Safety and Effectiveness of the PRESERFLO® MicroShunt in Primary Open-Angle Glaucoma: Results from a 2-Year Multicenter Study.

PURPOSE: To assess the safety and effectiveness of the PRESERFLO® MicroShunt (formerly InnFocus MicroShunt) in patients with primary open-angle glaucoma (POAG). DESIGN: The MicroShunt, a controlled ab externo glaucoma filtration surgery device, was investigated in a 2-year, multicenter, single-arm study. PARTICIPANTS: Eligible patients were aged 18-85 years with POAG inadequately controlled on maximal tolerated medical therapy with intraocular pressure (IOP) ≥18 and ≤35 mmHg or when glaucoma progression warranted surgery. METHODS: The MicroShunt was implanted as a stand-alone procedure with adjunctive use of topical mitomycin C (MMC; 0.2-0.4 mg/ml) for 2-3 minutes. MAIN OUTCOME MEASURES: The primary effectiveness outcome was IOP reduction and success (not requiring reoperation or pressure failures [IOP > 21 mmHg and < 20% reduction in IOP]) at year 1. Additional end points at year 2 included IOP reduction, success, glaucoma medications, adverse events (AEs), and reoperations. Results are reported in the overall population and subgroups of patients receiving 0.2 or 0.4 mg/ml MMC. RESULTS: In 81 patients, mean (± standard deviation [SD]) IOP decreased from 21.7 ± 3.4 mmHg at baseline to 14.5 ± 4.6 mmHg at year 1 and 14.1 ± 3.2 mmHg at year 2 (P < 0.0001). Overall success (with and without supplemental glaucoma medication use) at year 1 was 74.1%. Mean (± SD) number of medications decreased from 2.1 ± 1.3 at baseline to 0.5 ± 0.9 at year 2 (P < 0.0001), and 73.8% of patients were medication free. Most common nonserious AEs were increased IOP requiring medication or selective laser trabeculoplasty (25.9%) and mild-to-moderate keratitis (11.1%). There were 6 (7.4%) reoperations and 5 (6.2%) needlings by year 2. In an analysis (post hoc) according to MMC concentration, overall success was 78.1% (0.2 mg/ml) and 74.4% (0.4 mg/ml; P = 0.710). In the 0.2 and 0.4 mg/ml MMC groups, 51.9% and 90.3% of patients were medication free, respectively (P = 0.001). There was a trend toward lower IOP and higher medication reduction in the 0.4 mg/ml MMC subgroup. CONCLUSIONS: In this study, mean IOP and glaucoma medication reductions were significant and sustained over 2 years postsurgery. No long-term, sight-threatening AEs were reported. Further studies may confirm potential risk/benefits of higher MMC concentration.

Safety and Tolerability of Intravitreal Carotuximab (DE-122) in Patients With Persistent Exudative Age-Related Macular Degeneration: A Phase I Study.

Purpose: Carotuximab (DE-122) is a novel endoglin antibody that exhibits potent anti-angiogenic activity. The aim of this study was to evaluate the safety and tolerability of a single intravitreal injection of four ascending doses of carotuximab in patients with persistent exudative age-related macular degeneration (AMD). Methods: In an open-label, dose-escalating, sequential cohort study, patients with persistent exudative AMD were assigned to an intravitreal injection of carotuximab 0.5 mg, 1.0 mg, 2.0 mg, or 4.0 mg (n = 3 per group). Safety and change in central subfield thickness (CST), as measured by spectral domain-optical coherence tomography, were assessed from baseline until day 90. Rescue therapy with an anti-vascular endothelial growth factor medication was allowed on days 8, 30, and 60. Results: Seven patients (58%) experienced at least one adverse event (AE), including five patients (41.7%) who experienced one or more AEs in the study eye and two patients (16.7%) who experienced one or more non-ocular AEs. Posterior eye deposits were reported in one patient 2 days after receiving 1.0 mg, but they resolved spontaneously by day 43. A >50-µm reduction in CST on two consecutive visits was observed in four patients (33%), including one patient in each dose cohort. Conclusions: In this study, carotuximab was generally well tolerated, with no serious AEs reported, when administered as a single intravitreal injection to patients with persistent exudative AMD. Translational Relevance: Further characterization of the safety and efficacy of carotuximab will be needed to determine what role it may have in the treatment of exudative AMD.

