XEN® implantation: an effective strategy to stop glaucoma progression despite prior minimally invasive glaucoma surgery.

PURPOSE: The aim of this study was to evaluate whether XEN® implantation is a reasonable and safe method to lower the intraocular pressure (IOP) and amount of medication for adult primary open-angle glaucoma (POAG) over a 3-year period. The influence of the type of anesthesia, previous glaucoma surgery, and postoperative interventions on the outcome were examined. METHODS: In this retrospective study, 96 eyes were included. XEN® implantation was performed as sole procedure under general (n = 86) or local anesthesia (n = 10). IOP and number of glaucoma medication were assessed preoperatively: day 1, week 6, month 3, 6, 12, 24, and 36. Further outcome parameters were Kaplan-Meier success rates, secondary intervention, and complication rates. RESULTS: IOP decreased from 20.7 ± 5.1 to 12.8 ± 2.5 mmHg at the 36-month follow-up (p < 0.001) and glaucoma therapy was reduced from 3.3 ± 0.8 to 1.2 ± 1.6 (36 months, p < 0.001). Transient postoperative hypotony was documented in 26 eyes (27.1%). General anesthesia resulted in a significant improvement of the survival rate compared to local anesthesia (77% vs. 50%, p = 0.044). Prior iStent inject®, Trabectome®, or SLT laser had no significant impact, such as filter bleb revision. The number of postoperative needlings had a significantly negative influence (p = 0.012). CONCLUSION: XEN® implantation effectively and significantly lowers the IOP and number of glaucoma therapy in POAG in the 36-month follow-up with a favorable profile of side effects and few complications. In case of IOP, general anesthesia has a significant positive influence on the survival rate, whereas prior SLT or MIGS does not have significant impact.

Selective Laser Trabeculoplasty Versus MIGS: Forgotten Art or First-Step Procedure in Selected Patients with Open-Angle Glaucoma.

INTRODUCTION: To evaluate the long-term effect on intraocular pressure (IOP) and glaucoma medication of selective laser trabeculoplasty (SLT) compared to minimally invasive glaucoma surgery (MIGS) in primary open-angle glaucoma (POAG) and its potential in clinical practice. METHODS: A total of 342 consecutive patients (stand-alone procedures) were included. One hundred and five patients underwent SLT treatment (360° SLT, 95-105 spots, Trabeculas SLT ARCLaser, Nürnberg, DE), 107 patients had an ab interno-derived trabeculotomy (Trabectome®, NeoMedix, Tustin, USA), and 130 patients received iStent inject® implantation (2 implants-Glaukos, CA, USA). IOP and glaucoma therapy were evaluated preoperatively, 1 day, 6 weeks, 3 months, 6 months, and 1, 2, and 3 years postoperatively. Statistical analysis was performed using a regression model and propensity matching score (reduced cohort number) using SPSS v20.0. Kaplan-Meier analysis was included using the following six criteria: criterion A (IOP ≤ 21 mmHg with or without medication, qualified success), criterion B (IOP ≤ 18 mmHg with or without medication, qualified success), criterion C (IOP ≤ 21 mmHg without medication, complete success), criterion D (IOP ≤ 18 mmHg without medication, complete success), criterion E (IOP ≤ 21 mmHg and IOP reduction > 20% after therapy), and criterion F (IOP ≤ 18 mmHg and IOP reduction > 20% after therapy). RESULTS: In the matched cohort, the SLT cohort showed an IOP reduction of 31.2% from 19.9 ± 2.3 to 13.7 ± 2.7 mmHg (p < 0.001) 3 years postoperatively; in Trabectome® IOP decreased by 31.4% from 20.5 ± 1.3 to 13.8 ± 2.0 mmHg (p < 0.001) and in iStent inject® by 29.9% from 19.5 ± 2.0 to 13.8 ± 2.7 mmHg (p < 0.001). Trabectome® and iStent inject® could not demonstrate a significant reduction in glaucoma therapy (Trabectome® p = 0.138, iStent inject® p = 0.612); a significant drop was noted in SLT (2.2 ± 1.2 to 1.7 ± 1.2, p = 0.046). SLT and MIGS achieved good to moderate survival rates using criterion A (93.3% SLT, 79.7% Trabectome®, 77.6% iStent inject®) and criterion B (74.5% SLT, 48.0% Trabectome®, 56.2% iStent inject®). As expected, low survival rates were obtained with non-filtering procedures: criterion C 11.1% in SLT, 6.5% in Trabectome®, 7.0% in iStent inject® and criterion D 3.0% in SLT, 4.3% in Trabectome®, 3.7% in iStent inject® in 3-year follow-up. CONCLUSION: The SLT is a low-complication and effective method for reducing pressure in mild to moderate POAG. SLT is suitable as an initial procedure when setting up a step scheme; MIGS is the treatment of choice as a follow-up for mild to moderate forms of glaucoma and accepted topical therapy. Ethic approval had been given by the Ethikkommission Charité - Universitätsmedizin Berlin, EA4/047/20-retrospectively registered.

Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes.

BACKGROUND: To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG). METHODS: In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups. RESULTS: Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p >  0.05). The number of antiglaucoma medications did not change in both groups (p >  0.05) and showed no significant difference between the two groups (p >  0.05). CONCLUSION: Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation.

Ab interno canaloplasty (ABiC)-12-month results of a new minimally invasive glaucoma surgery (MIGS).

