CONTRIBUTION FACTORS OF EFFECTIVE LENS POSITION, TILT, AND DECENTRATION DURING FLANGED SCLERAL FIXATION OF INTRAOCULAR LENS: A Model Eye Study.

PURPOSE: The authors aimed to elucidate the factors related to effective lens position, tilt, and decentration of scleral fixed intraocular lenses (IOLs) with a flanged haptic technique in an artificial eye model using anterior segment optical coherence tomography. METHODS: Two bent 27-gauge needles were passed through a 1.0- or 2.0-mm scleral tunnel, 2.0 mm posterior to the limbus and 180° apart. Both haptics of a three-piece IOL were docked with guide needles and externalized. Factors related to the IOL position were analyzed using anterior segment optical coherence tomography and a stereomicroscope. RESULTS: The 1.0-mm scleral tunnel induced a significantly longer effective lens position than the 2.0-mm tunnel and suture fixation ( P < 0.05 and P < 0.01, respectively). Discrepancy in scleral tunnel length induced higher decentration of the optic to the opposite side of the haptic-embedded shorter tunnel and tilt perpendicular to the fixed axis than that in the scleral tunnel of the same length ( P < 0.001 and P < 0.05, respectively). If the scleral fixation points of both haptics are not exactly 180° apart, the IOL may become decentered and tilted ( P < 0.01 and P < 0.05, respectively). CONCLUSION: In the flanged haptic technique, the length, balance, and position of both scleral tunnels determine IOL effective lens position, tilt, and decentration.

Microfluidic gut-on-a-chip with three-dimensional villi structure.

Current in vitro gut models lack physiological relevance, and various approaches have been taken to improve current cell culture models. For example, mimicking the three-dimensional (3D) tissue structure or fluidic environment has been shown to improve the physiological function of gut cells. Here, we incorporated a collagen scaffold that mimics the human intestinal villi into a microfluidic device, thus providing cells with both 3D tissue structure and fluidic shear. We hypothesized that the combined effect of 3D structure and fluidic shear may provide cells with adequate stimulus to induce further differentiation and improve physiological relevance. The physiological function of our '3D gut chip' was assessed by measuring the absorptive permeability of the gut epithelium and activity of representative enzymes, as well as morphological evaluation. Our results suggest that the combination of fluidic stimulus and 3D structure induces further improvement in gut functions. Our work provides insight into the effect of different tissue environment on gut cells.

Impact of scleral tunnel length on the position of IOLs in flanged intrascleral haptic fixation.

PURPOSE: To investigate the effect of scleral tunnel length on the effective lens position and tilt of the intraocular lens (IOL) in flanged intrascleral haptic fixation (ISHF) using anterior segment optical coherence tomography (AS-OCT). SETTING: Tertiary institution. DESIGN: Retrospective case-control study. METHODS: This study included 55 and 42 eyes that underwent ISHF with 1.0- and 2.0-mm scleral tunnels, respectively. Twenty-three eyes that underwent sutured fixation were used as a control. The anterior chamber depth (ACD), scleral tunnel length, incident angle of haptic, and tilting of optic were analyzed using AS-OCT. RESULTS: The mean postoperative ACD, vertical tilt angle, and spherical equivalent of the 1.0-mm were 5.27 ± 0.39 mm, 6.04 ± 4.87°, and 0.38 ± 1.03 D, respectively. The ACD and vertical tilt angle of the 1.0-mm were larger than those of the others (p<0.001 and p<0.05, respectively), and the postoperative spherical equivalent was more hyperopic (p<0.05). The 2.0-mm exhibited a lower frequency of tilting greater than 7°. The inter-eye difference in ACD between in-the-bag fixation and ISHF of the1.0-mm tunnel was significantly greater than that in the 2.0-mm tunnel (p<0.05). The 1.0 mm tunnel had a significantly larger incident angle and a longer tunnel length (p<0.001, respectively) and showed a greater difference in the tunnel length on both sides (p<0.05). CONCLUSION: A shorter tunnel yielded a more unstable IOL position, greater variation in angle and tunnel length, and longer ACD during ISHF. An exact 2.0-mm tunnel must be created on both sides to achieve a stable and predictable IOL position.

Temporary Pupil Occlusion and Retrolenticular Air Bubble Injection for Descemet Membrane Endothelial Keratoplasty in Vitrectomized Unicameral Eyes.

