BLOG: The PTVT Trial and Clinical Applications

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The views expressed in this blog are those of their respective contributor(s) and do not represent the views of Ophthalmology Times® or MJH Life Sciences®

Background

Traditional glaucoma surgery (trabeculectomy and glaucoma drainage device implantation) is still considered the most effective surgical procedure for intraocular pressure (IOP) reduction despite many new surgical devices and procedures available to clinicians.

While there have been numerous studies investigating success rates of trabeculectomy and tube shunt implantation, it is difficult to compare these data directly because of varying outcome measures, a lack of standardized surgical techniques, and dissimilar patient populations. The Tube Versus Trabeculectomy (TVT) Study, a multicenter, prospective, randomized control trial, evaluated the success of tube shunt implantation vs trabeculectomy in patients with a history of prior cataract surgery and/or incisional glaucoma surgery and found the cumulative probability of failure during 5 years of follow-up was lower in the tube group compared to the trabeculectomy group (29.8% vs 46.9%, p=0.002).

Complications were higher in the trabeculectomy group compared to the tube shunt group, though most were transient and self-limited. This study provided valuable insights and comparative data to help guide clinicians in choosing the best surgical option for their patients; however, given that the TVT study assessed the efficacy and safety of incisional glaucoma surgery in patients with prior ocular surgery, clinicians still lacked robust data to help guide surgical decision making for patients with no prior surgery who had inadequate IOP control.

Study Design

The PTVT study was a multicenter, prospective, randomized control trial investigating the safety and efficacy of primary trabeculectomy with mitomycin-C (MMC) versus tube shunt implantation (350-mm² Baerveldt glaucoma implant) in eyes with no prior history of ocular surgery.

Patient population

Patients aged 18 to 85 years old with IOP ³18 mm Hg and £40 mm Hg on maximum medical therapy with no prior incisional surgery were eligible for the study. Patients were recruited at 16 clinical centers throughout the United States.

Outcome Measures

The primary endpoint of the PTVT study was the cumulative rate of surgical failure at 1 year. Surgical failure was defined as IOP >21 mm Hg or reduced less than 20% from baseline at 2 consecutive follow-up visits after 3 months, IOP £5 mm Hg, reoperation for glaucoma, or loss of light perception vision. Secondary outcomes included IOP, glaucoma medical therapy, visual acuity, and surgical complications.

Demographic Data

242 eyes of 242 patients were enrolled in the study. There were no statistically significant differences in demographics at the time of enrollment. Across the entire study population, mean age was 61.4 ± 11.8 years, 66% of patients were male, mean baseline IOP was 23.6 ± 5.3 mm Hg on 3.2 ± 1.1 glaucoma medications, and 90% of eyes had a diagnosis of primary open-angle glaucoma.

Primary Outcomes

Overall, the rate of failure was higher in the tube group compared to trabeculectomy at 1 year follow-up (20% vs 8%, p =0.02). At 3 years of follow up the failure rate remained higher in the tube group, but this difference did not reach statistical significance (39% vs 30%, p =0.17).

When comparing complete success at 1 year, defined as IOP > 5 mm Hg and < 21 mm Hg with no additional glaucoma medications, the percentage of patients in the tube group with complete success was significantly lower versus the trabeculectomy group (14% vs 59%, p < 0.001). At 3 years, 13% of patients in the tube group were still classified as complete successes versus 44% in the trabeculectomy group (p<0.001). The percentage of patients with qualified success (IOP within limits already defined but with topical glaucoma medications) at years 1 and 3 were 67% and 48%, respectively, in the tube group vs 33% and 27% in the trabeculectomy group.

Kaplan-Meier survival analysis showed that there was a 17.3% cumulative probability of surgical failure in the tube group compared to 7.9% in the trabeculectomy group at 1 year follow-up (p=0.01). Interestingly when comparing the failure rate of each group with more stringent IOP goals, the authors found that if the upper IOP limit was lowered to 17 mm Hg, the rate of failure was still significantly higher in the tube group compared to trabeculectomy group (20.6% vs 9.6% p=0.01). With an upper limit of 14 mm Hg, the difference did not reach statistical significance (28.1% vs 20.0%, p=0.15). At 3 years of follow-up, the cumulative failure rates were similar in both groups (33% tube shunt vs 28%, trabeculectomy p=0.17). When comparing failure rates at the different IOP cutoffs at 3 years, there was still a higher probability of failure in the tube group at an upper limit of 17 mm Hg, but no difference between groups at an IOP upper limit of 14 mm Hg.

Secondary Outcomes

Mean IOP at baseline was similar in the tube and trabeculectomy groups (23.3 ± 4.9 mm Hg vs 23.9 ± 5.7 mm Hg, p=0.35). The mean IOP at 1 year follow-up in the tube group was 13.8 ± 4.1 mm Hg compared to 12.4 ± 4.4 mm Hg in the trabeculectomy group (p=0.01). At 3 years, mean IOP in the tube group was 14.0 ± 4.2 mm Hg compared to 12.1 ± 4.8 mm Hg in the trabeculectomy group (p=0.008).

