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ORIGINAL ARTICLE
Year : 2019  |  Volume : 26  |  Issue : 4  |  Page : 229-234  

Real-world retrospective consecutive study of ab interno XEN 45 gel stent implant with mitomycin C in black and afro-latino patients with glaucoma: 40% required secondary glaucoma surgery at 1 year


1 Department of Ophthalmology, New York Eye and Ear of Mount Sinai, Icahn School of Medicine at Mount Sinai; Department of Ophthalmology, Advance Eyecare of New York, New York, NY, USA
2 Department of Ophthalmology, Advance Eyecare of New York, New York, NY, USA

Date of Submission17-Aug-2019
Date of Acceptance20-Jan-2020
Date of Web Publication29-Jan-2020

Correspondence Address:
Dr. Daniel Laroche
49 West 127th Street, New York 10027, NY
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/meajo.MEAJO_126_19

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   Abstract 


PURPOSE: The aim of this study was to determine the postoperative course after the ab interno XEN45 Gel Stent implantation in Black and Afro-Latino, patients with glaucoma.
METHODS: This was a single-center, retrospective study. All patients with glaucoma who underwent ab interno XEN implantation were included in the study. All of the patients were Black and Afro-Latino making up the demographics of the local community. Investigated parameters were intraocular pressure (IOP), the number of medications, visual acuity, IOP-follow-up, intraoperative and postoperative complications, and additionally performed surgeries.
RESULTS: Of 20 eyes that had undergone the procedure with 1-year follow-up, eight failed before 12 months requiring additional glaucoma surgery. Of the 12 that were successful at 1 year, 9 (75%) eyes underwent XEN + cataract surgery and 3 (25%) had XEN surgery alone. Of the eyes that completed 12-month follow-up, the mean medicated IOP was 15.3 ± 6.2 mmHg at baseline, and 12.9 ± 4.5 mmHg at 12 months, a 16% IOP reduction. Mean medications dropped from 3.58 ± 0.7 preoperatively to 1.75 ± 1.5 at 12 months.
CONCLUSIONS: The ab interno XEN gel implant as a standalone procedure or combined with cataract surgery demonstrated a safe and sustained IOP reduction for only 60% of patients after 12 months. In Black and Afro-Latino patients receiving the ab interno XEN implant, 40% of patients needed additional surgery within 12 months.

Keywords: Glaucoma, MIGS, XEN


How to cite this article:
Laroche D, Nkrumah G, Ng C. Real-world retrospective consecutive study of ab interno XEN 45 gel stent implant with mitomycin C in black and afro-latino patients with glaucoma: 40% required secondary glaucoma surgery at 1 year. Middle East Afr J Ophthalmol 2019;26:229-34

How to cite this URL:
Laroche D, Nkrumah G, Ng C. Real-world retrospective consecutive study of ab interno XEN 45 gel stent implant with mitomycin C in black and afro-latino patients with glaucoma: 40% required secondary glaucoma surgery at 1 year. Middle East Afr J Ophthalmol [serial online] 2019 [cited 2020 Feb 19];26:229-34. Available from: http://www.meajo.org/text.asp?2019/26/4/229/277260




   Introduction Top


Glaucoma is a leading cause of blindness diseases affecting 60 million worldwide; treatment is comprised medications, lasers, and surgeries.[1],[2],[3] The most common glaucoma surgeries are trabeculectomy and tube-shunt drainage devices that lower intraocular pressure (IOP) by draining aqueous humor from the anterior chamber (AC) to the subconjunctival space; these surgeries are performed through ab externo approach.[4] Trabeculectomy and shunt surgery come with a range of complications such as hypotony, leakage, shallowing of the AC, choroidal effusion, and valve-related complications as in encapsulation, tube blockage, erosion, and endothelial cell loss.[5] An alternative route through an ab interno approach through implantation of a collagen implant XEN® (Allergan, CA, USA) has been described in an attempt to overcome the different complications which are seen in both trabeculectomy and shunt operations.[6] XEN is a hydrophilic, noninflammatory, and subconjunctival gelatin stent. The gelatin stent swells when hydrated, which helps maintain its intended position as it adapts to the shape of surrounding tissues to create a permanent channel from the AC to the subconjunctival space.

