ORIGINAL STUDY
Trabeculectomy With Mitomycin-C Versus Trabeculectomy With Amniotic Membrane Transplant: A Medium-term Randomized, Controlled Trial Hany A. Khairy, FRCEd, FRCSG, MD and Moataz F. Elsawy, MD
Purpose: To evaluate the intraocular pressure (IOP)-lowering effect of trabeculectomy with the use of amniotic membrane transplant (AMT) compared with the standard trabeculectomy with Mitomycin-C (MMC) in patients with primary open-angle glaucoma. Patients and Methods: This study was a patient-masked, randomized, controlled comparison trial involving 52 eyes of 52 patients with bilateral primary open-angle glaucoma. Patients were randomized to receive trabeculectomy with AMT or trabeculectomy with MMC. The main outcome for comparison was the IOPlowering effect of both procedures. Surgical success was considered if the patient’s IOP was 20% without the use of any medication. Results: All surgeries passed uneventfully without intraoperative complications, and all patients showed significantly (P < 0.05) lower IOP on the first postoperative day compared with their respective preoperative IOP with nonsignificant (P > 0.05) difference between both study groups. All patients, irrespective of the operative procedure maintained significantly (P < 0.05) lower IOP compared with their respective preoperative IOP till the end of 24 months follow-up. Moreover, patients of the AMT group showed lower IOP compared with those included in the MMC group throughout the follow-up period; however, the difference was not statistically significant at any point of the study period. Conclusions: AMT exhibits potential as an alternative to MMC in trabeculectomy surgery. Over 24 months of follow-up, the use of AMT with trabeculectomy was safe and effective with an IOPlowering effect comparable to that achieved with the use of MMC, and a reduced rate of postoperative complication. Key Words: open-angle glaucoma, trabeculectomy, amniotic membrane transplant
It has the effect of suppressing transforming growth factor b.6,7 Other characteristics included: good integration with surrounding tissues, low healing response, poor immunogenicity, and yet a high hydraulic conductivity. Those characteristics might be of benefit in filtering bleb construction. This has led to its use as an adjuvant in high-risk glaucoma filtration surgery, and as a substrate for the repair of leaking glaucoma blebs.8,9 Amniotic membrane transplant (AMT) exhibits a potential as an alternative tissue to conjunctiva in the construction of glaucoma filtration blebs. In an experimental study on rabbits by Barton et al,8 the healing response of the glaucoma filtering bleb with the use of AMT (as demonstrated by fibroblast outgrowth) is retarded when compared with conventional conjunctival closure. Li et al10 using histology, immunohistochemistry, and real-time polymerase chain reaction demonstrated that trabeculectomy in combination with freeze-dried bilayered fibrin-binding amniotic membrane resulted in good wound healing and no scar formation. Since Fujishima et al in 199811 described the first use of AMT in trabeculectomy with success; the procedure has been used by many investigators with favorable outcome.12–18 In this prospective, randomized, patient-masked, controlled study, we have assessed the intraocular pressure (IOP)-lowering effect of this procedure compared with the standard trabeculectomy with Mitomycin-C (MMC) in patients with primary open-angle glaucoma.
(J Glaucoma 2015;24:556–559)
METHODS
A
lthough trabeculectomy is the standard primary treatment for glaucoma in the developing world, its success is often compromised with excessive fibrosis. Thereby the use of antifibrotic drugs remains the standard for augmented trabeculectomy.1–4 However, in some cases it does not achieve a good filtering effect despite the use of the antifibrotic agents.5 Human amniotic membrane is known for its antifibrotic, anti-inflammatory and antiangiogenic properties.
