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Achim Fieß,1,* Sandra Gißler,1,* Philipp S Wild,2– 4 Karl J Lackner,5 Thomas Münzel,6 Matthias Michal,7 Michael S Urschitz,8 Norbert Pfeiffer,1 Alexander K Schuster1 1Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 2Preventive Cardiology and Preventive Medicine - Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 3Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 4German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; 5Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 6Center for Cardiology – Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 7Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 8Division of Pediatric Epidemiology, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany*These authors contributed equally to this workCorrespondence: Achim Fieß, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Tel +49-6131-17-5150, Fax +49-6131-17-8495, Email Achim.fiess@gmail.comAbstract: This study investigates the association between self-reported birth weight (BW) and the prevalence of hypertensive retinopathy (HR) in a large population-based cohort in Germany, as part of the Gutenberg Health Study (GHS). The study involved analyzing fundus photographs of 6855 participants, aged 35 to 74, to assess signs of HR, classified according to the Mitchell-Wong Classification. The research aimed to explore the correlation between fetal growth restriction indicated by BW and the frequency of HR. The results showed that the frequency of HR did not significantly differ among groups with different BW ranges. In the univariable analysis, HR was initially associated with high BW, but this association disappeared after adjusting for age, sex, and cardiovascular risk factors. No association was found between low BW and HR. The study reveals novel insights as there are no prior population-based studies specifically exploring this association.Keywords: birth weight, hypertensive retinopathy, epidemiology, population-based study

Achim Fieß,1 Marilena Brandt,1 Eva Mildenberger,2 Michael Siegfried Urschitz,3 Felix Mathias Wagner,1 Stephanie Desiree Grabitz,1 Esther Maria Hoffmann,1 Norbert Pfeiffer,1 Alexander Konrad Schuster1 1Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; 2Division of Neonatology, Department of Pediatrics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; 3Division of Pediatric Epidemiology, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyCorrespondence: Achim Fieß, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany, Tel +49-6131-17-5150, Fax +49-6131-17-8495, Email Achim.fiess@gmail.comPurpose: Prenatal growth restriction is associated with impaired neurodevelopment in childhood. This study investigated the effects of being born small for gestational age (SGA) on peripapillary retinal nerve fiber layer (pRNFL) thickness in adults born at term.Methods: A retrospective cohort study was conducted with a prospective ophthalmologic examination of participants born at full-term (gestational age ≥ 37 weeks) between 1969 and 2002. All participants were examined with spectral-domain optical coherence tomography and grouped according to their birth weight in correlation to gestational age as former moderate (birth weight (BW) percentile 3rd to < 10th) and severe SGA (< 3rd percentile), normal (10th-90th percentile, AGA), and moderately (> 90th to 97th percentile) and severely (> 97th percentile) large for gestational age (LGA) adults (18 to 52 years).Results: Overall, 547 eyes of 285 individuals (age 29.9± 9.4 years, 151 females) born at term were included. Multivariable regression analyses revealed a strong association between a lower global pRNFL thickness in the severe SGA (B=− 8.99 [95%-CI: − 12.68; − 5.30] μm; p< 0.001) and in the moderate SGA groups (B=− 6.40 [95%-CI: − 10.29; − 2.50] μm; p=0.001) compared to the reference AGA group.Conclusion: Our results indicate that restricted fetal growth affects neurologic tissue development of the optic nerve head, particularly in individuals born severely SGA at term. This indicates that fetal growth restriction may exert disturbances in the development of neurologic tissue, which persists in adulthood.Keywords: birth weight, small for gestational age, large for gestational age, peripapillary retinal nerve fiber layer, optic nerve head, epidemiology

Heart rate variability (HRV) is a powerful measure to gain information on the activation of the central nervous system and is thus a strong indicator for the overall health and emotional state of a person. Currently, the gold standard for HRV analysis is the examination of R-peaks in electrocardiograms (ECG), which requires a placement of electrodes on the torso. This is often impracticable, especially for the use in daily routines or 24/7 measurements. Photoplethysmograms (PPG) are an alternative to ECG assessment and are easier to acquire, e.g. by using fitness trackers or smart watches. Nevertheless, PPG data is more susceptible to motion artifacts. Hence, goal of this work is to develop and evaluate an artificial neural network (ANN) approach to estimate the R-peak locations in complex PPG signals. Public data collections were used as benchmark to compare our ANN-based approach to state-of-the-art methods. Results show that ANNs can improve HRV estimation during motion. HRV estimations from baseline methods (decision-tree based and automatic multiscalebased peak detection) were compared with the best performing neural network (3L-GRU) using the TROIKA dataset with respect to reference parameters obtained from a manual selection of the peaks in ECG data. In most cases, the neural network based HRV estimation was closer to the reference HRV compared to baseline methods (lower μ and σ ) Also, σ is smaller for the best performing ANN approach across most HRV parameters. Inclusion of another PPG or acceleration channel did not affect HRV estimation. Although, the neural network learning approach outperforms conventional methods, the examined PPG-based HRV estimation has still accuracy limitations. Nonetheless, the proposed estimation approach opens up new directions for further improvement.

