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Trabeculectomy With or Without Intraoperative Sub-Tenon Injection of Triamcinolone Acetonide in Treating Secondary Glaucoma
Trabeculectomy With or Without Intraoperative Sub-Tenon Injection of Triamcinolone Acetonide in Treating Secondary Glaucoma KENYA YUKI, DAISUKE SHIBA, ITARU KIMURA, YUICHIRO OHTAKE, AND KAZUO TSUBOTA ● PURPOSE:
To investigate the efficacy of intraoperative sub-Tenon injection of triamcinolone acetonide (TA) in increasing the success rate of trabeculectomy for the treatment of secondary glaucoma. ● DESIGN: Prospective randomized controlled clinical trial. ● METHODS: Fifty-three consecutive eyes scheduled for trabeculectomy were randomly allocated in an institutional setting. In the study group (n ⴝ 26), TA was injected in the sub-Tenon at the conclusion of the surgery. In the control group (n ⴝ 27) surgery was completed without TA injection. Surgical success was defined as a complete success if the intraocular pressure (IOP) was 21 mm Hg or less with an IOP reduction of greater than or equal to 20% without any antiglaucoma medication. Success rates in both groups were compared using Kaplan-Meier survival curves and the log-rank test. The morphologic characteristics of the filtering blebs were evaluated using the Indiana Bleb Appearance Grading Scale. ● RESULTS: Fifty-three eyes completed the study (26 in the study group and 27 in the control group), with a follow-up of 12 months. Complete success rates were 65.4% for the study group and 63.0% for the control group (P ⴝ .77) at 12 months. The morphologic characteristics of the filtering blebs and postoperative complications were similar in the study and the control eyes (P > .40). IOP measurements in both groups were similar at all visits (P > .05). ● CONCLUSIONS: Trabeculectomy with intraoperative sub-Tenon injection of TA for the treatment of secondary glaucoma neither increased the intermediate-term success rate nor decreased postoperative complications. (Am J Ophthalmol 2009;147:1055–1060. © 2009 by Elsevier Inc. All rights reserved.)
Supplemental Material available at AJO.com. Accepted for publication Jan 9, 2009. From the Department of Ophthalmology (K.Y., D.S., I.K., Y.O., K.T.), Keio University School of Medicine; and the Division of Molecular and Cellular Biology (I.K.), National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. Inquiries to Kenya Yuki, Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 1608582 Japan; e-mail: [email protected] 0002-9394/09/$36.00 doi:10.1016/j.ajo.2009.01.007
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glaucoma filtering surgery is achieved through the inhibition of wound healing.1 The process of wound healing is composed of 2 processes: replacement and regeneration by collagen lay-down from fibroblasts. The initial steps in wound healing are inflammation and coagulation, leading to a cascade of biological events including cellular, hormonal, and growth factor release. These events finally lead to scar tissue formation. To reduce wound healing, mitomycin C is widely used to inhibit fibroblast proliferation in trabeculectomy and it results in relatively avascular filtration blebs with less fibrovascular scarring and an increased success rate.2 Corticosteroids also reduce and regulate wound healing through inhibition of macrophage functions such as phagocytosis and release of enzymes like collagenase, plasminogen activator, and growth factors and thus suppress inflammation. In the regeneration phase, corticosteroids inhibit conversion of membrane phospholipids to arachidonic acids, which act as chemotactic factors. Corticosteroids also inhibit vascular permeability and fibroblast proliferation.2 Postoperative topical corticosteroids have been reported to significantly increase the success of trabeculectomy by inhibiting wound healing as a result of suppression of inflammation and fibroblast proliferation.3 Tissue culture studies of human Tenon capsule fibroblasts have shown that corticosteroids inhibit cell attachment and proliferation.4 Sub-Tenon injection of triamcinolone acetonide (TA) is widely used for its safety and efficacy to treat uveitis,5 diabetic macular edema,6 macular edema post-branch, or central retinal vein occlusion.7 Direct injection of TA into the sub-Tenon area may be a more effective means of high-dose corticosteroid delivery and may inhibit wound healing and increase the success rate of glaucoma surgery against secondary glaucoma.8 Tham and associates reported use of TA (1.2 mg) injection into filtration blebs at the conclusion of trabeculectomy9 in a nonrandomized noncontrolled study and showed that good intraocular pressure (IOP) control was obtained at least by the third month. We conducted this prospective randomized study with the intention to determine whether intraoperative sub-Tenon injection of TA during trabeculectomy is an effective procedure for the treatment of secondary glaucoma or not.
ELSEVIER INC. ALL
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PATIENTS AND METHODS
TABLE 1. Demographic and Clinical Characteristics of Study and Control Groups
ALL PATIENTS WITH CONSECUTIVE UNCONTROLLED SEC-
