Comparing Outcomes of Tube Versus Trabeculectomy Among Patients With Angle-closure Glaucoma.

PURPOSE: Compare outcomes of tube shunt surgery (Tube) and trabeculectomy with mitomycin C (Trab-MMC) in patients with angle-closure glaucoma (ACG). DESIGN: Retrospective nonrandomized comparative study. PARTICIPANTS: A total of 80 eyes from 80 patients with ACG who underwent either Tube (N = 50) or Trab-MMC (N = 30) between January 2015 and January 2022 at Massachusetts Eye and Ear. METHODS: Reviewed and analyzed 390 visits from patient charts. MAIN OUTCOME MEASURES: Kaplan-Meier (KM) success rates, intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), adjusted hazard ratios (HRs), and complications. RESULTS: Baseline demographics were similar between both groups, except for a higher proportion of patients with pseudophakia and prior incisional ocular surgery in the Tube group. The Trab-MMC procedure had significantly higher KM complete success (CS) rates than the Tube procedure, but similar qualified success (QS) rates. Under QS, the cumulative probability of survival was 87% in the Tube group and 83% in the Trab-MMC group at year 1 (P = 0.77), and 75% in the Tube group and 58% in the Trab-MMC group at year 2 (P = 0.14). Under CS, the cumulative probability of survival was 13% in the Tube group and 59% in the Trab-MMC group at year 1 (P < 0.001), and 11% in the Tube group and 41% in the Trab-MMC group at year 2 (P < 0.001). Both Tube and Trab-MMC procedures resulted in significant patterns of IOP and medication reduction from baseline up to 2 years with mean IOP reduced to 12.6 ± 5.9 mmHg on 2.8 ± 1.4 medications after Tube and 12.1 ± 6.6 mmHg on 2.4 ± 1.7 medications after Trab-MMC. Patients who underwent Trab-MMC required less IOP-lowering medications at every follow-up visit up to year 1, but a similar number at year 2. No significant differences were found in IOP reduction, BCVA, or complication rates between groups. CONCLUSIONS: We demonstrate that Trab-MMC confers similar IOP reduction and QS rates to Tube placement in patients with ACG. Trab-MMC, however, demonstrated greater medication burden reduction up to 1 year, and more favorable CS rates up to 2 years, while still maintaining similar complication rates to Tube. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparing Outcomes of 45 µm Gelatin Stent Placed ab Externo with Open Conjunctiva to ab Externo with Closed Conjunctiva.

PURPOSE: Compare outcomes of a gelatin stent (XEN45 Gel Stent [XGS]) placed either ab externo with open conjunctiva (AEO) or ab externo with closed conjunctiva (AEC) with or without cataract surgery in patients with glaucoma. DESIGN: Retrospective nonrandomized comparative study. PARTICIPANTS: A total of 86 eyes from 86 glaucoma patients who received XGS placed either AEO (N = 49) or AEC (N = 37) with or without cataract surgery between May 2019 and April 2022 at Massachusetts Eye and Ear. METHODS: Reviewed and analyzed 809 visits from patient charts from a level 3 triage center. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), medication burden, Kaplan-Meier (KM) success rates, 5-fluorouracil (5-FU) impact, and complications. RESULTS: Baseline demographics were similar between both groups, except for baseline IOP and glaucoma type. Both AEO and AEC procedures resulted in significant patterns of IOP and medication reduction from baseline up to 1 year. The AEO procedure had significantly higher KM qualified success (QS) rates than the AEC procedure, but similar complete success (CS) rates. Under QS, the cumulative probability of survival was 73% in the AEO group and 51% in the AEC group at month 6 and 62% in the AEO group and 20% in the AEC group at year 1. Under CS, the cumulative probability of survival was 41% in the AEO group and 37% in the AEC group at month 6 and 29% in the AEO group and 14% in the AEC group at year 1. The AEO procedure had significantly more IOP reduction than the AEC procedure at all postoperative time points beyond week 2, but similar medication burden reduction. At postoperative year 1 (POY1), the mean IOP was reduced to 10.72 ± 5.71 mmHg on 1.16 ± 1.68 medications after AEO and 17.03 ± 2.37 mmHg on 1.59 ± 1.21 medications after AEC. Phacoemulsification (phaco) was not a significant factor while 5-FU usage trended toward significance. Procedure time was longer for standalone XGS AEO. CONCLUSIONS: We demonstrate that both placements reduce medication and IOP from baseline, with AEO placement having more favorable XGS success rates and IOP control at the expense of longer procedure time and greater 5-FU usage. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparing Outcomes of 45 Xen Implantation Ab Interno With Closed Conjunctiva to Ab Externo With Open Conjunctiva Approaches.

