Bleb-Forming Microshunts (PreserFlo) vs XEN Gel Stents: 2025 Review

The PreserFlo™ MicroShunt and XEN® Gel Stent are minimally invasive glaucoma surgery (MIGS) implants that create a subconjunctival drainage bleb, bridging between traditional trabeculectomy and ab interno angle procedures. These devices aim to lower intraocular pressure (IOP) in moderate-to-advanced glaucoma with fewer complications than trabeculectomy. Recent studies show that both implants produce significant IOP and medication reductions, but with some differences in efficacy and postoperative management (pmc.ncbi.nlm.nih.gov) (www.mdpi.com). Understanding their outcomes, bleb optimization (antifibrosis, imaging), and how they compare to trabeculectomy is crucial in 2025 practice.

IOP Reduction and Medication Burden

Clinical evidence shows consistent IOP lowering with both XEN and PreserFlo. In a two-year review, mean IOP fell ~28% with XEN (19.2→13.8 mmHg) and ~35–39% with PreserFlo (20.1→12.1 mmHg) (pmc.ncbi.nlm.nih.gov). Another series found PreserFlo produced slightly lower pressures than XEN at all follow-ups (e.g. 12.9 vs 14.2 mmHg at 6 months) (www.mdpi.com) (www.mdpi.com). On average, medication use after surgery dropped markedly: one comparative study noted a 62% med reduction with XEN and 69% with PreserFlo (pmc.ncbi.nlm.nih.gov). By 2 years roughly 60–65% of eyes were medication-free for either device (pmc.ncbi.nlm.nih.gov) (www.mdpi.com). These studies confirm that both implants substantially reduce IOP and glaucoma drops, though PreserFlo tends to achieve a slightly greater percent reduction and higher rate of complete success (no meds) than XEN (pmc.ncbi.nlm.nih.gov) (www.mdpi.com).

Needling and Reinterventions

A critical practical difference is the frequency of bleb interventions. Needling (bleb revision) is much more common after XEN than PreserFlo. In one review, about 20% of XEN eyes needed at least one needling, versus only ~5% of PreserFlo eyes (pmc.ncbi.nlm.nih.gov). A prospective series found only 13.3% of PreserFlo eyes required needling in the first year (pmc.ncbi.nlm.nih.gov). In contrast, meta-analyses report XEN needling rates typically in the 30–40% range (5–62% across studies) (pmc.ncbi.nlm.nih.gov). Needling tends to occur early (often within 1–3 months) to preserve bleb function (pmc.ncbi.nlm.nih.gov). Overall, wide evidence indicates that migrating from a closed-eyelid (ab interno) insertion (XEN) to an open or ab externo approach (PreserFlo) reduces needling rates (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Both devices, however, often require additional care: about 30–40% of XEN or PretserFlo eyes eventually needed some postoperative procedure (needling, 5-FU injection, or bleb revision) to maintain the bleb (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Bleb Morphology and Outcomes

Bleb appearance on high-resolution imaging correlates with success. Anterior segment OCT (AS-OCT) studies classify bleb structures. After XEN, an early “subconjunctival separation” bleb with multiple cystic spaces was most common and associated with lower IOP, while later a uniform, dense bleb often predicted higher IOP (pubmed.ncbi.nlm.nih.gov). In one cohort, uniform blebs on AS-OCT had significantly higher pressures (e.g. ~17.7 vs 11.3 mmHg at week 1) than “subconjunctival separation” blebs (pubmed.ncbi.nlm.nih.gov). Microcystic, multilayered blebs tended to fail by 3–9 months (higher failure risk of ~4× if 3-month bleb was microcystic) (pubmed.ncbi.nlm.nih.gov). Similarly, OCT analysis of XEN blebs found that intratenon or intraconjunctival stent position produced taller, sparser bleb walls and better IOP control than superficial placement (pmc.ncbi.nlm.nih.gov). In short, AS-OCT can reveal bleb height, cystic spaces, and wall reflectivity: blebs that are high, diffuse, and cystic usually indicate good filtration, whereas flat, fibrotic-appearing blebs predict failure (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

AS-OCT also highlights device differences. Studies observed that PreserFlo blebs tend to be thicker and more multilayered than XEN blebs (www.mdpi.com). For example, in one series PreserFlo blebs had a mean vertical (thickness) of ~432 μm vs ~359 μm for XEN blebs at 6 months, and more episodes of “posterior episcleral fluid lakes” (fluid pockets between Tenon’s and sclera) (www.mdpi.com). These structural differences may underlie the happier bleb function with PreserFlo. AS-OCT classification shows PreserFlo more often produces “microcystic multiform” blebs over time, whereas XEN blebs often evolve to a uniform, flat type (www.mdpi.com). In any case, AS-OCT imaging allows monitoring bleb growth longitudinally and predicting when interventions (needling, antifibrotic injection) are needed.

