Effects of Postoperative Intravitreal Injections on Outcomes of Traditional Glaucoma Surgery in Patients with Preoperative Intravitreal Injections

To compare outcomes of glaucoma drainage device (GDD) implantation and trabeculectomies with and without postoperative intravitreal injections (IVIs) in glaucoma patients with a history of preoperative IVIs. Retrospective cohort study. A total of 133 eyes of 133 glaucoma patients who underwent GDD implantation or trabeculectomy with at least 1 IVI preoperatively between January 2005 and October 2020 at Massachusetts Eye and Ear. Chart review of glaucoma patients with traditional glaucoma surgery and at least 1 IVI before surgery. All statistical analyses were conducted with R statistical programming software. Intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), Kaplan-Meier success rates, adjusted hazard ratios (HRs), and complications. Baseline demographics were similar between the groups with and without postoperative IVIs. The group with postoperative IVIs had a higher proportion of diabetic retinopathy and retinal vascular occlusions than the group without postoperative IVIs, which had more eyes with age-related macular degeneration. Intraocular pressure, medication burden, and visual acuity were similar between groups at all time points except for IOP at 6 weeks, which was lower in the group with postoperative IVIs. The group with postoperative IVIs had significantly more preoperative IVIs than the group without postoperative IVIs (6.6 vs. 3.3, P = 0.017). For success defined as IOP reduction ≥ 20% with 5 < IOP ≤ 21 mmHg, Kaplan-Meier analyses demonstrated similar success rates between groups with and without IVIs. When stratified by the number of IVIs, success rates for the group with 7 or more IVIs were significantly higher than the success rates for the group with 0-6 IVIs (P = 0.005). Each additional postoperative IVI resulted in a 7.2% decrease in the hazard of failure to achieve our stated success criteria. With regard to late complications, the group with postoperative IVIs had a higher incidence of vitreous hemorrhage (18.5% vs. 3.2%, P = 0.039) than the group without postoperative IVIs. A higher number of postoperative IVIs, specifically 7 or more IVIs, may be associated with improved success rates of traditional glaucoma surgery in glaucoma patients who received IVIs before surgery

Outcomes of a combination of augmented MicroPulse and limited Continuous Wave Cyclophotocoagulation in patients with refractory glaucoma

Abstract Purpose To assess the safety and effectiveness of augmented MicroPulse (MP-TSCPC) with limited Continuous Wave Transscleral Cyclophotocoagulation (CW-TSCPC) in patients with refractory glaucoma. Methods Thirty-eight eyes of 38 patients underwent combined MP-TSCPC and CW-TSCPC at Massachusetts Eye and Ear. Kaplan–Meier survival curves and Wilcoxon paired sign rank tests were performed to evaluate intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity (BCVA), and adverse events. Results With success defined as IOP reduction ≥ 30% and IOP between 5 and 18 mmHg, the cumulative probability of success at 1 year and 1.5 years were 0.81 (95% confidence interval (CI), 0.68–0.96) and 0.65 (95% CI, 0.50–0.86), respectively. With success defined as IOP reduction ≥ 50% and IOP between 5 and 18 mmHg, the success probability at 1 year and 1.5 years were 0.72 (95% CI, 0.57–0.89) and 0.56 (95% CI, 0.40–0.78), respectively. IOP and medication burden reductions were significant at all follow-up visits compared to baseline. Average IOP decreased from 27.9 mmHg at baseline to 11.4 mmHg at 1 year (p < 0.001) and 10.0 mmHg at 1.5 years (p < 0.001). Average medication burden decreased from 3.8 to 1.7 at 1.5 years (p = 0.001). No significant differences in visual acuity were observed at any time point. No long-term sight-threatening complications due to the combined procedure were observed, and most of the complications observed were mild and transient. Conclusion In patients with refractory glaucoma, the combination of augmented MP-TSCPC with limited CW-TSCPC provides a significant IOP-lowering effect and decrease in medication burden without increased risk of postoperative complications

Outcomes of Anterior Chamber, Sulcus, and Pars Plana Glaucoma Drainage Device Placement in Glaucoma Patients

Purpose. To assess outcomes of anterior chamber (AC), sulcus, and pars plana (PP) glaucoma drainage device (GDD) placement in glaucoma patients. Patients and Methods. Retrospective evaluation of glaucoma patients who underwent GDD insertion in the AC, sulcus, or PP at Massachusetts Eye and Ear between November 2016 and May 2021. Patients who received AC, sulcus, and pars plana tubes were selected using simple random sampling, and the first 40 patients meeting inclusion criteria were analyzed. Main outcome measures were cumulative success probabilities from Kaplan-Meier (KM) analyses, intraocular pressure (IOP), medication burden, and complication rates. Results. The PP group had a larger proportion of Ahmed GDDs and was younger on average with less severe glaucoma compared to patients with AC or sulcus tubes. The PP group had a higher proportion of mixed-mechanism glaucoma and lower proportion of primary open-angle glaucoma. With success defined as IOP reduction ≥20% and 5 < IOP ≤ 21 mm Hg, the Kaplan-Meier cumulative success probabilities for all three GDD locations were not significantly different. No significant differences were found in complication rates between all groups after 3 months. Patients with PP GDD had significantly lower medication burden than those with AC or sulcus GDDs up to 1.5 years postoperatively (1.7 ± 1.1, 3.0 ± 1.4, and 2.8 ± 1.2 for PP, AC, and sulcus, respectively; P=0.017). Conclusion. PP GDDs may be more effective in lowering medication burden than AC or sulcus tubes without compromising long-term safety

