ORIGINAL STUDY
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve: Long-term Outcomes of a Prospective Randomized Clinical Trial Alon Skaat, MD,*w Oded Sagiv, MD,*w Michael Kinori, MD,*w Guy J. Ben Simon, MD,*w Modi Goldenfeld, MD,*w and Shlomo Melamed, MD*w
Purpose: To compare long-term outcomes of Ahmed glaucoma valve (AGV), 24 mm Gold Micro-Shunt (GMS), and 48 mm GMS implantation for treatment of refractory glaucoma. Patients and Methods: This was a 3-armed randomized interventional prospective clinical trial. Within an institutional setting, 29 adults (29 eyes) with refractory glaucoma [mean baseline intraocular pressure (IOP) Z22 mm Hg on maximal medication, status post at least 1 failed trabeculectomy, defined visual field defect, and without recent glaucoma-related surgery] were randomly assigned to AGV, 24 mm GMS, or 48 mm GMS implantation. Exclusion criteria included uveitic, traumatic, or neovascular glaucoma. The 3 groups were comparatively evaluated preoperatively and 1, 2, 3, and 5 years postoperatively for IOP and numbers of glaucoma medications needed. Main outcome measures were implant survival rates. Results of the 24 and 48 mm GMS groups were also compared separately. Results: In all groups the final IOP (in mm Hg) was significantly lower than the preoperative IOP (17.3 ± 2.6 vs. 33.5 ± 6.7, P = 0.004; 17.8 ± 2.4 vs. 25.7 ± 0.7, P = 0.0001; and 19.6 ± 5.2 vs. 35.6 ± 2.2, P = 0.0001 in the AGV, 24 mm GMS, and 48 mm GMS groups, respectively). Differences between initial and final mean numbers of medications were not significant. Cumulative probabilities of success at 5 years were 77.8%, 77.8%, and 72.7%, respectively. Conclusions: During long-term follow-up, success rates in the 2 GMS groups and the AGV group were similar. Likewise, IOP reduction and the need for continued glaucoma medical therapy remained high and were similar for all devices. Key Words: open-angle glaucoma, Ahmed glaucoma valve, Gold Micro-Shunt
(J Glaucoma 2016;25:155–161)
S
urgical treatment is usually indicated when glaucomatous optic neuropathy worsens or visual field damage progresses despite laser trabeculoplasty or maximally tolerated medical therapy.1 Some of the accepted surgical approaches include filtration procedures such as trabeculectomy and the insertion of implants to connect the
Received for publication August 28, 2013; accepted September 3, 2014. From the *Department of Ophthalmology, The Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer; and wSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Disclosure: The authors declare no conflict of interest. Reprints: Alon Skaat, MD, Department of Ophthalmology, The Goldshleger Eye Institute, Sheba Medical Center, Tel Hashomer 52621, Israel (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000175
J Glaucoma
Volume 25, Number 2, February 2016
anterior chamber (AC) to the subconjunctival space. These procedures are reportedly effective in many cases,2 but they require the formation of a filtering bleb, and have long-term potential failure due to fibrosis and scarring.3 Filtering bleb can potentially be the source of a variety of complications,3,4 such as shallow AC owing to overfiltration, hypotony as a result of bleb leakage, choroidal detachment or hemorrhage, hyphema, blebitis, or endophthalmitis. The above surgical approaches are aimed mainly at circumventing the conventional aqueous outflow route (traditionally considered to be the major outflow pathway), comprising the trabecular meshwork, Schlemm canal, collector channels, and the episcleral venous plexus. Only a few approaches have been designed to increase the uveoscleral outflow pathway, which consists of the interstitium of the ciliary body, the suprachoroidal space, and the scleral vasculature. This pathway was reported to contribute up to 54% of the total egress of aqueous humor in young healthy subjects,5 and is apparently much lower with aging—about 10% to 15% of total outflow. In the nonglaucomatous cynomolgus monkey model, in which the natural pressure differential between the AC and the suprachoroidal space is 1 to 5 mm Hg, a change in intraocular pressure (IOP) was found to produce a corresponding change in the suprachoroidal space pressure when the AC and the suprachoroidal space were connected by cannulation.6 It was therefore assumed that physical communication between the AC and the suprachoroidal space will reduce the IOP. We previously described the short-term results of a novel approach that enhances uveoscleral outflow and reduces IOP in patients with glaucoma.7 This was done by implanting an ultrathin 24-karat Gold Micro-Shunt (GMS) that contains tubules to facilitate aqueous flow between the AC and the supraciliary/suprachoroidal space without the creation of a bleb. The procedure proved to be safe and effective, and resulted in a significant decrease in IOP at the follow-up examination 1 year after surgery. The purpose of this prospective study was to compare the long-term outcomes of implantation of the Ahmed glaucoma valve (AGV) (Ahmed FP7 Glaucoma Valve) with that of the 24 and 48 mm GMS in patients with refractory glaucoma.
PATIENTS AND METHODS The study was approved by the Sheba Medical Center Institutional Review Board committee and the Israeli Ministry of Health and was registered in the US National Institutes of Health (NIH) registry (NCT00382395). Patients gave informed consent to participate in the study. www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
155
Skaat et al
J Glaucoma
Volume 25, Number 2, February 2016
Setting The surgical procedures were conducted between January 2006 and July 2007 at the Sam Rothberg Glaucoma Center in the Goldschleger Eye Institute at Sheba Medical Center. The operations in all patients were performed by the same surgeon (S.M.)
Patient Population The study participants were 29 patients (29 eyes) with refractory glaucoma. Criteria for inclusion in the study were: (1) age 21 years or older; (2) a diagnosis of primary open-angle glaucoma, pseudoexfoliation glaucoma, or pigmentary dispersion glaucoma in 1 or both eyes; (3) average baseline IOP of Z22 mm Hg while on maximally tolerated medical treatment; (4) at least 1 failed trabeculectomy with at least 60 days since prior incisional glaucoma surgery; and (5) a visual field defect (MD score of 5 mg/ d; (4) intolerance to gonioscopy, slit-lamp examination, tonometry, or other study procedures; (5) mental impairment invalidating informed consent or disrupting followup; (6) pregnancy; (7) known sensitivity to medication needed during and after surgery; (8) significant comorbid disease that might interfere with follow-up; (9) current use of any other investigational drug or device; (10) a history of acute angle-closure glaucoma in the study eye within the past 12 months; (11) evidence of significant ocular disease other than glaucoma or cataract, or a history of previous ocular surgery (other than glaucoma, cataract, or cosmetic); or (12) active clinical ocular infection requiring treatment. Patients were evaluated preoperatively and 1, 2, 3, and 5 years postoperatively for IOP and numbers of glaucoma medications needed. The preoperative evaluation also included visual acuity assessment, slit-lamp biomicroscopy, IOP measurement with a Goldman applanation tonometer, ophthalmoscopy after pupil dilation, gonioscopy, and visual field analysis when applicable (24-2 program, Humphrey Field Analyzer HFA II-I; Carl Zeiss, Jena, Germany).
Randomization Technique After informed consent was given and confirmation of eligibility by the investigator, each enrolled patient was randomized to 1 of 3 treatment arms. The randomization was done using sealed envelopes that contained the randomly generated treatment allocation. Inside each envelope was a randomization assignment form with a sequence number matching the one on the outside of its envelope. The envelope was opened on the day of surgery or as close to the actual treatment as possible. Enrolled patients were allocated to one of the following strata: an AGV, a 24 mm GMS, or a 48 mm GMS.