XEN implant depends on the Hagen–Poiseuille equation, which allows us to calculate the resistance to flow through a cylindrical tube. Assuming laminar flow of a noncompressible fluid, the outflow resistance and therefore, pressure differential increases linearly in relation to the length of the tube and decrease to the fourth power of the lumen radius. A longer thinner tube will provide more resistance to flow than a shorter and wider tube. This equation was used as the principle of the XEN implant.[7],[8] XEN gel stent has been reported with success for glaucoma surgery.[9],[10] The small lumen has been known to obstruct with subconjunctival scarring and fibrin obstruction.[11],[12] We reviewed our data on XEN gel stent implanted in 20 Black and Afro-Latino patients with open-angle glaucoma. All of the patients had brown pigmented iris. We reviewed their charts to see the success of the surgery.


   Methods Top


This study is a retrospective, single-surgeon (DL) review. This study performed was in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. This retrospective included 20 eyes with primary open-angle glaucoma (POAG). Glaucoma was previously diagnosed by measured elevated IOP with associated optic nerve head changes detected clinically and confirmed by visual field and optical coherence tomography (OCT). Patients had been diagnosed with POAG with or without cataract whose eyes were above the target IOP with maximal therapy or requesting surgical intervention to reduce dependency on several medications leading to decreased compliance. Inclusion criteria also covered patients with medication intolerance or poor compliance.

POAG was noted in all patients after extensive ocular examination including slit-lamp examination, gonioscopy, and IOP measurement by the Goldmann Applanation Tonometry in addition to visual field and OCT of the nerve fiber layer. No patient had previous trabeculectomy surgery, any possible allergic reaction with the material of the implant, controlled IOP by <3 different medications, monocular patients, pseudoexfoliation, shallow AC, and angle-closure glaucoma.

Postoperative visits were noted for all patients at 1 day, 1 week, 1 month, 3 months, and 6 months after the surgery. A minimum follow-up period of 12 months was obtained on all eyes. In each postoperative visit following examination was performed, visual acuity, IOP measurement, and any complications were reported. Surgery was performed for all patients under local anesthesia, and the procedure included mitomycin C (MMC) 20 μg subconjunctival injection and insertion of ab interno XEN implant with or without cataract extraction.

The XEN implant (Allergan, CA, USA) is derived from collagen and made of gelatin. The implant is made from cross-linked porcine collagen. The XEN45 implant used in this study has a lumen diameter of 45 μ and a length of 6 mm that would provide aqueous filtration around 2–2.5 mL/min.[6] The gelatin imparts hydrophilic properties that allow the tube to expand when hydrated by contact with aqueous fluid. This expansion of the outer diameter of the tube aids in keeping the gelatin stent in its intended location after surgical implantation. The soft microimplant provides minimal resistance to flow and is designed to rely on subconjunctival resistance alone. A handheld disposable injector is designed specifically for the surgical implantation of the implant. The inserter has a 27G needle preloaded with the implant [Figure 1]. All surgeries were done by the same surgeon. After skin disinfection, proper field dressing, and speculum insertion, superior nasal conjunctiva was marked 2 and 3 mm from the limbus.
Figure 1: Xen Gel Stent being inserted steps (a-d)

