Trabeculectomy Versus Ex-Press Glaucoma Filtration Device in Silicomacrophagocytic Open Angle Glaucoma Secondary to Silicone Oil Emulsification.

PURPOSE: To compare the outcomes of Ex-PRESS device implantation versus trabeculectomy in patients with ocular hypertension after pars plana vitrectomy and silicone oil injection (SOI).
MATERIALS AND METHODS: Twenty-six consecutive eyes with ocular hypertension after pars plana vitrectomy and SOI were included in this study and randomized to one of two groups: A group treated with Ex-PRESS (model P50) placed under a scleral flap (Ex-PRESS group), and a group treated with trabeculectomy (trabeculectomy group). Complete success (intraocular pressure [IOP] <21 mmHg without medication) and qualified success rates (IOP <21 mmHg with one or two glaucoma medications) at 2 years postoperatively were analyzed. Between-groups comparison was performed with the Mann-Whitney U-test for continuous variables, and Fischer exact test for categorical data. Success rates between groups were compared using Kaplan-Meier life analysis and the log-rank test. P < 0.05 was considered statistically significant.
RESULTS: In the Ex-PRESS group, complete success was achieved in 73% eyes and qualified success in 81.8% of eyes. In the trabeculectomy group, complete success was achieved in 40% and qualified success was achieved in 60% of eyes. The difference in mean IOP between groups was statistically significant from the 3(rd) postoperative month onward (P = 0.007 at 3 months, P = 0.003 at 6 months, and P = 0.03 at 24 months).
CONCLUSION: Ex-PRESS implantation was more effective than trabeculectomy in controlling IOP in ocular hypertensives after pars plana vitrectomy and SOI, but the surgical technique may require improvement.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Silicone oil (SO) is widely used in the treatment of complex vitreoretinal diseases.12 However, a significant complication of intraocular SO is increased intraocular pressure (IOP). The etiopathogenesis of glaucoma after SO injection (SOI) is still not clear, and the real incidence varies in literature.345 IOP elevation has been observed in 5.9-48% of eyes.345

The cause of SO-related glaucoma could be a migration of emulsified oil into the anterior chamber and the trabecular meshwork, synechial angle closure, rubeosis iridis, pupillary block, and inflammation, or a combination of these factors. Prophylactic surgical inferior iridectomy reduces the risk of pupillary block glaucoma. Hence, in cases of increased IOP, SO removal is recommended.

Leaver et al.6 reported that 43% of the patients with postoperative glaucoma had SO bubbles in the anterior chamber angle. The term “emulsification” is used to describe tiny intraocular droplets of SO. One study reported emulsification of SO in 0.7%6 of oil-filled eyes, and another study reported emulsification of SO in 56%7 of oil-filled eyes. Leaver et al.6 reported one eye with glaucoma had histopathologic evidence of silicone-laden macrophages within the trabecular meshwork without evidence of structural damage to the collagen fibers and the trabecular endothelium. This observation strongly suggests obstruction as the cause of the elevated IOP.

Medical control of IOP varies considerably (30-78%)589 and more invasive treatment often required. Invasive procedures include trabeculectomy, cycloablation, and implantation of glaucoma drainage devices. Inferior outcomes have been reported with trabeculectomy and cycloablation compared to implantation of glaucoma drainage devices.8 Ishida et al.10 reported successful control of IOP over 4 years with an inferior-placed shunt tube in 76% of patients who were unresponsive to medications for minimizing the passage of SO into the bleb.

The Ex-PRESS® glaucoma filtration device (Alcon Inc., Fort Worth, TX, USA) is a small stainless steel, nonvalved flow-restricting implant, designed to lower IOP in glaucomatous eyes. Several studies have reported the efficacy of Ex-PRESS in reducing IOP in primary and secondary open angle glaucoma.111213

To date, only one series of 3 cases (case report) of Ex-PRESS implantation in open angle glaucoma secondary to SOI has been reported in the literature.14

This study compares the outcomes of the Ex-PRESS glaucoma filtration device to trabeculectomy in patients with ocular hypertension after pars plana vitrectomy and SOI.

MATERIALS AND METHODS

This was a single-center, randomized controlled study of patients with ocular hypertension after SO and par plana vitrectomy who underwent Ex-PRESS glaucoma filtration device or trabeculectomy to control IOP. The research adhered the tenets of the Declaration of Helsinki. The study was approved by the Local Ethics Committee. The procedures were fully explained to all patients, and each patient provided written informed consent.

