Risk factors for severe bleeding complications in glaucoma surgery and the role of antiplatelet or anticoagulant agents

PURPOSE: To evaluate the influences and risk factors for severe bleeding complications during glaucoma surgery, and to investigate the role of antiplatelet (AP) and anticoagulant (AC) agents. METHODS: This prospective study enrolled patients undergoing trabeculectomy, trabeculotomy (with Trabectome® or Kahook Dual Blade®), viscocanaloplasty and Ahmed or Baerveldt implants. Bleeding severity was graded on an ordinal scale ranging from 0 to 5. Immediately after surgery and one day later, the incidence and severity of bleeding events was documented on a standardized form. A grade ≥3 was defined as severe bleeding. The influence of known systemic disorders, the type of anesthesia, surgical procedure, intraoperative blood pressure, and the use of or change in AP or AC agents on intraoperative bleeding were analyzed. RESULTS: Data from 89 eyes undergoing glaucoma procedures were included (age 71.3y ± 10.5). We observed severe intraoperative bleeding in 8 eyes (9%) and found that concomitant diseases such as the history of a deep vein thrombosis or peripheral arterial occlusive disease, and the type of surgical procedure (trabeculectomy and viscocanaloplasty) were significantly associated with severe bleeding events. By contrast, the use of AP/ AC agents had no significant influence on severe intraoperative bleeding events. CONCLUSION: According to the results of our study cohort, glaucoma procedures entailing scleral manipulations (trabeculectomy and viscocanaloplasty) and concomitant diseases such as the history of a deep vein thrombosis or peripheral arterial occlusive disease influence the risk of severe intraoperative bleeding events, we detected no increased risk related to concomitant antiplatelet and/ or anticoagulant medication use

Quantification of Retrograde Axonal Transport in the Rat Optic Nerve by Fluorogold Spectrometry

PURPOSE: Disturbed axonal transport is an important pathogenic factor in many neurodegenerative diseases, such as glaucoma, an eye disease characterised by progressive atrophy of the optic nerve. Quantification of retrograde axonal transport in the optic nerve usually requires labour intensive histochemical techniques or expensive equipment for in vivo imaging. Here, we report on a robust alternative method using Fluorogold (FG) as tracer, which is spectrometrically quantified in retinal tissue lysate. METHODS: To determine parameters reflecting the relative FG content of a sample FG was dissolved in retinal lysates at different concentrations and spectra were obtained. For validation in vivo FG was injected uni- or bilaterally into the superior colliculus (SC) of Sprague Dawley rats. The retinal lysate was analysed after 3, 5 and 7 days to determine the time course of FG accumulation in the retina (n = 15). In subsequent experiments axona transport was impaired by optic nerve crush (n = 3), laser-induced ocular hypertension (n = 5) or colchicine treatment to the SC (n = 10). RESULTS: Spectrometry at 370 nm excitation revealed two emission peaks at 430 and 610 nm. We devised a formula to calculate the relative FG content (c(FG)), from the emission spectrum. c(FG) is proportional to the real FG concentration as it corrects for variations of retinal protein concentration in the lysate. After SC injection, c(FG) monotonously increases with time (p = 0.002). Optic nerve axonal damage caused a significant decrease of c(FG) (crush p = 0.029; hypertension p = 0.025; colchicine p = 0.006). Lysates are amenable to subsequent protein analysis. CONCLUSIONS: Spectrometrical FG detection in retinal lysates allows for quantitative assessment of retrograde axonal transport using standard laboratory equipment. It is faster than histochemical techniques and may also complement morphological in vivo analyses

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial - study protocol

Introduction: Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. Methods and analysis: Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. Ethics and dissemination: TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Trial registration number: NCT01962571

Zyklophotokoagulation – Vielfalt der Anwendungen

Zusammenfassung Die Zyklophotokoagulation (CPC) ist wenig invasiv, schnell durchführbar und eine der beliebtesten Glaukomoperationen in Deutschland. Glaukomatologisch wird sie aber eher als Eingriff 2. oder 3. Wahl gesehen. Nicht zuletzt erscheint das Prinzip der Verringerung der Kammerwasserproduktion bei häufig vorliegendem Abflussproblem unphysiologisch, was zu dem eher schlechten Ruf der Zyklophotokoagulation beiträgt. Wie die verschiedenen Modi der CPC in diesem Spannungsfeld eingeordnet werden können, soll dieser Übersichtsartikel beleuchten

