Update on XEN Gel Stent: A Narrative Review on Indications, Surgical Technique, and Postoperative Management

Abstract

Despite topical ocular hypotensive treatment and selective laser trabeculoplasty being the preferred first-line treatment modalities for lowering intraocular pressure, many patients require surgery for further controlling glaucoma progression. The XEN stent is a surgical device designed for the management of glaucoma where previous medical treatments have failed, offering greater predictability and fewer vision-threatening complications compared to trabeculectomy or tube shunts. This comprehensive and narrative review aims to assess different aspects related to XEN implant, including its efficacy, patient profile, surgical technique, and the identification of potential predictors of clinical outcomes. Additionally, this paper describes the most frequently reported adverse events associated with the XEN implant, with the objective of reducing their incidence through a comprehensive understanding of their underlying pathophysiology. Moreover, the authors draw on both existing literature and their clinical experience to provide recommendations for the optimization of the use of this implant.

Key Summary Points

Glaucoma remains a leading cause of irreversible blindness, and despite the availability of topical therapies and laser trabeculoplasty, many patients require surgical intervention due to inadequate intraocular pressure (IOP) control.

Traditional filtering surgeries such as trabeculectomy are effective but associated with higher rates of vision-threatening complications, creating an unmet need for safer alternatives.

This narrative review assessed the available evidence on the XEN Gel Stent, focusing on its efficacy, safety, patient selection, surgical techniques, and postoperative management compared with conventional surgical approaches.

Evidence demonstrated that the XEN stent achieved sustained IOP lowering into the mid- to low-teens, reduced medication burden, and maintained a favorable safety profile with mainly transient and manageable adverse events.

The incorporation of refined surgical techniques and individualized patient selection increased the versatility of the XEN implant, while challenges such as hypotony and bleb fibrosis highlighted the need for ongoing optimization and long-term evaluation.

Introduction

The term open-angle glaucoma (OAG) encompasses a broad spectrum of chronic and progressive optic neuropathies characterized by the degeneration of retinal ganglion cells and their axons, leading to visual field loss [1]. Lowering intraocular pressure (IOP) is currently regarded as the primary modifiable risk factor [2] for treating this pathology. First-line treatment for OAG typically involves the use of topical IOP-lowering medications [3, 4]. Medical treatment often follows a stepwise approach, beginning with a single topical drug and progressing to multidrug combinations or laser therapy if needed [3, 4].

According to the current European Glaucoma Society (EGS) guidelines, selective laser trabeculoplasty (SLT) may be offered as an initial treatment option. In cases where a lower target IOP is required, surgical intervention may also be considered as a first-line approach [4]. However, some patients fail to achieve adequate IOP control with initial therapies and ultimately require additional interventions [3–6], including surgical procedures such as trabeculectomy [7]. While effective, trabeculectomy is associated with a higher risk of sight-threatening complications [8].

Like other chronic diseases, poor adherence to daily medication is a significant barrier to effective glaucoma management. Adherence and persistence among patients with glaucoma using ocular hypotensive medications are generally low [9]. Furthermore, despite the proven overall efficacy of topical IOP-lowering treatments, they are not suitable for all patients. Various factors can impede patients' ability to strictly follow their prescribed daily eye drop regimen or sustain continuous long-term treatment. They include the complexity of treatment regimens, costs of treatments, lack of tolerance and side effects (i.e., itching, stinging, blurred vision), physical limitations, difficulty in properly administering eye drops, forgetfulness, incompatibility with lifestyle, and lack of education about the disease and its severity [10, 11].

Additionally, the presence of comorbidities must be also considered. Various conditions, such as neurodegenerative diseases that impair cognition and memory, motor disorders, and low vision, are common comorbidities that can negatively affect adherence to eye drop regimens.

Patients affected by these comorbidities may benefit from more proactive or interventional treatment strategies that reduce reliance on self-administered eye drops [12].

Consequently, inadequate treatment adherence can lead to suboptimal IOP control, increasing the risk of glaucomatous damage and visual impairment [13].

The limited effectiveness of medical treatments in many patients, together with the complications associated with traditional surgery, have led to the development of new, effective, and safe surgical techniques that enable earlier intervention [12].

Significant advancements have been made in glaucoma surgery over the past several years. One of the most notable developments was the advent of minimally or microinvasive glaucoma surgery (MIGS) and minimally invasive bleb-forming surgery (MIBS) devices [14, 15]. These devices have been engineered to provide safer and less traumatic methods for lowering IOP in patients with glaucoma [14, 15].

Although MIGS devices can be categorized into trabecular procedures/devices and suprachoroidal devices, the EGS Guidelines define MIGS strictly as ab interno, non-bleb-forming procedures [15]. In contrast, MIBS devices establish an alternative outflow pathway for aqueous humor to the subconjunctival space, akin to trabeculectomy, and can be implemented via either ab interno or ab externo approaches [15].

The XEN Gel Stent (AbbVie Inc., Chicago, USA) is a hydrophilic, 6-mm-long tube composed of porcine gelatin cross-linked with glutaraldehyde to prevent degradation post-implantation [16, 17]. The design of the XEN device is based on the Hagen–Poiseuille law of laminar flow, where the length and inner diameter of the tube dictate the flow resistance and, consequently, the flow rate. Currently, two models of the XEN Gel Stent are commercially available: the XEN45 Gel Stent and the XEN63 Gel Stent [16, 18]. The main difference between them lies in the internal lumen diameter, with the XEN63 Gel Stent featuring a larger inner diameter of 63 μm compared to 45 μm in the XEN45 Gel Stent [18]. This increased lumen size is designed to decrease outflow resistance, potentially enhancing IOP lowering. Despite this, the outer diameter of the XEN63 Gel Stent is only approximately 12% larger than that of the XEN45 Gel Stent, resulting in a comparable implant footprint and minimal additional tissue disruption. Both devices, in their updated versions, are implanted using a 27-gauge injector needle (outer diameter ~0.41 mm), enabling a less invasive delivery approach [19].

At the time of writing, the XEN 63 Gel Stent has obtained CE mark authorization for use in several regions, including Europe and Canada, but has not been approved by the US Food and Drug Administration (FDA) for clinical use.

This paper aimed to review the currently available scientific evidence evaluating different aspects, including indications, evolving surgical technique, and postoperative care associated with the XEN implant in different clinical paradigms.

Methods

We conducted a comprehensive but not systematic review of literature available on PubMed to July 15, 2024. The search was performed using the keywords [“Glaucoma” OR “Open-angle Glaucoma” OR “Primary open-angle glaucoma” OR “Secondary open-angle glaucoma”] AND [“XEN” OR “microinvasive glaucoma surgery/MIGS” OR “minimally invasive bleb surgery/MIBS”]. This study included papers involving human subjects and written in English, French, Italian, Portuguese, or Spanish. Additionally, the reference lists of included studies were manually checked to identify any further relevant publications for the review.

