Entwicklung eines resorbierbaren Vorderkammer-Glaukomimplantates

The glaucomas are potentially treatable diseases, either by medication or surgery. Ab externo Er:YAG-laser sclerostomy, as an alternative surgical glaucoma therapy, produces a drainage canal from the anterior chamber into subconjunctival space. The procedure by itself did not achieve the desired success, as postoperative scarring of episcleral tissue often resulted in occlusion of the canal. The implant concept introduced in this study modifies the Er:YAG-lasersclerostomy procedure. The aim is to obtain an intact corneoscleral canal during the postoperative inflammatory period by implanting a non-draining stent into the canal as a placeholder. This should make for more favourable conditions for long-term functionality of the drainage canal after explantation of the stent. To avoid the necessary explantation procedure of the silicone stent, biodegradable plastics were tested for applicability as a possible stent-material, as the second part of this study.The silicone implant consists of a 300µm pim which bottoms out into a small flag. After conduction of the laser-sclerostomy the stent was implanted into four chinchilla-rabbits. Six weeks after implantation two animals were enucleated with stent in situ to evaluate the sclerostomy-morphology around the stent as well as subconjunctival reactions to the stent site. Two further animals underwent stent-explantation at the same time, enucleation was conducted 14 weeks after stent explantation. Bulbi were histologically processed. Analysis of the biodegradable glycolid-copolymers and of multiblockcopolymer oligo(p-dioxanon)diol, oligo(alkylen-glykoladipat)diol and diisocyanat (PDA) included processing, degradation in phosphate buffer, degradation in L929-conjunctival fibroblast culture, and biocompatibility testing for multiblockcopolymer PDA, consisting of EB/FDA vital staining, BrDU-, WST-1-elisa and cellmorphologic analysis of L929-fibroblasts.Surgical practicability of stent implantation was documented as well as high acceptance of subconjunctival tissue for the silicone stent. Histology showed fibrocellular connective tissue in the canal with the stent luxated from the canal. A pronounced fibrocellular sheathing was seen around the stent flag. The implant could not be found in one eye. Only minor inflammation was persistent 14 weeks after explantation, with fibrocellular occlusion of the canal. Iris incarceration occured in one eye after stent explantation without further complications.In the course of material analysis the glycolid-polymers turned out to be unemployable for stent construction due to missing elasticity and acidic degradation. Multiblockcopolymer PDA showed comparable results as biofilm-reference for all cytotoxicity testings. The results of degradation analysis were linear degradation without noticeable loss of elasticity and a less pronounced pH-value decrease.Modification of the lasersclerostomy-procedure by stent implantation could serve as a method to ameliorate postoperative conditions for a functioning drainage canal. The surgical procedure is easy to do and requires little complexity. Implantation of the non-degradable implant would be possible, following a concise explantation procedure in local anesthesia. Application and evaluation of the degradable PDA-stent in an animal model would be the next step, thus avoiding the traumatising explantation of the permanent silicone stent. The main aim is to avoid a remaining immunogenic foreign body in subconjunctival space. The labelled aspects should be subjects of further research

