The Tube Trials: New Information to Guide Clinicians

Updates on six recent studies.

By Steven J. Gedde, MD

Tube shunts (also known as aqueous shunts, glaucoma drainage implants, glaucoma drainage devices and setons) are being used with increasing frequency in the surgical management of glaucoma. Medicare claims data showed a 184% increase in the number of tube shunt surgeries and a concurrent 43% decrease in trabeculectomies performed between 1995 and 2004.¹ Practice patterns in glaucoma surgery were also evaluated with sequential surveys of the American Glaucoma Society membership, and selection of tube shunts as the preferred surgical approach increased from 17.5% in 1996² to 50.8% in 2008.³ Concern about complications associated with a perilimbal filtering bleb, including bleb infections and dysesthesia, has contributed to the growing popularity of tube shunts as an alternative to trabeculectomy.

Several recent multicenter randomized clinical trials have provided valuable information to guide patient care. These studies have compared surgical outcomes with different types of implants,^4-8 and between trabeculectomy and tube shunt surgery^9-12 in specific patient groups. A summary of the design features and major findings from recent tube shunt trials is presented in Table 1. Here, I will provide updates on three recent studies designed to compare various implant types and three that compared tube shunts to trabeculectomy.

Comparison of Various Implant Types

■ Ahmed Baerveldt Comparison (ABC) Study

The ABC study is a multicenter randomized clinical trial designed to compare the efficacy and safety of the Ahmed glaucoma valve implant (New World Medical) and 350 mm² Baerveldt glaucoma implant (Abbott Medical Optics).

The study enrolled 276 patients with refractory glaucoma requiring tube shunt implantation at 16 clinical centers.⁴ Mean IOP was lower in the Baerveldt group at one year (15.4 mm Hg Ahmed group vs 13.2 mm Hg Baerveldt group, p = 0.007), and use of adjunctive glaucoma medications was similar between treatment groups (1.8 medications Ahmed group vs 1.5 medications Baerveldt group, p = 0.07).⁵ The cumulative probability of failure (IOP > 21 mm Hg or not reduced > 20% from baseline, IOP < 5 mm Hg, additional glaucoma surgery, removal of the implant, or loss of light perception vision) was not significantly different between the two groups after one-year follow-up (16.4% Ahmed group vs 14.0% Baerveldt group, p = 0.52).

More patients in the Baerveldt group experienced early postoperative complications during the first three months after surgery (43% Ahmed group vs 58% Baerveldt group, p = 0.016) and serious complications associated with reoperation and/or vision loss of two or more Snellen lines (20% Ahmed group vs 34% Baerveldt group, p = 0.014). No significant difference in the rate of late postoperative complications was observed between the two treatment groups (29% Ahmed group vs 37% Baerveldt group, p = 0.16).

■ Ahmed Glaucoma Valve and Single-Plate Molteno Implants Study

Nassiri and colleagues reported the results of a prospective randomized study that compared the Ahmed glaucoma valve implant and single-plate Molteno implant (Molteno Ophthalmic Limited) in 92 patients with refractory glaucoma conducted at three clinical centers in Iran.⁶

The Ahmed glaucoma valve implant.

A Baerveldt shunt being positioned for implantation.

The rate of surgical failure (IOP > 21 mm Hg, IOP < 5mm Hg, phthisis bulbi, loss of light perception vision, removal of the implant, reoperation for glaucoma, or any devastating intraoperative or postoperative complication) was similar for both treatment groups after two-year follow-up (16% Molteno group vs 18% Ahmed group). The Molteno group had a greater percentage drop in IOP from baseline at 2 years (49.7% Molteno group vs 41.9% Ahmed group, p = 0.049), but the mean number of glaucoma medications was not significantly different between the two groups (1.41 Molteno group vs 1.03 Ahmed group).

Patients were censored from analysis at the time of failure, which was related to inadequate IOP reduction in all patients. Postoperative complications were comparable between the Molteno and the Ahmed groups, and no devastating complications were observed in either treatment group.

■ Ahmed Versus Baerveldt (AVB) Study

AVB study is another multicenter randomized clinical trial comparing the safety and efficacy of the Ahmed glaucoma valve implant and 350 mm² Baerveldt glaucoma implant.

A total of 238 patients with refractory glaucoma were recruited at seven clinical centers.⁷ The cumulative probability of failure (IOP > 18 mm Hg or not reduced ≥ 20% from baseline, IOP < 5 mm Hg, vision-threatening complications, additional glaucoma procedures or loss of light perception vision) was higher in the Ahmed group at one year (43% Ahmed group vs 28% Baerveldt group, p = 0.02).⁸ The Baerveldt group had lower mean IOP (16.5 mm Hg Ahmed group vs 13.6 mm Hg Baerveldt group, p < 0.001) and required less medical therapy (1.6 medications Ahmed group vs 1.2 medications Baerveldt group, p = 0.03) after one year.

