ORIGINAL RESEARCH

Comparison of Minimally Invasive XEN45 Gel StentImplantation in Glaucoma Patients Without and WithPrior Interventional Therapies

Fritz H. Hengerer . Gerd Auffarth . Ina Conrad-Hengerer

Received: April 8, 2019 / Published online: June 13, 2019� The Author(s) 2019

ABSTRACT

Introduction: The aim of our analysis was tocompare the effectiveness of the XEN45 gelstent implantation in patients without and withprior glaucoma intervention.Methods: Retrospective analysis including 148medical records of consecutive glaucoma eyeswithout prior glaucoma intervention (group A,n = 45) or with prior glaucoma intervention(group B, n = 103). Follow-up data up to12 months after XEN45 gel implantation wereavailable for all eyes.Results: At 12 months, qualified success (IOPreduction of C 20% and IOP\18 mmHg with-out and with medication) was achieved in 76%of eyes in group A and in 72% of eyes in group

B; corresponding values for complete success(IOP reduction of C 20% and IOP\18 mmHgwithout medication) were 56% and 55%. MeanIOP was significantly reduced by 58% from36.0 ± 10.7 mmHg preoperatively to14.2 ± 3.4 mmHg at 12 months in group A(p = 0.000) and by 53% from 31.6 ± 8.9 mmHgto 14.3 ± 4.2 mmHg and in group B (p = 0.000).The mean number of hypotensive medicationshad significantly decreased from 3.6 ± 0.8 atbaseline to 0.3 ± 0.7 medications in group A(p = 0.000) and from 3.0 ± 1.0 to 0.3 ± 0.7medications in group B (p = 0.000). Needlingwas required in 29% of eyes in group A and in35% of group B within 12 months. No statisti-cally significant differences were observedbetween eyes without and with prior glaucomaintervention.Conclusion: The 1-year results of our retro-spective analysis indicate that patients withoutand with previous glaucoma intervention canbenefit from XEN45 gel stent implantation.Both groups achieved significant and similarreductions in IOP and hypotensive medication,with a slight trend towards greater reductions ineyes without prior glaucoma intervention. Fur-ther controlled prospective studies with longerfollow-ups are required.Funding: Editorial support and article process-ing charges were funded by Allergan.

Enhanced digital features To view enhanced digitalfeatures for this article go to https://doi.org/10.6084/m9.figshare.8224211.

F. H. Hengerer (&)Department of Ophthalmology, Burgerhospital undClementine Kinderhospital gemeinnutzige GmbH,Frankfurt am Main, Germanye-mail: f.hengerer@buergerhospital-ffm.de

F. H. Hengerer � G. Auffarth � I. Conrad-HengererInternational Vision Correction Research Center(IVCRC), University of Heidelberg, Heidelberg,Germany

G. AuffarthDepartment of Ophthalmology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany

Ophthalmol Ther (2019) 8:447–459

https://doi.org/10.1007/s40123-019-0193-7

Keywords: Glaucoma; Minimally invasiveglaucoma surgery; Prior glaucomaintervention; XEN45 gel implant