Consistent with the methodological framework of a narrative review, we did not apply predefined inclusion or exclusion criteria, nor did we conduct a formal, structured critical appraisal of individual studies. Instead, to provide readers with a clear understanding of the evidence base, we included a broad range of study types, comprising both regulatory registration trials and independent, non-sponsored research. These included randomized clinical trials, prospective and retrospective clinical studies, retrospective real-world cohort analyses, and multicenter registries. When clinically relevant, we also incorporated case reports and small case series, particularly those describing uncommon or rare adverse events not captured in larger datasets. This descriptive approach reflects the heterogeneity of the available literature while remaining aligned with the goals and methodological standards of a narrative review.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

XEN45 Gel Stent and XEN63 Gel Stent, Two Ways to Address IOP Lowering

A predictive model identified implant diameter and bleb pressure as key factors in IOP reduction, with minimal influence from tube length or position [20].

Unlike the XEN45 Gel Stent device, which has extensive clinical experience [21–26], the available evidence evaluating the efficacy and safety of the XEN63 Gel Stent is limited [18, 19, 27–30]. Moreover, to the best of our knowledge, only three papers have compared the efficacy and safety of the XEN45 Gel Stent versus XEN63 Gel Stent devices [18, 28, 31].

Hussein et al. [18] compared the efficacy, in terms of IOP lowering, and safety profile of the XEN63 Gel Stent with mitomycin C (MMC) with those of the XEN45 Gel Stent with MMC in 84 glaucomatous eyes with or without previous subconjunctival glaucoma surgery. This study demonstrated that the XEN63 Gel Stent implant achieved lower mean IOP than the XEN45 Gel Stent implant (12.7 ± 4.8 mmHg versus 15.5 ± 5.1 mmHg, P = 0.001) and required fewer classes of medications (0.6 ± 1.1 versus 1.7 ± 1.6, P = 0.0005) [18]. In a retrospective analysis, Evers et al. [28] evaluated the efficacy and safety of the XEN63 Gel Stent versus the XEN45 Gel Stent implants in patients with glaucoma. Both devices achieved substantial IOP reductions, with decreases of 44.6% for the XEN63 and 39.8% for XEN45 stent. Regarding IOP-lowering medications, both devices significantly reduced the need for IOP-lowering medications; however, the XEN63 Gel Stent achieved a greater reduction than the XEN45 Gel Stent (−3.1 ± 0.9 drugs [−93.9%] vs. −2.1 ± 1.8 drugs [−81.6%], respectively) [28]. This study did not find significant differences between devices in terms of IOP lowering, due mainly to the limited sample size [28]. No significant differences in safety outcomes were observed between the XEN63 and XEN45 Gel Stent groups. Rates of hypotony, anterior chamber hemorrhage, and transient choroidal changes were comparable, though one case of suprachoroidal hemorrhage occurred in the XEN63 Gel Stent group, associated with multiple high-risk factors [28].

Finally, a retrospective single-center study compared the efficacy and safety of XEN63 Gel Stent and XEN45 Gel Stent implants using an ab externo 30G needle approach [31]. Both devices showed similar surgical success and IOP reduction at 1 year, with no significant differences. The 63 µm implant showed a trend toward greater IOP reduction and reduced medication use but had a higher rate of hypotony-related complications, which were mostly managed conservatively [31].

Table 1 shows an overview of the main clinical outcomes achieved with the new XEN63 Gel Stent device.

Table 1.

An overview of the currently available scientific evidence with the XEN63 device

Study	Design	Number of eyes	Diagnosis	Follow-up (months)	Pre-op IOP, mmHg	Final IOP, mmHg	IOP lowering	Mean preoperative NOHM	Mean NOHM, last visit	Success rates (%)a
Fea et al. [19]	R	23	OAG	3	27.0 ± 7.8*	12.2 ± 3.4*	−14.8 (−20.1 to −9.5)**	2.3 ± 0.9*	0.1 ± 0.4*	69.6
Fea et al. [27]	R	23	Miscellanyb	18	27.0 ± 7.8*	14.1 ± 3.4*	−12.9 (−16.9 to −8.9)**	2.3 ± 0.9*	1.0 ± 1.4*	77.8
Evers et al. [28]	R	15	Miscellanyc	204 days (range 78–338 days)	18.1 ± 3.9*	9.1 ± 2.0*	−44.6 ± 16.5%	NA	0.2 ± 0.8d	80.0
Voykov et al. [29]	P	6	OAG	24	35.5 (25–4)†	11.5 (4–15)†	NA	4 (3–4)†	0 (0–1)†	83.3
Martínez-de-la-Casa et al. [30]	P	80	POAG	12	21.1 ± 4.5*	14.3 ± 4.5*	−6.9 (−8.2 to −5.6)**	2.3 ± 0.8*	0.3 ± 0.7*	68.8
Bertolani et al. [31]	R	28	Miscellanye	12	23.9 ± 2.5*	12.4 ± 4.2*	NA	2.6 ± 0.8*	0.3 ± 0.9*	71.4

Pre-op, preoperative; IOP, intraocular pressure; NOHM, number of ocular hypotensive medications; R, retrospective; P, prospective; OAG, open-angle glaucoma; POAG, primary open-angle glaucoma

*Mean (standard deviation)

**Mean (95% confidence interval)

^†Median (range)

^aComplete success

^bIncluded eyes with primary open-angle glaucoma (n = 14), uveitic glaucoma (n = 4), pseudoexfoliative glaucoma (n = 1), primary angle-closure glaucoma (n = 1), traumatic glaucoma (n = 1), and missing information (n = 2)

^cIncluded eyes with normal-tension glaucoma (n = 9), pseudoexfoliative glaucoma (n = 3), primary open-angle glaucoma (n = 2), and uveitic glaucoma (n = 1)

^dCompared to the baseline, the mean number of topical ocular hypotensive medications was reduced by 3.1 ± 0.9 agents (94.0%)

^eIncluded eyes with primary open-angle glaucoma (18), pseudoexfoliative glaucoma (3), juvenile (2), uveitic (2), other–did not specify (3)

Meta-analyses have consistently demonstrated the efficacy and safety of the XEN45 Gel Stent implant in glaucoma treatment [21–25]. One meta-analysis of 4410 eyes reported a mean IOP reduction of approximately 35%, with final IOP levels near 15 mmHg, regardless of whether the implant was used alone or combined with cataract surgery [24]. Another systematic review and meta-analysis of 78 studies (6554 eyes) confirmed significant IOP lowering, with a standardized mean difference (SMD) of 1.69 (95% confidence interval [CI] 1.52–1.86) [25]. The XEN45 Gel Stent also significantly reduced postoperative reliance on ocular hypotensive medications by about two agents [21–26]. Stratified analyses indicated that the stent’s effectiveness did not vary significantly across different ethnic groups [25].

