Glaucoma
Subconjunctival Versus Intrascleral Application of Mitomycin C During Trabeculectomy Miaomiao Zhang,1 Bin Li,1 Wei Liu,1 Jianrong Wang,1 and Xinyi Wu2 1 2
Department of Ophthalmology, The Second People’s Hospital of Jinan, Jinan, People’s Republic of China Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China
Correspondence: Miaomiao Zhang, Department of Ophthalmology, The Second People’s Hospital of Jinan, 148# Jingyi Road, Jinan, P.R. China 250001; [email protected]. Submitted: February 14, 2014 Accepted: June 10, 2014 Citation: Zhang Z, Li B, Liu W, Wang J, Wu X. Subconjunctival versus intrascleral application of mitomycin C during trabeculectomy. Invest Ophthalmol Vis Sci. 2014;55:4639–4644. DOI:10.1167/iovs.14-14159
PURPOSE. To compare the efficacy and safety between subconjunctival and intrascleral methods of mitomycin C (MMC) application during trabeculectomy. METHODS. This retrospective study included 165 eyes treated by trabeculectomy and compared clinical outcomes between eyes that received subconjunctival MMC (Group 1, 80 eyes, 48.5%) and eyes that received intrascleral (Group 2, 85 eyes, 51.5%) MMC. Surgical success was defined as an IOP of 6 to 21 mm Hg with or without topical antiglaucoma medication use. RESULTS. Mean IOP values were not significantly different between Groups 1 and 2 (P > 0.05) until 2 weeks after surgery, while they differed significantly at 1, 3, 6, 12, and 24 months after surgery (P < 0.05). The mean number of antiglaucoma medications was 3.6 6 0.6 and 3.5 6 0.7, respectively, before surgery (P ¼ 0.327), and 0.27 6 0.32 and 0.10 6 0.29, respectively, at 24 months after surgery (P ¼ 0.001). The surgical success rate at 24 months was 86.25% and 94.12% in Groups 1 and 2, respectively (P ¼ 0.041, log-rank test). Encysted blebs were observed in 17 and 8 patients in Groups 1 and 2 (P ¼ 0.034), respectively, at 24 months. There was no statistically significant difference in the incidence of hypotony, choroidal detachment, conjunctival leakage, cataract, and the rate of postoperative procedures between Groups 1 and 2 (P > 0.05). CONCLUSIONS. Compared to subconjunctival MMC application, intrascleral MMC application can increase the long-term success of trabeculectomy without increasing the complication rates. Keywords: mitomycin-C, trabeculectomy, glaucoma
rabeculectomy is the most common filtration procedure and the gold standard in the surgical treatment of glaucoma. Despite improvements in surgical treatment of glaucoma, the complex pathophysiological mechanisms involved in conjunctival and scleral wound healing have been one of the most important factors limiting surgical success.1 However, antiproliferative agents long have been used in conjunction with trabeculectomy to inhibit subconjunctival scarring by decreasing fibroblastic activity and modulating wound healing at the bleb site.1 Mitomycin C (MMC) originally was used as a systemic chemotherapeutic agent, and it has been used widely in ophthalmic practice, during and after surgery, for enhancing the success rate of glaucoma filtration surgery. Recent systematic reviews have identified significant improvements in success rates and decreases in postoperative IOP values by the use of MMC during glaucoma filtering surgery.2–4 Various toxic effects and complications secondary to the use of MMC are widely known, and several studies have evaluated the different application methods of this drug in terms of exposure time, dose, and surface area of application.5–11 Also, MMC is used frequently during trabeculectomy, either under the conjunctival flap (subconjuctival) at the proposed site of trabeculectomy or under a superficial scleral flap (intrascleral), to improve surgical success. However, the effectiveness and safety of application at these two sites have not yet been established.8–11 This study aimed to compare the IOP-lowering effect and complication rate between subconjunctival and intrascleral
T
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
methods of MMC application in eyes treated by MMCaugmented trabeculectomy. This is the first study in literature, to our knowledge, with a larger number of patients and longer follow-up periods comparing the clinical implications between subconjunctival and intrascleral MMC application.
