The Ahmed Versus Baerveldt Study Five-Year Treatment Outcomes
Panos G. Christakis, MD,1 Jeffrey W. Kalenak, MD,2 James C. Tsai, MD,3 David Zurakowski, PhD,4 Jeffrey A. Kammer, MD,5 Paul J. Harasymowycz, MD,6 Juan J. Mura, MD,7 Louis B. Cantor, MD,8 Iqbal I.K. Ahmed, MD1
Purpose: To compare 2 frequently used aqueous shunts for the treatment of glaucoma. Design: International, multicenter, randomized trial. Participants: Patients aged 18 years or older with uncontrolled glaucoma despite maximum tolerated medical therapy, many of whom had failed or were at high risk of failing trabeculectomy. Methods: Eligible patients were randomized to receive an Ahmed-FP7 valve implant (New World Medical, Inc, Rancho Cucamonga, CA) or a Baerveldt-350 implant (Abbott Medical Optics, Inc, Santa Ana, CA) using a standardized surgical technique. Main Outcome Measures: The primary outcome was failure, defined as intraocular pressure (IOP) outside the target range (5e18 mmHg) or reduced <20% from baseline for 2 consecutive visits after 3 months, severe vision loss, or de novo glaucoma surgery. Secondary outcomes measures included IOP, medication use, visual acuity, complications, and interventions. Results: A total of 238 patients were randomized; 124 received the Ahmed-FP7 implant, and 114 received the Baerveldt-350 implant. Baseline characteristics were similar between groups. Mean preoperative IOP was 31.4 10.8 mmHg on 3.1 1.0 glaucoma medications. At 5 years, the cumulative failure rate was 53% in the Ahmed group and 40% in the Baerveldt group (P ¼ 0.04). The main reason for failure in both groups was high IOP, and the cumulative de novo glaucoma reoperation rate was 18% in the Ahmed group and 11% in the Baerveldt group (P ¼ 0.22). Hypotony resulted in failure in 5 patients (4%) in the Baerveldt group compared with none in the Ahmed group (P ¼ 0.02). Mean IOP was 16.6 5.9 mmHg in the Ahmed group (47% reduction) and 13.6 5.0 mmHg in the Baerveldt group (57% reduction, P ¼ 0.001). Mean medication use was 1.8 1.5 mmHg in the Ahmed group (44% reduction) and 1.2 1.3 mmHg in the Baerveldt group (61% reduction, P ¼ 0.03). The 2 groups had similar complication rates (Ahmed 63%, Baerveldt 69%) and intervention rates (Ahmed 41%, Baerveldt 41%). Most complications were transient, and most interventions were slit-lamp procedures. Conclusions: Both implants were effective in reducing IOP and the need for glaucoma medications. The Baerveldt group had a lower failure rate and a lower IOP on fewer medications than the Ahmed group, but had a small risk of hypotony that was not seen in the Ahmed group. Ophthalmology 2016;-:1e10 ª 2016 by the American Academy of Ophthalmology.
Supplemental material is available at www.aaojournal.org.
The mainstay of glaucoma treatment is reducing intraoc- Patients who have failed trabeculectomy with antimetab- ular pressure (IOP) to prevent disease progression and olite or who have high risk disease (i.e., neovascular or vision loss.1,2 Treatment often begins with the use of uveitic glaucoma) may benefit from aqueous shunts.4,7 These topical medications and laser trabeculoplasty, with surgery implants shunt aqueous humor from the anterior chamber reserved for advanced or refractory cases, or for patients at using a long tube connected to a subconjunctival equatorial high risk of failing medical therapy.3 Traditional filtration end-plate that drains into the venous plexus. The 2 most surgery is trabeculectomy, which removes a block of commonly used aqueous shunts are the Ahmed valve (New limbal tissue to allow aqueous humor to flow through a World Medical Inc, Rancho Cucamonga, CA) and the scleral flap to an adjacent subconjunctival bleb. Baerveldt implant (Abbott Medical Optics, Santa Ana, CA). However, rates of failure of approximately 10% per year These shunts differ in that the Ahmed valve implant has a have been reported, as well as complications including built-in Venturi-based flow restrictor designed to prevent hypotony.4e6 postoperative hypotony and its complications. However, the
2016 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2016.06.035 1 Published by Elsevier Inc. ISSN 0161-6420/16 Ophthalmology Volume -, Number -, Month 2016
Ahmed implant has been associated with bleb encapsulation, Exclusion Criteria resulting in inadequate IOP reduction and the need for post- 1. Requires an additional procedure at the time of implanta- operative glaucoma medications or additional glaucoma tion (e.g., cataract surgery, corneal transplant). 8,9 fl surgery. The Baerveldt implant lacks built-in ow restric- 2. Unwilling or unable to provide informed consent or adhere tion and requires the surgeon to create a temporary tube to the study requirements, including implant randomization ligature to allow for healing to occur around the end plate to and follow-up visits. regulate flow. This limits postoperative flow until the ligature dissolves or is removed, at which point the Baerveldt implant Recruitment and Treatment achieves excellent IOP control because of its large end-plate 2 4,7 surface area (350 mm ). However, there is a risk of Patients were recruited from 6 international clinical centers by 9 hypotony should there be inadequate healing around the plate surgeons from 2005 to 2009 and randomized to an Ahmed-FP7 to regulate flow when the tube opens.10,11 valve implant or a Baerveldt-350 implant (Appendix, available A 2008 American Glaucoma Society survey showed a at: www.aaojournal.com). The surgical technique was significant change in practice patterns between 1996 and standardized, and Baerveldt implants were ligated 2008, with trabeculectomy use decreasing from 81% to 46% intraoperatively with a dissolvable or releasable suture. Tube and aqueous shunt use increasing from 18% to 