Ab externo implantation of the MicroShunt, a poly (styrene-block-isobutylene-block-styrene) surgical device for the treatment of primary open-angle glaucoma: a review.

Trabeculectomy remains the 'gold standard' intraocular pressure (IOP)-lowering procedure for moderate-to-severe glaucoma; however, this approach is associated with the need for substantial post-operative management. Micro-invasive glaucoma surgery (MIGS) procedures aim to reduce the need for intra- and post-operative management and provide a less invasive means of lowering IOP. Generally, MIGS procedures are associated with only modest reductions in IOP and are targeted at patients with mild-to-moderate glaucoma, highlighting an unmet need for a less invasive treatment of advanced and refractory glaucoma. The PRESERFLO® MicroShunt (formerly known as InnFocus MicroShunt) is an 8.5 mm-long (outer diameter 350 µm; internal lumen diameter 70 µm) glaucoma drainage device made from a highly biocompatible, bioinert material called poly (styrene-block-isobutylene-block-styrene), or SIBS. The lumen size is sufficiently small that at normal aqueous flow hypotony is avoided, but large enough to avoid being blocked by sloughed cells or pigment. The MicroShunt achieves the desired pressure range in the eye by draining aqueous humor from the anterior chamber to a bleb formed under the conjunctiva and Tenon's capsule. The device is implanted ab externo with intraoperative Mitomycin C via a minimally invasive (relative to incisional surgery) surgical procedure, enabling precise control of placement without the need for gonioscopy, suture tension control, or suture lysis. The implantation procedure can be performed in combination with cataract surgery or as a standalone procedure. The MicroShunt received Conformité Européenne (CE) marking in 2012 and is intended for the reduction of IOP in eyes of patients with primary open-angle glaucoma in which IOP remains uncontrolled while on maximum tolerated medical therapy and/or in which glaucoma progression warrants surgery. Three clinical studies assessing the long-term safety and efficacy of the MicroShunt have been completed; a Phase 3 multicenter, randomized clinical study comparing the MicroShunt to primary trabeculectomy is underway. In preliminary studies, the MicroShunt effectively reduced IOP and use of glaucoma medications up to 3 years after implantation, with an acceptable safety profile. This article summarizes current literature on the unique properties of the MicroShunt, the preliminary efficacy and safety findings, and discusses its potential use as an alternative to trabeculectomy for glaucoma surgery.

Evaluation of a new IOLMaster algorithm to measure axial length.

PURPOSE: To evaluate the ability of the new IOLMaster with Advanced Technology version 5 software (Carl Zeiss Meditec, AG) to measure axial length (AL) in patients having preoperative cataract extraction evaluation. SETTING: Private practice, Arizona, USA. METHODS: This single-center study comprised 54 eyes (33 patients) scheduled for cataract extraction. Visual acuity, manifest refraction, and Lens Opacities Classification System III (LOCS III) scores were recorded. Twenty AL measurements per eye were acquired using an IOLMaster with Advanced Technology version 5 software. The AL measurements were analyzed and classified into 4 methods: standard, standard manipulated, composite-5, and composite-20. RESULTS: Axial length measurements were successfully obtained in 55.6%, 94.4%, 92.6%, and 96.3% of eyes with the standard, standard manipulated, composite-5, and composite-20 methods, respectively. Axial length measurement availability (ability of the software to provide an AL measurement) was not statistically significantly affected by nuclear color, nuclear opalescence, or cortical changes with any method. However, posterior subcapsular changes statistically significantly affected the standard and composite methods (P< .05) and marginally affected the standard manipulated method in measuring the AL (P = .0868). Axial length availability was significantly reduced in eyes with posterior subcapsular cataract of LOCS III grade 5.0 or higher. CONCLUSIONS: The 2 composite methods performed as well as the more time consuming, complicated standard manipulated method in measuring AL. More than 90% of eyes could be measured by the composite methods. Dense posterior subcapsular cataracts significantly reduced the ability of the composite and standard manipulated methods to successfully measure AL.

Scanning laser polarimetry retinal nerve fiber layer thickness measurements after LASIK.

PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness measurements before and after LASIK. DESIGN: Cohort study. PARTICIPANTS: Twenty participants undergoing LASIK and 14 normal controls. METHODS: Retinal nerve fiber layer thickness was measured before LASIK and approximately 3 months after surgery in one eye each of 20 patients using a scanning laser polarimeter (GDx Nerve Fiber Analyzer) with fixed corneal compensation (FCC), one with variable corneal compensation (GDx VCC), and optical coherence tomography (OCT). Fourteen normal controls also were tested at baseline and approximately 3 months later. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thicknesses measured with the GDx FCC, GDx VCC, and OCT. RESULTS: At baseline, mean (95% confidence interval [CI]) RNFL thicknesses for the GDx FCC, GDx VCC, and OCT were 78.1 microm (72.2-83.9), 54.3 microm (52.7-56.0), and 96.8 microm (93.2-100.5), respectively. In both LASIK and control groups, there were no significant changes between baseline and follow-up examinations in GDx VCC and OCT RNFL thickness measurements globally or in the superior and inferior quadrants (mean change, <5 microm for each instrument). In the control group, there also was no significant change in GDx FCC measurements between baseline and follow-up. In LASIK patients, significant reductions were observed in GDx FCC RNFL measurements. Average absolute values of the mean (95% CI) change in thickness were 12.4 microm (7.7-17.2), 15.3 microm (9.6-20.9), and 12.9 microm (7.6-18.1) for GDx FCC RNFL measurements superiorly, inferiorly, and globally, respectively (all Ps < or = 0.001). CONCLUSIONS: LASIK does not seem to change RNFL thickness. Reduction in GDx FCC RNFL thickness measurements after LASIK is a measurement artifact and is most likely due to erroneous compensation for corneal birefringence. With scanning laser polarimetry, it is mandatory to compensate individually for change in corneal birefringence after LASIK to ensure accurate RNFL assessment.

Corneal changes after laser in situ keratomileusis: measurement of corneal polarization magnitude and axis.

PURPOSE: Laser in situ keratomileusis (LASIK) involves ablation of the corneal stroma, which may induce a change in birefringence. The purpose of this study was to determine the effect of LASIK on corneal birefringence by measuring corneal polarization magnitude (CPM) and axis (CPA). STUDY DESIGN: Cohort study. METHODS: In this prospective study, we measured the change in CPM and CPA before and after LASIK with a scanning laser polarimeter ([SLP] GDx-VCC; Laser Diagnostic Technologies, San Diego, California). Scans were completed on 23 subjects before and 3 months after LASIK. 14 normal controls were tested twice during the same time interval. Change in CPM, CPA, corneal thickness, and corneal curvature measurements were compared between LASIK and normal subjects. RESULTS: At baseline, the mean (95% confidence interval) values of CPM, CPA, corneal thickness, and corneal curvature measurements of the total population (n = 37) were 41.6 nm (36.6, 46.5); 31.5 degrees (25.7, 37.3); 548.4 microm (540.0, 556.7); and 7.6 mm (7.5, 7.7), respectively. There were no significant differences in baseline values between normal and LASIK subjects. The reproducibility, measured as the average standard deviation of CPM and CPA measurements in 30 normal control eyes, was 1.95 nm (1.43, 2.48) and 1.69 degrees (0.92, 2.46), respectively. Mean CPA, corneal thickness, and corneal curvature measurements were significantly different in patients after LASIK (all P <.0001). Mean absolute values of the change in both CPM and CPA were significantly greater in LASIK patients (4.8 nm [3.3, 6.4], and 10.4 degrees [6.8, 14.1], respectively) than in normal subjects (2.43 nm [1.53, 3.33], and 1.64 degrees [1.15, 2.14], respectively; both P < or =.05). The absolute value of change in CPA was linearly associated with the absolute value of change in both corneal thickness (R(2) = 0.46) and corneal curvature (R(2) = 0.44). CONCLUSIONS: LASIK causes a measurable change in corneal birefringence as measured by the CPM and CPA that may be related to loss of corneal tissue. Comparison of SLP measurements before and after LASIK requires eye-specific compensation to adjust for the change in corneal birefringence.