ondary glaucoma scheduled from January 1, 2005 to December 31, 2006 for trabeculectomy surgery without phacoemulsification attending the glaucoma clinic of Keio University Hospital were randomly allocated to 2 groups: trabeculectomy with intraoperative sub-Tenon injection of TA (study group, 26 eyes) and trabeculectomy without intraoperative sub-Tenon injection of TA (control group, 27 eyes; see Supplemental Figure available at AJO.com.). The eyes were randomized after enrollment using computer-generated randomized numbers when they were admitted. Bilateral patients were enrolled in this study separately when they were admitted. No patients were operated bilaterally during one admission. Exclusion criteria included age less than 20 years, mental illness, or dementia; no patients were excluded. All trabeculectomy surgeries were done by a single glaucoma specialist (K.Y.). A fornix-based or a limbalbased conjunctival flap was used. Because fornix-based trabeculectomy has been recommended in Japan since 2005, because of less avascular blebs than limbal-based trabeculectomy,10,11 we modified our procedures in 2006. Scleral tunnel use has also been recommended for fornixbased trabeculectomy to avoid avascular blebs. The results of IOP after fornix-based or limbal-based conjunctival flaps were not different.12 Sub-Tenon dissection and hemostasis were performed. A half-thickness 4.0 ⫻ 4.0-mm rectangular scleral flap was fashioned in the superior area. A 4 ⫻ 4-mm sponge soaked in a 0.4 mg/ml solution of mitomycin C was applied for 5 minutes, and the area was irrigated thoroughly with 500 ml physiological saline.13,14 A 3.0 ⫻ 4.0-mm-deep sclerectomy was done when the conjunctival flap was fornix based. The trabeculectomy was followed by a peripheral iridectomy. The scleral flap was sutured with 10-0 nylon mattress sutures (MANI, Tochigi, Japan). Just before finalizing the conjunctival incision closure, a 25gauge curved blunt cannula was inserted into the subTenon space around the equator to allow the infusion of 20 mg TA (Kenacort; 20 mg/ml; Bristol Pharmaceutical, YK, Tokyo, Japan) to the study group. The postoperative regimen for all participants included topical 0.5% levofloxacin (Cravit Ophthalmic Solutions; Santen Pharmaceutical Co Ltd, Osaka, Japan) 3 times per day for 1 month and betamethasone eye drops (Sanbetazone; Santen Pharmaceutical Co Ltd) 4 times per day for 1 month and 2 times per day for 2 months and once daily for 3 months. Suture lysis was performed after surgery to titrate IOP to the desired level. Antiglaucoma therapy was added for IOP control when bleb function was inadequate to achieve the target IOP. Preoperative data obtained for each patient included age, gender, type of glaucoma, previous intraocular surgery, number of antiglaucoma medications, IOP, and bestcorrected visual acuity (BCVA). Postoperative data, col1056
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Study Groupa (n ⫽ 26)
Control Groupb (n ⫽ 27)
Gender Male 22 (84.6%) 19 (70.4%) Female 4 (15.4%) 8 (29.6%) Age (y) 61.8 ⫾ 14.3 59.1 ⫾ 13.9 Range (y) 27 to 82 28 to 83 Eye Right eye 13 (50.0%) 14 (51.9%) Left eye 13 (50.0%) 13 (48.1%) Incision Limbal-based 3 (11.5%) 6 (22.2%) Fornix-based 23 (88.5%) 21 (77.8%) Type of glaucoma Neovascular glaucoma 13 (50.0%) 11 (40.7%) Glaucoma post-PKP 6 (23.1%) 4 (14.8%) Uveitic 4 (15.4%) 4 (14.8%) Exfoliative 2 (7.6%) 3 (11.1%) Post vitrectomy 1 (3.8%) 5 (18.5%) Previous intraocular surgery (total) Vitrectomy 12 20 PKP 7 5 Trabeculectomy 13 19 Preoperative visual acuity 0.96 ⫾ 0.78 0.79 ⫾ 0.88 (logMAR) Preoperative intraocular 31.34 ⫾ 4.68 34.30 ⫾ 10.94 pressure (mm Hg) Number of antiglaucoma 3.4 ⫾ 0.5 3.5 ⫾ 0.8 medications
P value
.20 — — .52 — .47 — — .47 — — .43 — — — — —
.37 .75 .51 .48 .20 .42
LogMAR ⫽ logarithm of the minimum angle of resolution; PKP ⫽ penetrating keratoplasty; y ⫽ year. a Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
lected 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery, included IOP, number of antiglaucoma medications, number of laser suture lysis, BCVA, and presence of complications. The primary outcome measures were defined as: 1) complete success, defined as having an IOP of 21 mm Hg or less and an IOP reduction of greater than or equal to 20% without antiglaucoma medication, and 2) qualified success, defined as having an IOP of 21 mm Hg or less and an IOP reduction of greater than or equal to 20% with antiglaucoma medication.15,16 Patients considered to have failed treatment were those requiring additional surgery, including needling, or those with an IOP of more than 22 mm Hg (after the 3-month visit) despite medication. The morphologic characteristics of the filtering bleb were evaluated using the Indiana Bleb Appearance Grading Scale, which is a reproducible system for classifying bleb OF
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TABLE 2. Mean Intraocular Pressure (mm Hg) at Baseline and Follow-up Visits of Complete Success for Study and Control Groups
Baseline Postoperative visit 1-week visit 1-month visit 3-month visit 6-month visit 9-month visit 12-month visit
Study Groupa (n ⫽ 17)
Control Groupb (n ⫽ 17)
P value
30.3 ⫾ 4.1
33.8 ⫾ 10.9
.16
6.9 ⫾ 4.7 10.5 ⫾ 3.7 12.9 ⫾ 5.7 11.0 ⫾ 2.9 12.7 ⫾ 4.6 12.9 ⫾ 5.9
7.6 ⫾ 3.6 11.3 ⫾ 7.4 11.1 ⫾ 5.7 11.7 ⫾ 4.4 11.6 ⫾ 3.8 12.1 ⫾ 4.1
.22 .65 .56 .54 .43 .62
a
FIGURE. Kaplan-Meier cumulative probability of complete success (intraocular pressure <21 mm Hg without medication) for the study (trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide (TA) in treating secondary glaucoma) and control (trabeculectomy without intraoperative sub-Tenon injection of TA in treating secondary glaucoma) groups (P ⴝ .77). Note the absence of failures between 3 and 9 months in both groups.
height, extent, vascularity, and leakage with the Seidel test.17 Hypotony was defined as an IOP less than 5 mm Hg. Statistical analysis was performed using SPSS software version 15.0 (SPSS Inc, Chicago, Illinois, USA). Continuous variables were analyzed using the unpaired Student t test or paired t test as appropriate. The number of preoperative and postoperative antiglaucoma medications and the number of laser suture lysis were analyzed by Mann– Whitney U test between study and control groups. The number of antiglaucoma medications between before and after trabeculectomy was analyzed by Wilcoxon signedrank test. The 2 or Fisher exact tests were used to evaluate categorical data as appropriate. Kaplan-Meier survival analysis and the log-rank test were used to determine success rates in both groups. P values of less than .05 were considered statistically significant. Assuming a standard deviation of the IOP measurement of 20% and setting an ␣ error of .05, the minimum sample size was set at 46 with a 0.8 power to detect a difference of 15% between the groups (one-tailed test).
