- Email: [email protected]
Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: Pilot study
ARTICLE
Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: Pilot study Arsham Sheybani, MD, Markus Lenzhofer, MD, Melchior Hohensinn, MD, Herbert Reitsamer, MD, Iqbal Ike K. Ahmed, MD
PURPOSE: To study the effect on intraocular pressure (IOP) of implanting a new gelatin stent at the time of cataract surgery in the treatment of open-angle glaucoma (OAG). SETTING: Multicenter university and private-practice settings. DESIGN: Nonrandomized prospective clinical trial. METHODS: The implantation of 2 models of a gelatin stent (Xen140 and Xen63) was performed at the time of cataract surgery without mitomycin-C. Complete success was defined as a postoperative IOP of less than 18 mm Hg and more than a 20% reduction in IOP at 12 months without glaucoma medication. Failure was defined as loss of light perception vision or worse, a need for additional glaucoma surgery, or less than a 20% reduction in the IOP from baseline. RESULTS: The study included 37 eyes of 37 patients. The mean preoperative IOP was 22.4 mm Hg G 4.2 (SD) on 2.5 G 1.4 medication classes. Twelve months postoperatively, the mean IOP was reduced to 15.4 G 3.0 mm Hg on 0.9 G 1.0 medication classes (P < .0001). This resulted in a qualified success of 85.3% and a complete success rate off medications of 47.1%. There were no failures. CONCLUSION: Cataract surgery combined with implantation of the gelatin stent resulted in a significant reduction in IOP in eyes with OAG. Financial Disclosure: Dr. Sheybani has received travel reimbursement from Aquesys, Inc. Dr. Ahmed is a paid consultant to Aquesys, Inc. No other author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2015; 41:1905–1909 Q 2015 ASCRS and ESCRS
Submitted: December 12, 2014. Final revision submitted: January 19, 2015. Accepted: January 25, 2015. From the Department of Ophthalmology and Visual Sciences (Sheybani), Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA; Department of Ophthalmology (Lenzhofer, Hohensinn, Reitsamer), University Clinic Salzburg/ SALK and Paracelsus Medical University (Reitsamer), Salzburg, Austria; Department of Ophthalmology and Vision Sciences (Ahmed), University of Toronto, Toronto, Credit Valley Eye Care (Ahmed), and Trillium Health Partners (Ahmed), Mississauga, Ontario, Canada. Supported by Aquesys, Inc., Aliso Viejo, California, USA. Corresponding author: Iqbal Ike K. Ahmed, MD, Credit Valley Eye Care, 3200 Erin Mills Parkway, Unit 1 Millway Plaza, Mississauga, Ontario L5L 1W8, Canada. E-mail: [email protected]. Q 2015 ASCRS and ESCRS Published by Elsevier Inc.
Glaucoma and cataract are often treated in a combined surgery, and this might decrease the burden of multiple surgeries.1,2 Although cataract surgery alone might result in a 2 to 4 mm Hg reduction in intraocular pressure (IOP),3,4 patients with glaucoma might require additional procedures to achieve IOP control. Depending on the surgical procedure, glaucoma surgery might add significant additional risk.5,6 In retrospective and prospective studies,5,7–9 combined phacoemulsification with trabeculectomy or tube shunt surgery has resulted in wound leaks, hypotony, shallow chambers, and choroidal effusions. The Xen microfistula implant (Aquesys, Inc.) is a new device that is delivered ab interno for the surgical treatment of glaucoma. The device shunts aqueous humor from the anterior chamber to the subconjunctival space. By design, it does not require a conjunctival http://dx.doi.org/10.1016/j.jcrs.2015.01.019 0886-3350
1905
1906
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
incision, which is a potential advantage over traditional filtering surgery.10 This study evaluated IOP reduction after combined phacoemulsification and implantation of the microfistula gelatin stent without adjuvant mitomycin-C (MMC) in the treatment of open-angle glaucoma (OAG). It analyzed the initial experience with 2 lumen width variations of the device. PATIENTS AND METHODS This nonrandomized prospective pilot study was performed at 7 international centers. The same surgeon at each site performed the operations. The institutional review board at each site approved the study. Before surgery, patients provided informed consent to the new procedure and lack of significant clinical experience with the implant. Patients were eligible if they had a diagnosis of OAG (including exfoliative and pigmentary glaucoma), a visually significant cataract, uncontrolled IOP despite maximum tolerated medical therapy, and at least 2 clock hours of mobile conjunctiva in the quadrant of planned device placement and if 2 consecutive IOP readings were more than 18 mm Hg and less than 35 mm Hg with or without medication. There was no medication washout period. Exclusion criteria included previous cataract surgery, a history of uveitis, or previous corneal surgery of any kind. Patients with glaucoma other than the types listed above were excluded. Patients with previous glaucoma surgery and/or laser treatment were eligible. After a complete preoperative clinical examination, postoperative evaluations were performed at 1 day; 1 and 2 weeks; and 1, 3, 6, 9, and 12 months, or more frequently as required. At every visit, a clinical history was taken and the following clinical assessments were performed: visual acuity, IOP measured by Goldmann applanation tonometry (2 measurements in each eye), slitlamp examination, gonioscopy, and posterior pole examination.