PRCIS: Ab externo with open conjunctiva placement may lead to improved gelatin stent (XEN Gel Stent; Allergan) success rate compared with ab interno with closed conjunctiva because it conferred more favorable intraocular pressure (IOP) and medication burden reduction based on our complete and qualified success criteria. PURPOSE: To compare outcomes of a gelatin stent (XEN 45 Gel Stent; Allergan) placed either ab interno with closed conjunctiva (AIC) or ab externo with open conjunctiva (AEO) with or without cataract surgery in patients with glaucoma. DESIGN: Retrospective, nonrandomized comparative study of 85 eyes from 85 glaucoma patients who received XEN 45 Gel Stent placed either AIC (N=32) or AEO (N=53) with or without cataract surgery between July 2018 and January 2022 at Massachusetts Eye and Ear. Patients were included if they were 18 years of age or above and had at least 30 days of follow-up without any disqualifying event. RESULTS: Baseline demographics were similar between both groups, except for the glaucoma type. Both AIC and AEO procedures resulted in significant patterns of IOP and medication reduction from baseline up to 1 year. At postoperative year (POY)1, mean IOP was reduced to 11.34±4 mmHg on 1.29±1.34 medications after AEO and 13.70±3.32 mmHg on 2±1.81 medications after AIC. The average IOP reduction was significantly greater in the AEO group at all postoperative time points beyond postoperative week 2. There were significant differences in the survival curves of AEO and AIC groups under both the complete success criteria and the qualified success criteria. Under the complete success criteria, the cumulative probability of survival at POY1 was 28.5% in the AEO group and 3.8% in the AIC group. Under the qualified success criteria, the cumulative probability of survival at POY1 was 60.3% in the AEO group and 21.9% in the AIC group. CONCLUSIONS: In our study, we demonstrate that both placements reduce IOP and medication from baseline, with AEO placement having more favorable success rates compared with AIC placement.

Remarkable Improvements After Cataract Surgery in a Presumed "End-Stage" Glaucoma Patient: A Case Report.

Predicting the visual outcome after cataract extraction can be challenging in glaucoma patients who develop cataracts. Here, we demonstrate the case of a patient with advanced glaucoma and a mild-to-moderate cataract at initial presentation, who demonstrated remarkable improvement in visual acuity following a period of controlled intraocular pressure (IOP) and the removal of a matured cataract at the time of surgery. A 64-year-old Haitian woman with severe mixed-mechanism glaucoma and hand motion vision in both eyes (OU) presented with intraocular pressures of 38 mmHg OD (oculus dexter/right eye) and 41 mmHg OS (oculus sinister/left eye) while on three IOP-lowering agents. Her medications were escalated to six IOP-lowering medications, and she underwent bilateral transscleral laser cyclophotocoagulation with both micropulse and continuous wave probes simultaneously. Postoperatively, IOPs dropped to 7 and 9 mmHg in the right and left eyes, respectively, and remained at or below target on three topical agents for the remainder of her follow-up. Contrastingly, the patient's cataract had progressed, and the decision was made to undergo cataract extraction OU sequentially. The subsequent clinical course demonstrated progressive visual improvement with 20/80 best-corrected visual acuity OU and increased independence with activities of daily living. This case illustrates the potential for visual improvement in an advanced glaucoma patient after removing a matured cataract despite limited prior expectations. Ocular comorbidities complicate but do not necessarily preclude appropriate interventions that may improve patients' vision-related quality of life.

Neurodegeneration Markers Galectin-3 and Apolipoprotein E Are Elevated in the Aqueous Humor of Eyes With Glaucoma.

