Xen Glaucoma Treatment System

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Background

Glaucoma is a leading cause of overall blindness, and the number one cause of irreversible blindness, both in the United States and worldwide.[1][2] An elevated intraocular pressure (IOP) has been considered as a major risk factor.[3]

The decrease in quality of life associated with glaucoma may occur earlier than previous thought, highlighting the importance of early diagnosis and treatment.[4] Reduction of IOP is the only proven method to treat glaucoma[5],preventing the development and slowing the disease’s progression.[6][7][8]

Current guidelines from the American Academy of Ophthalmology Preferred Practice Pattern recommend lowering the IOP to a target level, which is a value or range of values at which the rate of disease progression will be slowed sufficiently to avoid functional impairment from the disease.[9]

Glaucoma treatments include various topical and oral medications, cilioablative or trabecular meshwork laser procedures, and various surgical techniques designed to improve trabecular meshwork outflow, increase suprachoroidal drainage, or divert aqueous to the subconjunctival space. Subconjunctival drainage of aqueous humor (AH), resulting in bleb formation, has been a cornerstone of glaucoma surgery for more than a century.[10] However, the ‘gold standard’ trabeculectomy[11], has short-term problems like near 50% rate of transient perioperative complications[12] and long-term rates of failure, reported to be as high as 50% at 5 years.[13] Because of the tradition glaucoma surgeries potentially serious complications [3], glaucoma is entering a renaissance period where surgical management is implemented earlier to widen the sight spectrum of glaucoma patients. Minimally invasive surgeries obtain lower and less variable IOP on fewer medications, ideally addressing both the under-treatment and noncompliance issues.[11]

Minimally invasive glaucoma surgery (MIGS) meet the criteria of minimal tissue disruption, ab-interno implantation, short surgical time, IOP reduction, simple instrumentation, and fast postoperative recovery.[14] Xen Gel Implant is one of the MIGS alternatives. This subconjunctival implant is the world’s first ab-interno MIGS approach to subconjunctival outflow.[3] Bypassing the TM, Schlemm’s canal, and collector channels entirely, it eliminates the risk of reducing the efficacy due to any other outflow obstruction.[15]

Xen Gel Implant

XEN GEL Implant (Allergan Inc., CA, USA) is a 6-mm hydrophilic[15] tube of collagen-derived gelatin cross-linked with glutaraldehyde[3], non­inflammatory[16] and causing nearly absent extraocular fibrotic or vascular response to the implant material[11]. It decreases IOP by creating a permanent drainage shunt from the AC to the subconjunctival space through a scleral channel[15] The device hydrates on contact with water within 1–2 min, bending and conforming to tissue[3], minimizing many of the issues seen with synthetic materials such as migration, erosion and corneal endothelial damage.[16]

The design of the Xen Gel Stent is based upon the principles of laminar fluid dynamics (Hagen–Poiseuille equation)[15]. It calculates the required internal dimensions of a tube that would prevent hypotony at average aqueous humor production of 2–3 μl/min by providing a steady-state pressure of approximately 6–8 mmHg. Pressure difference across the tube (i.e. a theoretical IOP floor) can be estimated using the length and internal lumen diameter.[11] Lumen size was chosen to prevent postoperative hypotony by the primary flow resistance of the tube itself[17].

Three Xen models have been designed[11]: 45, 63, and 140 μm internal lumen diameters for varying levels of IOP control. The smallest one, XEN45, is the only one currently available.[15] The tube length of 6 mm is the ideal length for passage ab-interno from the trabecular meshwork to the subconjunctival space at an optimal distance from the limbus.[3] (add fig of implanted XEN)

Suitable and Non-suitable Patients

The most suitable patients for Xen implantation are:

  • Patients with uncontrolled glaucoma, primary open-­angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy.[7][13]


The XEN gel stent is generally contraindicated under the following circumstances or conditions:

  • Patients with angle ¬closure glaucoma where the angle has not been surgically opened; previous glaucoma shunt/valve or conjunctival scarring/pathologies in the target quadrant; active iris neovascularization or neovascularization of the iris within 6 months of the surgical date; active inflammation (eg, blepharitis, conjunctivitis, keratitis, and uveitis)[15]; anterior chamber intraocular lens; intraocular silicone oil; vitreous in the anterior chamber; impaired episcleral venous drainage (eg, Sturge–Weber or nanophthalmos or other evidence of elevated venous pressure) and known or suspected allergy or sensitivity to drugs required for the surgical procedure or any of the device components (eg, porcine products or glutaraldehyde).[15]