Martínez-de-la casa et al. [30] recently published a multicenter, prospective study that evaluated the efficacy and safety of the XEN63 Gel Stent device in patients with primary open-angle glaucoma (POAG). The results of this study showed that the XEN63 Gel Stent device either alone or in combination with phacoemulsification significantly reduced IOP (p < 0.0001 each, respectively) and the number of IOP-lowering medications (p < 0.00011 each, respectively), with a good safety profile [30].

Patient Profile

Patient Profiles and Clinical Use of XEN Gel Stents

The XEN Gel Stent was approved by the FDA for the treatment of POAG, including pseudoexfoliative (PEX) and pigmentary (PG) subtypes unresponsive to medical therapy, as well as for refractory cases after failed surgery [32, 33]. In Europe, it is indicated for POAG patients with inadequate response to medication [34]. The Italian XEN Glaucoma Treatment Registry (XEN-GTR) reported that most patients had POAG, with approximately 10% diagnosed with other glaucoma types such as PEX, uveitic, steroid-induced, and post-traumatic glaucoma [35, 36]. No significant differences in IOP lowering or medication reduction were found between POAG and PEX eyes [25], and multiple studies confirmed the safety and efficacy of the XEN45 Gel Stent in PEX and uveitic glaucoma populations [37–47]. Evidence also supported its use in narrow- or closed-angle glaucoma [48–52] and in some cases of moderate to severe disease, despite initial indications for mild to moderate glaucoma [34, 35, 53–57].

In patients with high myopia (≥ 6 diopters), data were limited but suggested comparable efficacy and safety to non-myopic eyes [56, 58–61]. XEN63 Gel Stent implants did not show increased risk of hypotony in this subgroup, although a careful surgical technique was recommended to avoid overfiltration [56, 59–61].

For patients with prior failed glaucoma surgeries, including trabeculectomy, XEN45 Gel Stent implantation demonstrated similar success and safety profiles, with reported IOP reductions up to 49.5%, and 70–83% of eyes achieving target IOP without medication [62–70]. Ab interno and ab externo approaches showed comparable outcomes even in eyes with prior conjunctival scarring [66]. When superior quadrant implantation was unfeasible, inferior quadrant placement of the XEN45 Gel Stent and XEN63 Gel Stent was explored as a viable and effective alternative in refractory cases [71, 72] (Fig. 1).

Fig. 1.

Ab interno implantation of a XEN Gel Stent in the infero-nasal quadrant through the phacoemulsification main incision. Courtesy of RGG

XEN Alone Versus XEN Combined with Phacoemulsification Procedure: Intraocular Pressure-Lowering Profile

Since the introduction of the XEN device into the glaucoma treatment armamentarium, an important question has arisen: whether XEN alone and XEN combined with phacoemulsification differ in their IOP-lowering profiles. Numerous studies [56, 73–88] and meta-analyses [21, 23–25] have evaluated the efficacy of the XEN45 Gel Stent implant, both as a standalone intervention and combined with cataract surgery (phacoemulsification). Upon review of the literature, the most reasonable conclusion is that there is no consensus about the superiority of the standalone procedure compared to the combined approach with cataract surgery (see Table 2).

Table 2.

Analysis of clinical outcomes comparing the XEN45 implant as a standalone procedure versus its combination with cataract surgery (phacoemulsification) reported by the different meta-analyses

	XEN alone		XEN + phaco		Mean difference (95% CI)a	p	XEN alone	XEN + phaco	Mean difference (95% CI)a	p
Study	N	IOP loweringa	N	IOP loweringa			NOHM	NOHM
Wang et al. [21]	559	NP	475	NP	0.22 (0.05 to 0.40)	0.01	NP	NP	−0.20 (−0.46 to 0.06)	0.14
Chen et al. [24]	1074	−7.80 (−9.97 to −7.38)	659	−8.35 (−9.82 to −6.88)	NP	NP	−1.97 (−2.19 to −1.75	−1.86 (−2.11 to −1.60)	NP	NP
Yan et al. [25]	1314	NP	1160	NP	−0.01 (−0.09 to 0.08)	0.894	NP	NP	0.09 (−0.04 to 0.23)	0.672

N, number of eyes; 95% CI, 95% confidence interval; NOHM, number of ocular hypotensive medications; NP, not provided

^aMean (95% CI) intraocular pressure (IOP) lowering (mm Hg)

According to the findings reported by Chen et al. [24], both the XEN implant alone (mean difference: −7.8 mmHg; 95% CI: −8.21 to −7.38 mmHg, p < 0.001) and XEN combined with phacoemulsification (mean difference: −8.35 mmHg; 95% CI: −9.82 to −6.88 mmHg, p < 0.001) significantly lowered IOP. Similarly, Yang et al. [25], in a systematic review and meta-analysis, reported no significant difference in IOP lowering between the XEN-alone and the combined phaco-XEN procedures (standardized mean difference: −0.01, 95% CI: −0.09 to 0.08, p = 0.894). However, the standalone XEN procedure was associated with a greater reduction in the number of ocular hypotensive medications (p = 0.019) [25].

Conversely, a systematic review and meta-analysis by Wang et al. [21] presented differing results, indicating that the XEN implant alone was more effective in lowering IOP than the combined XEN + phacoemulsification procedure (p = 0.01), though no significant difference was found in the reduction of ocular hypotensive medications (p = 0.93) [21].

Regarding the XEN63, Martínez-de-la-Casa et al. [30] did not find significant differences between XEN alone or in combination with phacoemulsification in mean IOP lowering (p = 0.8759), mean ocular hypotensive medication reduction (p = 0.0656), or success rates (p = 0.5555).

Considering the currently available scientific evidence and our own clinical experience, XEN, whether used alone or in combination with phacoemulsification, significantly reduces IOP and decreases the need for ocular hypotensive medications. Indeed, current data do not support the superiority of the combined procedure over the solo procedure, or vice versa.

XEN Versus Other Filtration Surgeries and Devices

XEN Versus Trabeculectomy

The XEN45 Gel Stent has been compared to traditional filtration surgery, particularly trabeculectomy, in several prospective studies. In a multicenter randomized controlled trial [89], the XEN45 Gel Stent demonstrated non-inferiority to trabeculectomy in achieving a ≥ 20% reduction in IOP at 12 months. While trabeculectomy generally achieves greater IOP reduction and a more substantial decrease in topical medication burden, it is also associated with a higher rate of postoperative complications [77, 90]. For instance, trabeculectomy has been linked to a more pronounced decline in corneal endothelial cell density compared to the XEN45 Gel Stent [91]. Long-term data further support the durability of XEN45 Gel Stent outcomes, with some studies showing sustained efficacy up to 3 years, albeit with slightly lower pressure-lowering efficacy than trabeculectomy [92]. Notably, there are currently no direct comparative studies evaluating the XEN63 Gel Stent device versus trabeculectomy, leaving a gap in the literature regarding newer XEN models.

