Assess the impact of false-positives (FP), false-negatives (FN), fixation losses (FL), and test duration (TD) on visual field (VF) reliability at different stages of glaucoma severity.
Retrospective.
...A total of 10 262 VFs from 1538 eyes of 909 subjects with suspect or manifest glaucoma and ≥5 VF examinations.
Predicted mean deviation (MD) was calculated with multilevel modeling of longitudinal data. Differences between predicted and observed MD (ΔMD) were calculated as a reliability measure. The impact of FP, FN, FL, and TD on ΔMD was assessed using multilevel modeling.
ΔMD associated with a 10% increment in FP, FN, and FL, or a 1-minute increase in TD.
FL had little impact on ΔMD (<0.2 decibels dB per 10% abnormal catch trials), and no level of FL produced ≥1 dB of ΔMD at any disease stage. FP yielded greater than expected MD, with a 10% increment in abnormal catch trials associated with a ΔMD = 0.42, 0.73, and 0.66 dB in mild (MD >-6 dB), moderate (-6 ≤MD <-12 dB), and severe (-12 ≤MD ≤-20 dB) disease, respectively, up to 20% abnormal catch trials, and a ΔMD = 1.57, 2.06, and 3.53 dB beyond 20% abnormal catch trials. FNs generally produced observed MDs below expected MDs. FN were minimally impactful up to 20% abnormal catch trials (ΔMD per 10% increment >-0.14 dB at all levels of severity). Beyond 20% abnormal catch trials, each 10% increment in abnormal catch trials was associated with a ΔMD = -1.27, -0.53, and -0.51 dB in mild, moderate, and severe disease, respectively. |ΔMD| ≥1 dB occurred with 22% FP and 26% FN in early, 14% FP and 34% FN in moderate, and 16% FP and 51% FN in severe disease. A 1-minute increment in TD produced ΔMDs between -0.35 and -0.40 dB.
FL have little impact on reliability in patients with established glaucoma. FP, and to a lesser extent FNs and TD, significantly affect reliability. The impact of FP and FN varies with disease severity and over the range of abnormal catch trials. On the basis of our findings, we present evidence-based, severity-specific standards for classifying VF reliability for clinical or research applications.
Abstract
Varicella Zoster Virus (VZV) is endemic worldwide, causing varicella in children and zoster upon reactivation in adults. This study concerned a metagenomic analysis of a throat swab sample ...collected in China, on a young patient suffering from Systemic Lupus Erythematosus (SLE) and diagnosed with varicella. The complete genome sequence of a VZV strain of clade 2 has been generated. Clade 2 strains are the most prevalent in Asian countries. A comparison of 223 VZV genomes identified 77 clade specific markers, 20 of them specific to clade 2. The metagenomic analysis also identified sequences covering most of the genome of the bacteria
Schaalia odontolytica
also known as
Actinomyces odontolyticus.
VZV infection and bacterial infection in the context of SLE is further discussed. Even though the patient presented only mild symptoms, this study is a reminder that vaccination against VZV is critical to avoid severe complications like bacterial superinfection or even death in the case of immunodeficiency.
Background:
Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited.
...Objective:
To compare visual and optical coherence tomography (OCT) measures following AQP4-ON, MOG-ON, and multiple sclerosis associated ON (MS-ON).
Methods:
In this cross-sectional study, 48 AQP4-ON, 16 MOG-ON, 40 MS-ON, and 31 healthy control participants underwent monocular letter-acuity assessment and spectral-domain OCT. Eyes with a history of ON >3 months prior to evaluation were analyzed.
Results:
AQP4-ON eyes exhibited worse high-contrast letter acuity (HCLA) compared to MOG-ON (−22.3 ± 3.9 letters; p < 0.001) and MS-ON eyes (−21.7 ± 4.0 letters; p < 0.001). Macular ganglion cell + inner plexiform layer (GCIPL) thickness was lower, as compared to MS-ON, in AQP4-ON (−9.1 ± 2.0 µm; p < 0.001) and MOG-ON (−7.6 ± 2.2 µm; p = 0.001) eyes. Lower GCIPL thickness was associated with worse HCLA in AQP4-ON (−16.5 ± 1.5 letters per 10 µm decrease; p < 0.001) and MS-ON eyes (−8.5 ± 2.3 letters per 10 µm decrease; p < 0.001), but not in MOG-ON eyes (−5.2 ± 3.8 letters per 10 µm decrease; p = 0.17), and these relationships differed between the AQP4-ON and other ON groups (p < 0.01 for interaction).
Conclusion:
AQP4-IgG seropositivity is associated with worse visual outcomes after ON compared with MOG-ON and MS-ON, even with similar severity of macular GCIPL thinning.