MATERIALS
AND
METHODS
This retrospective comparative study included 165 eyes in 165 consecutive patients with medically uncontrolled primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) who underwent trabeculectomy with adjunctive MMC application at The Second People’s Hospital of Jinan between November 2007 and March 2010. On the basis of MMC application method as revealed by surgical records, the patients were divided into Group 1, where MMC was applied under the conjunctival flap, and Group 2, where it was applied under a superficial scleral flap. The protocol was approved by the Institutional Ethics Committee of The Second People’s Hospital of Jinan and conformed to the tenets of the Declaration of Helsinki.
Preoperative Assessment Baseline clinical characteristics and demographic data were collected from the medical records of patients included in this study. Patients followed for less than 24 months, those younger 4639
IOVS j July 2014 j Vol. 55 j No. 7 j 4640
Application of Mitomycin C During Trabeculectomy than 25 years, and those with diabetes, secondary glaucoma, a history of ocular surgery, media opacity (keratoleukoma, cataract, etc.), or a history of laser trabeculoplasty were excluded. After applying the exclusion criteria, 226 patients were excluded from the analysis. Biomicroscopic, gonioscopic, and funduscopic examinations were performed in all patients before and after surgery, and IOP levels were measured using a Goldmann applanation tonometer (AT900; Haag-Streit, Koeniz, Switzerland).
Surgical Technique All surgeries were performed by the same surgeon using the following technique. After local anesthesia, the bulbus was stabilized with an atraumatic 4-0 silk traction suture suspending the superior rectus muscle. Trabeculectomy was performed by raising a fornix-based conjunctival fl ap (approximately between the 11 and 1 o’clock positions). A surgical sponge (Medtronic Xomed Surgical Products, Inc., Jacksonville, FL, USA) measuring 6 3 6 mm was soaked in a solution of 0.4 mg/mL MMC (MMC powder was reconstituted in sterile water to achieve the final concentration). In Group 1, this sponge was applied under the conjunctiva for 2 minutes. Then, the MMC application area was irrigated with balanced salt solution and a half-thickness, rectangular, 4 3 5-mm scleral flap was raised. When the entire corneoscleral limbus was exposed, trabeculectomy involving the excision of a trabecular block measuring approximately 1 3 3 mm in size was performed, followed by peripheral iridectomy. In Group 2, after the same scleral flap was raised, the MMC sponge was applied under the scleral flap for 2 minutes. Because the sponge was bigger than the scleral flap, the conjunctival flap outside the scleral flap also was exposed to MMC. Then, the tissue was irrigated with balanced salt solution and trabeculectomy was completed as described above. The scleral flap was sutured with 10/0 nylon sutures (one on each side and two at the apex) and adjusted such that the depth of the anterior chamber was maintained, allowing slow leakage from the edge of the scleral flap. Continuous suturing of the conjunctiva was performed using 10/0 nylon sutures. After surgery, the patients were instructed to stop their preoperative glaucoma medications and were prescribed 0.3% tobramycin four times daily for 1 week and 1% prednisolone acetate eye drops every 2 hours while awake for 2 weeks; this was decreased to 4 times daily for 4 weeks and tapered off over the subsequent 3 to 4 weeks. In addition, 1% atropine twice daily was prescribed if IOP was 0.05). Akarsu et al.25 reported hypotony in 17.6% patients who received 0.4 mg/mL of MMC. In this study, persistent hypotony, which was prolonged for more than 1 month, was observed in 2.5% and 4.7% patients in Groups 1 and 2, respectively (P ¼ 0.449). The incidence of hypotony in our study was not higher than that reported in the literature.8,9,11 Conjunctival leakage is a possible