Although drug-papilledema associations have been reported in numerous case reports and small case series, a large-scale pharmacovigilance evaluation across multiple drug categories remains lacking. This study aimed to identify drugs associated with papilledema using disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database covering the first quarter of 2004 to the fourth quarter of 2023. The term papilledema from the Medical Dictionary for Regulatory Activities (MedDRA) was used to identify relevant cases, and four disproportionality methods (ROR, PRR, BCPNN, and MGPS) were applied to detect positive signals. A total of 51 drugs were identified, of which 21 had been previously reported, and 30 were newly identified. Antineoplastic and immunomodulating agents were the most frequently implicated category, followed by anti-infectives for systemic use, genitourinary system, and sex hormones. The highest-risk drugs by BCPNN ranking were tetracycline, cytarabine, and medroxyprogesterone acetate, while fulvestrant, medroxyprogesterone acetate, and sevoflurane exhibited the shortest onset times. Subgroup analyses revealed distinct population-specific risk patterns: the pediatric population showed vulnerability to growth factor-related agents, testosterone showed a paradoxically stronger signal in females than in males, and doxycycline exhibited a high signal exclusively in off-label use. A sensitivity analysis restricted to physician-reported cases confirmed the robustness of the findings, with 33 drugs retaining positive signals. This study offers clinicians actionable guidance for individualized monitoring and drug safety management in patients at risk of drug-induced papilledema.
To compare the efficacy and safety of repeated low-level red-light (RLRL) therapy with that of low-concentration atropine (0.01%) for myopia control in children, a single-masked, two-center (Chongqing General Hospital and the First Affiliated Hospital of Chongqing Medical University), randomized controlled trial was conducted. Of the 128 enrolled children, 69 were assigned to the RLRL group (32 from Chongqing General Hospital and 37 from the First Affiliated Hospital of Chongqing Medical University) and 59 to the atropine group (24 and 35, respectively). After adjusting for age, sex, baseline axial length (AL), treatment group, visit, and group-by-visit interactions, the mean difference in axial elongation between the RLRL and 0.01% atropine groups among 117 participants was 0.42 mm (95% confidence interval [CI], 0.36 to 0.47 mm; p < 0.01). The mean difference in spherical equivalent refraction (SER) progression between the RLRL and 0.01% atropine groups was 0.86D (95% CI, 0.68 to 1.04D; p < 0.01). An increase in subfoveal choroidal thickness was observed with RLRL (+21.09 mu m), while a a decrease was observed with atropine (-15.60 mu m, p < 0.001). No functional visual loss or structural damage was observed in both groups. RLRL demonstrates superior efficacy for myopia control compared to 0.01% atropine, accompanied by a choroidal response and favorable safety profile.
This prospective cohort study tested whether baseline three-dimensional optical coherence tomography (OCT) and OCT angiography (OCTA) lesion volumes are associated with patient-reported visual function after anti-vascular endothelial growth factor (anti-VEGF) therapy in neovascular age-related macular degeneration (nAMD). Ninety-two treatment-na & iuml;ve nAMD eyes underwent volumetric segmentation of their baseline lesion components, including vascular subretinal hyper-reflective material (vSHRM), avascular subretinal hyper-reflective material (avSHRM), subretinal fluid, intraretinal fluid, and serous pigment epithelial detachment. The National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) was administered at the 2-year visit. Univariate standardized regressions across 36 biomarker-subscale pairs were corrected for multiple testing with the Benjamini-Hochberg false discovery rate (FDR). Three univariate associations survived FDR correction (q < 0.05). In multivariate analysis, baseline vSHRM volume was independently associated with a worse VFQ-25 composite score (standardized beta =-0.366, p = 0.001), and baseline avSHRM volume was independently associated with a worse near activities score (standardized beta = -0.370, p < 0.001), adding 8.0% and 11.9% incremental variance beyond clinical covariates. Baseline vSHRM and avSHRM volumes thus add prognostic information about patient-reported visual function beyond best-corrected visual acuity and clinical covariates. This study was registered in Chinese Clinical Trial Registry (www.chictr.org.cn/showproj.html?proj=173189; ID: ChiCTR2200063428; date of registration: 2022-09-06).
