Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

Wettability and Frictional Studies of PEEK Composites against Co-Cr Alloys with Surface Textures.

With the aim of promoting the qualities for total hip joint replacement, the wettability and tribological behaviors of PEEK composites pins with two sets of different fillers (PEEK/CF or PEEK/CF/PTFE/graphite) against Co-Cr alloy discs with five categories of surface textures (polished, orthogonal, spiral, r-θ, and orthogonal combined with spiral) were explored. It is revealed that the existence of CF in PEEK matrix increases the hydrophilicity in addition to the strength of PEEK, while the addition of PTFE increases the hydrophobicity of PEEK. The Co-Cr alloy discs with hydrophilic properties can be adjusted as hydrophobic, with the depth of textured grooves exceeding the critical sag height determined by the contact angle and the groove width. It can be concluded that PEEK/CF/PTFE/graphite composite has a lower wear rate than PEEK only reinforced with CF against Co-Cr alloy, both without surface texture and with shallow or deep grooves. The existence of shallow grooves on the disc surface could help the PEEK blends to achieve a steady friction against Co-Cr alloy in addition to collecting the worn debris. PEEK blend pins with 10 vol% CF, 10 vol% PTFE and 10 vol% graphite can achieve a lower friction coefficient of no more than 0.2 against Co-Cr alloy discs with shallow grooves around 3.5 µm in orthogonal or spiral textures.

TMT proteomics analysis of cerebrospinal fluid from patients with cerebral venous sinus thrombosis.

CVST is a type of venous stroke that mainly affects young adults with no reliable diagnostic markers and effective treatment strategies for secondary pathologies. However, the underlying pathological molecular mechanisms remain unclear. Here, we systematically analyzed the molecule profiling of the cerebrospinal fluid (CSF) in CVST patients via tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for the diagnosis and treatment of CVST. Five CVST patients and five control patients were selected, and CSF samples were analyzed by TMT proteomics. Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed. Besides, parallel reaction monitoring (PRM) was utilized to validate the DEPs. 468 differentially expressed proteins were screened, 185 of which were up-regulated and 283 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis displayed that these proteins were significantly enriched in multiple pathways related to a variety of pathophysiological processes. PRM verification showed that apolipoprotein E, MMP-2, neuroserpin, clusterin, and several other molecules were down-regulated. These identified proteins reveal unique pathophysiological characteristics secondary to CVST. Further characterization of these proteins in future research could enable their application as potential therapeutic targets and biomarkers in CVST therapy. SIGNIFICANCE: Cerebral venous sinus thrombosis (CVST) is an underrated and potentially fatal cause of stroke with a reported mortality of 5-10% worldwide. Currently, in addition to anticoagulant and thrombolytic therapy, effective treatments targeting the injured brain parenchyma after CVST remain limited. Besides, accurate diagnostic markers are still sorely lacking. In the present study, we will detect the alterations of the CSF protein spectrum of CVST patients by TMT technique, screen differentially expressed proteins, analyze the functions of these signals through bioinformatics methods, and finally validate the key molecules through parallel reaction monitoring (PRM) technique. Collectively, the study aimed to offer a reference for the discovery of specific protein/pathway alterations in the CSF of CVST patients and further reveal the underlying pathogenesis, thereby providing evidence for the diagnosis and treatment of CVST.

Tribological Properties of Carbon Fiber-Reinforced PEEK against 304 Stainless Steel with Reticulate Surface Texture.