Surgical Procedure

Xen comes preloaded in an injector (system with a 27 g sharp beveled needle tip)[11] and is implanted ab-interno: (surgical steps fig)

  1. After topical anesthesia, 0.05–0.2 ml MMC (0.1–0.2 mg/ml) is injected with a 30-gauge needle in the superonasal quadrant and massaged over the area of anticipated XEN Gel Implant insertion (off-label use) or a conjunctival flap is made and MMC applied on sponges.[3] This induces a hydroexpansion, which reduces tissue resistance, preparing the space for the implant and supporting the bleb formation.[15]
  2. Cataract surgery, if planned, may be performed after this step using miotic drugs after intraocular lens (IOL) implantation and ophthalmic viscosurgical device (OVD) removal.[15]
  3. The intended area of placement in the supero-nasal quadrant, which is 3 mm from the limbus, is marked.[15]
  4. Small, self-sealing corneal incisions are made, and viscoelastic is used to fill the AC.
  5. Injector tip is placed through an inferotemporal clear corneal incision (~2mm), whereas a second instrument is utilized for counter-traction through a superotemporal paracentesis (1 mm)
  6. The inserter needle (double-beveled 27 gauge) is directed[15] through the main incision and across the AC toward the superonasal quadrant (mirrored gonioscope can be used to confirm placement, but it is not mandatory, it is used at the discretion of the surgeon)
  7. XEN Gel Implant should be placed anterior to Schlemm’s canal to avoid bleeding (under direct observation using a gonioscope)
  8. The sharp tip is engaged at or slightly anterior to the trabecular meshwork and advanced through the sclera[11]
  9. The needle is tunneled through the sclera coming out subconjunctivally 3.0 mm from the limbus, as previously marked, using a second instrument to provide countertraction via the side port
  10. A sliding mechanism is then pushed forward to initially deploy the stent and then to retract the needle into the hub[11], without drawing the implant back[15]
  11. The injector is then withdrawn, subconjunctival and AC XEN Gel Implant placement is confirmed. The ideal stent placement should leave 2.0 mm of exposed implant in the subconjunctival space (preferentially in a more supercial layer than the sub-Tenon space), 1.0 mm in the AC, and 3.0 mm tunneled through sclera, that provides resistance
  12. Viscoelastic is removed from the AC
  13. Bleb morphology and function may be obtained by forced infusion of fluid through paracentesis at the end of the procedure.[15]

Perioperative Management

Pre-operative:

  • Patients are instructed to stop all glaucoma medications on the day of the operation.

Post-operative:

  • Patients are seen postoperative day 1 and followed up at the physician discretion.
  • Postoperative topical regimen includes topical antibiotic prophylaxis for 4 weeks and topical corticosteroid 4 times each day for a month followed by a slow taper over the second month.[18][19]
  • XEN implant location and subconjunctival bleb morphology require close biomicroscopic follow-up, complemented with UBM (FIG1) or AS-OCT.

Morphologic changes to the developing filtering bleb after surgery may help to predict early treatment failure and guide bleb revision and management. Fea et al.[20] reported that maximal height of the bleb and the total area of cystic hypoehoic spaces were significantly higher in the success group. Increased micro-cysts and loosely arranged connective tissue/low stromal reflectivity are suggestive of new or increased alternative outflow induced by the stent implantation. In the other hand, bleb wall reflectivity was significantly higher in the failure group.[20] (UBM assessment of XEN Fig.)

  • Needling may be performed in case of IOP increases and is greater than target IOP; there is a flat bleb or fibrotic bleb or the patient is at high risk of bleb failure.

Xen Implant Advantages

Xen Implant has some advantages over traditional surgeries such as trabeculectomy and tube shunt surgeries:[21]

  • Soft and flexible when wet;
  • Minimally invasive, pre-loaded injector;
  • Shorter surgical and recovery times;
  • Less side effects: Eg. Prevents chronic hypotony by an intrinsic flow-limiting design[11]
  • Keep postoperative options open, allowing physicians to use other IOP-reduction techniques that could be required after surgery [16]

Complications

Reported Intra- and post-operative complications are minor and inherent to the surgical technique. A critical point is the final placement of the XEN device.