Ab Interno Gel Stent The device has been described in detail.10 Briefly, the gelatin implant is manufactured from porcine- or bovinederived collagen. It is crosslinked to achieve permanence in tissue. Given the pilot nature of this study, 2 versions were used. The Xen140 has an inner diameter of 140 mm and an outer diameter of 310 mm and is 6.0 mm long. It offers virtually no resistance to flow. The Xen63 has an inner lumen of 63 mm and an outer diameter of 240 mm and is 6.0 mm long. If offers 2 to 3 mm Hg of outflow resistance at physiologic aqueous humor production rates calculated with the Hagen-Poiseuille equation.
Surgical Technique After routine clear corneal phacoemulsification with intraocular lens implantation, the anterior chamber was filled with a highly cohesive ophthalmic viscosurgical device (OVD) until the globe was fairly firm (approximately 30 mm Hg). An inserter preloaded with the implant was placed through the temporal clear corneal incision (CCI). Depending on the surgeon's preference, a mirrored gonioscopy lens was used to verify placement through the anterior chamber angle, avoiding the iris insertion; however, this
was not standardized. The handheld inserter consisted of a 27-gauge needle that housed the implant. This was used to penetrate the angle, tunnel through the sclera, and arise approximately 3.0 mm posterior to the limbus as marked by surgical blue ink. A dial on the inserter was then rotated, initially pushing the implant into the subconjunctival space. With further rotation of the dial, the implant remained in position and the needle housing the implant retracted without drawing the implant back into the anterior chamber. Ideal placement consisted of 2.0 mm of exposed implant in the subconjunctival space and 1.0 mm in the anterior chamber, with 3.0 mm tunneled through sclera. The OVD was then irrigated from the anterior chamber and the wounds hydrated and/or sutured to achieve a watertight CCI. The formation of a bleb was readily visible. Confirmation of placement in the anterior chamber was verified after each case (Figure 1). On the day of surgery, all glaucoma medications were discontinued in the operative eye. Postoperatively, prednisolone acetate 1.0% drops were placed in the operative eye 4 times each day for 1 month and then slowly tapered over the following month. Antibiotic drop prophylaxis was not standardized; the treating surgeon selected the medication and dosage. Glaucoma medications were added over the postoperative course as needed. Postoperative needling with MMC was performed as needed if the IOP was above target (as determined by the physician) and the bleb was flat. This was performed by sweeping a 27-gauge hypodermic needle in the subconjunctival space around the device with or without the use of an antimetabolite.
Statistical Analysis Complete success was defined as a postoperative IOP of more than 5 mm Hg and less than 18 mm Hg and a more than 20% reduction in IOP without glaucoma medications at 12 months. Qualified success was defined as a postoperative IOP of more than 5 mm Hg and less than 18 mm Hg with a 20% reduction in IOP at 12 months with or without glaucoma medication. Failure was defined as loss of light perception acuity or worse, the need for additional glaucoma surgery, an IOP of less than 5 mm Hg for 2 consecutive visits after 3 months or at the last visit, or a less than 20% reduction in IOP from baseline at 12 months. A P value less than 0.05 was considered statistically significant as calculated by a paired t test for normally distributed data determined by plotting a histogram. Data are presented with mean values and standard deviations where applicable and unless otherwise indicated.
RESULTS Thirty-seven eyes of 37 patients met inclusion and exclusion criteria and were included in the study. Table 1 shows the baseline patient demographics and characteristics. Two patients were intolerant to medications and were not on topical therapy before surgery. Three patients (8%) had previous cyclodestructive procedures. No patient had previous incisional glaucoma surgery. Three patients were lost to follow-up, and these results were censored. No patient required additional glaucoma surgery. All cataract surgeries were uneventful. The mean preoperative logMAR corrected
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
1907
Figure 1. Device implantation technique. Pictures from surgical videos showing the technique are not from any patient in this trial. A: Needle inserter housing the implant is placed through a CCI. B: Gonioscopy view of inserter engaging at the level of trabecular meshwork/ scleral spur. C: The inserter tunneled through sclera rising 3.0 mm posterior to limbus. D: The implant is visible beneath the conjunctiva after successful deployment. E: Bleb formation over the device after evacuation of the OVD and injection of a balanced salt solution in the anterior chamber. F: Visualization of the proper placement of the device in the angle.