Click here to view


Using an ab interno approach, the preloaded injector needle was inserted through a 1.2-mm corneal paracentesis incision opposite the site of the desired implantation after the AC was filled with the highly cohesive viscoelastic device. An intraoperative goniolens was used to verify placement through the angle to avoid iris and iris root trauma in all cases. The needle tip was then aligned with the desired entry point of the trabecular meshwork and advanced anterior to the trabecular meshwork (under gonioscopic guidance) and sclera, while the eye was stabilized to provide counterforce to the implanting needle. The bevel was visualized as it exited the sclera into the subconjunctival space, and small adjustments (forward or backward) could be made at this point to ensure visibility of the entire beveled tip in the subconjunctival space, as well as relative freedom of movement of the needle within the sclera. The gelatin stent was then released in the subconjunctival space and the injector removed from the eye. If the stent was properly positioned, approximately 2 mm and 1 mm of its length were visible in the subconjunctival space and AC, respectively. After implantation, 20 μg(0.02 mg/ml) of MMC was given subconjunctivally in the quadrant using a 27G hypodermic needle under tenon's capsule and spread under the conjunctiva in the superior nasal quadrant. No further sutures were applied, and at that point, the surgery is terminated.

In cases where cataract extraction was indicated, the main incision was performed at the steepest corneal axis and the paracentesis incisions were performed nasally and infratemporally at 7 o'clock position and 5 o'clock positions for the right and left eyes, respectively. The latest incision was done 2-3 mm central to the limbus and used for the insertion of the XEN45 into the superior nasal area.

After phacoemulsification was finished, viscoelastic material was used to implant the intraocular lens (IOL). After the IOL was properly placed in the bag, the AC was filled with the cohesive viscoelastic device, and a corneal suture was used to secure the principle 2.4 mm incision. XEN implantation followed as previously indicated. Viscoelastic was promptly removed from AC to prevent XEN implant potential blockage or partial closure after surgery.

Patients were prescribed Ciprofloxacin® (Alcon USA) four times a day and Pred Forte® (prednisolone acetate 1%, Allergan USA) every 2 h for 1 month then tapered over the next month to stop. The follow-up visits were reviewed at 1 day, 1 week, and 1, 3, and 6 months postoperatively.

Outcomes reviewed in each visit included BCVA, IOP, medications, possible complications, and management.

None of the patients had angle-closure glaucoma (where angles were not surgically opened), active neovascular glaucoma, previous glaucoma shunt/valve in the target quadrant, prior intraocular surgery (except uncomplicated phacoemulsification with IOL occurring >3 months), previous diagnosis of chronic uveitis in either eye, prior conjunctival surgery, conjunctival scarring, or other conjunctival pathologies in the target quadrant, clinically significant inflammation or infection, history of corneal surgery (including laser-assisted in situ keratomileusis and photorefractive keratectomy), opacities, or disease/pathology, central corneal thickness ≤490 μm or ≥620 μm, iris neovascularization (active or within 6 months of screening), aphakia, AC IOL, or previous complicated phacoemulsification surgery, presence of vitreous in the AC or intraocular silicone oil, active diabetic retinopathy, choroidal neovascularization, retinal vein occlusion, proliferative retinopathy, or other ophthalmic disease/disorder that could confound study results.

We worked with each patient's primary care physician to discontinue anticoagulation therapy (other than aspirin 81 mg) before surgery and resume it postoperatively. Patients received appropriate, unrestricted medical treatment (including IOP-lowering medications).

Postoperative management

Topical IOP-lowering medications for the treated eye, as well as systemic IOP-lowering medications, were suspended on the day of surgery but reintroduced postoperatively if required to manage any elevated IOP. No needling was performed, due to the recurrence of scarring often seen in this patient population.

Assessments and outcomes

IOP was assessed at all visits using Goldmann applanation tonometry.

Statistical analysis

We looked at baseline IOP, number of IOP-lowering medications used at baseline, last observed IOP, and last number of medications at the 12-month visit or later as explanatory variables.