XEN Versus Microshunt (Preserflo)

Two comparative studies evaluating the XEN Gel Stent (XEN45 Gel Stent and XEN63 Gel Stent) versus the poly(styrene-block-isobutylene-block-styrene) (SIBS) microshunt in patients with POAG reported no statistically significant differences in IOP lowering between devices [93, 94]. However, a multicenter retrospective study assessing 12-month outcomes of the SIBS microshunt, gelatin 45 μm microstent, and trabeculectomy with MMC indicated that the SIBS microshunt demonstrated superior surgical success rates and was associated with fewer postoperative complications, interventions, and reoperations compared to the other interventions [95].

Additionally, differences have been observed in their safety profiles and postoperative course. XEN implants have been more frequently associated with transient hypotony and the need for needling procedures, while Preserflo has shown a higher rate of bleb fibrosis and surgical revision [95, 96]. Furthermore, in cases requiring open bleb revision following surgical failure, the XEN45 Gel Stent device demonstrated a higher probability of achieving surgical success than the Preserflo implant [97]. It is important to note that in most comparative studies, XEN implantation was performed via an ab interno approach with closed conjunctiva, whereas Preserflo was placed ab externo with open conjunctiva, a difference in surgical techniques that may have influenced the outcomes and which limits direct comparison [20].

The Impact of XEN Implant on Patient Quality of Life

Glaucoma adversely impacts patients' quality of life. The awareness of having the disease itself detrimentally affects quality of life [98, 99]. Furthermore, the quality of life of patients with glaucoma is reduced not only by the disease itself but also by the treatment regimen. Indeed, topical ocular hypotensive medications or glaucoma filtering surgery may be responsible for or exacerbate a concurrent ocular surface disease [100, 101].

Several papers have evaluated the impact of XEN implant on patients’ quality of life [102–104].

Hassan et al. [102] conducted a retrospective study assessing the quality of life (using the Glaucoma Quality of Life-15 [GQL-15] questionnaire) in 52 patients (58 eyes) with POAG, who underwent XEN45 Gel Stent implant surgery. The results of this study demonstrated a significant improvement in mean summary scores when comparing preoperative and postoperative conditions [102].

Similarly, Pahljina et al. [103] conducted a cross-sectional study evaluating the quality of life (using the Glaucoma Symptom Scale (GSS) questionnaire) in a cohort of 80 patients who underwent a XEN implant procedure in combination with cataract surgery (phacoemulsification). This study found that the quality of life was significantly improved after the combined XEN45 Gel Stent + phacoemulsification procedure in those cases where the intervention reduced the need for ocular hypotensive medications [103].

An important factor influencing surgical decision-making is the fear or anxiety patients may experience, which can contribute to delays in electing surgical intervention [89]. In this context, the availability of a safe and minimally invasive procedure, such as the XEN implant, may encourage patients to consider surgery as a viable treatment option [89]. Supporting this, findings from the Gold-Standard Pathway Study (GPS) demonstrated that patients receiving the XEN implant reported lower frequency and severity of ocular symptoms and visual function disturbances postoperatively than those undergoing trabeculectomy, with statistically significant improvements observed at 6 months [89]. Moreover, patients in the XEN group resumed daily activities earlier and exhibited less work and activity impairment at key postoperative time points, particularly at week 1 and month 3, suggesting superior patient-reported outcomes [89].

A consensus document evaluating glaucoma management, focusing on the XEN Gel Stent implant, was published in 2024 [104]. The panel identified different issues potentially impacting patients' quality of life. Specifically, the experts emphasized the necessity of achieving concordance with patients on the therapeutic strategy and elucidating the disease progression and available treatment modalities [104]. Concerning topical therapy, the expert panel concurred that aesthetic considerations are significant for a substantial proportion of patients and that adherence is frequently compromised by lifestyle constraints or reliance on others for medication administration. Additionally, the panelists concurred that these obstacles related to nonadherence and potential intolerance can result in patient dissatisfaction. Finally, regarding surgery, the experts noted that patients' apprehension about surgery can defer their decision to opt for this treatment. On the other hand, the panel agreed that safer procedures with shorter recovery times, like the XEN implant, might serve as an incentive for selecting this procedure [104].

Perioperative Management

Anesthesia

The anesthetic technique will be determined primarily by the experience/preference of both the surgeon and the anesthesiologist. Additionally, this decision is also based on the clinical characteristics of both the patient and the eye [105–107].

It has been reported that pain prevention reduces the likelihood of proinflammatory cytokine release, which can contribute to scar tissue formation and bleb failure [107–109]. Surgeons may choose to employ a regional block, particularly in initial cases, to minimize the risk of patient or ocular movements that could result in iatrogenic trauma. Typically, the anesthesia requirements for gel stent implantation are comparable to those for other ocular surgeries, such as trabeculectomy [107]. Many surgeons find that using topical anesthesia with optional subconjunctival lidocaine injection alone provides adequate comfort for the procedure [107].

Surgical Technique

The XEN Gel Stent is supplied preloaded in an injector device, which is a sterile, single-handed plastic inserter equipped with a 27-gauge sharp beveled needle [33, 34, 110].

Although the XEN45 Gel Stent is approved by both the EMA and FDA for ab interno implantation, many surgeons have chosen to adopt the ab externo approach. As ophthalmologists have gained more experience with the device, the surgical technique has evolved considerably [111].

Updated Surgical Approaches to XEN Gel Stent

The classical ab interno/closed conjunctiva technique for the XEN Gel Stent is well known and has been extensively described elsewhere by Vera et al. [107] and other authors [33, 34, 110, 111].

Since the introduction and publication of the classical approach, the surgical technique with XEN has evolved significantly. Surgeons have developed different approaches and maneuvers that allow XEN surgery to be adapted to their preferences and patient needs to achieve better results. Many of these novel approaches share the common goal of creating and maintaining a space where the implant rests physically free from Tenon’s tissue [112]. After a successful ab interno/closed conjunctiva implantation, some authors recommend performing a primary needling with a 27G hypodermic needle or spatula [112].

Kerr et al. observed that primary needling decreased the number of postoperative needling and follow-up visits [113], while Buenasmañanas-Maeso et al. found fewer postoperative interventions but no significant differences in IOP reduction or medication use compared to non-primary needling cases [114]. Despite these promising findings, evidence remains limited and insufficient to recommend routine primary needling [113, 114]. Clinically, primary needling may be indicated when the XEN implant is twisted, trapped, or immobile in the subconjunctival space, or in eyes with prior failed glaucoma surgeries or elevated risk of conjunctival fibrosis [26, 113–115]

The open conjunctiva approach for Xen Gel Stent implantation offers key advantages, including suitability for patients with conjunctival scarring and precise control over stent placement [116] (Fig. 2). This technique allows for better positioning of the microstent, reducing the risk of conjunctival erosion and enhancing bleb formation [116].

Fig. 2.