Received for publication March 10, 2013; accepted October 26, 2013. From the Menoufia University Hospitals, Menoufia, Egypt. Disclosure: The authors declare no conflict of interest. Reprints: Hany A. Khairy, FRCEd, FRCSG, MD, Ophthalmology Department, Menoufia University Hospitals, Menoufia 32511, Egypt (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000060
This was patient-masked, randomized, controlled comparison trial involving 52 eyes of 52 patients. Patients were recruited from the Eye Outpatient Department at Menoufia University Hospital, Egypt between January 2010 and January 2011. Eligible patients were adults aged above 60 years. They had been diagnosed clinically with bilateral open-angle glaucoma with IOP > 21; had clinical evidence of glaucomatous optic disc cupping or visual field loss; had best corrected visual acuity of 6/36 or better in each eye; had central corneal thickness measuring 65-70 > 70-75 > 75 Sex Males Females Operated side Right Left
2014 Wolters Kluwer Health, Inc. All rights reserved.
Total [n (%)]
MMC [n (%)]
AMT [n (%)]
14 15 20 3
(26.9) (28.8) (38.5) (5.8)
7 (26.9) 8 (30.8) 11 (42.3) 0
7 7 9 3
32 (61.5) 20 (38.5) 31 (59.6) 21 (40.4)
P
(26.9) (26.9) (34.7) (11.5)
> 0.05
17 (65.4) 9 (34.6)
15 (57.7) 11 (42.3)
> 0.05
15 (57.7) 11 (42.3)
16 (61.5) 10 (38.5)
> 0.05
AMT indicates amniotic membrane transplant; MMC, Mitomycin-C.
www.glaucomajournal.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
557
Khairy and Elsawy
J Glaucoma
TABLE 2. Mean IOP Estimated Throughout 24-months Postoperative Follow-up in Both Groups
MMC Group Preoperative Day-1 postoperative Day-7 postoperative Month-1 postoperative Month-3 postoperative Month-6 postoperative Month-12 postoperative Month-24 postoperative
AMT Group
No. Antiglaucoma Medications
25.6 ± 1.6 25.1 ± 2.1 7.1 ± 2.3* 6.6 ± 1.8*
0.165 0.066
11.2 ± 3*
10.7 ± 1.9*
0.452
15.3 ± 1.7* 14.9 ± 1.4*
0.102
Mean ± SD Postoperative
16 ± 1.9* 14.5 ± 2.3*
0.151
Mean ± SD
15.9 ± 3.3* 15.8 ± 2.6*
0.374
16.1 ± 3.8* 15.8 ± 3.2*
0.112
15.9 ± 3.9* 15.7 ± 3.3*
0.113
group throughout the follow-up period; however, the difference was not statistically significant at any point of the study period (Table 2). There were no recorded serious complications in either group such as wound leaks, endophthalmitis, or hyphema. Three patients (2 in the MMC group and 1 in the AMT group) had transient hypotony and shallowing of the anterior chamber (due to overfiltration), but did not require further intervention. Most patients (47/52) were using 2 or 3 antiglaucoma medications preoperatively in both groups. The mean number of medications preoperatively in the MMC group was 2.38 ± 0.70, whereas in the AMT group it was 2.46 ± 0.65. Throughout the follow-up period, only 9 patients required further medication for control of their IOP: 6 in the MMC group and 3 in the AMT group. Six of the 9 patients (4 in the MMC group and 2 in the AMT group) required only 1 antiglaucoma medication, whereas the remaining 3 patients (2 in the MMC group and 1 in the AMT group) required 2 antiglaucoma medications. The mean number of medications postoperatively in the MMC group was 0.31 ± 0.62, whereas in the AMT group it was 0.15 ± 0.46. There was no significant difference (P > 0.05) between both groups as regards the number of medications used (Table 3). Three patients (all in the MMC group) with increased bleb vascularity required a single subconjunctival injection of 5-FU (5.0 mg/mL) at the seventh postoperative day. There were no further indications for repeat injection. Concerning the morphologic appearance of the bleb as determined at the 6-month postoperative period, 33 eyes had elevated bleb with normal vascularization, 15 eyes had flat mildly vascularized bleb, and 4 eyes had nonvascularized bleb with cystic wall. There was significantly (P < 0.05) higher frequency of elevated bleb with normal vascularization in the AMT group compared with the MMC group. There was no loss of follow-up at any point during the 2 years of follow-up for either group.
