It is hard to believe that it has been over 13 years since the iStent (Glaukos) trial began, and it has been over 9 years since the Cypass (Alcon) trial began. Although the US Food and Drug Administration (FDA) approval for such devices is often based on initial short-term clinical trial results, there have been increasing reports in the literature on the long-term durability of these devices. The iStent has the most data. Since Samuelson’s initial publication on the pivotal data in 2011,1 we have seen the 2-year follow-up and other long-term studies published.2
With growing use of the iStent, there have been increasing reports about its long-term efficacy and safety. Katz et al recently published the 42-month outcomes of 119 patients randomized to 1, 2, or 3 iStents as a standalone procedure, with 109 patients reaching 42-month follow-up.3 At 42 months, the mean medicated IOP was 15.0, 15.7, and 14.8 mmHg in the 3 groups, respectively, and the post-washout IOP was 17.4, 15.8, and 14.2 mmHg, respectively. The proportion of subjects who achieved ≥20% IOP lowering off medications was 61%, 91%, and 91%, respectively. The 54-month outcomes from this study demonstrated that the IOP lowering was sustained, with mean medicated IOP remaining ≤17.1 mmHg in all 3 groups.4
Tan et al published the 36-month outcomes of a series of 41 patients undergoing implantation of 1 iStent at the time of cataract surgery, with 36 patients reaching 36-month follow-up.5 At 36 months, the mean IOP was 17.1 mmHg on 1.3 drops, and this effect was sustained at 60 months, with a mean IOP of 17.7mm Hg on 1.2 drops.6 This is similar to the 2 year iStent results but sustained.
Chang et al reported the 36-month outcomes of 39 phakic patients undergoing implantation of 2 iStents as a standalone procedure, with adjuvant travoprost (Travatan Z; Novartis), with 37 patients reaching 36 month follow-up.7 At 36 months, mean IOP was 14.0±2.6 mmHg on 1 medication, 97% achieved ≥20% IOP reduction with a reduction of 1 medication, and 86% achieved IOP of ≤18 mmHg with a reduction of 1 medication. Donnenfeld reported that the effects were sustained at 48 months, with mean IOP ≤15.2 mmHg at all visits, 87% of subjects were off medications, and 90% of subjects achieved ≥20% lowering and IOP ≤18 mmHg off medications.8
Bacharach reported 60-month outcomes from a randomized trial comparing 2 iStents (n=54) vs travoprost (n=47) in patients with primary open-angle glaucoma (POAG) naïve to medical or surgical treatments.9 At 60 months, the mean IOP remained ≤16.5 mmHg in both groups. The proportion of subjects achieving IOP ≤18 mmHg off medications was 77% in the iStent group and 53% in the travoprost group. Stiles reported 60-month outcomes from a single-surgeon series of 50 eyes implanted with 1 iStent at the time of cataract surgery, with 27 eyes reaching 5 year follow-up.10 At 60 months, the mean IOP was 14.3±2.9 mmHg, and medication burden was reduced or maintained in 89% of eyes.
The results from these studies support the viability of iStent implantation as a standalone procedure or in combination with cataract surgery, as initial therapy for patients with newly diagnosed open-angle glaucoma, and for refractory glaucoma with IOP not controlled with topical therapy, achieving sustained IOP reduction, reduced medication burden, and favorable safety over a 4 to 5-year period.
The Hydrus microstent (Ivantis), which is not yet FDA approved, consists of an alloy scaffold that is inserted ab-interno into Schlemm’s canal to allow improved aqueous outflow. This implant is much larger than the iStent.
The 24-month results of the pivotal HORIZON trial were reported by Ahmed at ASCRS 2018; this multicenter US trial randomized 331 eyes with mild to moderate open angle glaucoma 2:1 to receive a Hydrus microstent at the time of cataract surgery vs cataract surgery alone.11 At 24 months, the percentage of eyes that achieved ≥20% IOP lowering off medication was 79% in the Hydrus group compared to 55% in the control group. The Hydrus group had a greater reduction in mean IOP (7.8 mmHg) compared to the control group (5.2 mmHg), and the proportion of eyes that remained off medications was 79% in the Hydrus group compared to 39% in the control group.
