TVT Results for Clinicians

The Tube Versus Trabeculectomy (TVT) Study is a multicenter, randomized clinical trial comparing the safety and efficacy of tube-shunt surgery to trabeculectomy with mitomycin C (MMC) in patients with previous cataract or glaucoma surgery. Results of the TVT Study have been published through 3 years of follow-up.^1-5 This review highlights major findings in the study and their application to clinical practice.

Methodology

The design and methods of the TVT Study were previously described in detail.¹ In summary, the study recruited patients ages 18 to 85 who had previous trabeculectomy or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with IOP between 18 and 40 mm Hg on maximum tolerated medical therapy. A total of 212 eyes of 212 patients were enrolled at 17 clinical centers and randomly assigned to treatment, which included placement of a tube shunt (350-mm² Baerveldt glaucoma implant) in 107 patients and trabeculectomy with MMC (0.4 mg/mL for 4 minutes) in 105 patients. Outcome measures that were used to discriminate the two treatment groups included IOP, visual acuity, visual fields, surgical complications, glaucoma drugs, and failure (IOP > 21 mm Hg or not reduced by 20%, IOP < 5 mm Hg, reoperation for glaucoma, or no light-perception vision).

Interpretation of Results

IOP Reduction

Trabeculectomy with MMC and tube-shunt surgery both produced sustained IOP reduction to the low teens. Data on IOP at baseline and at the annual follow-up visits are presented in Table 1. The trabeculectomy group achieved significantly lower mean IOPs than the tube group at all follow-up visits during the first 3 months postoperatively, but no significant difference in the degree of IOP reduction persisted between treatment groups after 3 months.^2,5

Table 1. Intraocular Pressure and Medical Therapy in the TVT Study

Data are presented as mean ± standard deviation.

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A recent ophthalmic technology assessment (OTA) issued by a panel of glaucoma specialists provided an evidence-based summary of aqueous shunts.⁶ The OTA concluded that “if a very low IOP goal range is desirable, an aqueous shunt may be a poor choice for IOP control… Generally, the IOP will settle at higher levels (approximately 18 mm Hg) than after trabeculectomy.” This observation is contradicted by the TVT Study, which found mean IOP reduction to the low teens in both treatment groups throughout the study. Furthermore, 62% of patients in the tube group and 58% of patients in the trabeculectomy group had IOP < 14 mm Hg at 3 years (p = 0.76).

The more favorable IOP results with tube shunts in the TVT Study may relate to enrollment of eyes at lower risk of surgical failure than have historically undergone tube-shunt surgery (e.g., eyes with only previous clear cornea cataract extraction), and the study excluded several secondary glaucomas with a poorer surgical prognosis (e.g., neovascular glaucoma) than were included in other case series of tube shunts.

Glaucoma Medications

Tube-shunt surgery required more medical therapy than trabeculectomy with MMC during the first 2 years of the study, but glaucoma medication use equalized with longer follow-up. Medical therapy data are shown in Table 1. The need for supplemental medical therapy was significantly greater in the tube group during the first 2 postoperative years.³ However, the use of glaucoma medications progressively increased in the trabeculectomy group and remained stable in the tube group such that the mean number of medications did not differ between treatment groups at 3 years.⁵

Failure Rate

Trabeculectomy with MMC had a higher failure rate compared with tube-shunt surgery. Kaplan-Meier survival curves are shown in Figure 1. Cumulative probability of failure was 15.1% in the tube group and 30.7% in the trabeculectomy group at 3 years (p = 0.010, HR = 2.2, 95% CI = 1.2-4.1).⁵ No significant difference in the distribution of reasons for treatment failure was observed between treatment groups (p = 0.71).

Figure 1. Kaplan-Meier Plots of the Probability of Failure in TVT Study

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Vision Loss

Vision loss occurred at a similar rate with tube-shunt surgery and trabeculectomy with MMC. Reduction in visual acuity was observed in both groups during 3 years of follow-up, but Snellen and ETDRS visual acuity were similar between treatment groups at baseline and at 3 years.⁵ The rate of loss of 2 or more lines of Snellen visual acuity was not significantly different between the tube group (31%) and the trabeculectomy group (34%) after 3 years (p = 0.65). Many of the causes of vision loss, such as macular degeneration and diabetic retinopathy, were not directly attributable to the surgical procedures under study.

