Longitudinal observation of the retinal nerve fibre layer in glaucoma patients treated with brimonidine combined with timolol or timolol alone

INTRODUCTION. The aim of the study was to evaluate the retinal nerve fibre layer (RNFL) thickness loss in primary open-angle glaucoma (POAG) patients treated topically with anti-glaucoma drops containing brimonidine and timolol combination or solely timolol. MATERIALS AND METHODS. Retrospective case series study of patients with POAG diagnosis followed up for a five-year period. Inclusion criteria were fulfilled by a group of 98 patients consisting of 53 combination and 45 monotherapy treatments. Intraocular pressure (IOP) at the level of 21 mm Hg or below for each measurement was observed in 52 patients, while incidences of pressure above 21 mm Hg were measured in 46 patients. POAG diagnosis was based on standard optical coherence tomography, IOP, and visual field examinations. RESULTS. Mean annual loss of RNFL thickness in the overall study group (if IOP levels are not taken into consideration) treated with timolol monotherapy was 1.8 ± 1.5 μm, while in group treated with brimonidine + timolol combination therapy it was 1.7 ± 1.5 μm (p > 0.05). In selected groups of patients with incidents of pressure rises, the mean annual loss of retinal nerve fibre layer thickness was 1.8 ± 1.6 and 1.9 ± 1.4 μm, respectively, for the monotherapy and combination therapy groups (p > 0.05). In the group of patients with no reported IOL rises, mean annual loss of RNFL thickness was 1.8 ± 0.9 and 1.1 ± 0.4 μm, respectively, for the monotherapy and combination therapy groups (p < 0.01). No significant differences were observed for the visual field mean deviation. CONCLUSIONS. POAG patients with low values of IOP might achieve slower progression of RNFL thinning on brimonidine combined with timolol therapy.

Molecular pathways in experimental glaucoma models

Glaucoma is a complex and progressive disease that primarily affects the optic nerve axons, leading to irreversible vision loss. Although the exact molecular mechanisms underlying glaucoma pathogenesis are not fully understood, it is believed that except increased intraocular pressure, a combination of genetic and environmental factors play a role in the development of the disease. Animal models have been widely used in the study of glaucoma, allowing researchers to better understand the underlying mechanisms of the disease and test potential treatments. Several molecular pathways have been implicated in the pathogenesis of glaucoma, including oxidative stress, inflammation, and excitotoxic-induced neurodegeneration. This review summarizes the most important knowledge about molecular mechanisms involved in the glaucoma development. Although much research has been done to better understand the molecular mechanisms underlying this disease, there is still much to be learned to develop effective treatments and prevent vision loss in those affected by glaucoma

Application of reflectance parameters in the estimation of the structural order of coals and carbonaceous materials. Precision and bias of measurements derived from the ICCP structural working group

Optical reflectance of vitrinite is one of the fundamental physical properties that have been used for the study of coal and carbonaceous materials. Organic matter in coals and carbonaceous matter consists mainly of aromatic lamellae, whose dimensions and spatial orientation define its internal structure. Various reflectance parameters describe well the average degree of order of the molecular structure of organic matter. Moreover, reflectance parameters are numerical values which characterize the samples unambiguously, facilitating the comparison of the optical properties of different carbonaceous materials as well as comparison between optical parameters and other physical or chemical factors. The focus of this study is the evaluation of the precision and bias of reflectance measurements (R and R) performed by various analysts in different laboratories in order to check the applicability of reflectance parameters to the estimation of the structural order of coals and carbonaceous materials. Additionally, it was desirable to compare reflectance parameters with other parameters obtained by different analytical methods able to provide structural information. The consistency and repeatability of the reflectance measurements obtained by different participants turned out to enable the drawing of similar conclusions regarding the structural transformation of anthracite during heating. Good correlations were found between the reflectance parameters studied and structural factors obtained by comparative methods. The reflectance parameters examined proved to be very sensitive to any changes of the structural order of coals and carbonaceous materials and seem to be a perfect complement to structural studies made by X-ray diffraction or Raman spectroscopy

Corneal Biomechanics in Ectatic Diseases: Refractive Surgery Implications.

