Purpose To investigate the role of N6-methyladenosine (m6A) RNA modification in the pathogenesis of Graves' ophthalmopathy (GO). Methods Surgically excised extraocular muscles from 7 patients with GO and 5 subjects without GO were used. The global m6A levels in the specimens were determined using an m6A RNA methylation quantification kit. RNA sequencing (RNA-seq) was used to analyze the molecules involved in the regulation of m6A RNA methylation and the differential expression of mRNAs between the two groups (4 eyes, respectively). The expression of m6A RNA modification genes was evaluated by real-time PCR. The functional implications of the gene alterations between the GO and control specimens were determined by Gene Ontology analysis. Results The m6A level was significantly increased in the specimens of GO patients compared to the control specimens (P < 0.05). The expression of m6A methylation regulators, such as WT1 associated protein (WTAP), alkylation repair homolog protein 5 (ALKBH5), E74 like ETS transcription factor 3 (ELF3), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), YTHDF3 and YTH domain containing 2 (YTHDC2), was significantly upregulated (P < 0.05). Gene Ontology enrichment analysis showed that the most highly upregulated genes and biological pathways were related to the immune response and inflammatory processes such as lymphocyte activation, leukocyte differentiation, cytokine production and cytokine-mediated signaling pathways. Conclusions Our results suggest that m6A methylation may play a critical role in the pathogenesis of GO and that targeting genes that regulate m6A methylation may provide a new therapeutic approach for GO.

BackgroundThis study sought to identify factors associated with retinal detachment and retreatment of aggressive posterior retinopathy of prematurity (APROP) initially treated with intravitreal ranibizumab (IVR) injection as well as the efficacy of IVR treatment.MethodsThis was a retrospective study. A total of 83 preterm infants (160 eyes) diagnosed with APROP who were primarily treated with IVR were included. The 160 eyes were divided into two groups based on the anatomic outcomes. Group A included 35 eyes that developed retinal detachment, and Group B included 125 eyes without retinal detachment. The following patient factors were retrospectively reviewed: gender, gestational age (GA), birth weight (BW), postmenstrual age (PMA) at first treatment, iris neovascularizations, retinal hemorrhage, neutrophil and lymphocyte counts before the first intravitreal injection, neutrophil-to-lymphocyte ratio (NLR), anatomical outcomes, additional treatment and follow-up time. Three dummy variables were created as dependent variables based on the methods of retreatment. The possible risk factors for APROP were evaluated, and statistical analyses included univariate and multivariate logistic regression.ResultsA total of 160 eyes from 83 preterm infants (56 males and 27 females) underwent initial IVR treatment with a follow-up time of 17.17 ± 10.54 months. Thirty-five of the 160 (21.9%) eyes progressed to retinal detachment, and 82 of the 125 (65.6%) non-retinal detachment eyes needed retreatment, with favorable anatomical outcomes. The disease improved approximately 1.5 ± 1.2 weeks after the first IVR treatment. The mean recurrence period of APROP was approximately 7.5 ± 6.9 weeks after the first IVR treatment. Multiple logistic regression analysis revealed postmenstrual age (P < 0.001) and neutrophil count (P = 0.009) as the most significant factors for retinal detachment in APROP. Retinal hemorrhage (P = 0.007) and BW (P = 0.04) were most significantly associated with APROP recurrence and retreatment.ConclusionsIVR injection is an effective treatment for APROP. In this study, older postmenstrual age and low neutrophil count were identified as risk factors for retinal detachment in APROP. In addition, retinal hemorrhage and low BW were significantly associated with recurrence and retreatment in non-retinal detachment APROP. Thus, patients with a lower BW, older postmenstrual age, low neutrophil count and retinal hemorrhage should be reexamined in a timely and more frequent manner.

Objective The objective is to describe the clinical features, treatments, and outcomes of a case series of patients with Onodi cell mucocele, with or without cholesterol granuloma (CG). Material and methods We retrospectively reviewed the medical records of eight patients diagnosed with Onodi cell mucocele at a single tertiary care university hospital in Beijing, China, between January 2017 and September 2020. Data regarding nasal symptoms, ocular symptoms, sinus computed tomography findings, treatments, histopathological results, and clinical outcomes were extracted. Results We identified eight patients (six men and two women) of an average age of 48.1 (range, 26–70) years. Four patients presented nasal symptoms. Three patients presented ocular symptoms. Among them, one patient experienced concurrent nasal and ocular symptoms. Two patients were diagnosed based on a physical examination in the absence of nasal or ocular symptoms. All patients underwent endoscopic sinus surgery. The pathological specimens showed mucocele in four cases and mucocele with CG in the other four cases. Among the four cases with CG, three cases presented with decreased vision. After endoscopic sinus surgery, one patient recovered completely, and two patients showed significant improvement. Conclusion If Onodi cell opacity is observed, especially with optic neuropathy, mucocele and CG are important differential diagnoses. The combination of mucocele and CG is more likely to promote bone destruction and cause serious optic neuropathy than simple mucocele. Endoscopic sinus surgery is appropriate. Diagnoses, treatments, and follow-up should be performed by a multidisciplinary team.