Discussion
Implantation of the CyPass supraciliary microstent was generally safe and well-tolerated in these eyes, with no device-related sight-threatening complications. Although 31.6% of eyes required subsequent glaucoma procedures, this rate is consistent with reoperation rates following other MIGS procedures, including implantation of the iStent trabecular bypass (38%)7 and Trabectome trabecular ablation (27%).8
Standalone microstent implantation resulted in sustained 16%–20% reduction in IOP through 3 years of postoperative follow-up and reduced IOP-lowering medication use by an average of 0.5–1 medications through the first 12–18 months of follow-up. At month 36, mean IOP reduction was 4.5 mm Hg (16.9%), with subjects using slightly fewer medications than at baseline.
IOP reductions were greater in eyes with higher (≥21 mm Hg) than lower (<21 mm Hg) baseline IOP, while reductions in medication use were comparable in the two subgroups. IOP reductions in eyes with lower baseline IOP were modest, ranging from 2%–9%, with subjects using 0.5–1 fewer medications after 12–18 months. In eyes with higher baseline IOP, the IOP reductions were 25%–30% at all postoperative time points. These results compare favourably with those of a protocol-based, multicentre, single-arm study of standalone microstent implantation in eyes with medicated IOP >21 mm Hg.9 In that study, IOP at 12 months postoperatively was reduced 35%, with subjects using 0.8 fewer medications per eye. The magnitude of IOP reduction observed in the current study was greater than expected when adding a single IOP-lowering medication to prostaglandin monotherapy,10–12 and more consistent with the addition of a fixed combination of two medications to prostaglandin monotherapy.13 14 This IOP reduction was also consistent with those of other MIGS procedures performed as standalone surgery, including canal based approaches such as the iStent trabecular bypass15 and Trabectome trabecular ablation.16 17 MIGS devices targeting the subconjunctival space and forming a bleb are generally indicated for refractory glaucoma. It is therefore interesting to compare the 12-month outcomes for the ab interno Xen gel stent with the uncontrolled IOP cohort from the present study. Baseline IOP and medication usage were similar; mean medicated IOP was 25.1 mm Hg on an average of 3.5 medications for the gel stent and 26.7 mm Hg on 2.2 medications for the ≥21 mm Hg cohort in the present study. At 12 months (the duration of the gel stent study), mean changes from baseline in IOP were −9.1 mm Hg and −7.9 mm Hg for the gel stent and CyPass microstent, respectively.18 Our finding, that 50% of eyes with baseline IOP >21 mm Hg achieved a mean IOP reduction ≥20% on the same or fewer medications at 3 years, was clinically significant.
It is important to consider that, had they not been enrolled in this study, many of these eyes likely would have undergone traditional glaucoma surgery (ie, trabeculectomy or another filtering procedure). Forty-four per cent of the eyes enrolled for the standalone microstent procedure had a history of prior glaucoma surgery, 53% had preoperative IOP ≥21 mm Hg, and 72% were being treated with ≥2 ocular hypotensive medications. Despite the inclusion of eyes with more advanced disease, only 31.6% required additional glaucoma surgery over the 3-year follow-up period of this study.
The performance of cataract surgery was an anticipated event for some proportion of patients, given the possibility of pre-existing cataract at baseline and the 3-year duration of the study. Nineteen eyes underwent cataract surgery during the course of study participation, 16 during the first postoperative year and the remaining three between 12 and 24 months. This additional procedure may have contributed to some level of additional IOP reduction in this subgroup. However, patients undergoing cataract surgery were not excluded from the analysis as, in our opinion, the performance of cataract operations closely reflects real-world situations and supports the overall generalisability of the study outcomes.
As a registry study, CyCLE included some patients who were (and remain) outside the labelled indication of primary open angle glaucoma (POAG). Indeed, seven (3.9%) eyes enrolled in the standalone cohort had narrow angles. This subgroup showed no obvious differences in safety outcomes compared with the study cohort as a whole. One phakic eye with narrow angles experienced an IOP elevation >10 mm Hg above baseline; an incidence of 14% compared with 9% (20 eyes) in the entire group.
This study had several limitations, including those common to real-world studies. It did not include a control group. Moreover, the study protocol did not standardise patient selection beyond basic eligibility criteria, recommended but did not confirm adherence to the manufacturer’s recommended surgical technique, and did not specify postoperative care. These methodological differences can account for differences in outcomes when compared with more robust clinical trials. However, the results of these clinical trials may not be broadly generalisable to target patient populations likely to undergo these interventions. Clinical trials often have narrow eligibility criteria to ensure homogeneity of study subjects and may require multiple IOP measurements using a specified type of tonometer to more robustly estimate efficacy outcomes. In the real world, however, most clinical centres care for broadly heterogeneous populations, and IOP is measured using a variety of tonometers and is rarely the average of multiple measurements. Clinical trials also tend to enrol subjects with a narrower spectrum of disease severity than was included in this study. Our study is not intended to substitute for robust clinical trial data but should rather be considered complementary to such studies.
In conclusion, this real-world study found that implantation of the CyPass supraciliary microstent, performed as a standalone procedure, safely and effectively lowered IOP in eyes with OAG. This device resulted in greater reductions in IOP in eyes with baseline IOP >21 mm Hg than in those with baseline IOP <21 mm Hg. Adverse event rates and IOP reductions were consistent with those reported for other MIGS procedures.