51%.12 The fenestrations were placed anterior to the ligation at the discretion of the performing surgeon in cases deemed requiring immediate impetus for this change may be based on the results of the postoperative IOP reduction. Follow-up occurred at scheduled in- Tube Versus Trabeculectomy (TVT) study, a multicenter tervals, including 9 appointments in the first postoperative year, 2 randomized trial that showed that Baerveldt-350 implanta- appointments in the second year, and annually through 5 years. At tion had a higher success rate with fewer complications than each visit, IOP, glaucoma medication use, visual acuity, and any trabeculectomy with mitomycin C after 5 years.4,5 Further- complications or interventions related to the implant were more, a 2015 meta-analysis comparing Ahmed valve recorded. implantation with trabeculectomy showed similar success rates, IOP reduction, and medication use, with fewer adverse Outcome Measures effects seen in the Ahmed group.13 The primary outcome was failure, defined as any one of the Until recently, selecting which aqueous shunt to use was following: dependent on surgeon and site preference given the lack of prospective data comparing the devices. Retrospective 1. IOP out of target range (5e18 mmHg inclusive) or <20% studies have yielded inconclusive results and have had reduction from baseline for 2 consecutive visits after 3 modest sample sizes, and pooling them is difficult given months. their heterogeneous patient populations, use of different 2. De novo glaucoma surgery required (e.g., cyclodestructive 9,14e16 procedure, additional tube shunt). device models, and varying success criteria. The 3. Removal of the implant. Ahmed Versus Baerveldt (AVB) study is an international, 4. Severe vision loss related to the surgery (endophthalmitis, multicenter, randomized trial that has provided evidence to suprachoroidal hemorrhage with vision loss, enucleation, 17e19 support a surgeon’s choice. Three-year results evisceration, or phthisis bulbi) or progression to no light demonstrated that the Baerveldt implant achieves a lower perception for any reason. IOP on fewer medications, but may have more safety issues, fi 19 Success was the absence of failure and was further classi ed as including hypotony. This article will present the 5-year complete or qualified. Complete success required IOP to be within treatment results of the AVB study. target range (5e18 mmHg) at all visits after 3 months without the use of glaucoma medications, without any additional surgical interventions, and without significant vision loss (within 2 Snellen Methods lines). Qualified success allowed nonconsecutive visits to be outside of the target IOP range, allowed the use of glaucoma The AVB study methodology is described in detail in our baseline medications, and allowed surgical interventions (including article17 and will be summarized in the current article. Institutional revisions), provided they were not de novo glaucoma procedures. review board approval was obtained at each clinical center, and the Alternate IOP success criteria of 21 mmHg and 14 mmHg study protocol is registered on www.ClinicalTrials.gov also were analyzed as recommended by the World Glaucoma (NCT00940823). Association.20 Secondary analyses compared groups on the basis of IOP, medication use, visual acuity, postoperative Inclusion Criteria complications, and interventions required. 1. Age 18 years or older. Data Censoring 2. Inadequately controlled glaucoma defined as IOP greater than clinical target despite maximum tolerated medical and Patients meeting the criteria for failure were included in secondary laser therapy. analyses unless they underwent de novo glaucoma procedures or 3. Failed trabeculectomy with antimetabolite or disease at device explantation, or experienced severe vision loss affecting high risk of failing trabeculectomy (e.g., neovascular or treatment goals. In these cases, IOP and medication use were uveitic glaucoma) and scheduled for aqueous shunt censored to prevent confounding, but visual acuity, complications, implantation. and interventions related to the original surgery were included. 4. Eyes with prior surgeries or significant conjunctival scar- Patients who underwent evisceration or enucleation, or progressed ring were included. to no light perception vision had their visual outcome carried 5. One eye enrolled per patient. forward for analysis.
2 Christakis et al The AVB Study: 5-Year Results
Statistical Analysis group), including 1 suprachoroidal hemorrhage requiring drainage in the Ahmed group and 2 serous choroidal detachments in the Statistical analysis was performed using IBM SPSS (version 23.0, Baerveldt group that did not require drainage.18 IBM Corp, Armonk, NY) using intention-to-treat analysis. All tests Retention rates were high in both groups, with 72% of patients were 2-sided, and statistical significance was defined as P 0.05. in each group reaching 5 years of follow-up (Fig 1). There was no Continuous and quantitative variables were compared between difference in the rates of loss to follow-up between the 2 groups groups using the Student t test or ManneWhitney U test. Discrete (P ¼ 0.51, chi-square test excluding deaths). and qualitative variables were compared using Pearson’s chi- > square test, except in cases when 25% of contingency cells had Treatment Outcomes an expected value <5 and Fisher exact test was used. Snellen vi- sual acuity was converted to logarithm of the minimum angle of At 5 years, the cumulative probability of failure (standard error) resolution (logMAR) acuity for analysis, with 0.1 logMAR cor- was 53.2% (4.7%) in the Ahmed group and 40.0% (5.0%) in the responding to 1 Snellen line. For the purpose of statistical analysis, Baerveldt