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Outcome of trabeculectomy with mitomycin-C in the iridocorneal endothelial syndrome
Outcome of Trabeculectomy with Mitomycin-C in the Iridocorneal Endothelial Syndrome Ines M. Lanzl, MD,1 Richard P. Wilson, MD,2 Denise Dudley, MD,2 James J. Augsburger, MD,3 Ioannis M. Aslanides, MD, George L. Spaeth, MD2 Purpose: Eyes with iridocorneal endothelial (ICE) syndrome have a high risk of failure in glaucoma filtering surgery failing. We investigated the efficacy of trabeculectomy with intraoperative mitomycin-C application in these patients. Design: Retrospective nonrandomized comparative trial with historical controls. Participants and Controls: Ten patients with unilateral iridocorneal endothelial (ICE) syndrome were reviewed. Their intraocular pressures could not be controlled medically. In five eyes, this was the primary surgery performed. Five of the patients had undergone prior intraocular pressure–(IOP) lowering surgery that had failed at the time enrolled. Results were compared with previously published case series of similar patients treated with trabeculectomy alone or trabeculectomy and subconjunctival 5-fluorouracil injections. Intervention: Intervention consisted of trabeculectomy with a limbus-based conjunctival flap and mitomycin-C application. The dosage of mitomycin-C was 0.4 mg/ml for 1 to 4 minutes (mean, 1.9 min). Main Outcome Measures: Adequate control of IOP (without medication lower than 21 mmHg). Results: In eight eyes the IOP remained well controlled (mean IOP, 12.1 mmHg) over the entire length of available of follow-up (mean, 14.9 months). Two eyes required implantation of an aqueous tube shunt at 4 and 11 months, respectively, after trabeculectomy with mitomycin-C. One eye experienced visual loss of 3 Snellen lines because of hypotony maculopathy. Conclusions: Trabeculectomy with mitomycin-C application offers a reasonable intermediate-term success rate in ICE patients, who are otherwise at high risk for failure of filtering surgery. Ophthalmology 2000;107: 295–297 © 2000 by the American Academy of Ophthalmology. The rate of achievement of satisfactory intraocular pressure (IOP) control after trabeculectomy in patients with prognostic risk factors for surgical failure, such as uveitic glaucoma, neovascular glaucoma, African-American race, or prior surgery, can be increased by applying mitomycin-C during surgery.1–3 Mitomycin-C is used as adjunctive chemotherapy during glaucoma-filtering surgery to suppress fibroblast proliferation.4 It reduces the likelihood of undesired scarring at the filtration site. Iridocorneal endothelial (ICE) syndrome is usually subdivided into Chandler’s syndrome, progressive essential iris atrophy, and Cogan-Reese syndrome. This spectrum of disease includes the following features to a variable degree: unilaterally, iris stromal abOriginally received:May 12, 1999. Accepted: September 29, 1999. Manuscript no. 99248. Reprint requests to Ines M. Lanzl, MD, Augenklinik der Technischen Universtita˜t Mu˜nchen, Ismaninger Str. 22, 81675 Mu¨nchen, Germany. 1 Augenklinik der Technischen Universita¨t Mu¨nchen, 81675 Mu¨nchen, Germany. 2 Glaucoma Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. 3 Retina Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Reprint requests to Ines M. Lanzl, MD, Augenklinik der Technischen Universita¨t Mu¨nchen, Ismaninger Str. 22, 81675 Mu¨nchen, Germany. © 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
normalities, abnormal corneal endothelium with proliferation and secondary glaucoma caused by formation of membranes composed of endothelial-like cells and a Descemet’s-like structure, as well as closure of the angle by broad-based peripheral anterior synechiae or both.5 The cause of the ICE syndrome is unknown. The natural history of the disease is progressive. There is no known means of arresting its progression. Medical treatment of the glaucoma associated with ICE syndrome is usually ineffective.6 A wide range of surgical procedures to control the IOP in ICE syndrome has been reported in the literature, all with relatively poor success rates compared with other forms of glaucoma. The results of trabeculectomy were investigated by Laganowski et al6 and Kidd et al.7 Trabeculectomy with postoperative subconjunctival injections of 5-fluorouracil was examined by Wright et al8 The success rate for first surgeries without antimetabolites in Laganowski’s study was 60% of 22 patients after 1 year. Second and third operations had a success rate of only 20% and 17%, respectively, after 1 year of follow-up. However, this group did not specify the exact criteria for “success” in their article. Postoperative 5-fluorouracil application in a group of nine patients, eight of which had undergone previous surgery, yielded sufficient IOP control in four eyes after 6 to 54 months of follow-up. The use of mitomycin-C ISSN 0161-6420/00/$–see front matter PII SO161-6420(99)00077-9
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Ophthalmology Volume 107, Number 2, February 2000 Table 1. Demographic and Clinical Information on 10 Patients with ICE Syndrome Patient No.
