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.

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.

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.

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.

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.

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.

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.

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.