INTRODUCTION

Glaucoma is one of the most common causes ofblindness and currently affects more than 64million people worldwide [1]. This chronic,progressive eye disease damages the nerve fiberlayer and the optical nerve and finally leads toloss of visual field and visual acuity [2]. Since anincreased intraocular pressure (IOP) is consid-ered a significant risk factor, treatment requiresan effective, long-term reduction in IOP forwhich various treatment methods are availabletoday [3]. Surgical treatments are necessary iftopical ocular hypotensive therapy is not suffi-cient, not adequately applied, or not tolerated[2]. While trabeculectomy is still the gold stan-dard filtering surgery and shows good efficacy, itrequires a strict postoperative follow-up andbrings with it a range of intra- and postoperativecomplications [4]. In order to make less invasivefiltrating therapy possible, various minimallyinvasive glaucoma surgery (MIGS) devices havebeen developed in recent years, all of which canbe implanted ab interno, but which differregarding the addressed drainage path of theaqueous humor [5]. The XEN45 gel implant(XEN45) (Allergan, Dublin, Ireland) is the onlycommercially available MIGS device that createsa permanent shunt from the anterior chamberto the subconjunctival space, thus bypassingthe natural drainage pathways which often areobstructed in glaucoma patients [6–8]. TheXEN45 gel implant is made of hydrophilicgelatin glutaraldehyde, making it non-degrad-ing, with good biocompatibility and tolerability[7, 9]. The dimensions of the tube (6 mm inlength; 45 lm inner diameter) were designed tomaximize long-term aqueous humor drainagewhile minimizing the risk of hypotension[7, 9–11]. At present, it is approved in Europeand USA with slightly different indications. InEurope, the XEN45 gel stent is indicated inpatients with primary open-angle glaucoma(POAG) who have failed previous medicaltreatments, while the US indication includes

management of refractory glaucomas, includingcases where previous surgical treatment hasfailed, cases of POAG, and pseudoexfoliative orpigmentary glaucomas with open angle that areunresponsive to maximum tolerated medicaltherapy [12, 13]. Clinical studies have shownthat the XEN45 can be implanted with andwithout combination of phacoemulsificationand effectively reduces IOP while maintaining agood safety profile [14–19]. Moreover, an inter-national multicenter retrospective study com-pared XEN gel stent implantation andtrabeculectomy in 354 eyes with refractoryglaucoma and no prior incisional filtering sur-gery. The results demonstrated that there wasno difference in efficacy, risk of failure, andsafety profile between the two surgical proce-dures [20].

Most of the studies included patients whoreceived the XEN45 stent as an initial surgicaltherapy. However, since glaucoma is a lifelongchronic disease, there are many patients withfailed previous incisional glaucoma therapieswho might benefit from an XEN45 stentimplantation. With regard to trabeculectomy,however, a previous study showed that eyeswith initial trabeculectomy (n = 75) had a sta-tistically significantly higher success rate andrequired statistically fewer medications at 3years postoperatively than those that under-went repeat trabeculectomy (n = 75) [21]. Eventhough individual studies on the XEN45 gelstent included patients with previous glaucomainterventions [14, 15, 22], to the best of ourknowledge no comparative analysis has yetbeen published in a peer review article.

The aim of our retrospective analysis was tocompare IOP-lowering and medication-reduc-ing effects of the XEN45 gel stent in glaucomapatients without and with prior glaucomainterventions in order to investigate whetherboth patient groups benefit from XEN45 gelimplantation.

METHODS

We conducted a retrospective analysis of allXEN45 gel stent implantations consecutivelyperformed between March 2014 and June 2015

448 Ophthalmol Ther (2019) 8:447–459

at the Department of Ophthalmology, GoetheUniversity, Frankfurt, Germany [14]. For thepresent comparative analysis, we included themedical records of 148 eyes for which12 months of data were available; 45 of theseeyes were without prior glaucoma interventionand 103 eyes had failed prior glaucoma inter-ventions. In general, patients presented with amoderate to advanced glaucoma stage. All pro-cedures performed in studies involving humanparticipants were in accordance with the ethicalstandards of the local Ethics Committee of theGoethe University, Frankfurt, and with the1964 Helsinki declaration and its later amend-ments or comparable ethical standards.According to the approval of the Ethics Com-mittee of the Goethe University, Frankfurt, thedata for this retrospective analysis were evalu-ated pseudonymized and no patient informedconsent was required.

