Central Visual Field Testing in Early Glaucoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the current published literature on the utility of the 10-2 visual field (VF) testing strategy for the evaluation and management of early glaucoma, defined here as mean deviation (MD) better than -6 decibels (dB). METHODS: A search of the peer-reviewed literature was last conducted in June 2023 in the PubMed database. Abstracts of 986 articles were examined to exclude reviews and non-English-language articles. After inclusion and exclusion criteria were applied, 26 articles were selected, and the panel methodologist rated them for strength of evidence. Thirteen articles were rated level I, and 8 articles were rated level II. The 5 level III articles were excluded. Data from the 21 included articles were abstracted and reviewed. RESULTS: The central 12 locations on the 24-2 VF test grid lie within the central 10 degrees covered by the 10-2 VF test. In early glaucoma, defects detected within the central 10 degrees generally agree between the 2 tests. Defects within the central 10 degrees of the 24-2 VF test can predict defects on the 10-2 VF test, although the 24-2 may miss defects detected on the 10-2 VF test. In addition, results from the 10-2 VF test show better association with findings from OCT scans of the macular ganglion cell complex. Modifications of the 24-2 test that include extra test locations within the central 10 degrees improve detection of central defects found on 10-2 VF testing. CONCLUSIONS: Evidence to date does not support routine testing using 10-2 VF for patients with early glaucoma. However, early 10-2 VF testing may provide sufficient additional information for some patients, particularly those with a repeatable defect within the central 12 locations of the standard 24-2 VF test or who have inner retinal layer thinning on OCT scans of the macula. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

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.

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 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 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.

Crystalline keratopathy following long-term netarsudil therapy.

Purpose: This case report highlights a possible association between netarsudil use and crystalline keratopathy. Observations: Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment. Conclusions and importance: Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.

Combined Microinvasive Glaucoma Surgery - A Review of the Literature and Future Directions.

The use of microinvasive invasive glaucoma surgery (MIGS) in the treatment of glaucoma has increased exponentially over the last 10 years. However, practice patterns vary widely given the relative newness of these technologies. Some surgeons perform two or more MIGS simultaneously, such as those that target aqueous production and those that target aqueous outflow. These combined MIGS (cMIGS) may result in lower intraocular pressure (IOP) and reduced medication burden as compared to single MIGS (sMIGS). Current evidence suggests some cMIGS are more effective in reducing medication burden for at least 12 months versus sMIGS. This review focuses on the current evidence related to the efficacy of cMIGS as well as novel combinations of standalone MIGS, limitations of the current literature, and future directions for research.

Comparing Outcomes of Phacoemulsification and Endocyclophotocoagulation with Either Dual Blade Goniotomy (PEcK) or Two Trabecular Stents (ICE2).

Purpose: To compare outcomes of phacoemulsification and endocyclophotocoagulation with either dual blade goniotomy (PEcK) or two trabecular stents (ICE2). Setting: Retrospective, nonrandomized comparative study from a level 3 triage center. Methods: One hundred and seventy charts and a total of 1294 visits were reviewed following either PEcK or ICE2 from 2018 to 2022. One hundred and twenty-eight patients had PEcK and 42 underwent ICE2. Patients with less than 30 days of follow-up were excluded. The mean follow-up time was 505 ± 308 days. Two Kaplan-Meier curves (KM) assessed survival with ≤ baseline medications while maintaining (1) [GIC - Goal IOP Criteria] IOP ≤ goal IOP or (2) [PRC - Percent Reduction Criteria] IOP reduction ≥ 20% with 5 mmHg ≤ IOP ≤ 21 mmHg for at least two consecutive visits. IOP and medication burden reduction were compared using a paired t-test. Results: Most patients were Caucasian (65%) and had mild-stage glaucoma (43%). The most common glaucoma type was primary open-angle glaucoma (58%). Average age was 72.2 years at the time of surgery. Mean preoperative IOP was 17.58 ± 4.98 mmHg on 3.00 ± 1.41 medications in PEcK and 15.36 ± 3.58 mmHg on 1.81 ± 1.11 medications in ICE2 (p = 0.015 for IOP; p < 0.001 for medications). Under GIC, the success rate was significantly higher in PEcK at POM6 (69% vs 46%, p < 0.001) and POY1 (63% vs 36%, p < 0.001). Under PRC, the success rate was significantly higher in PEcK at POM6 (73% vs 61%, p = 0.031) and POY1 (67% vs 50%, p = 0.028). Mean reductions at POY1 were 5.00 ± 4.31 mmHg on 1.35 ± 1.08 less medications after PEcK and 3.14 ± 2.83 mmHg on 1.01 ± 0.94 less medications after ICE2 (p < 0.001 at POY1 for IOP; p < 0.05 after POW6 for medications). Conclusion: Both PEcK and ICE2 reduce medication and IOP from baseline, with PEcK having more favorable GIC and PRC success rates and greater IOP and medication reduction at 1 year.

