Surgical outcomes of XEN45 implantation, trabeculectomy vs. penetrating canaloplasty in open-angle glaucoma: A non-randomized comparative study

Abstract

To the Editor: Glaucoma is a leading cause of irreversible blindness worldwide.[1] Trabeculectomy with mitomycin C (MMC) has been the standard surgical intervention for reducing intraocular pressure (IOP) and slow down the progression of glaucoma.[2] However, some serious complications with devastating consequences can occur after trabeculectomy, such as bleb-related infections, suprachoroidal hemorrhage, vitreous hemorrhage, and malignant glaucoma. Over the last decade, many novel ophthalmic surgical devices have been used in glaucoma. The XEN45 microstent (Allergan, Dublin, CA, USA) is a hydrophilic cross-linked porcine gelatin stent. It is implanted ab-interno, draining the aqueous humor into the subconjunctival space without the need to form a conjunctival flap, scleral flap, or iridectomy. Penetrating canaloplasty (PCP), first proposed by Liang et al[3], is a relatively new Schlemm's canal-based surgery. The procedure integrates the trabeculectomy procedures into canaloplasty, creating a direct communication between the anterior chamber and the ostia of Schlemm's canal to restore the internal drainage of aqueous humor. PCP restores the aqueous humor outflow in a bleb-independent manner and does not require MMC. The purpose of this study is to compare the surgical success and postoperative complications among XEN45 implantation, trabeculectomy with MMC, and PCP in Chinese patients with open-angle glaucoma over a 12-month period. This non-randomized comparison study was approved by the Ethics Committee of the Eye Hospital of Wenzhou Medical University (No. 2023-042-K-34) and was carried out in accordance with the tenets of the Declaration of Helsinki. Patients received glaucoma surgeries after being fully informed and signing an informed consent. Patients aged 18 years or older, demonstrating inadequately controlled open-angle glaucoma with an IOP of 18 mmHg or more on tolerated medical therapy, who underwent successful XEN45 implantation and trabeculectomy with MMC or PCP by a single experienced glaucoma surgeon (YBL) between May 1, 2019, and March 15, 2022, with a minimum follow-up of 12 months were included. Exclusion criteria included: (1) angle-closure glaucoma, exfoliation glaucoma, pigmentary glaucoma, or normal-tension glaucoma, (2) no light perception, (3) iris neovascularization, (4) signs of suprascleral venous hypertension (e.g., torturous and dilated suprascleral veins), (5) central corneal thickness ≤490 μm or ≥620 μm; (6) history of retinal surgery or corneal surgery (including laser-assisted in situ keratomileusis, laser subepithelial keratomileusis and photorefractive keratectomy), and (7) opacities, or disease/pathology of the cornea. Data including age, eye, gender, glaucoma diagnosis (primary open-angle glaucoma [POAG], juvenile glaucoma, or Posner–Schlossman syndrome [PSS]), prior glaucoma surgical therapy, and preoperative ocular characteristics were collected. Postoperative follow-up visits were scheduled at day 1, week 1, and at months 1, 3, 6, and 12. IOP, glaucoma medications, complications, need for postoperative interventions, slit-lamp photograph, and ultrasound biomicroscopy (UBM) image were collected at each postoperative time point. The conjunctiva of the target area was marked 3 mm from the limbus. Then, 0.1 mL of MMC (mitosol, 0.2–0.3 mg/mL) was injected into the subconjunctiva to enlarge the subconjunctival space. A preloaded injector was inserted through the main incision and the needle advanced through the sclera into the subconjunctival space. The subconjunctival XEN part was tested to ensure its mobility. Following a fornix-based conjunctival flap, a fluid-retaining sponge soaked in MMC (0.4 mg/mL) was applied to the superior sclera for 3–5 min. Balanced salt solution rinsing was then carried out. A 4.0 mm × 3.0 mm scleral flap was made. A 1.0 mm × 0.5 mm trabecular meshwork segment was excised, followed by peripheral iridectomy. Following a fornix-based conjunctival flap and a 4.0 mm × 3.0 mm superficial scleral flap, a 1.5 mm × 2.0 mm deep scleral flap was sculpted and removed. The external wall of the Schlemm's canal was opened and unroofed. A flexible microcatheter (iTrack by Ellex iScience, Inc., Fremont, CA, USA) was inserted into the Schlemm's canal and guided forward for 360° circumference. A 10-0 polypropylene suture was tied to the distal tip of the microcatheter, which was drawn through the Schlemm's canal as the microcatheter was withdrawn. A small amount of high-molecular-weight hyaluronic acid viscoelastic agent (Healon GV, Johnson&John Surgical Vision, Inc., Santa Ana, CA, USA) was injected into the Schlemm's canal. The suture was then tied with tension to inwardly indent the trabecular meshwork. A 1.0 mm × 0.5 mm trabecular meshwork segment anterior to the Schlemm's canal was excised, followed by peripheral iridectomy. Surgical success was defined as an IOP ≤21 mmHg and ≥5 mmHg without (complete success) or with/without (qualified success) glaucoma medications. Surgical failure was defined as an IOP >21 mmHg with maximum tolerated topical medication on two consecutive visits at 1 month, reoperation for glaucoma, or loss of light perception due to glaucoma progression or surgical-related complications. Postoperative interventions performed at the slit-lamp or suture wound were not considered as surgical failure. Statistical analysis can be seen in Supplementary Material, https://links.lww.com/CM9/B998. A total of 101 eyes of 78 patients were included in the study. Baseline characteristics of patients from three groups are presented in Supplementary Table 1, https://links.lww.com/CM9/B998. The patients in the XEN45 group (50.6 ± 16.1 years) and in the trabeculectomy group (56.7 ± 15.8 years) were significantly older than the patients in the PCP group (38.0 ± 11.5 years, F = 