Oxygen and blood flow: players in the pathogenesis of glaucoma

The increase of IOP in POAG is due an increased resistance of aqueous outflow through the trabecular meshwork (TM). The exact mechanisms leading to the corresponding changes in the TM are not yet known. We know, however, that all risk factors for arteriosclerosis are also risk factors for an increase in IOP. RESULTS: The association between IOP increase and these factors is relatively weak but nevertheless significant. Similar to the pathogenesis of arteriosclerosis, oxidative stress plays a role in the development of TM damage. Even less is known about the pathogenesis of glaucomatous optic neuropathy (GON). Obviously the risk factors for arteriosclerosis play a role via increasing the IOP. When corrected for IOP, however, these factors only play a minor role. In contrast, factors associated with disturbed autoregulation, in particular a systemic primary vascular dysregulation (PVD), increase the risk for GON. This is best observed in normal tension glaucoma patients. An insufficient autoregulation increases the chance for an unstable ocular perfusion and thereby an unstable oxygen supply. This, in turn, leads to oxidative stress. The concentration of superoxide (O(2)(-)) within the axons of the optic nerve head increases. If neighboring astrocytes are activated, either by mechanical or by ischemic stress, in excess produced nitric oxide (NO) molecules diffuse also into the axons and fuse with oxygen. The resulting peroxynitrat (ONOO(-)) diffuses within the axons towards the retina and the lateral geniculate nucleus and induces apoptosis

Suture Distension of Schlemm’s Canal in Canaloplasty: An Anterior Segment Imaging Study

Purpose. The object of this study was to investigate the role of the suture stent regarding its impact on reduction of intraocular pressure (IOP) in canaloplasty based on the distension of the inner wall of Schlemm’s canal. Methods. Nineteen glaucoma patients who underwent canaloplasty with successful positioning of the tensioning suture were included. The measurements were analyzed using linear mixed models, with the means adjusted to IOP, age, cup-to-disc ratio, and time of follow-up. Results. Mean follow-up time was 27.6 months (SD 10.5). Mean intraocular pressure (IOP) was 24.6 mmHg (SD 5.29), 13.8 (SD 2.65), and 14.5 (SD 0.71) before surgery, at 12 months, and at 36 months after surgery, respectively. 57.9% of patients had no medication at last evaluation. Differences and variations of measurements between the devices over a time of 12 months were not significant (p = 0.15 to 0.98). Some angles of distension associated with the suture stent inside SC were predictive for IOP reduction (p < 0.03 to < 0.001), but not for final IOP (p = 0.64 to 0.96). Conclusion. The angles of the inner wall of Schlemm’s canal generated by the suture stent were comparable between OCT and UBM and did not change significantly over time. There was a tendency towards a greater distension of Schlemm’s canal, when the difference was larger between pre- and postoperative IOP, suggesting the tensioning suture may contribute to IOP reduction

Insights into the Mechanism of Ligand Binding to Octopine Dehydrogenase from Pecten maximus by NMR and Crystallography

Octopine dehydrogenase (OcDH) from the adductor muscle of the great scallop, Pecten maximus, catalyzes the NADH dependent, reductive condensation of L-arginine and pyruvate to octopine, NAD+, and water during escape swimming and/or subsequent recovery. The structure of OcDH was recently solved and a reaction mechanism was proposed which implied an ordered binding of NADH, L-arginine and finally pyruvate. Here, the order of substrate binding as well as the underlying conformational changes were investigated by NMR confirming the model derived from the crystal structures. Furthermore, the crystal structure of the OcDH/NADH/agmatine complex was determined which suggests a key role of the side chain of L-arginine in protein cataylsis. Thus, the order of substrate binding to OcDH as well as the molecular signals involved in octopine formation can now be described in molecular detail

Is the medication used to achieve the target intraocular pressure in glaucoma therapy of relevance? : an exemplary analysis on the basis of two beta-blockers