group (P ¼ 0.037, log-rank test) (Fig 2). The most count fingers was considered 1/100, hand motions was considered common reason for failure in both groups was high IOP, which 1/800, light perception was considered 1/1600, and no light resulted in 56 (45%) Ahmed failures and 26 (23%) Baerveldt perception was considered 1/3200.20 Repeated-measures, mixed failures (Table 2). De novo glaucoma surgery was required in 19 model analysis of variance was used to compare change in quan- patients (15%) in the Ahmed group who failed because of high titative variables from baseline over time. KaplaneMeier analysis IOP and 11 patients (10%) in the Baerveldt group. Hypotony was used to compare failure rates between groups using the resulted in 5 (4%) failures in the Baerveldt group and none in log-rank test (Mantel-Cox), as well as to assess risk factors for the Ahmed group. Failure due to complications (severe vision treatment failure. Multivariate analysis was performed using Cox loss related to surgery, explantation, evisceration, enucleation, or proportional hazard regression analysis with forward stepwise phthisis bulbi) constituted 7 (6%) Ahmed failures and 9 (8%) elimination. Baerveldt failures. The rates of complete success were low in both groups, with only 3 patients (2%) in the Ahmed group and 5 patients (4%) in the Results Baerveldt group meeting these stringent criteria (P ¼ 0.49). At 5 years, 15 patients (12%) in the Ahmed group and 22 patients (19%) Baseline Characteristics in the Baerveldt group were qualified successes on no glaucoma medications (P ¼ 0.12). A total of 238 patients were recruited and randomized: 124 (52%) Univariate analysis found neovascular glaucoma to be a risk to the Ahmed group and 114 (48%) to the Baerveldt group. The factor for failure (56% failure rate vs. 40% for non-neovascular baseline characteristics of the study group were similar and are cases, P ¼ 0.04), although multivariate analysis showed no dif- presented in Table 1. Mean patient age was 66 years old with ference in success rates between devices for neovascular cases uncontrolled disease as evidenced by a mean preoperative IOP of (P ¼ 0.20). Not having had a prior trabeculectomy also was a risk 31 mmHg on 3 classes of glaucoma medications. Many patients factor for failure (52% failure rate vs. 29% for patients with a prior had failed trabeculectomy with antimetabolite (37%) or had high- trabeculectomy, P ¼ 0.001). This remained significant even when risk disease, including neovascular (21%) or uveitic (10%) accounting for known risk factors for failure, including glaucoma glaucoma. subtype (e.g., neovascular, uveitic), young age, and black race.21 All patients received the implant to which they were random- However, there was no interaction between device and prior ized. There were few intraoperative complications (4% in each trabeculectomy status (P ¼ 0.54).
Table 1. Baseline Demographic and Ocular Characteristics
Overall (n [ 238) Ahmed (n [ 124) Baerveldt (n [ 114) P Value Age, mean SD 66 16 65 17 67 15 0.29* Sex: female 132 (55%) 59 (48%) 73 (64%) 0.011y Ethnicity: white 170 (71%) 91 (73%) 79 (69%) 0.90y Glaucoma diagnosis Open-angle 119 (50%) 64 (52%) 55 (48%) 0.82y Neovascular 50 (21%) 28 (23%) 22 (19%) Uveitic 23 (10%) 10 (8%) 13 (11%) IOP (mmHg), mean SD 31.4 10.8 31.1 10.5 31.7 11.1 0.71* Glaucoma medications, mean SD 3.1 1.0 3.1 1.0 3.1 1.1 0.60* Previous surgery, mean SD 1.7 1.2 1.8 1.3 1.6 1.1 0.35* Cataract surgery 172 (72%) 90 (73%) 82 (72%) 0.91y Trabeculectomy 89 (37%) 41 (33%) 48 (42%) 0.15y Previous lasers, mean SD 0.9 1.1 0.8 1.1 1.0 1.1 0.17* Trabeculoplasty 60 (25%) 27 (22%) 33 (29%) 0.20y Visual acuity, median Snellen 20/100 20/100 20/100 0.67z
IOP ¼ intraocular pressure; SD ¼ standard deviation. *Student t test. yPearson chi-square. zManneWhitney U test.
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Table 2. Primary Reasons for Failure*
Ahmed Baerveldt (n [ 124) (n [ 114) High IOP (>18 mmHg or <20% reduction) 56 26 De novo glaucoma surgery required 19 11 Hypotony 0 5 Device explantation 1 2 No light perception 2 3 Enucleation/evisceration 3 0 Suprachoroidal hemorrhage with vision loss 1 2 Phthisis bulbi 0 2 Total 63 40
Figure 1. Patient retention at 5 years. IOP ¼ intraocular pressure. *The first reason for failure is reported (e.g., if a patient fails because of high When using an alternate IOP criteria of 21 mmHg, the IOP and later progresses to no light perception, high IOP is considered the primary reason for failure). cumulative probability of failure (standard error) was 49.1% (4.7%) in the Ahmed group and 38.3% (5.1%) in the Baerveldt group (P ¼ 0.057) (Fig 3, available at: www.aaojournal.com). When using an IOP criteria of 14 mmHg, the cumulative early postoperative period (1 day, 1 week, 2 weeks) and the probability of failure was 83.5% (3.6%) in the Ahmed group and Baerveldt group had a lower mean IOP at all visits from 1 year 72.2% (4.5%) in the Baerveldt group (P ¼ 0.050) (Fig 4, onward (P < 0.05, Table 3). Repeated-measures, mixed-model available at: www.aaojournal.com). analysis of variance demonstrated that both groups had significant mean IOP reduction over time (both P < 0.001), but that the Baerveldt group had a greater IOP reduction than the Ahmed group Intraocular Pressure at all follow-up visits beginning at 1 year and continuing to 5 years P ¼ Both implants were effective in lowering IOP (Table 3, Fig 5). ( 0.02). Mean IOP in the Ahmed group decreased from 31.1 10.5 mmHg preoperatively to 16.6 5.9 mmHg at 5 years (47% Glaucoma Medication Use P < reduction, 0.001). Mean IOP in the Baerveldt group Both implants were effective in lowering mean glaucoma medi- decreased from 31.9 11.0 mmHg preoperatively to 13.6 5.0 P < cation use (Table 3, Fig 6). Mean glaucoma medication use in the mmHg at 5 years (57% reduction, 0.001). When comparing Ahmed group decreased from 3.1 1.0 mmHg preoperatively to the 2 implants, the Ahmed group had a lower mean IOP in the 1.8 1.5 mmHg at 5 years (44% reduction, P < 0.001). Mean glaucoma medication use in the Baerveldt group decreased from 3.1 1.0 mmHg preoperatively to 1.2 1.3 mmHg at 5 years (61% reduction, P < 0.001). When comparing the 2 implants,
