Five-Year Clinical Outcomes of Trabectome Surgery at a Single Glaucoma Center

Purpose​: To analyze the five-year results of Trabectome ab interno trabeculectomy of a single glaucoma center. Method​: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤21 mm Hg, or >20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). Results: ​The retention rate for five years follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4 and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR=0.27, P=0.001), younger age (HR=0.25, P=0.02), and higher central corneal thickness (HR=0.18, P= 0.01). Pseudoexfoliation was associated with a higher success rate (HR= 0.39, P=0.02). ​IOP was decreased significantly from 20.0±5.6 mmHg at baseli​ne to 15.6±4.6 mmH​g at 5-year follow-up (P=0.001). The baseline number of glaucoma medications was 1.8±1.2, which decreased to 1.0±1.2 medications at 5 years. Conclusion​: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate. A higher baseline IOP, older age, thinner cornea, and pseudoexfoliation glaucoma were associated with a higher success rate.


Introduction
Management of glaucoma has undergone significant changes with a trend towards earlier microincisional glaucoma surgery (MIGS) instead of filtering surgery later in the course of the disease.Ab interno trabeculectomy (AIT) with the Trabectome (NeoMedix Corp., Tustin, CA, USA) was among the first MIGS procedures and ablates the trabecular meshwork and inner wall of Schlemm's canal (SC), the primary sites of outflow resistance in the pathophysiology of glaucoma [1] .The Trabectome surgical system creates a high-frequency alternating current at the tip of the handpiece to molecularize and aspirate the trabecular meshwork without dragging adjacent structures [2,3] .The released energy is limited to the space between the two electrodes, and the outer wall of SC is shielded by a footplate.The collapsible nature of the plasma bubble is akin to a disruptive laser and prevents thermal damage to the adjacent tissue.This process is different from cautery that generates heat to coagulate tissue, as occasionally mischaracterized.
Many of the reported case series involve a database that the manufacturer is required to maintain as part of a post-market surveillance, and it includes the first 20 surgeries when new Trabectome surgeons become certified [1,[12][13][14] .The most recent update on this dataset reported a 26% reduction of IOP from the baseline 7.5 years after surgery with a success rate of 60% on 1.6 drops [14] .While useful, this data may be biased by reporting more data of less experienced surgeons and have limited follow up and patient retention [15] .The largest and most recent study of these started with 5435 eyes, but only 37 remained for the final analysis [14] .
The purpose of our study was to report the long-term outcomes of Trabectome procedure in a cohort of patients in a single glaucoma center with a high retention rate.

Methods
An Institutional Review Board approval was obtained from the University of Pittsburgh Human Subjects Research Committee.We followed the tenets of the Declaration of Helsinki and regulations of the Health Insurance Portability and Accountability Act.Patients who underwent Trabectome surgery at our glaucoma center between September 2010 and December 2012 were identified using current procedural terminology (CPT) codes and included in the study.Patients were included regardless of same-session phacoemulsification because the impact of same-session phacoemulsification on IOP is negligible in Trabectome surgery [16,17] .
Exclusion criteria were a history of incisional and angle surgeries, combined glaucoma surgeries, and less than five years follow-up.Information collected included demographic data, types of glaucoma, preand postoperative intraocular pressures (IOP), baseline ocular biometric characteristics including axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), number of pre-and postoperative glaucoma medications, visual field mean deviation (MD), visual field index (VFI), type of surgery, and intra-and postoperative complications.Glaucoma severity was based on the Advanced Glaucoma Intervention Study (AGIS) system [18] .At each postoperative visit, BCVA, IOP, glaucoma medications, and complications were noted.The primary outcome measure was success and defined as 5 < IOP ≤ 21 mmHg, ≥ 20% reduction of IOP from baseline at two consecutive visits, no need for further glaucoma surgery, and no loss of light perception.Qualified success was defined as achieving success with or without medications.Patients who achieved success without medication were labeled as complete success.A Kaplan Meier survival analysis was used to evaluate the success rates.The secondary outcome measures were IOP, glaucoma medications, and complications.Risk factors for success and failure were identified using the Cox proportional hazards ratio (HR) model with multivariate analysis.

Surgical technique
Trabectome surgery was performed first in cases where a phacoemulsification and lens implantation was performed in the same surgery.The patient's head was rotated away from the surgeon by 30˚ while the microscope was tilted towards the surgeon by the same amount.A temporal 1.6 mm incision was made 2 mm anterior to the limbus and parallel to the iris plane.The Trabectome was inserted through the incision and positioned across the AC at the nasal angle.The tip of the Trabectome was inserted into Schlemm's canal and engaged with the TM.The aspiration and ablation were activated with the power set to 0.8 to 1 watts.The same was done in the opposite direction to remove the TM over approximately 160° total.The tip was withdrawn from the anterior chamber, and the incision was hydrated.All glaucoma medications were discontinued after the surgery and resumed if the IOP was not within the target range.All patients received pilocarpine four times a day for one month followed by three times a day for a second month, a practice recently demonstrated to be unnecessary [8] .