With the aim of improving the durability and reliability of polyetheretherketone (PEEK) composites reinforced with carbon fiber (CF) as thrust bearings without lubricants, a reticulate surface texture was fabricated by plane honing on a stainless steel (SS) counterpart to promote its tribological properties. Pin-on-disk experiments were designed, with the results showing that the reticulate surface texture effectively reduces the friction coefficient from 0.40 to 0.20 compared with the polished SS surface, within the range of the pv value from 0.185 to 1.85 MPa∙m/s. The wear mechanism of the polished SS surface against CF-PEEK, proven with SEM and EDS observations as well as AE measurements, is revealed, falling into abrasive wear with SS particles embedded in the friction interface around the CF strips, causing three-body contact. The reduction in the friction coefficient of the textured SS disk against the CF-PEEK pin can be achieved due to diminution of the CF wear debris and SS particles, which are scraped off by the groove edges and trapped by the groove valleys, reducing the three-body abrasive wear, while the honed plateau is used as a flank surface like a cutting tool to scratch more soft PEEK particles as the transferred film, owing to adhesive wear. This investigation suggests that the SS disk with a honed surface structure can be used as the counterpart of CF-PEEK bearings with a low friction coefficient and wear rate under dry friction.

Activating cGAS-STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis.

BACKGROUND: Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS-STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear. METHODS: A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2'3'-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry. RESULTS: cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS-STING axis. RU.521 decreased the levels of 2'3'-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1ß, and cleaved IL-1ß/pro-IL-1ß. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2'3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA. CONCLUSIONS: Our data demonstrate that repression of the cGAS-STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.

Refractive Lens Exchange Surgery in Early-Onset High Myopia Patients With Partial Cataract.

Purpose: By reporting clinical characteristics and retinal image quality before and after refractive lens replacement surgery in early-onset high myopia (eoHM) patients presenting with partial cataract, we emphasized the need for an objective way to grade the severity of partial cataracts. Methods: This retrospective, consecutive case series included six Chinese patients (nine eyes). Analysis of previous medical records, visual acuity, optometry, retinal image quality, and axial length (AXL) before surgery and after surgery was performed. Results: Five females and one male (nine eyes) with a mean (± SD) age of 11.6 ± 7.9 years (range: 4-25 years) were included in this study. The preoperative spherical power ranged from -7.5 to -42 D. The mean follow-up time was 36 months (range: 24-48 months). Phacoemulsification was followed by in-the-bag implantation of intraocular lens. For patients who were under 6 years old, posterior capsulotomy + anterior vitrectomy were performed simultaneously. All surgeries were uneventful and no postoperative complications occurred during the entire follow-up period. All patients' uncorrected visual acuity improved by ≥2 lines postoperatively(Snellen acuity). LogMAR best-corrected visual acuity was improved at 24-month (P = 0.042) and endpoint (P = 0.046) follow-ups. Modulation transfer function cutoff frequency (MTFcutoff) and objective scatter index (OSI) was significantly improved at 12-month (P = 0.025, P = 0.038), 24-month (P = 0.005, P = 0.007) and endpoint (P = 0.005, P = 0.008) follow-ups. Postoperative AXL remained stable during 2-4 year follow-ups (P > 0.05). Conclusion: Refractive lens replacement surgery is safe and effective for improving functional vision in eoHM patients presenting with partial cataract. Retinal image quality could provide a useful and objective way to facilitate partial cataract severity evaluation and surgery decision making.

Processing and Profile Control of Microhole Array for PDMS Mask with Femtosecond Laser.

Polydimethylsiloxane (PDMS) is hailed as one of the foundational materials that have been applied to different products in various fields because of its chemical resistance, low cost, excellent flexibility, and high molding capability. With the aim to achieve surface texture with high efficiency by means of electrochemical micromachining with PDMS mask, a femtosecond laser is utilized to process a precision array of micro-through-holes on PDMS films as the molds. The ablation process of PDMS with a femtosecond laser was investigated via numerical simulation verified with experiments indicating a laser energy density of 4.865 mJ/mm2 as the ablation threshold of PDMS with the melting temperature of 930 K. The spiral scanning path with optimized radial offset was developed to ablate materials from the PDMS film to form the laminated profiles, and a tapered through hole was then formed with multilayer scanning. The profile dimension and accuracy were examined as control targets in terms of laser pulse energy and scanning speed, showing that a 12 µJ femtosecond laser pulse energy and 1000 mm/s scanning speed could bring about a nearly circular laminating profile with expected smaller exit diameter than the entry diameter. All the cross-section diameters of the microcone decreased with the increase of laser scanning speed, while the taper increased gradually and then saturated around a laser scanning speed of 800 mm/s due to the energy absorption resulting in smaller ablation in diameter and depth.