RESULTS FIFTY-THREE EYES OF 48 PATIENTS WERE ENROLLED IN THE
study, of which 26 were assigned to receive trabeculectomy with intraoperative sub-Tenon injection of TA (study group) and 27 were assigned to trabeculectomy without intraoperative sub-Tenon injection of TA (control group). VOL. 147, NO. 6
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Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
All patients completed the study at the 12-month follow-up visit. Preoperative data are presented for both groups in Table 1. There were no significant differences between the groups in terms of gender, age, right or left eye, base of conjunctival flap, type of glaucoma, previous intraocular surgery, number of prescribed antiglaucoma medications, preoperative IOP, and preoperative visual acuity. The Figure illustrates Kaplan-Meier survival analysis and the P value measured by 2 test for the 2 patient groups using the complete success definition. Twelve months after surgery, 17 study eyes (65.4%) and 17 control eyes (62.9%) were considered to have a complete success (P ⫽ .77). Nineteen study eyes (73.1%) and 18 control eyes (66.6%) were regarded to have a qualified and a complete success (P ⫽ .61). Mean IOPs for both groups with complete success at all visits are listed in Table 2. Postoperative IOP levels were significantly lower than preoperative levels for the 2 groups at all intervals (P ⬍ .001). IOP measurements did not differ significantly between the groups at any interval. Postoperative BCVA at 12 months did not differ significantly between the groups (study group: 0.82 ⫾ 0.75; control group: 1.01 ⫾ 0.80, P ⫽ .71). The mean number of prescribed antiglaucoma medications used in the study group dropped from a preoperative mean of 3.4 ⫾ 0.5 to a 12-month postoperative mean of 0.8 ⫾ 1.3 (P ⬍ .001), and in the control group from 3.5 ⫾ 0.8 to 1.2 ⫾ 1.5 (P ⬍ .001). The mean number of argon laser suture lysis was 1.6 ⫾ 1.9 in the control group and 0.5 ⫾ 0.5 in the study group and there was a statistically significant difference between the 2 groups (P ⫽ .03). The morphologic characteristics of the filtering blebs for both groups, defined in terms of the Indiana Bleb Appearance Grading Scale, are shown in Table 3. Data from eyes WITH
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the number of argon laser suture lysis after trabeculectomy was significantly reduced in the study group vs the control group. It has been reported that eyes that undergo laser suture lysis are more likely to have poorer IOP controls than eyes not requiring laser suture lysis.18 TA may suppress wound healing around the scleral flap and reduce the number of argon laser suture lysis postoperatively. Three previous reports were published on using corticosteroids as adjunct to glaucoma filtration surgery. Seah and associates used Surodex (Oculex Pharmaceuticals, Sunnyvale, California, USA), incorporating 60 micrograms of dexamethasone in a pellet, in phacotrabeculectomy surgery for the treatment of primary open-angle glaucoma and compared the results with phacotrabeculectomy augmented with 50 mg/ml of intraoperative 5-fluorouracil (5-FU) during the same period. There was a 20.1% decrease in IOP in the Surodex group compared with 28.5% decrease in the 5-FU group (P ⫽ .6).19 Seah and associates suggested that Surodex during phacotrabeculectomy provides surgeons with a new option in filtering surgery. Tham and associates used TA (1.2 mg) injection into filtration bleb at the conclusion of filtration surgery such as trabeculectomy, phacotrabeculectomy, and needling.9 Eleven eyes (5 primary open-angle glaucoma, 6 chronic angle-closure glaucoma) were included in this study. Tham reported that good IOP control was obtained at least by the third month. The only complication was persistent subconjunctival TA deposit in one case. Giangiacomo and associates used TA (4 mg) injection subconjunctivally before trabeculectomy in 15 eyes.20 Fourteen eyes with controlled IOP had diffuse microcystic filtration blebs by slit-lamp examination and 1 eye had a surgical failure. They concluded that the use of TA did not appear to add any additional risks to the surgical procedure or to the postoperative period. All the studies previously reported were either nonrandomized prospective or retrospective and with a small sample size. We believe our study’s strength is based on the design of its randomized prospective clinical trial. The success rate of trabeculectomy with mitomycin C for the treatment of neovascular glaucoma at 1 year is reported in about 29% to 67% of cases.21,22 Our complete success rate for neovascular glaucoma with intraoperative sub-Tenon injection of TA was 76.9% (10 eyes) and without intraoperative sub-Tenon injection of TA was 54.5% (6 eyes). Our success rate of trabeculectomy with intraoperative sub-Tenon injection of TA for the treatment of neovascular glaucoma is better than previously reported, but no statistically significant difference between the success rates of the study and control groups was shown in this study (P ⫽ .39). Jonas and associates reported that the intravitreal TA injection to neovascular glaucoma reduced rubeosis iridis and IOP.23,24 This result may imply the anti-angiogenic effect of TA. Sub-Tenon injection of TA has the possibility to increase the success rate of
TABLE 3. Bleb Morphologic Characteristics (According to the Indiana Bleb Appearance Grading Scale) 1 Year After Surgery for Study and Control Groups
Height Horizontal extent Vascularity Leakage
Study Groupa (n ⫽ 17)
Control Groupb (n ⫽ 17)
P value
2.1 ⫾ 0.8 2.1 ⫾ 0.9 1.8 ⫾ 1.0 0
1.9 ⫾ 0.8 2.0 ⫾ 0.9 2.0 ⫾ 0.9 0
.73 .92 .61 .99
a
Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
TABLE 4. Postoperative Complications for Study and Control Groups
Postoperative complications Hypotony Choroidal detachment Leakage from suture
Study Groupa (n ⫽ 26)
Control Groupb (n ⫽ 27)
P value
6 (23.1%) 2 (7.7%) 2 (7.7%)
4 (14.8%) 1 (3.7%) 5 (18.5%)
.47 — — —
a Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
that underwent additional surgery were excluded from the analysis because the performed interventions intentionally interfered with the morphologic features of the blebs. The 2 groups were similar in terms of bleb height, extent, vascularity, and leakage (P ⬎ .5). The complications encountered at the postoperative period are listed in Table 4. The most frequent complications were hypotony (10 eyes; 18.9%) and bleb leak at the conjunctival suture site (7 eyes; 13.2%). No statistically significant difference was found between the study and control groups about postoperative complications (P ⫽ .47). Hypotony maculopathy, late bleb leak, bleb-associated infection, and corneal decompensation were not found in any of our patients.