Current Status and Future Perspectives of Optic Nerve Imaging in Glaucoma

Being the primary site of degeneration, the optic nerve has always been the focus of structural glaucoma assessment. The technical advancements, mainly of optical coherence tomography (OCT), now allow for a very precise quantification of the optic nerve head and peripapillary retina morphology. By far the most commonly used structural optic nerve parameter is the thickness of the parapapillary retinal nerve fiber, which has great clinical utility but also suffers from significant limitations, mainly in advanced glaucoma. Emerging novel imaging technologies, such as OCT angiography, polarization-sensitive or visible-light OCT and adaptive optics, offer new biomarkers that have the potential to significantly improve structural glaucoma diagnostics. Another great potential lies in the processing of the data already available. Artificial intelligence does not only help increase the reliability of current biomarkers but can also integrate data from various imaging modalities and other clinical measures to increase diagnostic accuracy. And it can, in a more efficient way, draw information from available datasets, such as an OCT scan, compared to the current concept of biomarkers, which only use a fraction of the whole dataset

Quantitative evaluation of an optimized Time of Flight Magnetic Resonance Imaging procedure using a phantom setup to simulate aqueous humor flow

Preclinical Magnetic Resonance Imaging at high field strength offers the great advantage of combining anatomical information and very high resolution of down to 25 µm in mice and even higher resolutions in ex vivo settings. The presented data is Time of Flight MR imaging data using a tube phantom and a given flow-rate to determine the lower limit of the flow rate that is detectable with an experimental set-up and a specifically optimized 2D TOF sequence.In this work we present data on a phantom study which shows the ability of Time of Flight MR Imaging to detect very low flow rates down to 25 µl/h at a velocity of 0.1 mm/s non-invasively in a phantom study

The Antiproliferative Effect of Bevacizumab on Human Tenon Fibroblasts Is Not Mediated by Vascular Endothelial Growth Factor Inhibition

PURPOSE. Vascular endothelial growth factor–signaling in human tenon fibroblasts (hTFs) has recently become a target for antifibrotic treatment in glaucoma filtration surgery. The anti- VEGF antibody bevacizumab (BVC) has been shown to increase filtration bleb size. Given the relatively high concentration of BVC needed to obtain an effect, we investigated whether BVC acts through VEGF inhibition or via non–antigen-dependent ways. METHODS. Human tenon fibroblast primary cultures were obtained from strabismus surgery subjects. Under low (0.2%) and high (10%) serum conditions, cells were incubated with BVC, ranibizumab (RNB), aflibercept (AFB), or rituximab (RTX) at different concentrations. Total number of cells and number of dead or proliferating (5-bromo-2-deoxy-uridinepositive) cells were assessed after 24 hours. Concentrations of VEGF-A in cell culture media was measured with ELISA. Intracellular IgG was detected with immunostaining and Western blot analysis. RESULTS. In quiescent hTF culture (0.2% serum) the addition of 5 mg/mL BVC induced widespread cell death. Under proliferative conditions (10% serum), BVC reduced the number of proliferating cells. No such effect was observed with 2.5 mg/mL BVC or with 10 mg/mL AFB or 2.5 mg/mL RNB, although they were equally effective in binding free VEGF-A in the culture media. Instead, the CD20 antibody RTX, which did not bind VEGF, induced hTF death and inhibited proliferation in a BVC-comparable fashion. Bevacizumab, AFB, and RTX were detected intracellularly in a concentration-dependent manner. CONCLUSIONS. The cell death–inducing and antiproliferative effect of 5 mg/mL BVC appeared not to depend on VEGF inhibition. Our data question a direct role of VEGF for hTF survival and proliferation

Influence of pars plana vitrectomy for macular surgery on the medium term intraocular pressure.

PurposeTo evaluate the long-term effect of 20 and 23 gauge pars plana vitrectomy (PPV) on intraocular pressure (IOP).MethodsStudy type: Monocentric retrospective cohort study. 249 eyes of 249 patients undergoing PPV due to epiretinal membrane (EM), idiopathic macular hole (IMH) or vitreoretinal traction (VT) were included. The fellow eye served as control. Exclusion criteria were factors known to influence the IOP, such as cataract surgery during follow-up, extended use of steroids, cryotherapy and silicone oil endotamponade. The relative change of IOP (operated vs. fellow eye) at 6-12 months after surgery was defined as primary endpoint. Secondary endpoints were the relative change of IOP at 3-6 and 12-24 months. Possible influencing cofactors were analysed using ANCOVA.ResultsThe primary endpoint did not show a significant IOP reduction of the operated eye relative to the fellow eye (P = 0.089, n = 84). However, the IOP of the operated eye alone was significantly reduced at 6-12 and 12-24 months after surgery (-0.75 ± 2.80 and -1.22 ± 3.29 mmHg, P = 0.008 and 0.007, respectively). The IOP of the fellow eye was also significantly reduced at the 12-24 months period (-0.75 ± 2.73 mmHg, P = 0.008). In the subgroup analysis, sclerotomy size was a significant influencing cofactor, leading to lower IOP after 20G compared to 23G vitrectomy (P = 0.04).ConclusionPars plana vitrectomy did not induce a significant long-term IOP reduction relative to the contralateral eye. However, we observed a IOP lowering potential in 20G vitrectomy