To report retinal vein occlusion (RVO) and age-related macular degeneration (AMD)-related submacular hemorrhage developing after administration of SARS-CoV-2 vaccines, a single-center, retrospective observational case series was conducted. Clinical data including fundus photographs and optical coherence tomography (OCT) scans were reviewed. Twenty-three eyes of 21 patients were included with the median age at symptom presentation being 77 years (range: 51–85 years). Twelve eyes (52.2%) had submacular hemorrhage and 11 (47.8%) had RVO. Twelve patients (60.9%) had been vaccinated with the Pfizer vaccine (BNT162b2) and 8 with the AstraZeneca (ChAdOx1) vaccine. Sixteen patients (76.2%) experienced ocular disease exacerbation after the first vaccination and 4 (19.0%) after the second vaccination. The median visual acuity (logarithm of the minimal angle of resolution; logMAR) before symptom development was 0.76 (interquartile range: 0.27–1.23); the median logMAR at symptom presentation was 1.40 (interquartile range 0.52–1.70). The median time between vaccination and symptom exacerbation was 2.0 days (interquartile range: 1.0–3.0 days). Five patients (23.8%) underwent tests for hematological abnormalities, including the presence of anti-PF4 antibodies; all were negative. Further studies with larger patient group for evaluation of effect of SARS-CoV-2 vaccination on retinal hemorrhage are necessary.

Background: In Graves' orbitopathy (GO), localized orbital inflammation within the fixed orbit often leads to a fibrotic phenotype resulting in restrictive myopathy or refractory proptosis. However, the molecular pathways related to the transition from inflammation to fibrosis in GO are less understood. Yes-associated protein (YAP) and its homolog, transcriptional coactivator with PDZ-binding motif (TAZ; a Hippo pathway effector), are critical mechanosensors of mechanical stimuli and activate signaling cascades for cell proliferation, differentiation, and transformation. In this study, we aimed to examine the role of YAP in both inflammatory and fibrotic GO pathogenesis. Methods: Based on RNA sequencing performed on freshly obtained orbital adipose tissue from patients with GO and healthy individuals, Gene Ontology analysis and gene set-enrichment analysis were performed to analyze gene-expression differences between GO and normal orbital tissues. The role of YAP in GO-related inflammation and fibrosis was studied in primary cultured orbital fibroblasts. The effects of interleukin-1β (IL-1β)-induced inflammation and transforming growth factor-beta (TGF-β)-induced fibrosis on YAP expression were evaluated using real-time polymerase chain reaction and Western blotting analyses. The effects of YAP on inflammatory and fibrotic responses were also examined by YAP silencing or treatment with pharmacological YAP inhibitors. Results: RNA sequencing revealed enhanced YAP expression in GO orbital tissues. Gene Ontology analysis indicated that “response to mechanical stimulus”-related genes were overexpressed in GO orbital tissues, along with those enriched for the “adipose proliferation,” “inflammatory responses,” and “hormone stimulus responses” terms. IL-1β did not enhance YAP expression, and YAP silencing decreased IL-1β-induced IL-6 expression while increasing prostaglandin-endoperoxide synthase 2 expression, leading to paradoxical pro-inflammatory effects. Conversely, TGF-β enhanced YAP expression, and YAP silencing and pharmacological YAP inhibitor (cerivastatin, verteporfin, TED-347, and CA3) treatment significantly reduced TGF-β-induced myofibroblast differentiation and collagen formation. Conclusion: YAP, a mechanotransducer responding to mechanical stimuli, was strongly expressed in GO orbital tissues, and YAP was induced by TGF-β in orbital fibroblasts. Our study establishes YAP as a novel mediator of GO pathobiology, potentially mediating the transition from early inflammation to chronic fibrosis in GO. The finding that YAP inhibition suppressed TGF-β-induced fibrotic response suggests YAP as a therapeutic target against the fibrotic mechanism of GO.