Visual Acuity-Related Outer Retinal Structural Parameters on Swept Source Optical Coherence Tomography and Angiography in XLRS Patients and Carriers.

Purpose: To assess the quantitative differences in vessel density and retinal thickness of X-linked retinoschisis (XLRS) patients and RS1 mutation carriers, and the correlation with best-corrected visual acuity (BCVA) with swept source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). Methods: We analyzed the correlation between the BCVA of XLRS patients and the SS-OCT and OCTA findings including the detailed structural characteristics of XLRS patients. Results: Besides the schitic changes in various retinal layers, the structural disturbance of outer retina was universally found. In 29 eyes included in the quantitative analysis, XLRS patients showed lower vessel density of the superficial capillary plexus, deep capillary plexus and lower thickness of the outer nuclear layer. BCVA was correlated with the thickness of the outer plexiform layer and outer nuclear layer and the thickness from the outer limiting membrane to the retinal pigment epithelium. Carriers showed higher thickness of outer plexiform layer and smaller foveal avascular zone area. Conclusions: SS-OCT and OCTA could identify the pathological alterations of the individual retinal layers and capillaries, which could pinpoint the exact location of the damages related to visual impairment. In the carriers, the subtle alterations that can be detected with SS-OCT, despite their normal visual acuity, may be caused by the lyonization. Translational Relevance: Swept source optical coherence tomography can be used as an efficient technique to expose the retinal damage related to visual impairment for prognosis and follow-up.

Blocking Th2 Signaling Pathway Alleviates the Clinical Symptoms and Inflammation in Allergic Conjunctivitis.

Purpose: To explore the role of Th2 signaling pathway in allergic conjunctivitis (AC). Methods: Serum Th2 cytokines IL-4 or IL-13 of patients with AC were detected using the Meso scale discovery assay to verify the correlation of Th2 immunity and AC pathogenesis. Wistar Han rats were intraperitoneally and subcutaneously injected with ovalbumin (OVA) to establish an experimental AC model and the Th2 signaling pathway was blocked by an investigational neutralizing antibody (CM310). Serum IgE and OVA-specific IgE were detected by ELISA. Conjunctivitis inflammation, infiltration of eosinophils, and mast cell degranulation were detected by histological examination. Immortalized human conjunctival epithelial cells, a conjunctival epithelial cell line, and peripheral blood mononuclear cells of patients with AC were used as the target cells to study the impact of IL-4 or IL-13 on AC progression. Finally, a STAT6 reporter gene system was constructed using immortalized human conjunctival epithelial cells to confirm whether the downstream signaling pathway activated by IL-4 or IL-13. Results: Serum IL-4 or IL-13 were increased in patients with AC versus healthy individuals. In an OVA-induced rat experimental AC model, blocking the Th2 signaling pathway with CM310, an investigational neutralizing antibody, alleviated the conjunctival symptoms, and decreased serum IgE, suppressed infiltration of eosinophils and mast cell degranulation. Further, an in vitro model showed CM310 suppressed the secretion of inflammatory cytokine from both immune cells and epithelial cells in both patients peripheral blood mononuclear cells and cell line. Conclusions: Blocking Th2 signaling pathway alleviates the clinical symptoms and inflammation in AC.

Dual-AAV split prime editor corrects the mutation and phenotype in mice with inherited retinal degeneration.

The prime editor (PE) can edit genomes with almost any intended changes, including all 12 possible types of base substitutions, small insertions and deletions, and their combinations, without the requirement for double strand breaks or exogenous donor templates. PE demonstrates the possibility of correcting a variety of disease-causing mutations and might expand the therapeutic application of gene editing. In this study, PE was optimized based on a dual-adeno-associated virus (AAV) split-intein system in vitro by screening different split sites and split inteins. We found that splitting PE before amino acid 1105(Ser) of SpCas9 with Rma intein resulted in the highest on-target editing. The orientations of pegRNA and nicking sgRNA in the AAV vector were further optimized. To test the in vivo performance of the optimized dual-AAV split-PE3, it was delivered by subretinal injection in rd12 mice with inherited retinal disease Leber congenital amaurosis. The prime editors corrected the pathogenic mutation with up to 16% efficiency in a precise way, with no detectable off-target edits, restored RPE65 expression, rescued retinal and visual function, and preserved photoceptors. Our findings establish a framework for the preclinical development of PE and motivate further testing of PE for the treatment of inherited retinal diseases caused by various mutations.

A Rare Case of Orbitocranial Penetrating Injury with Intracranial Wooden Foreign Body Residue.

Orbitocranial penetrating injuries (OPIs) caused by wooden foreign bodies (WFBs) are very rare and life threatening. Their diagnosis and treatment could be challenging for an ophthalmologist, requiring us to remain alert for possible intracranial extension. We present a case of a 52-year-old man with a residual wooden foreign body in the left frontal lobe. He had a notable history of trauma from a fall on a tree stump and surgical removal of a wooden foreign body from his left orbit 6 years ago. He was referred to us due to recurrent discharge from the eyelid wound. Wooden foreign body residue was successfully removed with a carefully planned craniotomy without complications. This case describes the clinical manifestation, radiographic features, and treatment of this rare trauma, with an emphasis on imaging diagnosis and multi-disciplinary management.

Case Report: A Case of Cotton-Wool Spots After Intravitreal Injection of Conbercept in an Infant With Incontinentia Pigmenti.

Introduction: Incontinentia pigmenti (IP) is a rare X-linked neuroectodermal dysplasia affecting multiple organs. One of its most significant ophthalmic manifestations is retinal neovascularization due to retinal ischemia, which has been traditionally treated with laser photocoagulation or cryotherapy. The application of anti-vascular endothelial growth factor (VEGF) has been reported for the treatment of retinopathy of IP with beneficial results. However, clinicians should be aware of the possible ocular and systemic side effects of the intravitreal injection of anti-VEGF agents. Case Report: A 4-month-old female infant with IP was treated with intravitreal injection of conbercept in both eyes. However, cotton-wool spots were noticed in the left eye 1 week after the injection. Laser photocoagulation was performed as an adjunct treatment. The cotton-wool spots were absorbed 1 month after the first intravitreal injection and have eventually disappeared. Discussion: The cotton-wool spots, after intravitreal injection of conbercept for the treatment of IP, indicated severe retinal ischemia resulting from the neutralization of excessive VEGF, which was shown on fundus photograph and fluorescent angiography. Anti-VEGF agents could cause retinal arteriolar vasoconstriction and artery occlusion on rare occasions. The administration of anti-VEGF agents in pediatric cases with severe neovascularization and retinal ischemia should be carefully considered.