distance visual acuity was 0.30, which improved to 0.12 at 12 months (P Z .01). Twelve patients (32%) required needling and of those, 6 were needled with MMC and 6 were needled with 5fluorouracil. Patients were needled by the first month (n Z 6), within 1 to 3 months (n Z 4), within 4 to 6 Table 1. Baseline patient demographics and characteristics (N Z 37). Parameter Age (y) Mean G SD Range Sex, n (%) Men Women Ethnicity, n (%) White Hispanic Asian Black Medicated IOP (mm Hg) Mean G SD Preoperative medications Mean G SD Glaucoma type, n (%) Primary open angle Exfoliation Pigmentary Previous glaucoma procedures, n (%) Argon or selective laser trabeculoplasty Transscleral cyclophotocoagulation IOP Z intraocular pressure
Value 69.6 G 7.7 48.4, 79.2 14 (38) 23 (62) 23 (62) 5 (13.5) 5 (13.5) 4 (11) 22.4 G 4.2 2.5 G 1.4 27 (73) 9 (24) 1 (3) 11 (30) 3 (8)
months (n Z 1), or within 7 to 12 months (n Z 1). The mean IOP before needling was 25.4 mm Hg. The mean postoperative needling IOP was 13.3 mm Hg (P ! .005). Two patients with the Xen140 had 1 anterior chamber refill in the first week, resulting in a stable anterior chamber by the second week. Thirteen patients (9 of which had the Xen140) had an IOP of less than 5 mm Hg 1 day postoperatively. At 1 week, 4 patients had an IOP of less than 5 mm Hg. By 2 weeks, 1 patient had an IOP of less than 5 mm Hg. No patient had an IOP of less than 5 mm Hg at the 1-month postoperative evaluation. Over 12 months, no endophthalmitis, wound leak, device exposure or migration, macular edema, choroidal effusion or hemorrhage, iritis, or retinal detachment occurred. Patients were on a mean of 2.5 G 1.4 medication classes with a mean preoperative IOP of 22.4 G 4.2 mm Hg. The mean IOP at 12 months was reduced to 15.4 G 3.0 mm Hg on a mean of 0.9 G 1.0 medication classes (P ! .0001 for IOP and medications) (Figure 2). This resulted in a qualified success of 85.3% (29 of 34 patients [3 were lost to follow-up]) and a complete success rate off medications of 47.1% (16 of 34) (Figure 3). Seventeen patients (50%) were completely off medications at 12 months compared with 2 patients (5%) preoperatively. No patient was on additional medications compared with baseline. There was no difference in outcomes or complications between the 2 models of the device. DISCUSSION The Xen microfistula implant is a new device that shunts aqueous from the anterior chamber to the
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
1908
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
Figure 2. Mean IOP, number of medications, and percentage change in IOP over time. Error bars represent standard deviation in mean IOP (IOP Z intraocular pressure; meds Z medications).
subconjunctival space. This is performed through an ab interno approach for the surgical treatment of OAG. The procedure can be done without a conjunctival incision, potentially avoiding early postoperative wound-associated complications. In this small pilot study, implantation of the gelatin stent resulted in a significant reduction in IOP when combined with cataract surgery. This study was neither powered nor designed to address safety, and given the lack of a control group, any comparisons to other combined glaucoma procedures are limited. The purpose of this pilot study was to determine whether phacoemulsification with concomitant placement of the gelatin implant would result in significantly lower IOPs from baseline with a reduction in medications. Intraocular pressure was reduced by a mean of 7.0 mm Hg with a mean reduction of 1.6 medication classes. This resulted in a qualified success rate of 85.3% after 12 months. The complete success rate of 47.1% should be analyzed with regard to the strict criteria for complete success (at least 20% IOP reduction from baseline without medications and no hypotony). We suspect that these rates would be higher and the needling rate of 32%
Figure 3. Kaplan-Meier survival curves of cumulative probability of success with and without glaucoma medications (med).
would be lower had this procedure been performed with MMC at the time of implantation (data collection and analysis ongoing). Performing the surgery with MMC might increase the risk for late bleb-related complications. A potential advantage of implanting the gelatin stent over performing trabeculectomy is that no conjunctival incision is required. Although this might reduce the risk for early bleb-related complications, we acknowledge that late bleb-related complications associated with MMC are possible with this device. There were no cases of prolonged hypotony, lens– corneal touch, or device erosion. There is concern that a subconjunctival device left bare might erode. We acknowledge this concern; however, the gel stent is approximately 100 times more flexible10 than the silicone tubing used in traditional tube-shunt surgery. This allows the device to conform to tissue, to bend more easily with blinking and compression, and theoretically to provide less force when contacting overlying conjunctival tissue. There are several limitations to this study. Given that it was a pilot trial, several issues arise from the study design. There was no control group for comparison, so the effect of phacoemulsification alone cannot be accounted for. Although previous studies show only mild IOP-lowering effects of phacoemulsification alone, in patients with uncontrolled glaucoma the risk for an IOP spike and need for additional surgery is significant.11–13 The device is still undergoing development; therefore, the inner lumen size was not standardized and 2 different lumen sizes were studied. In addition, postoperative management was not standardized across centers because these results are from the surgeons' first experiences with the implant. Theoretically, minimizing subconjunctival inflammation might improve success in bleb-forming procedures. Phacoemulsification combined with trabeculectomy can induce inflammation that might cause blebs to fail.14–16 The ability to implant the device ab interno might limit trauma to the subconjunctival space, limiting inflammation and decreasing the
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
risk for bleb failure. Given the risks associated with trabeculectomy, alternative methods for achieving subconjunctival filtration with a better safety profile might be beneficial for some patients. For these reasons, studies comparing phacoemulsification combined with trabeculectomy or tube-shunt surgery and phacoemulsification combined with implantation of these gel stents are needed. A U.S. Food and Drug Administration study analyzing the Xen45 (45 mm inner lumen) with adjuvant MMC is currently ongoing.17 In addition, a phase 4 trial comparing the IOP-lowering effect of the device to cataract surgery in combination with the device is underway in Europe. Pending those results, future studies directly comparing the device to trabeculectomy might be warranted. In conclusion, the gel stent combined with phacoemulsification reduced IOP and medications without significant complications in patients with OAG and cataract.
