TY - JOUR A1 - Leopold, Stephanie A. A1 - Zeilbeck, Ludwig F. A1 - Weber, Gregor A1 - Seitz, Roswitha A1 - Bösl, Michael R. A1 - Jägle, Herbert A1 - Fuchshofer, Rudolf A1 - Tamm, Ernst R. A1 - Ohlmann, Andreas T1 - Norrin protects optic nerve axons from degeneration in a mouse model of glaucoma JF - Scientific Reports N2 - Norrin is a secreted signaling molecule activating the Wnt/β-catenin pathway. Since Norrin protects retinal neurons from experimental acute injury, we were interested to learn if Norrin attenuates chronic damage of retinal ganglion cells (RGC) and their axons in a mouse model of glaucoma. Transgenic mice overexpressing Norrin in the retina (Pax6-Norrin) were generated and crossed with DBA/2J mice with hereditary glaucoma and optic nerve axonal degeneration. One-year old DBA/2J/Pax6-Norrin animals had significantly more surviving optic nerve axons than their DBA/2J littermates. The protective effect correlated with an increase in insulin-like growth factor (IGF)-1 mRNA and an enhanced Akt phosphorylation in DBA/2J/Pax6-Norrin mice. Both mouse strains developed an increase in intraocular pressure during the second half of the first year and marked degenerative changes in chamber angle, ciliary body and iris structure. The degenerations were slightly attenuated in the chamber angle of DBA/2J/Pax6-Norrin mice, which showed a β-catenin increase in the trabecular meshwork. We conclude that high levels of Norrin and the subsequent constitutive activation of Wnt/β-catenin signaling in RGC protect from glaucomatous axonal damage via IGF-1 causing increased activity of PI3K-Akt signaling. Our results identify components of a protective signaling network preventing degeneration of optic nerve axons in glaucoma. KW - glaucoma KW - neurotrophic factors Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173494 VL - 7 ER - TY - JOUR A1 - Verma-Fuehring, R. A1 - Dakroub, M. A1 - Han, H. A1 - Hillenkamp, J. A1 - Loewen, N. A. T1 - Trabeculopuncture as a predictive test of distal outflow resistance in canal-based surgery JF - Scientific Reports N2 - We investigated whether trabeculopuncture (TP) could detect distal outflow resistance to predict the outcome of canal-based glaucoma surgery such as ab interno trabeculectomy (AIT). These procedures have a high utilization in open angle glaucoma, but fail in eyes with an unidentified distal outflow resistance. We assigned 81 porcine eyes to two groups: trial (n = 42) and control (n = 39). At 24 h, four YAG-laser trabeculopunctures were placed nasally, followed by a 180° AIT at the same site at 48 h. The proportion of TP responders between both AIT groups was compared. Histology and outflow canalograms were determined. Both post-TP and post-AIT IOPs were lower than baseline IOP (p = 0.015 and p < 0.01, respectively). The success rates of TP and AIT were 69% and 85.7%, respectively. Sensitivity and specificity values of TP as predictive test for AIT success were 77.7% and 83.3%, respectively. The positive and negative predictive values were 96.6% and 38.5%, respectively. We conclude that a 10% reduction in IOP after TP can be used as a predictor for the success (> 20% IOP decrease) of 180° AIT in porcine eyes. KW - eye diseases KW - glaucoma Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299740 VL - 12 ER - TY - THES A1 - Dakroub, Mohamad T1 - Coarsened Exact Matching of Excisional to Plasma-Ablative Ab Interno Trabeculectomy T1 - Vergröbertes genaues Matching von exzisionaler zu plasmaablativer Ab-Interno-Trabekulektomie N2 - Abstract Purpose: To compare ab interno trabeculectomy by trabecular meshwork excision to plasma-mediated ablation in primary open-angle glaucoma. Methods: Retrospectively collected data of TrabEx+ (n=56) and Trabectome (n=99) were compared by coarsened exact matching to reduce confounding and matched based on baseline intraocular pressure and age. Primary outcomes were intraocular pressure and the number of glaucoma medications. Complications and the need for additional glaucoma surgery were assessed. Patients were followed for up to one year. Results: 53 TrabEx+ could be matched to Trabectome. Baseline intraocular pressure was 16.5 ± 4.6 mmHg in both; age was 73.7 ± 8.8 years and 71.5 ± 9.9 years in TrabEx+ and Trabectome, respectively. TrabEx+ were taking more medications than Trabectome (p<0.001). Intraocular pressure was reduced to 14.8±4.3 in TrabEx+ and 13.4±3.4 in Trabectome at 6 months, and to 14.9±6.0 (p=0.13) in TrabEx+ and to 14.1±3.8 mmHg (all p<0.05) in Trabectome at 12 months. Medications were reduced at both 6 and 12 months (p< 0.05). No differences were seen between both groups at 6 and 12 months. In TrabEx+, only one serious complication occurred, and two patients required further glaucoma surgery. Conclusion: Although both groups had a baseline intraocular