PURPOSE: The aim of this study is to assess whether the ab interno canaloplasty is a reasonable minimally invasive method to lower significantly the IOP level and number of antiglaucomatous medication over a certain period of time in adult primary open angle glaucoma (POAG). METHODS: In this retrospective cohort outcome study, 36 eyes of 28 POAG patients (mean age 74.8 ± 9.3 years) with an IOP above target pressure were included. Ab interno canaloplasty (ABiC) was performed in all subjects (MEyeTech GmbH, Alsdorf, Germany) as sole procedure in pseudophakic eyes (n = 20) or in combination with cataract surgery in phakic eyes (n = 16). The intraocular pressure (IOP) and the number of glaucoma medication were assessed preoperatively, day 1, week 6, month 3, month 6, and month 12. RESULTS: IOP decreased from 19.8 ± 4.1 to 13.8 ± 3 mmHg at 12 months follow-up (n = 21, p < 0.001). The IOP reduction showed significant results at all time points (1 day p < 0.001; 6 weeks p < 0.001; 3 months p < 0.001; 6 months p = 0.001; 12 months p < 0.001). Glaucoma therapy was stabilized at 2.1 ± 1.6 number of medications after 12 months postoperatively. There was no significant difference in the number of medication at 12 months follow-up (p = 1.0). No major perioperative complications can be reported. CONCLUSION: The ABiC effectively lowers the IOP in POAG in the short term follow-up of 12 months. A reduction of glaucoma therapy cannot be achieved and should be discussed with the patients prior to surgery.

Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b-HSVTK mouse model.

PURPOSE: To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b-HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells. METHODS: We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b-HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14. RESULTS: The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2 ) and peripheral retina (53 ± 20.6 cells/mm2 ); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2 , p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups. CONCLUSION: The CD11b-HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected.

iStent inject as a reasonable alternative procedure following failed trabeculectomy?

PURPOSE:: The aim of this study is to assess the intraocular pressure lowering effect and the performance of the glaucoma therapy of the iStent inject in glaucoma patients with uncontrolled intraocular pressure after failed trabeculectomy. METHODS:: In this retrospective study, iStent inject implantation (Glaukos Corporation, Laguna Hills, CA, USA) was performed in 22 eyes of 21 subjects suffering from glaucoma (n = 18 primary open angle glaucoma, n = 3 pseudoexfoliation glaucoma, and n = 1 for secondary glaucoma) with an intraocular pressure above target pressure after failed trabeculectomy (mean = 9.6 ± 8.1 years; range: 1-35 years). The intraocular pressure and the number of antiglaucomatous medication were assessed preoperatively, 1 day, 6 weeks, 3 months, 6 months, and 1 year after surgery and compared to preoperative findings (SPSS v23.0; Shapiro-Wilk test, Wilcoxon test, Friedman test). RESULTS:: The results showed a significant intraocular pressure decrease from 22.5 ± 4.6 to 15.5 ± 3.4 mmHg after 1 year follow-up (p = 0.012). The glaucoma therapy was 2.6 ± 1.2 preoperatively and reduced to 2.25 ± 1.5 number of medications after 1 year (p > 0.05). There was no significant difference in the number of medication during the whole follow-up period (1 year, p = 0.012). No significant intra- or postoperative complications were reported. CONCLUSION:: Minimal invasive glaucoma surgery (iStent inject) can offer an effective intraocular pressure reduction in advanced adult primary and secondary open angle glaucoma after failed trabeculectomy in a follow-up period of 1 year. Glaucoma therapy, however, needs to be maintained to achieve an individual target pressure and to prevent glaucoma progression. In addition, a failure rate of 27.3% makes it necessary to select carefully patients for this treatment option.

Inhibition of Placenta Growth Factor Reduces Subretinal Mononuclear Phagocyte Accumulation in Choroidal Neovascularization.

Purpose: The cellular immune response driven by mononuclear phagocytes (MPs) is crucial for choroidal neovascularization (CNV) progression. Case reports show that a switch from pure anti-vascular endothelial growth factor-A (VEGF-A) intravitreal treatment to aflibercept, a drug with combined anti-VEGF-A and anti-placenta growth factor (PlGF) activity, can be beneficial for patients who do not respond to anti-VEGF-A alone. Since MPs harbor VEGFR1, we hypothesize that the interplay of P1GF/vascular endothelial growth factor receptor 1 (VEGFR1) in immune cells plays a pivotal role for CNV. Methods: CNV was induced with laser, and immune cells and neovascularization were analyzed in vivo and ex vivo. Immunohistochemistry was employed for protein detection. Differential expression of angiogenic factors and macrophage polarization markers were assessed by quantitative PCR (qPCR). One day after laser, intravitreal injection of aflibercept or anti-PlGF was performed. Results: In the early inflammatory phase after laser, Plgf but not Vegfa was significantly upregulated. VEGF-A upregulation is limited to the scar, whereas PlGF shows a wider distribution. M1 (proinflammatory) macrophage markers were upregulated in the early phase of CNV. However, M2 (proangiogenic) markers showed more inconsistent dynamics. We demonstrated that both aflibercept and anti-PlGF treatments decrease the overall amount of activated subretinal MPs, and especially of those expressing PlGF. These data correlated with a reduction in leakage associated to CNV. Aflibercept showed a stronger reduction in both parameters. Conclusions: The results hint at an interplay between PlGF/VEGFR1 and MPs that is important in the early phase of CNV. A combined inhibition of VEGF-A and PlGF is superior to a specific anti-PlGF treatment in terms of subretinal MP recruitment.

Microglia inflict delayed brain injury after subarachnoid hemorrhage.

Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.