Prior to this, Pfeiffer et al published the 24-month outcomes from a European study of 100 eyes with open-angle glaucoma randomized 1:1 to receive Hydrus microstent at the time of cataract surgery vs cataract surgery alone.12 At 24 months, the proportion of eyes that achieved ≥20% IOP lowering off medication was 80% in the Hydrus group compared to 46% in the control group. The mean unmedicated IOP was 16.9 mmHg in the Hydrus group compared to 19.2 mmHg in the control group. The proportion of patients that remained off medications was 73% in the Hydrus group compared to 38% in the control group. Additionally, Fea et al published the 24-month outcomes from a European series of 92 eyes implanted with Hydrus at the time of cataract surgery, with 67 patients reaching 24-month follow-up.13 At 24 months, the mean IOP was 15.7 mmHg on 0.6 medications, and 64% of patients were off medications.
The results from these studies support the viability of Hydrus in combination with cataract surgery for patients with open angle glaucoma, achieving sustained IOP reduction, reduced medication burden, and favorable safety over a 2-year period, but long-term efficacy and safety beyond 2 years is currently unknown. We await the FDA approval.
Supraciliary and Suprachoroidal Outflow
The Cypass has been FDA approved and amassing follow-up data since July 2016. Vold et al published the 24-month results of the pivotal COMPASS trial randomizing 505 subjects with POAG to Cypass combined with cataract surgery vs cataract surgery alone.14 At 24 months, the proportion of patients achieving ≥20% unmedicated IOP lowering was 77% in the Cypass group compared to 60% in the control group, the mean IOP reduction was 7.4 mmHg in the Cypass group compared to 5.4 mmHg in the control group, and the mean number of medications was 0.2 in the Cypass group compared to 0.7 in the control group. Reiss recently reported the interim 36-month COMPASS results demonstrating that the proportion of patients off medications was 69% in the CyPass group compared to 57% in the control group.15
Höh et al published the 24-month outcomes of 136 subjects undergoing Cypass implantation at the time of cataract surgery,16 with 82 subjects achieving 24-month follow-up. At 24 months, the cohort with controlled and uncontrolled IOP at baseline had a mean IOP of 15.8 mmHg and 16.1 mmHg, respectively, and the mean number of medications was 1.0 and 1.1, respectively. The 36-month outcomes, which included a larger number of patients, demonstrated that the groups with controlled IOP (n=93) and uncontrolled IOP (n=152) at baseline had a higher proportion of subjects off medications (19% and 45%, respectively) and a lower proportion of subjects using 3 or more medications (23% and 15%, respectively) compared to baseline.17
Given the relative novelty of the Cypass, there remains a paucity of outcomes data beyond 36 months. Rau recently reported 60-month outcomes from a small cohort of 33 eyes implanted with Cypass (24 combined with cataract surgery and 9 as a standalone procedure).18 At 60 months, the mean IOP was 16.5 mmHg on 1.0 medications in the Cypass plus cataract surgery group and 14.5mm Hg on 1.5 medications in the Cypass alone group. In 2 patients, the Cypass was adherent to the iris, which was treated with YAG laser. In 1 patient, the IOP rose, and after a second Cypass was implanted, the pressure dropped to 12 mmHg. The results from these studies support the viability of Cypass as a standalone procedure or in combination with cataract surgery for patients with open angle glaucoma with controlled or uncontrolled IOP on medical therapy, achieving sustained IOP reduction, reduced medication burden, and favorable safety over a 3- to 5-year period.