Transscleral vs endoscopic cyclophotocoagulation: safety and efficacy when combined with phacoemulsification

To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. Retrospective cohort study of consecutive cases at Massachusetts Eye & Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively, undergoing additional glaucoma surgery, or the inability to maintain ≥ 20% IOP reduction from baseline with IOP between 5-18 mmHg while maintaining ≤ baseline medications. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. Sixty-four eyes from 64 patients (25 phaco/ECP, 20 phaco/MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 ± 6.7 years) or length of follow-up time. Baseline IOPs were significantly different between groups (15.78 ± 4.7 mmHg phaco/ECP, 18.37 ± 4.6 mmHg phaco/MP-TSCPC, 14.30 ± 4.2 mmHg phaco alone, p = 0.02). Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42%) and phaco/ECP (48%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40%). Surgical failure was less likely in eyes in the phaco/MP-TSCPC (3.40 times, p = 0.005) and phaco/ECP (1.40 times, p = 0.044) groups compared to phaco alone based on the Kaplan-Meier survival criteria. These differences maintained statistical significance when differences in preoperative IOP were taken into account using the Cox PH model (p = 0.011 and p = 0.004, respectively). Additionally, surgical failure was 1.98 times less likely following phaco/MP-TSCPC compared to phaco/ECP (p = 0.038). This difference only approached significance once differences in preoperative IOP were accounted for (p = 0.052). There was no significant difference in IOP reduction at 1 year between groups. Mean IOP reductions at 1 year were 3.07 ± 5.3 mmHg from a baseline of 15.78 ± 4.7 in the phaco/ECP group, 6.0 ± 4.3 mmHg from a baseline of 18.37 ± 4.6 in the phaco/MP-TSCPC group and 1.0 ± 1.6 from a baseline of 14.30 ± 4.2 mmHg in the phaco alone group. There were no differences in complication rates among the three groups. Both Phaco/MP-TSCPC and phaco/ECP appear to provide superior efficacy for IOP control when compared to phaco alone. All three procedures had similar safety profiles

Netarsudil as an Adjunctive Therapy: Efficacy and Factors Contributing to a Favorable IOP-Lowering Effect

Purpose. The aim of the study is to assess netarsudil's intraocular pressure (IOP)-lowering potential when prescribed as an adjunctive agent, to examine the effect of baseline IOP on patients' response to netarsudil, and to explore patients' characteristics predictive of pronounced responses to netarsudil. Methods. This is a single-center, multiprovider retrospective cohort study set at Massachusetts Eye and Ear. Patients with a diagnosis of glaucoma or ocular hypertension on netarsudil and at least one other hypotensive agent for glaucoma who had at least one month of follow-up were included. Patients with additional procedures or glaucoma medication changes were excluded. The main outcome measures were IOP reduction, Kaplan-Meier survival analyses, netarsudil responder type, and complication rates. Results. 236 eyes of 236 patients were included. The mean baseline IOP was 19.06 +/- 4.6 mmHg on an average of 4 ocular hypotensive medications. 196 (83.1%) patients experienced IOP reduction at the first follow-up visit of 2.84 +/- 0.30 mmHg at 55.66 +/- 51.89 days. IOP reduction at the second visit among these patients was 3.01 +/- 0.44 mmHg at 133.24 +/- 77.63 days. After starting netarsudil, 59% had a sustained response (median duration of 315 days), 25% had a robust response (>20% IOP reduction for at least 80% of visits), and 10% had a super response (>20% and >10 mmHg IOP reduction). Netarsudil was effective as an adjunctive therapy across all baseline IOP categories with greater relative IOP reduction in higher baseline IOP groups. Conclusions. Netarsudil is an effective adjunctive glaucoma therapy. IOP reductions between 2 and 3 mmHg are typical, but a minority had more pronounced and sustained effects (>10 mmHg). Further analysis is needed to assess specific demographic and clinical factors predictive of these robust responses

LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins

The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class-I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2-deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2-deficient lymphocytes show impaired degradation of key BH3-only proteins, resulting in elevated levels of pro-apoptotic BIM and increased cell death. Interestingly, LMP2 is the sole immunoproteasome subunit required for BIM degradation. Together, our results suggest LMP2 has important housekeeping functions and represents a viable therapeutic target for cancer

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used