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To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. Prospective 5-year study. Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], −2.8 decibels [dB]). The MD slope averaged −0.33 dB/year (median, −0.23; 95% confidence interval [CI], −0.44 to −0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55–78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37–60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38–71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3. In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was –0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression. [ABSTRACT FROM AUTHOR]

We previously reported that elevated pressure induces axonal swelling and facilitates the synthesis of the neurosteroid, allopregnanolone (AlloP), in the ex vivo rat retina. Exogenously applied AlloP attenuates the axonal swelling, suggesting that the neurosteroid plays a neuroprotective role against glaucomatous pressure-induced injuries, although mechanisms underlying neurosteroidogenesis have not been clarified. The aim of this study was to determine whether AlloP synthesis involves activation of translocator protein 18 kD (TSPO) and whether TSPO modulates pressure-induced retinal injury. Ex vivo rat retinas were exposed to various pressures (10, 35, or 75 mmHg) for 24 h. Expression of TSPO, 5α-reductase (5aRD), and AlloP was examined by quantitative real-time RT-PCR, ELISA, immunohistochemistry, and LC-MS/MS. We also examined the effects of TSPO ligands on AlloP synthesis and retinal damage. In this acute model, quantitative real-time RT-PCR and ELISA analyses revealed that elevated pressure facilitated TSPO expression. Similarly, these methods also detected enhanced 5aRD (mostly type II), which was observed in retinal ganglion cells (RGC) and the inner nuclear layer (INL). Atriol, a TSPO antagonist, suppressed pressure mediated AlloP synthesis and induced more severe histological changes in the inner retina when combined with elevated pressure. PK11195, a TSPO ligand that facilitates AlloP synthesis by itself, remarkably diminished pressure-mediated retinal degeneration. These results suggest that AlloP synthesis is induced by sequential activation of TSPO and 5aRD in an ex vivo glaucoma model, and that TSPO agonists may serve as potential therapeutic agents for the prevention of pressure-induced retinal damage. [ABSTRACT FROM AUTHOR]

The study focuses on obtaining the visco-elastic properties of the iris sphincter and dilator muscles. Two kinds of experiments were performed: the isometric contraction experiment and the isotonic quick release experiment. The length–tension relationship was obtained from the former experiment. This relationship clarified the contribution of each muscle in determining the statics of the pupil. The viscous and serial elastic properties were obtained from the latter experiment. The viscosity could be expressed by the expanded Hill’s equation as a function of velocity and contractile tension. We argue that serial elasticity is independent of contractile tension. These properties provide insights into the pupillary mechanism. [Copyright &y& Elsevier]

Purpose To investigate characteristics of lamina cribrosa (LC) defects in myopic eyes with open-angle glaucoma (OAG) using spectral-domain (SD) optical coherence tomography (OCT). Design Cross-sectional study. Participants One hundred thirty-three eyes with OAG and 83 eyes without OAG, with axial length of 24 mm or more. Methods Serial enhanced depth imaging SD OCT B-scans of the optic disc were acquired and reviewed for LC defects (diameter, ≥100 μm) and large pores (diameter, 60–100 μm). The numbers and locations of LC defects and large pores in each eye were assessed. In eyes with OAG, factors related to the number of LC defects were evaluated, as well as the association between the locations of LC defects and visual field (VF) defects (e.g., paracentral scotoma [PCS] and superior or inferior hemifield defects). Main Outcome Measures Numbers and locations of LC defects and large pores. Results In myopic eyes with and without OAG, the average numbers of LC defects were 3.8 and 0.8 and numbers of large pores were 1.9 and 1.6, respectively. In both groups, LC defects and large pores were located predominantly at the temporal periphery. Among eyes with OAG, the number of LC defects was relatively high in the eyes with greater optic disc tilt angle and worse mean deviation of the VF (both P < 0.001). The number of temporal LC defects and tilt angle were associated with presence of PCS, whereas the number of inferior and superior LC defects and torsion direction were associated with presence of superior and inferior VF defects. Conclusions Myopic eyes with OAG exhibited LC defects and large pores at similar locations as those without OAG, but in greater numbers, suggesting that these focal alternations of the LC in myopic eyes may evolve into larger defects when glaucoma develops in the eye. The number of LC defects, which was related to the optic disc tilt angle, was associated significantly with glaucomatous VF defects in both severity and location. This suggests that myopia may influence glaucomatous VF defects through optic disc tilt by way of an increased number of LC defects at the temporal periphery. [ABSTRACT FROM AUTHOR]

To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. Multicenter cross-sectional, observational cohort study. A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. Serum samples from patients with optic neuritis were tested for anti–aquaporin-4 antibodies (AQP4-Abs) and anti–myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. Antibody positivity, clinical and radiologic characteristics, and visual outcome. Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab–positive group), median VA improved to 0.4 logMAR in the AQP4-Ab–positive group, 0 logMAR in the MOG-Ab–positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab–positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab–positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab–positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti–aquaporin-4 antibody–positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory. [ABSTRACT FROM AUTHOR]

Purpose To investigate optic disc margin anatomic features in myopic eyes with open-angle glaucoma (OAG) using spectral-domain (SD) OCT. Design Cross-sectional study. Participants Two hundred four eyes of 102 participants with OAG and 106 eyes of 53 participants without glaucoma with axial length of 24 mm or more. Methods Radial SD OCT B-scans centered on the optic discs were acquired in each eye, and the SD OCT data were colocalized with the optic disc stereophotographs. Optic disc margin anatomic features were evaluated as (1) SD OCT structure coinciding with the disc margin identified in the stereophotograph, (2) border tissue configuration, and (3) presence of Bruch's membrane overhang, and their frequency was computed in each clock-hour position. Further, paired eyes of myopic participants with OAG were divided into eyes with better or worse visual field defect (VFD), according to the mean deviation of the Humphrey visual field test, and associated factors were compared. Main Outcome Measures Spectral-domain OCT structures coinciding with the visible optic disc margin in stereophotographs. Results In myopic eyes with OAG, mean axial length was 25.96±1.07 mm and mean deviation was –8.87±7.78 dB. In approximately 90% of the participants, anterior scleral opening (ASO) coincided with the temporal disc margin and Bruch's membrane opening (BMO) with the nasal disc margin. Border tissue configuration was externally oblique in the temporal region and internally oblique in the nasal region of the optic disc. Bruch's membrane overhang was observed in a relatively small percentage of eyes. The same pattern of disc margin anatomic features was observed in the myopic eyes without glaucoma. The myopic optic disc was shaped by the temporal shifting of the BMO from the ASO, and the extent of shifting was expressed as the width of γ zone parapapillary atrophy (PPA). The greater γ zone PPA width was associated significantly with the worse VFD between paired eyes. Conclusions The myopic eyes with OAG exhibited characteristic optic disc margin anatomic features that was considered to be derived from myopic deformation of the eye. The greater γ zone PPA width may increase susceptibility to the glaucomatous stress. [ABSTRACT FROM AUTHOR]