Intervention Procedures AGV model FP7 was used for all patients. The surgical technique for its implantation has been described previously.7 The GMS (SOLX Inc., Boston, MA) is a nonvalved, flat-plate drainage device made from 24-karat medical-
FIGURE 1. Drawing of the Gold Micro-Shunt with the shunt dimensions.
grade (99.95%) gold, previously shown to have good biocompatibility and to be inert as an intraocular foreign body.8 The shunt is shaped as a long rectangle with rounded edges and fin-like tabs at the distal end to allow anchoring of the device in the suprachoroidal space. The proximal end provides the ingress for aqueous humor. The distal end provides drainage of the fluid through microchannels from the AC into the suprachoroidal space. Two models, a 24 and a 48 mm GMS, were tested. The 24 mm GMS model is 5.2 mm long and 3.2 mm wide and weighs 6.2 mg. The 48 mm GMS model is as long and as wide as the 24 mm GMS but weighs 9.2 mg. The diameter of the microchannels is 24 mm in the lighter model and 48 mm in the heavier model. A detailed schematic drawing of the GMS implant is shown in Figure 1.
Surgical Technique With the GMS
As described previously,7 patients were operated on under local anesthesia using either a sub-Tenon or a peribulbar injection. A bridle suture was placed around the superior rectus muscle, or alternatively, a corneal traction suture was placed at 12 o’clock. A fornix-based conjunctival flap was fashioned, and this was followed by meticulous cautery of episcleral vessels. A 4 mm long, fullthickness scleral incision was made 2 mm posterior to the limbus to expose the supraciliary space. An AC maintainer was inserted through a peripheral paracentesis and a crescent knife was used to enter the AC at a plane of 90% scleral thickness, with careful dissection to avoid cyclodialysis. Dissection was then continued posteriorly into the suprachoroidal space for 2 to 3 mm using the same
156 | www.glaucomajournal.com Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 25, Number 2, February 2016
crescent blade or blunt spatula. The anterior segment of the GMS was then introduced into the AC and its posterior segment into the suprachoroidal space, making sure that the implant was placed posteriorly so that 1 to 1.5 mm of the GMS was visible in the AC. The scleral wound was tightly closed with two 10-0 nylon sutures and the conjunctiva was also closed with10-0 nylon sutures. At the end of the procedure the eye was patched, and treated with dexamethasone-neomycin eye drops 4 times daily for at least 2 weeks.
Main Outcome Measures Long-term follow-up was conducted by inviting each patient to appear for a clinical examination 1, 2, 3, and 5 years after the operation. Main outcome measures were implant survival rates. Secondary outcome measures included IOP, number of glaucoma medications, and comparison of the cumulative probabilities of success in the 3 groups. In addition, results of the 24 and 48 mm GMS groups were compared separately.
Statistical Analysis Mean preoperative and mean postoperative findings in 3 operated groups were compared by the use of a paired Student t test and ANOVA for both parametric (IOP) and nonparametric data [number of medications and logarithm of the minimum angle of resolution (logMAR)]. The main outcome measure was implant survival, with success defined as achievement of IOP > 5 mm Hg, 22 mm Hg on at least 2 consecutive follow-up visits, the need for additional glaucoma surgery to control IOP, or loss of light perception. To allow for transient hypertension associated with implantation procedures, criteria for pressure control were not applied during the first 6 months after surgery. In cases of failure, the date of failure was recorded as the date of the clinical examination on which failure criteria were first detected. The last follow-up day was defined as either the date at the end of the 5-year follow-up period or the failure date. Statistical analysis was carried out using SPSS version 13.0 (SPSS Inc., Chicago, IL) programs. Significance was defined as P < 0.05.
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve
RESULTS Detailed demographic data on each group are shown in Table 1. Duration of follow-up was documented as the length of time from surgery to the last follow-up visit or, in cases of failure, from time of surgery to the date of failure as defined above. The numbers of patients who met each study endpoints are shown in Table 2. The mean follow-up duration was 36.7 ± 7.5 months for the AGV group, 49.4 ± 5.2 months for the 24 mm GMS group, and 40.7 ± 4.4 months for the 48 mm GMS group (P = 0.31, ANOVA). Findings in the 3 groups were also similar with regard to the number of antiglaucoma medications taken preoperatively (P = 0.4), even though the preoperative IOP in the 24 mm GMS group was lower than in the other groups (P = 0.02, Table 3). Cumulative probabilities of success at 5 years were 77.8%, 77.8%, and 72.7% for the AGV, 24 mm GMS, and 48 mm GMS groups, respectively. Mean implant survival times in the 3 groups were 49.3 (95% CI, 36.4-62.2) months, 56.7 (95% CI, 51.8-61.2) months, and 50 (95% CI, 40.359.7) months, respectively. Overall, the success rates of the 3 groups were similar (P = 0.83). After surgery, all groups showed a statistically significant decline in IOP and in the numbers of glaucoma medications used (Figs. 2, 3). One year after surgery the mean IOP in the AGV group was 20.9 ± 5.8 mm Hg (compared with 33.5 ± 6.2 mm Hg preoperatively) on 1.3 ± 0.5 medications. The corresponding results in the 24 and 48 mm GMS groups were 20.0 ± 1.9 mm Hg (compared with 25.7 ± 0.7 mm Hg preoperatively) on 1.7 ± 0.8 medications and 17.9 ± 2.3 mm Hg (compared with 35.6 ± 2.2 mm Hg preoperatively) on 1.8 ± 0.4 medications, respectively. These results corresponded to a mean IOP reduction in the 3 groups of 37.6% (P = 0.04), 35.7% (P = 0.00001), and 35.7% (P = 0.00001), respectively. There were no differences between the groups with regard to their mean reduction in IOP (P = 0.65) or in the postoperative use of medications (P = 0.62). Two years after the operation (Figs. 2, 3), the mean IOP in the AGV group was 18.6 ± 3.0 mm Hg on 1.8 ± 0.7 medications. The corresponding results in the 24 and 48 mm GMS groups were 21.3 ± 3.4 mm Hg on 2.0 ± 0.4 medications and 21.3 ± 3.8 mm Hg on 2.3 ± 0.4 medications,
TABLE 1. Demographic Data, Lens Status, and Glaucoma Type
n (%) Total no. patients Mean age ± SD Sex Male Female Study eye Right eye Left eye Lens status Phakic Pseudophakic Glaucoma type Primary open angle Pseudoexfoliative
AGV
24 lm GMS
48 lm GMS
P
9 72 ± 4.1
9 72.6 ± 4.5
11 72.1 ± 4.9
0.9
5 (56) 4 (44)
4 (44) 5 (56)
5 (45) 6 (55)
0.8
6 (67) 3 (33)
4 (44) 5 (56)
4 (36) 7 (64)
0.5
4 (44) 5 (56)
2 (22) 7 (78)
4 (36) 7 (64)
0.7
5 (56) 4 (44)
8 (89) 1 (11)
8 (73) 3 (27)
0.1
AGV indicates Ahmed glaucoma valve; GMS, Gold Micro-Shunt; IOP, intraocular pressure.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
157
Skaat et al
J Glaucoma
TABLE 2. The Number of Patients Who Met Each Study’s Endpoints AGV 24 mm GMS 48 mm GMS
Preoperative
1y
2y
3y
5y
9 9 11
9 9 11
6 9 10
4 7 8
4 5 3
