Corneal Biomechanics Determination in Healthy Myopic Subjects

Purpose. To determine the corneal biomechanical properties by using the Ocular Response Analyzer™ and to investigate potential factors associated with the corneal biomechanics in healthy myopic subjects. Methods. 135 eyes from 135 healthy myopic subjects were included in this cross-sectional observational study. Cornea hysteresis (CH), corneal resistance factor (CRF), cornea-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg) were determined with the Reichert Ocular Response Analyzer (ORA). Univariate and multivariate regression analyses were performed to investigate factors associated with corneal biomechanics. Results. The mean CH and CRF were 9.82±1.34 mmHg and 9.64±1.57 mmHg, respectively. In univariate regression analysis, CH was significantly correlated with axial length, refraction, central corneal thickness (CCT), and IOPg (r=-0.27, 0.23, 0.45, and 0.21, resp.; all with p≤0.015), but not with corneal curvature or age; CRF was significantly correlated with CCT and IOPg (r=0.52 and 0.70, resp.; all with p<0.001), but not with axial length/refraction, corneal curvature, or age. In multivariate regression analysis, axial length, IOPcc, and CCT were found to be independently associated with CH, while CCT and IOPg were associated with CRF. Conclusions. Both CH and CRF were positively correlated with CCT. Lower CH but not CRF was associated with increasing degree of myopia. Evaluation of corneal biomechanical properties should take CCT and myopic status into consideration

Influence of optic disc-fovea distance on macular thickness measurements with OCT in healthy myopic eyes

Assessment of macular thickness is important in the evaluation of various eye diseases. This study aimed to determine the influence of the optic disc-fovea distance (DFD) on macular thickness in myopic eyes. We determined the DFD and the macular thickness in 138 eyes from 138 healthy myopic subjects using the Cirrus HD-OCT. Correlation analysis and multiple linear regression were performed to determine the influence of DFD, axial length, disc area, and β-PPA on macular thickness. To further remove the confounding effect of ocular magnification on the DFD and OCT scan area, a subgroup analysis was performed in eyes with a limited axial length range (24-25 mm). DFD was significantly correlated with both regional (central, inner, and outer ETDRS subfields) and overall average macular thickness at a Bonferroni corrected P value of 0.004 (r ranging from-0.27 to-0.47), except for the temporal outer (r =-0.15, P = 0.089) and inferior outer (r =-0.22, P = 0.011) macular thickness. In the multivariable analysis, DFD was significantly associated with the average inner and outer macular thickness, the central subfield thickness, and the overall macular thickness (all P < 0.001), independent of ocular magnification and other covariates. Our findings indicate that eyes with a greater DFD have a lower macular thickness

Relationship of corneal hysteresis and optic nerve parameters in healthy myopic subjects

Abstract The association between corneal biomechanical properties and glaucoma is an area of much interest. We determined the relationship between corneal hysteresis (CH) and optic nerve parameters in healthy myopic subjects in the current study. CH was measured with Reichert Ocular Response Analyzer in 108 eyes from 108 healthy myopic subjects. All subjects received retinal nerve fiber layer and optic disc imaging Cirrus HD-OCT, GDx ECC, and Heidelberg Retina Tomograph II. None of the tested optic nerve parameters showed statistical significance with CH by using correlation analysis. For RNFL parameters, there was a negative but not statistically significant correlation between CH and average RNFL thickness obtained with OCT (r = −0.15, p = 0.13). For optic disc parameters, there was a negative but not statistically significant correlation between CH and rim area measured with OCT (r = −0.10, p = 0.29). The current study did not find any statistically significant relationship between CH and optic nerve parameters as measured by all three imaging modalities in healthy myopic eyes. Therefore, the relationship observed previously in glaucoma subjects is likely coming to fruition as optic nerve damage is caused by the disease

Application of the ISNT rules on retinal nerve fibre layer thickness and neuroretinal rim area in healthy myopic eyes

PurposeWe determined the applicability of inferior>superior>nasal>temporal (ISNT) rules on retinal nerve fibre layer (RNFL) thickness and rim area and evaluated the impact of various ocular factors on the performance of the ISNT rules in healthy myopic eyes. MethodsA total of 138 eyes from 138 healthy myopic subjects were included in this cross-sectional observational study. The peripapillary RNFL and optic disc in each eye were imaged with Cirrus HD optical coherence tomography (OCT) and Heidelberg Retina Tomograph II (HRT2), respectively. The performance of the inferior>superior (IS), inferior>superior>nasal>temporal (IST) and ISNT rules on RNFL thickness and rim area was determined and compared between low-to-moderate myopia and high myopia. The effects of ocular factors [including axial length, disc area, disc tilt, disc torsion, disc-fovea angle (DFA) and retina artery angle] on the performance of ISNT rules were evaluated with logistic regression analysis. ResultsThe mean axial length and refractive error were 25.571.09mm (range, 22.52-28.77mm) and -5.12 +/- 2.30D [range, -9.63 to -0.50dioptres (D)], respectively. Sixty-three per cent of the healthy eyes were compliant with the ISNT rule on rim area, while ISNT rule on RNFL thickness was followed in only 11.6% of the included eyes. For rim area, smaller disc area was significantly associated with increased compliance of the IS rule (odds ratio: 0.46, p=0.039), IST rule (odds ratio: 0.46, p=0.037) and ISNT rule (odds ratio: 0.44, p=0.030). For RNFL thickness, greater DFA was significantly associated with increased compliance of the IS and IST rules (odds ratio: 1.30, p ConclusionIn healthy myopic subjects, 88.4% and 37% of eyes did not comply with the ISNT rule on RNFL thickness and rim area, respectively. Due to significant low compliance in healthy eyes, the ISNT rule and its variants have limited potential utility in diagnosing glaucoma in myopic subjects

Bioengineering thymus organoids to restore thymic function and induce donor-specific immune tolerance to allografts

One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine

Concerted Gating Mechanism Underlying K(ATP) Channel Inhibition by ATP

K(ATP) channels assemble from four regulatory SUR1 and four pore-forming K(ir)6.2 subunits. At the single-channel current level, ATP-dependent gating transitions between the active burst and the inactive interburst conformations underlie inhibition of the K(ATP) channel by intracellular ATP. Previously, we identified a slow gating mutation, T171A in the K(ir)6.2 subunit, which dramatically reduces rates of burst to interburst transitions in K(ir)6.2ΔC26 channels without SUR1 in the absence of ATP. Here, we constructed all possible mutations at position 171 in K(ir)6.2ΔC26 channels without SUR1. Only four substitutions, 171A, 171F, 171H, and 171S, gave rise to functional channels, each increasing K(i,ATP) for ATP inhibition by >55-fold and slowing gating to the interburst by >35-fold. Moreover, we investigated the role of individual K(ir)6.2 subunits in the gating by comparing burst to interburst transition rates of channels constructed from different combinations of slow 171A and fast T171 “wild-type” subunits. The relationship between gating transition rate and number of slow subunits is exponential, which excludes independent gating models where any one subunit is sufficient for inhibition gating. Rather, our results support mechanisms where four ATP sites independently can control a single gate formed by the concerted action of all four K(ir)6.2 subunit inner helices of the K(ATP) channel