Intra-operative complications:

  • Misplacement of the XEN Gel Implant at the first attempt;
  • Posterior placement of the implant, especially through ciliary body can lead to bleeding and hypotony;
  • Subconjunctival or AC bleeding during the implantation.

Post-operative complications:

  • Complications of relocation or reimplantation (misplaced XEN Fig);
  • Wound leak;[13]
  • Transient hypotony, AC shallowing, and choroidal detachment (less frequent with XEN 45);
  • Internal ostium occlusion with a blood clot leading to raised IOP and flat bleb.

Late complications:

  • Device erosion and exposure of implant (add XEN erosion Fig);
  • Implant migration [13]: Dislocation into AC, XEN-iris touch;
  • Bleb leak or dehiscence (may be due to thin or ischemic bleb with overfiltration);
  • Reported cases of blebitis and persistent hypotony[22], suprachoroidal bleeding[23], conjunctival perforation and late seidel.[24]

Efficacy and Safety Profile

The Implant was recently introduced to glaucoma surgeries, thus long-term results are not available yet. Studies with 1-year follow-up have found it to be efficacious in lowering IOP significantly and reducing the number of hypotensive medications used, with minimal complications or serious side effects[3]. Most studies document an IOP reduction of >29% (greater than the reduction demonstrated by isolated phacoemulsification in patients with primary open-angle glaucoma) and a significant reduction in the number of IOP-lowering medications.

In Galal et al. study,[25] 13 eyes with primary open angle glaucoma underwent XEN implantation with subconjunctival MM. Complete success (IOP reduction ≥20% from preoperative baseline at 1 year without any glaucoma medications) was achieved on 41.7% of patients, while qualified success rate (IOP reduction of ≥20% at 1 year with medications) was 66.7%. IOP reduction at 12 months was 16 ± 4 to 12 ± 3 mmHg (p ≤ 0.01) and medication’s reduction at 12 months was 1.9 ± 1 to 0.3 ± 0.49 (p = 0.003).

In a prospective, non-RCT by De Gregoria et al,[26] 41 eyes of 33 patients underwent a XEN Gel Implant procedure combined with cataract surgery. Outcomes of this study show that XEN45 implant is statistically effective in reducing IOP and medications even after 12 months. The complete success rate (≤18 mmHg without medications) after 12 months was achieved in 80.4% (33 of 41 eyes) and a qualified success (≤18 mmHg with medications) in 97.5% (40 of 41 eyes). IOP reduction at 12 months was 22.5 ± 3.7 to 13.1 ± 2.4 mmHg (p < 0.05) and medication’s reduction at 12 months was 2.5 ± 0.9 to 0.4 ± 0.8 (p < 0.05).

No serious complication was observed in studies highlighting the safety of the XEN Gel Implant. There was no report on loss or worsening of visual acuity.[3]

XEN Gel Implant Vs. Trabeculectomy

An international multicenter retrospective study has recently been published that compares the efficacy, safety, and risk factors for failure of standalone XEN45 gel stent implantation versus trabeculectomy, both with adjunctive MMC. In this study, 354 eyes with uncontrolled glaucoma and no prior incisional filltering surgery underwent microstent implantation (n 185) or trabeculectomy (n 169). The results demonstrated that there was no difference in efficacy, risk of failure, and safety profile between the 2 surgical procedures.[15]

Schlenker et al.[27] results found a median preoperative IOP of 24 mmHg on three medications, which decreased to 13 on zero medications for both the Xen45 and trabeculectomy groups, without any statistically significant difference.[11] There was no difference in the HRs of failure (defined as IOP outside of 6 – 17 mmHg on two consecutive visits at least 1 month after surgery) between the two procedures with both having a 75% survival of approximately 10 months for complete success (without glaucoma medications) and over 2 years for qualified success (with glaucoma medications). At last follow-up, a larger proportion of Xen45 patients were completely off medications (75.7 versus 67%), but this was not statistically significant[11]. The trabeculectomy group had more postoperative interventions (mostly laser suture lysis) and complications (bleb leak or dehiscence). Bleb needling was slightly higher for the XEN Gel Implant group but was not statistically significant.