Purpose: Galectin-3 (Gal-3) and apolipoprotein E (APOE) are markers of activated microglia in neurodegenerative diseases of the central nervous system, whose targeting is protective in mouse models of glaucoma. In this study, we examined levels of Gal-3 and APOE in human aqueous humor (AH) and defined their clinical associations with glaucoma. Methods: We collected AH from 59 glaucoma patients and 15 controls at the start of planned ophthalmic surgery. Gal-3 and APOE levels were quantified by enzyme-linked immunosorbent assay. Total protein in AH was quantified by bicinchoninic acid assay. Significant associations between Gal-3, APOE, and clinical covariates were defined using univariate and multivariate linear regression models. Results: Gal-3 and APOE levels were significantly elevated in the AH of glaucoma patients compared to controls (P = 0.004 and P < 0.001, respectively). Gal-3 and APOE were positively correlated across the entire cohort (r = 0.65, P = 6.2E-9). No association was observed between Gal-3 and total protein or APOE and total protein (P = 0.35 and P = 0.50, respectively), indicating that their levels were not increased in glaucomatous AH due to nonspecific protein accumulation. Multivariate linear regression modeling revealed significant associations between Gal-3 and maximum recorded intraocular pressure (P = 0.009) and between APOE and number of past ophthalmic surgeries (P = 0.031). Conclusions: We demonstrate that Gal-3 and APOE are significantly elevated in the AH of eyes with glaucoma and are associated with a history of poorly controlled disease. Translational Relevance: Gal-3 and APOE in AH may inform clinical decision-making as quantifiable readouts of microglial activation in eyes with glaucoma.

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.

Netarsudil-associated reticular corneal epithelial edema.

PURPOSE: To describe 8 cases of reversible reticular corneal epithelial edema of the cornea that developed after use of the topical Rho-kinase inhibitor netarsudil. METHODS: This is a retrospective chart review case series of 8 patients treated with netarsudil at an academic medical center. OBSERVATIONS: Patients had predisposing corneal conditions including penetrating keratoplasty, corneal decompensation after trabeculectomy-associated endophthalmitis, congenital glaucoma with Haab striae, aphakic bullous keratopathy, history of Ahmed valve and silicone oil, and Fuchs endothelial corneal dystrophy undergoing Descemet stripping only. One patient did not have clear predisposing corneal disease other than low endothelial cell density and a history of trabeculectomy. All patients developed reticular corneal epithelial edema, which appeared as collections of moderate sized superficial epithelial bullae arranged in a reticular pattern resembling a honeycomb. Most developed these changes within weeks of initiating netarsudil, but unique to this series are 2 cases in which netarsudil was tolerated by the cornea for months before developing reticular corneal epithelial edema after diode laser cyclophotocoagulation. In cases which underwent anterior segment optical coherence tomography, the imaging demonstrated that the corneal stroma was not edematous, and the reticular corneal epithelial edema involved both host and donor corneal epithelium in cases of penetrating keratoplasty. This fully resolved in all cases upon cessation of netarsudil, and this series is the first to document resolution via a pattern in which the individual bullae become smaller and more widely spaced apart. CONCLUSION: Netarsudil can cause a reversible reticular corneal epithelial edema.

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

PURPOSE: 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. DESIGN: Retrospective cohort study. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), Kaplan-Meier success rates, adjusted hazard ratios (HRs), and complications. RESULTS: 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. CONCLUSIONS: 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.

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.

Case Report: Reversal and subsequent return of optic disc cupping in a myocilin (MYOC) gene-associated severe Juvenile Open-Angle Glaucoma (JOAG) patient.

To our knowledge, this case report describes the first instance of reversal of glaucomatous optic nerve cupping in a young adult with a rare form of juvenile open-angle glaucoma (JOAG) associated with a novel variant of the myocilin gene (MYOC). This 25-year-old woman with severe-stage MYOC-associated JOAG presented with blurry vision and intermittent pain in her left eye. She had a strong family history of glaucoma in multiple first-degree relatives with an identified novel variant of MYOC. Examination revealed intraocular pressures (IOPs) of 10 mmHg OD and 46 mmHg OS, with cup-to-disc ratios of 0.90 and 0.80. The patient experienced substantial reversal of optic disc cupping OS following dramatic IOP reduction with trabeculectomy, and subsequently experienced a return of cupping after an IOP spike 15 months postoperatively. The reversal of cupping did not correspond to any changes in the patient's visual field. After an initial decrease in retinal nerve fiber layer (RNFL) thickness, RNFL remained stable for over 2 years after trabeculectomy as seen on Optical Coherence Tomography (OCT). This case suggests reversal of cupping can occur well into adulthood in a MYOC-associated JOAG patient, and it demonstrates the potential bidirectionality of this phenomenon. Moreover, it suggests that these structural changes may not correspond to any functional changes in visual fields or RNFL thickness.

Combined pars plana glaucoma drainage device placement and vitrectomy using a vitrectomy sclerotomy site for tube placement: a case series.

