoky environment. (3) Following the pterygium surgery our patients were again exposed to the same environmental irritants that might have initiated pterygium development. In one randomised trial the recurrence rate after postoperative MMC (0.2 mg/ml twice daily for five days) after BSE for primary pterygium in a predominantly southern California population with mean age of 43 years was 38%.[5]

Postoperative and intraoperative application of MMC has been associated with various postoperative complications.[18],[19],[20],[25],[26],[27] Minor complications like ocular pain, photophobia, lacrimation and foreign body sensation are common in MMC-treated patients, [6],[9],[12],[14],[15] but serious complications are rare.[11],[12] There are reports of serious ocular complications following postoperative use of 0.2 mg/ml - 0.4 mg/ml MMC drops 3 - 4 times daily for 1 - 3 weeks.[7],[18],[19],[20],[25][26],[27] They include scleral ulceration and calcification, necrotizing scleritis, perforation, uveitis, cataract, infection, glaucoma, symblepharon and corneoscleral, ciliary body and vitreoretinal toxicity. While there were reports of no scleral complications with postoperative 0.2 mg/ml MMC drops twice a day for five days as well as with 0.4 mg/ml MMC 4 times daily for two weeks,[5],[9],[10],[11],[12] complications have been reported even with a low dosage of MMC.[7] In contrast, serious complications are not reported following intraoperative application of MMC.[14],[15],[16],[17]

Avascularised sclera has been reported as the most common ocular complication following BSE with postoperative MMC 0.02%.[13] Canopara et al [16] observed characteristic avascular sclera in all eyes following intra-operative MMC 0.01% for 5 minutes. But none of these eyes developed any scleral thinning, ulceration, or necrosis.[16] Delayed epithelialisation of conjunctival wound for 1-5 weeks has also been described after postoperative and intraoperative MMC.[10],[14],[16].

In our study, the incidence of postoperative ocular pain was significantly higher in the patients of the three MMC-treated groups 2, 3, and 4 in comparison to the control group. Epithelialisation was delayed by 3-4 weeks in all patients of group 3 and 4 while avascularised sclera was noted in 8 eyes (40%) and 6 eyes (30%) of group 3 and 4 respectively. The incidence of these complications in our study is comparable to previous studies. The avascularized scleral bed following postoperative and intraoperative MMC application could be attributed to the toxic effect of MMC on vascular endothelial cells.[6] Delayed wound healing and avascularised sclera did not develop in any eye treated with single-drop MMC and were comparable to control group.

The high incidence of scleral defects such as scleral ulcer/ gutter and thinning in various sizes and shapes in groups 3 and 4 were intriguing. The incidence of scleral defects was equal (80%) in both postoperative and intraoperative groups whereas single-drop instillation of MMC resulted in significantly lower incidence (20%). Damage to sclera by episcleral excision or cautery was avoided in all patients. A uniform surgical technique was followed in all the cases by the same surgeon. The higher incidence of scleral ulceration in group 3 and 4 compared to group 2 patients could be explained on the basis that a relatively large dose of MMC (8 - 10 drops) was delivered to the operation site in postoperative and intraoperative MMC regimes. We believe that delayed epithelialisation, ischaemia of scleral bed and scleral ulceration could be due to toxic effect of MMC on pluripotent stem cells.[6],[16],[17],[18] Additionally increased tendency to localised dessication and dellen formation in the bare area might have also contributed to the pathogenesis of scleral defects. The increased bluish discoloration of scleral defects noted on patch removal and their disappearance on bandaging the eye supports this view.

Instillation of a single drop of 0.02 % MMC after bare sclera excision of pterygium, significantly reduced the recurrent rate compared to the control group and it was comparable with the recurrences following intraoperative and postoperative use of MMC. But other ocular complications were significantly reduced in the single-drop MMC regimen. We hypothesise that a single-drop instillation of MMC at the end of surgery has greater penetration through the epithelium as the fibrin complex in the wound is not formed yet and it is likely to affect the entire population of potentially "pterygium proliferating cells". Additionally, this regimen is simple, quick, least toxic and independent of patients' compliance.

To conclude, the single drop instillation of 0.02% MMC at the end of bare scleral excision of pterygium appears safe and efficacious compared to other MMC regimes in the treatment of pterygium. We suggest that further clinical trials using single-drop MMC regimen should be conducted prior to its widespread and routine use to prevent recurrence of pterygium.