pressure considered low for ab interno trabeculectomy, intraocular pressure and medications were reduced further at 6 and 12 months. Intraocular pressure reduction did not reach significance in TrabEx+ at 12 months. The inter-group comparison did not reveal any significant differences. Both had a low complication rate. N2 - Das Glaukom wird initial häufig mit topischen Medikamenten behandelt. Es ist jedoch oft der Fall, dass Patienten im Verlauf operiert werden. Ablation, Exzision und Disruption des Trabekelmaschenwerks senken bei einem primären Offenwinkelglaukom den Augeninnendruck effektiv, wenn der Ausflusswiderstand im proximalsten Anteil des konventionellen Ausflusstraktes liegt. Die plasma-vermittelte Ablation des Trabekelmaschenwerks mit dem Trabektom steht Chirurgen seit 2004 zur Verfügung, während die Exzision mit dem TrabEx+ 2014 erstmals eingeführt wurde. Diese Studie zielte darauf ab, beide Geräte zu vergleichen und verwendete Coarsened Exact Matching, um kleine, gerätespezifische Unterschiede zwischen Trabektom und TrabEx+ festzustellen. Trotz eines relativ niedrigen Augeninnendrucks reduzierten beide Geräte diesen Parameter nach 6 Monaten signifikant, aber nur das Trabektom schaffte dies nach 12 Monaten. Beide reduzierten die Anzahl der drucksenkenden Medikamente zu beiden Zeitpunkten (6 und 12 Monate) signifikant. Definiert man den chirurgischen Erfolg als Abnahme des Augeninnendrucks um mehr als 20%, so waren die Erfolgsraten in beiden Gruppen relativ niedrig. Erklärbar ist dies am ehesten durch die niedrigen Ausgangswerte des Augeninnendrucks. In Bezug auf Augeninnendruck, Sehschärfe, Erfolgsraten und Komplikationen gab es keine wesentlichen Unterschiede zwischen beiden Geräten. TrabEx+ Patienten applizierten zu allen Zeitpunkten mehr drucksenkende Augentropfen als Trabektom-Patienten. KW - Glaukom KW - glaucoma KW - glaucoma surgery KW - trabex+ KW - trabectome Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-296805 ER - TY - JOUR A1 - Klink, Thomas A1 - Sauer, Johannes A1 - Körber, Norbert J A1 - Grehn, Franz A1 - Much, Martin M A1 - Thederan, Luisa A1 - Matlach, Juliane A1 - Salgado, Josefina Parente T1 - Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy JF - Clinical Ophthalmology N2 - Purpose: To evaluate quality of life (QoL) with a new questionnaire after canaloplasty (CP) and trabeculectomy (TE). Patients and methods: We assessed outcomes of surgery, rate of revision surgeries, patients’ mood, and influence of postoperative care on QoL, surgery interference with daily activities, and postsurgical complaints. Patients completed the QoL questionnaire 24 months after surgery. Results: Patients who underwent CP (n=175) were compared to TE patients (n=152). In the CP group, 57% of patients expressed high satisfaction, while 41% of patients in the TE group said they were highly satisfied. The satisfaction difference was statistically significant (P=0.034). Significantly fewer second surgeries were needed after CP (8% CP versus 35% TE, P<0.001). Patients were more positive in the CP group (54% CP versus 37% TE, P<0.009). Stress related to postoperative care was lower in the CP group compared to the TE group (14% versus 46%). Difficulties with activities of daily living, such as reading, were much lower or even nonexistent after CP, and complaints like eye burning or stinging were significantly lower in the CP group. Conclusions: Compared with TE, CP is associated with less QoL impairment and higher patient satisfaction after surgery. However, long-term data on intraocular pressure reduction after surgery are needed to confirm long-term patient satisfaction with this surgery. KW - glaucoma KW - postoperative care KW - glaucoma surgery KW - non-penetrating glaucoma surgery Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149520 VL - 9 ER - TY - JOUR A1 - Han, Hong A1 - Kampik, Daniel A1 - Grehn, Franz A1 - Schlunck, Günther T1 - TGF-beta 2-Induced Invadosomes in Human Trabecular Meshwork Cells JF - PLoS ONE N2 - Primary open-angle glaucoma (POAG) is a leading cause of blindness due to chronic degeneration of retinal ganglion cells and their optic nerve axons. It is associated with disturbed regulation of intraocular pressure, elevated intraocular levels of TGF-β2, aberrant extracellular matrix (ECM) deposition and increased outflow resistance in the trabecular meshwork (TM). The mechanisms underlying these changes are not fully understood. Cell-matrix interactions have a decisive role in TM maintenance and it has been suggested that TGF-β-induced inhibition of matrix metalloproteases may drive aberrant ECM deposition in POAG. Invadopodia and podosomes (invadosomes) are distinct sites of cell-matrix interaction and localized matrix-metalloprotease (MMP) activity. Here, we report on the effects of TGF-β2 on invadosomes in human