respectively. There were no differences between the groups with regard to the mean reduction in IOP (P = 0.75) or in the postoperative use of medications (P = 0.23). At 3 and 5 years after the operation (Figs. 2, 3), the mean IOP values in the AGV group were 16.0 ± 1.3 mm Hg on 2.7 ± 0.8 medications and 16.3 ± 1.8 mm Hg on 3.0 ± 0.7 medications, respectively. The corresponding results in the 24 mm GMS group were 19.0 ± 1.8 mm Hg on 2.4 ± 0.8 medications and 16.5 ± 2.5 mm Hg on 3.5 ± 0.7 medications, respectively, and in the 48 mm GMS group they were 15.4 ± 2.7 mm Hg on 2.1 ± 0.8 medications and 14.0 ± 0.8 mm Hg on 2.7 ± 0.8 medications, respectively. There were no differences between the groups with regard to their mean IOP reduction (P = 0.3 and 0.89, respectively) or in their use of medications (P = 0.69 and 0.7, respectively). Figure 2 summarizes the IOP measurements (means ± SD) in the groups preoperatively and at the follow-up examinations 1, 2, 3, and 5 years after surgery. At the last follow-up visit the AGV group had a significantly reduced final mean IOP of 17.3 ± 2.6 mm Hg (compared with 33.5 ± 6.7 mm Hg preoperatively, P = 0.004), with no significant change in the final mean number of medications (2.1 ± 0.8 compared with 2.5 ± 0.6 preoperatively, P = 0.43). The corresponding results in the 24 mm GMS group were a significantly reduced final mean IOP of 17.8 ± 2.4 mm Hg (compared with 25.7 ± 0.7 mm Hg, P = 0.0001), with no significant final change in medications (2.9 ± 0.8 compared with 2.9 ± 0.6, P = 0.24), whereas the 48 mm GMS group showed a significantly reduced final mean IOP of 19.6 ± 5.2 mm Hg (compared with 35.6 ± 2.2 mm Hg, P = 0.0001), again without any significant final change in medications (2.5 ± 0.8 compared with 3.2 ± 0.5, P = 0.24). No significant change in the final BCVA compared with preoperative BCVA was recorded with any of the 3 drainage devices. Failures, defined on the basis of our IOP criteria, occurred in a total of 7 patients, in all cases as a result of inadequate high pressure, and in none of them because of
Volume 25, Number 2, February 2016
hypotony. The 2 failures that occurred in the AGV group were due to elevated IOP (> 22 mm Hg), but neither of these eyes progressed to no light perception. The 2 eyes in the 24 mm GMS group and the 3 eyes in the 48 mm GMS group that eventually failed also did so as a result of elevated IOP. None of the patients experienced major intraoperative or postoperative complications (such as endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or tube exposure). Some experienced minor postoperative complications (Table 4), all of which resolved within a few weeks. A comparison between 24 and 48 mm GMS groups is shown in Table 5. Over the study period following surgery, there were no significant postoperative differences between the 2 GMS groups with regard to IOP reduction or the number of antiglaucoma medications used (Table 5). In addition, a comparison between the AGV group and the combined group of GMS (24 and 48 mm together) is shown in Table 6. Over the study period following surgery, there were no significant postoperative differences between these 2 groups with regard to IOP reduction or the number of antiglaucoma medications used (Table 6).
DISCUSSION The results of this study confirm the efficacy and safety of GMS implantation in the supraciliary/suprachoroidal space in eyes with refractory glaucoma. In addition, because of its prospective, randomized design and the relatively longterm follow-up, the study makes it possible to compare, for the first time, the efficacy of AGV and GMS devices in lowering IOP over time. Our results indicate that the AGV and the 2 GMS devices used here were equally effective. AGV is widely known to be effective9–11 and its success in our study is not surprising. Several investigators have reported similar success rates in long-term studies using AGV.9–12 Similar aqueous drainage devices, such as Baerveldt implants, have also been found to be effective and some have even been described as comparable in outcome to trabeculectomy.13 Creation of a channel of communication from the AC to the supraciliary space, first described 10 years ago by Ozdamar et al,14 is an effective way to reduce IOP in patients with glaucoma.7,15,16 The approach is based on the concept that the suprachoroidal space in humans, as in monkeys,6 has a negative hydrostatic pressure relative to the ACT. Any operation that creates a direct link between
TABLE 3. Preoperative Data IOP (mm Hg) Mean ± SD Median No. medications Mean ± SD Median BCVA (logMAR) Mean Median
AGV
24 lm GMS
48 lm GMS
P
33.5 ± 6.2 31
25.7 ± 0.7 26
35.6 ± 2.2 35
0.017
2.5 ± 0.6 3
2.9 ± 0.6 2
3.2 ± 0.5 3
0.4
0.9 0.9
0.8 0.8
0.7 0.6
0.7
Bold values indicate statistically significant (P < 0.05). AGV indicates Ahmed glaucoma valve; BCVA, best-corrected visual acuity; GMS, Gold Micro-Shunt; IOP, intraocular pressure; logMAR, logarithm of the minimum angle of resolution.
158 | www.glaucomajournal.com Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 25, Number 2, February 2016
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve
45 40 35 30 mmHg 25 20 15 10 Pre-Op
1 Year AGV
2 Years 24µ GMS
3 Years 48µ GMS
5 Years
FIGURE 2. Comparison of intraocular pressure patterns, starting from the preoperative assessment, over 5 years of follow-up in patients treated for glaucoma by implantation with an Ahmed glaucoma valve, a 24 mm Gold Micro-Shunt, or a 48 mm Gold Micro-Shunt.
those 2 spaces will drain aqueous from the AC to the suprachoroidal space, thereby reducing IOP. The exact mechanism of IOP reduction after GMS implantation is not fully understood. It is believed that the communication created between the AC and supraciliary and suprachoroidal spaces enhances uveoscleral outflow by direct drainage through choroidal vessels or by increased scleral permeability, or by both. Both ocular coherence tomography of the AC and 20 MHz ultrasonography performed after successful GMS implantations disclosed a hypoechogenic space around the GMS tail as well as a spongy appearance of the sclera above the shunt, suggesting enhanced flow.7 In a pilot study of patients with refractory glaucoma who underwent GMS implantation we obtained a success rate of 79%, assessed 1 year after the operation.7 Subsequent reports from other centers confirmed our initial experience regarding the efficacy and safety of GMS. Mastropasqua et al15 reported a lower success rate of 57% after 15 months in patients with uncontrolled glaucoma, and Figus et al16 reported 67.3% success after 2 years of follow-up in refractory glaucoma patients. Other investigators have successfully used different devices to enable communication between the AC and the supraciliary space, such as silicone tubes
implanted ab-externo17 or ab-interno (CyPass Micro-Stent; Transcend Medical, Menlo Park, CA).18 Although not much is known about the inflammatory or healing processes triggered by insertion of a foreign body into the supraciliary or suprachoroidal space, it seems that fibrosis in this space, by obstructing flow at the tail of the GMS, maybe responsible for the eventual failure of the shunt in certain cases. Histologic studies of failed GMS cases disclosed fibrotic tissue in and around the shunt, impeding aqueous flow through the tubes.19 This fibrotic response is generally believed to be the main reason for the failure of IOP control in the long term. It should be noted, however, that no antimetabolites were used in any of our patients. We believe that application of antimetabolites in the operative field may well have a positive impact on long-term success, and we intend to use them in future studies when evaluating new GMS designs. Two GMS models were used in this study, one with 24 mm diameter and the other with 48 mm diameter tubes. We were interested in finding out whether the larger tubes would provide more copious aqueous flow to the supraciliary space, thus resulting in further reduction of IOP. The results after 5 years showed that the 2 devices were equally
FIGURE 3. Comparison of numbers of medications, starting from the preoperative assessment, over 5 years of follow-up in patients treated for glaucoma by implantation with an Ahmed glaucoma valve, a 24 mm Gold Micro-Shunt, or a 48 mm Gold Micro-Shunt.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
159
Skaat et al
J Glaucoma
TABLE 4. Summary of Minor Complications
Injection Hyphema Choroidals Shallow AC Hypotony
AGV 9 2 2 2 1
(100) (22) (22) (22) (11)
AGV
24 lm GMS
48 lm GMS
P
5 (56) 2 (23) 1 (11) 1 (11) None
6 (67) 1 (11) None 1 (11) None
0.05 0.7 (NS) 0.3 (NS) 0.8 (NS) 0.6 (NS)
Bold values indicate statistically significant (P < 0.05). AC indicates anterior chamber; AGV, Ahmed glaucoma valve; GMS, Gold Micro-Shunt; NS, not significant (cross tabs with w2 and Fisher exact test).