Material Removal Capability and Profile Quality Assessment on Silicon Carbide Micropillar Fabrication with a Femtosecond Laser.

Silicon carbide (SiC) has a variety of applications because of its favorable chemical stability and outstanding physical characteristics, such as high hardness and high rigidity. In this study, a femtosecond laser with a spiral scanning radial offset of 5 µm and a spot radius of 6 µm is utilized to process micropillars on a SiC plate. The influence of pulsed laser beam energies and laser translation velocities on the micropillar profiles, dimensions, surface roughness Ra, and material removal capability (MRC) of micropillars was investigated. The processing results indicate that the micropillar has the best perpendicularity, with a micropillar bottom angle of 75.59° under a pulsed beam energy of 50 µJ in the range of 10-70 µJ, with a pulsed repetition rate of 600 kHz and a translation velocity of 0.1 m/s. As the laser translation velocity increases between 0.2 m/s and 1.0 m/s under a fixed pulsed beam energy of 50 µJ and a constant pulsed repetition rate of 600 kHz, the micropillar height decreases from 119.88 µm to 81.79 µm, with the MRC value increasing from 1.998 µm3/µJ to 6.816 µm3/µJ, while the micropillar bottom angle increases from 68.87° to 75.59°, and the Ra value diminishes from 0.836 µm to 0.341 µm. It is suggested that a combination of a higher pulsed laser beam energy with a faster laser translation speed is recommended to achieve micropillars with the same height, as well as an improved processing efficiency and surface finish.

Homing peptide combined with DNAzyme-based ELISA-like assay for highly specific and sensitive detection of fibrin.

A highly sensitive and specific ELISA-like chemiluminescence method for detection of fibrin has been developed. In the sensing platform, the homing peptide (CREKA), as recognition molecule, which can specially recognize the fibrin on microtiter plate, combined with G-quadruplex-based DNAzyme to form the probe of G-quadruplex-hemin DNAzyme-CREKA. After the sample solution was coated on the plates, the probe was crosslinked with fibrin through the interaction of CREKA and fibrin. Finally, luminol-H2O2 chemiluminesecence (CL) reaction was exploited for quantitative analysis of fibrin. The liner range for fibrin detection was from 0.112 pmol L-1 to 5.6 pmol L-1 with the detection limit of fibrin as low as 0.04 pmol L-1, based on a signal-to-noise ratio (S/N) of 3. Furthermore, on the basis of the high amplification efficiency of the rolling circle amplification (RCA) reaction, the method enabled to analyze fibrin with a detection limit corresponding to 0.06 fmol L-1, whose sensitivity increased 3 orders of magnitude than that of above method in the absence of RCA reaction. In particular, combined with the separation and washing steps of ELISA, the proposed method possessed higher selectivity, high-throughput and low cost, which shows promise for applications in clinical diagnosis.

An Association between Inflammation and Cerebral Venous Thrombosis: A Retrospective Study.

OBJECTIVES: Evidence is currently accumulating for the role of inflammation in cerebral venous thrombosis (CVT). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/high-density lipoprotein ratio (MHR), and systematic immune-inflammation index (SII) are easily obtainable indicators of systemic inflammations. However, there were few studies on the relationship between them and CVT. Therefore, we aimed to evaluate the connection between the occurrence of CVT and the inflammatory markers described. MATERIALS AND METHODS: The samples from 150 participants (including 90 CVT and 60 primary headaches as controls) with similar baseline characteristics were collected in this retrospective study. The NLR, PLR, MHR, SII and file records were employed to compare CVT patients with the control group. RESULTS: The levels of NLR (3.93 [2.27, 7.87] vs. 1.65 [1.31, 2.06], P < 0.001), PLR (149.52 [98.39, 198.82] vs. 107.34 [83.31, 129.47], P < 0.001), SII (896.84 [559.89, 1591.87] vs. 382.45 [273.51, 520.92], P < 0.001) and MHR (0.51 [0.40, 0.64] vs. 0.41 [0.29, 0.53], P = 0.001) were significantly higher in the CVT group. After multivariate logistic regression analysis, the SII degree (13.136, [5.675, 30.407], P < 0.001) and MHR degree (2.620, [1.123, 6.113], P < 0.01) were found as independent predictors of CVT. CONCLUSIONS: NLR, PLR, SII, and MHR may be able to assist in the diagnosis of CVT which confirmed that inflammation played an important role in CVT.