Abstract The effect of sortilin inhibition on acute inner retinal neurodegeneration induced by optic nerve crush was investigated. Pharmacological sortilin inhibition using intravitreal delivery of a polyclonal antibody or a small-molecule inhibitor was evaluated in C57BL/6JRj male mice subjected to unilateral crush. Inner retinal thickness was evaluated by optical coherence tomography, and retinal ganglion cell density was determined in retinal flat mounts. Furthermore, the effect of constitutive sortilin deficiency was examined using Sort1-/- mice. Changes in protein and mRNA levels of sortilin, p75 NTR , and associated injury markers were analyzed. Neither pharmacological inhibition or constitutive loss of sortilin protected against inner retinal thinning or retinal ganglion cell loss following optic nerve crush. A transient 1.4-fold increase in p75 NTR mRNA was observed early after injury, accompanied by a two-fold increase in protein levels. While sortilin expression remained largely unchanged, sortilin deficiency was associated with an altered baseline retinal state, including increased GFAP, p75 NTR , and proBDNF levels. Following optic nerve crush, the induction of p75 NTR was significantly attenuated in sortilin-deficient retinas compared with wild type, without affecting the extent of RGC degeneration. In summary, sortilin inhibition does not preserve inner retinal structure following optic nerve crush, but modulates glial activation, inflammatory signaling, and proneurotrophin dynamics. These findings indicate that sortilin-dependent pathways are not key drivers of optic nerve crush-induced neurodegeneration but may be more relevant in disease contexts characterized by chronic stress and neuroinflammation.
Graves' ophthalmopathy (GO) is a debilitating autoimmune inflammatory disorder triggered by thyrotropin receptor antibody (TRAb). This study aimed to identify circulating inflammatory proteins mediating the causal pathway from TRAb to GO through a mediation Mendelian randomization (MR) framework. Genome-wide association study (GWAS) summary statistics for TRAb were obtained from the FinnGen project (n = 3,690). Data on circulating inflammatory proteins were derived from a meta-analysis of 11 population-based GWAS cohorts of European ancestry (n = 14,824). GWAS datasets for GO were obtained from the VA Million Veteran Program and UK Biobank for cross-validation. Genetically predicted TRAb levels were associated with an increased risk of GO in both the VA Million Veteran Program (odds ratio [OR] = 2.42, p = 0.008) and the UK Biobank (OR = 7.96, p = 0.005). CX3CL1 showed consistent mediation effects in both datasets. Additionally, CXCL10, CXCL9, and TNF-beta exhibited significant mediation effects in the UK Biobank. The identified mediators showed directionally consistent effects, supporting their potential roles in the TRAb-GO pathway. Network analysis highlighted chemokine signaling, leukocyte migration, T-cell activation, and NF-kappa B signaling as key pathways. These findings provide genetically supported evidence suggesting that TRAb may influence the GO risk through specific inflammatory mediators.
Diabetic retinopathy (DR) and diabetic nephropathy (DN) continue to develop even under optimal glycemic control, highlighting the urgent need for non-glucose-dependent protective strategies. Traditional Chinese Medicine offers a unique solution through its overall regulatory advantages of multiple components and multiple targets. This study explored the protective effect and mechanism of the 'Zi-Shen-Jian-Pi-Hua-Yu' (ZJHY) formula on DR and DN. In a diabetic rat model, ZJHY significantly alleviated retinal and renal damage independently of blood glucose control, improved lipid metabolism and renal function, and reduced systemic inflammation. This protective effect is related to reversing the upregulation of the orphan receptor Gpr83 induced by diabetes and restoring the function of the GPR83-ADM2-AKT signaling axis. In vitro mechanism verification indicates that under high glucose conditions, activation of the GPR83-ADM2-AKT axis can induce pro-inflammatory macrophage (M1) polarization and the secretion of inflammatory cytokines such as TNF-alpha, IL-6, and IL-1 beta, while knockdown of GPR83 can inhibit this process. In addition, based on hub genes including GPR83, we integrated multiple human datasets and applied machine learning methods to identify a robust five-gene immune marker (Acvr1c, Tnfsf9, GPR83, Shc4, Ednra), which can serve as an accurate tool for the joint screening and prediction of DR and DN.