In this study, the distributing characteristics of five-fluorine (F) species in loess from the Shaanxi Loess Plateau (SLP) were determined including unextractable residual F (F
re
), extractable ...water-soluble F (F
ws
), exchangeable F (F
ex
), F bound to Fe–Mn oxides (F
fm
), and F bound to organics (F
or
). The results show that unextractable F
re
represents the highest percentage of total F (F
tf
) in loess. Of the four extractable F species, the content of F
ws
is higher than contents of the other three extractable F species in most loess samples. Loess from the southeast SLP has the highest F
ws
content while loess in the southwest SLP has the highest F
tf
content. Loess from the north SLP contains the lowest overall concentrations of F
tf
and F
ws
. Similar to F
ws
, the respective contents of F
ex
, F
fm
, and F
or
in the loess are also very low. However, their total and F
ws
cannot be negligible for F mobility in loess. Overall, the loess in the SLP is of inferior quality in terms of F because of the high F
ws
content in most samples. Based on F speciation in loess, F exposure to grazing animals and humans (particularly to children) was assessed, indicating that F in loess from the southwest SLP might pose a much greater risk than in that of other part of the SLP as the loess contains more F
tf
. However, children’s exposure to loess F via ingestion in the study area is of no concern. Regarding the risk loess F imposes on groundwater, it can be concluded that not only F
ws
but also F
ex
, F
fm
, and F
or
may be responsible for the F enrichment in local groundwater observed in the area.
Retinal and choroidal neovascularization (NV) and vascular leakage contribute to visual impairment in several common ocular diseases. The angiopoietin/TIE2 (ANG/TIE2) pathway maintains vascular ...integrity, and negative regulators of this pathway are potential therapeutic targets for these diseases. Here, we demonstrated that vascular endothelial-protein tyrosine phosphatase (VE-PTP), which negatively regulates TIE2 activation, is upregulated in hypoxic vascular endothelial cells, particularly in retinal NV. Intraocular injection of an anti-VE-PTP antibody previously shown to activate TIE2 suppressed ocular NV. Furthermore, a small-molecule inhibitor of VE-PTP catalytic activity (AKB-9778) activated TIE2, enhanced ANG1-induced TIE2 activation, and stimulated phosphorylation of signaling molecules in the TIE2 pathway, including AKT, eNOS, and ERK. In mouse models of neovascular age-related macular degeneration, AKB-9778 induced phosphorylation of TIE2 and strongly suppressed NV. Ischemia-induced retinal NV, which is relevant to diabetic retinopathy, was accentuated by the induction of ANG2 but inhibited by AKB-9778, even in the presence of high levels of ANG2. AKB-9778 also blocked VEGF-induced leakage from dermal and retinal vessels and prevented exudative retinal detachments in double-transgenic mice with high expression of VEGF in photoreceptors. These data support targeting VE-PTP to stabilize retinal and choroidal blood vessels and suggest that this strategy has potential for patients with a wide variety of retinal and choroidal vascular diseases.
The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis NASH) trial demonstrated that pioglitazone and vitamin E improved ...liver histology to varying degrees, but the mechanisms are unknown. We conducted a study to examine the changes in adipose tissue insulin resistance (Adipo‐IR) during the PIVENS trial and its relationship to histological endpoints. Adipo‐IR (fasting nonesterified fatty acids NEFAs × fasting insulin) was calculated at baseline and after 16 and 96 weeks of therapy. Compared to placebo, the baseline Adipo‐IR was not different in either the vitamin E group (P = 0.34) or the pioglitazone group (P = 0.29). Baseline Adipo‐IR was significantly associated with fibrosis score (P = 0.02), but not with other histological features or nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 16 weeks, compared to placebo, the pioglitazone group had a significant reduction in Adipo‐IR (−15.7 versus −1.91; P = 0.02), but this effect did not persist at 96 weeks (−3.25 versus −4.28; P = 0.31). Compared to placebo, Adipo‐IR in the vitamin E group did not change significantly either after 16 weeks (P = 0.70) or after 96 weeks (P = 0.85). Change in Adipo‐IR at week 16 was not associated with changes in any histological parameters at week 96, but improvement in Adipo‐IR at week 96 was significantly associated with improvement in ballooning (P = 0.03), fibrosis (P = 0.004), and NAS (P = 0.01). Conclusion: Vitamin E improved liver histology independent of changes in Adipo‐IR, and pioglitazone treatment acutely improved Adipo‐IR, but this was not sustained. Changes in Adipo‐IR were associated with changes in liver histology, including fibrosis. (HEPATOLOGY 2012)