DISCUSSION WE DID NOT FIND ANY SIGNIFICANT DIFFERENCES BETWEEN
the success rates of trabeculectomy with intraoperative sub-Tenon injection of TA or without intraoperative injection within the 12-month follow-up period or postoperative IOP. Additionally, there was no significant difference in the morphologic characteristics of the filtering blebs and in the number of complications. However, 1058
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trabeculectomy for neovascular glaucoma with its antiangiogenic effect. Some complications associated with sub-Tenon injection of TA were previously reported. Ptosis,25 orbital fat prolapse,26 conjunctival ulceration,27 retinal and choroidal vascular occlusion,28 and cutaneous hypopigmentation29 were reported but no complications associated with intraoperative sub-Tenon injection of TA were observed in this study. Our study has several limitations. One of the limitations was that our sample size allowed us to detect only fairly large differences in success rates between trabeculectomy with or without intraoperative sub-Tenon injection of TA. Both groups included varied types of glaucomas such as neovascular glaucoma, glaucoma postpenetrating keratoplasty, uveitic glaucoma, exfoliative glaucoma, and aphakic glaucoma. TA is an anti-inflammatory drug, so the effect of TA for filtration surgery seems to be more effective for inflammatory glaucoma such as neovascular glaucoma, uveitic glaucoma, and glaucoma postpenetrating keratoplasty. Further investigation will be needed to evaluate trabeculectomy with intraoperative sub-Tenon injection
of TA for each type of glaucoma in the future. It should be noted that mitomycin C application might have masked the TA effects in this study. Future studies should incorporate an additional study group comprising only TA application in addition to the groups investigated in the current report. An interesting study group might be one receiving sub-Tenon corticosteroids at the end of the surgery, but no topical corticosteroids in the postoperative course. Given the nature of our study, another limitation was our inability to mask the intraoperative sub-Tenon TA injection procedure and the evaluation of bleb morphology, which was performed by the same investigator. This might have introduced bias in the interpretation of our results. Information from studies with such masking will provide invaluable information. In conclusion, trabeculectomy with intraoperative subTenon injection of TA for the treatment of secondary glaucoma neither increased the intermediate-term success rate nor decreased postoperative complications of trabeculectomy. Intraoperative sub-Tenon injection of TA was associated with a fewer number of laser suture lysis.
THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN DESIGN AND conduct of study (K.Y.); collection, management, analysis, and interpretation of data (K.Y., I.K.); provision of materials or patients (D.S.); critical revision and statistical expertise (Y.O.); and preparation, review, or approval of the manuscript (K.T.). This study was approved by the Ethics Committee of the Keio University School of Medicine and adhered to the tenets of the Declaration of Helsinki.
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9. Tham CC, Li FC, Leung DY, et al. Intrableb triamcinolone acetonide injection after bleb-forming filtration surgery (trabeculectomy, phacotrabeculectomy, and trabeculectomy revision by needling): a pilot study. Eye 2006;20:1484 –1486. 10. Kano K, Kuwayama Y. [Characteristics of filtering blebs after fornix-based trabeculectomy with a scleral tunnel]. Nippon Ganka Gakkai Zasshi 2005;109:285–291. 11. Kano K, Kuwayama Y, Mizunoya H. [Clinical results of fornix-based trabeculectomy with a scleral tunnel]. Nippon Ganka Gakkai Zasshi 2005;109:75– 82. 12. Shingleton BJ, Chaudhry IM, O’Donoghue MW, et al. Phacotrabeculectomy: limbus-based vs. fornix-based conjunctival flaps in fellow eyes. Ophthalmology 1999;106: 1152–1155. 13. Shigeeda T, Tomidokoro A, Chen YN, et al. Long-term follow-up of initial trabeculectomy with mitomycin C for primary open-angle glaucoma in Japanese patients. J Glaucoma 2006;15:195–199. 14. Al-Hazmi A, Zwaan J, Awad A, et al. Effectiveness and complications of mitomycin C use during pediatric glaucoma surgery. Ophthalmology 1998;105:1915–1920. 15. Lopes JF, Moster MR, Wilson RP, et al. Subconjunctival sodium hyaluronate 2.3% in trabeculectomy: a prospective randomized clinical trial. Ophthalmology 2006;113:756 –760. 16. Goulet RJ III, Phan AD, Cantor LB, WuDunn D. Efficacy of the Ahmed S2 glaucoma valve compared with the Baerveldt 250-mm2 glaucoma implant. Ophthalmology 2008;115:1141–1147. 17. Cantor LB, Mantravadi A, WuDunn D, et al. Morphologic classification of filtering blebs after glaucoma filtration surgery: the Indiana Bleb Appearance Grading Scale. J Glaucoma 2003;12:266 –271. WITH
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24. Jonas JB, Kreissig I, Degenring RF. Neovascular glaucoma treated by intravitreal triamcinolone acetonide. Acta Ophthalmol Scand 2003;81:540 –541. 25. Ideta S, Noda M, Kawamura R, Shinoda K, Inoue M, Tsubota K. Ptosis after sub-Tenon’s capsule triamcinolone. Ophthalmology 2008;115:410 – 410 e1. 26. Dal Canto AJ, Downs-Kelly E, Perry JD. Ptosis and orbital fat prolapse after posterior sub-Tenon’s capsule triamcinolone injection. Ophthalmology 2005;112:1092–1097. 27. Agrawal S, Agrawal J, Agrawal TP. Conjunctival ulceration following triamcinolone injection. Am J Ophthalmol 2003; 136:539 –540. 28. Moshfeghi DM, Lowder CY, Roth DB, Kaiser PK. Retinal and choroidal vascular occlusion after posterior sub-Tenon triamcinolone injection. Am J Ophthalmol 2002;134:132–134. 29. Gallardo MJ, Johnson DA. Cutaneous hypopigmentation following a posterior sub-Tenon triamcinolone injection. Am J Ophthalmol 2004;137:779 –780.
18. Ralli M, Nouri-Mahdavi K, Caprioli J. Outcomes of laser suture lysis after initial trabeculectomy with adjunctive mitomycin C. J Glaucoma 2006;15:60 – 67. 19. Seah SK, Husain R, Gazzard G, et al. Use of surodex in phacotrabeculectomy surgery. Am J Ophthalmol 2005;139:927–928. 20. Giangiacomo J, Dueker DK, Adelstein E. The effect of preoperative subconjunctival triamcinolone administration on glaucoma filtration. I. Trabeculectomy following subconjunctival triamcinolone. Arch Ophthalmol 1986;104:838 – 841. 21. Hyung SM, Kim SK. Mid-term effects of trabeculectomy with mitomycin C in neovascular glaucoma patients. Korean J Ophthalmol 2001;15:98 –106. 22. Kiuchi Y, Sugimoto R, Nakae K, et al. Trabeculectomy with mitomycin C for treatment of neovascular glaucoma in diabetic patients. Ophthalmologica 2006;220:383–388. 23. Jonas JB, Hayler JK, Sofker A, Panda-Jonas S. Regression of neovascular iris vessels by intravitreal injection of crystalline cortisone. J Glaucoma 2001;10:284 –287.
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Biosketch Kenya Yuki, MD was educated at and graduated from Keio University School of Medicine in Tokyo, Japan, where he completed his residency in ophthalmology, followed by a fellowship in glaucoma. He is currently pursuing his PhD, also at Keio University School of Medicine.