effective, indicating that the difference in tube diameter did not affect the extent of IOP reduction. We speculate that after a steady state is reached, a late biological response within the supraciliary/suprachoroidal space induces a similar flow restriction in both models. It should be noted that the preoperative IOP among the 9 patients who received a 24 mm GMS was lower than in the other 2 groups (Table 5). This might be secondary to the lower proportion of patients with pseudoexfoliation glaucoma in this group (Table 1). However, because of the small size of the study groups it was not feasible to carry out the statistical subgroup analysis that would be needed to support this possibility. Because of the obvious limitation of the small study population size, an important subgroup analysis of different glaucoma types was problematic. In the future we plan to specifically investigate the success of GMS on various types of glaucoma by recruiting a larger number of patients. An encouraging finding was that postoperative complications in all 3 groups were minimal and, if they occurred at all, were mostly transient. There were no cases of severe hypotony, choroidal hemorrhages, retinal detachment, or endophthalmitis in all implants. This excellent safety profile, along with its long-term efficacy, indicates that the GMS should be considered as an additional tool in glaucoma surgery. In conclusion, this prospective randomized study in patients with refractory glaucoma indicates that the success
TABLE 5. Comparison Between 24 and 48 mm GMS Groups
24 lm GMS Follow-up time (mo) 49.4 ± 5.2 IOP (mm Hg) (mean ± SD) Preoperative 25.7 ± 0.7 1 y postoperative 20.0 ± 1.9 2 y postoperative 21.3 ± 3.4 3 y postoperative 19.0 ± 1.8 5 y postoperative 16.5 ± 2.5 At last follow-up 17.8 ± 2.4 No. medications (mean ± SD) Preoperative 2.9 ± 0.6 1 y postoperative 1.7 ± 0.8 2 y postoperative 2.0 ± 0.4 3 y postoperative 2.4 ± 0.8 5 y postoperative 3.5 ± 0.7 At last follow-up 2.9 ± 0.8
Volume 25, Number 2, February 2016
TABLE 6. Comparison of the AGV Group Versus the Combined GMS (24 mm + 48 mm) Group
n (%) Complication
48 lm GMS
P
40.7 ± 7.4
0.2
35.6 ± 2.2 17.9 ± 2.3 21.3 ± 3.8 15.4 ± 2.7 14.0 ± 0.8 19.6 ± 5.2
0.01 0.3 0.9 0.2 0.3 0.6
3.2 ± 0.5 1.8 ± 0.4 2.3 ± 0.4 2.1 ± 0.8 2.7 ± 0.8 2.5 ± 0.8
0.6 0.8 0.1 0.8 0.5 0.5
Bold values indicate statistically significant (P < 0.05). GMS indicates Gold Micro-Shunt; IOP, intraocular pressure.
IOP (mm Hg) (mean ± SD) Preoperative 33.5 ± 6.2 1 y postoperative 20.9 ± 5.8 2 y postoperative 18.6 ± 3.0 3 y postoperative 16.0 ± 1.3 5 y postoperative 16.3 ± 1.8 At last follow-up 17.3 ± 2.6 No. medications (mean ± SD) Preoperative 2.5 ± 0.6 1 y postoperative 1.3 ± 0.5 2 y postoperative 1.8 ± 0.7 3 y postoperative 2.7 ± 0.8 5 y postoperative 3.0 ± 0.7 At last follow-up 2.1 ± 0.8
GMS
P
31.1 ± 1.3 18.9 ± 0.9 21.3 ± 2.6 17.1 ± 2.1 15.6 ± 1.4 18.8 ± 1.8
0.5 0.5 0.5 0.07 0.8 0.6
3.1 ± 0.2 1.8 ± 0.3 2.2 ± 0.3 2.3 ± 0.4 3.2 ± 0.5 33.5 ± 6.2
0.2 0.4 0.4 0.7 0.8 0.4
AGV indicates Ahmed glaucoma valve; GMS, Gold Micro-Shunt; IOP, intraocular pressure.
rates of AGV and GMS, after 5 years of follow-up, were comparable. In addition, in terms of both IOP reduction and use of supplemental medical therapy, the outcomes with all 3 tested devices were similar.
REFERENCES 1. Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors. Ophthalmology. 2009;116:200–207. 2. Landers J, Martin K, Sarkies N, et al. A twenty-year follow-up study of trabeculectomy: risk factors and outcomes. Ophthalmology. 2012;119:694–702. 3. Jampel HD, Solus JF, Tracey PA, et al. Outcomes and blebrelated complications of trabeculectomy. Ophthalmology. 2012;119:712–722. 4. Solus JF, Jampel HD, Tracey PA, et al. Comparison of limbusbased and fornix-based trabeculectomy: success, bleb-related complications, and bleb morphology. Ophthalmology. 2012; 119:703–711. 5. Toris CB, Yablonski ME, Wang YL, et al. Aqueous humor dynamics in the aging human eye. Am J Ophthalmol. 1999; 127:407–412. 6. Emi K, Pederson JE, Toris CB. Hydrostatic pressure of the suprachoroidal space. Invest Ophthalmol Vis Sci. 1989;30: 233–238. 7. Melamed S, Ben Simon GJ, Goldenfeld M, et al. Efficacy and safety of gold micro shunt implantation to the supraciliary space in patients with glaucoma: a pilot study. Arch Ophthalmol. 2009;127:264–269. 8. Sen SC, Ghosh A. Gold as an intraocular foreign body. Br J Ophthalmol. 1983;67:398–399. 9. Christakis PG, Kalenak JW, Zurakowski D, et al. The Ahmed Versus Baerveldt study: one-year treatment outcomes. Ophthalmology. 2011;118:2180–2189. 10. Wilson MR, Mendis U, Paliwal A, et al. Long-term follow-up of primary glaucoma surgery with Ahmed glaucoma valve implant versus trabeculectomy. Am J Ophthalmol. 2003;136: 464–470. 11. Nassiri N, Kamali G, Rahnavardi M, et al. Ahmed glaucoma valve and single-plate Molteno implants in treatment of refractory glaucoma: a comparative study. Am J Ophthalmol. 2010;149:893–902.
160 | www.glaucomajournal.com Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 25, Number 2, February 2016
12. Maris PJ Jr, Tsai JC, Khatib N, et al. Clinical outcomes of Ahmed glaucoma valve in posterior segment versus anterior chamber. J Glaucoma. 2013;22:183–189. 13. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153:789–803. 14. Ozdamar A, Aras C, Karacorlu M. Suprachoroidal seton implantation in refractory glaucoma: a novel surgical technique. J Glaucoma. 2003;12:354–359. 15. Mastropasqua L, Agnifili L, Ciancaglini M, et al. In vivo analysis of conjunctiva in gold micro shunt implantation for glaucoma. Br J Ophthalmol. 2010;94:1592–1596.
Copyright
r
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve
16. Figus M, Lazzeri S, Fogagnolo P, et al. Supraciliary shunt in refractory glaucoma. Br J Ophthalmol. 2011;95:1537–1541. 17. Jordan JF, Engels BF, Dinslage S, et al. A novel approach to suprachoroidal drainage for the surgical treatment of intractable glaucoma. J Glaucoma. 2006;15:200–205. 18. Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr Opin Ophthalmol. 2012;23:96–104. 19. Agnifili L, Costagliola C, Figus M, et al. Histological findings of failed gold micro shunts in primary open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 2012;250: 143–149.