Volume 24, Number 7, September 2015
TABLE 3. Number of Antiglaucoma Medications Used Preoperatively and Postoperatively
Statistical Difference (P)
Data are presented as mean ± SD. *Significant IOP versus preoperative IOP. P > 0.05: nonsignificant difference. AMT indicates amniotic membrane transplant; IOP, intraocular pressure; MMC, Mitomycin-C.
Preoperative
1 2 3 1 2
MMC Group AMT Group (No. Patients) (No. Patients) 3 10 13 2.38 ± 0.70 4 2 0.31 ± 0.62
2 10 14 2.46 ± 0.65 2 1 0.15 ± 0.46
AMT indicates amniotic membrane transplant; MMC, Mitomycin-C.
DISCUSSION Trabeculectomy augmented with antimetabolites is the standard primary treatment for glaucoma in the developing world.1–4 Marey et al1 in their study compared trabeculectomy augmented with MMC versus Ologen implant in an Egyptian population. At the end of 12 months postoperatively, the mean IOP was statistically lower in both groups, with complete success in all patients. Singh et al,2 in a short-term comparative study of 81 patients undergoing trabeculectomy with MMC or 5-FU in a Ghana population, reported a higher success rate with respect to the final IOP level in the MMC group. In a subsequent retrospective study with 3 years or longer follow-up, they reported that a significantly higher proportion of eyes with MMC augmentation achieved an IOP 3 years, significantly higher proportion of patients achieved an IOP < 21 mm Hg without medications, and the postoperative IOP was significantly lower in the MMC group at all follow-up visits except between 30 and 35 months.4 Our study in a similar population confirms their observations. MMC-augmented trabeculectomy was successful in lowering the IOP in all patients after 24 months of follow-up. All patients achieved an IOP of
Trabeculectomy With Mitomycin-C Versus Trabeculectomy With Amniotic Membrane Transplant: A Medium-term Randomized, Controlled Trial Hany A. Khairy, FRCEd, FRCSG, MD and Moataz F. Elsawy, MD
Purpose: To evaluate the intraocular pressure (IOP)-lowering effect of trabeculectomy with the use of amniotic membrane transplant (AMT) compared with the standard trabeculectomy with Mitomycin-C (MMC) in patients with primary open-angle glaucoma. Patients and Methods: This study was a patient-masked, randomized, controlled comparison trial involving 52 eyes of 52 patients with bilateral primary open-angle glaucoma. Patients were randomized to receive trabeculectomy with AMT or trabeculectomy with MMC. The main outcome for comparison was the IOPlowering effect of both procedures. Surgical success was considered if the patient’s IOP was 20% without the use of any medication. Results: All surgeries passed uneventfully without intraoperative complications, and all patients showed significantly (P < 0.05) lower IOP on the first postoperative day compared with their respective preoperative IOP with nonsignificant (P > 0.05) difference between both study groups. All patients, irrespective of the operative procedure maintained significantly (P < 0.05) lower IOP compared with their respective preoperative IOP till the end of 24 months follow-up. Moreover, patients of the AMT group showed lower IOP compared with those included in the MMC group throughout the follow-up period; however, the difference was not statistically significant at any point of the study period. Conclusions: AMT exhibits potential as an alternative to MMC in trabeculectomy surgery. Over 24 months of follow-up, the use of AMT with trabeculectomy was safe and effective with an IOPlowering effect comparable to that achieved with the use of MMC, and a reduced rate of postoperative complication. Key Words: open-angle glaucoma, trabeculectomy, amniotic membrane transplant
It has the effect of suppressing transforming growth factor b.6,7 Other characteristics included: good integration with surrounding tissues, low healing response, poor immunogenicity, and yet a high hydraulic conductivity. Those characteristics might be of benefit in filtering bleb construction. This has led to its use as an adjuvant in high-risk glaucoma filtration surgery, and as a substrate for the repair of leaking glaucoma blebs.8,9 Amniotic membrane transplant (AMT) exhibits a potential as an alternative tissue to conjunctiva in the construction of glaucoma filtration blebs. In an experimental study on rabbits by Barton et al,8 the healing response of the glaucoma filtering bleb with the use of AMT (as demonstrated by fibroblast outgrowth) is retarded when compared with conventional conjunctival closure. Li et al10 using histology, immunohistochemistry, and real-time polymerase chain reaction demonstrated that trabeculectomy in combination with freeze-dried bilayered fibrin-binding amniotic membrane resulted in good wound healing and no scar formation. Since Fujishima et al in 199811 described the first use of AMT in trabeculectomy with success; the procedure has been used by many investigators with favorable outcome.12–18 In this prospective, randomized, patient-masked, controlled study, we have assessed the intraocular pressure (IOP)-lowering effect of this procedure compared with the standard trabeculectomy with Mitomycin-C (MMC) in patients with primary open-angle glaucoma.