 
   References Top

1.D'Ombrain A. The surgical treatment of pterygium. Br J Ophthalmol 1948;32:65-71.  Back to cited text no. 1    
2.Anduze AL, Merritt JC. Pterygium: Clinical classification and management in Virgin Islands. Ann Ophthalmol 1985;17:92-5.   Back to cited text no. 2    
3.Sebban A, Hirst LW. Pterygium recurrence rate at the Princess Alexendra Hospital. Aust NZ J Ophthalmol 1991;19:203-6.  Back to cited text no. 3    
4.Tan DTH, Chee SP, Dear KBG, Lim ASM. Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision. Arch Ophthalmol 1997;115:1235-40.  Back to cited text no. 4    
5.Chen PP, Ariyasu RG, Kaza V, Labree LD, McDonnell PJ. A randomized trial comparing Mitomycin C and conjunctival autograft after excision of primary pterygium. Am J Ophthalmol 1995;120:151-60.  Back to cited text no. 5    
6.Singh G, Wilson MR, Foster S. Mitomycin eye drops as treatment for pterygium. Ophthalmology 1988;95:813-21.  Back to cited text no. 6    
7.Hayasaka S, Noda S, Yamamto Y, Setogawa T. Post-operative instillation of low-dose mitomycin C in the treatment of primary pterygium. Am J Ophthalmol 1988;106:715-18.  Back to cited text no. 7    
8.Hayasaka S, Noda S, Yamamoto Y, Setogawa T. Postoperative instillation of mitomycin C in the treatment of recurrent pterygium. Ophthalmic Surg 1989;20:580-83.  Back to cited text no. 8    
9.Singh G, Wilson M R, Foster C S. Long term follow up study of mitomycin eye drops as adjunctive treatment for pterygia and its comparison with conjunctival autograft transplantation. Cornea 1990;9:331-34.   Back to cited text no. 9    
10.Mahar PS, Nwokara GE. Role of mitomycin C in pterygium surgery. Br J Ophthalmol 1993;77:433-35.  Back to cited text no. 10    
11.Rosenthal G, Shoham A, Lifshitz T, Biedner B, Yassur Y. The use of mitomycin in pterygium surgery. Ann Ophthalmol 1993;23:427-28.  Back to cited text no. 11    
12.Frucht-Pery J, Ilsar M. The use of low dose mitomycin C for prevention of recurrent pterygium. Ophthalmology 1994;101:759-62.  Back to cited text no. 12    
13.Rachmiel R, Leiba H, Levartovsky. Results of treatment with topical mitomycin C 0.02 % following excision of primary pterygium. Br J Ophthalmol 1995;79:233-36.  Back to cited text no. 13    
14.Frucht-Pery J, Ilsar M, Hemo I. Single dose of mitomycin C for prevention of recurrent pterygium: Preliminary report. Cornea 1994;13:411-13.  Back to cited text no. 14    
15.Mastropasqua L, Carpineto P, Ciancaglini M, Lobefelo I, Gallenga PE. Effectiveness of intra-operative mitomycin C in the treatment of recurrent pterygium. Ophthalmologica 1994;208:247-49.  Back to cited text no. 15    
16.Cano-Parra J, Diaz-Llopis M, Maldonado MJ, Vila E, Menezo JL. Prospective trial of intra-operative mitomycin C in the treatment of primary pterygium. Br J Ophthalmol 1995;79: 439-41.  Back to cited text no. 16    
17.Panda A, Das G K, Tuli S W, Kumar A. Randomized trial of intra-operative mitomycin C in surgery for pterygium. Am J Ophthalmol 1998;125:59-63.  Back to cited text no. 17    
18.Fukamachi Y, Hikita N. Ocular complication following pterygium operation and instillation of mitomycin C. Folia Ophthalmol Jpn 1981;32:197-201.  Back to cited text no. 18    
19.Rubinfeld RS, Pfister RR, Stein RM, Foster CS, Martin NF, Stoleru S, et al. Serious complications of topical mitomycin C after pterygium surgery. Ophthalmology 1992;99:1647-54.  Back to cited text no. 19    
20.Fujitani A, Hayasaka S, Shibuya Y, Noda S. Corneoscleral ulceration and corneal perforation after pterygium excision and topical mitomycin C therapy. Ophthalmologica 1993;207:162-64.  Back to cited text no. 20    
21.Gilman AG, Rall TW, Nies AS, Taylor P. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York: Pergamon Press; 1990. pp 1247-48.   Back to cited text no. 21    
22.Bowman WC, Rand MJ. Textbook of Pharmacology . 2nd ed. Oxford: Blackwell, 1980; pp 14-15.  Back to cited text no. 22    
23.Craig CR, Stitzel RE. Modern Pharmacology . 3rd ed. Boston: Little, Brown, 1990. p 807.  Back to cited text no. 23    
24.Kunitomo N, Mori S. Studies on the pterygium. A treatment of the pterygium by mitomycin C instillation. Acta Soc Ophthalmol Jap 1963;67:601-7.  Back to cited text no. 24    
25.Yamanouchi U. A case of scleral calcification due to mitomycin C instillation after pterygium operation. Folia Ophthalmol Jon 1978;29:1221-25.  Back to cited text no. 25    
26.Dunn JP, Seamone CD, Ostler HB, Nickel BL, Beallo A. Development of scleral ulceration and calcification after pterygium excision and mitomycin therapy. Am J Ophthalmol 1991;112:343-44.  Back to cited text no. 26    
27.Gupta S, Basti S. Corneoscleral, ciliary body and vitreoretinal toxicity after excessive instillation of mitomycin C. Am J Ophthalmol 1992;114:503-4.  Back to cited text no. 27    


    Figures

[Figure - 1], [Figure - 2], [Figure - 3]

    Tables

[Table - 1], [Table - 2], [Table - 3]


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