Diagnosis
Age (yr)
1 2 3 4 5 6 7 8 9
EIA‡ Chandler Chandler EIA EIA EIA Chandler Chandler EIA
48 44 74 34 63 62 53 49 40
M F F F M F F F F
EIA
56
F
10
Sex
Prior Surgery Trabeculectomy Trabeculectomy None None None Trabeculectomy Trabeculectomy None Trabeculectomy ⫻ 2, penetrating keratoplasty with ECCE None
Duration of Mitomycin-C Application (min)
Success or Failure
1.0 3.5 1.5 1.5 4.0 4.0 2.0 1.5 1.0
Success Success Failure Failure Success Success Success Success Success
1.5
Success
Failure Time* (mos)
11 4
IOP Failure† (mmHg)
Total Length of Follow-up (mos)
12 13 30 42 9 13 13 4 17
12 15 17 30 9 19 11 9 1
16
10
*Failure time ⫽ length of follow-up until “failure” (as defined in “Methods”) occurred. †IOP at failure ⫽ intraocular pressure (applanation tonometry) recorded on date of “failure” (as defined in “Methods”) in patients in whom surgery failed or on last examination in patients in whom surgery did not fail. ‡EIA ⫽ essential iris atrophy.
in ICE syndrome to our knowledge has not been reported in detail. We present the results of 10 patients with ICE syndrome undergoing trabeculectomy with intraoperative mitomycin-C application for IOP control of their associated glaucoma.
Methods The charts of 10 patients with ICE syndrome and uncontrolled IOP who underwent trabeculectomy with intraoperative mitomycin-C application were reviewed retrospectively. The patients were seen between January 1996 and December 1997 in the Glaucoma Department of Wills Eye Hospital and underwent surgical management for otherwise uncontrolled IOP at that time. Uncontrolled IOP was defined as IOP ⬎ 21 mmHg on fully tolerated topical medication with progressing visual field defect. The number of medications used preoperatively ranged from 1 to 5 (mean, 2.7) different eyedrops. Surgery was performed by three different surgeons, each one using their standard technique. For their surgical management, all patients received a limbus-based conjunctival flap trabeculectomy. After hemostasis of the episclera was attained, mitomycin-C (0.4 mg/ml) was applied between the sclera and Tenon’s capsule with a Weckcell sponge for 1 to 4 minutes (mean, 1.9 min) according to the surgeon’s estimation of the desired effect in each individual patient. The entire area was carefully irrigated and the procedure continued by dissecting a limbus-based scleral flap and removing a 1.0 ⫻ 2.0-mm deep scleral block. Iridectomy was performed and the scleral flap closed with 10-0 nylon sutures followed by separate Tenon’s and conjunctival closure. The patients were followed for 9 to 30 months (mean, 14.9 months) after surgery. Time of failure was defined as the office visit at which IOP was deemed uncontrolled without IOP-lowering medication. Four patients had undergone one prior failed trabeculectomy without antimetabolites. One patient had undergone two previous filtering procedures as well as keratoplasty and cataract extraction. No antimetabolite was used in any of this patient’s previous surgeries. Characteristics of the 10 patients are shown in Table 1.