risk factor for these complications, and MMC is thought to increase the probability of bleb leakage.26 In this study, Group 1 encountered a higher incidence of conjunctival leakage, although the differences were not statistically significant. The inhibitory effects of MMC on subconjunctival fibroblast proliferation in vitro have been shown to be dose-dependent.19 In the subconjunctival MMC application group, the conjunctiva was directly exposed to a higher MMC dose, which can decelerate conjunctival wound healing. In this study, because of the fornix-based conjunctival flap, slower limbal conjunctival wound healing more easily resulted in leakage. Three patients with conjunctival leakage in each group underwent resuturing of the conjunctiva because of persistent leakage 2 weeks after surgery. Choroidal detachment after trabeculectomy was defined as a solid-appearing elevation of the retina and choroid. Because choroidal detachment is a transient complication of trabeculectomy, to our knowledge the risk factors have not been analyzed previously in a largescale case series.27 To treat patients suffering from persistent choroidal detachment, suprachoroidal fluid can be drained through a sclerotomy.28 In the present study, two patients in Group 2 had persistent choroidal detachment, which was resolved with surgical intervention (subretinal fluid drainage). Fortunately, there were no cases of bleb-related endophthalmitis, which has been described previously.29 In a study by Tressler et al.,9 the intrascleral MMC group required more postoperative procedures for IOP control compared to the subconjunctival MMC group. The results of this study are in agreement with the results of Prata et al.,10 who reported no significant difference in the rate of postoperative procedures between the two groups. We believe that there are two main reasons for these controversial results. First, the dose of MMC, which has a key role in its effectiveness, was different among studies. The dose was 0.4 mg/mL in our study and 0.5 mg/mL in the study of Prata et al.10 and the lowest dose of 0.27 mg/mL was used in the study of Tressler et al.9 Second, the latter study is limited by a small sample size, which can lead to bias. Our study has some limitations. First, there were individual factors affecting wound healing, such as immunity level, and this may have influenced the surgical outcomes. Second, the retrospective comparative nature of this study may have caused a bias. A prospective randomized controlled trial should be conducted in the future to clarify these results. In conclusion, intrascleral MMC application using a standard dose of 0.4 mg/mL seems to be more effective without increasing the complication rate compared to subconjunctival MMC application, and it can be considered as an alternative approach in filtrating surgery for clinically advanced glaucoma. However, further prospective randomized studies are expected to clarify the benefits of this application method.
Acknowledgments The authors alone are responsible for the content and writing of the paper. Disclosure: M. Zhang, None; B. Li, None; W. Liu, None; J. Wang, None; X. Wu, None
References 1. Matlach J, Panidou E, Grehn F, et al. Large-area versus smallarea application of mitomycin C during trabeculectomy. Eur J Ophthalmol. 2013;23:670–677. 2. Lin ZJ, Li Y, Cheng JW, et al. Intraoperative mitomycin C versus intraoperative 5-fluorouracil for trabeculectomy: a systematic review and meta-analysis. J Ocul Pharmacol Ther. 2012;28: 166–173. 3. Cheng JW, Cai JP, Li Y, et al. Intraoperative mitomycin C for nonpenetrating glaucoma surgery: a systematic review and meta-analysis. J Glaucoma. 2011;20:322–326. 4. Cheng JW, Xi GL, Wei RL, et al. Efficacy and tolerability of nonpenetrating glaucoma surgery augmented with mitomycin C in treatment of open-angle glaucoma: a meta-analysis. Can J Ophthalmol. 2009;44:76–82. 5. Membrey WL, Bunce C, Poinoosawmy DP, et al. Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma. Visual field progression. Br J Ophthalmol. 2001;85:696–701. 6. Singh K, Mehta K, Shaikh NM, et al. Trabeculectomy with intraoperative mitomyin C versus 5-fluorouracil. Prospective randomised clinical trial. Ophthalmology. 2000;107:2305– 2309. 7. Maquet JA, Dios E, Aragon J, et al. Protocol for mitomycin C use in glaucoma surgery. Acta Ophthalmol. 2005;83:196–200. 8. Agarwal HC, Saigal D, Sihota R. Assessing the role of subconjunctival versus intrascleral application of mitomycinC in high-risk trabeculectomies. Indian J Ophthalmol. 2001; 49:91–95. 9. Tressler CS, Cyrlin MN, Rosenshein JS. Subconjunctival versus intrascleral mitomycin-C in trabeculectomy. Ophthalmic Surg Lasers. 1996;27:661–666. 10. Prata JA, Minckler DS, Baerveldt G. Site of mitomycin C application during trabeculectomy. J Glaucoma. 1994;3:296– 301. 11. Vass C, Menapace R, Strenn K, et al. Episcleral versus combined episcleral and intrascleral application of mitomycin-C in trabeculectomy. Ophthalmic Surg Lasers. 1998;29: 714–721. 12. Wells AP, Ashraff NN, Hall RC, et al. Comparison of two clinical Bleb grading systems. Ophthalmology. 2006;113:77–83. 13. Kitazawa Y, Kawase K, Matsushita R, et al. Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol. 1991;109:1693–1698. 14. Lee DA, Lee TC, Corres AE, et al. Effects of mithramycin, mitomycin, daunorubicin and bleomiycin on human subconjunctival fibroblast attachment and proliferation. Invest Ophthalmol Vis Sci. 1990;31:2136–2144. 15. You YA, Gu YS, Fang CT, et al. Long term effects of simultaneus subconjunctival and subscleral mitomycin C application in repeat trabeculectomy. J Glaucoma. 2002;11:110–118. 16. Loon SC, Chew PT. A major review of antimetabolites in glaucoma therapy. Ophthalmologica. 1999;213:234–245. 17. Khaw PT, Doyle JW, Sherwood MB, et al. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol. 1993;111:263–267.
Application of Mitomycin C During Trabeculectomy 18. Lama PJ, Fechtner RD. Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol. 2003;48:314–346. 19. Nilforushan N, Yadgari M, Kish SK, et al. Subconjunctival bevacizumab versus mitomycin C adjunctive to trabeculectomy. Am J Ophthalmol. 2012;153:352–357. 20. Corderio MF, Constable PH, Alexander RA, et al. Effect of varying mitomycin-C treatment area in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 1997;38: 1639–1646. 21. Herscher J. The inhibitory factor in aqueous humour. Vis Res. 1981;21:163. 22. Herschler J, Claflin AJ, Fiorentino G. The effect of aqueous humor on the growth of subconjunctival fibroblasts in tissue culture and its implications for glaucoma surgery. Am J Ophthalmol. 1980;89:245–249. 23. Akkan JU, Cilsim S. Role of subconjunctival bevacizumab as an adjuvant to primary trabeculectomy: a prospective randomized comparative 1-year follow-up study [published online ahead of print May 8, 2013]. J Glaucoma.
IOVS j July 2014 j Vol. 55 j No. 7 j 4644 24. Feldman RM, Gross RL, Spaeth GL, et al. Risk factors for the development of Tenon’s capsule cysts after trabeculectomy. Ophthalmology. 1989;96:336–341. 25. Akarsu C, Onol M, Hasanreisoglu B. Postoperative 5-fluorouracil versus intraoperative mitomycin C in high-risk glaucoma filtering surgery: extended follow-up. Clin Exp Ophthalmol. 2003;31:199–205. 26. Kitazawa Y, Suemori-Matsushita H, Yamamoto T, et al. Low dose and high dose mitomycin trabeculectomy as an initial surgery in primary open angle glaucoma. Ophthalmology. 1997;100:1624–1628. 27. Haga A, Inatani M, Shobayashi K, et al. Risk factors for choroidal detachment after trabeculectomy with mitomycin C. Clin Ophthalmol. 2013;7:1417–1421. 28. Bellow AR, Chylack LT Jr, Hutchinson BT. Choroidal detachment. Clinical manifestation, therapy and mechanism of formation. Ophthalmology. 1981;88:1107–1115. 29. Kawakami H, Nakan Y, Inuzuka H, et al. Late-onset bleb-related endophthalmitis caused by Streptococcus pseudopneumoniae. Int Ophthalmol. 2014;34:643–646.