Ab interno/open conjuntiva implantation of a XEN Gel Stent in a pseudophakic patient. Courtesy of RGG

For the ab interno approach with the open conjunctiva technique [117, 118], a traction suture can be positioned superiorly if needed, followed by infraduction of the eye. A supero-nasal conjunctival limbal peritomy spanning approximately 3 clock-hours is performed. The anterior chamber (AC) is then filled with 1% sodium hyaluronate, and the XEN is implanted as in the classical technique. The conjunctiva and Tenon’s capsule are subsequently realigned and secured with polyglactin or nylon sutures. After stent placement, the 1% sodium hyaluronate is removed, and the AC is re-pressurized using a balanced salt solution.

Compared to ab interno placement, the ab externo placement of the Xen Gel Stent provides several advantages, prompting many surgeons to adopt this technique [116]. In addition to eliminating the need for viscoelastic injection, this approach offers greater flexibility in selecting the implant site, particularly beneficial for patients with prior trabeculectomy or scarring [116]. This approach minimizes intraocular maneuvers, reducing the risk of complications like endothelial loss, corneal wound leaks, or lens damage in phakic patients. Additionally, it requires no angle surgery skills, making it easier for surgeons transitioning from traditional glaucoma procedures, and it allows precise stent adjustments for optimal positioning [116] (Fig. 3).

Fig. 3.

Ab externo/open conjunctiva implantation of a XEN Gel Stent in a patient with prior penetrating keratoplasty. Courtesy of JVA

The ab externo approach can be executed with or without conjunctival dissection [110]. In the first technique, a closed ab externo approach, the conjunctiva is displaced anteriorly, and the needle penetrates the sclera 2.5 mm from the limbus, tunneling through the sclera before entering the AC, where the stent is then deployed. MMC is injected subconjunctivally either before or after implantation [111].

In both ab externo techniques, placement in the AC is confirmed using gonioscopic visualization. The stent can be gently repositioned with a bent tying forceps if it is either too short or too long in the anterior chamber. This repositioning can be performed through the conjunctiva if a closed technique is used [111].

Studies by Gallardo et al. [66], Ucar and Cetinkaya [119], Tan et al. [120], Do et al. [121], and Ruda et al. [122] have reported no significant differences in IOP reduction or success rates between ab interno and ab externo approaches for XEN implantation.

Some studies have indicated that the open conjunctiva approaches may reduce the need for postoperative needling, resulting in shorter surgical times and faster postoperative visual recovery, and exhibit more favorable success rates than the classical closed-conjunctiva approach [117, 118, 123–125].

The procedural steps for each approach are outlined in Table 3.

Table 3.

Main steps to be performed during XEN implant surgery in ab interno and ab externo procedures. Data from Fea et al. [110] and Vera et al. [111]

Step	Ab interno approach	Ab externo approach
Marking	Superior conjunctiva is marked 2.5–3.0 mm posterior to the limbus	Superior conjunctiva is marked ~ 2.5 mm posterior to the limbus
MMC injection	Injected subconjunctivally before or after implantation	Injected subconjunctivally before or after implantation
Incisions	Clear corneal incisions (main and side-port) are created	Optional side-port can be created
Filling of anterior chamber	Filled with cohesive viscoelastic	Optional
Needle insertion	Inserted through the main corneal incision and directed towards the superior area	Needle pierces the sclera 2.5 mm from the limbus and tunnels through the sclera before entering the AC
Gonio lens use	Used to assess positioning in the angle, ideally entering just above pigmented trabecular meshwork	Gonioscopic visualization to confirm placement in the anterior chamber (after placement)
Needle advancement	Advanced through the sclera into the subconjunctival space while stabilizing the eye with a second instrument in side-port	Advanced through subconjunctival space into the sclera while stabilizing the eye with counter traction
Stent deployment	Gelatin stent is released once the bevel is visualized exiting the sclera into the subconjunctival space	Gelatin stent is released once the bevel is visualized in the anterior chamber
Injector removal	Injector is removed from the eye	Injector is removed from the eye
Implant positioning	Approximately 1 mm remains in the AC, 2 mm in scleral wall, 3 mm under conjunctiva	Approximately 1 mm remains in the AC, 2 mm in scleral wall, 3 mm under conjunctiva
Viscoelastic removal	Washed out of the anterior chamber to create an early bleb and confirm device patency	If used, washed out of the anterior chamber to create an early bleb and confirm device patency

MMC, mitomycin C; AC, anterior chamber

Fibrosis Prevention Following XEN Gel Stent Implantation

Mitomycin C (MMC) is an antimetabolite widely used in glaucoma surgeries to inhibit fibroblast proliferation and reduce postoperative scarring, thereby decreasing the risk of surgical failure [126]. Despite its frequent use with the XEN Gel Stent, there is no established consensus on the optimal MMC concentration, which varies between 0.1 mg/mL and 0.4 mg/mL based on patient-specific considerations [23–26, 110]. Many clinicians therefore adopt a tailored approach. While higher MMC concentrations may improve surgical success, this must be balanced against the potential for increased postoperative complications [23–26, 110].

A retrospective study categorizing MMC doses into ≤ 20 mcg, 20–40 mcg (excluding 20 mcg), and > 40 mcg found no significant impact of MMC dose on IOP change, glaucoma medication usage, needling rates, or secondary surgeries [127]. Similarly, Monja-Alarcón et al. reported no significant differences in IOP reduction, medication use, or adverse event incidence between MMC 0.01% and 0.02%, suggesting that lower MMC doses may be equally effective without reducing adverse events [128].

Inflammation and fibrosis are principal causes of failure in filtering glaucoma surgeries [129, 130]. Effective postoperative inflammation management is critical to preserving bleb function, as early failure often results from excessive scarring and drainage pathway obstruction [129]. Corticosteroids remain the cornerstone for modulating inflammation and supporting IOP control [129, 130]. Postoperative care following XEN implantation typically includes topical broad-spectrum antibiotics early on to prevent infection and prolonged corticosteroid therapy to mitigate inflammation and prevent bleb fibrosis [19–30]. Although optimal medication type, route, frequency, and duration lack consensus, prolonged corticosteroid use is generally warranted given the heightened inflammatory response associated with glaucoma surgeries relative to cataract procedures [131].

Impact of Filtration Bleb Morphology on the XEN Implant Outcomes

In glaucoma surgical interventions involving the implantation of filtering blebs, postoperative assessment of these blebs is imperative. The morphology and functionality of the blebs are critical determinants of the surgery's success.

Current evidence indicates that anterior segment optical coherence tomography (AS-OCT) is a valuable tool for assessing the internal morphology of filtering blebs [132–134] (Fig. 4).

Fig. 4.

