Glaucoma filtering surgery is applied to reduce intraocular pressure (IOP) in cases of uncontrolled glaucoma. However, postoperative fibrosis reduces the long-term success of both standard trabeculectomy and microstents. The aim of this study was to test the antiproliferative and anti-inflammatory potential of ZnO-tetrapods (ZnO-T) on human Tenon’s fibroblasts (HTFs) for glaucoma surgery. The toxicity of ZnO-T on HTFs was determined using an MTT test. For analysis of fibroblast proliferation, migration, and transdifferentiation, cultures were stained for Ki67, alpha-smooth muscle actin (α-SMA), and p-SMAD. A fully quantitative multiplex ELISA was used to determine the concentrations of different cytokines, platelet-derived growth factor (PDGF), and hepatocyte growth factor (HGF) in culture supernatants with and without previous ZnO-T treatment. Treatment with higher concentrations (10 and 20 µg/mL) was associated with HTF toxicity, as shown in the wound healing assay. Furthermore, the number of Ki67, α-SMA-positive, and pSMAD-positive cells, as well as IL-6 and HGF in supernatants, were significantly reduced following incubation with ZnO-T. In conclusion, we were able to show the antiproliferative and anti-inflammatory potentials of ZnO-T. Therefore, the use of ZnO-T may provide a new approach to reducing postoperative fibrosis in glaucoma filtering surgery.

In our previous study we were able to show that zinc oxide (ZnO) tetrapods inhibit wound healing processes. Therefore, the aim of this study was to test the antiproliferative effect of two types of porous polydimethylsiloxane (PDMS)/ tetrapodal zinc oxide (ZnO-T) materials, as well as their usability for glaucoma implants. To find the best implant material, two different porous PDMS/ZnO-T materials were examined. One consisted of 3D interconnected PDMS coarse-pored foams with protruding ZnO-T particles; the other consisted of fine-pored 3D interconnected ZnO-T networks homogeneously coated by a thin PDMS film in the nanometer range. Fibroblast cell viability was investigated for both materials via MTT dye, and some implant material samples were further processed for electron microscopy. Both PDMS/ZnO-T materials showed reduced cell viability in the MTT staining. Furthermore, the electron microscopy revealed barely any fibroblasts growing on the implant materials. At the surface of the fine-pored implant material, however, fibroblasts could not be observed in the etched control samples without ZnO-T. It was found that post-processing of the material to the final stent diameter was highly challenging and that the fabrication method, therefore, had to be adapted. In conclusion, we were able to demonstrate the antiproliferative potential of the two different PDMS/ZnO-T materials. Furthermore, smaller pore size (in the range of tens of micrometers) in the implant material seems to be preferable.

To carry out the preclinical and histological evaluation of a novel nanotechnology-based microshunt for drainage glaucoma surgery. Twelve New Zealand White rabbits were implanted with a novel microshunt and followed up for 6 weeks. The new material composite consists of the silicone polydimethylsiloxane (PDMS) and tetrapodal Zinc Oxide (ZnO-T) nano-/microparticles. The microshunts were inserted ab externo to connect the subconjunctival space with the anterior chamber. Animals were euthanized after 2 and 6 weeks for histological evaluation. Ocular health and implant position were assessed at postoperative days 1, 3, 7 and twice a week thereafter by slit lamp biomicroscopy. Intraocular pressure (IOP) was measured using rebound tonometry. A good tolerability was observed in both short- and medium-term follow-up. Intraocular pressure was reduced following surgery but increased to preoperative levels after 2 weeks. No clinical or histological signs of inflammatory or toxic reactions were seen; the fibrotic encapsulation was barely noticeable after two weeks and very mild after six weeks. The new material composite PDMS/ZnO-T is well tolerated and the associated foreign body fibrotic reaction quite mild. The new microshunt reduces the IOP for 2 weeks. Further research will elucidate a tube-like shape to improve and prolong outflow performance and longer follow-up to exclude medium-term adverse effects.

Zusammenfassung: Hintergrund: Mikroinvasive Verfahren haben sich in der Glaukomchirurgie etabliert und werden bevorzugt für Patienten mit nicht zu niedrigen Zieldruckwerten eingesetzt. Die Excimer-Laser-Trabekulotomie (ELT) stellt einen solchen minimal-invasiven Ansatz dar und kann mit einer Kataraktoperation kombiniert werden. Ziel der Arbeit: Über 12 Monate wurden die Senkung des intraokularen Drucks (IOD), die Menge der drucksenkenden Lokaltherapie und das Auftreten unerwünschter Ereignisse mit dem neuen Elios^TM-Verfahren (Elios Vision GmbH, Germering, Deutschland) anhand von Real-Life-Daten einer heterogenen Patientenpopulation, die eine ELT in Kombination mit einer Kataraktoperation (Phako-ELT) erhielt, analysiert. Material und Methoden: Es wurden 20 Augen von 13 Patienten, die eine Phako-ELT erhalten haben, retrospektiv analysiert. Nach einer Standardphakoemulsifikation mit Hinterkammerlinsenimplantation wurden mit dem Excimer-Laser 10 Mikrokanäle angelegt. Die Patienten wurden über 12 Monate nachbeobachtet und der IOD, die drucksenkende Lokaltherapie und das Auftreten unerwünschter Ereignisse untersucht. Ergebnisse: Das Durchschnittsalter lag bei 65 Jahren. Präoperativ betrug der IOD 17,5 (± 5,3) mm Hg. Die IOD-Senkung lag im Mittel bei 4,8 mm Hg (27,4 %, p < 0,001) am ersten postoperativen Tag, 3,2 mm Hg (18,3 %, p = 0,22) nach 6 Monaten und 2,5 mm Hg (14,3 %, p = 0,14) nach 12 Monaten. Die Drucksenker konnten von im Durchschnitt 3,2 (± 1,3) Wirkstoffen präoperativ auf 0,5 (± 0,9) an Tag 1 (p < 0,001), 1,9 (± 1,2) nach 6 Monaten (p = 0,008) und 2,2 (± 1,3) nach 12 Monaten (p = 0,013) reduziert werden. Diskussion: In der hier untersuchten Kohorte ist die ELT in Kombination mit einer Kataraktoperation ein sicheres, minimal-invasives glaukomchirurgisches Verfahren, welches bei Patienten mit niedrigem Ausgangsdruck 1 Jahr postoperativ noch eine IOD-Senkung von 14,3 % aufweist, bei einer Reduktion der drucksenkenden Medikation um 1 Wirkstoff. Da bei der ELT kein Implantat zum Einsatz kommt und die Bindehaut unangetastet bleibt, sind Folgeeingriffe nicht beeinträchtigt und auch Filterkissenoperationen ohne Weiteres möglich.