Patients and Assessments

Patients with refractory open-angle glaucoma(OAG) had been referred to our departmentfrom private practices with a request for surgicalglaucoma therapy. Patients with an area ofhealthy, free, and mobile conjunctiva in thetarget quadrant and inadequately controlledIOP, optic disc damage, and progressive visualfield loss despite maximum hypotensive topicaltherapy and/or prior filtering, cyclophotocoag-ulation, or laser interventions were consideredsuitable for XEN45 implantation. Exclusioncriteria were angle-closure glaucoma, activeneovascular glaucoma, prior conjunctival sur-gery, conjunctival scarring, or other conjuncti-val pathologies in the target quadrant,pregnancy, age\18 years, condition after parsplana vitrectomy, flat anterior chamber andnarrow chamber angle. Prior to XEN45implantation a complete ophthalmic examina-tion including gonioscopy had been performed.Postoperative evaluations were conducted atday 1, week 1, and months 1, 3, 6, and 12. Ateach visit, slit-lamp examination, gonioscopy,IOP assessment by Goldmann applanationtonometry (the mean value of three measure-ments per visit was recorded), as well as

evaluation of the posterior pole were carriedout. Moreover, the number of medications,needling, and adverse events were documented.

Surgical Technique

All implantations were performed by one singlesurgeon (FHH) following a standardizedimplantation technique which has been descri-bed in detail in our recent publication [14]. Inbrief, the XEN45 was implanted ab interno underperibulbar anesthesia. In order to prevent con-junctival scarring, 0.1 ml of MMC solution(0.01% mitomycin C, a total dose of 10 lg) wasinjected subconjunctivally into the nasal supe-rior quadrant prior to XEN45 implantation.After a medium grade viscoelastic device wasused to stabilize the anterior chamber, the pre-loaded injector needle was inserted through a1.2-mm corneal paracentesis incision oppositethe desired implantation site. The needle wasthen directed across the anterior chamber andthe injector tip was used to penetrate throughthe chamber angle above the trabecular mesh-work and the sclera at least 3 mm in length inorder to place the implant properly. Viscoelasticsubstance was then thoroughly removed, para-centeses were hydrated, and the eye was cov-ered with a patch.

Postoperatively, topical antibiotics weregiven four times daily for 10 days in combina-tion with steroids six times daily and taperedout over 6 weeks. Antiglaucoma medication wasgiven until surgery and was suspended on theday of surgery. In case of elevated IOP in thepostoperative phase, additional antiglaucomamedication or secondary intervention was givenat the discretion of the surgeon. In case ofconjunctival scarring and bleb failure due toTenon’s cyst formation, a needling procedurewas performed under microscopic view in theoperating room. The needling technique hasrecently been described in detail [14]. Theadministration of additional drugs during theneedling was considered on a case-by-case basis.Only in cases of pronounced fibrosis 10 lgmitomycin C was injected during needling,while in eyes with cystic fibroses no additionaldrugs were used.

Ophthalmol Ther (2019) 8:447–459 449

Statistical Analysis

For comparative analysis, the following twosubgroups were defined: (a) eyes that had noprior glaucoma intervention but were on med-ication only, (b) eyes that had prior glaucomainterventions such as trabeculectomy, micro-bypass stent implantation, cyclophotocoagula-tion, laser procedures, and phacoemulsification.For more detailed analyses, group B was thenfurther subdivided according to the variousprevious interventions.

Effectiveness variables were the success ratesdetermined on the basis of the following defini-tions: ‘‘Complete success’’ was defined as an IOPreduction of at least 20% and an IOP value below18mmHgwithoutmedication. ‘‘Qualified success’’wasdefinedas an IOP reductionof at least 20%andan IOP value below 18mmHg without or withmedication. Additional effectiveness variableswere mean IOP and the mean number ofantiglaucoma medications, and their changes ascompared to baseline, as well as the proportion ofpatients achieving a target IOP ofB 18 mmHg, B 15 mmHg, and B 13 mmHg at12 months and needling rates. Safety outcomesincluded hypotony rate (IOP B 6 mmHg) as wellas intra- and postoperative complications. Datawere presented as mean and standard deviation,unless otherwise indicated. Boxplots of IOPdata at12 months were used to display the IOP distribu-tion in both groups and to identify outliers. Base-line IOP was the IOPmeasured at the preoperativevisit on medications. In order to calculate differ-ences between pre- and postoperative values, theparametric t test was used. Also, the non-para-metric Wilcoxon sign rank test was used fordetermining statistical significance within a group(p\0.05 considered statistically significant). Fordetermining statistical significance between bothgroups, t test for independent samples was applied(p\0.05 considered statistically significant). Chi-square tests were performed in all other cases(p\0.05 considered statistically significant).