Peripheral arterial filling time and peripheral retina fluorescence features in ultra-widefield angiography.

AIM: To evaluate the peripheral arterial filling time (PAFT) and venous filling time (VFT) in eyes without known diseases that may influence filling process using ultra-widefield (UWF) fluorescein angiography (FA), and to review the peripheral retina fluorescence features. METHODS: A total of 30 eyes of 30 patients were retrospectively reviewed in this observational study. UWF-FA was performed using Optos 200Tx. PAFT and VFT was recorded. The interval between the arterial or venous filling completion and the previous photo was documented. The appearance of the far peripheral retina was described as either granular background fluorescence or mottled fluorescent band or vascular leakage. Terminal vascular patterns was described as loop pattern or branching pattern. Microvascular abnormalities such as arteriovenous shunting, vessels crossing the horizontal raphe, right angle vessels, terminal networks, capillary nonperfusion, drusen or microaneurysms were evaluated. RESULTS: The normal limits of PAFT was 3.397-8.984s and 4.399-11.753s for VFT. The appearance of the far peripheral retina, defined as granular background (63%), mottled fluorescence (20%), or vascular leakage (17%), was symmetrical between both eyes. Capillary nonperfusion (23%) and microaneurysms (40%) were more frequently found in eyes with loop pattern than in eyes with branching pattern. Other peripheral signs such as right-angle vessels (73%), and terminal networks (80%) were commonly seen on UWF-FA in the normal peripheral retina. CONCLUSION: The main courses of retinal artery and vein filling time are overlapping with each other on UWF-FA. Notably, the arterial filling process is completed in the arteriovenous phase rather than the traditionally named arterial phase. There are various manifestations in the peripheral retina of normal eyes.

Prevalence and Clinical Characteristics of Myelinated Retinal Nerve Fibres in a Chinese Teleophthalmology System.

Purpose: To investigate the prevalence and clinical characteristics of myelinated retinal nerve fibre (MRNF) in a large teleophthalmology system.Methods: All records between January 2015 and December 2015 from Daheng Prust teleophthalmology system were reviewed by 2 ophthalmologists independently. MRNF was classified into continuous group and discontinuous group according to the relationship between MRNF patches and optic disc. The number, total area and location of MRNF patches were analysed. Concomitant ocular diseases were documented.Results: Out of 51469 subjects, MRNF was detected in 304 eyes of 263 subjects with a prevalence rate of 0.51 ± 7.1% per subject and 0.30 ± 5.4% per eye. Among 304 eyes with MRNF, 239 (78.6%) eyes were in continuous group and 65 (21.4%) eyes were in discontinuous group. Single MRNF patch was found in 249 (81.9%) eyes and multiple MRNF patches were found in 55 (18.1%) eyes. MRNF of small size was found in 150 (49.3%) eyes. The ratios of multiple MRNF patches and small-sized MRNF in the continuous group were significantly higher than those in the discontinuous group (P = .014 and P < .001). In continuous group, the MRNF patches were located most frequently in the superior region (68.6%) of the optic disc; In discontinuous group, the MRNF patches were located most frequently in the inferotemporal region (38.5%) of the retina. Epiretinal membrane (12 eyes, 3.9%) was the most common concomitant ocular disease.Conclusion: MRNF is uncommon in China. MRNF usually presents unilaterally and as a single small whitish patch that is connected with optic disc.