5.
6.
7.
8.
9.
10.
WHAT WAS KNOWN Subconjunctival filtration surgery can be combined with cataract surgery to decrease the IOP for the treatment of OAG. WHAT THIS PAPER ADDS Ab interno placement of a gel stent shunting aqueous humor from the anterior chamber to the subconjunctival space reduced IOP without requiring a conjunctival incision. Cataract surgery performed in conjunction with placement of the microfistula gel implant achieved a significant reduction in IOP with few complications.
REFERENCES
11.
12.
13.
14.
15.
1. Verges C, Cazal J, Lavin C. Surgical strategies in patients with cataract and glaucoma. Curr Opin Ophthalmol 2005; 16:44–52 2. Casson RJ, Salmon JF. Combined surgery in the treatment of patients with cataract and primary open-angle glaucoma. J Cataract Refract Surg 2001; 27:1854–1863 3. Poley BJ, Lindstrom RL, Samuelson TW. Long-term effects of phacoemulsification with intraocular lens implantation in normotensive and ocular hypertensive eyes. J Cataract Refract Surg 2008; 34:735–742 4. Mansberger SL, Gordon MO, Jampel H, Bhorade A, Brandt JD, Wilson B, Kass MA; for the Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study.
16.
17.
1909
Ophthalmology 2012; 119:1826–1831. Available at: http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3426647/pdf/nihms36 1980.pdf. Accessed June 29, 2015 Tham CCY, Kwong YYY, Baig N, Leung DYL, Li FCH, Lam DSC. Phacoemulsification versus trabeculectomy in medically uncontrolled chronic angle-closure glaucoma without cataract. Ophthalmology 2013; 120:62–67 Samuelson TW, Katz LJ, Wells JM, Duh Y-J, Giamporcaro JE; for the US iStent Study Group. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthalmology 2011; 118:459–467 Liaska A, Papaconstantinou D, Georgalas I, Koutsandrea C, Theodosiadis P, Chatzistefanou K. Phaco-trabeculectomy in controlled, advanced, open-angle glaucoma and cataract: parallel, randomized clinical study of efficacy and safety. Semin Ophthalmol 2014; 29:226–235 Hoffman KB, Feldman RM, Budenz DL, Gedde SJ, Chacra GA, Schiffman JC. Combined cataract extraction and Baerveldt glaucoma drainage implant; indications and outcomes. Ophthalmology 2002; 109:1916–1920 € ke C, Dietlein TS, Lu €ke M, Konen W, Krieglstein GK. A proLu spective trial of phaco-trabeculotomy combined with deep sclerectomy versus phaco-trabeculectomy. Graefes Arch Clin Exp Ophthalmol 2008; 246:1163–1168 Lewis RA. Ab interno approach to the subconjunctival space using a collagen glaucoma stent. J Cataract Refract Surg 2014; 40:1301–1306 Slabaugh MA, Bojikian KD, Moore DB, Chen PP. The effect of phacoemulsification on intraocular pressure in medically controlled open-angle glaucoma patients. Am J Ophthalmol 2014; 157:26–31 Iancu R, Corbu C. Intraocular pressure after phacoemulsification in patients with uncontrolled primary open angle glaucoma. J Med Life 2014; 7:11–16. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3956089/pdf/JMedLife-07-11.pdf. Accessed June 29, 2015 Slabaugh MA, Bojikian KD, Moore DB, Chen PP. Risk factors for acute postoperative intraocular pressure elevation after phacoemulsification in glaucoma patients. J Cataract Refract Surg 2014; 40:538–544 Siriwardena D, Kotecha A, Minassian D, Dart JKG, Khaw PT. Anterior chamber flare after trabeculectomy and after phacoemulsification. Br J Ophthalmol 2000; 84:1056–1057. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1723662/pdf/ v084p01056.pdf. Accessed June 29, 2105 Friedman DS, Jampel HD, Lubomski LH, Kempen JH, Quigley H, Congdon N, Levkovitch-Verbin H, Robinson KA, Bass EB. Surgical strategies for coexisting glaucoma and cataract; an evidence-based update. Ophthalmology 2002; 109:1902–1913 Lochhead J, Casson RJ, Salmon JF. Long term effect on intraocular pressure of phacotrabeculectomy compared to trabeculectomy. Br J Ophthalmol 2003; 87:850–852. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1771770/pdf/ bjo08700850.pdf. Accessed June 29, 2015 U.S. National Institutes of Health Clinical Trials. AqueSys XEN 45 Glaucoma Implant in Refractory Glaucoma. NCT02036541. Available at: https://clinicaltrials.gov/ct2/show/NCT02036541. Accessed June 29, 2015
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: Pilot study Arsham Sheybani, MD, Markus Lenzhofer, MD, Melchior Hohensinn, MD, Herbert Reitsamer, MD, Iqbal Ike K. Ahmed, MD
