0000000000448223
AUTHOR
Katharina Bell
Reproducibility and Daytime-Dependent Changes of Corneal Epithelial Thickness and Whole Corneal Thickness Measured With Fourier Domain Optical Coherence Tomography.
To evaluate the reproducibility of Fourier domain anterior segment optical coherence tomography (RTVue) based on repeated measurements of corneal thickness (CT) and epithelial thickness (ET) and to test daytime-dependent changes of these parameters.Twenty-three eyes from 23 healthy volunteers were included in this prospective study. Three clinical observers performed 3 consecutive measurements each of CT and ET in 3 sessions using RTVue, resulting in 9 measurements per session. Session 1 was performed at 9 AM ± 1 hour, session 2 at 4 PM ± 1 hour on the same day, and session 3 at 9 AM ± 1 hour 2 days later. CT and ET were assessed in 9 areas: corneal vertex, 4 paracentral zones, and 4 periph…
Autoimmune biomarkers in glaucoma patients.
There is growing evidence showing an autoimmune involvement in the pathogenesis of glaucoma, and that alterations in natural occurring autoantibody levels play a key role. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also protective characteristics and influence the protein expression of neuroretinal cells. A disbalance of natural occurring autoantibodies may shift the physiological equilibrium of protective immunity leading to a predisposition for developing glaucoma. This article highlights recent advances in understanding of autoimmune mechanisms in the pathogenesis of glaucoma.
Elevated Regulatory T Cell Levels in Glaucoma Patients in Comparison to Healthy Controls.
Many studies analyzing neurodegenerative diseases demonstrate altered frequencies of regulatory T cells (Tregs). Till date, there is hardly any information concerning Tregs in glaucoma. To gather first results concerning Treg levels in glaucoma patients, we aimed to investigate whether the number of CD4(+)CD25(+)T cells vary in the patients suffering from primary open-angle glaucoma (POAG) and healthy controls.Heparinized blood samples were collected from 16 healthy individuals and 16 POAG patients. The groups were age and gender matched. A density gradient centrifugation over Ficoll-Paque was performed to isolate the peripheral blood mononuclear cells. The resulting cells were stained with…
Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension.
Purpose: To evaluate the additive intraocular pressure–lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) as an adjunct to a prostaglandin analog (PGA) in patients with open-angle glaucoma or ocular hypertension insufficiently controlled with PGA monotherapy. Methods: In this Phase 4, double-masked trial, patients aged ⩾18 years, with a mean intraocular pressure of ⩾19 and <32 mm Hg in at least one eye were randomized (1:1) to receive BBFC + PGA ( n = 96) or vehicle + PGA ( n = 92) for 6 weeks. The primary endpoint was the mean change in diurnal intraocular pressure from baseline (averaged over 09:00 and 11:00 h) at Week 6. Results: The mean diu…
Learning from the past: Mitomycin C use in trabeculectomy and its application in bleb-forming minimally invasive glaucoma surgery.
Trabeculectomy has been performed since the mid-1960s and remains the gold standard for glaucoma surgery. Newer surgical options have evolved, collectively referred to as minimally invasive glaucoma surgeries. Despite producing large intraocular pressure decreases, full-thickness procedures into the subconjunctival space may be limited by fibrosis. Mitomycin C (MMC) and 5-fluorouracil have been in use with trabeculectomy with good evidence of significantly increased success at the cost, however, of an increased risk of complications. Off-label MMC application can be found in almost all clinical trials, including in combination with minimally invasive glaucoma surgeries. We explore current e…
Supplementary_information – Supplemental material for Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension
Supplemental material, Supplementary_information for Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension by Fotis Topouzis, Ivan Goldberg, Katharina Bell, Andrew J Tatham, Antonia Ridolfi, Douglas Hubatsch, Marcelo Nicolela, Phillipe Denis and S Fabian Lerner in European Journal of Ophthalmology
Does autoimmunity play a part in the pathogenesis of glaucoma?
Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Several risk factors have been described, e.g. an elevated intraocular pressure (IOP), oxidative stress or mitochondrial dysfunction. Additionally, alterations in serum antibody profiles of glaucoma patients, upregulation (e.g. anti-HSP60, anti-MBP) and downregulation (e.g. anti-14-3-3), have been described, but it still remains elusive if the autoantibodies seen in glaucoma are an epiphenomenon or causative. However, it is known that elicited autoimmunity causes retinal ganglion cell loss resulting in glaucomatous-like damage and according to the autoaggressive nature of some autoantibodies we found…
Modulation of the Immune System for the Treatment of Glaucoma
Background At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Substantial amount of research concerning the role of the immune system in glaucoma has been performed in the recent years. This review aims to analyse changes found in the peripheral immune system, as well as selected local changes of retina immune cells in the glaucomatous retina. Methods By dividing the immune system into the innate and the adaptive immune system, a systematic literature research was performed to find recent approaches concerning the modulation of the immune …
Role of α1-adrenoceptor subtypes on corneal epithelial thickness and cell proliferation in mice
Adrenergic stimuli are important for corneal epithelial structure and healing. The purpose of the present study was to examine the hypothesis that the lack of a single α1-adrenoceptor (α1-AR) subtype affects corneal epithelial thickness and cell proliferation. Expression levels of α1-AR mRNA were determined in mouse cornea using real-time PCR. In mice devoid of one of the three α1-AR subtypes (α1A-AR−/−, α1B-AR−/−, α1D-AR−/−) and in wild-type controls, thickness of individual corneal layers, the number of epithelial cell layers, and average epithelial cell size were determined in cryosections. Endothelial cell density and morphology were calculated in corneal explants, and epithelial cell p…
Synthetic Polyclonal-Derived CDR Peptides as an Innovative Strategy in Glaucoma Therapy
The pathogenesis of glaucoma is strongly associated with the occurrence of autoimmune-mediated loss of retinal ganglion cells (RGCs) and additionally, recent evidence shows that specific antibody-derived signature peptides are significantly differentially expressed in sera of primary-open angle glaucoma patients (POAG) compared to healthy controls. Synthetically antibody-derived peptides can modulate various effector functions of the immune system and act as antimicrobial or antiviral molecules. In an ex vivo adolescent glaucoma model, this study, for the first time, demonstrates that polyclonal-derived complementarity-determining regions (CDRs) can significantly increase the survival rate …
Autoimmune aspects in glaucoma
The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in glaucoma patients. Furthermore we found antibody deposits in human glaucomatous retinae in a pro-inflammatory environment. Clinical studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies belong to the natural autoimmunity. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also neuroprotective characteristics and influence the protein expression …
Serum and antibodies of glaucoma patients lead to changes in the proteome, especially cell regulatory proteins, in retinal cells.
