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.

Disproportion of lamellar capillary non-perfusion in proliferative diabetic retinopathy on optical coherence tomography angiography.

PURPOSE: To characterise the non-perfused areas (NPAs) in the superficial and deep capillary layers (sNPAs and dNPAs, respectively) in the posterior pole in proliferative diabetic retinopathy (PDR) on wide-field optical coherence tomography angiography (OCTA) images. METHODS: We retrospectively reviewed 104 eyes of 70 patients with PDR from whom wide-field swept source OCTA images were acquired. sNPAs and dNPAs were manually measured in each quadrant of the inner (1-3 mm diameter), intermediate (3-6 mm), and outer (6-10 mm) rings centred on the fovea. Two qualitative findings, that is, segmented NPAs and periarteriolar NPAs, were also compared. RESULTS: The dNPAs were greater than the sNPAs (p<0.001) in each subfield. The outer ring had higher rates of deep NPAs than did the intermediate ring in the superior, inferior and temporal quadrants (p=0.010, p=0.004 and p<0.001, respectively), whereas no differences were detected in the nasal quadrant (p=1.000). Similarly, sNPA rates were higher in the outer ring than in the intermediate ring in the inferior and temporal subfields (p=0.003 and p<0.001, respectively). In 45 eyes with extensive NPAs, there were modest correlations between the dNPAs in the nasal and temporal quadrants in the intermediate (ρ=0.341, p=0.026) and outer (ρ=0324, p=0.032) rings, whereas sNPAs exhibited no associations. Segmented NPAs were delineated more frequently in the superficial layer than in the deep layer (p<0.001). Periarteriolar NPAs were more frequent in the deep layer (p<0.001). CONCLUSIONS: Three-dimensional assessment of wide-field OCTA promotes a better understanding of the enigmatic disproportion of lamellar NPAs in the posterior pole in PDR.

Characteristics of Diabetic Capillary Nonperfusion in Macular and Extramacular White Spots on Optical Coherence Tomography Angiography.

Purpose: To compare the characteristics of macular and extramacular white spots on wide-field swept-source optical coherence tomography angiography (SS-OCTA) and optical coherence tomography (OCT) images in diabetic retinopathy (DR). Methods: We retrospectively reviewed 107 eyes of 64 patients with DR, of whom nominal 12 × 12 mm SS-OCTA images centered on the optic disc and ultrawide field photographs were acquired. White spots on fundus photographs corresponded to hyperreflective lesions in the superficial en-face OCT images, and the characteristics of these white spots were investigated. We compared such OCT findings with the vertical and horizontal extents of nonperfused areas (NPAs) on OCTA images. Results: We observed 136 white spots and corresponding hyperreflective lesions in 49 eyes. The hyperreflective lesions in the extramacular areas had greater areas (P < 0.001) and more frequently spanned from the nerve fiber layer to the outer plexiform layer (P < 0.001), while those in the macula were superficial. All of macular hyperreflective lesions were accompanied with nerve fiber layer defects, whereas only 18 (15.4%) of 117 extramacular lesions had them (P < 0.001). Comparative studies showed that most extramacular hyperreflective lesions corresponded to the NPAs in the whole layers on OCTA images, compared to the lamellar NPAs of the superficial layer in most of the macular lesions (P < 0.001). The NPAs extended to the peripheral side more frequently in the extramacular hyperreflective lesions compared with macular lesions (P < 0.001). Conclusions: This study proposed that most of the extramacular white spots may be discriminated from macular spots with respect to diabetic NPAs on OCTA images.

Diabetic Nonperfused Areas in Macular and Extramacular Regions on Wide-Field Optical Coherence Tomography Angiography.

Purpose: To investigate the nonperfused areas (NPAs) in each subfield segmented by large arterioles on wide-field swept-source optical coherence tomography angiography (SS-OCTA) images in diabetic retinopathy. Methods: We retrospectively reviewed 101 consecutive eyes of 67 patients with severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), for whom 12 × 12-mm SS-OCTA images centered on the optic disc were acquired. Both eyes were included in 34 patients. NPAs in the whole retinal layers were measured in each subfield segmented by large arterioles encompassing both the superficial and deep layers. We compared the percentage of NPAs between individual subfields, considering the overlapping of the feeding arterioles. Results: Extramacular areas had higher rates of NPAs than macular areas in the inner (0.75-3 mm) and outer (3-5.5 mm) rings (P < 0.001 in both comparisons). The arteriolar arcades contacting the NPAs on the extramacular side were significantly longer than those contacting the NPAs on the macular side (P < 0.001). In particular, the extramacular areas between two arteriolar branches had a higher percentage of NPAs than those between two arterioles. The macular NPAs were greater in eyes with PDR than in those with severe NPDR, whereas there were no differences in the NPAs in the outer ring of extramacular areas. Conclusions: Wide-field OCTA images delineated that large arterioles residing in both the superficial and deep layers appear to be the perfusion boundaries, and the overlapping perfusion mediated via collateral vessels may affect the likelihood of diabetic NPAs in each subfield.

Decorrelation Signal of Diabetic Hyperreflective Foci on Optical Coherence Tomography Angiography.

Diabetic hyperreflective foci in the outer retinal layers are a clinically relevant finding on optical coherence tomography (OCT) images, although their characteristics remain to be elucidated. Here we investigated the decorrelation signal around hyperreflective foci on OCT angiography (OCTA) images in diabetic retinopathy (DR). We retrospectively reviewed sufficient quality OCTA images from 102 eyes of 66 patients that were obtained using split-spectrum amplitude-decorrelation angiography algorithm. Most confluent hyperreflective foci were randomly deposited or appeared in a radiating array on the en-face structural OCT images in the inner nuclear layer (INL) or Henle's fiber layer (HFL), respectively. Within the INL, hyperreflective foci were not accompanied by decorrelation signals and attached to capillaries on OCTA images. Decorrelation signals were sometimes delineated in hyperreflective foci in the HFL and other times appeared to be pseudopod-like or wrapping around hyperreflective foci, referred to as reflectance-decorrelated foci. The decorrelation signal intensity of hyperreflective foci in the HFL was associated with logMAR VA (R = 0.553, P < 0.001) and central subfield thickness (R = 0.408, P < 0.001) but not with DR severity. These data suggest that reflectance-decorrelated foci on OCTA images are clinically relevant as well as shed lights on the properties in diabetic hyperreflective foci.