Mean IOP reduction from baseline at 1 year follow-up was greater in the trabeculectomy group (46.0% vs 37.5%, p=0.02) and a higher percentage of patients in the trabeculectomy group were able to achieve an IOP <14 mm Hg at 1 year follow up, although this was not statistically significant (71% vs 60%, p=0.11). At the 3 year follow-up, mean IOP reduction from baseline was still higher in the trabeculectomy group compared to tube group, but this did not reach statistical significance (46% vs 39%, p=0.08). Baseline number of glaucoma medications was also similar in the trabeculectomy and tube groups (3.2 ± 1.1 vs 3.1 ± 1.1, p=0.56). At 3 years, patients in the trabeculectomy group were using fewer glaucoma medications compared to patients in the tube group (1.2 ± 1.5 vs 2.1 ± 1.4, p <0.001).

The rates of surgical complications were also compared between groups. Early complications were those occurring within 1 month of surgery, while late complications were categorized as any complications after that. There were more early complications in the trabeculectomy group (33% vs 20%, p=0.03), while the number of late complications were similar in both groups at 3 years (22% in tube group vs 25% in trabeculectomy group, p=0.65).

Clinical Applications

The PTVT study is the first prospective head-to-head comparison data of the safety and efficacy of tube shunt implantation versus trabeculectomy in surgery-naïve eyes in a large study with standardized surgical procedures, a patient population stratified by age and ethnicity, and with similar baseline characteristics. The data from the PTVT study provide valuable insights that will undoubtedly help clinicians in deciding the appropriate procedure for their patients with inadequate IOP control on maximal medical therapy.

There are numerous clinical pearls to be gleaned from the 1 year and 3 year PTVT follow-up data.

First, the traditional thinking amongst clinicians tends to be that patients have final IOPs in the mid-high teens range after tube shunt implantation. However, the PTVT data demonstrated that lower mean IOPs can be achieved. IOP in the tube shunt group at 3 years was 14.0 ± 4.2 mm Hg with 61% of tube shunt patients achieving an IOP below 14 mm Hg.

Second, trabeculectomy had a lower rate of failure and higher likelihood of achieving complete success at both 1 year and 3 years of follow-up. In patients who have trouble with adherence to glaucoma medications or have ocular surface conditions that preclude the use of topical medications, trabeculectomy may be the preferred option for IOP reduction.

Third, the rate of failure differed based on baseline IOP. In a report published in Ophthalmology, the authors performed a risk factor analysis to identify any demographic or clinical factors that may have predicted failure in either group. Only baseline IOP was found to be significantly associated with failure in both univariate (P<0.001) and multivariate (P<0.001) analyses. Patients were stratified by baseline IOP into three groups: IOP less than 21 mm Hg, IOP of 21 to 25 mm Hg, and IOP greater than 25 mm Hg. In the tube group, the cumulative failure rate was 60% in patients with baseline IOP < 21 mm Hg, 21% in patients with baseline IOP 21 to 25 mm Hg, and 10% in patients with baseline IOP > 25 mm Hg. In the trabeculectomy group, the cumulative probability of failure was 39% in patients with baseline IOP < 21 mm Hg, 14% in patients with baseline IOP 21 to 25 mm Hg, and 30% in patients with baseline IOP > 25 mm Hg. These data suggest that baseline IOP is an important clinical factor in deciding the optimal procedure for patients. In patients with lower baseline IOP, trabeculectomy is more likely to succeed compared to a tube shunt.

The data from the PTVT study are highly valuable in providing clinicians guidance when they need to choose the most appropriate next step in management for glaucoma patients with inadequately controlled IOP on maximum medical therapy and no history of ocular surgery. In an environment of ever-expanding possible surgical interventions for IOP reduction including innumerable MIGS procedures, which overall are safer but less effective in reducing IOP, clinicians will need to critically assess the degree of IOP reduction desired, the risk of surgical complications, and patient factors including ability to tolerate glaucoma medications when choosing the best procedure for each patient. The PTVT data thus far and the upcoming 5 year follow-up data will continue to be important in guiding this decision.

Take-Home-Points

Patients may require 1 or more glaucoma medications after tube shunt implantation, but a majority of patients can achieve an IOP of <14 mm Hg long-term.

Trabeculectomy has a lower risk of failure when compared to tube shunt implantation at 1 year of follow-up, and a lower but not statistically significant risk of failure at 3 years of follow-up. At both time points, a higher percentage of trabeculectomy patients required no additional glaucoma medications.

Baseline IOP is an important independent predictor of surgical failure, and tube shunts are more likely to fail in patients with baseline IOP < 21 mm Hg than in those with higher baseline IOP.