PURPOSE: To study the effect on intraocular pressure (IOP) of implanting a new gelatin stent at the time of cataract surgery in the treatment of open-angle glaucoma (OAG). SETTING: Multicenter university and private-practice settings. DESIGN: Nonrandomized prospective clinical trial. METHODS: The implantation of 2 models of a gelatin stent (Xen140 and Xen63) was performed at the time of cataract surgery without mitomycin-C. Complete success was defined as a postoperative IOP of less than 18 mm Hg and more than a 20% reduction in IOP at 12 months without glaucoma medication. Failure was defined as loss of light perception vision or worse, a need for additional glaucoma surgery, or less than a 20% reduction in the IOP from baseline. RESULTS: The study included 37 eyes of 37 patients. The mean preoperative IOP was 22.4 mm Hg G 4.2 (SD) on 2.5 G 1.4 medication classes. Twelve months postoperatively, the mean IOP was reduced to 15.4 G 3.0 mm Hg on 0.9 G 1.0 medication classes (P < .0001). This resulted in a qualified success of 85.3% and a complete success rate off medications of 47.1%. There were no failures. CONCLUSION: Cataract surgery combined with implantation of the gelatin stent resulted in a significant reduction in IOP in eyes with OAG. Financial Disclosure: Dr. Sheybani has received travel reimbursement from Aquesys, Inc. Dr. Ahmed is a paid consultant to Aquesys, Inc. No other author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2015; 41:1905–1909 Q 2015 ASCRS and ESCRS
Submitted: December 12, 2014. Final revision submitted: January 19, 2015. Accepted: January 25, 2015. From the Department of Ophthalmology and Visual Sciences (Sheybani), Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA; Department of Ophthalmology (Lenzhofer, Hohensinn, Reitsamer), University Clinic Salzburg/ SALK and Paracelsus Medical University (Reitsamer), Salzburg, Austria; Department of Ophthalmology and Vision Sciences (Ahmed), University of Toronto, Toronto, Credit Valley Eye Care (Ahmed), and Trillium Health Partners (Ahmed), Mississauga, Ontario, Canada. Supported by Aquesys, Inc., Aliso Viejo, California, USA. Corresponding author: Iqbal Ike K. Ahmed, MD, Credit Valley Eye Care, 3200 Erin Mills Parkway, Unit 1 Millway Plaza, Mississauga, Ontario L5L 1W8, Canada. E-mail: [email protected]. Q 2015 ASCRS and ESCRS Published by Elsevier Inc.
Glaucoma and cataract are often treated in a combined surgery, and this might decrease the burden of multiple surgeries.1,2 Although cataract surgery alone might result in a 2 to 4 mm Hg reduction in intraocular pressure (IOP),3,4 patients with glaucoma might require additional procedures to achieve IOP control. Depending on the surgical procedure, glaucoma surgery might add significant additional risk.5,6 In retrospective and prospective studies,5,7–9 combined phacoemulsification with trabeculectomy or tube shunt surgery has resulted in wound leaks, hypotony, shallow chambers, and choroidal effusions. The Xen microfistula implant (Aquesys, Inc.) is a new device that is delivered ab interno for the surgical treatment of glaucoma. The device shunts aqueous humor from the anterior chamber to the subconjunctival space. By design, it does not require a conjunctival http://dx.doi.org/10.1016/j.jcrs.2015.01.019 0886-3350
1905
1906
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
incision, which is a potential advantage over traditional filtering surgery.10 This study evaluated IOP reduction after combined phacoemulsification and implantation of the microfistula gelatin stent without adjuvant mitomycin-C (MMC) in the treatment of open-angle glaucoma (OAG). It analyzed the initial experience with 2 lumen width variations of the device. PATIENTS AND METHODS This nonrandomized prospective pilot study was performed at 7 international centers. The same surgeon at each site performed the operations. The institutional review board at each site approved the study. Before surgery, patients provided informed consent to the new procedure and lack of significant clinical experience with the implant. Patients were eligible if they had a diagnosis of OAG (including exfoliative and pigmentary glaucoma), a visually significant cataract, uncontrolled IOP despite maximum tolerated medical therapy, and at least 2 clock hours of mobile conjunctiva in the quadrant of planned device placement and if 2 consecutive IOP readings were more than 18 mm Hg and less than 35 mm Hg with or without medication. There was no medication washout period. Exclusion criteria included previous cataract surgery, a history of uveitis, or previous corneal surgery of any kind. Patients with glaucoma other than the types listed above were excluded. Patients with previous glaucoma surgery and/or laser treatment were eligible. After a complete preoperative clinical examination, postoperative evaluations were performed at 1 day; 1 and 2 weeks; and 1, 3, 6, 9, and 12 months, or more frequently as required. At every visit, a clinical history was taken and the following clinical assessments were performed: visual acuity, IOP measured by Goldmann applanation tonometry (2 measurements in each eye), slitlamp examination, gonioscopy, and posterior pole examination.