The rate of postoperative complications was similar with both implants (45% Ahmed group vs 54% Baerveldt group, p = 0.19). A greater number of interventions were needed in the Baerveldt group during the first year of follow-up (26% Ahmed group vs 42% Baerveldt group, p = 0.007).

Comparing Tube Shunts and Trabeculectomy

■ Ahmed Vs. Trabeculectomy Study

Wilson and coworkers compared the outcomes of the Ahmed glaucoma valve implant and trabeculectomy in a randomized clinical trial involving 117 patients.⁹ The study was performed in Saudi Arabia and Sri Lanka, and it involved patients with all glaucoma types and some eyes that had undergone previous ocular surgery.

Mean IOP was lower in the trabeculectomy group at one year (11.4 mm Hg trabeculectomy group vs 17.2 mm Hg Ahmed group, p = 0.01), and the Ahmed group required more medical therapy at last follow-up (16% trabeculectomy group vs 35% Ahmed group, p = 0.01). The cumulative probability of success (IOP < 21 mm Hg and > 15% reduction from baseline, IOP > 5 mm Hg, no additional glaucoma surgery, and no loss of light perception vision) was similar between the two treatment groups after one-year follow-up (83.6% trabeculectomy group vs 88.1% Ahmed group, p = 0.43).

A follow-up study continued recruitment in Sri Lanka to enroll a total of 123 patients with primary open-angle or angle-closure glaucoma without prior ocular surgery.¹³ With a mean follow-up of 31 months, no significant differences between the trabeculectomy and Ahmed groups were observed with respect to mean IOP (13.6 mm Hg trabeculectomy group vs 13.1 mm Hg Ahmed group) and mean number of glaucoma medications (0.93 medications trabeculectomy group vs 1.13 medications Ahmed group, p = 0.34) at final follow-up. The cumulative probability of success was also similar between treatment groups at last follow-up (68.1% trabeculectomy group vs 69.8% Ahmed group, p = 0.86).

The Molteno glaucoma implant.

■ Primary Tube Versus Trabeculectomy (PTVT) Study

The Primary TVT study is a multicenter randomized clinical trial designed to compare the safety and efficacy of tube shunt surgery and trabeculectomy in patients without prior ocular surgery. The trial is currently recruiting a total of 242 patients with low-risk glaucoma and no previous incisional eye surgery at 15 clinical centers. Enrolled patients are randomly assigned to treatment with a 350-mm² Baerveldt glaucoma implant or trabeculectomy with MMC (0.4 mg/ml for two minutes). The study currently has 168 patients and results will be provided when they become available.

■ Tube Versus Trabeculectomy (TVT) Study

The TVT study is a multicenter randomized clinical trial comparing the safety and efficacy of tube shunt surgery to trabeculectomy with MMC in patients with previous ocular surgery. A total of 212 patients were enrolled at 17 clinical centers who had prior cataract and/or glaucoma filtering surgery, and they were randomly assigned to treatment with a 350-mm² Baerveldt glaucoma implant or trabeculectomy with MMC (0.4 mg/ml for four minutes).¹⁰ A higher success rate (IOP < 21 mm Hg and > 20% reduction from baseline, IOP > 5 mm Hg, no additional glaucoma surgery and no loss of light perception vision) was seen in the tube group after five years of follow-up (70.2% tube group vs 53.1% trabeculectomy group, p = 0.002).¹¹ Both treatment groups had similar mean IOP (14.4 mm Hg tube group vs 12.6 mm Hg trabeculectomy group, p = 0.12) and mean number of glaucoma medications (1.4 medications tube group vs 1.2 medications trabeculectomy group, p = 0.23) at five years.

Postoperative complications were more common in the trabeculectomy group during the first five years of the study (43% tube group vs 63% trabeculectomy group, p = 0.006), but no significant difference in the rate of serious complications associated with reoperation and/or vision loss of two or more Snellen lines was observed between treatment groups (22% tube group vs 20% trabeculectomy group, p = 0.79).¹²

Conclusions

Numerous retrospective case series and non-randomized prospective studies have provided important information comparing glaucoma surgical procedures. However, results from these studies must be interpreted with caution because selection biases may produce treatment groups with different underlying risk factors for failure. Randomized clinical trials aim to produce comparison groups that differ only by the treatment that their subjects receive, and they offer the highest level of evidence-based medicine for comparing treatments.

