Oxidative stress-mediated retinal pigment epithelium (RPE) degeneration plays a vital role in retinal degeneration with irreversible visual impairment, most notably in age-related macular degeneration (AMD), but a key pathogenic factor and the targeted medical control remain controversial and unclear. In this work, by sophisticated high-throughput sequencing and biochemistry investigations, the major pathologic processes during RPE degeneration in the sodium iodate-induced oxidative stress model has been identified to be heme oxygenase-1 (HO-1)-regulated ferroptosis, which is controlled by the Nrf2-SLC7A11-HO-1 hierarchy, through which ferrous ion accumulation and lethal oxidative stress cause RPE death and subsequently photoreceptor degeneration. By direct knockdown of HO-1 or using HO-1 inhibitor ZnPP, the specific inhibition of HO-1 overexpression has been determined to significantly block RPE ferroptosis. In mice, treatment with ZnPP effectively rescued RPE degeneration and achieved superior therapeutic effects: substantial recovery of the retinal structure and visual function. These findings highlight that targeting HO-1-mediated RPE ferroptosis could serve as an effectively retinal-protective strategy for retinal degenerative diseases prevention, including AMD.

The aim of this study was to compare the accuracy of Barrett Universal II and Hill-Radial Basis Function with other four popular formulas for the calculation of intraocular lens power in high myopic eyes. A total of 56 eyes with an axial length of more than 26.0 mm were retrospectively reviewed. Six intraocular lens power calculation methods, including Barrett Universal II, Hill-Radial Basis Function, SRK/T, Haigis, Holladay 2 and Holladay 1, were evaluated. The difference between the postoperative actual refraction and the refraction predicted by the six methods was evaluated as the prediction error. The absolute prediction error was also calculated. The mean numerical prediction error ± standard deviation of the six intraocular lens power calculation methods, in order of lowest to highest, was Barrett Universal II (0.37 ± 0.54 D), Hill-Radial Basis Function (0.40 ± 0.56 D), SRK/T (0.44 ± 0.56 D), Haigis (0.53 ± 0.54 D), Holladay 2 (0.88 ± 0.62 D) and Holladay 1 (1.00 ± 0.60 D). The median absolute errors predicted by the Barrett (0.46 D), Hill-Radial Basis Function (0.47 D), SRK/T (0.53 D) and Haigis (0.58 D) were significantly lower than those of the Holladay 1 (0.90 D) and Holladay 2(1.10 D; all p < 0.001). There was no significant difference among the median absolute errors of Barrett, Hill-Radial Basis Function, SRK/T and Haigis (all p > 0.05). The prediction errors differed for each method in the selection of intraocular lens power for the long eyes. In terms of overall accuracy, the Barrett Universal II formula provided the lowest prediction error. The Hill-Radial Basis Function method was comparable to the theoretical formulas, such as SRK/T and Haigis.

Background: Appropriate vault height of implantable collamer lens (ICL) implantation matters for it has risks of corneal endothelial cell loss, cataract formation and intraocular pressure elevation, which could lead to irreversible damage to optic nerve. Therefore, pre-operative prediction for an ideal vault height is a hotspot. However, few data exist regarding quantitative effect of ICL orientation on vault height. This study is aimed to quantitatively investigate the effect of ICL implantation orientation on vault height, and built a machine-learning (ML)-based vault prediction model taking implantation orientation into account.Methods: 473 consecutive case series treated with ICL implantation were retrospectively analyzed (408 were horizontally implanted, and 65 were vertically implanted). Multivariable logistic regression analysis was performed to determine the association between ICL orientation and achieved vault. ML was performed to develop a new vault height prediction model taking ICL orientation into account. Receiver operating characteristic curve (ROC) and net reclassification index (NRI) were obtained to assess the prediction ability.Results: 95% of all the patients achieved 20/20 uncorrected distance visual acuity (UDVA) or better. No complications including cataract formation, dispersion or optic nerve injury were observed in any cases. Sex, sphere power, cylinder power, axis, ICL size and ICL orientation were all significant risk factors associated to vault height, and age was positively co-related. Of note, ICL size and ICL orientation were the top-ranking risk factors. Comparing to conventional horizontal implantation, vertical implantation could reduce the achieved vault by 81.187 μm (p < 0.001). In regarding to different ICL sizes, vertical implantation had no good to vault reduction when using ICL of 12.1 mm. However, it could reduce the vault by 59.351 μm and 160.992 μm respectively when ICL of 12.6mm and 13.2 mm were implanted (p = 0.0097 and p = 0.0124). For prediction of vault height, ML based model significantly outperformed traditional multivariable regression model.Conclusion: We provide quantitative evidence that vertical implantation of ICL could effectively reduce the achieved vault height, especially when large size ICL was implanted, comparing to traditional horizontal implantation. ML is extremely applicable in development of vault prediction model.

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age -related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide -modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2 -DG interfered with Nglycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.

To compare the mesopic contrast sensitivity (CS) and higher order aberrations (HOAs) at 3 months after femtosecond-laser in situ keratomileusis (LASIK) (FS-LASIK), wave front-guided femtosecond LASIK (WF-LASIK), and femtosecond lenticule extraction (FLEx) for the correction of myopia and myopic astigmatism. In this prospective nonrandomized study, 332 right eyes of 332 patients were treated with FS-LASIK, WF-LASIK, or FLEx. The HOAs and mesopic CS were evaluated preoperatively and at 3 months postoperatively. At 3 months of follow-up, 98 eyes (96.1%) of the FS-LASIK group, 92 eyes (98.9%) of the WF-LASIK group, and 133 eyes (96.4%) of the FLEx group had an uncorrected distance visual acuity of 20/20 or better. The HOAs improved from 0.34 μm during preoperative examination to 0.56 μm of the end of the follow-up in the FS-LASIK group, from 0.31 to 0.41 μm in the WF-LASIK group, and from 0.32 to 0.54 μm in the FLEx group (all P < 0.01). At a spatial frequency of 12 cycles per degree, a better mesopic CS was observed in the WF-LASIK group (1.47) than in the FS-LASIK (1.36) and FLEx (1.33) groups (P < 0.01); a better mesopic CS with glare was also noted in the WF-LASIK group (1.37) than in the FS-LASIK (1.25) and FLEx (1.29) groups (P < 0.01). The FS-LASIK, WF-LASIK, and FLEx procedures result in comparable refractive results at 3 months postoperatively. However, there is improvement in the mesopic CS and HOAs after WF-LASIK.