Statistical analysis
All analyses were performed using SPSS software (SPSS Statistics for Windows, Version 25, Armonk, NY, IBM Corporation).Frequency, percent, mean±SD, median, and range were used to describe the data.To compare the change in IOP and number of medications, we used an interaction analysis within a linear mixed model.To evaluate the baseline differences between groups, we used the T-test, Chi-Square, and Fisher's exact test.Kaplan-Meier survival plots were constructed to assess the long-term survival rates and compared using the log-rank test.A Cox proportional Hazard model was used to find risk factors for failure and to estimate the adjusted hazard ratio of each factor.Statistical significance was set at p<0.05.Success was defined as IOP <21 mmHg and a >20% reduction from baseline with no need for additional glaucoma surgery.

Results
Patients typically had open angle glaucoma refractory to medical therapy, or they had visually significant cataracts in the setting of glaucoma on medical therapy.Ninety-three eyes underwent AIT during this period of which 32 were excluded for the following reasons: four (12.5%) individuals died before the 5-year visit, 18 (56%) eyes had AIT combined with a Baerveldt glaucoma implant [19] , four (9.3%) eyes had a complicated cataract surgery after AIT, and seven (21.8%) eyes were resident cases.All patients were phakic at the time of surgery and phacoemulsification was combined with AIT in all cases.
Table 1 presents baseline demographics.The mean age of study participants was 71.9 ±10.2 years, and 50.8% of the patients were female (P=0.911).Primary open-angle glaucoma (POAG) was the most common diagnosis (62.3%) followed by exfoliation glaucoma (XFG, 14.8%), primary angle closure glaucoma (PACG, 8.2%), pigmentary glaucoma (PG, 6.6%), and others that included steroid-induced or anti-VEGF agent related glaucoma (8.2%).The baseline glaucoma severity was characterized based on the AGIS system [18] was mild in (34.4%), moderate (26.3%), and severe (39.9%) of eyes.days after the surgery.Temporary postoperative IOP surges of more than 10 mmHg were observed in 27.4% of patients, and almost all them occurred within the first month.No serious vision-threatening complications occurred.

Discussion
Trabectome surgery was effective in reducing the IOP and number of glaucoma medications at the 5-year follow-up visit.The success rate at five years was 68%, higher than in case series derived from the manufacturer maintained dataset [1,[12][13][14] .The main reason for failure was uncontrolled IOP.A possible explanation for a higher success rate in our study is that all surgeries were performed by a more experienced surgeon.On average, new surgeons need at least five eyes to become comfortable and safe with the procedure [20] , but it takes almost 30 eyes to consistently maximize outflow [20] , well beyond the initial 20 cases included the manufacturer dataset.It is still possible that our study underestimates current success rates because the device had only been introduced in our clinic in 2009.Additionally, many patients who reside in more remote locations with successful outcomes can be managed by their primary eye care provider and do not always follow up with the surgeon unless the necessity arises.
On average, the IOP was lowered by approximately 20% to near 15 mm Hg while decreasing medications by less than one, with a low rate of serious complications.As seen in previous reports, IOP remained mostly stable six months postoperatively [13,21,22] .Two patients in our study lost two lines of visual acuity during the five years observed and had advanced glaucoma with splitting fixation with a baseline HVF MD of -18.23 and -23.7 dB.Phacoemulsification combined with AIT does not in itself cause a change of the refractive outcomes when compared to phacoemulsification alone [23] .Ahuja et al. noted that 5% of patients in their series lost more than two lines of Snellen visual acuity, but a cause was not provided [24] .
The multivariate analysis of risk factors showed that patients with pseudoexfoliation glaucoma have a 36% higher chance of success in comparison to POAG reflecting the experience of other investigators [24][25][26][27] .
Similar to other secondary open angle glaucomas that primarily affect the trabecular meshwork [5,7,28] , exfoliation glaucoma responds well to trabecular ablation that removes the diseased tissues while at the same time one of the primary sources of the pseudoexfoliative material, the lens, is removed in cataract surgery.Our results also match the previously reported findings that a higher baseline IOP is associated with higher IOP reduction [13,22,27] .
We observed an association between a thicker CCT and risk of failure.CCT is reflecting the corneal and scleral biomechanical prop erties, in particular, corneal rigidity [29][30][31][32] .After trabecular ablation, outflow is only limited by the remaining downstream outflow resistance in the outer wall of Schlemm's canal, in collector channels and episcleral veins.These channels have features that indicate that they may be able to regulate the outflow resistance [33][34][35] .More research is needed to clarify the role of corneal biomechanics in the outcome of angle surgeries.
Our study was limited by its retrospective nature and a relatively low number of patients which is the result of only including patients with full, 5-year datasets.A ll patients underwent Trabectome surgery combined with cataract extraction which we have shown does not affect the IOP reduction [12,16,22] but may create a bias towards milder glaucomas at baseline.This study was conducted at a single tertiary academic referral center, and the results cannot easily be generalized to other practice facilities.
In summary, this single-center case series had a high patient retention rate and showed a high long-term safety and efficacy of Trabectome surgery.Risk factors for failure were a lower baseline IOP, younger age, and higher central corneal thickness while pseudoexfoliation glaucoma increased the chances of success.

Figure 1 :
Figure 1: Kaplan-Meier survival plots with success defined as a final IOP of ≤ 21 mmHg and a 20% reduction from baseline.A) Plot for all eyes.B) Preoperative intraocular pressure of 21 mmHg or higher versus less than 21 mmHg.C) Age 65 or older versus younger than 65 years.

Figure 2 :
Figure 2: Preoperative and postoperative mean IOP within five years follow up.