Inverted Pedicled Internal Limiting Membrane Flap Attached to an Optic Disc with Autologous Blood Clot for Large Macular Holes.

Purpose: An inverted ILM flap might be accidentally separated from the retina or sucked away during surgery for large macular holes (MHs). This article is to determine the efficacy of a new inverted pedicled internal limiting membrane (ILM) flap attached to an optic disc with an autologous blood clot (ABC) technique for the treatment of large MHs. Methods: An inverted pedicled ILM flap connected to the optic disc with ABC was used to treat 12 consecutive patients with significant macular holes (>600 m). The ILM was first peeled off around MH as a semidiameter of about 1.5 diameters of the optic disc. The superior residual ILM was used to produce a pedicled ILM flap that was connected to the optic disc and was later inverted to cover the MH. The macular hole was covered with a repositioned flap larger than 2 MH diameters in an inverted way. ABC was used to fasten the flap, followed by fluid-air exchange with air or C3F8 as tamponade. Spectral domain-optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA) were performed at each postoperative follow-up. Results: The mean aperture and base macular hole diameters were 737.9 ± 109.6 µm (range, 607-982 µm) and 1244.3 ± 227.4 µm (range, 975-1658 µm). All macular holes (100%) were closed after a single surgery without intraoperative or postoperative complications related to the ILM transposition technique. At the last postoperative visit, we found one eye with a U-shaped closure, three eyes with W-shaped closures, and eight eyes with V-shaped closures. No postoperative flap closures were noted in all cases. The preoperative mean BCVA was 1.5 ± 0.3 (range, 1.1-2.0). After a mean follow-up of 5.3 ± 4.8 (range, 3-16) months, the postoperative mean BCVA was 0.8 ± 0.2 (range, 0.6-1.1), and the difference was statistically significant (p < 0.05). Conclusion: This novel technique is safe and suitable for large MHs and can be an alternative option for accidental ILM flap loss during other inverted ILM flap operations.

Metagenomic Next-Generation Sequencing to Investigate Infectious Endophthalmitis of Brucella: A Case Report.

Introduction: Brucellosis is a systemic disease that exists prevalently in clinical manifestations. The symptoms present in organs such as the eyes (in ocular brucellosis) can lead to misdiagnosis or even failure to diagnose. Metagenomic Next-Generation Sequencing (mNGS), a high-throughput sequencing approach, could be applied for the detection of microorganisms. Case Presentation: A 57-year-old female with acute right-eye vision loss, treated with clindamycin and dexamethasone sodium phosphate for 1.5 months, was difficult to diagnose using regular methods. mNGS was utilized for the aqueous fluid from the patient, and Brucella melitensis was identified. The inflammation was treated with 3 months of antibiotherapy. However, even with specific medicine and surgery, the vision remained poor because severe ocular conditions last for a long time. Conclusion: It suggests that brucella should still be a probable pathogen in endophthalmitis despite its low incidence in non-epidemic areas. Moreover, mNGS can achieve early diagnosis and timely treatment for difficult-to-diagnose ocular infections.

CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy.

Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI-anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes.

Biomarkers in retinoblastoma.

Retinoblastoma (RB) is the most common intraocular malignancy of childhood caused by inactivation of the Rb genes. The prognosis of RB is better with an earlier diagnosis. Many diagnostic approaches and appropriate clinical treatments have been developed to improve clinical outcomes. However, limitations exist when utilizing current methods. Recently, many studies have identified identify new RB biomarkers which can be used in diagnosis, as prognostic indicators and may contribute to understanding the pathogenesis of RB and help determine specific treatment strategies. This review focuses on recent advances in the discovery of RB biomarkers and discusses their clinical utility and challenges from areas such as epigenetics, proteomics and radiogenomics.

Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans.

The rescue effect of mesenchymal stem cell on sodium iodate-induced retinal pigment epithelial cell death through deactivation of NF-κB-mediated NLRP3 inflammasome.

Age-related macular degeneration (AMD) is a multifactorial disease resulting in the gradual loss of retinal pigment epithelium (RPE) and the permanent visual damage. Various risk factors, including oxidative stress, form a complex network at the confluence of inflammation. Mesenchymal stem cell (MSC) is a well-studied population of adult stem cell with strong neuroprotective and immunoregulatory properties. Here, we reported the protective effect of MSC on sodium iodate (NaIO3)-triggered RPE degeneration. Sodium iodate (NaIO3)-induced RPE cell death was remarkably reduced when cocultured with MSC. Inhibition of several cell death pathways mediated by mitochondrial instability and its subsequent caspase-1/3/8 activation was implicated in this process. In addition, NLRP3 inflammasome, the upstream of caspase-1 activation, was also found downregulated via suppressing its priming signal NF-κB pathway. Taken together, MSC protected against NaIO3-triggered RPE death via deactivating NF-κB-mediated NLRP3 inflammasome and maintaining mitochondrial integrity. This study highlights the significant role of MSC in modulating the proinflammatory environment of AMD, and suggests the clinical value of MSC in treating AMD as well as RPE replacement therapy.