Ab Interno Gel Stent The device has been described in detail.10 Briefly, the gelatin implant is manufactured from porcine- or bovinederived collagen. It is crosslinked to achieve permanence in tissue. Given the pilot nature of this study, 2 versions were used. The Xen140 has an inner diameter of 140 mm and an outer diameter of 310 mm and is 6.0 mm long. It offers virtually no resistance to flow. The Xen63 has an inner lumen of 63 mm and an outer diameter of 240 mm and is 6.0 mm long. If offers 2 to 3 mm Hg of outflow resistance at physiologic aqueous humor production rates calculated with the Hagen-Poiseuille equation.
Surgical Technique After routine clear corneal phacoemulsification with intraocular lens implantation, the anterior chamber was filled with a highly cohesive ophthalmic viscosurgical device (OVD) until the globe was fairly firm (approximately 30 mm Hg). An inserter preloaded with the implant was placed through the temporal clear corneal incision (CCI). Depending on the surgeon's preference, a mirrored gonioscopy lens was used to verify placement through the anterior chamber angle, avoiding the iris insertion; however, this
was not standardized. The handheld inserter consisted of a 27-gauge needle that housed the implant. This was used to penetrate the angle, tunnel through the sclera, and arise approximately 3.0 mm posterior to the limbus as marked by surgical blue ink. A dial on the inserter was then rotated, initially pushing the implant into the subconjunctival space. With further rotation of the dial, the implant remained in position and the needle housing the implant retracted without drawing the implant back into the anterior chamber. Ideal placement consisted of 2.0 mm of exposed implant in the subconjunctival space and 1.0 mm in the anterior chamber, with 3.0 mm tunneled through sclera. The OVD was then irrigated from the anterior chamber and the wounds hydrated and/or sutured to achieve a watertight CCI. The formation of a bleb was readily visible. Confirmation of placement in the anterior chamber was verified after each case (Figure 1). On the day of surgery, all glaucoma medications were discontinued in the operative eye. Postoperatively, prednisolone acetate 1.0% drops were placed in the operative eye 4 times each day for 1 month and then slowly tapered over the following month. Antibiotic drop prophylaxis was not standardized; the treating surgeon selected the medication and dosage. Glaucoma medications were added over the postoperative course as needed. Postoperative needling with MMC was performed as needed if the IOP was above target (as determined by the physician) and the bleb was flat. This was performed by sweeping a 27-gauge hypodermic needle in the subconjunctival space around the device with or without the use of an antimetabolite.
Statistical Analysis Complete success was defined as a postoperative IOP of more than 5 mm Hg and less than 18 mm Hg and a more than 20% reduction in IOP without glaucoma medications at 12 months. Qualified success was defined as a postoperative IOP of more than 5 mm Hg and less than 18 mm Hg with a 20% reduction in IOP at 12 months with or without glaucoma medication. Failure was defined as loss of light perception acuity or worse, the need for additional glaucoma surgery, an IOP of less than 5 mm Hg for 2 consecutive visits after 3 months or at the last visit, or a less than 20% reduction in IOP from baseline at 12 months. A P value less than 0.05 was considered statistically significant as calculated by a paired t test for normally distributed data determined by plotting a histogram. Data are presented with mean values and standard deviations where applicable and unless otherwise indicated.
RESULTS Thirty-seven eyes of 37 patients met inclusion and exclusion criteria and were included in the study. Table 1 shows the baseline patient demographics and characteristics. Two patients were intolerant to medications and were not on topical therapy before surgery. Three patients (8%) had previous cyclodestructive procedures. No patient had previous incisional glaucoma surgery. Three patients were lost to follow-up, and these results were censored. No patient required additional glaucoma surgery. All cataract surgeries were uneventful. The mean preoperative logMAR corrected
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
1907
Figure 1. Device implantation technique. Pictures from surgical videos showing the technique are not from any patient in this trial. A: Needle inserter housing the implant is placed through a CCI. B: Gonioscopy view of inserter engaging at the level of trabecular meshwork/ scleral spur. C: The inserter tunneled through sclera rising 3.0 mm posterior to limbus. D: The implant is visible beneath the conjunctiva after successful deployment. E: Bleb formation over the device after evacuation of the OVD and injection of a balanced salt solution in the anterior chamber. F: Visualization of the proper placement of the device in the angle.
