AIM: To investigate Omicron's impact on clinical presentation of acute primary angle closure (APAC) in China. METHODS: A consecutive case series with historical controls was conducted at Shenzhen Eye Hospital, the largest specialized hospital in Shenzhen, China. Medical records from a two-month period during the Omicron pandemic (December 1, 2022, to January 31, 2023) were compared with records from two control groups (12/2018–1/2019 and 12/2021–1/2022) before pandemic. Patients with APAC were included, and the prevalence of APAC and demographic characteristics in Omicron-infected and non-infected patients were compared. RESULTS: Seventy-one (23.43%) out of 303 patients were diagnosed with APAC in the pandemic cohort, which was 2.98 and 2.61 times higher than that in control cohorts (7.87% in 2019, 8.96% in 2022, P<0.001). The pandemic cohort has significantly higher Omicron-infected rate (78.87% vs 0 vs 0; P<0.001), lower proportion of glaucoma history (16.90% vs 42.86% vs 41.67%, P=0.005), higher surgical rate (95.77% vs 83.33% vs 78.57%, P=0.024), higher total medical costs and larger pupil diameter (5.63±0.15 vs 4.68±0.15 vs 4.69±0.22 mm, P<0.01). In 83% Omicron-infected patients, ocular symptoms appeared within 3d after systemic symptoms onset. In multivariate analysis, Omicron infection (P<0.001) was the only independent predictor of pupil diameter. CONCLUSION: In the Omicron epidemic in China, there is an increase of prevalence and severity of APAC, particularly focusing on the first 3d following infection.

Retinitis pigmentosa (RP) is the most common inherited blinding retinal degenerative disease characterized by the progressive loss of photoreceptors and retinal pigment epithelium (RPE) that eventually causes retinal degeneration. However, the mechanisms that initiate RP and drive retinal vulnerability remain incompletely understood, and new strategies for its prevention and therapy are urgently needed. Mitochondrial dysfunction is the initiator of a variety of neurodegeneration, whether mitochondrial dysfunction is an important pathogenic factor of RP is still unknown. Our single-cell RNA sequencing, transmission electron microscopy, and enzyme-linked immunosorbent assay revealed that both photoreceptor cells and RPE cells of RP rats have abnormal mitochondria, accompanied by decreased levels of nicotinamide adenine dinucleotide (NAD+) metabolism which rendered the lack of NAD+ vulnerable to disease-related insults. Moreover, similar experimental results were observed in an in vitro RP model established by human primary RPE cells. Furthermore, electroretinography combined with hematoxylin-eosin, immunofluorescence analysis, and fundus photograph investigations revealed that oral administration of the NAD+ precursor nicotinamide (NMN) protected RP rats against retinal degeneration. Mechanistically, single-cell RNA sequencing, siRNA targeting, and AAV virus applications demonstrated the therapeutic effect of NMN on RP through the glyceraldehyde-phosphate dehydrogenase-mitochondria pathway. Collectively, these findings indicate that mitochondrial abnormalities may be the drivers of RP and NMN has a therapeutic effect on RP.

Abnormal angiogenesis is associated with myriad human diseases, including proliferative diabetic retinopathy (PDR). Signaling transduction through phosphoinositide 3-kinases (PI3Ks) plays a critical role in angiogenesis. Herein, we showed that p110δ, the catalytic subunit of PI3Kδ, was highly expressed in pathological retinal vascular endothelial cells (ECs) in a mouse model of oxygen-induced retinopathy (OIR) and in fibrovascular membranes from patients with PDR. To explore novel intervention with PI3Kδ expression, we developed a recombinant dual adeno-associated viral (rAAV) system for delivering CRISPR/Cas9 in which Streptococcus pyogenes (Sp) Cas9 expression was driven by an endothelial specific promoter of the intercellular adhesion molecule 2 (pICAM2) to edit genomic Pik3cd, the gene encoding p110δ. We then demonstrated that infection of cultured mouse vascular ECs with the dual rAAV1s of rAAV1-pICAM2-SpCas9 and rAAV1-SpGuide targeting genomic Pik3cd resulted in 80% DNA insertion/deletion in the locus of genomic Pik3cd and 70% depletion of p110δ expression. Furthermore, we showed that in the mouse model of OIR editing retinal Pik3cd with the dual rAAV1s resulted in not only a significant decrease in p110δ expression, and Akt activation, but also a dramatic reduction in pathological retinal angiogenesis. These findings reveal that Pik3cd editing is a novel approach to treating abnormal retinal angiogenesis.

Abstract Globally, irreversible blindness is mainly caused by glaucoma, characterized by the selective loss of retinal ganglion cells (RGCs). Reducing pathologically high intraocular pressure (ph-IOP) is clinically effective but fails to halt disease progression. Oxidative stress-induced RGC ferroptosis contributes to poor outcomes after ph-IOP reduction. Thus, drugs to alleviate oxidative stress and inhibit RGC ferroptosis have therapeutic potential for glaucoma treatment. Herein, we first attempted to apply black phosphorus quantum dots (BPQDs) ophthalmologically, primarily exploiting its reactive oxygen species (ROS) scavenging abilities and non-toxic degradation. Briefly, BPQDs were injected into the vitreous chamber of ph-IOP-injured glaucomatous rats. Injected BPQDs maintained therapeutic effectiveness for almost one week without significant cellular toxicity. Meanwhile, BPQDs demonstrated potent ROS scavenging and cellular redox repairing abilities, ultimately inhibiting RGC ferroptosis and improving both morphological and functional outcomes in glaucomatous rats. Thus, BPQDs represent the first and potential anti-ferroptosis nano-drug to treat glaucoma and other ferroptosis-related diseases.