All the patients were admitted to “Cardinal G. Panico” Hospital of Tricase for examination at the glaucoma unit. Twenty-six consecutive Caucasian patients (26 eyes) with ocular hypertension after pars plana vitrectomy and SOI were included in the study. Patients were randomly divided into two groups: One group underwent Ex-PRESS (model P50) glaucoma filtration device placement under a scleral flap (Ex-PRESS group) and; the other group underwent trabeculectomy (trabeculectomy group) [Table 1]. Low dose of mitomycin C (0.1 mg/mL) was used in both surgical procedures.

Table 1

Patient demographics and mean postoperative follow-up of patients with silcomacrophagocytic open angle glaucoma secondary to silicone oil emulsification with uncontrolled intraocular pressure who underwent treatment for elevated intraocular pressure with one of two surgeries

All patients had previously undergone scleral buckling and 23 gauge three-port pars plana vitrectomy and SO (SO - 1000 centistokes – Micromed, Pomezia, Rome) injection in the vitreous chamber for retinal detachment with giant retinal tear. Four months later, temporal access clear cornea phacoemulsification and pars plana SO extraction were performed.

Before the surgical procedure, all patients underwent a baseline examination including measurement of best-corrected visual acuity, visual field examination (24-2, Humphrey field analyzer, Humphrey Instruments, Munich, Germany), biomicroscopy, gonioscopy (Posner Diagnostic and Surgical gonioprism; Ocular Instruments Inc., Bellevue, WA, USA), fundus examination (stereoscopic retinal view using Volk +90 D lens [Volk Optical Inc., Mentor, OH, USA]), and Goldmann applanation tonometry (model AT 900; Goldmann Applanation tonometer, Haag Streit-Berne, Mason, OH, USA).

Patients were included if they had silcomacrophagocytic open angle glaucoma secondary to SO emulsification with uncontrolled IOP (>22 mmHg) under maximal tolerable antiglaucoma therapy.

Exclusion criteria were patients with IOP <22 mmHg with or without therapy, signs of neovascularization and angle closure.

Surgical procedure

A standardized surgical technique was used throughout the study period. The first part of the surgical procedure was similar between groups. The operation was performed under monitored anesthesia care using a peribulbar block; a 6-0 silk stay suture (B Braun Aesculap, Tuttlingen, Germany) was placed in the superior cornea, and the eye moved inferiorly. A 30 gauge needle was passed through the conjunctiva (at 7 mm from limbus) and it was advanced laterally in Tenon's capsule, creating a bubble; the wound bed was treated with 0.1 mg/mL mitomycin c to prevent spread over the future site of the conjunctival wound. After 3 min, the perilimbal conjunctiva was opened 5-7 mm and saline solution was injected into Tenon's capsule. The process was repeated 3 times until a total of 10 mL of balanced saline solution was used. The exposed sclera under the conjunctival flap was cleaned with gentle bipolar diathermy.

A scleral flap (4 mm × 3 mm) was created first by cutting a horizontal incision parallel to the limbus using a blade calibrated at 250 μm (BD, Waltham, MA, USA). Subsequently, a partial thickness scleral pocket was dissected with a crescent knife angled bevel up (Alcon Ophthalmic, Fort Worth, TX, USA), and finally, cutting the two side incisions.

A 4 mm × 4 mm piece of sponge soaked in mitomycin c (0.1 mg/mL) was placed under the dissected scleral flap. After an exposure time of 2 min, the sponge was removed, and the area was irrigated with 20 mL of balanced saline solution. A paracentesis was created using a 15° slit knife (Pearsalls Ltd., Taunton, UK), followed by injection of carbacolo solution (Farmigea, Pisa, Italy) and viscoelastic solution (Healon GV Pharmacia, Uppsala, Sweden) in the anterior chamber.

Then, in the trabeculectomy group, the 2.85 mm blade (Peasralls Limited) was used to enter the anterior chamber and create a sclerotomy. A 1.5 mm diameter hemispherical block of corneal trabecular tissue was excised using a trabeculectomy punch (E Janach, Como, Italy) beneath the scleral flap. An iridotomy was performed in all cases. In the Ex-PRESS group, a 27 gauge needle was used to create the sclerotomy through which the Ex-PRESS device was placed [Figure 1].

