Five-year clinical outcomes of combined phacoemulsification and trabectome surgery at a single glaucoma center

Abstract

Purpose

To analyze the 5-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 mmHg, and > 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 5-year 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). Exfoliative glaucoma was associated with a higher success rate (HR = 0.39, P = 0.02). IOP was decreased significantly from 20.0 ± 5.6 mmHg at baseline to 15.6 ± 4.6 mmHg 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.

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.

Trabectome surgery has a nearly 15-year track record of use in different types of glaucoma including exfoliation [4], inflammatory [5], pigmentary [6], steroid induced [7], angle-closure glaucoma [8, 9], and complex glaucomas that have led to failure of other surgeries [10, 11].

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, 12–14]. 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-year follow-up. Information collected included demographic data, types of glaucoma, pre- and 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 [5, 19–21]. 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 1W. 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 1 month followed by three times a day for the 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 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.

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, 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. 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 (39.3%) of eyes.

Table 1.

Baseline characteristics

Variable		Value
Age (years)	Mean ± SD	71.9 ± 10.2
Gender	Female	31 (50.8%)
Eye	Right	34 (55.7%)
Axial Length (millimeter)	Mean ± SD	24 ± 1.5
CCT (micron)	Mean ± SD	548 ± 37
	Median (range)	547 (445 to 606)
AC Depth (millimeter)	Mean ± SD	3.35 ± 0.68
	Median (range)	3.24 (2 to 5.03)
Lens Thickness (milimeter)	Mean ± SD	4.23 ± 1.22
HVF MD (decibel)	Mean ± SD	−7.5 ± 8.9
HVFVFI	Mean ± SD	79 ± 28
	Median (range)	94 (2 to 100)
logMAR	Mean ± SD	0.56 ± 0.61
Baseline IOP (mmHg)	Mean ± SD	20 ± 5.6
	Median (range)	18 (9 to 30)
Baseline medications	Mean ± SD	1.84 ± 1.15
	Median (range)	1 (0 to 4)
Glaucoma type	POAG	38 (62.3%)
	XFG	9 (14.8%)
	CACG	5 (8.2%)
	PG	4 (6.6%)
	Mixed mechanism	5 (8.2%)
Glaucoma AGIS Stage	Mild	21 (34.4%)
	Moderate	16 (26.3%)
	Severe	24 (39.3%)

CCT central corneal thickness, AC anterior chamber, HVF Humphrey visual field, MD mean deviation, VFI visual field index, IOP intraocular pressure, POAG primary open angle glaucoma, XFG exfoliation glaucoma, CACG chronic angle closure glaucoma, PG pigmentary glaucoma, AGIS Advanced Glaucoma Intervention Study

Surgical success and risk factors for failure

The Kaplan-Meier survival curves (Fig. 1) indicated a mean survival of 49.8 ± 2.8 months. 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%. Corresponding values for the POAG subgroup was 83.7%, 78.3%, 76.7%, 70.1%, and 65.1%.

Fig. 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

The multivariate Cox regression model was stratified by age, gender, baseline IOP, number of medications, glaucoma type, central corneal thickness (CCT), anterior chamber depth (AC depth), lens thickness, axial length, Humphrey visual field mean deviation (HVF MD), and Humphrey visual field index (HVF VFI). The risk factors for failure were a lower baseline IOP (HR = 0.27, P = 0.001), younger age (HR = 0.25, P = 0.02), and a higher CCT (HR = 0.18, P = 0.01). Diagnosis of XFG (HR = 0.39, P = 0.02) was associated with higher chance of success at final follow up (Table 2).

Table 2.

Cox proportional hazard regression model

		Hazard ratio	P value
Gender		0.851 (0.458–1.65)	0.622
XFG		0.39 (0.29–0.46)	0.022
Lens thickness		0.83 (0.66–1.05)	0.134
Axial length		1.01 (0.8–1.25)	0.571
Baseline BCVA		0.87 (0.54–1.4)	0.933
Baseline medications	1 Medication	0.46 (0.107–1.98)	0.298
	2 Medications	0.82 (0.26–2.53)	0.732
	3 Medications	0.79 (0.79–3.05	0.735
	4 Medications	0.52 (0.52–5.8)	0.604
Baseline IOP		0.27 (0.13–0.59)	0.001

XFG pseudoexfoliation glaucoma, BCVA best corrected visual acuity, IOP: intraocular pressure

Intraocular pressure

IOP was decreased significantly from 20 ± 5.6 mmHg at baseline to 15.6 ± 4.6 mmHg at the 5-year follow-up (P = 0.001). The mean IOP at 1, 2, 3, and 4th year was 13.6 ± 3.4, 14.3 ± 3.9, 14.5 ± 3.9, and 14.7 ± 3.8. (P < 0.001) IOP remained unchanged 6 months after the surgery (Fig. 2). The baseline number of glaucoma medications was 1.84 ± 1.15. Patients received 0.79 ± 1.14, 1.03 ± 1.15, 1.07 ± 1.3, 1.09 ± 1.23, and 1.01 ± 1.15 medications at 1, 2, 3, 4, and 5 years follow up. However, only the difference between the first year and the baseline was statistically significant (P = 0.006). At the 5-year visit, 22 eyes (36%) did not have to use any glaucoma medications.

Fig. 2.

Preoperative and postoperative mean IOP within 5 years follow-up

Best corrected visual acuity

The mean BCVA at the baseline was 0.56 ± 0.61 logMAR, which changed to 0.42 ± 0.65 logMAR at final visit (P = 0.40). Only two patients lost more than two lines of visual acuity. Almost 40% of all cases had an advanced preoperative visual field loss. The mean deviation in this subgroup was −19.2 ± 6.2. The final visual acuity in this group was 0.53 ± 0.21 logMAR compared to 0.21 ± 0.13 in milder glaucoma (P = 0.02).

Reoperation for glaucoma

Subsequent glaucoma surgery was done when the IOP could not be controlled within the individual target range or when there was evidence of disease progression. Additional glaucoma surgeries included two Ahmed glaucoma valve (AGV) implantations, one trabeculectomy with MMC, and one cyclophotocoagulation.

Postoperative observations and complications

The most common observation was a postoperative microhyphema or layered hyphema on postoperative day 1 that occurred in 48.4%. The mean duration was 11.7 ± 10.0 days. Late-onset hyphema, defined as occurring more than 2 months postoperatively, was noted in 4.9% of eyes and ranged from 64 to 634 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 5 years was 68%, higher than in case series derived from the manufacturer-maintained dataset [1, 12–14]. 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 [22], but it takes almost 30 eyes to consistently maximize outflow [22], 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 nearly 15 mmHg while decreasing medications by less than one, with a low rate of serious complications. As seen in previous reports, IOP remained mostly stable 6 months postoperatively [13, 23, 24]. Two patients in our study lost two lines of visual acuity during the 5 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 [25]. 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 [26].

The multivariate analysis of risk factors showed that patients with exfoliation glaucoma have a 36% higher chance of success in comparison to POAG reflecting the experience of other investigators [26–29]. Similar to other secondary open angle glaucomas that primarily affect the trabecular meshwork [5, 7, 30], 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, 24, 29].

We observed an association between a thicker CCT and risk of failure. CCT is reflecting the corneal and scleral biomechanical properties, in particular, corneal rigidity [31–34]. 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 [35–37]. 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. All patients underwent Trabectome surgery combined with cataract extraction which we have shown does not affect the IOP reduction [12, 16, 24] 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 exfoliation glaucoma increased the chances of success.