Complications

Early postoperative complications occurred more frequently after trabeculectomy with MMC than after tube-shunt surgery, but both procedures had similar rates of late postoperative or serious complications. Complications developing in the first month after surgery were significantly more common in the trabeculectomy group (37%) than the tube group (21%) (p = 0.026).⁵ Complications occurring after 1 month were similar in the tube group (28%) and trabeculectomy group (36%) through 3 years of follow-up (p = 0.70). The frequency of serious complications requiring a reoperation or producing loss of 2 or more Snellen lines of vision was not significantly different in the tube group (22%) and trabeculectomy group (20%) at 3 years (p = 0.58). Wound leaks (p = 0.004), dysesthesia (p = 0.018) and bleb leaks (p = 0.028) were significantly more common in the trabeculectomy group compared with the tube group. New motility disturbances developed more frequently in the tube group (9.9%) than the trabeculectomy group (0%) during the first year of follow-up (p = 0.005),⁴ and diplopia was more common in the tube group (5%) compared with the trabeculectomy group (0%) (p = 0.06).^4,5

Misinterpretation of Results

Complications

Some readers have mistakenly claimed that the rate of surgical complications after trabeculectomy with MMC was excessively high in the TVT Study. The overall rates of postoperative complications after trabeculectomy were actually comparable in the TVT Study to several other multicenter randomized clinical trials. Notably, the rate of perioperative complications during the first month after trabeculectomy was 50% in the Collaborative Initial Glaucoma Treatment Study (CIGTS)⁷ and 35% in the TVT Study.⁵ With longer follow-up, the rate of trabeculectomy complications was 60% in the TVT Study at 3 years, which is comparable to the rate of 53.6% in the Advanced Glaucoma Intervention Study (AGIS) among patients with at least 3 months of follow-up.⁸

The rates of specific complications are also remarkably consistent across these clinical trials, despite differences in study populations and length of follow-up. Many of the surgical complications observed in each of the clinical trials were transient and self-limited, such as anterior chamber shallowing and choroidal effusions. Prospective studies generally report higher complication rates than retrospective case series, because prospective designs actively seek to detect complications. For example, the TVT Study protocol required Seidel testing at every follow-up visit to accurately determine the incidences of wound and bleb leaks. Moreover, even when surgical complications are observed, these instances may not be documented in the medical record (especially if they are believed to be insignificant).

Success Rate

Some readers have incorrectly claimed that the success rate of trabeculectomy with MMC was lower than expected in the TVT Study. A recent ophthalmic technology assessment of aqueous shunts in glaucoma concluded that clinical failure of the various devices over time occurs at a rate of approximately 10% per year, which is approximately the same as the failure rate for trabeculectomy.⁶ The trabeculectomy failure rates in the TVT Study (13.5% at 1 year² and 30.7% at 3 years⁵) and Fluorouracil Filtering Surgery Study (FFSS) (16% at 1 year,⁹ 29% at 3 years,¹⁰ and 51% at 5 years¹¹) were consistent with this estimate, and both are multicenter, randomized clinical trials that recruited patients with previous cataract or glaucoma surgery and employed similar success and failure criteria.

In contrast, the failure rate of tube-shunt surgery averaged about 5% per year in the TVT Study (3.9% at 1 year² and 15.1% at 3 years⁵). The difference in treatment outcomes observed in the TVT Study was not the result of a trabeculectomy failure rate that was higher than expected, but rather relates to a tube-shunt failure rate that was lower than what has been reported in prior studies. The lower failure rate of tube-shunt surgery in the TVT Study likely involves enrollment of eyes at lower risk of failure than have historically undergone tube-shunt surgery.