Similar results were reported in the ABC study and ABV study.^5,8 Both studies observed significantly greater IOP reduction with the Baerveldt implant compared with the Ahmed implant. A lesser need for glaucoma medical therapy was also seen after Baerveldt implantation in both trials, although this difference did not quite reach the level of statistical significance in the ABC study. The larger end plate of the Baerveldt implant likely explains its greater efficacy, as larger surface area plates are associated with greater pressure reduction.¹⁴ The Ahmed implant had a significantly lower rate of early postoperative complications relative to the Baerveldt implant in the ABC study, and a tendency toward a higher rate of postoperative complications following Baerveldt implantation was also seen in the AVB study. The valve mechanism in the Ahmed implant appears to provide an additional level of safety by minimizing the risk of hypotony-related complications in the immediate period after surgery.

Studies by Wilson and collaborators found similar success rates with the Ahmed glaucoma valve implant and trabeculectomy.^9,13 In contrast, the TVT study found that Baerveldt implantation had a higher success rate compared with trabeculectomy with MMC.¹¹ The differences in study findings may relate to differences in study populations, success and failure criteria, and retention during follow-up. Additionally, the Baerveldt glaucoma implant has an end plate with a larger surface area than the Ahmed implant, and evidence suggests that implants with larger surface area plates are more effective in reducing IOP.^5,8,14

Each of the landmark randomized clinical trials involving tube shunts has provided useful information to assist in surgical decision-making in similar patient groups. However, other factors must be considered when selecting a surgical procedure, including the surgeon's skill and experience with each operation and the characteristics of the individual patient. We look forward to additional follow-up data from several of these clinical trials. OM

References

1. Ramulu PY, Corcoran KJ, Corcoran SL, Robin AL. Utilization of various glaucoma surgeries and procedures in Medicare beneficiaries from 1995 to 2004. Ophthalmology. 2007;114:2265-2270.
2. Chen PP, Yamamoto T, Sawada A, et al. Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glaucoma Societies. J Glaucoma. 1997;6:192-196.
3. Desai MA, Gedde SJ, Feuer WJ, Whi W, Chen PP, Parrish RK. Practice preferences for glaucoma surgery: A survey of the American Glaucoma Society in 2008. Ophthalmic Surg Lasers Imaging. 2011;42:202-208.
4. Barton K, Gedde SJ, Budenz DL, et al. The Ahmed Baerveldt Comparison Study: Methodology, baseline patient characteristics, and intraoperative complications. Ophthalmology. 2011;118:435-442.
5. Budenz DL, Barton K, Feuer WJ, et al. Treatment outcomes in the Ahmed Baerveldt Comparison Study after one year of follow-up. Ophthalmology. 2011;118:443-452.
6. 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.
7. Christakis PG, Kalenak JW, Zurakowski D, et al. The Ahmed Versus Baerveldt Study. Design, baseline characteristics, and intraoperative complications. Ophthalmology. 2011;118:2172-2179.
8. Christakis PG, Tsai JC, Zurakowski D, et al. The Ahmed Versus Baerveldt Study. One-year treatment outcomes. Ophthalmology. 2011;118:2180-2189.
9. Wilson MR, Mendis U, Smith SD, Paliwal A. Ahmed glaucoma valve implant vs. trabeculectomy in the surgical treatment of glaucoma: A randomized clinical trial. Am J Ophthalmol. 2000;130:267-273.
10. Gedde SJ, Schiffman JC, Feuer WJ, et al. The Tube Versus Trabeculectomy Study: Design and baseline characteristics of study patients. Am J Ophthalmol. 2005;140:275-287.
11. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus Trabeculectomy Study after five years of follow-up. Am J Ophthalmol. In press.
12. Gedde SJ, Herndon LW, Brandt JD, et al. Postoperative complications in the Tube Versus Trabeculectomy Study (TVT) during five years of follow-up. Am J Ophthalmol. In press.
13. Wilson MR, Mendis U, Paliwal A, Haynatzka V. Long-term follow-up of primary glaucoma surgery with Ahmed glaucoma valve implant versus trabeculectomy. Am J Ophthalmol. 2003;136:464-470.
14. Heuer DK, Lloyd MA, Abrams DA, et al. Which is better? One or two? A randomized clinical trial of single-plate versus double-plate Molteno implantation for glaucomas in aphakia and pseudophakia. Ophthalmology. 1992;99:1512-1519.

Dr. Gedde is professor of Ophthalmology and Residency Program Director at Bascom Palmer Eye Institute in Miami. He is a study chairman for the Tube Versus Trabeculectomy (TVT) Study and Primary Tube Versus Trabeculectomy (PTVT) Study, and an investigator in the Ahmed Baerveldt Comparison (ABC) Study. He is also a consultant for Alcon, Allergan, Lumenis and Merck.