296
Results Eight of the 10 patients studied had adequate IOP control without additional topical glaucoma medication after trabeculectomy with the adjunctive use of mitomycin-C. The follow-up period ranged from 9 to 19 months. The IOP achieved was in the range of 4 to 17 mmHg (mean, 12.1 mmHg). One of these patients had visual loss of 3 Snellen lines because of hypotony maculopathy. This patient had a postoperative IOP of 4 mmHg. No other complications were noted within the follow-up period. Of the two patients with inadequate IOP control, one failed 4 months after surgery, and the other at 11 months after surgery. Their pressures were also not manageable by reinstitution of medical therapy. These two eyes were subsequently treated successfully with aqueous tube shunt surgery. (see Table 1).
Discussion Patients with ICE syndrome undergoing filtering surgery are believed to have a lower success rate than patients with most other types of glaucoma.6,9 The high failure rate in this patient population is partly attributed to their younger age and to the progressive nature of the ICE syndrome with membrane proliferation and formation of anterior synechiae, all of which can obstruct the ostium of the filtration site. Our two patients with failure, however, did not show any obstruction of their ostium on gonioscopy. Laganowski et al noticed marked subconjunctival fibrosis in his series of filter failure patients and discusses the possibility of an aggressive inflammatory response in ICE patients and subsequent increased scarring of the bleb.6 Therefore, it seems logical to try to add adjunctive antimetabolites to the filtering procedure in these high-risk patients. 5-Fluorouracil given as an antifibroblastic adjunct in the postoperative phase was investigated by Wright et al8 and described as relatively ineffective by the authors. Their patient population, however, consisted of nine patients, eight of whom had
Lanzl et al 䡠 Trabeculectomy with MMC in ICE syndrome previously failed filtration surgery. The large number of patients that previously had failed surgery might introduce a bias to the study because this constitutes an additional risk factor for failing further trabeculectomies. In this study, 8 of 10 patients had adequate IOP control after filtering surgery with mitomycin-C, with a mean follow-up of 14.9 months. Primary surgery seems to yield the best results in this patient population.6 Our study population was not homogenous in this respect either, because five patients had undergone previous surgery. However, these five patients were not the ones for whom surgery failed. Mitomycin-C inhibits or destroys fibroblasts and thus prevents excessive scarring in the bleb area, ensuring better bleb survival in high-risk cases. In addition, it is believed to reduce the ciliary body aqueous production.4 Whether it has an effect on membrane formation by ICE cells is unknown. However, mitomycin-C seems to display some kind of inhibitory effect on epithelial cells in other models of epithelial cell proliferation, such as posterior capsule opacification. Shin et al10 noted a decrease of capsular opacification with adjunctive mitomycin-C in combined glaucoma and cataract surgery. Additional surgical options include tube shunt implantation or cyclodestructive procedures. Tube shunt implantation is a more invasive procedure than trabeculectomy. In ICE syndrome it is associated with a possible dysfunction caused by membranous overgrowth of the tube lumen and dislocation of the tube. Possible damage to the already altered corneal endothelium might be another concern. In our opinion, however, it has a role in cases that have a history of failed trabeculectomies and are unmanageable otherwise, as was the case with the two failures in our study. Kim et al11 present a case series of 10 patients undergoing aqueous tube shunt surgery for management of IOP in ICE syndrome. Eight of their patients had undergone previous surgery. With a median follow-up of 55 months four of their patients had adequate IOP control, defined as IOP ⬍ 21 mmHg with or without medication, and didn’t require further interventions during the observation period. Another three eyes achieved adequate IOP control after revision of the initial aqueous shunt surgery. Cyclodestructive procedures are irreversible and in our opinion present a rather drastic measure for eyes that still have a good visual potential.
The results of our study suggest that trabeculectomy with adjunctive mitomycin-C may offer better intermediate-term success than trabeculectomy alone or with 5-fluorouracil. A large, randomized, prospective study would be necessary to prove this conclusion, a difficult proposal considering the infrequency of patients with ICE syndrome.