Subconjunctival Versus Intrascleral Application of Mitomycin C During Trabeculectomy Miaomiao Zhang,1 Bin Li,1 Wei Liu,1 Jianrong Wang,1 and Xinyi Wu2 1 2
Department of Ophthalmology, The Second People’s Hospital of Jinan, Jinan, People’s Republic of China Department of Ophthalmology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China
Correspondence: Miaomiao Zhang, Department of Ophthalmology, The Second People’s Hospital of Jinan, 148# Jingyi Road, Jinan, P.R. China 250001; [email protected]. Submitted: February 14, 2014 Accepted: June 10, 2014 Citation: Zhang Z, Li B, Liu W, Wang J, Wu X. Subconjunctival versus intrascleral application of mitomycin C during trabeculectomy. Invest Ophthalmol Vis Sci. 2014;55:4639–4644. DOI:10.1167/iovs.14-14159
PURPOSE. To compare the efficacy and safety between subconjunctival and intrascleral methods of mitomycin C (MMC) application during trabeculectomy. METHODS. This retrospective study included 165 eyes treated by trabeculectomy and compared clinical outcomes between eyes that received subconjunctival MMC (Group 1, 80 eyes, 48.5%) and eyes that received intrascleral (Group 2, 85 eyes, 51.5%) MMC. Surgical success was defined as an IOP of 6 to 21 mm Hg with or without topical antiglaucoma medication use. RESULTS. Mean IOP values were not significantly different between Groups 1 and 2 (P > 0.05) until 2 weeks after surgery, while they differed significantly at 1, 3, 6, 12, and 24 months after surgery (P < 0.05). The mean number of antiglaucoma medications was 3.6 6 0.6 and 3.5 6 0.7, respectively, before surgery (P ¼ 0.327), and 0.27 6 0.32 and 0.10 6 0.29, respectively, at 24 months after surgery (P ¼ 0.001). The surgical success rate at 24 months was 86.25% and 94.12% in Groups 1 and 2, respectively (P ¼ 0.041, log-rank test). Encysted blebs were observed in 17 and 8 patients in Groups 1 and 2 (P ¼ 0.034), respectively, at 24 months. There was no statistically significant difference in the incidence of hypotony, choroidal detachment, conjunctival leakage, cataract, and the rate of postoperative procedures between Groups 1 and 2 (P > 0.05). CONCLUSIONS. Compared to subconjunctival MMC application, intrascleral MMC application can increase the long-term success of trabeculectomy without increasing the complication rates. Keywords: mitomycin-C, trabeculectomy, glaucoma
rabeculectomy is the most common filtration procedure and the gold standard in the surgical treatment of glaucoma. Despite improvements in surgical treatment of glaucoma, the complex pathophysiological mechanisms involved in conjunctival and scleral wound healing have been one of the most important factors limiting surgical success.1 However, antiproliferative agents long have been used in conjunction with trabeculectomy to inhibit subconjunctival scarring by decreasing fibroblastic activity and modulating wound healing at the bleb site.1 Mitomycin C (MMC) originally was used as a systemic chemotherapeutic agent, and it has been used widely in ophthalmic practice, during and after surgery, for enhancing the success rate of glaucoma filtration surgery. Recent systematic reviews have identified significant improvements in success rates and decreases in postoperative IOP values by the use of MMC during glaucoma filtering surgery.2–4 Various toxic effects and complications secondary to the use of MMC are widely known, and several studies have evaluated the different application methods of this drug in terms of exposure time, dose, and surface area of application.5–11 Also, MMC is used frequently during trabeculectomy, either under the conjunctival flap (subconjuctival) at the proposed site of trabeculectomy or under a superficial scleral flap (intrascleral), to improve surgical success. However, the effectiveness and safety of application at these two sites have not yet been established.8–11 This study aimed to compare the IOP-lowering effect and complication rate between subconjunctival and intrascleral
T
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
methods of MMC application in eyes treated by MMCaugmented trabeculectomy. This is the first study in literature, to our knowledge, with a larger number of patients and longer follow-up periods comparing the clinical implications between subconjunctival and intrascleral MMC application.