BACKGROUND: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. METHOD: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgerate GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. CONCLUSIONS: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy.(undefined)info:eu-repo/semantics/publishedVersio

Electrical synapses interconnecting axons revealed in the optic nerve head – a novel model of gap junctions’ involvement in optic nerve function

Abstract Purpose To characterize newly discovered electrical synapses, formed by connexin (Cx) 36 and 45, between neighbouring axons within the optic nerve head. Methods Twenty-five Wistar rats were killed by CO2 inhalation. Proximal and distal optic nerve (ON) stumps were collected and processed for immunostainings, electron microscopy (EM) with immunogold labelling, PCR and Western blots (WB). Additional 15 animals were deeply anaesthetized, and flash visual evoked potentials (fVEP) after retrobulbar injection of saline (negative control) or 100 ?m meclofenamic acid solution (gap junctions? blocker) were recorded. Human paraffin cross-sections of eyeballs for immunostainings were obtained from the Human Eye Biobank for Research. Results Immunostainings of both rat and human ON revealed the presence of Cx45 and 36 colocalizing with ?3-tubulin, but not with glial fibrillary acidic protein (GFAP). In WB, Cx36 content in optic nerve was approximately halved when compared with retina (0.58 ± 0.005 in proximal stump and 0.44 ± 0.02 in distal stump), Cx45 showed higher levels (0.68 ± 0.01 in proximal stump and 0.9 ± 0.07 in distal stump). In immunogold-EM of optic nerve sections, we found electric synapses (formed mostly by Cx45) directly coupling neighbouring axons. In fVEP, blocking of gap junctions with meclofenamic acid resulted in significant prolongation of the latency of P1 wave up to 160% after 30 min (p Peer reviewe

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

Retinal neurons are not able to undergo spontaneous regeneration in response to damage. A variety of stressors, i.e., UV radiation, high temperature, ischemia, allergens, and others, induce reactive oxygen species production, resulting in consecutive alteration of stress-response gene expression and finally can lead to cell apoptosis. Neurons have developed their own endogenous cellular protective systems. Some of them are preventing cell death and others are allowing functional recovery after injury. The high efficiency of these mechanisms is crucial for cell survival. In this review we focus on the contribution of the most recently studied endogenous neuroprotective factors involved in retinal ganglion cell (RGC) survival, among which, neurotrophic factors and their signaling pathways, processes regulating the redox status, and different pathways regulating cell death are the most important. Additionally, we summarize currently ongoing clinical trials for therapies for RGC degeneration and optic neuropathies, including glaucoma. Knowledge of the endogenous cellular protective mechanisms may help in the development of effective therapies and potential novel therapeutic targets in order to achieve progress in the treatment of retinal and optic nerve diseases

Predegenerated Schwann cells-a novel prospect for cell therapy for glaucoma : neuroprotection, neuroregeneration and neuroplasticity

Glaucoma is an optic neuropathy that leads to irreversible blindness. Because the current therapies are not sufficient to protect against glaucoma-induced visual impairment, new treatment approaches are necessary to prevent disease progression. Cell transplantation techniques are currently considered to be among the most promising opportunities for nervous system damage treatment. The beneficial effects of undifferentiated cells have been investigated in experimental models of glaucoma, however experiments were accompanied by various barriers, which would make putative treatment difficult or even impossible to apply in a clinical setting. The novel therapy proposed in our study creates conditions to eliminate some of the identified barriers described for precursor cells transplantation and allows us to observe direct neuroprotective and pro-regenerative effects in ongoing optic neuropathy without additional modifications to the transplanted cells. We demonstrated that the proposed novel Schwann cell therapy might be promising, effective and easy to apply, and is safer than the alternative cell therapies for the treatment of glaucoma.Peer reviewe

FluoroGold-Labeled Organotypic Retinal Explant Culture for Neurotoxicity Screening Studies

Preclinical toxicity screening of the new retinal compounds is an absolute requirement in the pathway of further drug development. Since retinal neuron cultivation and in vivo studies are relatively expensive and time consuming, we aimed to create a fast and reproducible ex vivo system for retinal toxicity screening. For this purpose, we used rat retinal explant culture that was retrogradely labeled with the FluoroGold before the isolation. Explants were exposed to a toxic concentration of gentamicin and ciliary neurotrophic factor (CNTF), a known neuroprotective agent. The measured outcomes showed the cell density in retinal ganglion cell layer (GCL) and the activity of lactate dehydrogenase (LDH) in the culture medium. Gentamicin-induced oxidative stress resulted in retinal cell damage and rapid LDH release to the culture medium (p<0.05). Additional CNTF supplementation minimized the cell damage, and the increase of LDH release was insignificant when compared to LDH levels before gentamicin insult (p>0.05). As well as this, the LDH activity was directly correlated with the cell count in GCL (R=−0.84, p<0.00001), making a sensitive marker of retinal neuron damage. The FLOREC protocol could be considered as a fast, reproducible, and sensitive method to detect neurotoxicity in the screening studies of the retinal drugs