Figure 1

Ex-PRESS under scleral flap

Subsequently, in both groups, the scleral flap was closed with two 10-0 nylon interrupted sutures (Sharpoint Surgical Specialties Corporation, Reading, PA, USA) (one at each corner, with knots buried in the sclera). The conjunctiva was closed using 8-0 Safil quick interrupted sutures (B Braun Aesculap, Tuttlingen, Germany). Postoperatively, a topical fixed combination of betamethasone and chloramphenicol was instilled 4 times daily for 4 weeks and cyclopentolate 1% 1 drop 2 times daily for 2 weeks.

All procedures were performed by one surgeon from January 2012 to November 2012, and all eyes in the study had at least 2 years of postoperative follow-up. Postoperative data were collected on day 1, 7, 15 and months 1, 2, 3, 6, 12, 18, and 24 postoperatively. Complete surgical success was defined as IOP ranging from 7 mmHg to 21 mmHg without glaucoma medication. Qualified success was defined as IOP ≤21 mmHg with one or two topical medications.

Two consecutive examinations with IOP >22 mmHg with two glaucoma medications were considered a surgical failure.

Statistical analysis

Statistical data analysis was performed with MedCalc version 10.2 (MedCalc Software Bvba, Ostend, Belgium). The two groups were compared with Mann-Whitney U-test for continuous variables, and the Fischer exact test for categorical data. Success rates between groups were compared with Kaplan-Meier life analysis and the log-rank test. P < 0.05 was considered statistically significant.

RESULTS

All 26 patients (26 eyes) completed the study. IOP data for both groups are reported in Table 2.

Table 2

Postoperative intraocular pressure of patients with silcomacrophagocytic open angle glaucoma secondary to silicone oil emulsification with uncontrolled intraocular pressure who underwent treatment for elevated intraocular pressure with one of two surgeries

In the Ex-PRESS group, mean postoperative IOP was 11.54 mmHg (standard deviation [SD] 2.25) at 2 weeks, 17.4 mmHg (SD 5.1) after 12 months, and 17.8 mmHg (SD 6.2) after 24 months [Table 2].

In the trabeculectomy group, mean postoperative IOP was 10.6 mmHg (SD 1.5) at 2 weeks, 20.2 mmHg (SD 6.1) at 12 months, and 20.7 mmHg (SD 4.2) at 24 months [Table 2].

The mean IOP differences from preoperative to postoperatively were statistically significant for each treatment group (P < 0.001).

In the Ex-PRESS group, complete success was achieved in 73% eyes at 24 months postoperatively, and qualified success was achieved in 81.8% of eyes [Figure 2]. In the trabeculectomy group, at 24 months postoperatively, the complete success was achieved in 40% eyes and qualified success was achieved in 60% of eyes [Figure 2]. The number of glaucoma medications decreased from 2.8 (SD 0.42) preoperatively to 1.3 (SD 0.82) after 24 months in the trabeculectomy group. In the Ex-PRESS group, the number of glaucoma medications decreased from 2.7 (SD 0.46) preoperatively to 0.8 (SD 0.94) after 2 years. The most common early postoperative complications over the first 2 postoperative weeks were hyphema (1 [6.25%] eye in the Ex-PRESS group; 2 [18.2%] eyes in trabeculectomy group), and serous choroidal detachments (3 [18.75%] eyes in Ex-PRESS group; 1 [9%] eye in trabeculectomy group). None of the choroidal detachments required surgical drainage during the follow-up period.

Figure 2

Ex-PRESS in situ after 2 years of follow-up. It is evident the wide bleb

Six (37.5%) eyes in Ex-PRESS group and 7 (63.6%) eyes in trabeculectomy group underwent needling of the bleb for cyst formation at 6 months. There were no cases of persistent or late bleb leakage or severe complications, such as bleb infection, endophthalmitis, or choroidal hemorrhages, in both groups.

Figure 3 presents the Kaplan-Meier survival group curves for both procedures. At 2 months, there were no statistically significant differences in IOP between groups with a surgical success rate of 100%. Surgical success was achieved in 94% (SD 0.06) of eyes and 64% (SD 0.14) eyes at 3 months; 81% (SD 0.09) of eyes and 36% (SD 0.15) of eyes at 6 months; and 73% (SD 0.11) of eyes and 36% (SD 0.15) of eyes at 1 year and 2 years in the Ex-PRESS and trabeculectomy groups, respectively. After the 3rd month, Kaplan-Mayer survival analysis showed a statistically significant difference in success between groups (log-rank test 4.6; P = 0.03) for the remainder of follow-up in this study. The mean difference in IOP between groups was statistically significant from the 3rd month onward (P = 0.007 at 3 months, P = 0.003 at 6 months, and P = 0.03 at 12 and 24 months).