Ultrasound biomicroscopy (UBM) can also image bleb anatomy, though it is used less frequently than OCT. UBM can visualize fluid cavities under the conjunctiva and sclera, as well as the surgeon’s flap or shunt position (pmc.ncbi.nlm.nih.gov). In trabeculectomy literature, UBM has been useful to measure bleb height, intrascleral channels, and scleral flap reflectivity, which correlate with outflow (pmc.ncbi.nlm.nih.gov). By analogy, UBM may help detect Tenon’s encapsulation or subscleral fluid in PreserFlo blebs. In general, imaging blebs (OCT or ultrasound) is becoming a key part of postoperative care – for example, identifying a thick, highly vascular bleb on OCT leads surgeons to perform early needling or 5-FU to preserve function.

Antifibrotic Strategies to Optimize Bleb

Preventing scarring is critical with any bleb-forming procedure. Mitomycin-C (MMC) remains the antimetabolite of choice. Regimens vary: XEN studies have used 10–40 µg MMC, either by subconjunctival injection or soaked sponge. Recent evidence suggests lower doses suffice. A randomized pilot found XEN outcomes were equivalent with 5, 10 or 20 µg MMC – IOP lowering and success rates did not differ by dose (pmc.ncbi.nlm.nih.gov), implying the lowest dose is adequate. Another study showed no meaningful difference between 0.01% and 0.02% MMC for XEN (i.e. ~10 vs 20 µg) (pubmed.ncbi.nlm.nih.gov). Thus many surgeons now use roughly 10–20 µg for XEN to reduce toxicity risk.

For PreserFlo, MMC is usually higher. Early trials used 0.2–0.4 mg/mL (200–400 µg/mL) applied for 2–3 minutes on sponge (equivalent to ~30–60+ µg). Meta-analysis indicates that 0.4 mg/mL near the limbus produces higher success than 0.2 mg/mL (pmc.ncbi.nlm.nih.gov). However, higher MMC also yields more hypotony. A 2024 series comparing MMC delivery in PreserFlo (sponge vs sub-Tenon injection) found subtle differences: sub-Tenon injection gave slightly higher success (qualified success 43.4% vs 31.9%) and similar mean IOP, but sponge and injection were otherwise comparable (pmc.ncbi.nlm.nih.gov). In practice, surgeons balance dose vs safety: common practice is to inject 0.1–0.2 mL of 0.2–0.4 mg/mL spacer drilling near limbus, or place soaked sponges just under Tenon’s. Safety note: MMC must be injected carefully. A case report warned that injecting MMC too anteriorly (or after the stent) allows reflux into the eye, causing toxicity (large avascular bleb, persistent hyperemia, keratopathy) (pmc.ncbi.nlm.nih.gov). To avoid this, experts recommend injecting at least 8–10 mm posterior to the limbus (well into Tenon’s) and preferably before implant placement (pmc.ncbi.nlm.nih.gov).

5-Fluorouracil (5-FU) remains an important adjunct. In practice, any sign of encysted bleb or rising IOP triggers 5-FU: serial needling is often combined with 5-FU injection. Several studies show that adding post-op 5-FU dramatically improves XEN outcomes, lowering IOP and needling requirement. For example, needling with adjunctive 5-FU lowered IOP from ~26 to 15 mmHg in one series (pubmed.ncbi.nlm.nih.gov), and a prospective report emphasized routine early 5-FU helps maintain bleb function. Thus, many surgeons plan on at least one 5-FU injection if needed.

Beyond classic antifibrosis, novel strategies are emerging. Anti-VEGF agents have been tested: adding subconjunctival bevacizumab (an angiogenesis inhibitor) to MMC significantly reduced needling after PreserFlo (pmc.ncbi.nlm.nih.gov). In one 2025 study, 42% of eyes with MMC alone required revision (5-FU/needling/revision) by 6 months, but only ~10% did so when bevacizumab was added (p=0.002) (pmc.ncbi.nlm.nih.gov). This suggests suppressing bleb vascularity can help maintain filtration. Likewise, a preliminary study of cross-linked hyaluronic acid (Healaflow®) injection as an adjunct in XEN63 surgery showed promise: over 3 months, eyes with Healaflow had similar IOP drop but far fewer postoperative procedures (only 2 vs 8 in controls, p=0.004) (pmc.ncbi.nlm.nih.gov). Healaflow likely acts as a physical spacer and fibrosis modulator. Such innovations may improve early bleb survival.

