Area-divided OCTA quantification shows the appearance of spatial biases of macular capillary dropout with the onset of DR, suggesting that DR-related macular capillary dropout occurs locally and randomly. Future studies are necessary to determine the clinical relevance of the spatial pattern of capillary dropout in DR.

Approximately 40% of patients with diabetic macular edema (DME) are resistant to anti-vascular endothelial growth factor (VEGF) therapy (rDME). Here, we demonstrate that significant correlations between inflammatory cytokines and VEGF, as observed in naive DME, are lost in patients with rDME. VEGF overexpression in the mouse retina caused delayed inflammatory cytokine upregulation, monocyte/macrophage infiltration (CD11b 1 Ly6C 1 CCR2 1 cells), macrophage/microglia activation (CD11b 1 CD80 1 cells), and blood-retinal barrier disruption due to claudin-5 redistribution, which did not recover with VEGF blockade alone. Phosphorylated protein analysis of VEGFoverexpressed retinas revealed rho-associated coiled-coilcontaining protein kinase (ROCK) activation. Administration of ripasudil, a selective ROCK inhibitor, attenuated retinal inflammation and claudin-5 redistribution. Ripasudil also contributed to the stability of claudin-5 expression by both transcriptional enhancement and degradation suppression in inflammatory cytokine-stimulated endothelium. Notably, the anti-VEGF agent and the ROCK inhibitor were synergic in suppressing cytokine upregulation, monocyte/macrophage infiltration, macrophage/microglia activation, and claudin-5 redistribution. Furthermore, in vitro analysis confirmed that claudin-5 redistribution depends on ROCK2 but not on ROCK1. This synergistic effect was also confirmed in human rDME cases. Our results suggest that ROCKmediated claudin-5 redistribution by inflammation is a key mechanism in the anti-VEGF resistance of DME.

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PurposeThe purpose of this study was to determine the degree of metamorphopsia using M-CHARTS™ in patients with idiopathic macular hole before and after pars plana vitrectomy and internal limiting membrane (ILM) peeling.Patients and methodsThe records of 22 eyes of 22 patients with a full-thickness macular hole who underwent pars plana vitrectomy and ILM peeling were reviewed. All patients underwent a complete ophthalmic examination including spectral-domain optical coherence tomography (OCT). Horizontal metamorphopsia (MH) and vertical metamorphopsia (MV) scores were determined using M-CHARTS at the same time. The time course of changes in metamorphopsia and the relationship between best-corrected visual acuity (BCVA) and OCT parameters were assessed.ResultsSealing of the macular hole was noted in all eyes after surgery. BCVA improved significantly from 1 month after surgery (P<0.001). The MV score was significantly higher than the MH score before surgery (P<0.05) and improved significantly from 1 month after surgery (P<0.03). The MH score improved significantly at 6 months after surgery (P<0.001). The postoperative MV and MH scores became closer to one another from 1 month after surgery. Moreover, the MV score was higher than the MH score at all postoperative assessments. There was a significant correlation between the MV and MH scores at all follow-up assessments. There was no significant correlation between BCVA and the MV or MH score at any follow-up assessment.ConclusionThe satisfaction of the patients with macular hole after surgery cannot be necessarily measured by BCVA alone, because M-scores were not correlated to BCVA in postoperative evaluation. Therefore, evaluation of the MV and MH scores can be an independent treatment outcome in addition to BCVA.

Rho-associated kinase (Rho-kinase/ROCK) was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs. The importance of ROCK in pathological vitreoretinal conditions has also been elucidated and is attracting attention as a potential therapeutic target. ROCK is involved in angiogenesis and hyperpermeability and also in the pathogenesis of various pathologies such as inflammation and fibrosis. It has been expected that ROCK inhibitors will become new molecular target drugs for vitreoretinal diseases. This review summarizes the recent progress on the mechanisms of action of ROCK and their applications in disease treatment.