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
161
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve: Long-term Outcomes of a Prospective Randomized Clinical Trial Alon Skaat, MD,*w Oded Sagiv, MD,*w Michael Kinori, MD,*w Guy J. Ben Simon, MD,*w Modi Goldenfeld, MD,*w and Shlomo Melamed, MD*w
Purpose: To compare long-term outcomes of Ahmed glaucoma valve (AGV), 24 mm Gold Micro-Shunt (GMS), and 48 mm GMS implantation for treatment of refractory glaucoma. Patients and Methods: This was a 3-armed randomized interventional prospective clinical trial. Within an institutional setting, 29 adults (29 eyes) with refractory glaucoma [mean baseline intraocular pressure (IOP) Z22 mm Hg on maximal medication, status post at least 1 failed trabeculectomy, defined visual field defect, and without recent glaucoma-related surgery] were randomly assigned to AGV, 24 mm GMS, or 48 mm GMS implantation. Exclusion criteria included uveitic, traumatic, or neovascular glaucoma. The 3 groups were comparatively evaluated preoperatively and 1, 2, 3, and 5 years postoperatively for IOP and numbers of glaucoma medications needed. Main outcome measures were implant survival rates. Results of the 24 and 48 mm GMS groups were also compared separately. Results: In all groups the final IOP (in mm Hg) was significantly lower than the preoperative IOP (17.3 ± 2.6 vs. 33.5 ± 6.7, P = 0.004; 17.8 ± 2.4 vs. 25.7 ± 0.7, P = 0.0001; and 19.6 ± 5.2 vs. 35.6 ± 2.2, P = 0.0001 in the AGV, 24 mm GMS, and 48 mm GMS groups, respectively). Differences between initial and final mean numbers of medications were not significant. Cumulative probabilities of success at 5 years were 77.8%, 77.8%, and 72.7%, respectively. Conclusions: During long-term follow-up, success rates in the 2 GMS groups and the AGV group were similar. Likewise, IOP reduction and the need for continued glaucoma medical therapy remained high and were similar for all devices. Key Words: open-angle glaucoma, Ahmed glaucoma valve, Gold Micro-Shunt
(J Glaucoma 2016;25:155–161)
S
urgical treatment is usually indicated when glaucomatous optic neuropathy worsens or visual field damage progresses despite laser trabeculoplasty or maximally tolerated medical therapy.1 Some of the accepted surgical approaches include filtration procedures such as trabeculectomy and the insertion of implants to connect the
Received for publication August 28, 2013; accepted September 3, 2014. From the *Department of Ophthalmology, The Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer; and wSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Disclosure: The authors declare no conflict of interest. Reprints: Alon Skaat, MD, Department of Ophthalmology, The Goldshleger Eye Institute, Sheba Medical Center, Tel Hashomer 52621, Israel (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000175
J Glaucoma
Volume 25, Number 2, February 2016
anterior chamber (AC) to the subconjunctival space. These procedures are reportedly effective in many cases,2 but they require the formation of a filtering bleb, and have long-term potential failure due to fibrosis and scarring.3 Filtering bleb can potentially be the source of a variety of complications,3,4 such as shallow AC owing to overfiltration, hypotony as a result of bleb leakage, choroidal detachment or hemorrhage, hyphema, blebitis, or endophthalmitis. The above surgical approaches are aimed mainly at circumventing the conventional aqueous outflow route (traditionally considered to be the major outflow pathway), comprising the trabecular meshwork, Schlemm canal, collector channels, and the episcleral venous plexus. Only a few approaches have been designed to increase the uveoscleral outflow pathway, which consists of the interstitium of the ciliary body, the suprachoroidal space, and the scleral vasculature. This pathway was reported to contribute up to 54% of the total egress of aqueous humor in young healthy subjects,5 and is apparently much lower with aging—about 10% to 15% of total outflow. In the nonglaucomatous cynomolgus monkey model, in which the natural pressure differential between the AC and the suprachoroidal space is 1 to 5 mm Hg, a change in intraocular pressure (IOP) was found to produce a corresponding change in the suprachoroidal space pressure when the AC and the suprachoroidal space were connected by cannulation.6 It was therefore assumed that physical communication between the AC and the suprachoroidal space will reduce the IOP. We previously described the short-term results of a novel approach that enhances uveoscleral outflow and reduces IOP in patients with glaucoma.7 This was done by implanting an ultrathin 24-karat Gold Micro-Shunt (GMS) that contains tubules to facilitate aqueous flow between the AC and the supraciliary/suprachoroidal space without the creation of a bleb. The procedure proved to be safe and effective, and resulted in a significant decrease in IOP at the follow-up examination 1 year after surgery. The purpose of this prospective study was to compare the long-term outcomes of implantation of the Ahmed glaucoma valve (AGV) (Ahmed FP7 Glaucoma Valve) with that of the 24 and 48 mm GMS in patients with refractory glaucoma.
PATIENTS AND METHODS The study was approved by the Sheba Medical Center Institutional Review Board committee and the Israeli Ministry of Health and was registered in the US National Institutes of Health (NIH) registry (NCT00382395). Patients gave informed consent to participate in the study. www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
155
Skaat et al
J Glaucoma
Volume 25, Number 2, February 2016
Setting The surgical procedures were conducted between January 2006 and July 2007 at the Sam Rothberg Glaucoma Center in the Goldschleger Eye Institute at Sheba Medical Center. The operations in all patients were performed by the same surgeon (S.M.)
Patient Population The study participants were 29 patients (29 eyes) with refractory glaucoma. Criteria for inclusion in the study were: (1) age 21 years or older; (2) a diagnosis of primary open-angle glaucoma, pseudoexfoliation glaucoma, or pigmentary dispersion glaucoma in 1 or both eyes; (3) average baseline IOP of Z22 mm Hg while on maximally tolerated medical treatment; (4) at least 1 failed trabeculectomy with at least 60 days since prior incisional glaucoma surgery; and (5) a visual field defect (MD score of 5 mg/ d; (4) intolerance to gonioscopy, slit-lamp examination, tonometry, or other study procedures; (5) mental impairment invalidating informed consent or disrupting followup; (6) pregnancy; (7) known sensitivity to medication needed during and after surgery; (8) significant comorbid disease that might interfere with follow-up; (9) current use of any other investigational drug or device; (10) a history of acute angle-closure glaucoma in the study eye within the past 12 months; (11) evidence of significant ocular disease other than glaucoma or cataract, or a history of previous ocular surgery (other than glaucoma, cataract, or cosmetic); or (12) active clinical ocular infection requiring treatment. Patients were evaluated preoperatively and 1, 2, 3, and 5 years postoperatively for IOP and numbers of glaucoma medications needed. The preoperative evaluation also included visual acuity assessment, slit-lamp biomicroscopy, IOP measurement with a Goldman applanation tonometer, ophthalmoscopy after pupil dilation, gonioscopy, and visual field analysis when applicable (24-2 program, Humphrey Field Analyzer HFA II-I; Carl Zeiss, Jena, Germany).
Randomization Technique After informed consent was given and confirmation of eligibility by the investigator, each enrolled patient was randomized to 1 of 3 treatment arms. The randomization was done using sealed envelopes that contained the randomly generated treatment allocation. Inside each envelope was a randomization assignment form with a sequence number matching the one on the outside of its envelope. The envelope was opened on the day of surgery or as close to the actual treatment as possible. Enrolled patients were allocated to one of the following strata: an AGV, a 24 mm GMS, or a 48 mm GMS.