Acriflavine, a fluorescent drug previously used for bacterial and trypanosomal infections, reduces hypoxia-inducible factor-1 (HIF-1) and HIF-2 transcriptional activity. In mice with oxygen-induced ...ischemic retinopathy, intraocular or intraperitoneal injections of acriflavine caused dose-dependent suppression of retinal neovascularization (NV) and significantly reduced expression of HIF-1-responsive genes. Intraocular injection of 100 ng caused inner retina fluorescence within 1 h that was seen throughout the entire retina between 1 and 5 days, and at 7 days after injection, strongly suppressed choroidal NV at Bruch’s membrane rupture sites. After suprachoroidal injection of 300 ng in rats, there was retinal fluorescence in the quadrant of the injection at 1 h that spread throughout the entire retina and choroid by 1 day, was detectable for 5 days, and dramatically reduced choroidal NV 14 days after rupture of Bruch’s membrane. After topical administration of acriflavine in mice, fluorescence was seen in the retina and retinal pigmented epithelium within 5 min and was detectable for 6–12 h. Administration of 0.5% drops to the cornea twice a day significantly reduced choroidal NV in mice. Electroretinographic b-wave amplitudes were normal 7 days after intravitreous injection of 100 ng of acriflavine in mice, showed mild threshold reductions at highest stimulus intensities after injection of 250 ng, and more extensive changes after injection of 500 ng. These data provide additional evidence for an important role for HIF-1 in retinal and choroidal NV and suggest that acriflavine can target HIF-1 through a variety of modes of administration and has good potential to provide a novel therapy for retinal and choroidal vascular diseases.
Key message
Acriflavine, an inhibitor of HIF-1, suppresses retinal and choroidal neovascularization.
HIF-1 plays a critical role in ocular neovascularization.
Acriflavine’s fluorescence provides a mean to track its entry and exit from the retina.
Acriflavine has therapeutic potential for the treatment of ocular neovascularization.
To determine the extent that auditory force feedback (AFF) substitution improves performance during a simulated ophthalmic peeling procedure.
A 25-gauge force-sensing microforceps was linked to two ...AFF modes. The "alarm" AFF mode sounded when the force reached 9 mN. The "warning" AFF mode made beeps with a frequency proportional to the generated force. Participants with different surgical experience levels were asked to peel a series of bandage strips off a platform as quickly as possible without exceeding 9 mN of force. In study arm A, participants peeled with alarm and warning AFF modes, the order randomized within the experience level. In study arm B, participants first peeled without AFF, then alarm or warning AFF (order randomized within the experience level), and finally without AFF.
Of the 28 "surgeon" participants, AFF improved membrane peeling performance, reducing average force generated (P < 0.01), SD of forces (P < 0.05), and force × time above 9 mN (P < 0.01). Short training periods with AFF improved subsequent peeling performance when AFF was turned off, with reductions in average force, SD of force, maximum force, time spent above 9 mN, and force × time above 9 mN (all P < 0.001). Except for maximum force, peeling with AFF reduced all force parameters (P < 0.05) more than peeling without AFF after completing a training session.
AFF enables the surgeon to reduce the forces generated with improved precision during phantom membrane peeling, regardless of surgical experience. New force-sensing surgical tools combined with AFF offer the potential to enhance surgical training and improve surgical performance.
Ferroptosis, a newly defined and iron-dependent cell death, morphologically and biochemically differs from other cell deaths. Melanoma is a serious type of skin cancer, and the poor efficacy of ...current therapies causes a major increase in mortality. Sorafenib, a multiple kinase inhibitor, has been evaluated in clinical phase trials of melanoma patients, which shows modest efficacy. Emerging evidence has demonstrated that arginase 2 (Arg2), type 2 of arginase, is elevated in various types of cancers including melanoma. To investigate the role and underlying mechanism of Arg2 in sorafenib-induced ferroptosis in melanoma, reverse transcriptase-quantitative polymerase chain reaction, western blot analysis, adenovirus and lentivirus transduction, and
tumor homograft model experiments were conducted. In this study, we show that sorafenib treatment leads to melanoma cell death and a decrease in Arg2 at both the mRNA and protein levels. Knockdown of
increases lipid peroxidation, which contributes to ferroptosis, and decreases the phosphorylation of Akt. In contrast, overexpression of Arg2 rescues sorafenib-induced ferroptosis, which is prevented by an Akt inhibitor. In addition, genetic and pharmacological suppression of Arg2 is able to ameliorate the anticancer activity of sorafenib in melanoma cells
and in tumor homograft models. We also show that Arg2 suppresses ferroptosis by activating the Akt/GPX4 signaling pathway, negatively regulating sorafenib-induced cell death in melanoma cells. Our study not only uncovers a novel mechanism of ferroptosis in melanoma but also provides a new strategy for the clinical applications of sorafenib in melanoma treatment.
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