Juliane Matlach,1 Sandra Bender,2 Jochem König,2 Harald Binder,2,3 Norbert Pfeiffer,1 Esther M Hoffmann1 1Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany; 2Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany; 3Institute of Medical Biometry and Statistics, Medical Center – University of Freiburg, Freiburg, Germany Purpose: Since the role of short- and long-term intraocular pressure (IOP) fluctuation as a predictor of glaucoma progression is still controversial, the purpose of this study was to investigate the role of IOP fluctuation in a non-selected patient cohort. Materials and methods: Two-hundred and forty eyes of 120 glaucoma patients (51% female) with a mean age of 64.5 years were included. Inclusion criteria were at least a visual field (VF) and a 48-hour diurnal phasing of IOP including nocturnal measurement. Glaucoma progression was defined as – if available – confirmed progression of reproducible VF defects in at least three VF examinations or increase of cup area on optic nerve imaging (Heidelberg Retina Tomograph [HRT]) with at least two images after baseline. If results were stable or less than previously mentioned VF or HRT examinations were available, it was classified as “no progression”. Results: Glaucoma progression was seen in seven of 240 eyes in the VF analysis and ten of 240 eyes on HRT. Of all 240 eyes, 92 and 41 eyes fulfilled the criteria to be included for progression evaluation on VF and HRT analysis, respectively. Mean time to progression ± standard error was 3.6±0.2 years on VF and 4.5±0.3 years on HRT. Univariate and multivariate Cox regression analyses revealed short-term IOP fluctuation (P

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Lutz E Pillunat,1 Carl Erb,2 Auli Ropo,3 Friedemann Kimmich,4 Norbert Pfeiffer5 1Department of Ophthalmology, University Hospital Carl Gustav Carus, Dresden, 2Augenklinik am Wittenbergplatz, Berlin, Germany; 3Santen Europe, Helsinki, Finland; 4eyecons, Pfinztal, 5Department of Ophthalmology, Mainz University Medical Center, Mainz, Germany Background: Efficacy, tolerability and safety of the novel preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% (Taptiqom®) were investigated in an observational study in Germany.Objective: To assess efficacy, tolerability and safety of the preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% in a real-life setting.Methods: Intraocular pressure (IOP) was recorded for each eye at baseline (any previous therapy or untreated) and 4–16 weeks after changing medical treatment to or initiating treatment with the preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5%. Change in IOP was evaluated over the study period for all patients and for specific pretreatment subgroups. Clinical signs such as conjunctival hyperemia and lid-parallel conjunctival folds (LIPCOF) were recorded using standardized comparative photographs. Corneal staining, subjective symptoms and local comfort were measured using a four-step scale. All adverse events were recorded.Results: Among 1,157 patients enrolled, 1,075 patients were treated with the preservative-free fixed combination as the only medication at the final visit. Medical treatment was initiated in 741 patients because of an insufficient IOP-lowering effect of the prior medication. In 343 patients, medication was changed because of tolerability issues. The preservative-free fixed combination lowered IOP significantly in the subgroup of naïve patients, all subgroups with prior monotherapy and patients with prior fixed combinations: naïve patients: −8.9 mmHg, alpha-2-agonists: −6.4 mmHg, beta-blockers: −5.7 mmHg, carbonic anhydrase inhibitors: −5.2 mmHg, prostaglandins: −4.7 mmHg, fixed-combination prostaglandins/timolol: −2.4 mmHg. At the final visit, clinical signs and subjective symptoms were improved in patients with prior medical therapy. Local comfort was rated as “very good” or “good” by 89.1% of patients at the final visit. Only few adverse events occurred during the treatment period.Conclusion: The preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% was effective, well tolerated and showed a good safety profile. Keywords: fixed combination, tafluprost, timolol, glaucoma, preservative-free medication, preservatives