References 1. Mietz H, Krieglstein GK. Mitomycin-C for trabeculectomy in complicated glaucoma: preliminary results after 6 months. Ger J Ophthalmol 1994;3:164 –7. 2. Prata JA, Jr, Neves RA, Minckler DS, et al. Trabeculectomy with mitomycin-C in glaucoma associated with uveitis. Ophthalmic Surg 1994;25:616 –20. 3. Mermoud A, Salmon JF, Murray ADN. Trabeculectomy with mitomycin-C for refractory glaucoma in blacks. Am J Ophthalmol 1993;116:72– 8. 4. Nuyts RMMA, Felten PC, Pels E, et al. Histopathologic effects of mitomycin-C after trabeculectomy in human glaucomatous eyes with persistent hypotony. Am J Ophthalmol 1994;118:225–37. 5. Campbell DG, Shields MB, Smith TR. The corneal endothelium and the spectrum of essential iris atrophy. Am J Ophthalmol 1978;86:317–24. 6. Laganowski HC, Kerr Muir MG, Hitchings RA. Glaucoma and the iridocorneal endothelial syndrome. Arch Ophthalmol 1992;110:346 –50. 7. Kidd M, Hetherington J, Magee S. Surgical results in iridocorneal endothelial syndrome. Arch Ophthalmol 1988;106: 199 –201. 8. Wright MM, Grajewski AL, Cristol SM, Parrish RK. 5-Fluorouracil after trabeculectomy and the iridocorneal endothelial syndrome. Ophthalmology 1991;98:314 – 6. 9. Shields MB, Campbell DG, Simmons RJ. The essential iris atrophies. Am J Ophthalmol 1978;85:749 –59. 10. Shin DH, Kim YY, Ren J, et al. Decrease of capsular opacification with adjunctive mitomycin-C in combined glaucoma and cataract surgery. Ophthalmology 1998;105:1222– 6. 11. Kim DK, Aslanides IM, Schmidt CM Jr, et al. Long-term outcome of aqueous shunt surgery in ten patients with iridocorneal endothelial syndrome. Ophthalmology 1999; 106:1030 – 4.
297
normalities, abnormal corneal endothelium with proliferation and secondary glaucoma caused by formation of membranes composed of endothelial-like cells and a Descemet’s-like structure, as well as closure of the angle by broad-based peripheral anterior synechiae or both.5 The cause of the ICE syndrome is unknown. The natural history of the disease is progressive. There is no known means of arresting its progression. Medical treatment of the glaucoma associated with ICE syndrome is usually ineffective.6 A wide range of surgical procedures to control the IOP in ICE syndrome has been reported in the literature, all with relatively poor success rates compared with other forms of glaucoma. The results of trabeculectomy were investigated by Laganowski et al6 and Kidd et al.7 Trabeculectomy with postoperative subconjunctival injections of 5-fluorouracil was examined by Wright et al8 The success rate for first surgeries without antimetabolites in Laganowski’s study was 60% of 22 patients after 1 year. Second and third operations had a success rate of only 20% and 17%, respectively, after 1 year of follow-up. However, this group did not specify the exact criteria for “success” in their article. Postoperative 5-fluorouracil application in a group of nine patients, eight of which had undergone previous surgery, yielded sufficient IOP control in four eyes after 6 to 54 months of follow-up. The use of mitomycin-C ISSN 0161-6420/00/$–see front matter PII SO161-6420(99)00077-9
295
Ophthalmology Volume 107, Number 2, February 2000 Table 1. Demographic and Clinical Information on 10 Patients with ICE Syndrome Patient No.
Diagnosis
Age (yr)
1 2 3 4 5 6 7 8 9
EIA‡ Chandler Chandler EIA EIA EIA Chandler Chandler EIA
48 44 74 34 63 62 53 49 40
M F F F M F F F F
EIA
56
F
10
Sex
Prior Surgery Trabeculectomy Trabeculectomy None None None Trabeculectomy Trabeculectomy None Trabeculectomy ⫻ 2, penetrating keratoplasty with ECCE None
Duration of Mitomycin-C Application (min)
Success or Failure
1.0 3.5 1.5 1.5 4.0 4.0 2.0 1.5 1.0
Success Success Failure Failure Success Success Success Success Success
1.5
Success
Failure Time* (mos)
11 4
IOP Failure† (mmHg)
Total Length of Follow-up (mos)
12 13 30 42 9 13 13 4 17
12 15 17 30 9 19 11 9 1
16
10
*Failure time ⫽ length of follow-up until “failure” (as defined in “Methods”) occurred. †IOP at failure ⫽ intraocular pressure (applanation tonometry) recorded on date of “failure” (as defined in “Methods”) in patients in whom surgery failed or on last examination in patients in whom surgery did not fail. ‡EIA ⫽ essential iris atrophy.
in ICE syndrome to our knowledge has not been reported in detail. We present the results of 10 patients with ICE syndrome undergoing trabeculectomy with intraoperative mitomycin-C application for IOP control of their associated glaucoma.