Addendum (September 7, 2018): On August 29th, 2018, Alcon announced a voluntary global market withdrawal of the Cypass device due to the results of the recently completed COMPASS-XT study. This study followed COMPASS patients for 5 years and found that endothelial cell loss was more likely in patients who had undergone Cypass implantation, especially if they had 2 or more retention rings visible in the anterior chamber on gonioscopy. In the press release, Dr. Stephen Lane, Chief Medical Officer at Alcon, said, “Although we are removing the product from the market now out of an abundance of caution, we intend to partner with the FDA and other regulators to explore labeling changes that would support the reintroduction of the Cypass microstent in the future.”
The Xen gel stent (Allergan) was FDA approved in 2016 and consists of a porcine gelatin stent that is inserted usually ab-interno into the subconjunctival space to improve aqueous outflow by create a low-lying subconjunctival bleb. This differs from the prior 2 implants.
A growing number of studies with 12-month follow-up have provided evidence for the short-term efficacy and safety of the Xen gel stent.19-24 At 12 months, the mean postoperative IOP from these reports ranged from 12.6 mmHg to 16.1 mmHg, the proportion of patients who achieved ≥20% IOP reduction ranged from 62% to 75%, the mean number of medications ranged from 0.4 to 1.7 medications. There remains a paucity of Xen outcomes data beyond 12 months. The 24-month results from the APEX study, an ongoing randomized, large, multicenter trial of 215 eyes comparing Xen with cataract surgery vs Xen alone, were recently presented at the European Glaucoma Society 2018 meeting, but these results have not yet been published.
Kersten-Gomez et al reported the 48-month outcomes from a series of 66 eyes implanted with the Xen gel stent, with 39 eyes reaching 48-month follow-up.25 In this series, the mean IOP at 48 months was 13.5 mmHg on 1.1 medications, and there were no significant changes in visual fields in this cohort. However, a large proportion (40.9%) of patients were lost to follow-up or were excluded due to the need for secondary IOP lowering procedures.
Overall, the Xen gel stent achieves lower short-term IOP than iStent or Cypass but has a higher rate of hypotony and need for bleb needling. More data are needed to fully assess the long-term efficacy of the Xen gel stent.
The InnFocus MicroShunt
The InnFocus MicroShunt (Santen), which is not yet FDA approved, consists of a polystyrene shunt inserted ab-externo that shunts aqueous into the subconjunctival space, and has been proposed as a safer and more predictable alternative to the traditional trabeculectomy. Batlle et al published the 36-month outcomes of a series of 23 eyes with POAG not controlled on topical medication that were implanted with the InnFocus MicroShunt with Mitomycin C (14 as a standalone procedure, and 9 combined with cataract surgery), with 22 eyes reaching 36 month follow-up.26 At 36 months, the proportion of eyes that achieved IOP ≤14 mmHg and IOP reduction ≥20% was 95%, the mean medicated IOP was 10.7 mmHg on 0.7 medications. The most common complications were transient hypotony in 3 patients and transient choroidal effusions in 2 patients, which resolved spontaneously, and there were no leaks, infections, migrations, erosions, persistent corneal edema, or serious long-term adverse events. The 48-month outcomes from this cohort were reported by Palmberg at the American Glaucoma Society Meeting in 2017.27 At 48 months, the mean IOP was 11.7 mmHg, 65% of subjects were off medications, and the diffuse posterior blebs had no leaks or infections.
The results from this small cohort support the viability of the InnFocus MicroShunt in combination with cataract surgery or as a standalone procedure for patients with open-angle glaucoma, achieving sustained IOP reduction, reduced medication burden, and favorable safety (with only transient adverse effects occurring within the first 3 months after surgery) over a 4-year period, but there are currently no larger-scale randomized controlled trials comparing the InnFocus MicroShunt to traditional trabeculectomy.
While the critics of these less invasive surgeries are quick to say it is “not as good as a trab,” patients are drawn to these new options to avoid all the complications of a traditional trabeculectomy. We are now seeing that these less invasive surgical options, with additional medication use, can achieve a similar IOP to what we have historically seen with a standard filtering surgery. GP
- Samuelson TW, Katz LJ, Wells JM, Duh Y-J, Giamporcaro JE; US iStent Study Group. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthalmology. 2011;118(3):459-467.