Intervention Procedures AGV model FP7 was used for all patients. The surgical technique for its implantation has been described previously.7 The GMS (SOLX Inc., Boston, MA) is a nonvalved, flat-plate drainage device made from 24-karat medical-
FIGURE 1. Drawing of the Gold Micro-Shunt with the shunt dimensions.
grade (99.95%) gold, previously shown to have good biocompatibility and to be inert as an intraocular foreign body.8 The shunt is shaped as a long rectangle with rounded edges and fin-like tabs at the distal end to allow anchoring of the device in the suprachoroidal space. The proximal end provides the ingress for aqueous humor. The distal end provides drainage of the fluid through microchannels from the AC into the suprachoroidal space. Two models, a 24 and a 48 mm GMS, were tested. The 24 mm GMS model is 5.2 mm long and 3.2 mm wide and weighs 6.2 mg. The 48 mm GMS model is as long and as wide as the 24 mm GMS but weighs 9.2 mg. The diameter of the microchannels is 24 mm in the lighter model and 48 mm in the heavier model. A detailed schematic drawing of the GMS implant is shown in Figure 1.
Surgical Technique With the GMS
As described previously,7 patients were operated on under local anesthesia using either a sub-Tenon or a peribulbar injection. A bridle suture was placed around the superior rectus muscle, or alternatively, a corneal traction suture was placed at 12 o’clock. A fornix-based conjunctival flap was fashioned, and this was followed by meticulous cautery of episcleral vessels. A 4 mm long, fullthickness scleral incision was made 2 mm posterior to the limbus to expose the supraciliary space. An AC maintainer was inserted through a peripheral paracentesis and a crescent knife was used to enter the AC at a plane of 90% scleral thickness, with careful dissection to avoid cyclodialysis. Dissection was then continued posteriorly into the suprachoroidal space for 2 to 3 mm using the same
156 | www.glaucomajournal.com Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 25, Number 2, February 2016
crescent blade or blunt spatula. The anterior segment of the GMS was then introduced into the AC and its posterior segment into the suprachoroidal space, making sure that the implant was placed posteriorly so that 1 to 1.5 mm of the GMS was visible in the AC. The scleral wound was tightly closed with two 10-0 nylon sutures and the conjunctiva was also closed with10-0 nylon sutures. At the end of the procedure the eye was patched, and treated with dexamethasone-neomycin eye drops 4 times daily for at least 2 weeks.
Main Outcome Measures Long-term follow-up was conducted by inviting each patient to appear for a clinical examination 1, 2, 3, and 5 years after the operation. Main outcome measures were implant survival rates. Secondary outcome measures included IOP, number of glaucoma medications, and comparison of the cumulative probabilities of success in the 3 groups. In addition, results of the 24 and 48 mm GMS groups were compared separately.
Statistical Analysis Mean preoperative and mean postoperative findings in 3 operated groups were compared by the use of a paired Student t test and ANOVA for both parametric (IOP) and nonparametric data [number of medications and logarithm of the minimum angle of resolution (logMAR)]. The main outcome measure was implant survival, with success defined as achievement of IOP > 5 mm Hg, 22 mm Hg on at least 2 consecutive follow-up visits, the need for additional glaucoma surgery to control IOP, or loss of light perception. To allow for transient hypertension associated with implantation procedures, criteria for pressure control were not applied during the first 6 months after surgery. In cases of failure, the date of failure was recorded as the date of the clinical examination on which failure criteria were first detected. The last follow-up day was defined as either the date at the end of the 5-year follow-up period or the failure date. Statistical analysis was carried out using SPSS version 13.0 (SPSS Inc., Chicago, IL) programs. Significance was defined as P < 0.05.
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve
RESULTS Detailed demographic data on each group are shown in Table 1. Duration of follow-up was documented as the length of time from surgery to the last follow-up visit or, in cases of failure, from time of surgery to the date of failure as defined above. The numbers of patients who met each study endpoints are shown in Table 2. The mean follow-up duration was 36.7 ± 7.5 months for the AGV group, 49.4 ± 5.2 months for the 24 mm GMS group, and 40.7 ± 4.4 months for the 48 mm GMS group (P = 0.31, ANOVA). Findings in the 3 groups were also similar with regard to the number of antiglaucoma medications taken preoperatively (P = 0.4), even though the preoperative IOP in the 24 mm GMS group was lower than in the other groups (P = 0.02, Table 3). Cumulative probabilities of success at 5 years were 77.8%, 77.8%, and 72.7% for the AGV, 24 mm GMS, and 48 mm GMS groups, respectively. Mean implant survival times in the 3 groups were 49.3 (95% CI, 36.4-62.2) months, 56.7 (95% CI, 51.8-61.2) months, and 50 (95% CI, 40.359.7) months, respectively. Overall, the success rates of the 3 groups were similar (P = 0.83). After surgery, all groups showed a statistically significant decline in IOP and in the numbers of glaucoma medications used (Figs. 2, 3). One year after surgery the mean IOP in the AGV group was 20.9 ± 5.8 mm Hg (compared with 33.5 ± 6.2 mm Hg preoperatively) on 1.3 ± 0.5 medications. The corresponding results in the 24 and 48 mm GMS groups were 20.0 ± 1.9 mm Hg (compared with 25.7 ± 0.7 mm Hg preoperatively) on 1.7 ± 0.8 medications and 17.9 ± 2.3 mm Hg (compared with 35.6 ± 2.2 mm Hg preoperatively) on 1.8 ± 0.4 medications, respectively. These results corresponded to a mean IOP reduction in the 3 groups of 37.6% (P = 0.04), 35.7% (P = 0.00001), and 35.7% (P = 0.00001), respectively. There were no differences between the groups with regard to their mean reduction in IOP (P = 0.65) or in the postoperative use of medications (P = 0.62). Two years after the operation (Figs. 2, 3), the mean IOP in the AGV group was 18.6 ± 3.0 mm Hg on 1.8 ± 0.7 medications. The corresponding results in the 24 and 48 mm GMS groups were 21.3 ± 3.4 mm Hg on 2.0 ± 0.4 medications and 21.3 ± 3.8 mm Hg on 2.3 ± 0.4 medications,
TABLE 1. Demographic Data, Lens Status, and Glaucoma Type
n (%) Total no. patients Mean age ± SD Sex Male Female Study eye Right eye Left eye Lens status Phakic Pseudophakic Glaucoma type Primary open angle Pseudoexfoliative
AGV
24 lm GMS
48 lm GMS
P
9 72 ± 4.1
9 72.6 ± 4.5
11 72.1 ± 4.9
0.9
5 (56) 4 (44)
4 (44) 5 (56)
5 (45) 6 (55)
0.8
6 (67) 3 (33)
4 (44) 5 (56)
4 (36) 7 (64)
0.5
4 (44) 5 (56)
2 (22) 7 (78)
4 (36) 7 (64)
0.7
5 (56) 4 (44)
8 (89) 1 (11)
8 (73) 3 (27)
0.1
AGV indicates Ahmed glaucoma valve; GMS, Gold Micro-Shunt; IOP, intraocular pressure.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
157
Skaat et al
J Glaucoma
TABLE 2. The Number of Patients Who Met Each Study’s Endpoints AGV 24 mm GMS 48 mm GMS
Preoperative
1y
2y
3y
5y
9 9 11
9 9 11
6 9 10
4 7 8
4 5 3