Methods The charts of 10 patients with ICE syndrome and uncontrolled IOP who underwent trabeculectomy with intraoperative mitomycin-C application were reviewed retrospectively. The patients were seen between January 1996 and December 1997 in the Glaucoma Department of Wills Eye Hospital and underwent surgical management for otherwise uncontrolled IOP at that time. Uncontrolled IOP was defined as IOP ⬎ 21 mmHg on fully tolerated topical medication with progressing visual field defect. The number of medications used preoperatively ranged from 1 to 5 (mean, 2.7) different eyedrops. Surgery was performed by three different surgeons, each one using their standard technique. For their surgical management, all patients received a limbus-based conjunctival flap trabeculectomy. After hemostasis of the episclera was attained, mitomycin-C (0.4 mg/ml) was applied between the sclera and Tenon’s capsule with a Weckcell sponge for 1 to 4 minutes (mean, 1.9 min) according to the surgeon’s estimation of the desired effect in each individual patient. The entire area was carefully irrigated and the procedure continued by dissecting a limbus-based scleral flap and removing a 1.0 ⫻ 2.0-mm deep scleral block. Iridectomy was performed and the scleral flap closed with 10-0 nylon sutures followed by separate Tenon’s and conjunctival closure. The patients were followed for 9 to 30 months (mean, 14.9 months) after surgery. Time of failure was defined as the office visit at which IOP was deemed uncontrolled without IOP-lowering medication. Four patients had undergone one prior failed trabeculectomy without antimetabolites. One patient had undergone two previous filtering procedures as well as keratoplasty and cataract extraction. No antimetabolite was used in any of this patient’s previous surgeries. Characteristics of the 10 patients are shown in Table 1.
296
Results Eight of the 10 patients studied had adequate IOP control without additional topical glaucoma medication after trabeculectomy with the adjunctive use of mitomycin-C. The follow-up period ranged from 9 to 19 months. The IOP achieved was in the range of 4 to 17 mmHg (mean, 12.1 mmHg). One of these patients had visual loss of 3 Snellen lines because of hypotony maculopathy. This patient had a postoperative IOP of 4 mmHg. No other complications were noted within the follow-up period. Of the two patients with inadequate IOP control, one failed 4 months after surgery, and the other at 11 months after surgery. Their pressures were also not manageable by reinstitution of medical therapy. These two eyes were subsequently treated successfully with aqueous tube shunt surgery. (see Table 1).
Discussion Patients with ICE syndrome undergoing filtering surgery are believed to have a lower success rate than patients with most other types of glaucoma.6,9 The high failure rate in this patient population is partly attributed to their younger age and to the progressive nature of the ICE syndrome with membrane proliferation and formation of anterior synechiae, all of which can obstruct the ostium of the filtration site. Our two patients with failure, however, did not show any obstruction of their ostium on gonioscopy. Laganowski et al noticed marked subconjunctival fibrosis in his series of filter failure patients and discusses the possibility of an aggressive inflammatory response in ICE patients and subsequent increased scarring of the bleb.6 Therefore, it seems logical to try to add adjunctive antimetabolites to the filtering procedure in these high-risk patients. 5-Fluorouracil given as an antifibroblastic adjunct in the postoperative phase was investigated by Wright et al8 and described as relatively ineffective by the authors. Their patient population, however, consisted of nine patients, eight of whom had