Overall, modern antifibrotic strategy for these microshunts follows trabeculectomy principles: judicious MMC use (lowest effective dose), timely 5-FU needling, and even adjunctive biologics (anti-VEGF or biomaterials) to optimize bleb morphology. By flattening bleb vessels and maintaining a diffuse, cystic bleb structure, these measures aim to prevent scar-induced failure.

Comparison to Trabeculectomy

In moderate-to-advanced glaucoma, traditional trabeculectomy remains the gold standard for maximal IOP lowering. Meta-analyses show trabeculectomy typically achieves slightly greater pressure reduction than microshunts (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, one updated review found that after 2 years trabeculectomy lowered IOP on average ~2.5 mmHg more than the PreserFlo microshunt (mean difference −2.52 mmHg, favoring trab; p=0.0003) (pubmed.ncbi.nlm.nih.gov). In direct comparisons, XEN stents often produce ~35–45% IOP drops, whereas trabeculectomy frequently produces ~50–80% reductions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In concrete terms, if a patient with baseline 25 mmHg would drop to ~13–15 mmHg with a stent, trabeculectomy might lower it into single digits more comfortably.

The reason for the smaller IOP effect is multifactorial: IOP with a non-valved 45 μm XEN stent or 70 μm PreserFlo flows through a fixed resistance, whereas trabeculectomy flow is determined by flap sutures and implantable suture techniques (allowing even lower IOP). Consequently, the “success” rate for low targets (<12 mmHg) tends to favor trabeculectomy. For instance, one study noted that complete success (20% IOP reduction to ≤18 mmHg without meds) was achieved in only ~40% of XEN eyes vs ~54% of trabeculectomy eyes at one year (pmc.ncbi.nlm.nih.gov).

However, trabeculectomy is also riskier: it carries higher rates of early hypotony, flat chambers, choroidal detachment, and wound leaks (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The same analyses show trabeculectomy eyes had more transient complications (e.g. >20% trab eyes had hypotony-related issues vs ~8–24% of microshunts (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov)). Trabeculectomy also often causes more endothelial cell loss and reoperations for leaks (pmc.ncbi.nlm.nih.gov).

Conversely, microshunts like XEN/PreserFlo have more modest risk profiles: low rates of flat anterior chamber (<< trabecu), and far lower chronic hypotony rates. For example, in matched studies the only significant differences were higher IOP lowering with trab and more needling with XEN; both had similar visual-field change rates (pubmed.ncbi.nlm.nih.gov). In one comparative series, trabeculectomy did produce greater IOP drop than XEN (p<0.01) but also induced more endothelial cell loss and anterior segment changes (pmc.ncbi.nlm.nih.gov). Yet in that study the relative surgical failure rates (tra vs XEN) were similar over 2–3 years.

Positioning: In practice, bleb-forming MIGS are often used in moderate glaucoma where trabeculectomy risks are to be avoided. For mild–moderate cases they may be preferred over trab. In moderate-to-advanced cases, current evidence suggests trabeculectomy remains the most potent option, especially if very low targets are needed (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). That said, microshunts have made inroads even in advanced disease – e.g. a patient intolerant of trab risks may receive XEN/PreserFlo with augmented antifibrotics as a “gentler” alternative. Emerging data show similar overall success rates between PreserFlo and trabeculectomy in moderate/severe eyes, albeit with higher reintervention after the shunt (pubmed.ncbi.nlm.nih.gov). Thus, many surgeons consider microshunts as part of a stepwise approach: angle-based MIGS for mild cases, bleb-forming MIGS (XEN/PreserFlo) for moderate, and trabeculectomy or drainage tubes for the most severe refractory cases.

In summary, trabeculectomy is unmatched for maximum pressure lowering in severe glaucoma, but PreserFlo and XEN offer a compelling compromise: substantial IOP reduction and drop-sparing with fewer vision-threatening complications (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Advances in antifibrotic dosing (e.g. leaner MMC protocols, anti-VEGF) and bleb imaging (AS-OCT, OCTA vessel mapping) are helping surgeons optimize these devices’ outcomes. In 2025, these subconjunctival microshunts stand as safer, though slightly less effective, alternatives to trabeculectomy for appropriate patients, with ongoing research refining their use.

Tags: glaucoma, microshunt, XEN gel stent, PreserFlo, MIGS, trabeculectomy, bleb imaging, anterior segment OCT, mitomycin C, needling