respectively. There were no differences between the groups with regard to the mean reduction in IOP (P = 0.75) or in the postoperative use of medications (P = 0.23). At 3 and 5 years after the operation (Figs. 2, 3), the mean IOP values in the AGV group were 16.0 ± 1.3 mm Hg on 2.7 ± 0.8 medications and 16.3 ± 1.8 mm Hg on 3.0 ± 0.7 medications, respectively. The corresponding results in the 24 mm GMS group were 19.0 ± 1.8 mm Hg on 2.4 ± 0.8 medications and 16.5 ± 2.5 mm Hg on 3.5 ± 0.7 medications, respectively, and in the 48 mm GMS group they were 15.4 ± 2.7 mm Hg on 2.1 ± 0.8 medications and 14.0 ± 0.8 mm Hg on 2.7 ± 0.8 medications, respectively. There were no differences between the groups with regard to their mean IOP reduction (P = 0.3 and 0.89, respectively) or in their use of medications (P = 0.69 and 0.7, respectively). Figure 2 summarizes the IOP measurements (means ± SD) in the groups preoperatively and at the follow-up examinations 1, 2, 3, and 5 years after surgery. At the last follow-up visit the AGV group had a significantly reduced final mean IOP of 17.3 ± 2.6 mm Hg (compared with 33.5 ± 6.7 mm Hg preoperatively, P = 0.004), with no significant change in the final mean number of medications (2.1 ± 0.8 compared with 2.5 ± 0.6 preoperatively, P = 0.43). The corresponding results in the 24 mm GMS group were a significantly reduced final mean IOP of 17.8 ± 2.4 mm Hg (compared with 25.7 ± 0.7 mm Hg, P = 0.0001), with no significant final change in medications (2.9 ± 0.8 compared with 2.9 ± 0.6, P = 0.24), whereas the 48 mm GMS group showed a significantly reduced final mean IOP of 19.6 ± 5.2 mm Hg (compared with 35.6 ± 2.2 mm Hg, P = 0.0001), again without any significant final change in medications (2.5 ± 0.8 compared with 3.2 ± 0.5, P = 0.24). No significant change in the final BCVA compared with preoperative BCVA was recorded with any of the 3 drainage devices. Failures, defined on the basis of our IOP criteria, occurred in a total of 7 patients, in all cases as a result of inadequate high pressure, and in none of them because of
Volume 25, Number 2, February 2016
hypotony. The 2 failures that occurred in the AGV group were due to elevated IOP (> 22 mm Hg), but neither of these eyes progressed to no light perception. The 2 eyes in the 24 mm GMS group and the 3 eyes in the 48 mm GMS group that eventually failed also did so as a result of elevated IOP. None of the patients experienced major intraoperative or postoperative complications (such as endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or tube exposure). Some experienced minor postoperative complications (Table 4), all of which resolved within a few weeks. A comparison between 24 and 48 mm GMS groups is shown in Table 5. Over the study period following surgery, there were no significant postoperative differences between the 2 GMS groups with regard to IOP reduction or the number of antiglaucoma medications used (Table 5). In addition, a comparison between the AGV group and the combined group of GMS (24 and 48 mm together) is shown in Table 6. Over the study period following surgery, there were no significant postoperative differences between these 2 groups with regard to IOP reduction or the number of antiglaucoma medications used (Table 6).
DISCUSSION The results of this study confirm the efficacy and safety of GMS implantation in the supraciliary/suprachoroidal space in eyes with refractory glaucoma. In addition, because of its prospective, randomized design and the relatively longterm follow-up, the study makes it possible to compare, for the first time, the efficacy of AGV and GMS devices in lowering IOP over time. Our results indicate that the AGV and the 2 GMS devices used here were equally effective. AGV is widely known to be effective9–11 and its success in our study is not surprising. Several investigators have reported similar success rates in long-term studies using AGV.9–12 Similar aqueous drainage devices, such as Baerveldt implants, have also been found to be effective and some have even been described as comparable in outcome to trabeculectomy.13 Creation of a channel of communication from the AC to the supraciliary space, first described 10 years ago by Ozdamar et al,14 is an effective way to reduce IOP in patients with glaucoma.7,15,16 The approach is based on the concept that the suprachoroidal space in humans, as in monkeys,6 has a negative hydrostatic pressure relative to the ACT. Any operation that creates a direct link between
TABLE 3. Preoperative Data IOP (mm Hg) Mean ± SD Median No. medications Mean ± SD Median BCVA (logMAR) Mean Median
AGV
24 lm GMS
48 lm GMS
P
33.5 ± 6.2 31
25.7 ± 0.7 26
35.6 ± 2.2 35
0.017
2.5 ± 0.6 3
2.9 ± 0.6 2
3.2 ± 0.5 3
0.4
0.9 0.9
0.8 0.8
0.7 0.6
0.7
Bold values indicate statistically significant (P < 0.05). AGV indicates Ahmed glaucoma valve; BCVA, best-corrected visual acuity; GMS, Gold Micro-Shunt; IOP, intraocular pressure; logMAR, logarithm of the minimum angle of resolution.
158 | www.glaucomajournal.com Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 25, Number 2, February 2016
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve
45 40 35 30 mmHg 25 20 15 10 Pre-Op
1 Year AGV
2 Years 24µ GMS
3 Years 48µ GMS
5 Years
FIGURE 2. Comparison of intraocular pressure patterns, starting from the preoperative assessment, over 5 years of follow-up in patients treated for glaucoma by implantation with an Ahmed glaucoma valve, a 24 mm Gold Micro-Shunt, or a 48 mm Gold Micro-Shunt.
those 2 spaces will drain aqueous from the AC to the suprachoroidal space, thereby reducing IOP. The exact mechanism of IOP reduction after GMS implantation is not fully understood. It is believed that the communication created between the AC and supraciliary and suprachoroidal spaces enhances uveoscleral outflow by direct drainage through choroidal vessels or by increased scleral permeability, or by both. Both ocular coherence tomography of the AC and 20 MHz ultrasonography performed after successful GMS implantations disclosed a hypoechogenic space around the GMS tail as well as a spongy appearance of the sclera above the shunt, suggesting enhanced flow.7 In a pilot study of patients with refractory glaucoma who underwent GMS implantation we obtained a success rate of 79%, assessed 1 year after the operation.7 Subsequent reports from other centers confirmed our initial experience regarding the efficacy and safety of GMS. Mastropasqua et al15 reported a lower success rate of 57% after 15 months in patients with uncontrolled glaucoma, and Figus et al16 reported 67.3% success after 2 years of follow-up in refractory glaucoma patients. Other investigators have successfully used different devices to enable communication between the AC and the supraciliary space, such as silicone tubes
implanted ab-externo17 or ab-interno (CyPass Micro-Stent; Transcend Medical, Menlo Park, CA).18 Although not much is known about the inflammatory or healing processes triggered by insertion of a foreign body into the supraciliary or suprachoroidal space, it seems that fibrosis in this space, by obstructing flow at the tail of the GMS, maybe responsible for the eventual failure of the shunt in certain cases. Histologic studies of failed GMS cases disclosed fibrotic tissue in and around the shunt, impeding aqueous flow through the tubes.19 This fibrotic response is generally believed to be the main reason for the failure of IOP control in the long term. It should be noted, however, that no antimetabolites were used in any of our patients. We believe that application of antimetabolites in the operative field may well have a positive impact on long-term success, and we intend to use them in future studies when evaluating new GMS designs. Two GMS models were used in this study, one with 24 mm diameter and the other with 48 mm diameter tubes. We were interested in finding out whether the larger tubes would provide more copious aqueous flow to the supraciliary space, thus resulting in further reduction of IOP. The results after 5 years showed that the 2 devices were equally
FIGURE 3. Comparison of numbers of medications, starting from the preoperative assessment, over 5 years of follow-up in patients treated for glaucoma by implantation with an Ahmed glaucoma valve, a 24 mm Gold Micro-Shunt, or a 48 mm Gold Micro-Shunt.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
159
Skaat et al
J Glaucoma
TABLE 4. Summary of Minor Complications
Injection Hyphema Choroidals Shallow AC Hypotony
AGV 9 2 2 2 1
(100) (22) (22) (22) (11)
AGV
24 lm GMS
48 lm GMS
P
5 (56) 2 (23) 1 (11) 1 (11) None
6 (67) 1 (11) None 1 (11) None
0.05 0.7 (NS) 0.3 (NS) 0.8 (NS) 0.6 (NS)
Bold values indicate statistically significant (P < 0.05). AC indicates anterior chamber; AGV, Ahmed glaucoma valve; GMS, Gold Micro-Shunt; NS, not significant (cross tabs with w2 and Fisher exact test).