Anterior segment optical coherence tomography (AS-OCT) of different patients implanted with XEN Gel Stent. A Supra-scleral XEN stent with a patent bleb and multiple small, diffuse cysts. B. Tenon cyst after XEN Gel Stent implantation. C. Intra-Tenon XEN Gel Stent showing scarce cystic spaces. D. Anterior chamber assessment of a XEN Gel Stent in a phakic patient measuring the distance from the implant to the endothelium. Courtesy of JVA

However, bleb morphology of XEN and that of trabeculectomy may differ, since, unlike trabeculectomy, expected uniform flow of aqueous humor through the stent is expected [135, 136]. XEN blebs, indeed, were found to be significantly flatter than trabeculectomy blebs [135, 137].

Different studies have assessed bleb morphology in eyes that underwent XEN implantation [112, 137–142].

Lenzhofer et al. [137] found that the appearance of blebs following XEN surgery appears to differ from that reported in the literature on traditional trabeculectomy. The results of their prospective study suggested a correlation between IOP and long-term surgical success with bleb morphology as visualized by AS-OCT. The presence of small, diffuse cysts is directly associated with lower IOP, whereas cystic encapsulation at 3 months is predictive of higher rates of surgical failure [137].

Additionally, Kim et al. [139] reported that evaluating blebs with AS-OCT was valuable for correlating tip location and bleb morphology with clinical profiles, noting that a lower early postoperative IOP is associated with surgical success.

Furthermore, Chen et al. [140] demonstrated that AS-OCT offers a comprehensive evaluation of bleb morphology, which may aid in identifying causes of impaired outflow, determining the timing, and assessing the efficacy of needling interventions in eyes with suboptimal bleb function or intraocular pressure control, particularly in the early postoperative period.

Finally, Wy et al. [142] observed that a greater height of the internal cavity of the bleb was associated with lower IOP following XEN Gel Stent implantation.

In summary, current evidence suggests that AS-OCT evaluation of bleb morphology after XEN implantation reveals that flatter blebs and greater internal cavity heights are associated with lower IOP, contributing to surgical success, while cystic encapsulation predicts higher failure rates [117, 137–142].

Impact on Endothelial Cells

Preservation of corneal endothelial cells is a key consideration in glaucoma surgery, particularly in procedures involving the anterior chamber. The XEN Gel Stent has demonstrated a favorable safety profile in this regard. In a comparative study, XEN implantation resulted in significantly less endothelial cell loss than trabeculectomy in the short term [91]. Long-term data further support these findings; a 5-year follow-up study by Lenzhofer et al. reported stable endothelial cell density after transscleral ab interno XEN implantation, with no clinically significant loss over time [143]. Additionally, when combined with cataract surgery, the endothelial cell loss associated with phaco-XEN appears to be comparable to that of phacoemulsification alone, as shown in data from the Italian XEN-GTR registry [144] and corroborated by Gillmann et al. in a 2-year follow-up study [79]. These findings highlight the endothelial safety of the XEN procedure, both as a standalone intervention and when performed in combination with phacoemulsification.

Real Clinical Impact of “Hypotony” after XEN Implant Surgery

Hypotony refers to an abnormally low IOP following the surgical procedure. It can be classified as numerical or clinical.

Numerical hypotony is generally defined as an IOP below 5–6 mmHg, in the absence of clinical symptoms. In contrast, clinical hypotony is characterized by the manifestation of ocular signs or symptoms directly attributable to low IOP. These may include choroidal effusion, hypotony maculopathy, a decrease in visual acuity by two or more lines consistent with hypotony maculopathy, or corneal edema in the setting of an IOP less than 6 mmHg [18, 24, 26, 85, 145–147].

Chen et al. [24] reported an incidence rate of hypotony after XEN45 Gel Stent of 9.59%. However, Betzler et al. [145], using the same criterion, found an incidence rate of 20% (95% CI: 10–31%).

Galimi et al. observed that numerical hypotony was common after XEN implant, affecting 57% of eyes. Nevertheless, it was predominantly asymptomatic, most frequently occurred within the first week post-surgery, and resolved spontaneously [146].

A comprehensive understanding of the different risk factors associated with clinically significant hypotony might be useful for implementing proactive strategies to limit its impact on surgery outcomes [147].

Hypotony following XEN Gel Stent implantation can present in several forms, each requiring tailored management [147]. Early postoperative hypotony is common and usually transient, occurring due to excessive initial outflow. Persistent hypotony, which lasts longer, may result from insufficient tissue resistance causing overfiltration or peritubular filtration. Additionally, complications such as bleb-related hypotony can arise from overfiltration into thin blebs, while rare ciliary shutdown hypotony results from reduced aqueous production [147]. Overfiltration hypotony, linked to excessive drainage through the stent, may necessitate interventions like bleb revision or viscoelastic injections to stabilize intraocular pressure [147].

The primary step in managing hypotony involves identifying and addressing the underlying cause. Leaks or surgical issues may be treated with options like bandage contact lenses, patching, or suturing. For hypotony due to overfiltration or ciliary body shutdown, conservative management is often preferred. Prompt intervention for complications, such as choroidal detachment or corneal–lenticular contact, along with close monitoring, is essential for effective recovery [147].

In some cases, the XEN45 Gel Stent implant could be preferred over the XEN63 Gel Stent in patients considered to be at higher risk of postoperative hypotony, due to its lower internal lumen diameter, which provides greater outflow resistance. This characteristic makes the XEN45 Gel Stent a safer choice in patients with thinner sclera, such as those with high myopia, or in individuals with a history of overfiltration or hypotony-related complications following prior ocular surgery [145–147]. It is also considered more appropriate in patients with uveitic glaucoma, where unpredictable inflammatory responses may increase the risk of sudden hypotony, and in elderly or frail patients with lower ocular rigidity. By offering a more controlled outflow of aqueous humor, the XEN45 Gel Stent helps reduce the likelihood of early postoperative hypotony, shallow anterior chamber, or choroidal effusion—potential complications more frequently reported with lower-resistance devices such as the XEN63 Gel Stent [145–147].

Management of Dysfunctional Bleb

Secondary needling and open bleb revision serve as rescue techniques for bleb failure [24, 26, 148].

Bleb fibrosis is a frequent complication after XEN implantation, occurring in up to 45% of cases [148]. Secondary needling, a minimally invasive procedure, is routinely employed to restore function in failed filtering blebs [149]. Prospective studies report needling rates as high as 46.2% within 12 months, with 39.2% of eyes requiring multiple needlings within 24 months—most commonly within the first 3 months postoperatively [148]. Overall needling rates range between 5% and 62% [24, 26].

Elevated IOP on postoperative day 1 is a strong predictor for subsequent needling following standalone XEN implantation. Midha et al. demonstrated that postoperative IOP > 20 mmHg increases the likelihood of needling to 80%, while IOP < 10 mmHg reduces it to 35% [150]. Fea et al. further established significant correlations between the number of needlings and IOP measurements at day 1, week 1, and month 1 postoperatively [82]. Cutolo et al. suggested that an early postoperative IOP ≤ 9 mmHg predicts procedural success over 1 year, whereas requiring more than two needlings predicts failure [151]. Conversely, Sng et al. found no association between demographic or clinical factors (age, sex, glaucoma subtype, preoperative medications, or IOP) and increased needling risk [152].