PURPOSE: The purpose of this study is to report the safety and efficacy of pars plana glaucoma drainage devices with pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement in patients with refractory glaucoma. METHODS: Retrospective case series of 28 eyes of 28 patients who underwent combined pars plana glaucoma drainage device and pars plana vitrectomy between November 2016 and September 2019 at Massachusetts Eye and Ear. Main outcome measures were intraocular pressure (IOP), glaucoma medication burden, best corrected visual acuity, and complications. Statistical tests were performed with R and included Kaplan-Meier analyses, Wilcoxon paired signed-rank tests, and Fisher tests. RESULTS: Mean IOP decreased from 22.8 mmHg to 11.8 mmHg at 1.5 years (p = 0.002), and mean medication burden decreased from 4.3 to 2.1 at 1.5 years (p = 0.004). Both IOP and medication burden were significantly lower at all follow-up time points. The probability of achieving 5 < IOP ≤ 18 mmHg with at least 20% IOP reduction from preoperative levels was 86.4% at 1 year and 59.8% at 1.5 years. At their last visit, three eyes (10.7%) achieved complete success with IOP reduction as above without medications, and 14 eyes (50.0%) achieved qualified success with medications. Hypotony was observed in 1 eye (3.6%) prior to 3 months postoperatively and 0 eyes after 3 months. Visual acuity was unchanged or improved in 23 eyes (82.1%) at their last follow-up. Two patients had a visual acuity decrease of > 2 lines. Two eyes required subsequent pars plana vitrectomies for tube obstruction, and one eye had transient hypotony. CONCLUSIONS: The results of pars plana glaucoma drainage device and pars plana vitrectomy using one of the vitrectomy sclerotomy sites for tube placement are promising, resulting in significant IOP and medication-burden reductions through postoperative year 1.5 without additional risk of postoperative complications. Inserting glaucoma drainage devices into an existing vitrectomy sclerotomy site may potentially save surgical time by obviating the need to create another sclerotomy for tube placement and suture one of the vitrectomy ports.

Urinary neutrophil gelatinase-associated lipocalin predicts mortality and identifies acute kidney injury in cirrhosis.

BACKGROUND: Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. AIMS: We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. METHODS: Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. RESULTS: One hundred eighteen patients were enrolled. Fifty-two (44 %) patients had normal kidney function, 14 (12 %) stable chronic kidney disease, 17 (14 %) prerenal azotemia, 20 (17 %) HRS, and 15 (13 %) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5-387.5) vs. 20 (15-45) ng/mL, p = 0.004] and iAKI [325 (100-700), p < 0.001]. Fifteen (13 %) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95 % CI 1.36-2.94) and mortality or liver transplantation (OR 2.01, 95 % CI 1.42-2.85). In multiple regression models, uNGAL > 110 ng/mL (OR 6.05, 95 % CI 1.35-27.2) and HRS (OR 6.71, 95 % CI 1.76-25.5) independently predicted mortality, adjusting for age and serum creatinine >1.5 mg/dL. CONCLUSIONS: uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.

Urinary NGAL is a useful clinical biomarker of HIV-associated nephropathy.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is expressed by kidney tubules that are acutely damaged, but few studies have investigated the association of neutrophil gelatinase-associated lipocalin (NGAL) with different forms of chronic kidney disease (CKD). HIV-associated nephropathy (HIVAN) is a progressive form of CKD characterized by collapsing focal segmental glomerulosclerosis and microcytic tubular dilatation that typically leads to end-stage renal disease (ESRD). METHODS: Previously, we reported that microcystic tubular dilatations specifically expressed NGAL RNA, implying that the detection of uNGAL protein could mark advanced HIVAN. To test this idea, we performed a comparative study of diverse proteinuric glomerulopathies in 25 patients who were HIV positive. RESULTS: Eighteen patients had HIVAN and seven had other glomerulopathies (four membranoproliferative glomerulonephritis, one membranous glomerulonephritis, one amyloid and one malarial GN). HIVAN and non-HIVAN patients did not differ with respect to age, ethnicity, serum creatinine, estimated GFR, proteinuria or the prevalence of hypocomplementemia (6 versus 29%, P = 0.18), but HIVAN patients were less likely to have HCV infections. HIVAN patients expressed 4-fold higher levels of uNGAL than the patients with other glomerulopathies [387 ± 338 versus 94 ± 101 µg/g urine creatinine (uCr), P = 0.02]. A cutpoint of 121.5 µg uNGAL/g uCr demonstrated 94% sensitivity and 71% specificity for the diagnosis of HIVAN, with an area under the receiver operator characteristic curve of 0.88. CONCLUSION: In summary, while HIVAN disease is currently diagnosed only by kidney biopsy, uNGAL can distinguish HIVAN from other proteinuric glomerulopathies in the HIV-infected patient, likely because of its specific expression from characteristic microcysts.