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SUPPLEMENTAL FIGURE. Flow chart shows the total numbers of eyes enrolled, operated, and observed during the follow-up of the study.
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To investigate the efficacy of intraoperative sub-Tenon injection of triamcinolone acetonide (TA) in increasing the success rate of trabeculectomy for the treatment of secondary glaucoma. ● DESIGN: Prospective randomized controlled clinical trial. ● METHODS: Fifty-three consecutive eyes scheduled for trabeculectomy were randomly allocated in an institutional setting. In the study group (n ⴝ 26), TA was injected in the sub-Tenon at the conclusion of the surgery. In the control group (n ⴝ 27) surgery was completed without TA injection. Surgical success was defined as a complete success if the intraocular pressure (IOP) was 21 mm Hg or less with an IOP reduction of greater than or equal to 20% without any antiglaucoma medication. Success rates in both groups were compared using Kaplan-Meier survival curves and the log-rank test. The morphologic characteristics of the filtering blebs were evaluated using the Indiana Bleb Appearance Grading Scale. ● RESULTS: Fifty-three eyes completed the study (26 in the study group and 27 in the control group), with a follow-up of 12 months. Complete success rates were 65.4% for the study group and 63.0% for the control group (P ⴝ .77) at 12 months. The morphologic characteristics of the filtering blebs and postoperative complications were similar in the study and the control eyes (P > .40). IOP measurements in both groups were similar at all visits (P > .05). ● CONCLUSIONS: Trabeculectomy with intraoperative sub-Tenon injection of TA for the treatment of secondary glaucoma neither increased the intermediate-term success rate nor decreased postoperative complications. (Am J Ophthalmol 2009;147:1055–1060. © 2009 by Elsevier Inc. All rights reserved.)
Supplemental Material available at AJO.com. Accepted for publication Jan 9, 2009. From the Department of Ophthalmology (K.Y., D.S., I.K., Y.O., K.T.), Keio University School of Medicine; and the Division of Molecular and Cellular Biology (I.K.), National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. Inquiries to Kenya Yuki, Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 1608582 Japan; e-mail: [email protected] 0002-9394/09/$36.00 doi:10.1016/j.ajo.2009.01.007
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U
NLIKE MOST SURGICAL PROCEDURES, SUCCESS OF
glaucoma filtering surgery is achieved through the inhibition of wound healing.1 The process of wound healing is composed of 2 processes: replacement and regeneration by collagen lay-down from fibroblasts. The initial steps in wound healing are inflammation and coagulation, leading to a cascade of biological events including cellular, hormonal, and growth factor release. These events finally lead to scar tissue formation. To reduce wound healing, mitomycin C is widely used to inhibit fibroblast proliferation in trabeculectomy and it results in relatively avascular filtration blebs with less fibrovascular scarring and an increased success rate.2 Corticosteroids also reduce and regulate wound healing through inhibition of macrophage functions such as phagocytosis and release of enzymes like collagenase, plasminogen activator, and growth factors and thus suppress inflammation. In the regeneration phase, corticosteroids inhibit conversion of membrane phospholipids to arachidonic acids, which act as chemotactic factors. Corticosteroids also inhibit vascular permeability and fibroblast proliferation.2 Postoperative topical corticosteroids have been reported to significantly increase the success of trabeculectomy by inhibiting wound healing as a result of suppression of inflammation and fibroblast proliferation.3 Tissue culture studies of human Tenon capsule fibroblasts have shown that corticosteroids inhibit cell attachment and proliferation.4 Sub-Tenon injection of triamcinolone acetonide (TA) is widely used for its safety and efficacy to treat uveitis,5 diabetic macular edema,6 macular edema post-branch, or central retinal vein occlusion.7 Direct injection of TA into the sub-Tenon area may be a more effective means of high-dose corticosteroid delivery and may inhibit wound healing and increase the success rate of glaucoma surgery against secondary glaucoma.8 Tham and associates reported use of TA (1.2 mg) injection into filtration blebs at the conclusion of trabeculectomy9 in a nonrandomized noncontrolled study and showed that good intraocular pressure (IOP) control was obtained at least by the third month. We conducted this prospective randomized study with the intention to determine whether intraoperative sub-Tenon injection of TA during trabeculectomy is an effective procedure for the treatment of secondary glaucoma or not.
ELSEVIER INC. ALL
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PATIENTS AND METHODS
TABLE 1. Demographic and Clinical Characteristics of Study and Control Groups
ALL PATIENTS WITH CONSECUTIVE UNCONTROLLED SEC-