Similar success rates and relatively similar complication rates are encouraging to continue the evaluation of this new device considering the good safety profile, short duration procedure, and being less invasive.[3]

XEN Implant in Refractory Glaucoma

Previous studies have documented the efficacy and safety of XEN Implant in moderate to advanced glaucomas. Grover et al.[28] evaluated the IOP-lowering effect and safety of the XEN Gel Implant patients with refractory glaucoma (previously failed filtering or cycloablative procedure and/or uncontrolled IOP on maximally tolerated medical therapy). In 76.3% of patients there was ≥20% reduction of IOP on same or fewer medications. The mean (SD) medication use reduced from 3.5 (1) at baseline to 1.7 (1.5) at 12-month follow-up. There was 75% probability of success reported at 12 months (Kaplan–Meier analysis). Visual recovery post-surgery was rapid with most patients experiencing either no change in vision or improvement in BCVA. This study clearly demonstrates the effectiveness and good safety profile of XEN Gel Implant in refractory glaucoma.

Complications like endophthalmitis, loss of light perception, retinal detachment, or tube obstruction at 1 year reported for Baerveldt implant and Ahmed valve[29][30], widely used in refractory glaucoma, are not observed with XEN Gel Implant.

XEN-augmented Baerveldt surgical technique

D’Alessandro et al.[31] reported a new surgical technique of using the XEN Gel Implant in combination with the Baerveldt tube in refractory glaucoma. Baerveldt tube is one of the drainage devices that have been used for patients with refractory glaucoma. These devices are prone to early hypotony and late corneal decompensation. Controlling leakage in the early postoperative period is crucial in avoiding these complications.[3] XEN Gel Implant offers the appropriate resistance, it’s inner diameter prevents early hypotony, plus implantation using the injector places it in the AC at the right location avoiding corneal touch as well.

Surgically, after placing the Baerveldt tube, XEN Gel Implant is inserted ab-externo using the injector, and once it is accurately placed, it is inserted into the Baerveldt tube’s lumen.[3]

The outcome of this novel surgical technique is, as reported, an average IOP of 9.1 mmHg (±2.7 mmHg) on day 1. No case of postoperative hypotony or corneal decompensation was observed.[31]

Some anticipated disadvantages of using XEN–Baerveldt technique are: XEN Gel Implant fracture or dislocation from the Baerveldt tube; leak around the XEN Gel Implant due to XEN–Baerveldt tube lumen size mismatch; hypotony and increased surgical costs.[32] Long-term follow-up is required to confirm and ruled out these risks.

Conclusion

Earlier surgical intervention appears to be the future of glaucoma management. Lower and less variable IOP and decreased reliance on patient compliance with medications with these devices will likely play a significant role in that goal.[11]

In the new era of microstent surgeries, Xen Gel Implant is a recent introduction. Studies are on early follow-up, and long-term efficacy and safety are yet to be demonstrated. However, all the studies with a 1- year follow-up report good efficacy with a favorable safety profile.[3]

XEN Gel Implant has the potential to postpone more invasive surgery to later stages of glaucoma patients’ disease course. It may further be effective in some refractory cases where other surgeries have failed or in rare syndromes which are difficult to manage otherwise, as ICE syndrome reports.[33] Another interesting area of research would be use of XEN Gel Implant in angle-closure glaucoma.

Despite the encouraging early results, more patients and longer follow-up periods will be warranted, preferably in the form of prospective, randomized, controlled trials, to verify the durability and long-term safety of the devices, especially in comparison with each other and the existing traditional glaucoma surgeries.[11]

References

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  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Ankita Chaudhary, Lauriane Salinas, Jacopo Guidotti, André Mermoud & Kaweh Mansouri (2017): XEN Gel Implant: a new surgical approach in glaucoma, Expert Review of Medical Devices, DOI: 10.1080/17434440.2018.1419060
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  28. Grover DS, Flynn WJ, Bashford KP, et al. Performance and safety of a new ab interno gelatin stent in refractory glaucoma at 12 months. Am J Ophthalmol. 2017;183:25–36.
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  33. Hohberger B, Welge-Lüen VC, Lämmer R. ICE-syndrome: a case report of implantation of a microbypass XEN gel stent after DMEK transplantation. J Glaucoma. 2017;26:e103–4.