Autoantibodies Activating the β2-Adrenergic Receptor Characterize Patients With Primary and Secondary Glaucoma

Recently, agonistic autoantibodies (agAAb) activating the β2-adrenergic receptor were detected in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients and were linked to intraocular pressure (IOP) (1). The aim of the present study was to quantify β2-agAAb in the sera of glaucoma suspects and patients with primary and secondary glaucoma. Patients with OHT (n = 33), pre-perimetric POAG (pre-POAG; n = 11), POAG (n = 28), and 11 secondary OAG (SOAG) underwent ophthalmological examinations including examinations with Octopus G1 perimetry and morphometry. Twenty-five healthy individuals served as controls. Serum-derived IgG samples were analyzed for β2-agAAb using a functional bioassay. The beat-rate-increase of spontaneously beating cultured neonatal rat cardiomyocytes was monitored with 1.6 beats/15 s as cut-off. None of the sera of normal subjects showed β2-agAAb. In POAG or OHT patients increased beating rates of 4.1 ± 2.2 beats/15 s, and 3.7 ± 2.8 beats/15 s were detected (p > 0.05). Glaucoma patients with (POAG) and without perimetric (pre-POAG) defects did not differ (pre-POAG 4.4 ± 2.6 beats/15 s, POAG 4.1 ± 2.0 beats/15 s, p > 0.05). Patients with SOAG yielded mean beating rates of 4.7 ± 1.7 beats/15 s (p > 0.05). β2-agAAb were seen in 73% of OHT, 82% of pre-POAG, 82% of POAG, and 91% SOAG patients (p 0.05). The robust β2-agAAb seropositivity in patients with OHT, pre-POAG, POAG, and SOAG suggest a primary common role for β2-agAAb starting early in glaucoma pathophysiology and turned out to be a novel marker identifying all patients with increased IOP independent of glaucoma stage and entity

Verfahren zur Bestimmung einer Verlustzeit, Verfahren zur dynamischen Steuerung einer Signalanlage und Vorrichtung zur Bestimmung einer Verlustzeit

Patentschrift DE 10 2012 220 094 B

Germany: Longitudinal analysis of intraocular pressure in healthy eyes

Purpose: The knowledge of physiology of intraocular pressure (IOP) is important for the interpretation of pathophysiological alterations of IOP in glaucoma patients. Thus, the purpose of this study was a retrospective analysis of follow-up data of IOP in normal subjects in Germany. Methods: A retrospective analysis of IOP data of 112 eyes of 112 normal subjects (age: 18–81 years) of the Erlangen Glaucoma Registry (NCT00494923; ISSN 219-5008, CS-2011) was performed. Data of normal subjects with annual visits (with a number of 2–18) were analyzed. IOP was measured by Goldmann applanation tonometry at each visit in the morning. After IOP correction by the Dresdner correction table (according to the central corneal thickness, CCT), different statistical models were applied taking in account the influence of age and gender. Results: A significant influence of age and gender was observed on CCT (p < 0.001). Additionally, age affected IOP (p = 0.0018), yet, gender did not show any dependency on IOP. A significant age effect was observed on IOPcorr without differences between female and male. Quantile analysis yielded a significant change of the 0.25 percentile of IOP (p < 0.0001) and a slightly change for the 0.75 percentile of IOP (p = 0.05) over time in women. In men, a significant change was seen for the 0.5 percentile of IOP over time (p = 0.04). Conclusion: An age-dependency on CCT and IOP was observed in the German population. Additionally, gender affected CCT, yet not IOP

Longitudinal stability of the diurnal rhythm of intraocular pressure in subjects with healthy eyes, ocular hypertension and pigment dispersion syndrome

Background The diurnal fluctuation of intraocular pressure may be relevant in glaucoma. The aim of this study was to find out whether the timing of diurnal fluctuation is stable over the years. Methods Long-term IOP data from the Erlangen Glaucoma Registry, consisting of several annual extended diurnal IOP profiles for each patient, was retrospectively analyzed. Normal subjects, patients with ocular hypertension and with pigment dispersion syndrome were included because these subjects had not been treated with antiglaucomatous medications at the time of data acquisition. A cosine curve was fitted to the IOP data and the stability of individual rhythms over the years was tested using the Rayleigh test. To compare the peak times among groups, means were calculated only from subjects with a significant Rayleigh test. Results Of the fifty-two eligible subjects, a total of 364 extended diurnal IOP profiles measured in a sitting position had been collected over a period of 114 ± 39 months. The Rayleigh test indicated intraindividual stability of phase timing only in 19 subjects (36%). In subjects with pigment dispersions syndrome, peak IOP occurred on average two hours and seven minutes later during the day compared with subjects without this condition (p = 0.05). Conclusions Fitting of cosine curves to the clinical IOP profiles was generally feasible, although careful interpretation is warranted due to lack of measurements in supine position and between midnight and 7 am. The interesting observation of a phase lag in eyes with pigment dispersion syndrome warrants confirmation and exploration in future prospective studies. The analysis of the IOP data showed no stable individual rhythm in the long term in a majority of patients

Baseline magnetic resonance imaging of the optic nerve provides limited predictive information on short-term recovery after acute optic neuritis.

BACKGROUND: In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome. PURPOSE: To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity. METHODS: Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days. RESULTS: Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02). CONCLUSION: Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve

Influence of short and long chain Amyloid β peptides on the clenbuterol induced β2-adrenoceptor desensitization.

Influence of short and long chain Amyloid β peptides on the clenbuterol induced β2-adrenoceptor desensitization.</p

Fig 4 -

Influence of the Aβ peptides on the clenbuterol induced β2-adrenoceptor desensitization: The desensitization of the β-AR response by clenbuterol, was not influenced by the short chain Aβ peptides (a). However, the long chain Aβpeptides Aβ 10–37, Aβ1–40, and Aβ1–42 prevent the desensitization and exert a permanent stimulation of the β2-AR signal cascade (b).</p

Comparison of the activity of the functional β2-adrenoceptor autoantibodies (β2-AAb) of patients with glaucoma (POAG) (n = 12) and Alzheimer’s disease (AD) (n = 11).

Both agonist-like effects were blocked by the β2-adrenoceptor antagonist ICI 118.551 (0.1μM), (p˂ 0.001). The experiments with the AAb of the AD patients were done in the presence of the α1- adrenoceptor antagonist urapidil to block the agAAb against the α1-adrenoceptor that are also present in the sera of AD patients.</p

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