Notably, Kiessling et al. reported that in patients receiving bilateral XEN implants, the probability of revision in the second eye was 55.2% if revision was needed in the first eye, compared to only 18.9% if the first eye did not require revision. The outcome of the first eye and the type of surgical procedure influence predictive value and can inform surgical planning for the fellow eye [153].

Open bleb revision in XEN implant surgery is a procedure performed to address complications related to excessive or inadequate bleb formation, such as bleb leakage, overfiltration, or thin-walled blebs [147, 154]. The technique involves surgically exposing the conjunctiva and Tenon’s capsule to assess the bleb's characteristics and make necessary adjustments. The surgeon may perform suturing to reinforce the bleb wall, reposition the stent, or adjust its position to regulate aqueous outflow [147, 154]. Outcomes of open bleb revision are generally favorable, with improved intraocular pressure control and reduced risk of hypotony or bleb-related complications. The procedure can also help optimize the long-term success of the XEN implant by promoting a more stable and functional bleb [147, 154].

Main Challenges Associated with XEN Implant

As demonstrated in multiple studies, the XEN stent has proven to be a safe and effective intervention for the long-term management of glaucoma [21–26]. However, several clinical challenges have emerged that require careful consideration by ophthalmologists [155].

These challenges include the prevention and management of postoperative hypotony and bleb fibrosis (see Table 4) [130, 147, 156]; reported cases of stent lumen obstruction [115, 157, 158]; recanalization of the device [159]; postoperative bleb management requiring wound-healing modulation with agents such as 5-fluorouracil [128, 160, 161]; the need for surgical revision of the implant [97, 162, 163]; stent migration or dislocation [164, 165]; bleb leaks and/or erosion [166–170]; the formation of prominent or symptomatic blebs [171–177]; and the development of avascular blebs [154, 178].

Table 4.

Diverse approaches for reducing bleb failure following XEN surgery. Data from Vera et al. [130] and Vera et al. [156]

Strategy	Description
Patient-specific factors	Consideration of individual patient characteristics, such as age, ocular anatomy, and previous surgeries, in surgical technique planning
Preoperative steroids	Topical steroids a few days/weeks before surgery to reduce ocular surface inflammation and ocular surface disease
Topical glaucoma medications	When possible, reduce the number of IOP-lowering medications
MMC application	Use of MMC during surgery to inhibit fibroblast proliferation and reduce scar formation. Techniques such as soaked sponges or direct application via injection ensures controlled and effective delivery of MMC
Postoperative steroids	Systemic or topical steroids to minimize inflammation and scarring post-surgery
Postoperative antifibrotic agents	Consider alternative antifibrotic agents (e.g. anti-VEGF) or combination therapies to enhance bleb survival and function after surgery
Regular monitoring	Vigilant postoperative monitoring of bleb morphology during biomicroscopy evaluation and function using imaging techniques like AS-OCT
Early intervention with needling	Prompt needling of the bleb to disrupt early fibrosis and enhance outflow in cases of suboptimal bleb function
Nd:YAG laser	In patients where occlusion of the implant is suspected (i.e., with a sudden IOP increase), consider using Nd:YAG laser instead of needling

IOP, intraocular pressure; MMC, mitomycin C; anti-VEGF, anti-vascular endothelial growth factor inhibitors; AS-OCT, anterior segment optical coherence tomography; Nd:YAG, neodymium-doped yttrium–aluminum–garnet

Discussion

The evolution of glaucoma surgery over the past decade represents a major shift in clinical practice, primarily driven by the development of safer and less invasive techniques [14, 15]. Trabeculectomy and tube shunt implantation are generally reserved for cases requiring a very low target IOP, where their superior efficacy may justify the higher risk profile. Although these procedures are associated with potential complications (e.g., hypotony, bleb-related infection), their efficacy may justify the associated risks. The introduction of MIBS, particularly the XEN Gel Stent and the Preserflo MicroShunt, has enabled earlier surgical intervention, even in patients with mild to moderate disease. These procedures offer favorable safety profiles, shorter recovery times, and reduced incidence of severe adverse events, thus broadening their appeal to both clinicians and patients [32–34, 53–55].

Evidence from a randomized, multicenter trial and complementary observational studies indicated that the XEN Gel Stent achieved non-inferior outcomes compared with other surgical techniques, while requiring fewer postoperative interventions and allowing faster visual recovery [89, 102, 179]. In parallel, patient-reported outcomes and comparative studies suggested that quality-of-life metrics were at least non-inferior, and in some contexts superior, relative to those observed with more invasive filtering procedures [25, 26, 102]. Taken together, these findings support the consideration of the XEN implant as a viable alternative for patients who might otherwise have been candidates for traditional, more invasive glaucoma surgeries [25, 26, 89, 102, 179].

This paradigm shift is reflected in real-world clinical data. Morales-Fernández et al. [180] reported a decade-long trend in a tertiary Spanish hospital showing a marked decline in traditional filtering surgeries, paralleled by increased uptake of MIGS. Similarly, Palma et al. [181] noted significant changes in patient profiles undergoing glaucoma surgery in recent years, characterized by earlier disease stages, fewer prior treatments, and better baseline visual function. These trends underscore a broader reorientation in glaucoma management philosophy, toward earlier, quality-of-life–oriented intervention that prioritizes long-term visual preservation.

The incorporation of the XEN Gel Stent has significantly influenced therapeutic algorithms. Since the introduction of the XEN45 Gel Stent, surgical indications have expanded to include patients previously excluded due to age, ocular surface disease, or systemic frailty. The transition from the XEN45 Gel Stent to XEN63 Gel Stent has further enhanced clinical versatility, with the latter offering a larger lumen and potentially more substantial IOP reduction—an advantage for patients that need lower IOP to control their disease [21–26, 35, 36, 56, 57, 145, 154].

In addition to differences in lumen diameter, the XEN63 Gel Stent implant presents several advantages over the XEN45 Gel Stent. Notably, the lower risk of peritubular leakage with the XEN63 Gel Stent may contribute to improved bleb stability in the early postoperative period. These features, along with the lower outflow resistance of the XEN63 Gel Stent, may influence the surgical indication profile, making it a potentially better option in certain clinical scenarios where a lower IOP is needed or improved patient experience or recovery is desired. In contrast, for some authors, the XEN45 Gel Stent remains preferable in patients at higher risk of hypotony—particularly those with low baseline IOP or thin sclera—due to its smaller lumen and increased outflow resistance.

Intraoperative use of antimetabolites such as MMC is tailored to individual patient risk profiles. The authors of this review suggest modulating the concentration (0.02%–0.04%) and mode of application—either with pre-implantation-soaked sponges or via post-implantation subconjunctival injection—based on conjunctival quality and fibrosis risk [18, 23–26, 28, 30, 110, 127].