MATERIALS
AND
METHODS
This retrospective comparative study included 165 eyes in 165 consecutive patients with medically uncontrolled primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) who underwent trabeculectomy with adjunctive MMC application at The Second People’s Hospital of Jinan between November 2007 and March 2010. On the basis of MMC application method as revealed by surgical records, the patients were divided into Group 1, where MMC was applied under the conjunctival flap, and Group 2, where it was applied under a superficial scleral flap. The protocol was approved by the Institutional Ethics Committee of The Second People’s Hospital of Jinan and conformed to the tenets of the Declaration of Helsinki.
Preoperative Assessment Baseline clinical characteristics and demographic data were collected from the medical records of patients included in this study. Patients followed for less than 24 months, those younger 4639
IOVS j July 2014 j Vol. 55 j No. 7 j 4640
Application of Mitomycin C During Trabeculectomy than 25 years, and those with diabetes, secondary glaucoma, a history of ocular surgery, media opacity (keratoleukoma, cataract, etc.), or a history of laser trabeculoplasty were excluded. After applying the exclusion criteria, 226 patients were excluded from the analysis. Biomicroscopic, gonioscopic, and funduscopic examinations were performed in all patients before and after surgery, and IOP levels were measured using a Goldmann applanation tonometer (AT900; Haag-Streit, Koeniz, Switzerland).
Surgical Technique All surgeries were performed by the same surgeon using the following technique. After local anesthesia, the bulbus was stabilized with an atraumatic 4-0 silk traction suture suspending the superior rectus muscle. Trabeculectomy was performed by raising a fornix-based conjunctival fl ap (approximately between the 11 and 1 o’clock positions). A surgical sponge (Medtronic Xomed Surgical Products, Inc., Jacksonville, FL, USA) measuring 6 3 6 mm was soaked in a solution of 0.4 mg/mL MMC (MMC powder was reconstituted in sterile water to achieve the final concentration). In Group 1, this sponge was applied under the conjunctiva for 2 minutes. Then, the MMC application area was irrigated with balanced salt solution and a half-thickness, rectangular, 4 3 5-mm scleral flap was raised. When the entire corneoscleral limbus was exposed, trabeculectomy involving the excision of a trabecular block measuring approximately 1 3 3 mm in size was performed, followed by peripheral iridectomy. In Group 2, after the same scleral flap was raised, the MMC sponge was applied under the scleral flap for 2 minutes. Because the sponge was bigger than the scleral flap, the conjunctival flap outside the scleral flap also was exposed to MMC. Then, the tissue was irrigated with balanced salt solution and trabeculectomy was completed as described above. The scleral flap was sutured with 10/0 nylon sutures (one on each side and two at the apex) and adjusted such that the depth of the anterior chamber was maintained, allowing slow leakage from the edge of the scleral flap. Continuous suturing of the conjunctiva was performed using 10/0 nylon sutures. After surgery, the patients were instructed to stop their preoperative glaucoma medications and were prescribed 0.3% tobramycin four times daily for 1 week and 1% prednisolone acetate eye drops every 2 hours while awake for 2 weeks; this was decreased to 4 times daily for 4 weeks and tapered off over the subsequent 3 to 4 weeks. In addition, 1% atropine twice daily was prescribed if IOP was 0.05). Akarsu et al.25 reported hypotony in 17.6% patients who received 0.4 mg/mL of MMC. In this study, persistent hypotony, which was prolonged for more than 1 month, was observed in 2.5% and 4.7% patients in Groups 1 and 2, respectively (P ¼ 0.449). The incidence of hypotony in our study was not higher than that reported in the literature.8,9,11 Conjunctival leakage is a possible risk factor