Extended pharmacological miosis is superfluous after glaucoma angle surgery: A retrospective study

Study design

This retrospective comparative study included all patients who underwent Trabectome surgery between July 2012 and October 2017 at the Eye and Ear Institute of the University of Pittsburgh, School of Medicine, in Pittsburgh, PA, United States. Patients were identified using current procedural terminology codes of Eye and Ear Institute, University of Pittsburgh.

Participants

Patients were included regardless of same-session phacoemulsification, because the impact of same-session phacoemulsification on IOP is negligible in trabectome surgery^17,18. Eyes were categorized as P- if no pilocarpine was used after the surgery, and P+ if pilocarpine was administered postoperatively.

Exclusion criteria were a history of incisional and angle surgeries, combined glaucoma surgeries, use of pilocarpine in the contralateral eye, any systemic medication with parasympathomimetic activities, and less than 3 months 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), number of pre-and postoperative glaucoma medications, visual field mean deviation (MD), visual field index (VFI), type of surgery, use of pilocarpine eye drop after the surgery, and intra- and postoperative complications.

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 success rates. The secondary outcome measures were IOP, glaucoma medications, and complications.

Surgical technique

In the case of combined phacoemulsification, trabectome (NeoMedix, Tustin, CA, USA) portion was performed first. Both the patient’s head and microscope were tilted 30° away from the surgeon. 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 along the nasal angle. The tip of the trabectome was inserted into Schlemm’s canal and engaged with the TM. The aspiration and ablation was activated with the power set to 0.8 to 1W and the TM removed over approximately 160°. The tip was withdrawn from anterior chamber and the incision was hydrated to achieve watertightness. All glaucoma medications were discontinued after the surgery and were resumed if IOP was not within target range. In P+, 1% pilocarpine was used 4 times a day for one month followed by three times a day for a second month.

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 evaluate the baseline differences between the two study groups, we used the T-test, Mann Whitney, and Chi-Square test. To compare the change in IOP and number of medications between the two groups or within a group, we used an interaction analysis within a linear mixed model. To compare the amount of IOP reduction between the groups adjusted for the baseline values, we used an Analysis of Covariance (ANCOVA). Kaplan-Meier survival plots were constructed to assess the long-term survival rates and compared by 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. In the last step to obtain the most important factors, we used a backward variable elimination method based on the LR test. 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.

Baseline characteristics

A total of 187 eyes were included in this study. Eighty-six (46%) eyes in P- did not receive pilocarpine, while 101 (54%) in P+ did (Table 1). All patients were phakic at the time of surgery. Phacoemulsification was combined in 147 (79%) eyes (TP) while 40 eyes had trabectome surgery alone (T). The mean age of participants was 69.8±10.1 in P- and 70.5±9.4 in P+. Primary open-angle glaucoma was the most common diagnosis in both groups (73.3% and 63.2% in P- and P+, respectively, P=0.64). There were no significant differences between the study groups in terms of gender, preoperative intraocular pressure, central corneal thickness, axial length, visual field mean deviation, anterior chamber depth, baseline number of glaucoma medications, and type of glaucoma (Table 1).

Surgical success and risk factors for failure

Kaplan-Meier survival curves (Figure 1) indicated a mean survival of 34.03±2.35 months in P- and 38.32±1.94 months in P+ with no statistically significant difference between two groups (log rank:0.87 P=0.35). The addition of phacoemulsification did not make a difference on survival (T: 33.9±3.2 months; TP: 32.3±1.7, log-rank:0.81 P=0.36). Similarly, pilocarpine did not have a significant effect on survival in T or TP: T in P- had a survival of 32.5±5.4 and T in P+ had a survival of 33.3±3.9 months (log-rank:0.06, P=0.8). TP in P- had a survival of 33.6±2.4 and TP in P+ had a survival of 36.2±2.2 months (log-rank:0.81, P=0.36). The multivariate Cox regression model was stratified by group, age, baseline IOP, number of medications, glaucoma type, CCT, AC depth, lens thickness, axial length, Humphrey visual field (HVF) MD and VFI (Table 2). The final model with backward elimination only included baseline IOP (mmHg) and CCT (micron) with HR of 4.1 for 22<IOP<28, 3.7 for IOP>28, and 1.03 for CCT. This means that in patients with 22<IOP<28 the risk of failure was 4.1 times higher compared to patients with IOP<18 (P=0.015). Every 10 micron increase in baseline CCT increased the risk of failure by 30% (P=0.005).

Figure 1. Kaplan-Meier survival plots for P- and P+ with success defined as a final intraocular pressure of ≤ 21 mmHg and a 20% reduction from baseline.

Success rates were similar in both groups. Survival plots of P- and P+ for subgroup analysis separated by B) glaucoma surgery alone and C) same session phacoemulsification.

IOP change

IOP was decreased significantly from 20.2±6.8 mmHg at baseline to 15.0±4.8 mmHg at 12 months follow-up in P- (P=0.001, Figure 2). The corresponding numbers for P+ were 18.8±5.3 and 14.7±4.1, respectively (P=0.001). There was no significant difference in IOP at each follow-up visit between the two groups (Table 3). In subgroup analysis, considering the effect of phacoemulsification, there was no significant difference between IOPs of both groups in T and TP throughout the course of follow-up (Figure 2). Seven (8.1%) cases in P- and five (5%) in P+ experienced IOP spikes. There was no significant difference between the groups (P=0.153, based on the Chi-square test). The baseline number of glaucoma medications was 1.4±1.2 in P- and 1.4±1.2 in P+ (P=0.910). At month 12, the number of glaucoma medications was 1.0±1.2 drops in P- and 0.7±1.0 in P+ (P=0.082, Table 4).

Figure 2. Intraocular pressure (IOP) in P- and P+ groups.

A) IOP in P- was similar to P+ through follow-up duration. IOP in both groups for subgroup analysis separated by B) glaucoma surgery alone. Patients who received pilocarpine showed lower IOPs during the first month but the difference was not statistically significant. C) Same session phacoemulsification. Error bars represent standard deviations.

The postoperative hyphema was observed in 49% of the eyes. The mean duration of hyphema was 10.68±9.96 days in P- and 12±4.30 days in P+ (P= 0.48).