Table 3. Mean Intraocular Pressure and Medication Use
Ahmed Baerveldt P Value* Baseline IOP (mmHg) 31.1 10.5 31.9 11.0 0.60 Glaucoma medications 3.1 1.0 3.1 1.0 0.75 1 year IOP (mmHg) 16.5 5.1 13.8 4.6 <0.001 Glaucoma medications 1.7 1.3 1.2 1.3 0.017 2 years IOP (mmHg) 16.5 5.1 13.8 4.6 0.026 Glaucoma medications 1.8 1.4 1.0 1.2 <0.001 3 years IOP (mmHg) 16.2 4.8 14.6þ5.0 0.047 Glaucoma medications 1.8 1.4 1.1 1.3 <0.001 4 years IOP (mmHg) 16.0 4.5 14.4 4.8 0.049 Glaucoma medications 1.9 1.5 1.2 1.3 0.004 5 years IOP (mmHg) 16.6 5.9 13.6 5.0 0.001 Glaucoma medications 1.8 1.5 1.2 1.3 0.033
Figure 2. Cumulative failure rate (5 mmHg intraocular pressure [IOP] ¼ e IOP intraocular pressure. criteria 18 mmHg). Kaplan Meier analysis using the log-rank test. Data presented as mean standard deviation. Censored patients are denoted by vertical tick marks. Errors bars showing *Student t test. the standard error of the mean are included at 1 year, 3 years, and 5 years.
4 Christakis et al The AVB Study: 5-Year Results
Figure 5. Mean intraocular pressure (IOP) over 5 years of follow-up. Error bars represent standard deviation. the Ahmed group required fewer glaucoma medications in the early De Novo Glaucoma Procedures postoperative period (1 day, 1 week, 2 weeks) and the Baerveldt group required fewer medications at all visits after 1 month The cumulative proportion of patients requiring de novo glaucoma (P < 0.05). At 5 years, the Baerveldt group required a median of surgery (standard error) was 17.7% (3.7%) in the Ahmed group 1 glaucoma medication (confidence interval, 0e2) compared and 11.0% (3.2%) in the Baerveldt group (P ¼ 0.22) (Fig 8). To with 2 glaucoma medications (confidence interval, 0e2) in the evaluate for a potential bias in the decision to reoperate, the Ahmed group (P ¼ 0.038, ManneWhitney U test). mean IOP and medication use at the time de novo glaucoma surgery was scheduled were compared between devices. At this time, the 2 groups had similar mean IOPs (Ahmed 30.0 10.8 Visual Acuity mmHg, Baerveldt 28.9 10.9 mmHg, P ¼ 0.79) and were taking a similar mean number of glaucoma medications (Ahmed Both groups had a moderate but similar reduction in visual acuity 2.8 1.2, Baerveldt 1.8 1.5, P ¼ 0.06). The most common over 5 years of follow-up (P ¼ 0.88). Mean logMAR visual acuity procedure was cyclodestruction, which was required in 10 in the Ahmed group decreased from 1.3 1.0 at baseline to 1.6 1.0 patients (8%) in the Ahmed group and 3 patients (3%) in the at 5 years (P < 0.001). Mean logMAR visual acuity in the Baer- Baerveldt group (P ¼ 0.09). Transscleral cyclophotocoagulation veldt group decreased from 1.2 1.0 at baseline to 1.6 1.2 at 5 was used in all cases except for 2 cases of malignant glaucoma years (P < 0.001). The distribution of change in Snellen visual in which endocyclophotocoagulation was used. Placement of an acuity from baseline to 5 years is shown in Figure 7. additional aqueous shunt (all Baerveldt implants) was required in
Figure 6. Mean glaucoma medication use over 5 years of follow-up. Error bars represent standard deviation.
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Figure 7. Distribution of change in visual acuity from baseline to 5 years.
7 patients (6%) in the Ahmed group and 4 patients (4%) in the (Ahmed 15%, Baerveldt 10%), device explantation (Ahmed 2%, Baerveldt group. A gold shunt was required in 1 patient (1%) in Baerveldt 3%), enucleation or evisceration (Ahmed 2%, Baerveldt the Ahmed group and 3 patients (3%) in the Baerveldt group. 0%), and vision loss altering treatment goals (Ahmed 0%, Baer- Selective laser trabeculoplasty was performed in 1 patient (1%) veldt 4%). Censoring due to vision loss occurred in 4 patients in in each group with an IOP modestly higher than target. the Baerveldt group; 2 patients developed phthisis bulbi, 1 patient had a large suprachoroidal hemorrhage, and 1 patient progressed to Censoring no light perception and glaucoma medications were withdrawn. A total of 43 patients were censored from analysis: 25 (20%) in the Ahmed group and 18 (16%) in the Baerveldt group (P ¼ 0.25). The Complications reasons for censoring included additional glaucoma surgery After 5 years of follow-up, 78 patients (63%) in the Ahmed group and 79 patients (69%) in the Baerveldt group experienced a complication (P ¼ 0.30) (Table 4). The most common complications were shallow anterior chamber (15% Ahmed, 17% Baerveldt), choroidal effusions (13% Ahmed, 16% Baerveldt), tube complications (13% Ahmed, 16% Baerveldt), persistent corneal edema (11% Ahmed, 12% Baerveldt), and persistent iritis (7% Ahmed, 12% Baerveldt). Clinical bleb encapsulation was defined as visible fibrosis of the endplate in the setting of an elevated IOP and was more common in the Ahmed group (11% Ahmed, 4% Baerveldt, P ¼ 0.023). Refractory hypotony needing surgery was required in 1 patient (1%) in the Ahmed group and 6 patients (5%) in the Baerveldt group (P ¼ 0.057). Of these patients, 1 in each group had early postoperative overfiltration requiring temporary tube ligation with an absorbable suture; in both cases, hypotony resolved and patients were qualified successes at last follow-up. Persistent diplopia or a motility disorder occurred in 6 patients (5%) in the Ahmed group and 2 patients (2%) in the Baerveldt group (P ¼ 0.28).