for these complications, and MMC is thought to increase the probability of bleb leakage.26 In this study, Group 1 encountered a higher incidence of conjunctival leakage, although the differences were not statistically significant. The inhibitory effects of MMC on subconjunctival fibroblast proliferation in vitro have been shown to be dose-dependent.19 In the subconjunctival MMC application group, the conjunctiva was directly exposed to a higher MMC dose, which can decelerate conjunctival wound healing. In this study, because of the fornix-based conjunctival flap, slower limbal conjunctival wound healing more easily resulted in leakage. Three patients with conjunctival leakage in each group underwent resuturing of the conjunctiva because of persistent leakage 2 weeks after surgery. Choroidal detachment after trabeculectomy was defined as a solid-appearing elevation of the retina and choroid. Because choroidal detachment is a transient complication of trabeculectomy, to our knowledge the risk factors have not been analyzed previously in a largescale case series.27 To treat patients suffering from persistent choroidal detachment, suprachoroidal fluid can be drained through a sclerotomy.28 In the present study, two patients in Group 2 had persistent choroidal detachment, which was resolved with surgical intervention (subretinal fluid drainage). Fortunately, there were no cases of bleb-related endophthalmitis, which has been described previously.29 In a study by Tressler et al.,9 the intrascleral MMC group required more postoperative procedures for IOP control compared to the subconjunctival MMC group. The results of this study are in agreement with the results of Prata et al.,10 who reported no significant difference in the rate of postoperative procedures between the two groups. We believe that there are two main reasons for these controversial results. First, the dose of MMC, which has a key role in its effectiveness, was different among studies. The dose was 0.4 mg/mL in our study and 0.5 mg/mL in the study of Prata et al.10 and the lowest dose of 0.27 mg/mL was used in the study of Tressler et al.9 Second, the latter study is limited by a small sample size, which can lead to bias. Our study has some limitations. First, there were individual factors affecting wound healing, such as immunity level, and this may have influenced the surgical outcomes. Second, the retrospective comparative nature of this study may have caused a bias. A prospective randomized controlled trial should be conducted in the future to clarify these results. In conclusion, intrascleral MMC application using a standard dose of 0.4 mg/mL seems to be more effective without increasing the complication rate compared to subconjunctival MMC application, and it can be considered as an alternative approach in filtrating surgery for clinically advanced glaucoma. However, further prospective randomized studies are expected to clarify the benefits of this application method.
Acknowledgments The authors alone are responsible for the content and writing of the paper. Disclosure: M. Zhang, None; B. Li, None; W. Liu, None; J. Wang, None; X. Wu, None
References 1. Matlach J, Panidou E, Grehn F, et al. Large-area versus smallarea application of mitomycin C during trabeculectomy. Eur J Ophthalmol. 2013;23:670–677. 2. Lin ZJ, Li Y, Cheng JW, et al. Intraoperative mitomycin C versus intraoperative 5-fluorouracil for trabeculectomy: a systematic review and meta-analysis. J Ocul Pharmacol Ther. 2012;28: 166–173. 3. Cheng JW, Cai JP, Li Y, et al. Intraoperative mitomycin C for nonpenetrating glaucoma surgery: a systematic review and meta-analysis. J Glaucoma. 2011;20:322–326. 4. Cheng JW, Xi GL, Wei RL, et al. Efficacy and tolerability of nonpenetrating glaucoma surgery augmented with mitomycin C in treatment of open-angle glaucoma: a meta-analysis. Can J Ophthalmol. 2009;44:76–82. 