PURPOSE: The aim of this study was to describe a surgical method that can be easily and safely performed during Descemet membrane endothelial keratoplasty in patients who had previously undergone pars plana vitrectomy with transscleral fixation of the intraocular lens. METHODS: This report reviewed 2 Descemet membrane endothelial keratoplasty procedures performed in patients with vitrectomized unicameral eyes. The proposed technique is characterized by the temporary suture of the pupillary aperture to block the forward flow of vitreous humor and prevent the abrupt loss of air tamponade due to backward movement of the air bubble into the vitreous cavity. At the same time, another air bubble is injected behind the scleral-fixated intraocular lens to induce forward movement of the iris-intraocular lens diaphragm through buoyancy. Thus, the depth of the anterior chamber is reduced, allowing easier unscrolling of the Descemet membrane endothelial keratoplasty lenticule. RESULTS: Pupil closure and buoyancy of the air bubble allow the anterior chamber to be separated from the inflow of vitreous cavity fluid and maintained adequately shallow. During the keratoplasty, the graft is then easily unscrolled without the support of the capsular diaphragm. Postoperatively, the air bubble is maintained in the anterior chamber for a sufficient period. Nd:YAG laser suture lysis is performed after complete absorption of the air bubble during outpatient follow-up. CONCLUSIONS: Temporary pupil occlusion and retrolenticular air bubble injection provide a stable surgical approach in challenging cases of postvitrectomized unicameral eyes.

Maternal exposure to nanoplastic induces transgenerational toxicity in the offspring of rotifer Brachionus koreanus.

Nanoplastics have received a great deal of attention as evidence of their potential harmful effects on aquatic biota. In zooplankton, ingestion is known as a major uptake route of nanoplastics due to the low feeding selectivity of filter-feeding organisms. In this study, we propose maternal transfer as an alternative uptake route of nanoplastic in the rotifer Brachionus koreanus. Exposure to nanoplastics in parental rotifers induced maternal transfer in offspring, as revealed by fluorescence in rotifer eggs. We further verified that egg shells are not permeable to nanoplastics, and the observed fluorescence was associated with nanoplastic particles, not leached fluorescent dye, supporting the idea that nanoplastics can be transferred through an intrinsic maternal transfer route. This maternal transfer induced adverse effects on life-cycle parameters, including development and reproduction, in offspring rotifers, and was associated with oxidative stress. The results of this study shed light on the ecological impacts of nanoplastics in marine environments.

Toxicological effects of tire rubber-derived 6PPD-quinone, a species-specific toxicant, and dithiobisbenzanilide (DTBBA) in the marine rotifer Brachionus koreanus.

The ingredients of tire-rubber products include a complex range of chemicals additives, most of which are leached into surrounding water as unmeasured toxicants with unexplored ecotoxicological impacts. The present study summarizes the reported species-specific acute toxicity of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), the ozonation product of anti-oxidant 6PPD used in tire rubber. Also, chronic toxicity and oxidative response of 6PPD-Q and another tire-rubber derivative, 2',2'''-dithiobisbenzanilide (DTBBA), in rotifer Brachionus koreanus were investigated. Although 6PPD-Q has been reported to be highly toxic to several species of salmonids, only moderate chronic toxicity was observed in B. koreanus. In contrast, DTBBA significantly retarded the population growth and fecundity. The varying toxicity of 6PPD-Q and DTBBA was linked to the level of reactive oxygen species in which DTBBA exposure caused a significant concentration-dependent increase. Our results imply unanticipated risks to aquatic species posed by chemical additives in tire-rubber which may be considered emerging contaminants of toxicological concern.

Environmental DNA surveillance of biocontamination in a drinking water treatment plant.

A clean and adequate supply of drinking water is essential to life and good health. However, despite the risk of biologically derived contamination of drinking water, monitoring of invertebrate outbreaks has relied primarily on naked-eye inspections that are prone to errors. In this study, we applied environmental DNA (eDNA) metabarcoding as a biomonitoring tool at seven different stages of drinking water treatment, from prefiltration to release from household faucets. While the composition of invertebrate eDNA communities reflected the communities of the source water in earlier stages of the treatment, several predominant invertebrate taxa (e.g., rotifer) were shown to be introduced during purification, but most were eliminated in later treatment stages. In addition, the limit of detection/quantification of PCR assay and read capacity of high-throughput sequencing was assessed with further microcosm experiments to estimate the applicability eDNA metabarcoding to the biocontamination surveillance in drinking water treatment plants (DWTPs). Here we propose a novel eDNA-based approach for sensitive and efficient surveillance of invertebrate outbreaks in DWTPs.