(J Glaucoma 2015;24:556–559)
METHODS
A
lthough trabeculectomy is the standard primary treatment for glaucoma in the developing world, its success is often compromised with excessive fibrosis. Thereby the use of antifibrotic drugs remains the standard for augmented trabeculectomy.1–4 However, in some cases it does not achieve a good filtering effect despite the use of the antifibrotic agents.5 Human amniotic membrane is known for its antifibrotic, anti-inflammatory and antiangiogenic properties.
Received for publication March 10, 2013; accepted October 26, 2013. From the Menoufia University Hospitals, Menoufia, Egypt. Disclosure: The authors declare no conflict of interest. Reprints: Hany A. Khairy, FRCEd, FRCSG, MD, Ophthalmology Department, Menoufia University Hospitals, Menoufia 32511, Egypt (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000060
This was patient-masked, randomized, controlled comparison trial involving 52 eyes of 52 patients. Patients were recruited from the Eye Outpatient Department at Menoufia University Hospital, Egypt between January 2010 and January 2011. Eligible patients were adults aged above 60 years. They had been diagnosed clinically with bilateral open-angle glaucoma with IOP > 21; had clinical evidence of glaucomatous optic disc cupping or visual field loss; had best corrected visual acuity of 6/36 or better in each eye; had central corneal thickness measuring 65-70 > 70-75 > 75 Sex Males Females Operated side Right Left
2014 Wolters Kluwer Health, Inc. All rights reserved.
Total [n (%)]
MMC [n (%)]
AMT [n (%)]
14 15 20 3
(26.9) (28.8) (38.5) (5.8)
7 (26.9) 8 (30.8) 11 (42.3) 0
7 7 9 3
32 (61.5) 20 (38.5) 31 (59.6) 21 (40.4)
P
(26.9) (26.9) (34.7) (11.5)
> 0.05
17 (65.4) 9 (34.6)
15 (57.7) 11 (42.3)
> 0.05
15 (57.7) 11 (42.3)
16 (61.5) 10 (38.5)
> 0.05
AMT indicates amniotic membrane transplant; MMC, Mitomycin-C.