Endoplasmic reticulum stress and oxidative stress contribute to neuronal pyroptosis caused by cerebral venous sinus thrombosis in rats: Involvement of TXNIP/peroxynitrite-NLRP3 inflammasome activation.

Cerebral venous sinus thrombosis (CVST) is a rare type of stroke, which is life-threatening in severe cases. However, considerably less attention has been concentrated on the mechanism of neural cell damage after CVST. This study aims to investigate the role of endoplasmic reticulum stress, oxidative stress, and pyroptosis in a well-established rodent model of CVST. Rat brains were harvested at 0 h, 6 h, days 1, days 3, days 7, and days 14 post-CVST for measurement of corresponding indexes. Endoplasmic reticulum stress sensors (including protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme-1α (IRE1α)), oxidative stress markers (thioredoxin-interacting protein (TXNIP) and peroxynitrite), NLRP3, caspase p20, IL-1ß, and gasdermin D (GSDMD, an indicator of pyroptosis) were separately evaluated by Western-blot and Immunohistochemistry/Immunofluorescence. Co-immunoprecipitation and Fluorescent double-labeling were employed to probe into the relationship between TXNIP/peroxynitrite and NLRP3 inflammasome. In the damaged cortex region, profuse p-PERK, p-IRE1α, TXNIP were produced and predominantly localized in neurons accompanied by a small amount expressed in microglia and astrocytes. The levels of 3-nitrotyrosine (3-NT, as a footprint of peroxynitrite), NLRP3, caspase p20, IL-1ß, and GSDMD were distinctly elevated post-CVST and cellular localization of peroxynitrite, NLRP3, caspase p20, and IL-1ß was largely observed in neurons and/or microglia. Importantly, sites of enhanced TXNIP and 3-NT immunoreactivity were colocalized with increased NLRP3 staining, indicating the involvement of TXNIP and peroxynitrite in NLRP3 inflammasome activation and subsequent pyroptosis. Besides, co-immunoprecipitation also hinted that there might be an interaction or causality between TXNIP/peroxynitrite and NLRP3 inflammasome. We concluded that endoplasmic reticulum stress and oxidative stress may jointly lead to neuronal NLRP3 inflammasome activation and pyroptosis after CVST.

Analysis of related factors of optical quality in healthy Chinese adults: a community-based population study.

BACKGROUND: In recent years, visual quality has been extensively investigated in various conditions. In this community-based population study, we analyzed the effects of aging, refraction, and Lens Opacification Classification System III (LOCSIII) score on retinal imaging quality in healthy Chinese adults. METHODS: This cross-sectional study was conducted on sub-group subjects from The Handan Eye Study between October 2012 and January 2013. Healthy subjects over 30-years-old with logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) less than 0 were included. Retinal image quality was measured by optical quality analysis system (OQAS) and recorded as modulation transfer function cutoff frequency (MTFcutoff), OQAS value (OV) 100%, OV20%, OV9%, Strehl ratio (SR), and objective scatter index (OSI). The correlation between age, spherical equivalent refraction (SE), LOCSIII score, and optical quality parameters were investigated by multivariate analysis. RESULTS: Among 1108 verified subjects, 690 subjects (1380 eyes) met the inclusion criteria. Their age ranged from 30 to 76 years, SE ranged from -4.75 to 2.75 D. They were divided into five age groups (30-39, 40-49, 50-59, 60-69, and ≥70 years) for further analysis. After multivariate analysis by mixed-effect linear model, SR (t =  -3.03, P = 0.002), OV20% (t = -2.39, P = 0.017), and OV9% (t = -3.16, P = 0.001) significantly decreased with the increasing age, whereas logMAR BCVA (t = 4.42, P < 0.001) and OSI (t = 4.46, P < 0.001) significantly increased with age. As SE increased, SR (t = 2.74, P = 0.01), OV20% (t = 2.31, P = 0.02), and OV9% (t = 2.79, P = 0.005) significantly elevated, and OSI (t = -3.38, P < 0.001) significantly decreased. With the increase in cortical opacity score, all optical quality parameters except for SR significantly decreased, including MTFcutoff (t = -2.78, P = 0.01), OV100% (t = -2.78, P = 0.005), OV20% (t = -2.60, P = 0.009), and OV9% (t = -2.05, P = 0.040). As posterior sub capsular opacity score increased, MTFcutoff (t = -2.40, P = 0.02) and OV100% (t = -2.40, P = 0.01) significantly decreased, while OSI (t = 7.56, P < 0.001) significantly increased. CONCLUSIONS: In healthy Chinese adult population, optical quality-related parameters significantly decrease with the increasing age, and OSI significantly increases with age. In normal BCVA subjects, optical quality is significantly impacted by cortical and posterior sub capsular opacity rather than by nuclear opacity.

