Highly myopic optic nerve head (ONH) abnormalities encompass a series of complications resulting from the stretching of papillary and peripapillary structures during significant axial elongation. The morphological changes in the ONH typically initiate with disk tilting or rotation, progressing to PHOMS and PPA. Tissue defects in each layer manifest as focal lamina cribrosa defects (FLDs), peripapillary intrachoroidal cavitations (PICCs), and acquired pits of the optic nerve (APON). Anterior vitreous/vascular traction and posterior scleral protrusion may lead to prelaminar schisis as well as paravascular cysts and holes, which can potentially develop into retinoschisis. Traditional color fundus photography (CFP) is often insufficient for visualizing most of these lesions, yet their description and quantification benefit significantly from the advancements in optical coherence tomography (OCT) and OCT angiography (OCTA), complemented by fundus autofluorescence (FAF), indocyanine green angiography (ICGA), and three-dimensional imaging. The effective diagnosis and classification of ONH abnormalities heavily rely on a comprehensive understanding of their multimodal imaging features, as outlined in this review. These findings provide valuable insights into optic neuropathy in high myopia, establishing a solid foundation for future endeavors in disease monitoring and treatment guidance.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical manifestations of WD are complex and variable, with Kayser-Fleischer ring (K-F ring) and the sunflower cataract being the most common ocular findings. Visual impairment is rare in patients with WD. We report the case of a 17-year-old female with bilateral optic atrophy associated with WD and summarize the clinical features of previously reported cases of optic neuropathy in WD, Clinicians should be aware that WD is a rare cause of optic neuropathy and that optic neuropathy in patients with WD may need to be recognized and screened.

Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.

UNASSIGNED: This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population.
UNASSIGNED: Clinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed.
UNASSIGNED: The study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%).
UNASSIGNED: OTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

UNASSIGNED: In the last two decades, electrical stimulation (ES) has been tested in patients with various eye diseases and shows great treatment potential in retinitis pigmentosa and optic neuropathy. However, the clinical application of ES in ophthalmology is currently limited. On the one hand, optimization and standardization of ES protocols is still an unmet need. On the other hand, poor understanding of the underlying mechanisms has hindered clinical exploitation.
UNASSIGNED: Numerous experimental studies have been conducted to identify the treatment potential of ES in eye diseases and to explore the related cellular and molecular mechanisms. In this review, we summarized the in vitro and in vivo evidence related to cellular and tissue response to ES in eye diseases. We highlighted several pathways that may be utilized by ES to impose its effects on the diseased retina.
UNASSIGNED: Therapeutic effect of ES in retinal degenerative diseases might through preventing neuronal apoptosis, promoting neuronal regeneration, increasing neurotrophic factors production in Müller cells, inhibiting microglial activation, enhancing retinal blood flow, and modulating brain plasticity. Future studies are suggested to analyse changes in specific retinal cells for optimizing the treatment parameters and choosing the best fit ES delivery method in target diseases.

Optic neuropathy is the leading cause of irreversible blindness and is characterized by progressive degeneration of retinal ganglion cells (RGCs). Several studies have demonstrated that transplantation of Schwann cells (SCs) is a promising candidate therapy for optic neuropathy and that intravitreally transplanted cells exert their effect via paracrine actions. Extracellular vesicle (EV)-based therapies are increasingly recognized as a potential strategy for cell replacement therapy. In this study, we aimed to investigate the neuroprotective and regenerative effects of SC-EVs following optic nerve injury. We found that SC-EVs were internalized by RGCs in vitro and in vivo without any transfection reagents. Intriguingly, SC-EVs significantly enhanced the survival and axonal growth of primary RGCs in a coculture system. In a rat optic nerve crush model, SC-EVs mitigated RGC degeneration, prevented RGC loss, and preserved the thickness of the ganglion cell complex, as demonstrated by the statistically significant improvement in RGC counts and thickness measurements. Mechanistically, SC-EVs activated the cAMP-response element binding protein (CREB) signaling pathway and regulated reactive gliosis in ONC rats, which is crucial for RGC protection and axonal regeneration. These findings provide novel insights into the neuroprotective and regenerative properties of SC-EVs, suggesting their potential as a cell-free therapeutic strategy and natural biomaterials for neurodegenerative diseases of the central nervous system.

Retinal ganglion cells (RGCs) are the sole output neurons conveying visual stimuli from the retina to the brain, and dysfunction or loss of RGCs is the primary determinant of visual loss in traumatic and degenerative ocular conditions. Currently, there is a lack of RGC-specific Cre mouse lines that serve as invaluable tools for manipulating genes in RGCs and studying the genetic basis of RGC diseases. The RNA-binding protein with multiple splicing (RBPMS) is identified as the specific marker of all RGCs. Here, we report the generation and characterization of a knock-in mouse line in which a P2A-CreERT2 coding sequence is fused in-frame to the C-terminus of endogenous RBPMS, allowing for the co-expression of RBPMS and CreERT2. The inducible Rbpms-CreERT2 mice exhibited a high recombination efficiency in activating the expression of the tdTomato reporter gene in nearly all adult RGCs as well as in differentiated RGCs starting at E13.5. Additionally, both heterozygous and homozygous Rbpms-CreERT2 knock-in mice showed no detectable defect in the retinal structure, visual function, and transcriptome. Together, these results demonstrated that the Rbpms-CreERT2 knock-in mouse can serve as a powerful and highly desired genetic tool for lineage tracing, genetic manipulation, retinal physiology study, and ocular disease modeling in RGCs.