This study compared the surgical outcomes in eyes with myopic foveoschisis (MF) according to the recently developed ATN classification system. This was an observational case series of 64 consecutive eyes that underwent vitrectomy for MF. Eyes were classified into severe myopic maculopathy (MM) (n = 43) and non-severe MM (n = 21) groups according to the ATN classification system. The primary outcome measures constituted best-corrected visual acuity (BCVA) and anatomical changes. In total, BCVA improved from 0.97 to 0.53 (P < 0.001) after surgery. The ATN score was significantly lower in the eyes with vision improvement than those without vision improvement (P < 0.001). In the subgroup, BCVA improved from 0.79 to 0.28 in the non-severe MM group (P < 0.001), and improved from 1.05 to 0.65 in the severe MM group (P = 0.001) after surgery. The non-severe MM group achieved better postoperative BCVA (P = 0.001) and were more likely to gain vision improvement (P < 0.001) after surgery compared with the severe MM group. Anatomical success was achieved in 62 of the 64 eyes (96.88%). Two eyes with anatomical failure developed full-thickness macular holes postoperatively; both were in the severe MM group. For patients with MF, different severity of MM based on ATN classification could lead to a significantly different prognosis after surgery. For patients with high ATN scores, the operative decision should be made cautiously for the worse anatomical and visual prognosis. ATN system is instructive in making operative proposals for MF. On the basis of the newly developed ATN classification system, we found significant differences in postoperative visual acuity, the rate of vision improvement, and the rate of primary retinal reattachment after vitrectomy between the severe and non-severe myopic maculopathy groups in patients with myopic foveoschisis.

Purpose: To compare the morphologic characteristics and response to surgery of myopic foveoschisis (MF) with different patterns of vitreomacular interface abnormalities (VMIAs). Methods: In this observational case series, 158 eyes of 121 MF patients with epiretinal membrane (ERM) or vitreomacular traction (VMT) based on optical coherence tomography (OCT) were enrolled. All the eyes were divided into two groups by the pattern of VMIAs: ERM and VMT group. Sixty-one eyes underwent pars plana vitrectomy (PPV) and were followed up for at least 6 months. The morphologic characteristics based on OCT and the surgical outcome were evaluated. Outcome: ERM and VMT were found in 47.47 and 52.53% of the cases, respectively. A higher rate of foveal detachment (61.4 vs. 26.7%; p < 0.001) and a higher rate of outer lamellar macular hole (45.8 vs. 21.3%; p = 0.001) were detected in the eyes with VMT compared with those with ERM. In contrast, a lower rate of inner lamellar macular hole (28.9 vs. 60.0%; p = 0.001) was detected in the eyes with VMT compared with those with ERM. The disruption of the external limiting membrane (ELM) was more common in the eyes with VMT than in those with ERM (45.8 vs. 21.3%; p = 0.001). PPV was performed in 61 eyes with a mean follow-up time of 23.55 ± 19.92 months. After surgery, anatomical resolution was achieved in 51 eyes (83.6%). At the final visit, the mean central foveal thickness (CFT) decreased significantly from 547.83 to 118.74 μm, and the mean LogMAR BCVA improved significantly from 0.92 to 0.57. The VMT group was associated with a higher proportion of eyes with visual acuity improvement postoperatively (p = 0.02) and had more a decrease of CFT (P = 0.007) compared with the ERM group. Conclusion: In the eyes with MF, outer retinal lesions occurred more frequently in the eyes with VMT, whereas inner retinal lesions occurred more frequently in the eyes with ERM. Tangential force generated by ERM may act as a causative factor for the inner retinal lesions in MF, and inward-directed force resulting from VMT may act as a causative factor for outer retinal lesions in MF.

Proliferative vitreoretinopathy (PVR), an inflammatory and fibrotic blinding disease, is still a therapeutic challenge. Retinal pigment epithelial (RPE) cells dislodged in the vitreous play a central role in the PVR pathogenesis. To identify potential novel contributors to the pathogenesis of PVR, we investigated a profile of vitreous-induced changes in ARPE-19 cells by RNA sequencing. Bioinformatics analysis of the sequencing data showed that there were 258 genes up-regulated and 835 genes down-regulated in the ARPE-19 cells treated with human vitreous. Among these genes, there were three genes related to eye disease with more than threefold changes. In particular, quantitative PCR and western blot results showed that interleukin 13 receptor (IL13R)α2 that is over-expressed in a variety of cancers was up-regulated more than three times in the vitreous-treated ARPE-19 cells. Immunofluorescence analysis indicated that interleukin-13 receptor subunit α2 (IL13Rα2) was highly expressed in ARPE-19 cells within epiretinal membranes from patients with PVR. Importantly, blocking IL13Rα2 with its neutralizing antibody significantly inhibited vitreous-induced contraction of ARPE-19 cells, suggesting a novel role of IL13Rα2 in the PVR pathogenesis. These findings will improve our understanding of the molecular mechanisms by which PVR develops and provides potential targets for PVR therapeutics.