PURPOSE: Previous studies show significantly specifically changed autoantibody reactions against retinal antigens in the serum of glaucoma and ocular hypertension (OHT) patients in comparison to healthy people. As pathogenesis of glaucoma still is unknown the aim of this study was to analyze if the serum and antibodies of glaucoma patients interact with neuroretinal cells. METHODS: R28 cells were incubated with serum of patients suffering from primary open angle glaucoma (POAG), normal tension glaucoma (NTG) or OHT, POAG serum after antibody removal and serum from healthy people for 48 h under a normal or an elevated pressure of 15000 Pa (112 mmHg). RGC5 cells were additionally incubated wi…
Influence of Corneal Opacity on Intraocular Pressure Assessment in Patients with Lysosomal Storage Diseases
Aims To investigate an influence of mucopolysaccharidosis (MPS)- and Morbus Fabry-associated corneal opacities on intraocular pressure (IOP) measurements and to evaluate the concordance of the different tonometry methods. Methods 25 MPS patients with or without corneal clouding, 25 Fabry patients with cornea verticillata ≥ grade 2 and 25 healthy age matched controls were prospectively included into this study. Outcome measures: Goldmann applanation tonometry (GAT); palpatory assessment of IOP; Goldmann-correlated intraocular pressure (IOPg), corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF) and corneal hysteresis (CH) assessed by Ocular Response Analyzer (ORA…
Efficacy and safety of preoperative IOP reduction using a preservative-free fixed combination of dorzolamide/timolol eye drops versus oral acetazolamide and dexamethasone eye drops and assessment of the clinical outcome of trabeculectomy in glaucoma
Introduction To demonstrate that preoperative treatment for 28 days with topical dorzolamide/timolol is non-inferior (Δ = 4 mm Hg) to oral acetazolamide and topical dexamethasone (standard therapy) in terms of intraocular pressure (IOP) reduction 3 and 6 months after trabeculectomy in glaucoma patients. Materials and methods Sixty-two eyes undergoing trabeculectomy with mitomycin C were included in this monocentric prospective randomized controlled study. IOP change between baseline and 3 months post-op was defined as the primary efficacy variable. Secondary efficacy variables included the number of 5-fluorouracil (5-FU) injections, needlings, suture lyses, preoperative IOP change, hyperten…
Peptides of the variable IgG domain as potential biomarker candidates in primary open-angle glaucoma (POAG)
Autoantibody profiling has gained increasing interest in the research field of glaucoma promising the detection of highly specific and sensitive marker candidates for future diagnostic purposes. Recent studies demonstrated that immune responses are characterized by the expression of congruent or similar complementarity determining regions (CDR) in different individuals and could be used as molecular targets in biomarker discovery. Main objective of this study was to characterize glaucoma-specific peptides from the variable region of sera-derived immunoglobulins using liquid chromatography--mass spectrometry (LC-MS)-based quantitative proteomics. IgG was purified from sera of 13 primary open…
Comparative Quantitative Analysis of Porcine Optic Nerve Head and Retina Subproteomes
Optic nerve head (ONH) and retina (RET) are the main sites of damage in neurodegenerative optic neuropathies including glaucoma. Up to date, little is known about the molecular interplay between these two adjoining ocular components in terms of proteomics. To close this gap, we investigated ONH and RET protein extracts derived from porcine eyes (n = 12) (Sus scrofa domestica Linnaeus 1758) using semi-quantitative mass spectrometry (MS)-based proteomics comprising bottom-up LC&ndash
Neuroprotective effects of antibodies on retinal ganglion cells in an adolescent retina organ culture
Glaucoma, a neurodegenerative disease, is characterized by a progressive loss of retinal ganglion cells (rgc). Up- and down-regulated autoantibody immunoreactivities in glaucoma patients have been demonstrated. Previous studies showed protective effects of down-regulated antibodies [gamma (γ)-synuclein and glial fibrillary acidic protein [GFAP]) on neuroretinal cells. The aim of this study was to test these protective antibody effects on rgc in an organ culture model and to get a better understanding of cell-cell interactions of the retina in the context of the protective effect. We used an adolescent retinal organ culture (pig) with an incubation time of up to 4 days. Retinal explants were…