RESULTS

Overall, medical records of 148 eyes wereincluded in this analysis. Of these, 45 eyes had

no prior glaucoma intervention but were onmedication only, while 103 eyes had failed aprior glaucoma intervention, including tra-beculectomy (31 eyes), micro-bypass stentimplantation (31 eyes), cyclophotocoagulation(24 eyes), phacoemulsification (11 eyes), andlaser procedures (6 eyes). Within the group ofeyes without prior glaucoma intervention, theXEN45 gel stent was implanted as standaloneprocedure in 32 eyes (71%) and in combinationwith phacoemulsification in 13 eyes (29%).Within the group of eyes with prior glaucomainterventions, 92 eyes (91%) received theXEN45 stent as standalone procedure and 9 eyes(9%) as combined procedure. For two eyes withprior glaucoma intervention, this informationwas missing.

Demographics and baseline ocular parametersof both groups (without/with prior glaucomaintervention) are displayed in Table 1. No sta-tistically significant differences existed indemographic characteristics between the twogroups (p[0.05). Regarding baseline character-istics, eyes without prior intervention had a sig-nificantly higher mean baseline IOP than eyeswith prior intervention (36.0 ± 10.7 mmHg vs.31.6 ± 8.9 mmHg; p = 0.01; t test). Moreover,the mean number of hypotensive medicationswas significantly higher in eyes without priorintervention (3.6 ± 0.8 vs. 2.1 ± 1.0; p = 0.001;t test) (Table 1).

One year after XEN45 implantation, 76%(34/45) of eyes without prior intervention and72% (74/103) of eyes with prior interventionachieved an IOP reduction of at least 20% andan IOP value below 18 mmHg with or withoutmedication (qualified success). Complete suc-cess, i.e., an IOP reduction of at least 20% andan IOP value below 18 mmHg without medica-tion, was experienced by 56% (25/45) of eyeswithout prior intervention and by 55% (57/103)of eyes with prior intervention 12 months afterXEN45 implantation. There were no statisticallysignificant differences between both groupsregarding results of complete and qualifiedsuccess (p = 0.994 and p = 0.665 respectively;chi-square test).

In both groups a significant reduction of themean IOP was observed from the first postop-erative day which lasted up to 1 year

450 Ophthalmol Ther (2019) 8:447–459

postoperatively. In eyes without prior glaucomaintervention, the mean IOP decreased signifi-cantly by 58% from preoperatively 36.0 ±

10.7 mmHg to 14.2 ± 3.4 mmHg at 12 monthspostoperatively (p = 0.000; Wilcoxon test),while in eyes with prior glaucoma interventiona mean IOP reduction by 53% from31.6 ± 8.9 mmHg to 14.3 ± 4.2 mmHg was

observed at 1 year postoperatively (p = 0.000;Wilcoxon test). No significant differences inmean IOP were found between the two groupsat any visit during follow-up observation(p[ 0.374 at each postoperative visit; t test)(Fig. 1). The box plots of the IOP at 12 monthsdisplay a median IOP of 14 mmHg in bothgroups, with an interquartile range from 13 to15 mmHg in eyes without prior glaucomaintervention and from 13 to 16 mmHg in eyeswith prior glaucoma intervention (Fig. 2). Withregard to the outliers, we carefully checked theirmedical history; however, no specific parame-ters could be identified that could explain thehigh IOP in these eyes.

Also, the proportion of eyes achieving targetpressure values of 18 mmHg, 15 mmHg, and13 mmHg at 1 year postoperatively did not dif-fer significantly between both groups (p[ 0.05;chi-square test) (Fig. 3).