14.796, P <0.001). All groups produced a significant reduction in IOP [Supplementary Figure 1, https://links.lww.com/CM9/B998] and glaucoma medications postoperatively [Supplementary Table 2, https://links.lww.com/CM9/B998]. There was no significant difference in the mean IOP among the three groups at 12 months (F = 0.264, P = 0.769). The XEN group had significantly lower mean IOPs than the other two groups at all follow-up visits during the first postoperative month (all P <0.05). There was a higher failure rate in the XEN45 group than in the other groups during the 12 months of follow-up [Figure 1]. The Kaplan–Meier survival analysis showed that the cumulative probability of complete success rate and qualified success rate was 65.8% and 74.5% in the XEN45 group at one year. In all, four patients with four eyes (4/33, 12.1%) in the trabeculectomy group failed within 6 months postoperatively, yielding a one-year complete success rate of (25/33, 75.7%) and a qualified success rate of (29/33, 87.9%). Similarly, the PCP group had a one-year complete success rate of (27/36, 75.0%) and a qualified success rate of (32/36, 88.9%), with four patients (4/36, 11.1%) experiencing failure between 6 months and 12 months postoperatively. The postoperative complications and interventions are listed in Supplementary Table 3, https://links.lww.com/CM9/B998. During the first year of follow-up, 18 eyes (18/32, 56.3%) in the XEN45 group, 24 eyes (24/33, 72.7%) in the trabeculectomy group, and 24 eyes (24/36, 66.7%) in the PCP group experienced one or more postoperative complications. Transient IOP elevation (≥21 mmHg) at early follow-up visits was the most-common complication in the PCP (18/36, 50.0%) and the trabeculectomy groups (12/33, 36.4%). The most-common complication in the XEN45 group was shallow anterior chamber (8/32, 25.0%). Regarding postoperative interventions, 19 eyes (19/32, 59.4%) in the XEN45 group and 21 eyes (21/33, 63.6%) in the trabeculectomy group experienced one or more postoperative interventions, but no eye in the PCP group needed interventions. Bleb management procedures such as bleb needling, 5-fluorouracil injection, and bleb massage were the most-common postoperative interventions in the XEN45 and trabeculectomy groups.Figure 1: Kaplan–Meier curve for the (A) complete success and (B) qualified success of follow-up in the XEN45 group, trabeculectomy group and PCP group. PCP: Penetrating canaloplasty; Trab: Trabeculectomy.The current study on Chinese patients with open-angle glaucoma compared the surgical success rate of XEN45 implantation with MMC, trabeculectomy with MMC, and PCP. All surgical procedures effectively reduced IOP and glaucoma medications without significant difference at 12-months follow-up. However, the XEN45 group had lower IOPs than the other groups at all time points during the first postoperative month. The pressure differential across XEN45 is proportional to the resistance to flow. If there is no subconjunctival resistance, an IOP value of approximately 6 mmHg is theoretically possible.[4] Thus, the early postoperative IOP of XEN45 is low and fairly constant. As a result, shallow anterior chamber was the most-common complication, and hypotony was not observed in the XEN45 group in this study. In the current study, the outcomes showed that the complete and qualified successe rate of all the three interventions were similar in the first 9 months, wherein XEN45 decreased in the 9- to 12-month timeframe. Bleb management is very important for bleb-based procedures. Postoperative interventions were undertaken with similar frequency in the trabeculectomy and XEN45 groups in our study. However, an insufficient experience in bleb management for XEN45 implantation may decrease the success rate of the XEN45 group. In addition, the age of the patient can influence the success rate of external filtration surgery, leading to a lower success rate of XEN in younger patients in our study. As demonstrated in this study, the success rate of PCP is comparable to eyes that underwent trabeculectomy with MMC. The notable high complete success rate of PCP may be attributed to several factors. The surgery involves the enlargement of the Schlemm's canal and the creation of a direct fistula between the anterior chamber and the Schlemm's canal. This bypasses the main area of resistance in the damaged trabecular meshwork, facilitating the internal drainage of aqueous humor from the anterior chamber to the Schlemm's canal. As a bleb-independent surgery, PCP was free from postoperative intervention, and the majority of the eyes (81.3%–100%) displayed no observable subconjunctival bleb during the follow-up after PCP surgery.[3,5] This study was limited by its non-randomized nature and may have inherently created information and selection bias. However, the clinical data from this study represent real-world results. In contrast, the monocentric and comparative aspects of this study having three procedures performed by the same surgeon, as well as having a reasonably high sample size for a single-center study should be considered as an asset during the analysis of these results. This study would help to plan for prospective studies with larger sample sizes to investigate the long-term outcomes of XEN45 implantation, trabeculectomy, and PCP. In conclusion, XEN45 implantation, trabeculectomy, and PCP resulted in sufficiently low postoperative IOP values. Trabeculectomy and PCP showed comparable complete and qualified surgical success rate after 12 months and better outcomes than XEN45, although trabeculectomy was associated with more postoperative interventions. Acknowledgments We wish to thank Weihe Zhou for statistical consultation. Funding This study was supported by grants from the Program for Zhejiang Leading Talent of S&T Innovation (No. 2021R52012), the Key Research and Development Projects of Zhejiang Province (No. 2022C03112), and the Wenzhou Innovation Team. Conflicts of interest None.