ondary glaucoma scheduled from January 1, 2005 to December 31, 2006 for trabeculectomy surgery without phacoemulsification attending the glaucoma clinic of Keio University Hospital were randomly allocated to 2 groups: trabeculectomy with intraoperative sub-Tenon injection of TA (study group, 26 eyes) and trabeculectomy without intraoperative sub-Tenon injection of TA (control group, 27 eyes; see Supplemental Figure available at AJO.com.). The eyes were randomized after enrollment using computer-generated randomized numbers when they were admitted. Bilateral patients were enrolled in this study separately when they were admitted. No patients were operated bilaterally during one admission. Exclusion criteria included age less than 20 years, mental illness, or dementia; no patients were excluded. All trabeculectomy surgeries were done by a single glaucoma specialist (K.Y.). A fornix-based or a limbalbased conjunctival flap was used. Because fornix-based trabeculectomy has been recommended in Japan since 2005, because of less avascular blebs than limbal-based trabeculectomy,10,11 we modified our procedures in 2006. Scleral tunnel use has also been recommended for fornixbased trabeculectomy to avoid avascular blebs. The results of IOP after fornix-based or limbal-based conjunctival flaps were not different.12 Sub-Tenon dissection and hemostasis were performed. A half-thickness 4.0 ⫻ 4.0-mm rectangular scleral flap was fashioned in the superior area. A 4 ⫻ 4-mm sponge soaked in a 0.4 mg/ml solution of mitomycin C was applied for 5 minutes, and the area was irrigated thoroughly with 500 ml physiological saline.13,14 A 3.0 ⫻ 4.0-mm-deep sclerectomy was done when the conjunctival flap was fornix based. The trabeculectomy was followed by a peripheral iridectomy. The scleral flap was sutured with 10-0 nylon mattress sutures (MANI, Tochigi, Japan). Just before finalizing the conjunctival incision closure, a 25gauge curved blunt cannula was inserted into the subTenon space around the equator to allow the infusion of 20 mg TA (Kenacort; 20 mg/ml; Bristol Pharmaceutical, YK, Tokyo, Japan) to the study group. The postoperative regimen for all participants included topical 0.5% levofloxacin (Cravit Ophthalmic Solutions; Santen Pharmaceutical Co Ltd, Osaka, Japan) 3 times per day for 1 month and betamethasone eye drops (Sanbetazone; Santen Pharmaceutical Co Ltd) 4 times per day for 1 month and 2 times per day for 2 months and once daily for 3 months. Suture lysis was performed after surgery to titrate IOP to the desired level. Antiglaucoma therapy was added for IOP control when bleb function was inadequate to achieve the target IOP. Preoperative data obtained for each patient included age, gender, type of glaucoma, previous intraocular surgery, number of antiglaucoma medications, IOP, and bestcorrected visual acuity (BCVA). Postoperative data, col1056
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Study Groupa (n ⫽ 26)
Control Groupb (n ⫽ 27)
Gender Male 22 (84.6%) 19 (70.4%) Female 4 (15.4%) 8 (29.6%) Age (y) 61.8 ⫾ 14.3 59.1 ⫾ 13.9 Range (y) 27 to 82 28 to 83 Eye Right eye 13 (50.0%) 14 (51.9%) Left eye 13 (50.0%) 13 (48.1%) Incision Limbal-based 3 (11.5%) 6 (22.2%) Fornix-based 23 (88.5%) 21 (77.8%) Type of glaucoma Neovascular glaucoma 13 (50.0%) 11 (40.7%) Glaucoma post-PKP 6 (23.1%) 4 (14.8%) Uveitic 4 (15.4%) 4 (14.8%) Exfoliative 2 (7.6%) 3 (11.1%) Post vitrectomy 1 (3.8%) 5 (18.5%) Previous intraocular surgery (total) Vitrectomy 12 20 PKP 7 5 Trabeculectomy 13 19 Preoperative visual acuity 0.96 ⫾ 0.78 0.79 ⫾ 0.88 (logMAR) Preoperative intraocular 31.34 ⫾ 4.68 34.30 ⫾ 10.94 pressure (mm Hg) Number of antiglaucoma 3.4 ⫾ 0.5 3.5 ⫾ 0.8 medications
P value
.20 — — .52 — .47 — — .47 — — .43 — — — — —
.37 .75 .51 .48 .20 .42
LogMAR ⫽ logarithm of the minimum angle of resolution; PKP ⫽ penetrating keratoplasty; y ⫽ year. a Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
lected 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery, included IOP, number of antiglaucoma medications, number of laser suture lysis, BCVA, and presence of complications. The primary outcome measures were defined as: 1) complete success, defined as having an IOP of 21 mm Hg or less and an IOP reduction of greater than or equal to 20% without antiglaucoma medication, and 2) qualified success, defined as having an IOP of 21 mm Hg or less and an IOP reduction of greater than or equal to 20% with antiglaucoma medication.15,16 Patients considered to have failed treatment were those requiring additional surgery, including needling, or those with an IOP of more than 22 mm Hg (after the 3-month visit) despite medication. The morphologic characteristics of the filtering bleb were evaluated using the Indiana Bleb Appearance Grading Scale, which is a reproducible system for classifying bleb OF
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TABLE 2. Mean Intraocular Pressure (mm Hg) at Baseline and Follow-up Visits of Complete Success for Study and Control Groups
Baseline Postoperative visit 1-week visit 1-month visit 3-month visit 6-month visit 9-month visit 12-month visit
Study Groupa (n ⫽ 17)
Control Groupb (n ⫽ 17)
P value
30.3 ⫾ 4.1
33.8 ⫾ 10.9
.16
6.9 ⫾ 4.7 10.5 ⫾ 3.7 12.9 ⫾ 5.7 11.0 ⫾ 2.9 12.7 ⫾ 4.6 12.9 ⫾ 5.9
7.6 ⫾ 3.6 11.3 ⫾ 7.4 11.1 ⫾ 5.7 11.7 ⫾ 4.4 11.6 ⫾ 3.8 12.1 ⫾ 4.1
.22 .65 .56 .54 .43 .62
a
FIGURE. Kaplan-Meier cumulative probability of complete success (intraocular pressure <21 mm Hg without medication) for the study (trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide (TA) in treating secondary glaucoma) and control (trabeculectomy without intraoperative sub-Tenon injection of TA in treating secondary glaucoma) groups (P ⴝ .77). Note the absence of failures between 3 and 9 months in both groups.
height, extent, vascularity, and leakage with the Seidel test.17 Hypotony was defined as an IOP less than 5 mm Hg. Statistical analysis was performed using SPSS software version 15.0 (SPSS Inc, Chicago, Illinois, USA). Continuous variables were analyzed using the unpaired Student t test or paired t test as appropriate. The number of preoperative and postoperative antiglaucoma medications and the number of laser suture lysis were analyzed by Mann– Whitney U test between study and control groups. The number of antiglaucoma medications between before and after trabeculectomy was analyzed by Wilcoxon signedrank test. The 2 or Fisher exact tests were used to evaluate categorical data as appropriate. Kaplan-Meier survival analysis and the log-rank test were used to determine success rates in both groups. P values of less than .05 were considered statistically significant. Assuming a standard deviation of the IOP measurement of 20% and setting an ␣ error of .05, the minimum sample size was set at 46 with a 0.8 power to detect a difference of 15% between the groups (one-tailed test).