Interventions After 5 years of follow-up, 64 patients (51%) in the Ahmed group and 58 patients (51%) in the Baerveldt group required an inter- vention (P ¼ 0.99) (Table 5). The most common interventions were anterior chamber reformation (Ahmed 11%, Baerveldt 13%), paracentesis (4% Ahmed, 14% Baerveldt, P ¼ 0.007), Figure 8. Cumulative de novo glaucoma reoperation rates. KaplaneMeier tube-related interventions (10% Ahmed, 17% Baerveldt), cataract analysis using the log-rank test. Censored patients are denoted by vertical surgery (26% Ahmed, 38% Baerveldt), vitrectomy (7% Ahmed, tick marks. Errors bars showing the standard error of the mean are included 7% Baerveldt), and corneal transplantation (7% Ahmed, 4% at 1 year, 3 years, and 5 years. Baerveldt).
6 Christakis et al The AVB Study: 5-Year Results
Table 4. Complications in 5 Years of Follow-up Device explantation was required in 3 patients (3%) in each group. In the Ahmed group, explantation occurred for malposition Ahmed Baerveldt P and corneal decompensation (1 patient) and to allow for subsequent Complication (n [ 124) (n [ 114) Value replacement with a Baerveldt implant (2 patients). In the Baerveldt y group, explantation occurred for refractory hypotony (1 patient), Shallow anterior chamber 18 (15%) 19 (17%) 0.65 Choroidal effusions 16 (13%) 18 (16%) 0.53y persistent motility disorder (1 patient), and corneal decompensation Tube complications 17 (14%) 19 (17%) 0.41y (1 patient). Enucleation was required in 1 patient in the Ahmed Tube obstruction 7 (6%) 10 (9%) 0.35y group for endophthalmitis, and evisceration for a blind painful eye Tube malposition 8 (6%) 7 (6%) 0.92y was required in 2 patients in the Ahmed group. Tube erosion 5 (4%) 2 (2%) 0.45z Corneal edema 14 (11%) 14 (12%) 0.81y Iritis 9 (7%) 14 (12%) 0.19y Discussion Cataract progression 11 (32%)* 13 (41%)* 0.49y y Encapsulated bleb 14 (11%) 4 (4%) 0.023 The AVB study is an international, multicenter, randomized Hyphema 4 (3%) 6 (5%) 0.43y z trial comparing the 2 most frequently used aqueous shunts. Motility disorder 6 (5%) 2 (2%) 0.28 Aqueous misdirection 2 (2%) 4 (4%) 0.43z Enrolled patients had uncontrolled glaucoma despite Suprachoroidal hemorrhage 2 (2%) 3 (3%) 0.67z maximum tolerated medical therapy, with 37% of patients Phthisis bulbi 1 (1%) 2 (2%) 0.61z having failed trabeculectomy with mitomycin C and 31% of Retinal detachment 1 (1%) 0 1.0z patients having neovascular or uveitic glaucoma. Aqueous Endophthalmitis 1 (1%) 0 1.0z y shunts are being increasingly used in this patient popula- Progression to no light perception 7 (6%) 7 (6%) 1.0 12 z tion. An IOP target of 18 mmHg was selected on the Hypotony requiring surgery 1 (1%) 6 (5%) 0.057 High IOP requiring de novo surgery 19 (15%) 11 (10%) 0.19y basis of Advanced Glaucoma Intervention Study data y fi Other 6 (5%) 7 (6%) 0.66 suggesting that higher pressures may be insuf cient to Total 78 (63%) 79 (69%) 0.30y prevent disease progression, and our patient population required on average a 40% reduction in IOP to meet this 2 IOP ¼ intraocular pressure. target. De novo glaucoma surgery, severe vision loss *Corrected for number of phakic patients. secondary to a complication of surgery, and progression to yPearson chi-square test. no light perception were considered failures. z Fisher exact test. After 5 years of follow-up, the Ahmed group had a higher failure rate of 53% compared with 40% in the Baerveldt group (P ¼ 0.04). This failure rate is similar to the Table 5. Interventions in 5 Years of Follow-up 10% failure rate per year quoted by the American Academy of Ophthalmology report on aqueous shunts.7 The main Ahmed Baerveldt P reason for failure in both groups was high IOP, and the Interventions (n [ 124) (n [ 114) Value cumulative glaucoma reoperation rate was 18% in the Anterior chamber reformation 13 (11%) 15 (13%) 0.52y P ¼ y Ahmed group and 11% in the Baerveldt group ( Paracentesis 5 (4%) 16 (14%) 0.007 0.22). The most common de novo glaucoma surgery was Tube interventions 12 (10%) 19 (17%) 0.11y z cyclodestruction (8% Ahmed, 3% Baerveldt) and Laser for obstruction 0 3 (3%) 0.11 Iris sweep 1 (1%) 4 (4%) 0.20z Baerveldt implantation (6% Ahmed, 4% Baerveldt). Tube irrigation 1 (1%) 2 (2%) 0.61z Visual potential guided de novo glaucoma procedure Tube ligation 2 (2%) 4 (4%) 0.43z selection; the majority of patients who underwent Tube reposition 6 (5%) 7 (6%) 0.66y cyclodestruction had count fingers or worse vision z Tube patch graft 2 (2%) 0 0.50 compared with 20/60 or better vision in patients who Tube explanted 1 (1%) 1 (1%) 1.0z y underwent additional Baerveldt implantation. Failure due Phacoemulsification 9 (26%)* 12 (38%)* 0.92 Vitrectomyx 8 (7%) 8 (7%) 0.86y to hypotony was rare, occurring in 5 patients (4%) in the Corneal transplant 8 (7%) 5 (4%) 0.48y Baerveldt group and zero patients in the Ahmed group Bleb needling 4 (3%) 3 (3%) 1.0z (P ¼ 0.02). Hypotony is a known complication of Laser iridotomy 2 (2%) 2 (2%) 1.0z Baerveldt implantation given the lack of built-in flow re- z Nd:YAG capsulotomy 5 (4%) 4 (4%) 1.0 striction and may occur if there is a ligature malfunction or Nd:YAG hyaloidotomy 0 1 (1%) 0.48z z insufficient healing around the plate to regulate flow once Drainage suprachoroidal hemorrhage 1 (1%) 2 (2%) 0.61 10 Device explanted 3 (3%) 3 (3%) 0.92z the tube is patent. Enucleation/evisceration 3 (3%) 0 0.25z Neovascular glaucoma was a risk factor for failure, as has 22 De novo glaucoma surgery 19 (15%) 11 (10%) 0.19y been reported in the literature, although no device Other 4 (4%) 4 (4%) 1.0z conferred an advantage in these patients. Not having had a Total 63 (51%) 58 (51%) 0.99y prior trabeculectomy also was a risk factor for failure, which we attribute to a selection bias in that patients Nd:YAG ¼ neodymium doped yttrium aluminum garnet. scheduled for a primary tube likely have disease at higher *corrected for phakic patients. y risk for failure. Although our multivariate model Pearson chi-square test. attempted to correct for the presence of known risk factors zFisher exact test. xincludes unplanned vitrectomies during initial surgery. for failure, including neovascular glaucoma, younger age, and black race, factors such as poor conjunctival health