In both groups, the mean number of medi-cations was significantly reduced at every visitfrom postoperative day one to the end of the1-year follow-up period. Within eyes withoutprior glaucoma intervention, the mean numberof antiglaucoma medications had significantlydecreased from 3.6 ± 0.8 at baseline to0.3 ± 0.7 medications at 12 months postopera-tively (p = 0.000; Wilcoxon test), while in eyeswith prior glaucoma intervention it haddecreased from 3.0 ± 1.0 to 0.3 ± 0.7 medica-tions (p = 0.000; Wilcoxon test). No significantdifferences between the groups were observed atany time during follow-up (p[0.436 at eachpostoperative visit; t test) (Fig. 4).

While at baseline 60% (27/45) of eyes with-out prior glaucoma intervention required morethan three medications, this was the case in31% (32/103) of patients with prior glaucomaintervention. At 12 months all eyes withoutprior intervention and all but one eye with priorintervention needed less than three medica-tions. Moreover, 78% (35/45) of eyes withoutprior glaucoma intervention and 83% (85/103)of eyes with prior glaucoma intervention werecompletely off drops 1 year postoperatively(Fig. 5).

Needling was required in 29% (13/45) of eyeswith no prior glaucoma intervention and 35%(36/103) of eyes with prior glaucoma

Table 1 Demographics and baseline ocular parameters

Withoutpriorglaucomaintervention(n = 45)

With priorglaucomaintervention(n = 103)

p value§

Age (years),

mean ± SD

(range)

68.4 ± 13.9

(28–89)

68.8 ± 14.87

(30–91)

0.851

Gender, n (%)a

Male 17 (37.8) 42 (40.8) 0.855

Female 28 (62.2) 61 (59.2)

Operated eye, n (%)a

OD (right

eye)

21 (46.7) 52 (50.5) 0.723

OS (left eye) 24 (53.3) 51 (49.5)

Cup to disc

ratio,

mean ± SD

(range)

0.80 ± 0.11

(0.5–1.0)

0.84 ± 0.12

(0.4–1.0)

0.05

IOP (mmHg),

mean ± SD

(range)

36.0 ± 10.7

(20–60)

31.6 ± 8.9

(18–65)

0.01

Number of

medication,

mean ± SD

(range)

3.6 ± 0.8

(2–5)

3.0 ± 1.0

(0–5)

0.001

IOP intraocular pressure, SD standard deviationa Percentages refer to the respective group (with/withoutprior intervention)§ Independent t test was performed to compare bothgroups; P value lower than 0.05 was determined to bestatistically significant

Ophthalmol Ther (2019) 8:447–459 451

intervention within the 1-year follow-up per-iod, with most procedures being performedwithin the early postoperative phase (betweenweek 1 and month 3). The difference betweenboth groups was not statistically significant(p = 0.57; chi-square test). Three eyes (6.7%)without prior glaucoma intervention and 8 eyes(7.8%) with prior glaucoma intervention pre-sented with uncontrolled IOP during the fol-low-up phase. Together with the patients, it wasdecided to implant a second XEN gel stent inorder to generate the possibility of additionalaqueous humor drainage.

Hypotony (IOP B 6 mmHg) was present inone eye without prior glaucoma intervention(2.2%) and in six eyes (5.8%) with prior glau-coma intervention at month 1 (p = 0.676; chi-square test). Within the group of eyes withoutprior glaucoma intervention, the single case ofhypotony had resolved by month 3, whilewithin the group of eyes with prior glaucomaintervention two cases of hypotony persisteduntil month 6. Both cases required filling of theanterior chamber and were resolved at 1 year.

No macular folds, choroidal effusion or hem-orrhage, choroidal detachment, or visual lossrelated to hypotony were observed. Moreover,no cases of device exposure or migration, cor-neal alterations, wound leakage, or endoph-thalmitis were observed in either group duringthe entire follow-up period. Complications oradverse events that were documented duringthe 1-year follow-up period are summarized inTable 2.