www.glaucomajournal.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
557
Khairy and Elsawy
J Glaucoma
TABLE 2. Mean IOP Estimated Throughout 24-months Postoperative Follow-up in Both Groups
MMC Group Preoperative Day-1 postoperative Day-7 postoperative Month-1 postoperative Month-3 postoperative Month-6 postoperative Month-12 postoperative Month-24 postoperative
AMT Group
No. Antiglaucoma Medications
25.6 ± 1.6 25.1 ± 2.1 7.1 ± 2.3* 6.6 ± 1.8*
0.165 0.066
11.2 ± 3*
10.7 ± 1.9*
0.452
15.3 ± 1.7* 14.9 ± 1.4*
0.102
Mean ± SD Postoperative
16 ± 1.9* 14.5 ± 2.3*
0.151
Mean ± SD
15.9 ± 3.3* 15.8 ± 2.6*
0.374
16.1 ± 3.8* 15.8 ± 3.2*
0.112
15.9 ± 3.9* 15.7 ± 3.3*
0.113
group throughout the follow-up period; however, the difference was not statistically significant at any point of the study period (Table 2). There were no recorded serious complications in either group such as wound leaks, endophthalmitis, or hyphema. Three patients (2 in the MMC group and 1 in the AMT group) had transient hypotony and shallowing of the anterior chamber (due to overfiltration), but did not require further intervention. Most patients (47/52) were using 2 or 3 antiglaucoma medications preoperatively in both groups. The mean number of medications preoperatively in the MMC group was 2.38 ± 0.70, whereas in the AMT group it was 2.46 ± 0.65. Throughout the follow-up period, only 9 patients required further medication for control of their IOP: 6 in the MMC group and 3 in the AMT group. Six of the 9 patients (4 in the MMC group and 2 in the AMT group) required only 1 antiglaucoma medication, whereas the remaining 3 patients (2 in the MMC group and 1 in the AMT group) required 2 antiglaucoma medications. The mean number of medications postoperatively in the MMC group was 0.31 ± 0.62, whereas in the AMT group it was 0.15 ± 0.46. There was no significant difference (P > 0.05) between both groups as regards the number of medications used (Table 3). Three patients (all in the MMC group) with increased bleb vascularity required a single subconjunctival injection of 5-FU (5.0 mg/mL) at the seventh postoperative day. There were no further indications for repeat injection. Concerning the morphologic appearance of the bleb as determined at the 6-month postoperative period, 33 eyes had elevated bleb with normal vascularization, 15 eyes had flat mildly vascularized bleb, and 4 eyes had nonvascularized bleb with cystic wall. There was significantly (P < 0.05) higher frequency of elevated bleb with normal vascularization in the AMT group compared with the MMC group. There was no loss of follow-up at any point during the 2 years of follow-up for either group.
Volume 24, Number 7, September 2015
TABLE 3. Number of Antiglaucoma Medications Used Preoperatively and Postoperatively
Statistical Difference (P)
Data are presented as mean ± SD. *Significant IOP versus preoperative IOP. P > 0.05: nonsignificant difference. AMT indicates amniotic membrane transplant; IOP, intraocular pressure; MMC, Mitomycin-C.
Preoperative
1 2 3 1 2
MMC Group AMT Group (No. Patients) (No. Patients) 3 10 13 2.38 ± 0.70 4 2 0.31 ± 0.62
2 10 14 2.46 ± 0.65 2 1 0.15 ± 0.46
AMT indicates amniotic membrane transplant; MMC, Mitomycin-C.
DISCUSSION Trabeculectomy augmented with antimetabolites is the standard primary treatment for glaucoma in the developing world.1–4 Marey et al1 in their study compared trabeculectomy augmented with MMC versus Ologen implant in an Egyptian population. At the end of 12 months postoperatively, the mean IOP was statistically lower in both groups, with complete success in all patients. Singh et al,2 in a short-term comparative study of 81 patients undergoing trabeculectomy with MMC or 5-FU in a Ghana population, reported a higher success rate with respect to the final IOP level in the MMC group. In a subsequent retrospective study with 3 years or longer follow-up, they reported that a significantly higher proportion of eyes with MMC augmentation achieved an IOP 3 years, significantly higher proportion of patients achieved an IOP < 21 mm Hg without medications, and the postoperative IOP was significantly lower in the MMC group at all follow-up visits except between 30 and 35 months.4 Our study in a similar population confirms their observations. MMC-augmented trabeculectomy was successful in lowering the IOP in all patients after 24 months of follow-up. All patients achieved an IOP of