7 Ophthalmology Volume -, Number -, Month 2016 and long-standing antiglaucoma medication use are difficult drainage. One patient in the Ahmed group had an intra- to account for.21 However, an important finding is that operative suprachoroidal hemorrhage that required drainage, patients in our study cohort who had previously failed and 1 patient had a suprachoroidal hemorrhage after a tube trabeculectomy had a 71% success rate at 5 years, reposition at 18 months. suggesting that tube surgery may be an effective treatment The most common long-term complication was corneal option in these patients. edema, which affected 11% of the Ahmed group and 12% of Both implants were effective in lowering IOP, but the the Baerveldt group, of whom 7% of the Ahmed group and Baerveldt provided a 3 mmHg lower IOP at 5 years (Ahmed 4% of the Baerveldt group required a corneal transplant. 16.6 mmHg, Baerveldt 13.6 mmHg, P ¼ 0.001). Both im- This is similar to the TVT study, which reported a 16% plants also reduced the need for glaucoma medications, and persistent corneal edema rate at 5 years, with a 9% corneal the Baerveldt group required a median of 1 glaucoma graft rate.5 The high rates of corneal decompensation are medication at 5 years compared with 2 glaucoma medica- likely a result of endothelial cell failure from multiple tions in the Ahmed group (P ¼ 0.04). The lower IOP and prior surgeries, postoperative IOP fluctuations (especially need for medications may be attributed to the Baerveldt hypotony and flat anterior chamber, tube-cornea touch) implant having a larger end-plate size (184 mm2 Ahmed, and chronic inflammation, which can accelerate endothelial 350 mm2 Baerveldt), and clinical studies have shown a cell loss.29,31 Persistent iritis occurred in 7% of patients in relationship between end-plate size and filtration.23,24 The the Ahmed group and 12% of patients in the Baerveldt Ahmed group also had a higher rate of clinical bleb group (P ¼ 0.19). The rate of motility disorder or persistent encapsulation than the Baerveldt group (11% Ahmed, 4% diplopia was 5% in the Ahmed group and 2% in the Baer- Baerveldt, P ¼ 0.02), as has been shown in previous veldt group (P ¼ 0.28), which is lower than the 6% reported retrospective comparisons.9 The early exposure of the in the TVT study and may reflect the worse vision of our Ahmed bleb to mechanical compression from aqueous patient population, revealing less symptomatic diplopia.5 flow, as well as exposure to proinflammatory cytokines Cataract progression occurred frequently in both groups, incited by surgery, has been postulated to stimulate bleb with 26% of phakic Ahmed cases and 38% of phakic encapsulation and influence the fibrosis pathway.25e29 In Baerveldt cases requiring cataract surgery within 5 years addition, although both implants are made of silicone, of device implantation. electron microscopy has shown that the Ahmed implant Our results are comparable to the Ahmed Baerveldt topography has more a 10-fold greater roughness than the Comparison (ABC) study, a concurrent independent ran- Baerveldt implant, which in vitro was associated with domized trial comparing the Ahmed implant with the increased tenon fibroblast adhesion that may predispose to Baerveldt implant.32,33 Baseline patient characteristics in the fibrous encapsulation.30 ABC study were similar to our study (AVB), with the study Both groups experienced a moderate but similar reduc- group having a mean preoperative IOP of 31.5 mmHg tion in visual acuity over the duration of the study, with 43% (AVB: 31.4 mmHg) on an average of 3.4 glaucoma medi- of the Ahmed group and 46% of the Baerveldt group losing cations (AVB: 3.1). Many patients had secondary glaucoma, 2 or more lines of vision. Visual outcomes were modestly including 29% with neovascular glaucoma (AVB: 21%) and better in patients with 20/50 or better vision at baseline 7% with uveitic glaucoma (AVB: 10%). Eighty percent of (n ¼ 80), with 36% of patients losing 2 or more lines of patients had previously undergone ocular surgery (AVB: vision after 5 years of follow-up. Ascertaining the cause 89%), including 42% who had failed prior trabeculectomy of vision loss was difficult because of the high rates of (AVB: 37%). Study design and outcome measures were concomitant eye disease (e.g., diabetic retinopathy, corneal similar between studies, although the primary IOP criterion pathology). Progression to no light perception occurred in for the ABC study was 6 to 21 mmHg inclusive compared 6% of both groups; half (7/14) of these patients had neo- with 5 to 18 mmHg inclusive for the AVB study. However, vascular