In order to further investigate if variousprevious glaucoma interventions may have dif-ferent effects on the efficacy of a subsequentXEN gel implantation, we further subdividedthe group of eyes with prior glaucoma inter-ventions and analyzed mean IOP as well asmean number of medications at baseline and12 months after XEN45 implantation. More-over, we analyzed needling rates at 12 monthspostoperatively. Results are presented inTable 3. There was no statistically significantdifference between the eyes without previousglaucoma intervention and eyes with the

Fig. 1 Mean IOP at each study visit in eyes without priorinterventional glaucoma therapy (n = 45) and eyes withprior interventional glaucoma therapy (n = 103). Errorbars indicate SD for the mean. Within each group, themean IOP was significantly reduced from baseline at anyvisit during the follow-up period (p = 0.000; Wilcoxon

test). Preoperatively, significant differences were observedbetween both groups (p = 0.01; t test), while at each visitafter gel stent implantation no significant differences wereobserved between groups regarding mean IOP (p[ 0.374;t test)

452 Ophthalmol Ther (2019) 8:447–459

Fig. 2 Box plot of IOP at 12 months in eyes without priorglaucoma intervention (n = 45) and eyes with priorglaucoma intervention (n = 103), with 50% of IOP values

(interquartile range) lying between 13 and 15 mmHg ineyes without prior glaucoma intervention and between 13and 16 mmHg in eyes with prior glaucoma surgery

Fig. 3 Proportion of eyes reaching a certain target pressure at 12 months postoperatively. Comparison of eyes without orwith prior interventional therapy

Ophthalmol Ther (2019) 8:447–459 453

respective prior glaucoma interventions(p[ 0.5; chi-square test).

DISCUSSION

The aim of our retrospective analysis was tocompare the efficacy of the XEN45 gel implantin patients with and without prior glaucomaintervention. Despite several studies demon-strating the efficacy and good safety profile ofthe XEN45 stent as initial surgical intervention[14, 16, 19, 20], there is not yet sufficientinformation available as to whether the XEN45stent has comparable performance in patientswho failed previous glaucoma interventions.

The results of our retrospective study showthat patients with and without prior glaucomaintervention can benefit from the implantationof the XEN45gel stent. Both groups achieved aneffective IOP and drug reduction that lasteduntil the end of the 1-year follow-up period. Nosignificant differences were observed betweenthe two groups. Overall, 76% of eyes withoutprior glaucoma intervention and 72% of theeyes with prior glaucoma intervention achieved

qualified success (i.e., an IOP reduction of atleast 20% and an IOP value below 18 mmHgwith or without medication). In both groups,the mean IOP was effectively reduced from over30 mmHg at baseline to under 15 mmHg at12 months. Moreover, an IOP reduction of morethan 50% was observed on the first day afterXEN45 implantation and was sustained duringthe complete follow-up period in both groups.Also, the mean number of antiglaucoma medi-cations was effectively reduced in both groups,from at least 3 to 0.3 medications, with morethan three-quarters of eyes being completely offdrops 1 year after XEN45 implantation in bothgroups. At the same time, hypotony was rarelyobserved in both groups. All cases of hypotonywere completely resolved at 1 year and were notassociated with complications threateningvisual acuity. Also with regard to the require-ment of a second filtrating implant or needlingprocedure, no significant differences betweenthe two groups were found in our analysis. Asubgroup analysis revealed that eyes with pre-vious trabeculectomy had a tendency to have ahigher needling rate at 12 months than eyeswithout prior glaucoma intervention (48% vs.

Fig. 4 Mean number of antiglaucoma medications at eachstudy visit in eyes without prior glaucoma intervention(n = 45) and eyes with prior glaucoma intervention(n = 103). The mean number of medication was

significantly reduced from baseline at all visits(p = 0.000; Wilcoxon test). Between groups, no significantdifferences were observed (p[ 0.436; t test). Error barsindicate SD for the mean

454 Ophthalmol Ther (2019) 8:447–459

29%) or with any other prior intervention(Table 3). However, the differences were notstatistically significant, which may be due tolow case numbers.