Efficacy of Topical 0.05% Cyclosporine A for Ocular Surface Disease Related to Topical Anti-Glaucoma Medications.

Purpose: We aimed to determine the therapeutic efficacy of 0.05% topical cyclosporine A (CsA) for chronic ocular surface disease (OSD) in patients using benzalkonium chloride (BAK)-preserved antiglaucoma eye drops. Methods: A prospective, randomized, paired-eye, controlled clinical trial was conducted with participants who had been instilling at least one BAK-preserved topical antiglaucoma drug in both eyes for at least 6 months. Topical CsA was only applied in randomly selected unilateral eyes. Visual field (VF) indices, ocular surface parameters, tear meniscus height (TMH), and matrix metalloproteinase-9 (MMP-9) immunoassay were evaluated at baseline and at 2 and 4 months. Results: Seventy eyes from 35 participants were included in the study. The Schirmer I, tear breakup time, and TMH increased by 4.5 ± 8.6 mm (P < 0.01), 5.0 ± 5.3 s (P < 0.001), and 85.4 ± 159.0 µm (P < 0.01) in the treated eyes at 4 months from baseline, respectively. The ocular staining score and MMP-9 positivity in the treated eyes decreased by 2.2 ± 1.3 (P < 0.001) and 0.7 ± 0.9 points (P < 0.001), respectively, at 4 months. In untreated eyes, only TMH increased by 41.4 ± 92.1 µm (P = 0.016) from baseline to 4 months. In VF indices, the tracking failure frequency was 19.09% ± 21.62%, and the test duration was 336.0 ± 79.5 s in the treated eyes at 4 months, which were lower than 34.37% ± 23.13% (P < 0.001) and 375.9 ± 70.7 s (P < 0.05) in the nontreated eyes. Conclusion: Application of topical 0.05% CsA significantly improved the OSD parameters and the reliability indices of VF tests. This study was registered with the Clinical Research Information Service (CRIS) (number KCT0007124).

Effects of atrazine and diuron on life parameters, antioxidant response, and multixenobiotic resistance in non-targeted marine zooplankton.

Atrazine and diuron are among the most widely used antifoulant biocides in the world. Due to their persistence in the environment, they can induce adverse effects on non-targeted organisms. In this study, we investigated the chronic in vivo toxicity of atrazine and diuron with further assessments on oxidative stress responses (e.g., oxidative stress, antioxidant) and multixenobiotic resistance (MXR) function in the rotifer Brachionus koreanus, a non-targeted microzooplanktonic grazer at the primary level of the marine food chain. Although similar oxidative response was shown by both biocides, diuron induced stronger retardation on reproduction and population growth rates of B. koreanus while moderate effects were observed by atrazine. This higher toxicity of diuron was shown to be associated with its stronger inhibition of MXR conferred by P-glycoprotein and multidrug resistance proteins which play as a first line of defense by transporting various toxicants out of a cell. Our study provides new insight into non-targeted effects of biocides on marine zooplankton and mechanisms beyond their different degrees of toxicity.

Phenotypic toxicity, oxidative response, and transcriptomic deregulation of the rotifer Brachionus plicatilis exposed to a toxic cocktail of tire-wear particle leachate.

Tire-wear particles (TWPs) are potential source of microplastic (MP) pollution in marine environments. Although the hazardous effects of MPs on marine biota have received considerable attention, the toxicity of TWPs and associated leachates remain poorly understood. Here, to assess the toxicity of TWP leachate and the underlying mechanisms of toxicity, the phenotypic and transcriptomic responses of the rotifer Brachionus plicatilis were assessed with chemistry analysis of a TWP leachate. Although acute toxicity was induced, and a variety of metals and polyaromatic hydrocarbons were detected in the leachate, levels were below the threshold for acute toxicity. The results of particle analysis suggest that the acute toxicity observed in our study is the result of a toxic cocktail of micro- and/or nano-sized TWPs and other additives in TWP leachate. The adverse effects of TWP leachate were associated with differential expression of genes related to cellular processes, stress response, and impaired metabolism, with further oxidative stress responses. Our results imply that TWPs pose a greater threat to marine biota than other plastic particles as they constitute a major source of nano- and microplastics that have synergistic effects with the additives contained in TWP leachate.