Entwicklung eines resorbierbaren Vorderkammer-Glaukomimplantates

The glaucomas are potentially treatable diseases, either by medication or surgery. Ab externo Er:YAG-laser sclerostomy, as an alternative surgical glaucoma therapy, produces a drainage canal from the anterior chamber into subconjunctival space. The procedure by itself did not achieve the desired success, as postoperative scarring of episcleral tissue often resulted in occlusion of the canal. The implant concept introduced in this study modifies the Er:YAG-lasersclerostomy procedure. The aim is to obtain an intact corneoscleral canal during the postoperative inflammatory period by implanting a non-draining stent into the canal as a placeholder. This should make for more favourable conditions for long-term functionality of the drainage canal after explantation of the stent. To avoid the necessary explantation procedure of the silicone stent, biodegradable plastics were tested for applicability as a possible stent-material, as the second part of this study.The silicone implant consists of a 300µm pim which bottoms out into a small flag. After conduction of the laser-sclerostomy the stent was implanted into four chinchilla-rabbits. Six weeks after implantation two animals were enucleated with stent in situ to evaluate the sclerostomy-morphology around the stent as well as subconjunctival reactions to the stent site. Two further animals underwent stent-explantation at the same time, enucleation was conducted 14 weeks after stent explantation. Bulbi were histologically processed. Analysis of the biodegradable glycolid-copolymers and of multiblockcopolymer oligo(p-dioxanon)diol, oligo(alkylen-glykoladipat)diol and diisocyanat (PDA) included processing, degradation in phosphate buffer, degradation in L929-conjunctival fibroblast culture, and biocompatibility testing for multiblockcopolymer PDA, consisting of EB/FDA vital staining, BrDU-, WST-1-elisa and cellmorphologic analysis of L929-fibroblasts.Surgical practicability of stent implantation was documented as well as high acceptance of subconjunctival tissue for the silicone stent. Histology showed fibrocellular connective tissue in the canal with the stent luxated from the canal. A pronounced fibrocellular sheathing was seen around the stent flag. The implant could not be found in one eye. Only minor inflammation was persistent 14 weeks after explantation, with fibrocellular occlusion of the canal. Iris incarceration occured in one eye after stent explantation without further complications.In the course of material analysis the glycolid-polymers turned out to be unemployable for stent construction due to missing elasticity and acidic degradation. Multiblockcopolymer PDA showed comparable results as biofilm-reference for all cytotoxicity testings. The results of degradation analysis were linear degradation without noticeable loss of elasticity and a less pronounced pH-value decrease.Modification of the lasersclerostomy-procedure by stent implantation could serve as a method to ameliorate postoperative conditions for a functioning drainage canal. The surgical procedure is easy to do and requires little complexity. Implantation of the non-degradable implant would be possible, following a concise explantation procedure in local anesthesia. Application and evaluation of the degradable PDA-stent in an animal model would be the next step, thus avoiding the traumatising explantation of the permanent silicone stent. The main aim is to avoid a remaining immunogenic foreign body in subconjunctival space. The labelled aspects should be subjects of further research

Multiplex Cytokine Analysis of Aqueous Humor in Juvenile Idiopathic Arthritis-Associated Anterior Uveitis With or Without Secondary Glaucoma

Patients with juvenile idiopathic arthritis often develop chronic anterior uveitis (JIAU). JIAU patients possess a particularly high risk for developing secondary glaucoma when inflammatory inactivity has been achieved. By using multiplex bead assay analysis, we assessed levels of pro-and anti-inflammatory cytokines, chemokines, or metalloproteinases in the aqueous humor (AH) of patients with clinically inactive JIAU with (JIAUwG) or without secondary glaucoma (JIAUwoG), or from patients with senile cataract as controls. Laser-flare photometry analysis prior to surgery showed no significant differences between JIAUwG or JIAUwoG. Compared with the control group, levels of interleukin-8, matrix metalloproteinase-2, -3, -9, serum amyloid A (SAA), transforming growth factor beta-1, -2, -3 (TGF beta-1, -2, -3), and tumor necrosis factor-alpha in the AH were significantly higher in patients with clinically inactive JIAUwG or JIAUwoG. Samples from JIAwoG patients displayed significantly higher levels of SAA (P < 0.0116) than JIAUwG patients. JIAUwG patients showed an increased level of TGF beta-2 in AH samples compared with JIAUwoG (P < 0.0009). These molecules may contribute to the clinical development of glaucoma in patients with JIAU

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy

Purpose: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. Design: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. Participants: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. Methods: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. Main Outcome Measures: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included bestcorrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. Results: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 +/- 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. Conclusions: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD. (C) 2022 by the American Academy of Ophthalmolog