Key procedural insights have emerged through cumulative clinical experience. One critical factor in long-term success is the creation and maintenance of a functioning subconjunctival space.

The XEN implant was originally designed for ab interno implantation, and performing the procedure with a closed conjunctiva preserves its fundamental objective of being a minimally invasive surgical approach [15, 16].

Some authors consider that opening the conjunctiva and suturing it not only extends the duration of the procedure but may also increase the risk of postoperative inflammation and fibrosis due to greater tissue manipulation and surgical trauma, while performing a systematic primary needling after closed conjunctiva implantation in order to create a filtration space significantly improves outcomes by facilitating the development of a more diffuse, posterior bleb, and may reduce the need for secondary needling procedures during follow-up [116].

Instrumentation for this primary needling technique varies based on intraoperative conditions, with both 27G and 30G needles [31, 112], as well as blunt cannulas, being employed according to tissue resistance and mobility (Fig. 5).

Fig. 5.

Peribleb fibrotic “ring of steel” and resolution by primary needling. A “ring of steel” with formation of dense, fibrous scar tissue encircling the bleb, creating a restrictive band that impairs the proper function of the bleb by limiting aqueous humor outflow. This complication may be avoided by the systematic use of primary needling. B, C Intraoperative AS-OCT of a subconjunctival XEN Gel Stent before (B) and after (C) primary needling, with patent bleb formation after the maneuver. Courtesy of EMG

Importantly, a closed technique does not preclude subsequent conjunctival opening if needed for repositioning or revision.

On the other hand, some authors consider that technical refinements, including the adoption of open conjunctiva implantation techniques, both ab interno and ab externo, allow for a more reproducible creation of a subconjunctival space where the implant is totally free from Tenon’s capsule, and also have expanded surgical options in complex eyes—such as those with prior surgeries or limited conjunctival mobility, while also increasing the likelihood of surgical success and decreasing secondary needling rates, and thus providing more reproducible results [117, 118, 123–125]. These approaches are now routinely considered as a first option for some of the authors of this review.

The choice between closed- versus open-conjunctiva and ab interno versus ab externo approaches has also evolved with experience. In combined procedures with phacoemulsification, some favor a closed-conjunctiva, ab interno technique due to its convenience within the shared surgical approach and reduced operative time. The use of a gonio lens aids precise placement of the implant and minimizes intraocular manipulation. Conversely, the ab externo technique under open conjunctiva may be required in eyes with prior scarring or limited conjunctival mobility, although visualization of the anterior chamber angle is more limited and implantation is effectively performed “blind.”

These authors consider that a unique advantage of the XEN device is its adaptability in quadrant selection, enabling implantation in areas with more favorable conjunctival integrity or surgical history. Notably, studies have demonstrated comparable efficacy and safety for both superior and inferior placements of the XEN45 Gel Stent (when superior quadrants are not suitable), further supporting individualized surgical planning and preserving future filtering options [71, 72].

Finally, the prevention and management of complications such as postoperative hypotony remain essential to optimizing outcomes. Intraoperatively, it is advised to avoid excessive subconjunctival dissection and limit antimetabolite use in low-risk cases. Postoperatively, close monitoring of anterior chamber depth is critical. Conservative measures, such as cycloplegics and observation, are typically sufficient, but anterior chamber reformation or viscoelastic injection may be employed if hypotony persists. Ultimately, the success of XEN implantation hinges on tailored surgical planning, meticulous technique, and proactive postoperative care. This study is limited by the fact that the literature review performed was comprehensive but not systematic. While we aimed to identify and include all relevant evidence available to date using predefined keywords and search filters, the absence of a fully standardized systematic review methodology may introduce selection bias and limit reproducibility. Future research could benefit from a formal systematic review or meta-analysis to strengthen the robustness and generalizability of the conclusions. Another limitation of this study is that some authors were employees of the company marketing the product, which might introduce a potential conflict of interest. Nonetheless, the analytical methods, data interpretation, and reporting processes were conducted with full transparency and adherence to standardized research practices. This procedural rigor aims to mitigate bias and support the credibility of the findings.

Conclusions

The XEN Gel Stent has emerged as a significant innovation in the surgical management of glaucoma.

Current evidence demonstrates that the XEN stent effectively lowers IOP, achieving mean IOP levels in the mid-teens for the XEN45 Gel Stent and in the low teens for XEN63 Gel Stent, sustained up to 4 years postoperatively, while also reducing dependency on ocular hypotensive medications. This device, particularly in its XEN45 Gel Stent and XEN63 Gel Stent iterations, is demonstrating the ability to offer meaningful clinical outcomes with a favorable safety profile, marked by transient and manageable adverse events.

Crucially, recent advancements in surgical techniques, including the adoption of both ab interno and ab externo approaches, have expanded the versatility and applicability of the XEN Gel Stent. These approaches allow for customization based on the individual patient's ocular condition, optimizing the surgical outcome and potentially reducing the need for postoperative interventions. They are pivotal in enhancing the device's success rate and ensuring long-term benefits for diverse patient profiles.

Despite these advances, challenges such as managing postoperative hypotony and bleb-related complications remain. These require ongoing attention to patient selection criteria and postoperative care strategies. Future research should aim to further refine these surgical techniques and explore predictive factors for surgical success, thereby enhancing patient outcomes across varying clinical scenarios.

In essence, the XEN Gel Stent may be a useful option within the spectrum of glaucoma treatments, depending on individual patient characteristics. Its continued development and integration into clinical practice will likely be shaped by ongoing innovations in surgical techniques and a deeper understanding of its application across different patient demographics.

Author Contributions

Elena Millá Griñó, Rafael Giménez Gómez, and Almudena Asorey García were responsible for designing the review protocol, interpreting results, and creating “Summary of findings” tables. José M Larrosa Poves and Jorge Vila Arteaga were responsible for screening potentially eligible studies, extracting and analyzing data, interpreting results, and updating reference lists. Fernando Giacomini and Vanessa Vera contributed to writing the report, updating reference lists, and data extraction. All authors contributed to the development and critical revision of the manuscript, commented on the various versions of the manuscript, as well as reading the final manuscript and approving it for submission.

Funding

The journal's Rapid Service Fee was funded AbbVie S.L.U. AbbVie participated in writing, reviewing, and approving the publication. No honoraria or payments were made for authorship.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Elena Millá Griñó: Received speaker fees from AbbVie, Santen, Brill, Viu 20/20, Glaukos, and Visufarma. Rafael Giménez Gómez has nothing to disclose. José M Larrosa Poves: Received speaker and consulting fees from AbbVie, Bausch & Lomb, and Santen. Jorge Vila Arteaga: Received speaker and consulting fees from AbbVie, Bausch & Lomb, Santen, and Glaukos. Almudena Asorey-García is an AbbVie employee and may own AbbVie stocks/options. Fernando Giacomini is an AbbVie employee and may own AbbVie stocks/options. Vanessa Vera is an AbbVie employee and may own AbbVie stocks/options.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.