   Results Top


Of 20 eyes that had undergone the procedure with 1-year follow-up, 8 failed before 12 months requiring additional glaucoma surgery. A total of 9 of the 12 (75%) eyes underwent XEN + cataract surgery and 3 (25%) had XEN surgery alone. Of the eyes that completed 12-month follow-up, the mean medicated IOP was 15.3 ± 6.2 mmHg at baseline, and 12.9 ± 4.5 mmHg at 12 months, a 16% IOP reduction. Mean medications dropped from 3.58 ± 0.7 preoperatively to 1.75 ± 1.5 at 6 months.

In all, 40% of 20 patients required secondary glaucoma filtration surgery by 12 months.

Safety

There were no reports of Descemet's membrane detachment, iris damage, lens contacts, vitreous bulge or loss, retrobulbar hemorrhage, conjunctival perforation, flat AC with iridocorneal touch extending to the pupil, or any other intraoperative complications.

Postoperative adverse events (AEs) through month 12 were mostly mild or moderate and transient, resolving without sequelae, and none were unexpected in this population of patients with refractory glaucoma. Four patients experienced transient hypotony (defined as IOP <6 mm Hg regardless of outcome) that neither required surgical intervention nor had clinically significant consequences; there were no reports of associated choroidal effusion, suprachoroidal hemorrhage, or maculopathy.

No stent migration, exposure, or extrusion was noted. No corneal edema, bleb leak, Dellen, macular edema or macular pucker was noted. No clinically significant consequences were associated with these hypotony cases (e.g. choroidal effusions, suprachoroidal hemorrhage, or hypotony maculopathy). There were no cases of persistent hypotony (defined as IOP <6 mm Hg on two consecutive visits >30 days apart) and none required surgical intervention. Five were converted to a glaucoma procedure and/or explanted.

Overall, visual recovery following implantation of the gelatin stent was relatively rapid; the percentage of patients experiencing no change (including ≤1 line loss) or improvement in BCVA from baseline.

During the 12-month period, no needling was performed. Due to the well-known history of subconjunctival scarring in this patient population needling was not performed. Medical therapy was added or another surgery was performed as needed. The ostium is not able to be needled in the manner a trabeculectomy ostium can be. Internal obstruction of the XEN by pigment cannot be needled either. Scarring of the conjunctiva over the Xen was seen in most of the patients.


   Discussion Top


In this retrospective single-surgeon study conducted in a group of Black and Afro-Latino glaucoma patients, 40% failed by 12 months requiring a second procedure. About 60% had a successful lowering of the IOP and decrease medication use. Mean medication use decreased from 3.58 to 1.75, further supporting the benefits of the gelatin stent for the treatment of refractory glaucoma in just over half of the patients.

There were no reports of intraoperative complications. During the 12-month follow-up, there were no cases of suprachoroidal hemorrhage, diplopia, severe corneal issues, retinal detachment, flat AC, choroidal effusion requiring drainage, loss of light perception, blebitis, iritis, endophthalmitis, or hypotony maculopathy. The most common AEs included transient hypotony (requiring no surgical intervention but captured as AEs per protocol regardless of outcome), increased IOP requiring glaucoma-related secondary surgical intervention. None, however, were unexpected in this population of patients with refractory glaucoma.

The lower success rate seen in Blacks and Afro-Latino patients in our series compared to previous studies in a predominately white population,[13] may be multifactorial, including, but not limited to scarring and pigment obstruction of XEN intraluminally. Yag laser treatment of pigment obstruction of the Xen tip in the AC has been described. However, in 8 of the 12 patients that required revision, only one had a patent lumen. Seven of the eight did not have a patent lumen and we identified pigment obstruction intraluminally in two patients. There was device obstruction by pigment seen in two patients whom had removal of the gel stent. Intraluminal obstruction and loss of function were present in other failures as characterized by no aqueous outflow after removing any potential Tenon's and subconjunctival obstruction, but no etiology was identified. No known intervention has been able to restore the intraluminal obstruction of Xen from pigment or other obstruction within the device. We believe that this is the first report of intraluminal obstruction of the Xen gel stent in Black and Afro-Latino glaucoma patients. Pigment liberation has been noted in Black patients who are phakic with glaucoma,[14] and the presence of aqueous cytokines leads to subconjunctival scarring.[15] The aqueous in patients with glaucoma have proinflammatory cytokines,[16] elevated levels of transforming growth factor-beta and prostaglandin E2, and TGFB2.[17] Many cases of pigment obstruction have been observed in phakic patients who have undergone trabeculectomy. Pigment liberation from iris lens contact leads to the pigment in the bleb and is a reason for failure [Figure 2]. We have also seen pigment obstruction of the XEN gel stent [Figure 3].
Figure 2: Pigment obstructing bleb in phakic patient with failed trabeculectomy