glaucoma. both study groups followed the World Glaucoma Associa- Both implants had high rates of postoperative compli- tion consensus guidelines and analyzed alternate IOP cations, although most were transient or required minimal criteria to allow for valid comparison with one another. At 5 intervention. The most common early postoperative years, the ABC study reported failure rates of 60% in the complication was hypotony, resulting in shallow anterior Ahmed group and 46% in the Baerveldt group (using an chambers (Ahmed 15%, Baerveldt 17%) and choroidal ef- IOP criterion of <18 mmHg), with the majority of failures fusions (Ahmed 13%, Baerveldt 16%), which resolved over in both groups secondary to inadequate IOP reduction.33 time. Early postoperative IOP spikes requiring paracentesis The Baerveldt achieved a 2 mmHg lower IOP, and a were more common in the Baerveldt group while the tubes greater proportion of patients in the Ahmed group were ligated (Ahmed 4%, Baerveldt 14%, P ¼ 0.007). Tube required de novo glaucoma surgery.33 However, more complications occurred in 14% of the Ahmed group and patients in the Baerveldt group failed because of persistent 17% of the Baerveldt group, with tube obstruction and tube hypotony, device explantation, and loss of light malposition being the most common. Tube interventions perception.33 were required in 10% of the Ahmed group and 17% of the P ¼ Baerveldt group ( 0.11), with tube reposition being the Study Limitations most common. Serious early postoperative complications included suprachoroidal hemorrhage, which occurred in 3 There are several limitations that should be considered when patients (3%) in the Baerveldt group, in whom 2 required interpreting the results of the AVB study. Although IOP
8 Christakis et al The AVB Study: 5-Year Results criteria are used in glaucoma surgical trials because they are selecting a device should balance patient factors, such as the only known modifiable risk factor for disease progres- goals of therapy, target IOP, and medication compliance, with sion, they remain a surrogate marker of success.1,2 An IOP surgeon factors, including familiarity with each device and target of 18 mmHg was selected on the basis of Advanced personal outcomes. Glaucoma Intervention Study data2; however, each patient had his/her own individual target IOP that may have been References higher or lower than this and guided treatment decisions. A stable patient with an IOP of 19 mmHg on no medications would be considered a failure, whereas a 1. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intra- progressing patient with an IOP of 15 mmHg receiving ocular pressure and glaucoma progression: results from the maximum tolerated medical therapy would be considered Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120: a success. Likewise, hypotony was defined as <5 mmHg 1268–79. as per the World Glaucoma Association guidelines,20 2. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual although it should be a clinical diagnosis that incorporates fi visual function and whether there are any hypotony- eld deterioration. The AGIS Investigators. Am J Ophthalmol 2000;130:429–40. related complications, including shallow anterior chamber, 3. Prum BE Jr, Rosenberg LF, Gedde SJ, et al. Primary Open- corneal edema, or kissing choroidal effusions. Simply using Angle Glaucoma Preferred Practice Pattern((R)) Guidelines. an IOP cutoff would classify a patient with an IOP of 4 Ophthalmology 2016;123:P41–111. mmHg and excellent vision as a failure, whereas a patient 4. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes with an IOP of 6 mmHg and poor vision secondary to in the Tube Versus Trabeculectomy (TVT) study after five hypotony maculopathy would be classified as a success. In years of follow-up. Am J Ophthalmol 2012;153:789–803.e2. addition, averaging IOP over a population may not appro- 5. Gedde SJ, Herndon LW, Brandt JD, et al. Postoperative priately reflect clinical outcomes and is susceptible to skew complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol from outliers or bias introduced from censoring patients who – underwent de novo glaucoma surgery or experienced vision- 2012;153:804 814.e1. 6. Five-year follow-up of the Fluorouracil Filtering Surgery threatening complications. Thus, applying our results to Study. The Fluorouracil Filtering Surgery Study Group. Am J clinical decision making requires careful balancing of suc- Ophthalmol 1996;121:349–66. cess criteria, IOP, medication use, de novo glaucoma sur- 7. Minckler DS, Francis BA, Hodapp EA, et al. Aqueous shunts gery and device-related complications, and interventions in glaucoma: a report by the American Academy of Ophthal- required. mology. Ophthalmology 2008;115:1089–98. Furthermore, although IOP is useful clinically to monitor 8. Ayyala RS, Zurakowski D, Smith JA, et al. A clinical study of glaucoma given that it is quantifiable and reproducible, the the Ahmed glaucoma valve implant in advanced glaucoma. main goal of glaucoma therapy is preserving visual function. Ophthalmology 1998;105:1968–76. Unfortunately, the poor baseline visual acuity of our patient 9. Tsai JC, Johnson CC, Kammer JA, Dietrich MS. The Ahmed population made analyzing visual fields difficult, although shunt versus the Baerveldt shunt for refractory glaucoma II: longer-term outcomes from a single surgeon. Ophthalmology they were used to guide clinical