- Craven ER, Katz LJ, Wells JM, Giamporcaro JE, iStent Study Group. Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract: Two-year follow-up. J Cataract Refract Surg. 2012;38(8):1339-1345.
- Katz LJ, Erb C, Carceller Guillamet A, et al. Long-term titrated IOP control with one, two, or three trabecular micro-bypass stents in open-angle glaucoma subjects on topical hypotensive medication: 42-month outcomes. Clin Ophthalmol. 2018;12:255-262.
- Lewis RA, Katz LJ. Long-Term IOP Control with 1, 2, or 3 Trabecular Microbypass Stents for OAG: 54-Month Outcomes. Presented at: the American Society of Cataract and Refractive Surgery annual meeting; April 14, 2018; Washington, DC. https://ascrs.confex.com/ascrs/18am/meetingapp.cgi/Paper/44711 . Accessed June 1, 2018.
- Tan SZ, Au L. Manchester iStent study: 3-year results and cost analysis. Eye. 2016;30(10):1365-1370.
- Tan SZ, Walkden A, Au L. Manchester iStent study: five-year results and cost analysis. Presented at: the American Academy of Ophthalmology annual meeting; October 17, 2016; Chicago, Illinois. https://aao.scientificposters.com/epsAbstractAAO.cfm?id=18 . Accessed June 1, 2018.
- Chang DF, Donnenfeld ED, Katz LJ, et al. Efficacy of two trabecular micro-bypass stents combined with topical travoprost in open-angle glaucoma not controlled on two preoperative medications: 3-year follow-up. Clin Ophthalmol. 2017;Volume 11:523-528.
- Donnenfeld E, Solomon K, Voskanyan L, Chang D. Outcomes through 48 months after MIGS with 2 trabecular bypass stents in eyes with open-angle glaucoma not controlled on 1 medication. Presented at: the American Society of Cataract and Refractive Surgery annual meeting; April 16, 2018; Washington, DC. https://ascrs.confex.com/ascrs/18am/meetingapp.cgi/Paper/44145 . Accessed June 1, 2018.
- Bacharach J. Five-year results of a prospective study of 2 trabecular microbypass stents versus prostaglandin in newly diagnosed open-angle glaucoma. Presented at: the American Society of Cataract and Refractive Surgery annual meeting; April 16, 2018; Washington, DC. https://ascrs.confex.com/ascrs/18am/meetingapp.cgi/Paper/43141 . Accessed May 31, 2018.
- Stiles M. Five-year single-site outcomes of trabecular bypass stent and cataract surgery in eyes with previous medical and/or surgical glaucoma therapy. Presented at: the American Society of Cataract and Refractive Surgery annual meeting; April 16, 2018; Washington, DC. https://ascrs.confex.com/ascrs/18am/meetingapp.cgi/Paper/43011 . Accessed May 31, 2018.
- Ahmed I. Multicenter randomized study of a schlemm canal microstent for reduction of IOP. Presented at: the American Society of Cataract and Refractive Surgery annual meeting; April 16, 2018; Washington, DC. https://ascrs.confex.com/ascrs/18am/meetingapp.cgi/Paper/45349 . Accessed May 31, 2018.
- Pfeiffer N, Garcia-Feijoo J, Martinez-de-la-Casa JM, et al. A randomized trial of a Schlemm’s canal microstent with phacoemulsification for reducing intraocular pressure in open-angle glaucoma. Ophthalmology. 2015;122(7):1283-1293.
- Fea AM, Rekas M, Au L. Evaluation of a Schlemm canal scaffold microstent combined with phacoemulsification in routine clinical practice: two-year multicenter study. J Cataract Refract Surg. 2017;43(7):886-891.
- Vold S, Ahmed IIK, Craven ER, et al. Two-year COMPASS trial results: supraciliary microstenting with phacoemulsification in patients with open-angle glaucoma and cataracts. Ophthalmology. 2016;123(10):2103-2112.