Repeatability and agreement of two anterior segment OCT in myopic patients before implantable collamer lenses implantation.

AIM: To evaluate the intra-operator repeatability of time domain and swept-source Fourier domain anterior segment optical coherence tomography (AS-OCT), namely, Visante AS-OCT and Casia SS-1000 OCT, in measuring the preoperative parameters of implantable collamer lens (ICL) in myopic eyes, as well as the agreement between the two devices. METHODS: A total of 97 eyes from 49 myopes were investigated in this prospective case series study. The anterior chamber depth (ACD), angle-to-angle distance (ATA), pupil diameter (PD) and crystalline lens rise (CLR) in all subjects were measured for three times during one session by the same operator. The repeatability was evaluated using the within-subject standard deviation (Sw), repeatability limits and intraclass correlation coefficients (ICC). The agreement between the two systems was evaluated using the Bland-Altman plots and 95% limits of agreement (LoA). RESULTS: The repeatability limits of Visante AS-OCT in measuring ACD, ATA, PD and CLR were 0.099, 0.141, 0.304, and 0.079 mm, respectively. The repeatability limits of Casia SS-1000 OCT in measuring ACD, ATA, PD, and CLR were 0.105, 0.127, 0.357, and 0.082 mm, respectively. Excellent repeatability could be attained in both devices, with the ICC>0.8 for all the measured variables. The interdevice agreement was excellent (P>0.05) for ACD and ATA, but poor (P<0.05) for PD and CLR. CONCLUSION: Good repeatability can be attained by time domain and swept-source Fourier-domain OCT for all the measured variables. Moreover, interdevice agreement analysis suggests that interchangeable measurements between two devices can be achieved for ACD and ATA, but not for PD and CLR; but the differences in measurements were not clinically significant.

Macular retinal thickness and flow density change by optical coherence tomography angiography after posterior scleral reinforcement.

Optical coherence tomography angiography (Angio-OCT) has introduced a new non-invasive, quantitative method to assess superficial and deep capillary networks of the retina. In this study, we investigated macular retinal thickness and flow density change following posterior scleral reinforcement (PSR) surgery, using an RTVue XR Avanti Angio-OCT (A2016.2.0.35, Optovue, Fremont, CA), in patients with pathological myopia. A total of 13 patients with pathological myopia were recruited and all patients completed the 6 months follow-up visit. Data from 22 eyes were used in this study. The mean age was 36.23±15.29 years, and 43% (n=6) were men. Spherical equivalent refractive error (SE) ranged from -8.0 to -24.0 D. Post-operative axial length, best-corrected visual acuity and SE did not change significantly at each follow-up, compared with preoperative measure (all P>0.05). Postoperative flow density of superficial and deep retinal layers at each sector did not change significantly at each follow-up, compared to pre-operative measure (all P>0.05). However, we found significant decrease in retinal thickness of parafovea-inferior sector after PSR surgery (P<0.01), indicating potential relaxation of vitreofoveal traction after PSR surgery.

Diagnostic ability of ganglion cell complex thickness to detect glaucoma in high myopia eyes by Fourier domain optical coherence tomography.