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.

Combined MIGS: Comparing Additive Effects of Phacoemulsification, Endocyclophotocoagulation, and Kahook Dual Blade.

Purpose: Combining two or more MIGS (cMIGS) promises to be more efficacious than single MIGS (sMIGS). This study compared the efficacy of PEcK, which combines Phacoemulsification (Phaco), Endocyclophotocoagulation (ECP), and Kahook dual blade (KDB), relative to both of its constituent sMIGS, Phaco/ECP (Endo Optiks, NJ) and Phaco/KDB (New World Medical, CA) for the first time. Patients and methods: Data was collected retrospectively from 1833 visits of 271 patients who underwent PEcK, Phaco/ECP, or Phaco/KDB from 2016-2021 at Massachusetts Eye and Ear. Primary outcomes included Generalized Estimating Equations (GEE) of intraocular pressure (IOP) and medication burden, as well as survival models. Results: Mean preoperative IOP was 17.6 ± 5.0 (SD) mmHg on 3.0 ± 1.4 medications in the PEcK group (n = 128), 17.9 ± 5.1 mmHg on 2.2 ± 1.5 medications in the Phaco/ECP group (n = 78), and 16.1 ± 4.3 mmHg on 0.4 ± 1.0 medications in the Phaco/KDB group (n = 65). For more than 36 months, all procedures resulted in significant patterns of IOP and medication reduction (all p < 0.001), before and after statistical adjustment. The reduction pattern in IOP was significantly different when comparing all groups over time and favored PEcK (p = 0.04), but the reduction pattern in medications was not significantly different (p = 0.11). Procedures did not differ in procedural time (p = 0.18) or in survival to maintain ≥20% IOP reduction (p = 0.43) without additional medication or procedure. There was a trend toward significant difference in maintaining IOP ≤ goal IOP that favored PEcK over Phaco/ECP after adjustment (p = 0.09). Conclusion: PEcK may confer greater IOP reduction without added procedural time compared to Phaco/ECP and Phaco/KDB in predominantly mild or moderate glaucoma. Further research on cMIGS may benefit from adopting this comparative analysis to constituent MIGS.

Comparing Outcomes of Trabeculotomy with Mitomycin C to 45-µm Gelatin Stent Placed Ab Externo with Open Conjunctiva.

PURPOSE: To compare trabeculectomy with mitomycin C (trab-MMC) and XEN45 Gel Stent placed ab externo with open conjunctiva (XGS AEO) with or without cataract surgery in patients with glaucoma. DESIGN: Nonrandomized, retrospective, comparative study. SUBJECTS: A total of 204 eyes from 204 glaucoma patients who received XGS AEO or underwent trab-MMC with or without cataract surgery between July 2018 and August 2021 at Massachusetts Eye and Ear. METHODS: Visits from 204 patient charts were reviewed after either trab-MMC or XGS AEO from 2018 to 2021 from a level 3 triage center. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), medication burden, Kaplan-Meier success rates, 5-fluorouracil impact, and complications. RESULTS: One hundred fifty-seven patients underwent trab-MMC and 47 underwent XGS AEO. Groups had similar baseline intraocular pressure (IOP) and medications (meds). Intraocular pressure and meds decreased similarly at 1.5 years (11.2 mmHg vs. 7.4 mmHg, P = 0.62; 2.9 vs. 2.8 meds, P = 0.92, respectively for trab-MMC and XGS AEO). Success was defined as IOP reduction ≥ 20% with 5 mmHg ≤ IOP ≤ 18 mmHg for 2 consecutive visits. Complete success (CS) did not allow meds; qualified success (QS) allowed for ≤ baseline meds. When IOP fluctuations in the first 60 days were not counted as failures, CS was 43% for trab-MMC, about 8.5% higher than for XGS AEO (P < 0.01). Qualified success was similar between the groups (65%-67%). Procedure time was shorter for XGS AEO than trab-MMC (44 vs. 63 minutes, P < 0.01). CONCLUSIONS: XEN45 Gel Stent AEO may provide similar benefits to trab-MMC, especially for patients who tolerate some meds, with shorter procedure times. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Neurofilament Light Chain in Aqueous Humor as a Marker of Neurodegeneration in Glaucoma.