Lanzl et al 䡠 Trabeculectomy with MMC in ICE syndrome previously failed filtration surgery. The large number of patients that previously had failed surgery might introduce a bias to the study because this constitutes an additional risk factor for failing further trabeculectomies. In this study, 8 of 10 patients had adequate IOP control after filtering surgery with mitomycin-C, with a mean follow-up of 14.9 months. Primary surgery seems to yield the best results in this patient population.6 Our study population was not homogenous in this respect either, because five patients had undergone previous surgery. However, these five patients were not the ones for whom surgery failed. Mitomycin-C inhibits or destroys fibroblasts and thus prevents excessive scarring in the bleb area, ensuring better bleb survival in high-risk cases. In addition, it is believed to reduce the ciliary body aqueous production.4 Whether it has an effect on membrane formation by ICE cells is unknown. However, mitomycin-C seems to display some kind of inhibitory effect on epithelial cells in other models of epithelial cell proliferation, such as posterior capsule opacification. Shin et al10 noted a decrease of capsular opacification with adjunctive mitomycin-C in combined glaucoma and cataract surgery. Additional surgical options include tube shunt implantation or cyclodestructive procedures. Tube shunt implantation is a more invasive procedure than trabeculectomy. In ICE syndrome it is associated with a possible dysfunction caused by membranous overgrowth of the tube lumen and dislocation of the tube. Possible damage to the already altered corneal endothelium might be another concern. In our opinion, however, it has a role in cases that have a history of failed trabeculectomies and are unmanageable otherwise, as was the case with the two failures in our study. Kim et al11 present a case series of 10 patients undergoing aqueous tube shunt surgery for management of IOP in ICE syndrome. Eight of their patients had undergone previous surgery. With a median follow-up of 55 months four of their patients had adequate IOP control, defined as IOP ⬍ 21 mmHg with or without medication, and didn’t require further interventions during the observation period. Another three eyes achieved adequate IOP control after revision of the initial aqueous shunt surgery. Cyclodestructive procedures are irreversible and in our opinion present a rather drastic measure for eyes that still have a good visual potential.
The results of our study suggest that trabeculectomy with adjunctive mitomycin-C may offer better intermediate-term success than trabeculectomy alone or with 5-fluorouracil. A large, randomized, prospective study would be necessary to prove this conclusion, a difficult proposal considering the infrequency of patients with ICE syndrome.
References 1. Mietz H, Krieglstein GK. Mitomycin-C for trabeculectomy in complicated glaucoma: preliminary results after 6 months. Ger J Ophthalmol 1994;3:164 –7. 2. Prata JA, Jr, Neves RA, Minckler DS, et al. Trabeculectomy with mitomycin-C in glaucoma associated with uveitis. Ophthalmic Surg 1994;25:616 –20. 3. Mermoud A, Salmon JF, Murray ADN. Trabeculectomy with mitomycin-C for refractory glaucoma in blacks. Am J Ophthalmol 1993;116:72– 8. 4. Nuyts RMMA, Felten PC, Pels E, et al. Histopathologic effects of mitomycin-C after trabeculectomy in human glaucomatous eyes with persistent hypotony. Am J Ophthalmol 1994;118:225–37. 5. Campbell DG, Shields MB, Smith TR. The corneal endothelium and the spectrum of essential iris atrophy. Am J Ophthalmol 1978;86:317–24. 6. Laganowski HC, Kerr Muir MG, Hitchings RA. Glaucoma and the iridocorneal endothelial syndrome. Arch Ophthalmol 1992;110:346 –50. 7. Kidd M, Hetherington J, Magee S. Surgical results in iridocorneal endothelial syndrome. Arch Ophthalmol 1988;106: 199 –201. 8. Wright MM, Grajewski AL, Cristol SM, Parrish RK. 5-Fluorouracil after trabeculectomy and the iridocorneal endothelial syndrome. Ophthalmology 1991;98:314 – 6. 9. Shields MB, Campbell DG, Simmons RJ. The essential iris atrophies. Am J Ophthalmol 1978;85:749 –59. 10. Shin DH, Kim YY, Ren J, et al. Decrease of capsular opacification with adjunctive mitomycin-C in combined glaucoma and cataract surgery. Ophthalmology 1998;105:1222– 6. 11. Kim DK, Aslanides IM, Schmidt CM Jr, et al. Long-term outcome of aqueous shunt surgery in ten patients with iridocorneal endothelial syndrome. Ophthalmology 1999; 106:1030 – 4.
297