- Reiss G, Patel S. COMPASS XT Study Interim Report: Thirty-Six-Month Outcomes of the CyPass Micro-Stent in Primary Open-Angle Glaucoma Patients. Presented at: the American Academy of Ophthalmology annual meeting; November 13, 2017; New Orleans, Louisiana.
- Höh H, Grisanti S, Grisanti S, Rau M, Ianchulev S. Two-year clinical experience with the CyPass micro-stent: safety and surgical outcomes of a novel supraciliary micro-stent. Klin Monbl Augenheilkd. 2014;231(04):377-381.
- Höh H, Scott R. Three-year results from the CyCLE study for supraciliary micro-stent implantation combined with cataract surgery for open-angle glaucoma. Presented at: The XXXV Congress of the European Society of Cataract and Refractive Surgeons; October 9, 2017; Lisbon, Portugal. http://www.escrs.org/abstracts/details.asp?confid=24&sessid=1036&type=free&paperid=28120 . Accessed May 31, 2018.
- Rau M. Supraciliary microstent implantation with cataract surgery in patients with open-angle glaucoma: five-year experience. Presented at: the American Society of Cataract and Refractive Surgery annual meeting; April 17, 2018; Washington, DC. https://ascrs.confex.com/ascrs/18am/meetingapp.cgi/Paper/45343 . Accessed May 31, 2018.
- Mansouri K, Guidotti J, Rao HL, et al. Prospective evaluation of standalone XEN gel implant and combined phacoemulsification-XEN gel implant surgery. J Glaucoma. 2017;27(2):1.
- Grover DS, Flynn WJ, Bashford KP, et al. Performance and safety of a new ab interno gelatin stent in refractory glaucoma at 12 months. Am J Ophthalmol. 2017;183:25-36.
- De Gregorio A, Pedrotti E, Russo L, Morselli S. Minimally invasive combined glaucoma and cataract surgery: clinical results of the smallest ab interno gel stent. Int Ophthalmol. 2018;38(3):1129-1134.
- Au L, Lavin C, Fea A, Reitsamer H. Combined cataract and minimally invasive glaucoma surgery vs minimally invasive glaucoma surgery alone: 1 year results of an ab-interno gelatin stent for the treatment of primary-angle glaucoma. Presented at: The XXXII Congress of the European Society of Cataract and Refractive Surgeons; 2015; Barcelona, Spain. http://www.escrs.org/abstracts/details.asp?confid=20&sessid=669&type=Free&paperid=24400 . Accessed June 2, 2018.
- Stalmans I. The role for the Xen gel stent implant in glaucoma treatment. Acta Ophthalmol. 2016;94.
- Economou M. XEN implant alone vs phaco-XEN for POAG/PXG: the Stockholm experience. Presented at: The XXXIII Congress of the European Society of Cataract and Refractive Surgeons; November 9, 2016; Copenhagen, Denmark. http://www.escrs.org/abstracts/details.asp?confid=22&sessid=792&type=Free&paperid=26977 . Accessed May 31, 2018.
- Kersten-Gomez I, Lenzhofer M, Eisenkopf L, Ahmed I, Reitsamer H, Dick B. 4th year long-term follow-up results after minimally invasive transscleral XEN glaucoma gel stent ab interno implantation in a prospective multicenter trial. Presented at: The XXXIII Congress of the European Society of Cataract and Refractive Surgeons; November 9, 2016; Copenhagen, Denmark. http://www.escrs.org/abstracts/details.asp?confid=22&sessid=792&type=Free&paperid=26975 . Accessed June 2, 2018.
- Batlle JF, Fantes F, Riss I, et al. Three-year follow-up of a novel aqueous humor microshunt. J Glaucoma. 2016;25(2):e58-e65.
- Palmberg P, Batlle J, Riss I, Alburquerque R, Corona A, Parel JM. Two-center results of a SIBS-based micro shunt at 1 to 4 years. Presented at: American Glaucoma Society 27th Annual Meeting. 2017; Coronado, CA.