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Figure 3: Pigment blocking Xen Gel Stent

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The findings are clinically relevant considering that other XEN studies have been performed in a predominately Caucasian population with less iris pigment in the eye. This may have reduced the incidence of obstruction of the XEN and increased the success rate. Studies have shown pigment liberation with lens zonules rubbing against the posterior iris pigment epithelium.[18] In patients with similar clinical presentations, consideration should be given to only place XEN in after the cataract extraction and thus removing the pigment liberation stimulus that can occur from iridolenticular contact and long anterior zonules.

Intraluminal obstruction of XEN gel stent has been previously reported. In a recent study by Rigo et al., a hyperreflective intraluminal material was found in about one-third of their cases. They hypothesized that a material derived from the AC and flowing through the lumen deposits in the subconjunctival layer or a bleb that occurred initially fibrosed.[19] A case report by Gillmann et al. demonstrated XEN micro stent obstruction with dense fibrin plug in an aphakic patient who had developed ocular hypertension. Based on the patient's ocular morbidities, they suggested the obstruction could be a result of chronic inflammation causing a fibrin plug.[11]

In the study population, we hypothesize that the XEN 45 material and pigment liberation from iris into the AC in our population of patients flows through the lumen of the implant to cause the obstruction

We recommend caution when using XEN ab internally in Black and Afro-Latino patients as the success rate in our practice is lower than that of other studies performed in a predominately Caucasian population. The difference for this may be due to the amount of pigment in the iris, pigment liberation and pigment obstruction of the XEN gel stent, Tenon's obstruction, and subconjunctival fibrosis. Recently, interest has developed in ab externo XEN gel stent to ensure the device is mostly subconjunctival to reduce the risk of obstruction by Tenon's capsule. Perhaps, further study can be done to see if a Xen device with a larger lumen may ensure a greater success rate longer term. The Inn Focus shunt has a larger lumen of 70 μm compared to XEN's 45–60 μm. This may have greater success in Black and Afro Latino patients with glaucoma. The Hydrus stent has a larger lumen with a 290 μm inlet that directs aqueous to bypass the obstructed trabecular meshwork directly to the naturally draining collector channels and subconjunctival and episcleral aqueous veins. Furthermore, further study is recommended for this device being implanted ab externally and in pseudophakic patients where the AC is deeper and there is less risk of obstruction from the iris or pigment liberation from lens iris contact. Patients and surgeons should be aware of the higher risk of failure in this patient population. Less expensive, more effective alternative surgery may be more suitable in this patient population. Limitations of this study include the small sample size and retrospective nature. Further studies should be performed to further investigate this. Recently, on October 12, 2019, there is a global recall of the Xen Gel Stent. An inspection showed trace amounts of polishing compounds used in the needle sleeve manufacturing process. Allergan issued a product hold of XEN 45 devices while investigating these findings. It will be interesting to see whether or not this can also contribute to intraluminal obstruction of the XEN Gel stent.

