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1. The Relationship between Intracranial Pressure and Visual Field Zones in Normal-Tension Glaucoma Patients

   https://doi.org/10.3390/diagnostics13020174  

   Stoskuviene, Akvile ; Siaudvytyte, Lina ; Januleviciene, Ingrida ; Vaitkus, Antanas ; Simiene, Evelina ; Bakstyte, Viktorija ; Ragauskas, Arminas ; Antman, Gal ; Siesky, Brent ; Harris, Alon ( January 2023 , Diagnostics)

   Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP’s relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management. 

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2. Accommodative Exercises to Lower Intraocular Pressure

   https://doi.org/10.1155/2020/6613066  

   Stokkermans, Thomas J. ; Reitinger, Jeremy C. ; Tye, George ; Kao, Chiu-Yen ; Ragupathy, Sangeetha ; Wang, Huachun A. ; Toris, Carol B. ( December 2020 , Journal of Ophthalmology)

   Costagliola, Ciro (Ed.)

   Purpose. This study investigated how a conscious change in ocular accommodation affects intraocular pressure (IOP) and ocular biometrics in healthy adult volunteers of different ages. Methods. Thirty-five healthy volunteers without ocular disease or past ocular surgery, and with refractive error between −3.50 and +2.50 diopters, were stratified into 20, 40, and 60 year old (y.o.) age groups. Baseline measurements of central cornea thickness, anterior chamber depth, anterior chamber angle, cornea diameter, pupil size, and ciliary muscle thickness were made by autorefraction and optical coherence tomography (OCT), while IOP was measured by pneumotonometry. Each subject’s right eye focused on a target 40 cm away. Three different tests were performed in random order: (1) 10 minutes of nonaccommodation (gazing at the target through lenses that allowed clear vision without accommodating), (2) 10 minutes of accommodation (addition of a minus 3 diopter lens), and (3) 10 minutes of alternating between accommodation and nonaccommodation (1-minute intervals). IOP was measured immediately after each test. A 20-minute rest period was provided between tests. Data from 31 subjects were included in the study. ANOVA and paired t-tests were used for statistical analyses. Results. Following alternating accommodation, IOP decreased by 0.7 mmHg in the right eye when all age groups were combined ( p  = 0.029). Accommodation or nonaccommodation alone did not decrease IOP. Compared to the 20 y.o. group, the 60 y.o. group had a thicker ciliary muscle within 75 μm of the scleral spur, a thinner ciliary muscle at 125–300 μm from the scleral spur, narrower anterior chamber angles, shallower anterior chambers, and smaller pupils during accommodation and nonaccommodation ( p ’s < 0.01). Conclusion. Alternating accommodation, but not constant accommodation, significantly decreased IOP. This effect was not lost with aging despite physical changes to the aging eye. A greater accommodative workload and/or longer test period may improve the effect. 

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3. Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics

   https://doi.org/10.3390/photonics9030158  

   Verticchio Vercellin, Alice ; Harris, Alon ; Belamkar, Aditya ; Zukerman, Ryan ; Carichino, Lucia ; Szopos, Marcela ; Siesky, Brent ; Quaranta, Luciano ; Bruttini, Carlo ; Oddone, Francesco ; et al ( March 2022 , Photonics)

   Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude. 

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4. Mitochondrial DNA: a novel indicator of active inflammation in ANCA-associated vasculitides

   https://doi.org/10.1093/rheumatology/kead015  

   Giaglis, Stavros ; Daoudlarian, Douglas ; Thiel, Jens ; Rizzi, Marta ; Kyburz, Diego ; Venhoff, Nils ; Walker, Ulrich A. ( January 2023 , Rheumatology)

   ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). ANCA triggers neutrophil extracellular trap formation, which releases either mitochondrial (mt) DNA or nuclear DNA (n) DNA, contributing to inflammation. Our aim was to prospectively examine the extent and nature of circulating DNA in AAV and the clinical utility of DNA quantification.

   DNA was isolated from platelet-free plasma of consecutive GPA and MPA patients and healthy controls (HCs). mtDNA and nDNA copy numbers were quantified by PCR. Clinical data, including the BVAS, were collected.