RESULTS FIFTY-THREE EYES OF 48 PATIENTS WERE ENROLLED IN THE
study, of which 26 were assigned to receive trabeculectomy with intraoperative sub-Tenon injection of TA (study group) and 27 were assigned to trabeculectomy without intraoperative sub-Tenon injection of TA (control group). VOL. 147, NO. 6
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Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
All patients completed the study at the 12-month follow-up visit. Preoperative data are presented for both groups in Table 1. There were no significant differences between the groups in terms of gender, age, right or left eye, base of conjunctival flap, type of glaucoma, previous intraocular surgery, number of prescribed antiglaucoma medications, preoperative IOP, and preoperative visual acuity. The Figure illustrates Kaplan-Meier survival analysis and the P value measured by 2 test for the 2 patient groups using the complete success definition. Twelve months after surgery, 17 study eyes (65.4%) and 17 control eyes (62.9%) were considered to have a complete success (P ⫽ .77). Nineteen study eyes (73.1%) and 18 control eyes (66.6%) were regarded to have a qualified and a complete success (P ⫽ .61). Mean IOPs for both groups with complete success at all visits are listed in Table 2. Postoperative IOP levels were significantly lower than preoperative levels for the 2 groups at all intervals (P ⬍ .001). IOP measurements did not differ significantly between the groups at any interval. Postoperative BCVA at 12 months did not differ significantly between the groups (study group: 0.82 ⫾ 0.75; control group: 1.01 ⫾ 0.80, P ⫽ .71). The mean number of prescribed antiglaucoma medications used in the study group dropped from a preoperative mean of 3.4 ⫾ 0.5 to a 12-month postoperative mean of 0.8 ⫾ 1.3 (P ⬍ .001), and in the control group from 3.5 ⫾ 0.8 to 1.2 ⫾ 1.5 (P ⬍ .001). The mean number of argon laser suture lysis was 1.6 ⫾ 1.9 in the control group and 0.5 ⫾ 0.5 in the study group and there was a statistically significant difference between the 2 groups (P ⫽ .03). The morphologic characteristics of the filtering blebs for both groups, defined in terms of the Indiana Bleb Appearance Grading Scale, are shown in Table 3. Data from eyes WITH
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the number of argon laser suture lysis after trabeculectomy was significantly reduced in the study group vs the control group. It has been reported that eyes that undergo laser suture lysis are more likely to have poorer IOP controls than eyes not requiring laser suture lysis.18 TA may suppress wound healing around the scleral flap and reduce the number of argon laser suture lysis postoperatively. Three previous reports were published on using corticosteroids as adjunct to glaucoma filtration surgery. Seah and associates used Surodex (Oculex Pharmaceuticals, Sunnyvale, California, USA), incorporating 60 micrograms of dexamethasone in a pellet, in phacotrabeculectomy surgery for the treatment of primary open-angle glaucoma and compared the results with phacotrabeculectomy augmented with 50 mg/ml of intraoperative 5-fluorouracil (5-FU) during the same period. There was a 20.1% decrease in IOP in the Surodex group compared with 28.5% decrease in the 5-FU group (P ⫽ .6).19 Seah and associates suggested that Surodex during phacotrabeculectomy provides surgeons with a new option in filtering surgery. Tham and associates used TA (1.2 mg) injection into filtration bleb at the conclusion of filtration surgery such as trabeculectomy, phacotrabeculectomy, and needling.9 Eleven eyes (5 primary open-angle glaucoma, 6 chronic angle-closure glaucoma) were included in this study. Tham reported that good IOP control was obtained at least by the third month. The only complication was persistent subconjunctival TA deposit in one case. Giangiacomo and associates used TA (4 mg) injection subconjunctivally before trabeculectomy in 15 eyes.20 Fourteen eyes with controlled IOP had diffuse microcystic filtration blebs by slit-lamp examination and 1 eye had a surgical failure. They concluded that the use of TA did not appear to add any additional risks to the surgical procedure or to the postoperative period. All the studies previously reported were either nonrandomized prospective or retrospective and with a small sample size. We believe our study’s strength is based on the design of its randomized prospective clinical trial. The success rate of trabeculectomy with mitomycin C for the treatment of neovascular glaucoma at 1 year is reported in about 29% to 67% of cases.21,22 Our complete success rate for neovascular glaucoma with intraoperative sub-Tenon injection of TA was 76.9% (10 eyes) and without intraoperative sub-Tenon injection of TA was 54.5% (6 eyes). Our success rate of trabeculectomy with intraoperative sub-Tenon injection of TA for the treatment of neovascular glaucoma is better than previously reported, but no statistically significant difference between the success rates of the study and control groups was shown in this study (P ⫽ .39). Jonas and associates reported that the intravitreal TA injection to neovascular glaucoma reduced rubeosis iridis and IOP.23,24 This result may imply the anti-angiogenic effect of TA. Sub-Tenon injection of TA has the possibility to increase the success rate of
TABLE 3. Bleb Morphologic Characteristics (According to the Indiana Bleb Appearance Grading Scale) 1 Year After Surgery for Study and Control Groups
Height Horizontal extent Vascularity Leakage
Study Groupa (n ⫽ 17)
Control Groupb (n ⫽ 17)
P value
2.1 ⫾ 0.8 2.1 ⫾ 0.9 1.8 ⫾ 1.0 0
1.9 ⫾ 0.8 2.0 ⫾ 0.9 2.0 ⫾ 0.9 0
.73 .92 .61 .99
a
Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
TABLE 4. Postoperative Complications for Study and Control Groups
Postoperative complications Hypotony Choroidal detachment Leakage from suture
Study Groupa (n ⫽ 26)
Control Groupb (n ⫽ 27)
P value
6 (23.1%) 2 (7.7%) 2 (7.7%)
4 (14.8%) 1 (3.7%) 5 (18.5%)
.47 — — —
a Trabeculectomy with intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma. b Trabeculectomy without intraoperative sub-Tenon injection of triamcinolone acetonide in treating secondary glaucoma.
that underwent additional surgery were excluded from the analysis because the performed interventions intentionally interfered with the morphologic features of the blebs. The 2 groups were similar in terms of bleb height, extent, vascularity, and leakage (P ⬎ .5). The complications encountered at the postoperative period are listed in Table 4. The most frequent complications were hypotony (10 eyes; 18.9%) and bleb leak at the conjunctival suture site (7 eyes; 13.2%). No statistically significant difference was found between the study and control groups about postoperative complications (P ⫽ .47). Hypotony maculopathy, late bleb leak, bleb-associated infection, and corneal decompensation were not found in any of our patients.