distance visual acuity was 0.30, which improved to 0.12 at 12 months (P Z .01). Twelve patients (32%) required needling and of those, 6 were needled with MMC and 6 were needled with 5fluorouracil. Patients were needled by the first month (n Z 6), within 1 to 3 months (n Z 4), within 4 to 6 Table 1. Baseline patient demographics and characteristics (N Z 37). Parameter Age (y) Mean G SD Range Sex, n (%) Men Women Ethnicity, n (%) White Hispanic Asian Black Medicated IOP (mm Hg) Mean G SD Preoperative medications Mean G SD Glaucoma type, n (%) Primary open angle Exfoliation Pigmentary Previous glaucoma procedures, n (%) Argon or selective laser trabeculoplasty Transscleral cyclophotocoagulation IOP Z intraocular pressure
Value 69.6 G 7.7 48.4, 79.2 14 (38) 23 (62) 23 (62) 5 (13.5) 5 (13.5) 4 (11) 22.4 G 4.2 2.5 G 1.4 27 (73) 9 (24) 1 (3) 11 (30) 3 (8)
months (n Z 1), or within 7 to 12 months (n Z 1). The mean IOP before needling was 25.4 mm Hg. The mean postoperative needling IOP was 13.3 mm Hg (P ! .005). Two patients with the Xen140 had 1 anterior chamber refill in the first week, resulting in a stable anterior chamber by the second week. Thirteen patients (9 of which had the Xen140) had an IOP of less than 5 mm Hg 1 day postoperatively. At 1 week, 4 patients had an IOP of less than 5 mm Hg. By 2 weeks, 1 patient had an IOP of less than 5 mm Hg. No patient had an IOP of less than 5 mm Hg at the 1-month postoperative evaluation. Over 12 months, no endophthalmitis, wound leak, device exposure or migration, macular edema, choroidal effusion or hemorrhage, iritis, or retinal detachment occurred. Patients were on a mean of 2.5 G 1.4 medication classes with a mean preoperative IOP of 22.4 G 4.2 mm Hg. The mean IOP at 12 months was reduced to 15.4 G 3.0 mm Hg on a mean of 0.9 G 1.0 medication classes (P ! .0001 for IOP and medications) (Figure 2). This resulted in a qualified success of 85.3% (29 of 34 patients [3 were lost to follow-up]) and a complete success rate off medications of 47.1% (16 of 34) (Figure 3). Seventeen patients (50%) were completely off medications at 12 months compared with 2 patients (5%) preoperatively. No patient was on additional medications compared with baseline. There was no difference in outcomes or complications between the 2 models of the device. DISCUSSION The Xen microfistula implant is a new device that shunts aqueous from the anterior chamber to the
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
1908
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
Figure 2. Mean IOP, number of medications, and percentage change in IOP over time. Error bars represent standard deviation in mean IOP (IOP Z intraocular pressure; meds Z medications).
subconjunctival space. This is performed through an ab interno approach for the surgical treatment of OAG. The procedure can be done without a conjunctival incision, potentially avoiding early postoperative wound-associated complications. In this small pilot study, implantation of the gelatin stent resulted in a significant reduction in IOP when combined with cataract surgery. This study was neither powered nor designed to address safety, and given the lack of a control group, any comparisons to other combined glaucoma procedures are limited. The purpose of this pilot study was to determine whether phacoemulsification with concomitant placement of the gelatin implant would result in significantly lower IOPs from baseline with a reduction in medications. Intraocular pressure was reduced by a mean of 7.0 mm Hg with a mean reduction of 1.6 medication classes. This resulted in a qualified success rate of 85.3% after 12 months. The complete success rate of 47.1% should be analyzed with regard to the strict criteria for complete success (at least 20% IOP reduction from baseline without medications and no hypotony). We suspect that these rates would be higher and the needling rate of 32%
Figure 3. Kaplan-Meier survival curves of cumulative probability of success with and without glaucoma medications (med).
would be lower had this procedure been performed with MMC at the time of implantation (data collection and analysis ongoing). Performing the surgery with MMC might increase the risk for late bleb-related complications. A potential advantage of implanting the gelatin stent over performing trabeculectomy is that no conjunctival incision is required. Although this might reduce the risk for early bleb-related complications, we acknowledge that late bleb-related complications associated with MMC are possible with this device. There were no cases of prolonged hypotony, lens– corneal touch, or device erosion. There is concern that a subconjunctival device left bare might erode. We acknowledge this concern; however, the gel stent is approximately 100 times more flexible10 than the silicone tubing used in traditional tube-shunt surgery. This allows the device to conform to tissue, to bend more easily with blinking and compression, and theoretically to provide less force when contacting overlying conjunctival tissue. There are several limitations to this study. Given that it was a pilot trial, several issues arise from the study design. There was no control group for comparison, so the effect of phacoemulsification alone cannot be accounted for. Although previous studies show only mild IOP-lowering effects of phacoemulsification alone, in patients with uncontrolled glaucoma the risk for an IOP spike and need for additional surgery is significant.11–13 The device is still undergoing development; therefore, the inner lumen size was not standardized and 2 different lumen sizes were studied. In addition, postoperative management was not standardized across centers because these results are from the surgeons' first experiences with the implant. Theoretically, minimizing subconjunctival inflammation might improve success in bleb-forming procedures. Phacoemulsification combined with trabeculectomy can induce inflammation that might cause blebs to fail.14–16 The ability to implant the device ab interno might limit trauma to the subconjunctival space, limiting inflammation and decreasing the
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015
COMBINED PHACO WITH AN AB INTERNO GEL STENT FOR OAG
risk for bleb failure. Given the risks associated with trabeculectomy, alternative methods for achieving subconjunctival filtration with a better safety profile might be beneficial for some patients. For these reasons, studies comparing phacoemulsification combined with trabeculectomy or tube-shunt surgery and phacoemulsification combined with implantation of these gel stents are needed. A U.S. Food and Drug Administration study analyzing the Xen45 (45 mm inner lumen) with adjuvant MMC is currently ongoing.17 In addition, a phase 4 trial comparing the IOP-lowering effect of the device to cataract surgery in combination with the device is underway in Europe. Pending those results, future studies directly comparing the device to trabeculectomy might be warranted. In conclusion, the gel stent combined with phacoemulsification reduced IOP and medications without significant complications in patients with OAG and cataract.