effective, indicating that the difference in tube diameter did not affect the extent of IOP reduction. We speculate that after a steady state is reached, a late biological response within the supraciliary/suprachoroidal space induces a similar flow restriction in both models. It should be noted that the preoperative IOP among the 9 patients who received a 24 mm GMS was lower than in the other 2 groups (Table 5). This might be secondary to the lower proportion of patients with pseudoexfoliation glaucoma in this group (Table 1). However, because of the small size of the study groups it was not feasible to carry out the statistical subgroup analysis that would be needed to support this possibility. Because of the obvious limitation of the small study population size, an important subgroup analysis of different glaucoma types was problematic. In the future we plan to specifically investigate the success of GMS on various types of glaucoma by recruiting a larger number of patients. An encouraging finding was that postoperative complications in all 3 groups were minimal and, if they occurred at all, were mostly transient. There were no cases of severe hypotony, choroidal hemorrhages, retinal detachment, or endophthalmitis in all implants. This excellent safety profile, along with its long-term efficacy, indicates that the GMS should be considered as an additional tool in glaucoma surgery. In conclusion, this prospective randomized study in patients with refractory glaucoma indicates that the success
TABLE 5. Comparison Between 24 and 48 mm GMS Groups
24 lm GMS Follow-up time (mo) 49.4 ± 5.2 IOP (mm Hg) (mean ± SD) Preoperative 25.7 ± 0.7 1 y postoperative 20.0 ± 1.9 2 y postoperative 21.3 ± 3.4 3 y postoperative 19.0 ± 1.8 5 y postoperative 16.5 ± 2.5 At last follow-up 17.8 ± 2.4 No. medications (mean ± SD) Preoperative 2.9 ± 0.6 1 y postoperative 1.7 ± 0.8 2 y postoperative 2.0 ± 0.4 3 y postoperative 2.4 ± 0.8 5 y postoperative 3.5 ± 0.7 At last follow-up 2.9 ± 0.8
Volume 25, Number 2, February 2016
TABLE 6. Comparison of the AGV Group Versus the Combined GMS (24 mm + 48 mm) Group
n (%) Complication
48 lm GMS
P
40.7 ± 7.4
0.2
35.6 ± 2.2 17.9 ± 2.3 21.3 ± 3.8 15.4 ± 2.7 14.0 ± 0.8 19.6 ± 5.2
0.01 0.3 0.9 0.2 0.3 0.6
3.2 ± 0.5 1.8 ± 0.4 2.3 ± 0.4 2.1 ± 0.8 2.7 ± 0.8 2.5 ± 0.8
0.6 0.8 0.1 0.8 0.5 0.5
Bold values indicate statistically significant (P < 0.05). GMS indicates Gold Micro-Shunt; IOP, intraocular pressure.
IOP (mm Hg) (mean ± SD) Preoperative 33.5 ± 6.2 1 y postoperative 20.9 ± 5.8 2 y postoperative 18.6 ± 3.0 3 y postoperative 16.0 ± 1.3 5 y postoperative 16.3 ± 1.8 At last follow-up 17.3 ± 2.6 No. medications (mean ± SD) Preoperative 2.5 ± 0.6 1 y postoperative 1.3 ± 0.5 2 y postoperative 1.8 ± 0.7 3 y postoperative 2.7 ± 0.8 5 y postoperative 3.0 ± 0.7 At last follow-up 2.1 ± 0.8
GMS
P
31.1 ± 1.3 18.9 ± 0.9 21.3 ± 2.6 17.1 ± 2.1 15.6 ± 1.4 18.8 ± 1.8
0.5 0.5 0.5 0.07 0.8 0.6
3.1 ± 0.2 1.8 ± 0.3 2.2 ± 0.3 2.3 ± 0.4 3.2 ± 0.5 33.5 ± 6.2
0.2 0.4 0.4 0.7 0.8 0.4
AGV indicates Ahmed glaucoma valve; GMS, Gold Micro-Shunt; IOP, intraocular pressure.
rates of AGV and GMS, after 5 years of follow-up, were comparable. In addition, in terms of both IOP reduction and use of supplemental medical therapy, the outcomes with all 3 tested devices were similar.
REFERENCES 1. Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors. Ophthalmology. 2009;116:200–207. 2. Landers J, Martin K, Sarkies N, et al. A twenty-year follow-up study of trabeculectomy: risk factors and outcomes. Ophthalmology. 2012;119:694–702. 3. Jampel HD, Solus JF, Tracey PA, et al. Outcomes and blebrelated complications of trabeculectomy. Ophthalmology. 2012;119:712–722. 4. Solus JF, Jampel HD, Tracey PA, et al. Comparison of limbusbased and fornix-based trabeculectomy: success, bleb-related complications, and bleb morphology. Ophthalmology. 2012; 119:703–711. 5. Toris CB, Yablonski ME, Wang YL, et al. Aqueous humor dynamics in the aging human eye. Am J Ophthalmol. 1999; 127:407–412. 6. Emi K, Pederson JE, Toris CB. Hydrostatic pressure of the suprachoroidal space. Invest Ophthalmol Vis Sci. 1989;30: 233–238. 7. Melamed S, Ben Simon GJ, Goldenfeld M, et al. Efficacy and safety of gold micro shunt implantation to the supraciliary space in patients with glaucoma: a pilot study. Arch Ophthalmol. 2009;127:264–269. 8. Sen SC, Ghosh A. Gold as an intraocular foreign body. Br J Ophthalmol. 1983;67:398–399. 9. Christakis PG, Kalenak JW, Zurakowski D, et al. The Ahmed Versus Baerveldt study: one-year treatment outcomes. Ophthalmology. 2011;118:2180–2189. 10. Wilson MR, Mendis U, Paliwal A, et al. Long-term follow-up of primary glaucoma surgery with Ahmed glaucoma valve implant versus trabeculectomy. Am J Ophthalmol. 2003;136: 464–470. 11. Nassiri N, Kamali G, Rahnavardi M, et al. Ahmed glaucoma valve and single-plate Molteno implants in treatment of refractory glaucoma: a comparative study. Am J Ophthalmol. 2010;149:893–902.
160 | www.glaucomajournal.com Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 25, Number 2, February 2016
12. Maris PJ Jr, Tsai JC, Khatib N, et al. Clinical outcomes of Ahmed glaucoma valve in posterior segment versus anterior chamber. J Glaucoma. 2013;22:183–189. 13. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153:789–803. 14. Ozdamar A, Aras C, Karacorlu M. Suprachoroidal seton implantation in refractory glaucoma: a novel surgical technique. J Glaucoma. 2003;12:354–359. 15. Mastropasqua L, Agnifili L, Ciancaglini M, et al. In vivo analysis of conjunctiva in gold micro shunt implantation for glaucoma. Br J Ophthalmol. 2010;94:1592–1596.
Copyright
r
Gold Micro-Shunt Implants Versus Ahmed Glaucoma Valve
16. Figus M, Lazzeri S, Fogagnolo P, et al. Supraciliary shunt in refractory glaucoma. Br J Ophthalmol. 2011;95:1537–1541. 17. Jordan JF, Engels BF, Dinslage S, et al. A novel approach to suprachoroidal drainage for the surgical treatment of intractable glaucoma. J Glaucoma. 2006;15:200–205. 18. Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr Opin Ophthalmol. 2012;23:96–104. 19. Agnifili L, Costagliola C, Figus M, et al. Histological findings of failed gold micro shunts in primary open-angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 2012;250: 143–149.
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
161
