Effect of Duration of Macular Detachment on Visual Prognosis after Surgery for Macula-Off Retinal Detachment: Japan-Retinal Detachment Registry.

PURPOSE: To evaluate the association between the duration of macular detachment (DMD) and visual prognosis in patients with macula-off rhegmatogenous retinal detachment (RD). DESIGN: Prospective observational cohort study. PARTICIPANTS: This study analyzed 719 eyes with macula-off rhegmatogenous RD registered with the Japan-Retinal Detachment Registry created by the Japan Retina and Vitreous Society. METHODS: We included patients with macular detachment without a history of prior surgery, except cataract surgery and vitrectomy. Reoperation cases, hereditary RD, and macular hole RD were excluded. We compared the visual prognosis between patients with DMD of N days or less and those with DMD of N + 1 days or more (N = 2-5). For these 4 comparisons, the inverse probability of treatment weighting (IPTW) methodology was employed, to balance 20 baseline characteristics between the shorter and longer DMD groups. The baseline characteristics included age, sex, axial length, baseline visual acuity, operative procedures, and detailed characteristics of RD. P-values < 0.01 were considered statistically significant. MAIN OUTCOME MEASURES: The best-corrected visual acuity (BCVA) 6 months after surgery. RESULTS: The final analysis included 719 eyes. For all comparisons, the patients' backgrounds were well balanced after IPTW with standardized differences < 0.10. The IPTW regression analysis revealed that the BCVA after 6 months was significantly better after surgeries for DMD of ≤ 2 days than that for DMD of ≥ 3 days. Similarly, the 6-month BCVA for surgeries for DMD of ≤ 3 days was significantly better than that for surgeries for DMD of ≥ 4 days (differences in logarithm of the minimum angle of resolution: -0.113, P = 9.1 × 10-7; -0.076, P = 1.6 × 10-3, respectively). On the other hand, there were no statistically significant differences for the other comparisons. CONCLUSIONS: Earlier surgical treatment within 3 days from the onset of macular detachment should be considered, after accounting for social circumstances, such as weekends. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

The N6-methyladenosine methyltransferase METTL16 enables erythropoiesis through safeguarding genome integrity.

During erythroid differentiation, the maintenance of genome integrity is key for the success of multiple rounds of cell division. However, molecular mechanisms coordinating the expression of DNA repair machinery in erythroid progenitors are poorly understood. Here, we discover that an RNA N6-methyladenosine (m6A) methyltransferase, METTL16, plays an essential role in proper erythropoiesis by safeguarding genome integrity via the control of DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation capacity, DNA damage and activation of the apoptotic program. Mechanistically, METTL16 controls m6A deposition at the structured motifs in DNA-repair-related transcripts including Brca2 and Fancm mRNAs, thereby upregulating their expression. Furthermore, a pairwise CRISPRi screen revealed that the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts. Collectively, our study uncovers that METTL16 and the MTR4-nuclear RNA exosome act as essential regulatory machinery to maintain genome integrity and erythropoiesis.