DISCUSSION WE DID NOT FIND ANY SIGNIFICANT DIFFERENCES BETWEEN
the success rates of trabeculectomy with intraoperative sub-Tenon injection of TA or without intraoperative injection within the 12-month follow-up period or postoperative IOP. Additionally, there was no significant difference in the morphologic characteristics of the filtering blebs and in the number of complications. However, 1058
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trabeculectomy for neovascular glaucoma with its antiangiogenic effect. Some complications associated with sub-Tenon injection of TA were previously reported. Ptosis,25 orbital fat prolapse,26 conjunctival ulceration,27 retinal and choroidal vascular occlusion,28 and cutaneous hypopigmentation29 were reported but no complications associated with intraoperative sub-Tenon injection of TA were observed in this study. Our study has several limitations. One of the limitations was that our sample size allowed us to detect only fairly large differences in success rates between trabeculectomy with or without intraoperative sub-Tenon injection of TA. Both groups included varied types of glaucomas such as neovascular glaucoma, glaucoma postpenetrating keratoplasty, uveitic glaucoma, exfoliative glaucoma, and aphakic glaucoma. TA is an anti-inflammatory drug, so the effect of TA for filtration surgery seems to be more effective for inflammatory glaucoma such as neovascular glaucoma, uveitic glaucoma, and glaucoma postpenetrating keratoplasty. Further investigation will be needed to evaluate trabeculectomy with intraoperative sub-Tenon injection
of TA for each type of glaucoma in the future. It should be noted that mitomycin C application might have masked the TA effects in this study. Future studies should incorporate an additional study group comprising only TA application in addition to the groups investigated in the current report. An interesting study group might be one receiving sub-Tenon corticosteroids at the end of the surgery, but no topical corticosteroids in the postoperative course. Given the nature of our study, another limitation was our inability to mask the intraoperative sub-Tenon TA injection procedure and the evaluation of bleb morphology, which was performed by the same investigator. This might have introduced bias in the interpretation of our results. Information from studies with such masking will provide invaluable information. In conclusion, trabeculectomy with intraoperative subTenon injection of TA for the treatment of secondary glaucoma neither increased the intermediate-term success rate nor decreased postoperative complications of trabeculectomy. Intraoperative sub-Tenon injection of TA was associated with a fewer number of laser suture lysis.
THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN DESIGN AND conduct of study (K.Y.); collection, management, analysis, and interpretation of data (K.Y., I.K.); provision of materials or patients (D.S.); critical revision and statistical expertise (Y.O.); and preparation, review, or approval of the manuscript (K.T.). This study was approved by the Ethics Committee of the Keio University School of Medicine and adhered to the tenets of the Declaration of Helsinki.
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9. Tham CC, Li FC, Leung DY, et al. Intrableb triamcinolone acetonide injection after bleb-forming filtration surgery (trabeculectomy, phacotrabeculectomy, and trabeculectomy revision by needling): a pilot study. Eye 2006;20:1484 –1486. 10. Kano K, Kuwayama Y. [Characteristics of filtering blebs after fornix-based trabeculectomy with a scleral tunnel]. Nippon Ganka Gakkai Zasshi 2005;109:285–291. 11. Kano K, Kuwayama Y, Mizunoya H. [Clinical results of fornix-based trabeculectomy with a scleral tunnel]. Nippon Ganka Gakkai Zasshi 2005;109:75– 82. 12. Shingleton BJ, Chaudhry IM, O’Donoghue MW, et al. Phacotrabeculectomy: limbus-based vs. fornix-based conjunctival flaps in fellow eyes. Ophthalmology 1999;106: 1152–1155. 13. Shigeeda T, Tomidokoro A, Chen YN, et al. Long-term follow-up of initial trabeculectomy with mitomycin C for primary open-angle glaucoma in Japanese patients. J Glaucoma 2006;15:195–199. 14. Al-Hazmi A, Zwaan J, Awad A, et al. Effectiveness and complications of mitomycin C use during pediatric glaucoma surgery. Ophthalmology 1998;105:1915–1920. 15. Lopes JF, Moster MR, Wilson RP, et al. Subconjunctival sodium hyaluronate 2.3% in trabeculectomy: a prospective randomized clinical trial. Ophthalmology 2006;113:756 –760. 16. Goulet RJ III, Phan AD, Cantor LB, WuDunn D. Efficacy of the Ahmed S2 glaucoma valve compared with the Baerveldt 250-mm2 glaucoma implant. Ophthalmology 2008;115:1141–1147. 17. Cantor LB, Mantravadi A, WuDunn D, et al. Morphologic classification of filtering blebs after glaucoma filtration surgery: the Indiana Bleb Appearance Grading Scale. J Glaucoma 2003;12:266 –271. WITH
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24. Jonas JB, Kreissig I, Degenring RF. Neovascular glaucoma treated by intravitreal triamcinolone acetonide. Acta Ophthalmol Scand 2003;81:540 –541. 25. Ideta S, Noda M, Kawamura R, Shinoda K, Inoue M, Tsubota K. Ptosis after sub-Tenon’s capsule triamcinolone. Ophthalmology 2008;115:410 – 410 e1. 26. Dal Canto AJ, Downs-Kelly E, Perry JD. Ptosis and orbital fat prolapse after posterior sub-Tenon’s capsule triamcinolone injection. Ophthalmology 2005;112:1092–1097. 27. Agrawal S, Agrawal J, Agrawal TP. Conjunctival ulceration following triamcinolone injection. Am J Ophthalmol 2003; 136:539 –540. 28. Moshfeghi DM, Lowder CY, Roth DB, Kaiser PK. Retinal and choroidal vascular occlusion after posterior sub-Tenon triamcinolone injection. Am J Ophthalmol 2002;134:132–134. 29. Gallardo MJ, Johnson DA. Cutaneous hypopigmentation following a posterior sub-Tenon triamcinolone injection. Am J Ophthalmol 2004;137:779 –780.
18. Ralli M, Nouri-Mahdavi K, Caprioli J. Outcomes of laser suture lysis after initial trabeculectomy with adjunctive mitomycin C. J Glaucoma 2006;15:60 – 67. 19. Seah SK, Husain R, Gazzard G, et al. Use of surodex in phacotrabeculectomy surgery. Am J Ophthalmol 2005;139:927–928. 20. Giangiacomo J, Dueker DK, Adelstein E. The effect of preoperative subconjunctival triamcinolone administration on glaucoma filtration. I. Trabeculectomy following subconjunctival triamcinolone. Arch Ophthalmol 1986;104:838 – 841. 21. Hyung SM, Kim SK. Mid-term effects of trabeculectomy with mitomycin C in neovascular glaucoma patients. Korean J Ophthalmol 2001;15:98 –106. 22. Kiuchi Y, Sugimoto R, Nakae K, et al. Trabeculectomy with mitomycin C for treatment of neovascular glaucoma in diabetic patients. Ophthalmologica 2006;220:383–388. 23. Jonas JB, Hayler JK, Sofker A, Panda-Jonas S. Regression of neovascular iris vessels by intravitreal injection of crystalline cortisone. J Glaucoma 2001;10:284 –287.
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Biosketch Kenya Yuki, MD was educated at and graduated from Keio University School of Medicine in Tokyo, Japan, where he completed his residency in ophthalmology, followed by a fellowship in glaucoma. He is currently pursuing his PhD, also at Keio University School of Medicine.
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SUPPLEMENTAL FIGURE. Flow chart shows the total numbers of eyes enrolled, operated, and observed during the follow-up of the study.
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