Review of Relevant Literature
Technology Assessments:
American Academy of Ophthalmology (AAO): The American Academy of Ophthalmology (AAO) (Minckler, et al., 2008) conducted a technology assessment on aqueous shunts for the treatment of Glaucoma. Following a systematic review of the literature, AAO made the following conclusions:
• Aqueous shunts are comparable to trabeculectomy for IOP control and duration of benefit.
• Larger explant surface area is related to better IOP control.
• Although primary indication for aqueous shunts is when prior medical or surgical therapy has failed, they may be used as primary surgical therapy for selected conditions such as trauma, chemical burns or pemphigoid.
• There is sufficient level I evidence that demonstrates no benefit in using antifibrotic agents as adjuncts to aqueous shunt procedures.
• There is sufficient level I evidence that demonstrates no benefit of systemic corticosteroids as adjuncts to aqueous shunt procedures.
• There are insufficient published data to draw any definitive conclusions about the relative likelihood of early postoperative hypotony with implantation of valved or nonvalved devices.
The assessment concluded that "based on level I evidence, aqueous shunts offer a valuable alternative to standard filtering surgery or to cyclodestructive therapy for many refractory glaucomas. The failure rate is approximately the same rate for trabeculectomy with adjunctive antifibrotic agents and in favorable cases shunts may continue to function to control IOP for more than 2 decades.”
In a prospective randomized controlled multi-center (29 sites) clinical trial, Craven et al. (2012) evaluated the long-term safety and effectiveness of a single trabecular micro-bypass stent with concomitant cataract surgery versus cataract surgery alone for mild-to-moderate OAG. Eyes with mild-to-moderate glaucoma with an unmedicated IOP of 22 mmHg or higher and 36 mmHg or lower were randomly assigned to have cataract surgery with iStent® trabecular micro-bypass stent implantation (stent group) or cataract surgery alone (control group). Patients were followed for 24 months postoperatively. The incidence of adverse events was low in both groups through 24 months of follow-up. At 24 months, the proportion of patients with an IOP of 21 mmHg or lower without ocular hypotensive medications was significantly higher in the stent group than in the control group (p = 0.036). Overall, the mean IOP was stable between 12 months and 24 months (17.0 mm Hg ± 2.8 [SD] and 17.1 ± 2.9 mm Hg, respectively) in the stent group but increased (17.0 ± 3.1 mm Hg to 17.8 ± 3.3 mm Hg, respectively) in the control group. Ocular hypotensive medication was statistically significantly lower in the stent group at 12 months; it was also lower at 24 months although the difference was no longer statistically significant. The authors concluded that patients with combined single trabecular micro-bypass stent and cataract surgery had significantly better IOP control on no medication through 24 months than patients having cataract surgery alone. Both groups had a similar favorable long-term safety profile.
On June 25, 2012, the FDA approved the iStent® Trabecular Micro-Bypass Stent System, Model GTS100R/L. This is the first device approved for use in combination with cataract surgery to reduce IOP in adult patients with mild or moderate OAG and a cataract who are currently being treated with medication to reduce IOP. The safety and effectiveness of the iStent® Trabecular Micro-Bypass Stent has not been established as an alternative to the primary treatment of glaucoma with medications. The effectiveness of this device has been demonstrated only in patients with mild to moderate OAG who are currently treated with ocular hypotensive medication and who are undergoing concurrent cataract surgery for visually significant cataract.
In a retrospective, cohort study, Jea and colleagues (2012) compared the effect of ab interno trabeculectomy with trabeculectomy. A total of 115 patients who underwent ab interno trabeculectomy (study group) were compared with 102 patients who underwent trabeculectomy with intra-operative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were OAG, aged greater than or equal to 40 years and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. Clinical variables were collected from patient medical records. Main outcome measures included IOP and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP greater than 21 mmHg or less than 20 % reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP less than or equal to 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery or loss of light perception vision. Secondary outcome measures included number of glaucoma medications and occurrence of complications. Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intra-ocular pressure decreased from 28.1 +/- 8.6 mmHg at baseline to 15.9 +/- 4.5 mmHg (43.5 % reduction) at month 24 in the study group and from 26.3 +/- 10.9 mmHg at baseline to 10.2 +/- 4.1 mmHg (61.3 % reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4 % and 76.1 % in the study and trabeculectomy groups, respectively (p < 0.001). Younger age (p = 0.037; adjusted HR, 0.98 per year; 95 % CI: 0.97 to 0.99) and lower baseline IOP (p = 0.016; adjusted HR, 0.96 per 1 mmHg; 95 % CI: 0.92 to 0.99) were significant risk factors for failure in the multi-variate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (p < 0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5 %) than after trabeculectomy (10.8 %, p < 0.001). The authors concluded that ab interno trabeculectomy has a lower success rate than trabeculectomy.
In 2016, the XEN® Glaucoma Treatment System (Allergan, Inc. Aliso Viejo, CA) was FDA 510(k) approved as a Class II aqueous shunt indicated “for the management of refractory glaucomas, including cases where previous surgical treatment has failed, cases of primary open angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy”.
The XEN® Glaucoma Treatment System consists of the XEN®45 Gel Stent preloaded into the XEN® Injector. The XEN®45 Gel Stent is composed of a gelatin derived from porcine dermis, formed into a tube, and then cross-linked with glutaraldehyde.
Ab Interno Gel Stent (i.e., XEN® Glaucoma Treatment System): Clinical trials evaluating the safety and effectiveness of the XEN® system with phacoemulsification are lacking. Studies have primarily been in the form of case series with small patient populations (n=30) with short-term follow-ups (12 months) (Pérez-Torregrosa, et al., 2016).
After receiving FDA approval in July 2016 based on the 2-year safety and efficacy results of the COMPASS study, Alcon announced a voluntary worldwide market withdrawal of the CyPass Micro-Stent® on August 29, 2018, after 5-year postoperative data from the COMPASS-XT safety study indicated a statistically significant corneal endothelial cell loss associated with this device.
Several additional devices are under development/investigation but have not yet received FDA approval.