5. Membrey WL, Bunce C, Poinoosawmy DP, et al. Glaucoma surgery with or without adjunctive antiproliferatives in normal tension glaucoma. Visual field progression. Br J Ophthalmol. 2001;85:696–701. 6. Singh K, Mehta K, Shaikh NM, et al. Trabeculectomy with intraoperative mitomyin C versus 5-fluorouracil. Prospective randomised clinical trial. Ophthalmology. 2000;107:2305– 2309. 7. Maquet JA, Dios E, Aragon J, et al. Protocol for mitomycin C use in glaucoma surgery. Acta Ophthalmol. 2005;83:196–200. 8. Agarwal HC, Saigal D, Sihota R. Assessing the role of subconjunctival versus intrascleral application of mitomycinC in high-risk trabeculectomies. Indian J Ophthalmol. 2001; 49:91–95. 9. Tressler CS, Cyrlin MN, Rosenshein JS. Subconjunctival versus intrascleral mitomycin-C in trabeculectomy. Ophthalmic Surg Lasers. 1996;27:661–666. 10. Prata JA, Minckler DS, Baerveldt G. Site of mitomycin C application during trabeculectomy. J Glaucoma. 1994;3:296– 301. 11. Vass C, Menapace R, Strenn K, et al. Episcleral versus combined episcleral and intrascleral application of mitomycin-C in trabeculectomy. Ophthalmic Surg Lasers. 1998;29: 714–721. 12. Wells AP, Ashraff NN, Hall RC, et al. Comparison of two clinical Bleb grading systems. Ophthalmology. 2006;113:77–83. 13. Kitazawa Y, Kawase K, Matsushita R, et al. Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol. 1991;109:1693–1698. 14. Lee DA, Lee TC, Corres AE, et al. Effects of mithramycin, mitomycin, daunorubicin and bleomiycin on human subconjunctival fibroblast attachment and proliferation. Invest Ophthalmol Vis Sci. 1990;31:2136–2144. 15. You YA, Gu YS, Fang CT, et al. Long term effects of simultaneus subconjunctival and subscleral mitomycin C application in repeat trabeculectomy. J Glaucoma. 2002;11:110–118. 16. Loon SC, Chew PT. A major review of antimetabolites in glaucoma therapy. Ophthalmologica. 1999;213:234–245. 17. Khaw PT, Doyle JW, Sherwood MB, et al. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol. 1993;111:263–267.
Application of Mitomycin C During Trabeculectomy 18. Lama PJ, Fechtner RD. Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol. 2003;48:314–346. 19. Nilforushan N, Yadgari M, Kish SK, et al. Subconjunctival bevacizumab versus mitomycin C adjunctive to trabeculectomy. Am J Ophthalmol. 2012;153:352–357. 20. Corderio MF, Constable PH, Alexander RA, et al. Effect of varying mitomycin-C treatment area in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 1997;38: 1639–1646. 21. Herscher J. The inhibitory factor in aqueous humour. Vis Res. 1981;21:163. 22. Herschler J, Claflin AJ, Fiorentino G. The effect of aqueous humor on the growth of subconjunctival fibroblasts in tissue culture and its implications for glaucoma surgery. Am J Ophthalmol. 1980;89:245–249. 23. Akkan JU, Cilsim S. Role of subconjunctival bevacizumab as an adjuvant to primary trabeculectomy: a prospective randomized comparative 1-year follow-up study [published online ahead of print May 8, 2013]. J Glaucoma.
IOVS j July 2014 j Vol. 55 j No. 7 j 4644 24. Feldman RM, Gross RL, Spaeth GL, et al. Risk factors for the development of Tenon’s capsule cysts after trabeculectomy. Ophthalmology. 1989;96:336–341. 25. Akarsu C, Onol M, Hasanreisoglu B. Postoperative 5-fluorouracil versus intraoperative mitomycin C in high-risk glaucoma filtering surgery: extended follow-up. Clin Exp Ophthalmol. 2003;31:199–205. 26. Kitazawa Y, Suemori-Matsushita H, Yamamoto T, et al. Low dose and high dose mitomycin trabeculectomy as an initial surgery in primary open angle glaucoma. Ophthalmology. 1997;100:1624–1628. 27. Haga A, Inatani M, Shobayashi K, et al. Risk factors for choroidal detachment after trabeculectomy with mitomycin C. Clin Ophthalmol. 2013;7:1417–1421. 28. Bellow AR, Chylack LT Jr, Hutchinson BT. Choroidal detachment. Clinical manifestation, therapy and mechanism of formation. Ophthalmology. 1981;88:1107–1115. 29. Kawakami H, Nakan Y, Inuzuka H, et al. Late-onset bleb-related endophthalmitis caused by Streptococcus pseudopneumoniae. Int Ophthalmol. 2014;34:643–646.