Relationship between proteinuria and optical coherence tomographic features of the chorioretina in patients with pre-eclampsia.

This retrospective study aimed to evaluate the correlation between ophthalmologic factors and proteinuria in patients with pre-eclampsia using swept-source optical coherence tomography (OCT) and OCT angiography. In total, 61 pregnant patients diagnosed with pre-eclampsia were recruited during their hospital stay. The authors investigated the relationship between urine protein-creatinine ratio (PCR) and chorioretinal measurements including choroidal thickness (CT), choroidal vascularity index (CVI), foveal avascular zone (FAZ), vascular density (VD), ganglion cell layer+ (GCL+) and GCL++. The associations between mean arterial pressure (MAP) and ophthalmologic factors were also evaluated. Central subfield CT of the right eye (p = 0.031) and paracentral CT of both eyes were related to higher PCR (≥1.35 mg/mg). A significant association with PCR after logarithm transformation was noted (r = 0.284, p = 0.026). Retinal measurements (FAZ, VD, GCL+ and GCL++) and CVI were not related with PCR. There was a positive association between MAP and PCR after logarithm transformation (r = 0.296, p = 0.021); however, chorioretinal factors were not related with MAP. In pregnant women with pre-eclampsia, CT using OCT is a novel factor that is correlated with PCR. Ocular structural alteration in patients with pre-eclampsia may be one of systemic vascular changes caused by pre-eclampsia rather than hypertension.

Association of tear matrix metalloproteinase 9 immunoassay with signs and symptoms of dry eye disease: A cross-sectional study using qualitative, semiquantitative, and quantitative strategies.

PURPOSE: This study aimed to analyze the association of tear matrix metalloproteinase 9 (MMP-9) immunoassay with the severity of dry eye (DE) signs and symptoms through qualitative, semiquantitative, and quantitative evaluations of immunoassay band. MATERIALS AND METHODS: This cross-sectional study enrolled 320 eyes of 320 patients. The clinical signs of DE were assessed using the Ocular Surface Disorder Index (OSDI) score, visual analogue scale (VAS), tear breakup time (tBUT), tear volume evaluation by tear meniscometry, and staining scores of the cornea and conjunctiva by the Oxford grading scheme. The tear MMP-9 immunoassay results were interpreted using qualitative (positive or negative), semi-quantitative (reagent band density on a four-point scale: 0 = negative; 1 = weakly positive; 2 = moderately positive; 3 = strongly positive), and quantitative (ratio of reagent band density to control band density) indicators. RESULTS: Positive MMP-9 immunoassay results were significantly related to shorter tBUT, tBUT ≤3 seconds, higher corneal staining score, corneal staining score ≥2, and conjunctival staining score ≥2. The semi-quantitative results of the MMP-9 immunoassay were positively correlated with higher corneal staining score (r = 0.122, p = 0.029) and negatively correlated with tBUT (r = -0.125, p = 0.025). However, in the quantitative analysis, none of the DE signs or symptoms were correlated to the band density of the MMP-9 immunoassay. CONCLUSIONS: The positive MMP-9 immunoassay results were related to the severity of ocular signs of DE. However, using quantitative measures of the MMP-9 immunoassay to assess the clinical severity of DE requires further investigation.

Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells.

Uncontrolled retinal pigment epithelial (RPE) cell proliferation/migration contribute to the pathological tractional membrane development in proliferative vitreoretinopathy. Recent studies reported that microRNA (miR)-124 controls various cellular functions via the direct targeting of small Ras homolog family member G (RHOG). Therefore, we investigated the role of the neuron-specific miR-124 and RHOG in RPE cell proliferation/migration. Alterations in miR-124 and RhoG expression, as per cell confluence were evaluated through quantitative real-time PCR and western blotting, respectively. After transfection with miR-124, we quantified RPE cell viability and migration and observed cell polarization and lamellipodia protrusions. We evaluated the expression of RHOG/RAC1 pathway molecules in miR-124-transfected RPE cells. Endogenous miR-124 expression increased proportionally to RPE cell density, but decreased after 100% confluence. Overexpression of miR-124 decreased cell viability and migration, BrdU incorporation, and Ki-67 expression. Inhibition of endogenous miR-124 expression promoted RPE cell migration. Transfection with miR-124 reduced cell polarization, lamellipodia protrusion, and RHOG mRNA 3' untranslated region luciferase activity. Like miR-124 overexpression, RhoG knockdown decreased RPE cell viability, wound healing, and migration, and altered the expression of cell cycle regulators. These results suggest that miR-124 could be a therapeutic target to alleviate fibrovascular proliferation in retinal diseases by regulating RPE proliferation/migration via RHOG.

Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study.

BACKGROUND: Typhoid causes significant mortality among young children in resource-limited settings. Conjugate typhoid vaccines could significantly reduce typhoid-related child deaths, but only one WHO-prequalified typhoid conjugate vaccine exists for young children. To address this gap, we investigated the safety, immunogenicity and dose-scheduling of Vi-DT typhoid conjugate vaccine among children aged 6-23 months. METHODS: In this single center, observer blind, phase II trial, participants were randomly assigned (2:2:1) to receive one or two doses of Vi-DT or comparator vaccine. Anti-Vi IgG titer and geometric mean titers (GMT) were determined at 0, 4, 24 and 28 weeks. Data were analyzed using per-protocol and immunogenicity (a subset of intention-to-treat analysis) sets. The trial is registered with ClinicalTrials.gov (NCT03527355). FINDINGS: Between April and July 2018, 285 children were randomized; 114 received one or two doses of Vi-DT while 57 received comparator. 277 completed the study follow-up per protocol; 112 and 110 from single- and two-dose Vi-DT schedules, respectively and 55 from the placebo group were included in the per protocol analysis. Safety profile is satisfactory. Thirteen serious adverse events were reported during the 28-week follow-up, none of which were related to Vi-DT. The seroconversion rate four weeks after the first dose was 100% (95% CI 98·3-100) in Vi-DT recipients and 7·0% (95% CI 2·8-16·7) in comparator recipients (p<0·0001). Similarly, the seroconversion rate 4 weeks after the second dose was 98·2% (95% CI 93· 6-99·5) and 21·8% (95% CI 13·0-34·4) among Vi-DT and comparator groups, respectively (p<0·0001). Anti-Vi IgG GMT was significantly higher in Vi-DT than in control group at all post-vaccination visits (p<0·0001). INTERPRETATION: Both single and two doses of Vi-DT vaccine are safe, well tolerated, and immunogenic for infants and toddlers in a moderately endemic setting.

Ocular manifestations in a patient with de novo Fabry disease.

Fabry disease (FD) is an X-linked, recessively inherited, rare, progressive, disorder of glycosphingolipid metabolism affecting multiple organs resulting in organ dysfunction. It is rare to find only one FD affected subject with a de novo mutation. Here we report a case of a 41-year-old Asian male diagnosed with de novo FD. Comprehensive ophthalmological evaluation was performed using slit lamp, color fundus photography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. On slit lamp examination, cornea verticillata and slightly tortuous, and aneurysmal dilatation of inferior bulbar conjunctival vessels were observed. Other imaging modalities showed unremarkable findings. Cornea verticillata and inferior bulbar conjunctival vascular abnormalities may be detected earlier than other ocular abnormalities in de novo FDs like hereditary FDs.

Hydrogel-based three-dimensional cell culture for organ-on-a-chip applications.

Recent studies have reported that three-dimensionally cultured cells have more physiologically relevant functions than two-dimensionally cultured cells. Cells are three-dimensionally surrounded by the extracellular matrix (ECM) in complex in vivo microenvironments and interact with the ECM and neighboring cells. Therefore, replicating the ECM environment is key to the successful cell culture models. Various natural and synthetic hydrogels have been used to mimic ECM environments based on their physical, chemical, and biological characteristics, such as biocompatibility, biodegradability, and biochemical functional groups. Because of these characteristics, hydrogels have been combined with microtechnologies and used in organ-on-a-chip applications to more closely recapitulate the in vivo microenvironment. Therefore, appropriate hydrogels should be selected depending on the cell types and applications. The porosity of the selected hydrogel should be controlled to facilitate the movement of nutrients and oxygen. In this review, we describe various types of hydrogels, external stimulation-based gelation of hydrogels, and control of their porosity. Then, we introduce applications of hydrogels for organ-on-a-chip. Last, we also discuss the challenges of hydrogel-based three-dimensional cell culture techniques and propose future directions. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:580-589, 2017.