management. Assessing 2006;113:913–7. structural outcomes such as glaucomatous cupping also 10. Stein JD, McCoy AN, Asrani S, et al. Surgical management of would provide useful data if there was a standardized means hypotony owing to overfiltration in eyes receiving glaucoma of comparison; however, the study commenced before the drainage devices. J Glaucoma 2009;18:638–41. routine use of ocular tomography. Our results also may have 11. Nguyen QH, Budenz DL, Parrish RK 2nd. Complications of been influenced by our surgeon’s relative experience and skill Baerveldt glaucoma drainage implants. Arch Ophthalmol with each device. To minimize this bias, only surgeons with 1998;116:571–5. extensive experience in implanting both shunts participated 12. Desai MA, Gedde SJ, Feuer WJ, et al. Practice preferences for glaucoma surgery: a survey of the American Glaucoma Soci- in the study as determined by the study chair (IIKA). – In conclusion, both the Ahmed FP7-valve implant and the ety in 2008. Ophthalmic Surg Lasers Imaging 2011;42:202 8. 13. HaiBo T, Xin K, ShiHeng L, Lin L. Comparison of Ahmed Baerveldt-350 implant were effective in lowering IOP and the glaucoma valve implantation and trabeculectomy for glau- need for glaucoma medications in patients with refractory or coma: a systematic review and meta-analysis. PLoS One high-risk glaucoma. When comparing the implants, the 2015;10:e0118142. Baerveldt implant had a lower failure rate and yielded a 14. Goulet RJ 3rd, Phan AD, Cantor LB, WuDunn D. Efficacy of moderately lower IOP on fewer medications than the Ahmed the Ahmed S2 glaucoma valve compared with the Baerveldt implant. Thus, the Baerveldt implant may be a good choice in 250-mm2 glaucoma implant. Ophthalmology 2008;115: patients with a low long-term IOP target or in patients intol- 1141–7. erant to topical medications. However, patients need to be 15. Syed HM, Law SK, Nam SH, et al. Baerveldt-350 implant versus Ahmed valve for refractory glaucoma: a case-controlled followed closely in the early postoperative period while the – tube is ligated because IOP volatility is common, and there is comparison. J Glaucoma 2004;13:38 45. 16. Wang JC, See JL, Chew PT. Experience with the use of a risk of hypotony. The Ahmed valve implant may be a good Baerveldt and Ahmed glaucoma drainage implants in an Asian choice in patients who need an immediate postoperative population. Ophthalmology 2004;111:1383–8. reduction in IOP and have moderate long-term IOP targets. 17. Christakis PG, Tsai JC, Zurakowski D, et al. The Ahmed Versus However, glaucoma medications and additional glaucoma Baerveldt study: design, baseline patient characteristics, and surgery may be necessary to achieve this goal. Ultimately, intraoperative complications. Ophthalmology 2011;118:2172–9.
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Footnotes and Financial Disclosures
Originally received: January 18, 2016. Financial Disclosure(s): Final revision: June 8, 2016. The author(s) have made the following disclosure(s): P.J.H.: Personal fees e Accepted: June 9, 2016. Abbott Medical Optics. Available online: ---. Manuscript no. 2016-114. I.I.K.A.: Personal fees e Abbott Medical Optics and New World Medical. 1 Department of Ophthalmology and Vision Sciences, University of Tor- The AVB study is supported by a research grant from the Glaucoma onto Faculty of Medicine, Toronto, Canada. Research Society of Canada, Toronto, Canada (I.I.K.A., P.G.C.) and a 2 Drs. Massaro & Kalenak SC, Milwaukee, Wisconsin. departmental challenge grant from the Research to Prevent Blindness, Inc, New York, New York (J.C.T.). Our research funding sponsors had no role 3 Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, in the design or conduct of the study. New York, New York. Author Contributions: 4 Department of Anesthesiology, Children’s Hospital Boston, Harvard Conception and design: Christakis, Kalenak, Tsai, Zurakowski, Kammer, Medical School, Boston, Massachusetts. Harasymowycz, Mura, Cantor, Ahmed 5 Department of Ophthalmology and Visual Sciences, Vanderbilt Univer- Data collection: Christakis, Kalenak, Tsai, Zurakowski, Kammer, Har- sity School of Medicine, Nashville, Tennessee. asymowycz, Mura, Cantor, Ahmed 6 Department of Ophthalmology, University of Montreal, Montreal, Analysis and interpretation: Christakis, Kalenak, Tsai, Zurakowski, Kam- Canada. mer, Harasymowycz, Mura, Cantor, Ahmed 7 Obtained funding: Not applicable Clinic of Las Condes, Santiago, Chile. 8 Overall responsibility: Christakis, Kalenak, Tsai, Zurakowski, Kammer, Eugene and Marilyn Glick Eye Institute, Indiana University School of Harasymowycz, Mura, Cantor, Ahmed Medicine, Indianapolis, Indiana. Abbreviations and Acronyms: Presented at: American Academy of Ophthalmology, October 22e25, ABC ¼ Ahmed Baerveldt Comparison; AVB ¼ Ahmed Versus Baerveldt; 2011, Orlando, Florida; November 10e13, 2012, Chicago, Illinois; IOP ¼ intraocular pressure; logMAR ¼ logarithm of the minimum angle of November 13e17, 2015, Las Vegas, Nevada; American Glaucoma Society, resolution; TVT ¼ Tube Versus Trabeculectomy. March 1e4, 2012, New York, New York; Canadian Ophthalmological Correspondence: Society, June 26e29, 2010, Quebec City, Canada; June 9e12, 2011, Iqbal I.K. Ahmed, MD, 3200 Erin Mills Parkway, Mississauga, Ontario e Vancouver, Canada; June 26 30, 2012, Toronto, Canada. L5L 1W8. E-mail: [email protected].
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