Macrophage migration inhibitory factor (MIF), a multifunctional cytokine, is secreted by various cells and participates in inflammatory reactions, including innate and adaptive immunity. There are some evidences that MIF is involved in many vitreoretinal diseases. For example, MIF can exacerbate many types of uveitis; measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment. MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage. Furthermore, MIF is critical for retinal/choroidal neovascularization, especially complex neovascularization. MIF exacerbates retinal degeneration; thus, anti-MIF therapy may help to mitigate retinal degeneration. MIF protects uveal melanoma from attacks by natural killer cells. The mechanism underlying the effects of MIF in these diseases has been demonstrated: it binds to cluster of differentiation 74, inhibits the c-Jun N-terminal kinase pathway, and triggers mitogen-activated protein kinases, extracellular signal-regulated kinase-1/2, and the phosphoinositide-3-kinase/Akt pathway. MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway. This review focuses on the structure and function of MIF and its receptors, including the effects of MIF on uveal inflammation, retinal degeneration, optic neuropathy, retinal/choroidal neovascularization, and uveal melanoma.

FDXR: associated disease is characterized by optic atrophy, acoustic neuropathy, and developmental delays. This study evaluated the ocular phenotypes and genetic features of patients with biallelic FDXR variants. Five individuals from unrelated non-consanguineous Chinese families with biallelic FDXR variants were identified using whole exome sequencing, Sanger sequencing, and co-segregation validation. In addition to optic atrophy and diverse extraocular manifestations, all patients presented with retinal dystrophy, and electroretinogram showed severely impaired cone and rod functions in their first decades. Three of the five patients showed attenuated retinal vessels that appeared as white lines on the fundus, and fundus fluorescein angiography (FFA) further revealed vascular abnormalities including delayed filling, completely occluded retinal vasculature, and severe retinal vascular nonperfusion of the peripheral retina. Five novel FDXR variants were identified: c.383C > T (p.A128V), c.963delG (p.R322fs*7), c.1052_1053delTC (p.L351Pfs*12), c.394-11T > G and c.1002+1G > A. Retinal dystrophy with attenuated retinal vessels appearing as white lines was observed in this cohort, and the FFA images revealed that retinal vascular occlusion could be a distinct clinical characteristic of FDXR-associated disease. Probands with FDXR revealed severe early onset ophthalmic features with rapid-progression, indicating the importance of early diagnosis and treatment. Moreover, this is the first study to report FFA manifestations in an FDXR cohort, expanding the FDXR-associated ocular disease phenotype and genetic spectrum.

OBJECTIVE: To investigate the brain functional alterations in dysthyroid optic neuropathy (DON) by evaluating spontaneous neural activity, using functional magnetic resonance imaging (fMRI) with regional homogeneity (ReHo), and its relationship with ophthalmologic performance.
METHODS: Forty-seven patients with thyroid-associated ophthalmopathy (TAO; 20 with DON, 27 with non-DON) and 33 age-, sex-, and education-matched healthy controls (HCs) underwent fMRI. ReHo values were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). Correlations between ReHo values and ophthalmological metrics were assessed for DONs, with Bonferroni correction for multiple comparisons (p < 0.004). ROC curves were applied to evaluate the diagnostic performance of ReHo metrics.
RESULTS: ReHo values were significantly lower in the left insula and right superior temporal gyrus, and higher in the left posterior cingulate cortex (LPCC), of DON than of non-DON patients. ReHo values were also significantly lower in the right middle temporal, left insula, and left precentral gyrus in DON than in HCs. Meanwhile, ReHo values were higher in LPCC in non-DON than in HCs. ReHo values correlated with ophthalmic examinations to varying degrees in DON. For distinguishing DON, the ReHo values in LPCC showed optimal individually (AUC = 0.843), the combination of the ReHo in both the left insula and LPCC performed better (AUC = 0.915).
CONCLUSIONS: Spontaneous brain activity differed between TAO with and without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker.
CONCLUSIONS: Spontaneous brain activity in DON differed from that in TAO without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker for early detection of DON.
CONCLUSIONS: • Dysthyroid optic neuropathy (DON) affects brain activity, which contributes in the understanding of its visual dysfunction. • Regional homogeneity values differ between thyroid-associated ophthalmopathy with and without DON in various brain regions. • Regional homogeneity values can be used as a biomarker in the differential diagnosis of DON.