Figure 3

At 2 months, there was no statistically significant difference in intraocular pressure between the two groups. After the 3rd month, Kaplan-Mayer survival analysis showed a mean statistically significant difference in success between the two groups (P < 0.05) for the entire follow-up period

DISCUSSION

Elevation of IOP is a common complication of pars plana vitrectomy with SOI. There are several underlying mechanisms that may be interrelated that cause elevated IOP. In a significant proportion of cases, IOP elevation is directly related to the presence of SO in the anterior chamber, with or without emulsification and regardless of the duration of SO tamponade.

Although the removal of SO reduces IOP, 7.1-10%1516 of patients develop uncontrolled glaucoma despite medical therapy. Moisseiev et al.7 reported improved IOP in only 1 of 11 eyes after removal of emulsified oil. Honavar et al.8 observed success in 15 of 35 patients who underwent only SO removal, and in 3 of 5 patients (60%) who underwent trabeculectomy with mitomycin C (0.4 mg/ml for 3 min). However, the follow-up duration was not documented.8 Casswell and Gregor17 reported success in 5 of 9 eyes (55.55%) after trabeculectomy preceded by SO removal and no medical therapy.

A number of studies105 have suggested that implantation of glaucoma drainage device improves outcomes in lowering IOP in SO glaucoma compared to trabeculectomy. In glaucomatous eyes with and without SO endotamponade, treated with the Ahmed glaucoma valve, Ishida et al.10 reported a success rate of 47% in SO group and 76% in the group without SO (4 years follow-up). SO was identified as a risk factors for surgical failure by the Cox hazard model (risk ratio = 3.43; P = 0.04). Nguyen et al.5 reported a 60% (3 of 5 eyes) success rate with the Molteno implant and Scott et al.18 reported a 78% success rate at 1 year follow-up after implantation of the 350 mm2 Baerveldt device.

Wickham et al.19 documented ultrastructural evidence of SO in trabecular meshwork associated with a macrophage response. This study19 suggested a trabecular infiltration of SO with an associated trabeculitis and macrophages often contained phagocytosed SO.

These changes likely persist even after oil removal, and may account for the chronically raised IOP seen in eyes that had previously intraocular SO.19

Trabeculectomy in silicomacrophagocytic open-angle glaucoma is technically difficult because of conjunctival scarring from the vitreoretinal surgery resulting in poor prognosis.5

Failed trabeculectomy can be due to the presence of macrophages and an inflammatory reaction in internal ostium.

The best results obtained with glaucoma drainage device510 corroborate this hypothesis.

In our study, we recorded a statistically significant difference in success rate (37%) between Ex-PRESS device and trabeculectomy at 2 years follow-up (P = 0.03). This outcome could be because the Ex-PRESS device eliminates deposition of macrophages and subsequent inflammatory reaction to internal ostium of the trabeculectomy.

Glaucoma drainage implants are an alternative surgical option, but oil migration can occur through the tube into the subconjunctival space inciting an inflammatory reaction.2021 Souza et al.22 suggested that previous conjunctival surgery changed the conjunctival environment, and the subsequent surgical procedure can induce a proliferation of fibrous cells causing bleb encapsulation.

There are two hypotheses for the failure of surgery in silicomacrophagocytic open-angle glaucoma: The first is the scar reaction induced by the previous vitreoretinal surgery; the second is the inflammatory reaction induced by the presence of micro-droplets of SO in the subconjunctival space. The same assumptions are valid both for glaucoma drainage device and for Ex-PRESS. The outcomes of this study with Ex-PRESS are inferior to previous studies with glaucoma drainage device where the success rate ranged between 78%18 and 100%10 at 2 years follow-up.

In this study, we used low doses of mitomycin C (0.1 mg/mL) for 5 min, which has been reported as the effective dose in primary open-angle glaucoma.23 Low doses of mitomycin C may be unable to control the development of a severe reaction scar, and the use of higher doses may improve long-term results of trabeculectomy with Ex-PRESS. One drawback of our work was the small sample sizes for both groups. However, this is a relatively rare type of secondary glaucoma and enrolling a large number of patients would have taken inordinately long.

CONCLUSION

This technique could be a less-invasive surgical alternative to the drainage valves, but further follow-up studies may help establish a more effective therapeutic and surgical strategy.