Superiority

Some readers have inappropriately claimed that the TVT Study showed that tube-shunt surgery is a superior glaucoma procedure to trabeculectomy with MMC. Major outcomes of the TVT Study are summarized in Table 2. Patients who underwent tube-shunt surgery had a higher rate of surgical success than those who had trabeculectomy with MMC.⁵ Early postoperative complications also occurred less frequently after tube-shunt surgery compared with trabeculectomy with MMC. However, early IOP control and medication use favored trabeculectomy with MMC over tube-shunt surgery in the TVT Study.² A recent cost analysis indicated that the cumulative expense associated with tube-shunt surgery was significantly greater than with trabeculectomy with MMC during 5 years of follow-up in the TVT Study.¹² No significant differences between the two procedures were observed in IOP after 3 months, medication use after 2 years, vision loss, or the rates of late postoperative or serious complications.⁵

Table 2. Summary of Major Outcomes in the TVT Study

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The TVT Study does not demonstrate clear superiority of one operation over the other. Other factors must be considered when selecting a surgical procedure, including the surgeon’s skill and experience, the patient’s willingness to undergo repeat glaucoma surgery, and the surgeon’s planned surgical approach should failure occur. Additionally, the results of the TVT Study cannot be generalized to dissimilar patient groups.

Clinical Application

The TVT Study supports the expanded use of tube shunts beyond the surgical management of only refractory glaucoma. Tube-shunt surgery was shown to be effective in a patient population at lower risk of surgical failure than has traditionally had this procedure.⁵ The study results have prompted another multicenter, randomized clinical trial comparing tube-shunt surgery and trabeculectomy with MMC as an initial surgical procedure in low-risk eyes (i.e., the Primary Tube Versus Trabeculectomy Study). The TVT Study also demonstrated that low levels of IOP can be achieved with tube shunts in this patient group.⁵ The study offers a wealth of information that further defines the relative risks and benefits of two commonly performed glaucoma procedures. TVT Study data should be analyzed and interpreted critically, and appropriate conclusions may then be made to help surgeons in selecting the optimal glaucoma procedure for individual patients.¹³

References

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Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL, The Tube Versus Trabeculectomy Study Group. Treatment outcomes in the Tube Versus Trabeculectomy Study after one year of follow-up. Am J Ophthalmol. 2007;143(1):9-22.
Gedde SJ, Herndon LW, Brandt JD, BudenzDL, Feuer WJ, Schiffman JC, The Tube Versus Trabeculectomy Study Group. Surgical complications in the Tube Versus Trabeculectomy Study during the first year of follow-up. Am J Ophthalmol. 2007;143(1):23-31.
Rauscher FM, Gedde SJ, Schiffman JC, Feuer WJ, Barton K, Lee RK, Tube Versus Trabeculectomy Study Group. Motility disturbances in the Tube Versus Trabeculectomy Study during the first year of follow-up. Am J Ophthalmol. 2009;147(3):458-466.
Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL, TubeVersusTrabeculectomyStudy Group. Three-year follow-up of the Tube Versus Trabeculectomy Study. Am J Ophthalmol. 2009;148(5):670-84.
Minckler DS, Francis BA, Hodapp EA, Jampel HD, Lin SC, Samples JR, et al. Aqueous shunts in glaucoma: a report by the American Academcy of Ophthalmology. Ophthalmology. 2008;115(6):1089-1098.
Jampel HD, Musch DC, Gillespie BW, Lichter PR, Wright MM, Guire KE, Collaborative Initial Glaucoma Treatment Study Group. Perioperative complications of trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Am J Ophthalmol. 2005;140(1):16-22.
AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): Risk factors for failure of trabeculectomy and argon laser trabeculoplasty. Am J Ophthalmol. 2002;134:481-498.
The Fluorouracil Filtering Surgery Study Group. Fluorouracil filtering surgery study one-year follow-up. Am J Ophthalmol. 1989;108:625-635.
The Fluorouracil Filtering Surgery Study Group. Three-year follow-up of the fluorouracil filtering surgery study. Am J Ophthalmol. 1993;115:82-92.
The Fluorouracil Filtering Surgery Study Group. Five-year follow-up of the fluorouracil filtering surgery study. Am J Ophthalmol. 1996;121:349-366.
Challa P, Datta SK, Gedde SJ, Feuer WJ, Schiffman JC. Cost consequence analysis of the Tube vs. Trabeculectomy (TVT) Study l. Poster presented at: The 21st Annual AGS Meeting; March 4, 2011; Dana Point, CA.
Singh K, Gedde SJ, the Tube Versus Trabeculectomy Study Group. Interpretation and misinterpretation of results from the Tube Versus Trabeculectomy (TVT) Study. Int Ophthalmol Clin. 2011;51:141-154.