AIM: To evaluate the ability of macular ganglion cell complex (GCC) thickness using Fourier domain optical coherence tomography (FD-OCT) to detect glaucoma in highly myopic eyes. METHODS: Cross-sectional study. A total of 114 participants, consecutively were enrolled. Macular GCC thickness and peripapillary retinal nerve fiber layer (RNFL) thickness were obtained with RTVue FD-OCT. Receiver operating characteristics curves were constructed for each measurement parameter, and areas under the curves (AUCs) were compared. RESULTS: Both the average GCC and average RNFL thickness showed negative correlations with axial length (rGCC=-0.404, P=0.001; rRNFL=-0.561, P<0.001). The largest AUCs from GCC, and RNFL parameters were 0.968 [global loss volume (GLV)], and 0.855 (average RNFL), respectively. GLV was significantly better for detecting high myopic glaucoma than average RNFL (P<0.001). CONCLUSION: Macular GCC thickness has higher diagnostic power than peripapillary RNFL thickness to discriminate glaucoma patients from non-glaucoma subjects in high myopia.

Advanced oxidation protein products promote NADPH oxidase-dependent ß-cell destruction and dysfunction through the Bcl-2/Bax apoptotic pathway.

The accumulation of plasma advanced oxidation protein products (AOPPs) has been linked with diverse disorders, including diabetes, chronic kidney disease, obesity, and metabolic syndrome. The aim of the present study was to evaluate the pathophysiological relevance of AOPPs in ß-cell destruction and dysfunction. Exposure of cultured rat ß-cells (INS-1) to AOPPs induced an increase in Bax expression, caspase-3 activity, and apoptosis as well as a decrease in Bcl-2 expression in a dose- and time-dependent manner. AOPP challenge rapidly increased the production of intracellular superoxide by activation of NADPH oxidases, demonstrated by p47phox translocation and interaction with p22phox and gp91phox, and this in turn led to apoptosis. AOPPs treatment resulted in ß-cell apoptosis, AOPPs accumulation, and decreased insulin content in pancreas and plasma in unilateral nephrectomized rats. Chronic inhibition of NADPH oxidase by apocynin prevented ß-cell apoptosis and ameliorated insulin deficiency in AOPP-challenged rats. This study demonstrates for the first time that accumulation of AOPPs promotes NADPH oxidase-dependent ß-cell destruction and dysfunction by the Bcl-2/Bax-caspase apoptotic pathway. This finding may provide a mechanistic explanation for ß-cell destruction and dysfunction in patients with diverse disorders.

Comparison of time-domain, spectral-domain and swept-source OCT in evaluating aqueous cells in vitro.

Different optical coherence tomography (OCT), both time-domain OCT and spectral-domain OCT, has been used to evaluate anterior chamber cells in previous studies. Recently, commercial swept-source OCT was available. The comparison among three kinds of OCTs have not been done before. Here, we compared their feasibility in discerning aqueous cells in vitro. The peripheral blood was diluted to eight different cell concentrations and was packed into plastic-film bag. Each sample was tested using different scan modes of three OCTs. It was easy to discern aqueous cells from background noise in both Visante AS-OCT and RTVue XR Avanti OCT, but difficult in Casia SS-1000 OCT. The measured blood cell densities in high-resolution corneal cross-sectional scan of Visante AS-OCT, cornea line scan and 3D cornea scan of RTVue XR Avanti OCT were highly correlated with the actual blood cell concentration (Pearson correlation=0.991, 0.989, and 0.993 respectively). The mean adjusted cell densities of cornea line scan (10.46±2.87 spots mm-2) and 3D cornea scan (11.01±2.47 spots mm-2) of RTVue XR Avanti OCT were significantly larger than that of Visante AS-OCT (1.55±1.75 spots mm-2) (P<0.01). Our study demonstrated that RTVue XR Avanti OCT, a spectral-domain OCT, is superior to other two OCTs in evaluating aqueous cells.