trabecular meshwork cells. Human TM (HTM) cells were derived from donor tissue and pretreated with vehicle or TGF-β2 (2 ng/ml) for 3d. Invadosomes were studied in ECM degradation assays, protein expression and MMP-2 activity were assessed by western blot and zymography and ECM protein transcription was detected by RT-qPCR. HTM cells spontaneously formed podosomes and invadopodia as detected by colocalization of Grb2 or Nck1 to sites of gelatinolysis. Pretreatment with TGF-β2 enhanced invadosomal proteolysis and zymographic MMP-2 activity as well as MMP-2, TIMP-2 and PAI-1 levels in HTM cell culture supernatants. Rho-kinase inhibition by H1152 blocked the effects of TGF-β2. Concomitant transcription of fibronectin and collagens-1, -4 and -6 was increased by TGF-β2 and fibrillar fibronectin deposits were observed in areas of invadosomal ECM remodelling. In contrast to a current hypothesis, our data indicate that TGF-β2 induces an active ECM remodelling process in TM cells, characterized by concurrent increases in localized ECM digestion and ECM expression, rather than a mere buildup of material due to a lack of degradation. Invadosomal cell adhesion and signaling may thus have a role in POAG pathophysiology. KW - intraocular pressure KW - cell cultures KW - cell staining KW - proteolysis KW - glaucoma KW - extracellular matrix KW - actins KW - trabecular meshwork Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130074 VL - 8 IS - 8 ER - TY - JOUR A1 - Klink, Thomas A1 - Sauer, Johannes A1 - Körber, Norbert J. A1 - Grehn, Franz A1 - Much, Martin M. A1 - Thederan, Luisa A1 - Matlach, Juliane A1 - Salgado, Josefina Parente T1 - Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy N2 - Purpose: To evaluate quality of life (QoL) with a new questionnaire after canaloplasty (CP) and trabeculectomy (TE). Patients and methods: We assessed outcomes of surgery, rate of revision surgeries, patients’ mood, and influence of postoperative care on QoL, surgery interference with daily activities, and postsurgical complaints. Patients completed the QoL questionnaire 24 months after surgery. Results: Patients who underwent CP (n=175) were compared to TE patients (n=152). In the CP group, 57% of patients expressed high satisfaction, while 41% of patients in the TE group said they were highly satisfied. The satisfaction difference was statistically significant (P=0.034). Significantly fewer second surgeries were needed after CP (8% CP versus 35% TE, P<0.001). Patients were more positive in the CP group (54% CP versus 37% TE, P<0.009). Stress related to postoperative care was lower in the CP group compared to the TE group (14% versus 46%). Difficulties with activities of daily living, such as reading, were much lower or even nonexistent after CP, and complaints like eye burning or stinging were significantly lower in the CP group. Conclusions: Compared with TE, CP is associated with less QoL impairment and higher patient satisfaction after surgery. However, long-term data on intraocular pressure reduction after surgery are needed to confirm long-term patient satisfaction with this surgery. KW - glaucoma KW - postoperative care KW - glaucoma surgery KW - non-penetrating glaucoma surgery Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113596 ER - TY - JOUR A1 - Freiberg, Florentina Joyce A1 - Matlach, Juliane A1 - Grehn, Franz A1 - Karl, Sabine A1 - Klink, Thomas T1 - Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy JF - Clinical Ophthalmology N2 - Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU) injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP) outcome, bleb morphology, postoperative medications, and complications was evaluated. Methods: Glaucoma patients (N = 61) who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months). Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab. Results: Group 1 had 6.4 ± 3.3 (0–15) (mean ± standard deviation and range, respectively) 5-FU injections. Group 2 had 4.0 ± 2.8 (0–12) (mean ± standard deviation and range, respectively) 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005). There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU), yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008). No significant difference in best corrected visual acuity (P = 0.852) and visual field testing (P = 0.610) between preoperative to last follow-up could be found between the two groups. Conclusion: The postoperative injection of bevacizumab reduced the number of subconjunctival 5-FU injections significantly by 2.4 injections. A significant difference in postoperative IOP reduction, bleb morphology, and postoperative medication was not detected. KW - bevacizumab KW - 5-fluorouracil KW - glaucoma KW - trabeculectomy KW - bleb failure KW - bleb scarring Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96546 ER -