In both groups, some eyes received theXEN45 gel implant in combination with pha-coemulsification (21% of eyes without and 9%of eyes with prior glaucoma intervention).However, as shown in our analysis of the totalpopulation as well as in the preliminary resultsfrom the APEX study, the XEN45 gel stentresults in a comparable and effective IOPreduction both as a sole procedure and incombination with phacoemulsification [14, 23].It can therefore be assumed that the small

number of combined procedures had no rele-vant influence on the results of the presentcomparison analysis.

Although we did not find any statisticallysignificant differences, our data do providesome indications suggesting that eyes withoutprior glaucoma intervention might tend torespond slightly better to the XEN45 stent thanpretreated eyes. Eyes without prior glaucomatreatment achieved a numerically higher suc-cess rate and greater reductions in IOP andantiglaucoma medication. At the same time,needling was numerically required less often inthese eyes. Moreover at 12 months postopera-tively, the IOP values in eyes with prior

Fig. 5 Proportion of eyes requiring 0–5 antiglaucoma medications at a baseline and b at 12 months postoperatively.Comparison of eyes without prior glaucoma intervention (n = 45) and eyes with prior glaucoma intervention (n = 103)

Ophthalmol Ther (2019) 8:447–459 455

intervention indicated a slightly greater vari-ance with a tendency towards higher IOP ascompared to eyes without prior glaucomaintervention (Fig. 2). However, these assump-tions must be treated with utmost caution, asno statistically significant differences wereobserved within 1-year follow-up within ouranalysis.

Overall, our data are in good agreement withthe results of previously published retrospectiveand prospective studies, showing that theXEN45 gel stent is an effective method with asafe profile for controlling IOP in glaucomapatients. Furthermore, our results are consistentwith the data of a recently published retro-spective case series with 17 eyes receiving a

XEN45 gel implant after failed trabeculectomy[22]. At month 12, the mean IOP was effectivelyreduced in these pretreated eyes from21.5 mmHg preoperatively to 13.6 mmHg(p\ 0.05) and at the same time medication wasreduced from 2.8 preoperatively to 1.0(p\ 0.05). Hypotony (IOP\6 mmHg) wasobserved in four cases that all resolved sponta-neously, secondary filtration surgery wasrequired in two cases, and postoperative blebintervention was required in nine cases. More-over, our data are also in line with the resultsfrom a post hoc data analysis of a prospectivestudy presented during ASCRS 2018 [24]. In thisanalysis, 1-year results of the XEN45 stent inpatients without (n = 24) and with (n = 41) andprevious incisional glaucoma procedures werecompared. It also revealed a similar effective-ness of the XEN45 stent regarding IOP and drugreduction in both groups. For instance, successrates were 83% in eyes without prior incisionalsurgery and 71% in eyes with prior incisionalsurgery, with success rate defined as proportionof patients achieving at least 20% IOP reductionon the same number or fewer medications ascompared to baseline. Moreover, mean IOP wasreduced from 25.7 to 14.9 mmHg in eyes with-out prior incisional surgery and from24.8 mmHg at baseline to 16.6 mmHg at12 months in eyes with prior incisional surgery.It is interesting to note that this analysis alsofound a trend towards greater reductions in IOPand antiglaucoma medication in eyes withoutprior incisional surgery; however, no statisti-cally significant differences were observed.Taken together, these results demonstrate con-sistently that the XEN45 stent appears to besimilarly effective in eyes without prior glau-coma intervention as well as in eyes with priorglaucoma intervention.

