Thin minimal rim width at Bruch’s membrane opening is associated with glaucomatous paracentral visual field loss

Elise V Taniguchi,1–3 Eleftherios I Paschalis,1,2 Dejiao Li,1,4 Kouros Nouri-Mahdavi,5 Stacey C Brauner,1 Scott H Greenstein,1 Angela V Turalba,1 Janey L Wiggs,1 Louis R Pasquale,1,6 Lucy Q Shen1 1Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston, MA, 2Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear – Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA; 3Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil; 4Department of Ophthalmology, Beijing China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Department of Ophthalmology, David Geffen School of Medicine and Stein Eye Institute, Los Angeles, CA, USA; 6Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Purpose: To compare optic nerve head (ONH) measurements in glaucomatous eyes with paracentral visual field (VF) loss to eyes with peripheral VF loss and controls.Methods: Open-angle glaucoma (OAG) patients with early paracentral VF loss or isolated peripheral VF loss as well as control subjects underwent ONH imaging with swept-source optical coherence tomography (OCT) and retinal nerve fiber layer (RNFL) imaging with spectral-domain OCT. Minimum rim width at Bruch’s membrane opening (BMO-MRW), lamina cribrosa depth (LCD), and RNFL thickness were compared among the glaucoma and control groups with one-way analysis of variance, Kruskal–Wallis test, and multiple regression analysis.Results: Twenty-nine eyes from 29 OAG patients (15 early paracentral and 14 isolated peripheral VF loss) and 20 eyes of 20 control subjects were included. The early paracentral and isolated peripheral VF loss groups had similar VF mean deviation (MD) (–5.3±2.7 dB and –3.7±3.0 dB, p=0.15, respectively). Global BMO-MRW was lower in OAG eyes than in controls (193.8±40.0 vs 322.7±62.2 µm, p<0.001), but similar between eyes with early paracentral VF loss and those with isolated peripheral VF loss (187.6±43.4 vs 200.6±36.3 µm; p>0.99). In contrast, the minimal BMO-MRW was lower in eyes with early paracentral loss (69.0±33.6 µm) than in eyes with isolated peripheral loss (107.7±40.2 µm; p=0.03) or control eyes (200.1±40.8 µm; p<0.001). Average and thinnest RNFL thickness did not differ between OAG groups (p=0.61 and 0.19, respectively). Horizontal and vertical LCD did not differ among the OAG groups and controls (p=0.80 and 0.82, respectively). Multivariable linear regression analysis among OAG cases confirmed the association between lower minimal BMO-MRW and early paracentral VF loss (β=–38.3 µm; 95% confidence interval, –69.8 to –6.8 µm; p=0.02) after adjusting for age, gender, MD, and disc size.Conclusion: Thin minimal BMO-MRW may represent a new structural biomarker associated with early glaucomatous paracentral VF loss. Keywords: paracentral loss, BMO-MRW, open angle glaucoma, optic nerve damage, swept-source OC

Chronic administration of aripiprazole activates GSK3β-dependent signalling pathways and up-regulates GABAA receptor expression and CREB1 activity in rats

Aripiprazole is a D2-like receptor (D2R) partial agonist with a favourable clinical profile. Previous investigations indicated that acute and short-term administration of aripiprazole had effects on PKA activity, GSK3β-dependent pathways, GABAA receptors, NMDA receptor and CREB1 in the brain. Since antipsychotics are used chronically in clinics, the present study investigated the long-term effects of chronic oral aripiprazole treatment on these cellular signalling pathways, in comparison with haloperidol (a D2R antagonist) and bifeprunox (a potent D2R partial agonist). We found that the Akt-GSK3β pathway was activated by aripiprazole and bifeprunox in the prefrontal cortex; NMDA NR2A levels were reduced by aripiprazole and haloperidol. In the nucleus accumbens, all three drugs increased Akt-GSK3β signalling; in addition, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3, β-catenin and GABAA receptors, NMDA receptor subunits, as well as CREB1 phosphorylation levels. The results suggest that chronic oral administration of aripiprazole affects schizophrenia-related cellular signalling pathways and markers (including Akt-GSK3β signalling, Dvl-GSK3β-β-catenin signalling, GABAA receptor, NMDA receptor and CREB1) in a brain-region-dependent manner; the selective effects of aripiprazole on these signalling pathways might be associated with its unique clinical effects