5.
6.
7.
8.
9.
10.
WHAT WAS KNOWN Subconjunctival filtration surgery can be combined with cataract surgery to decrease the IOP for the treatment of OAG. WHAT THIS PAPER ADDS Ab interno placement of a gel stent shunting aqueous humor from the anterior chamber to the subconjunctival space reduced IOP without requiring a conjunctival incision. Cataract surgery performed in conjunction with placement of the microfistula gel implant achieved a significant reduction in IOP with few complications.
REFERENCES
11.
12.
13.
14.
15.
1. Verges C, Cazal J, Lavin C. Surgical strategies in patients with cataract and glaucoma. Curr Opin Ophthalmol 2005; 16:44–52 2. Casson RJ, Salmon JF. Combined surgery in the treatment of patients with cataract and primary open-angle glaucoma. J Cataract Refract Surg 2001; 27:1854–1863 3. Poley BJ, Lindstrom RL, Samuelson TW. Long-term effects of phacoemulsification with intraocular lens implantation in normotensive and ocular hypertensive eyes. J Cataract Refract Surg 2008; 34:735–742 4. Mansberger SL, Gordon MO, Jampel H, Bhorade A, Brandt JD, Wilson B, Kass MA; for the Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study.
16.
17.
1909
Ophthalmology 2012; 119:1826–1831. Available at: http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC3426647/pdf/nihms36 1980.pdf. Accessed June 29, 2015 Tham CCY, Kwong YYY, Baig N, Leung DYL, Li FCH, Lam DSC. Phacoemulsification versus trabeculectomy in medically uncontrolled chronic angle-closure glaucoma without cataract. Ophthalmology 2013; 120:62–67 Samuelson TW, Katz LJ, Wells JM, Duh Y-J, Giamporcaro JE; for the US iStent Study Group. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthalmology 2011; 118:459–467 Liaska A, Papaconstantinou D, Georgalas I, Koutsandrea C, Theodosiadis P, Chatzistefanou K. Phaco-trabeculectomy in controlled, advanced, open-angle glaucoma and cataract: parallel, randomized clinical study of efficacy and safety. Semin Ophthalmol 2014; 29:226–235 Hoffman KB, Feldman RM, Budenz DL, Gedde SJ, Chacra GA, Schiffman JC. Combined cataract extraction and Baerveldt glaucoma drainage implant; indications and outcomes. Ophthalmology 2002; 109:1916–1920 € ke C, Dietlein TS, Lu €ke M, Konen W, Krieglstein GK. A proLu spective trial of phaco-trabeculotomy combined with deep sclerectomy versus phaco-trabeculectomy. Graefes Arch Clin Exp Ophthalmol 2008; 246:1163–1168 Lewis RA. Ab interno approach to the subconjunctival space using a collagen glaucoma stent. J Cataract Refract Surg 2014; 40:1301–1306 Slabaugh MA, Bojikian KD, Moore DB, Chen PP. The effect of phacoemulsification on intraocular pressure in medically controlled open-angle glaucoma patients. Am J Ophthalmol 2014; 157:26–31 Iancu R, Corbu C. Intraocular pressure after phacoemulsification in patients with uncontrolled primary open angle glaucoma. J Med Life 2014; 7:11–16. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3956089/pdf/JMedLife-07-11.pdf. Accessed June 29, 2015 Slabaugh MA, Bojikian KD, Moore DB, Chen PP. Risk factors for acute postoperative intraocular pressure elevation after phacoemulsification in glaucoma patients. J Cataract Refract Surg 2014; 40:538–544 Siriwardena D, Kotecha A, Minassian D, Dart JKG, Khaw PT. Anterior chamber flare after trabeculectomy and after phacoemulsification. Br J Ophthalmol 2000; 84:1056–1057. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1723662/pdf/ v084p01056.pdf. Accessed June 29, 2105 Friedman DS, Jampel HD, Lubomski LH, Kempen JH, Quigley H, Congdon N, Levkovitch-Verbin H, Robinson KA, Bass EB. Surgical strategies for coexisting glaucoma and cataract; an evidence-based update. Ophthalmology 2002; 109:1902–1913 Lochhead J, Casson RJ, Salmon JF. Long term effect on intraocular pressure of phacotrabeculectomy compared to trabeculectomy. Br J Ophthalmol 2003; 87:850–852. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1771770/pdf/ bjo08700850.pdf. Accessed June 29, 2015 U.S. National Institutes of Health Clinical Trials. AqueSys XEN 45 Glaucoma Implant in Refractory Glaucoma. NCT02036541. Available at: https://clinicaltrials.gov/ct2/show/NCT02036541. Accessed June 29, 2015
J CATARACT REFRACT SURG - VOL 41, SEPTEMBER 2015