Financial support and sponsorship

This study was supported by Daniel Laroche MD who is a speaker for Valent and Aerie, Bausch Health, and Ivantis.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006;90:262-7.  Back to cited text no. 1
    
2.
Friedman DS, Wolfs RC, O'Colmain BJ, Klein BE, Taylor HR, West S, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol 2004;122:532-8.  Back to cited text no. 2
    
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Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology 2014;121:2081-90.  Back to cited text no. 3
    
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Gedde SJ, Feuer WJ, Shi W, Lim KS, Barton K, Goyal S, et al. Treatment outcomes in the primary tube versus trabeculectomy study after 1 year of follow-up. Ophthalmology 2018;125:650-63.  Back to cited text no. 4
    
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Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC, et al. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol 2012;153:804-140.  Back to cited text no. 5
    
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Lewis RA. Ab interno approach to the subconjunctival space using a collagen glaucoma stent. J Cataract Refract Surg 2014;40:1301-6.  Back to cited text no. 6
    
7.
Vera VI, Horvath C. XEN gel stent: The solution designed by AqueSys®. In: Samples JR, Ahmed II. editors. Surgical Innovations in Glaucoma. New York: Springer Science+Business Media; 2014.  Back to cited text no. 7
    
8.
Sheybani A, Reitsamer H, Ahmed II. Fluid dynamics of a novel micro-fistula implant for the surgical treatment of glaucoma. Invest Ophthalmol Vis Sci 2015;56:4789-95.  Back to cited text no. 8
    
9.
Mansouri K, Guidotti J, Rao HL, Ouabas A, D'Alessandro E, Roy S, et al. Prospective evaluation of standalone XEN Gel implant and combined phacoemulsification-XEN Gel implant surgery: 1-Year Results. J Glaucoma 2018;27:140-7.  Back to cited text no. 9
    
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Sheybani A, Lenzhofer M, Hohensinn M, Reitsamer H, Ahmed II. Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: Pilot study. J Cataract Refract Surg 2015;41:1905-9.  Back to cited text no. 10
    
11.
Gillmann K, Mansouri K, Bravetti GE, Mermoud A. Chronic intraocular inflammation as a risk factor for XEN gel stent occlusion: A case of microscopic examination of a fibrin-obstructed XEN stent. J Glaucoma 2018;27:739-41.  Back to cited text no. 11
    
12.
Laroche D, Ng C, Lynch G. Baerveldt attached to XEN: A new technique to manage failed XEN glaucoma surgery. J Glaucoma 2018;27:382-4.  Back to cited text no. 12
    
13.
Kalina AG, Kalina PH, Brown MM. EN® Gel stent in medically refractory open-angle glaucoma: results and observations after one year of use in the United State. Ophthalmol Ther 2019;8:435-46.  Back to cited text no. 13
    
14.
Semple HC, Ball SF. Pigmentary glaucoma in the Black population. Am J Ophthalmol 1990;109:518-22.  Back to cited text no. 14
    
15.
Freedman J, Iserovich P. Pro-inflammatory cytokines in glaucomatous aqueous and encysted Molteno implant blebs and their relationship to pressure. Invest Ophthalmol Vis Sci 2013;54:4851-5.  Back to cited text no. 15
    
16.
Freedman J, Goddard D. Elevated levels of transforming growth factor beta and prostaglandin E2 in aqueous humor from patients undergoing filtration surgery for glaucoma. Can J Ophthalmol 2008;43:370.  Back to cited text no. 16
    
17.
Tripathi RC, Li J, Chan WF, Tripathi BJ. Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res 1994;59:723-7.  Back to cited text no. 17
    
18.
Roberts DK, Newman TL, Roberts MF, Teitelbaum BA, Winters JE. Long anterior lens zonules and intraocular pressure. Invest Ophthalmol Vis Sci 2018;59:2015-23.  Back to cited text no. 18
    
19.
Rigo J, Castany M, Banderas S, Pujol O, Amilburu M, Dou A. Possible intraluminal obstruction of the XEN45 Gel stent observed with anterior segment Optical coherence tomography. J Glaucoma 2019;28:1095-101.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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