Glaucoma, the most common optic neuropathy (GON) is characterised by the loss of retinal ganglion cells and their axons, as well as tissue remodelling of both the retina and the optic nerve head with corresponding visual field defects. Elevated intraocular pressure (IOP) is generally regarded as the major risk factor for glaucoma and its reduction is the most common target for therapy of GON. There are indications that the greater the IOP reduction, the better is the visual field prognosis. This article investigates, on the basis of two beta-blockers, betaxolol and timolol, whether the amount of IOP reduction is truly a good surrogate for successful glaucoma therapy with respect to visual field outcome. Contrary to what is generally expected, our analysis of the literature exemplifies that despite a smaller IOP reduction, patients treated with betaxolol had a smaller rate of visual field deterioration than patients treated with timolol. Based on the dissociation of IOP reduction and visual field prognosis, we postulate that for successful treatment in glaucoma not only the amount of IOP reduction is relevant but also the drug by which the reduction is achieved. This seeming paradox phenomenon highlights that ocular hypotensive drugs have relevant effects on GON other than IOP-related. Some of these effects on retinal ganglion cells (neuroprotection) or on ocular blood flow are mediated by calcium- and sodium channels. Future studies on glaucoma treatment should focus on their effect on visual field function, and not just on IOP. This should particularly be considered when comparing drugs from different classes

Update on Minimally Invasive Glaucoma Surgery (MIGS) and New Implants

Traditional glaucoma surgery has been challenged by the advent of innovative techniques and new implants in the past few years. There is an increasing demand for safer glaucoma surgery offering patients a timely surgical solution in reducing intraocular pressure (IOP) and improving their quality of life. The new procedures and devices aim to lower IOP with a higher safety profile than fistulating surgery (trabeculectomy/drainage tubes) and are collectively termed “minimally invasive glaucoma surgery (MIGS).” The main advantage of MIGS is that they are nonpenetrating and/or bleb-independent procedures, thus avoiding the major complications of fistulating surgery related to blebs and hypotony. In this review, the clinical results of the latest techniques and devices are presented by their approach, ab interno (trabeculotomy, excimer laser trabeculotomy, trabecular microbypass, suprachoroidal shunt, and intracanalicular scaffold) and ab externo (canaloplasty, Stegmann Canal Expander, suprachoroidal Gold microshunt). The drawback of MIGS is that some of these procedures produce a limited IOP reduction compared to trabeculectomy. Currently, MIGS is performed in glaucoma patients with early to moderate disease and preferably in combination with cataract surgery

Structure and Function Relationship of Activated Retinal Glia in Primary Open-Angle Glaucoma Patients

Purpose. To evaluate clinically activated retinal astrocytes and Müller cells (ARAM) regarding retinal sensitivity and retinal nerve fiber layer (RNFL) thickness in primary open-angle glaucoma (POAG). Methods. Central visual field (VF; i.e., retinal sensitivity) was measured with a custom-made macular pattern by microperimetry and correlated with the presence (ARAM+) or absence (ARAM−) of ARAM on red-free fundus photography and with the corresponding RNFL by optical coherence tomography (OCT). Results. In the eyes of POAG patients, ARAM+ had overall a significantly lower retinal sensitivity (ARAM+: 7.34 dB, ARAM−: 11.9 dB; p<0.001) and lower RNFL thickness in the inferior peripapillary quadrants compared to ARAM− (RNFL superior: ARAM+ 74.2 μm, ARAM− 77.5 μm; RNFL temporal: ARAM+ 46.8 μm, ARAM− 53.0 μm, p<0.001; and RNFL inferior: ARAM+ 63.2 μm, ARAM− 73.1 μm, p<0.001). Within the same eye, ARAM+ showed a lower retinal sensitivity compared to ARAM− ([ARAM− (11.13 dB)] − [ARAM+ (9.56 dB) = 1.57 dB; p=0.25). The proportion of ARAM+ per eye correlated strongly with reduced retinal light sensitivity (p=0.02), corresponding lower peripapillary RNFL thickness (p=0.02), and lower RNFL temporal quadrant thickness (p<0.01), but not with greater age (p=0.45). Conclusion. ARAM was more frequently identified in the eyes with a lower retinal sensitivity and peripapillary RNFL thickness and may be a clinical sign in the macula for an advanced stage of POAG

Circumferential viscocanalostomy and suture canal distension (canaloplasty) for whites with open-angle glaucoma

To assess the safety and efficacy of canaloplasty (360-degree viscodilation and tensioning of the Schlemm canal) in Whites with open-angle glaucoma (OAG)