Our study has several limitations. First, it wasa retrospective analysis of data from a singlecenter, which might have led to bias. Never-theless, this approach reflects the clinical rou-tine and provides important insights into theefficiency of the XEN45 implant in clinicalroutine. Second, our results are limited to12 months, which is a relatively short period ina lifetime of chronic disease. Thirdly, there wasno control group, as both groups received the

Table 2 Documented complications and adverse eventsduring the 12 months follow-up

Complication oradverse event[n (%)]

Without priorglaucomaintervention(n = 45)

With priorglaucomaintervention(n = 103)

Subconjunctival

hemorrhage

intraoperatively

0 1 (1.0)

Device fracture

or migration

0 0

Hyphema 1 (2.2) 0

Second XEN45

gel stent

3 (6.7) 8 (7.8)

Hypotony

(\ 6 mmHg)

at 1 month

1 (2.2) 6 (5.8)

Macular folds 0 0

Choroidal

effusion/

hemorrhage

0 0

Choroidal

detachment

0 0

Macular edema 0 0

Endophthalmitis 0 0

456 Ophthalmol Ther (2019) 8:447–459

XEN45 implant, and finally the number of casesin our analysis may have been too small todetect statistically significant differencesbetween the two groups.

CONCLUSION

The 1-year results of our retrospective analysisindicate that patients without and with previ-ous glaucoma intervention can benefit from animplantation of the XEN45 gel stent. Reductioneffects for IOP and antiglaucoma medicationwere similar in both groups, with a slight trendtowards greater reductions in eyes without priorglaucoma intervention. Further controlledprospective studies with longer follow-ups arerequired to confirm our results.

ACKNOWLEDGEMENTS

Funding. No funding or sponsorship wasreceived for this study. Article processing char-ges were funded by Allergan.

Editorial Assistance. Editorial support wasfunded by Allergan. The authors maintainedcomplete control over the content of the paper.No payment was received for authorship of thedocument. All authors had full access to all of

the data in this study and take completeresponsibility for the integrity of the data andaccuracy of the data analysis.

Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship for thisarticle, take responsibility for the integrity ofthe work as a whole, and have given theirapproval for this version to be published.

Disclosures. Fritz Hengerer, Ina Conrad-Hengerer, and Gerd Auffarth have nothing todisclose.

Compliance with Ethics Guidelines. Allprocedures performed in studies involvinghuman participants were in accordance withthe ethical standards of the local Ethics Com-mittee of the Goethe University, Frankfurt, andwith the 1964 Helsinki declaration and its lateramendments or comparable ethical standards.According to the approval of the Ethics Com-mittee of the Goethe University, Frankfurt, thedata for this retrospective analysis were evalu-ated pseudonymized and no patient informedconsent was required.

Data Availability. AThe data sets generatedduring and/or analyzed during the currentstudy are available from the correspondingauthor on reasonable request.

Table 3 IOP, number of medication, and needling rate 1 year after XEN45 implantation in eyes without prior glaucomaintervention and eyes with different previous glaucoma interventions

IOP (mean – SD; [mmHg]) Number of medication(mean – SD)

Eyes with needlingat 12 months (%)

Baseline 12 months Baseline 12 months

No prior intervention (n = 45) 36.04 ± 10.73 14.06 ± 3.41 3.56 ± 0.84 0.33 ± 0.67 29

Trabeculectomy (n = 31) 33.71 ± 9.13 15.84 ± 5.70 3.10 ± 1.19 0.45 ± 0.81 48

Micro-bypass stent (n = 31) 29.48 ± 8.9 14.13 ± 2.72 2.87 ± 1.09 0.35 ± 0.76 26

Cyclophotocoagulation (n = 24) 29.67 ± 5.2 12.38 ± 2.45 2.92 ± 0.83 0.13 ± 0.45 33

Phacoemulsification (n = 11) 30.45 ± 4.41 13.36 ± 2.29 2.82 ± 1.17 0.00 ± 0.00 36

Laser procedure (n = 6) 41.67 ± 16.29 16.17 ± 6.46 3.33 ± 0.52 0.33 ± 0.82 17

Ophthalmol Ther (2019) 8:447–459 457

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any non-commercial use, distribution, and reproductionin any medium, provided you give appropriatecredit to the original author(s) and the source,provide a link to the Creative Commons license,and indicate if changes were made.

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