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The Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruption to the normal operation of the healthcare system. On a worldwide scale, hospitals suspended non-urgent surgeries and outpatient visits to downsized clinical loadings to redistribute manpower to counteract the pandemic's impact. So far, there is no evidence-based guideline defining a clear line between urgent and non-urgent indications of intravitreal injections (IVI). Herein, we aimed to summarize IVI algorithm modifications and discuss the patient prioritization according to medical needs in the hostile environment in the COVID crisis. Assessing current literature, we found that neovascular age-related macular degeneration is considered the utmost priority among conditions that require IVI. Other conditions assigned with a high priority include monocular or quasi-monocular patients (only one eye > 20/40), neovascular glaucoma, and new patients with significant vision loss. Although patients with central retinal vein occlusion and proliferative diabetic retinopathy are not advised to delay treatments, we found no consistent evidence that correlated with a worse outcome. Diabetic macular edema and branched retinal vein occlusion patients undertaking treatment delay should be regularly followed up every 2-3 months. Serving as the principle of management behind the algorithm modifications, the reduction of both patient visit and IVI therapy counts should be reckoned together with the risk of permanent visual loss and COVID infection.

Backgrounds: Leber’s hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON.

Significance This is the first study to validate the repeatability of objective measurements of amplitude of accommodation (AA) using the TONOREF III (NIDEK Co., Ltd., Japan), which can measure the AA in 30 seconds. Purpose To evaluate the repeatability of objective measurements of AA using the TONOREF III and explored the association between objectively measured AA and factors, including age, sex, spherical equivalent, baseline pupil size and pupil size change during accommodation. Methods This cross-sectional study recruited 35 healthy subjects aged 26 to 52 years. The Bland-Altman method and intraclass correlation coefficients (ICCs) were used to assess the repeatability of TONOREF III measurements. The relationships between AA and age, sex, baseline pupil size, changes in pupil size (ΔPS) during accommodation were analyzed using linear regression for univariate and multivariate analysis. Results The mean difference in AA (ΔAA) between two sessions of TONOREF III measurements was 0.23 D (95% CI: -1.07 to +1.53 D), while no significant correlation was found between the mean and ΔAA (p = .14). The ICCs of the TONOREF III was 0.96. Age, sex, and ΔPS during accommodation were significant factors affecting the AA in multivariate analysis. Conclusions The repeatability of objective AA measurements using the TONOREF III was good. Measuring AA using the TONOREFTM III in clinical practice is feasible.