   Ninety-two HCs (median age 51 years, 58.7% female) and 101 AAV patients (80 GPA, 21 MPA, median age 64 years, 50.5% female, BVAS range: 0–30) were included. Median mtDNA copies were 13-fold higher in patients with AAV than in HCs; nDNA concentrations did not differ. Patients with active AAV (BVAS > 0) had 4-fold higher median mtDNA copies than patients in remission (P = 0.03). mtDNA, unlike nDNA, correlated with BVAS (r = 0.30, P = 0.002) and was associated with AAV activity at multivariable analysis. Receiver operating characteristic curve analysis indicated that mtDNA quantification differentiates patients with active AAV (BVAS > 0) from HCs with 96.1% sensitivity and 98.9% specificity (area under the curve 0.99). In 27 AAV patients with follow-up, mtDNA changes but not CRP or ANCA-titres correlated with BVAS changes (r = 0.56, P = 0.002).

   mtDNA, unlike nDNA, is elevated in the plasma of AAV patients and may contribute to systemic inflammation. mtDNA could be superior to established biomarkers in the laboratory monitoring of AAV activity.

    

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5. DNA methylation age at birth and childhood: performance of epigenetic clocks and characteristics associated with epigenetic age acceleration in the Project Viva cohort

   https://doi.org/10.1186/s13148-023-01480-2  

   Bozack, Anne K. ; Rifas-Shiman, Sheryl L. ; Gold, Diane R. ; Laubach, Zachary M. ; Perng, Wei ; Hivert, Marie-France ; Cardenas, Andres ( December 2023 , Clinical Epigenetics)

   Epigenetic age acceleration (EAA) and epigenetic gestational age acceleration (EGAA) are biomarkers of physiological development and may be affected by the perinatal environment. The aim of this study was to evaluate performance of epigenetic clocks and to identify biological and sociodemographic correlates of EGAA and EAA at birth and in childhood. In the Project Viva pre-birth cohort, DNA methylation was measured in nucleated cells in cord blood (leukocytes and nucleated red blood cells, N = 485) and leukocytes in early (N = 120, median age = 3.2 years) and mid-childhood (N = 460, median age = 7.7 years). We calculated epigenetic gestational age (EGA; Bohlin and Knight clocks) and epigenetic age (EA; Horvath and skin & blood clocks), and respective measures of EGAA and EAA. We evaluated the performance of clocks relative to chronological age using correlations and median absolute error. We tested for associations of maternal-child characteristics with EGAA and EAA using mutually adjusted linear models controlling for estimated cell type proportions. We also tested associations of Horvath EA at birth with childhood EAA.

   Bohlin EGA was strongly correlated with chronological gestational age (Bohlin EGAr = 0.82,p < 0.001). Horvath and skin & blood EA were weakly correlated with gestational age, but moderately correlated with chronological age in childhood (r = 0.45–0.65). Maternal smoking during pregnancy was associated with higher skin & blood EAA at birth [B(95% CI) = 1.17 weeks (− 0.09, 2.42)] and in early childhood [0.34 years (0.03, 0.64)]. Female newborns and children had lower Bohlin EGAA [− 0.17 weeks (− 0.30, − 0.04)] and Horvath EAA at birth [B(95% CI) = − 2.88 weeks (− 4.41, − 1.35)] and in childhood [early childhood: − 0.3 years (− 0.60, 0.01); mid-childhood: − 0.48 years (− 0.77, − 0.18)] than males. When comparing self-reported Asian, Black, Hispanic, and more than one race or other racial/ethnic groups to White, we identified significant differences in EGAA and EAA at birth and in mid-childhood, but associations varied across clocks. Horvath EA at birth was positively associated with childhood Horvath and skin & blood EAA.

   Maternal smoking during pregnancy and child sex were associated with EGAA and EAA at multiple timepoints. Further research may provide insight into the relationship between perinatal factors, pediatric epigenetic aging, and health and development across the lifespan.

    

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