Purpose: Neurofilament light chain (NfL) is a neuronal cytoskeletal protein that has been identified as a marker of neurodegeneration in diseases of the central nervous system. In this study, we investigated whether NfL in the aqueous humor (AH) can serve as a marker of neurodegeneration in glaucoma in a racially diverse North American population. Design: Single-center, case-control study. Participants: We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract. Methods: We collected AH from 39 glaucoma patients and 10 patients without glaucoma. AH NfL was quantified using the Single-Molecule Array (Simoa)® NF-light assay (Quanterix). Demographic information, such as age, body mass index, sex, and self-reported race, as well as clinical information, such as pre-operative intraocular pressure (IOP), maximum IOP, and number of pre-operative glaucoma medications, was obtained by reviewing the medical record. Main Outcome Measures: Levels of AH NfL. Results: In a model controlling for age and body mass index (BMI), NfL was significantly elevated in AH from glaucoma patients (mean: 429 pg/mL; standard deviation [SD]: 1136 pg/mL) compared to AH from patients without glaucoma (mean: 3.1 pg/mL; SD: 1.9 pg/mg): P = 0.002. Higher AH NfL was associated with higher maximum IOP (R = 0.44, P = 0.005), higher pre-operative IOP (R = 0.46, P = 0.003), and more pre-operative glaucoma medications (Rs = 0.61, P < 0.001). There was no association between AH NfL and Humphrey visual field mean deviation (R = -0.20, P = 0.220), retinal nerve fiber layer thickness as measured with optical coherence tomography (R = 0.07, P = 0.694), or glaucoma stage (Rs = 0.015, P = 0.935). Conclusion: Our findings suggest that AH NfL may have clinical utility as a marker of glaucomatous neurodegeneration.

NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, P<0.001), interstitial fibrosis (mild vs. severe disease; mean 54 vs. 167 µg uNGAL/g Cr, P<0.01), and tubular atrophy (mild vs. severe disease; mean 54 vs. 164 µg uNGAL/g Cr, P<0.01). Monospecific assays of the NGAL monomer demonstrated a correlation with histology that typifies progressive, severe CKD.

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.

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.

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.

Outcomes of phacoemulsification and endoscopic cyclophotocoagulation performed with dual blade ab interno trabeculectomy or trabecular micro-bypass stent insertion.

BACKGROUND/OBJECTIVE: To report the initial outcomes of phacoemulsification, endoscopic cyclophotocoagulation, and dual blade ab interno trabeculectomy (PEcK), and compare them to those of phacoemulsification, endoscopic cyclophotocoagulation, and trabecular micro-bypass stent insertion (ICE-1). SUBJECTS/METHODS: Patients from January 2018 to December 2019 that underwent PEcK or ICE-1 at a tertiary referral centre were included in this retrospective comparative case series. Patients were excluded if they had additional concomitant procedures, less than 6 weeks (42 days) of follow-up or were not at least 18 years old. Intraocular pressure (IOP), number of glaucoma medications, and best-corrected visual acuity were collected preoperatively and postoperatively at 6 weeks, 3, 6, and 12 months. Kaplan-Meier survival analysis and Cox proportional-hazards regression were conducted to elucidate any factors associated with survival time. RESULTS: The mean preoperative IOP was 18.3 ± 5.9 mmHg in the PEcK group (53 eyes) and 14.7 ± 4.3 mmHg in the ICE-1 group (23 eyes) (p = 0.004) on 3.3 ± 1.3 and 1.7 ± 0.93 glaucoma medications (p < 0.001), respectively. Twelve months postoperatively the mean IOP reduction was 5.1 ± 4.4 mmHg and 2.3 ± 4.0 mmHg (p = 0.08), and the mean medication reduction was 1.6 ± 1.5 and 0.97 ± 0.66 (p = 0.10), in the PEcK and ICE-1 groups, respectively. Kaplan-Meier survival analysis did not reveal any differences in treatment survival. CONCLUSIONS: Both PEcK and ICE-1 provide clinically relevant reductions in IOP and glaucoma medication burden, however the PEcK procedure may confer greater reductions in IOP. The procedures did not differ with regard to Kaplan-Meier survival probability.

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.