The ocular motor functions, including accommodation and vergence, are correlated with extensive brain regions. These functions may change after refractive surgery, but this is unclear in implantable collamer lens (ICL) implantation. To assess the accommodative and vergence functions after ICL implantation, 35 high myopic patients were enrolled. Accommodative and vergence functions were assessed preoperatively and 1 week, 1 month, 3 months, and 6 months postoperatively. The amplitude of accommodation reduced from 13.33 D (interquartile range [IQR], 11.11 to 15.38 D) preoperatively to 10.00 D (IQR, 9.09 to 12.50 D) at 1 week (p < 0.001). The distance negative fusional vergence reduced from 8 triangle (IQR, 6 to 10 triangle) preoperatively to 7 triangle (IQR, 6 to 8 triangle) at 1 week (p = 0.007). The near negative fusional vergence reduced from 21 triangle (IQR, 15 to 24 triangle) preoperatively to 16 triangle (IQR, 13 to 19 triangle) at 1 week (p < 0.001). These parameters remained at the reduced level through 6 months. The positive relative accommodation reduced from -2.50 D (IQR, -3.75 to -2.50 D) preoperatively to -2.25 D (IQR, -2.75 to -1.75 D) at 1 week (p = 0.003) and recovered at 1 month. The accommodative facility reduced from 9 cpm (IQR, 6 to 11 cpm) preoperatively to 7 cpm (IQR, 4 to 9 cpm) at 1 week (p = 0.039), but increased to 9 cpm (IQR, 7 to 12 cpm) at 3 months (p = 0.006). The near phoria reduced from -5 triangle (IQR, -8 to 0 triangle) preoperatively to -1 triangle (IQR, -5 to 3 triangle) at 1 week (p = 0.008) and recovered at 3 months. The vergence facility increased from 9 cpm (IQR, 7 to 12 cpm) preoperatively to 10 cpm (IQR, 9 to 16 cpm) at 3 months (p = 0.004). ICL implantation in high myopia induces alterations in binocular visual functions. It suggests the requirement to establish a binocular visual function evaluation criterion for high myopic patients undergoing refractive surgery, which may provide a potential physiological basis for understanding postoperative visual fatigue.
Hippo and Wnt//-catenin signaling are associated with retinal M & uuml;ller cell proliferation and dedifferentiation into stem cells (precursor cells). However, in mammals, M & uuml;ller cells are difficult to dedifferentiate into stem cells in retinal injury and diseases, which may be related to the altered retinal micro-environment. TNF-alpha is a major inflammatory cytokine released by activated retinal glial cells in glaucoma. Here, we investigated the roles and underlying mechanisms ofTNF-alpha on Hippo and Wnt//-catenin signaling in chronic ocular hypertension (COH) experimental glaucoma and primary cultured M & uuml;ller cells. The activities of /-catenin and YAP, the key effective factors of Wnt and Hippo signaling, were inhibited by TNF-alpha in COH retinas. In activated M & uuml;ller cells, TNF-alpha inhibited the activity of /-catenin and YAP. Following intervention with the TNFR1 antagonist R7050, Wnt3a protein levels increased,/-catenin, Stat3, and YAP phosphorylation decreased, and the activities of GSK3/ and MST1 were suppressed. Additionally, R7050 elevated M & uuml;ller cell proliferation and increased cyclin D1/D2 and Nestin protein expression. In COH retinas, intravitreal injection of R7050 increased Nestin and Ascl1 expression in M & uuml;ller cells. These results demonstrate that TNF-alpha inhibits the proliferation and reprogramming of M & uuml;ller cells by awakening the Hippo pathway and inhibiting the Wnt//-catenin pathway in COH retinas.
Diabetic retinopathy (DR) is a leading cause of vision impairment, yet the role of chemerin receptor 23 (ChemR23) in its progression remains unclear. This study aimed to explore the function of ChemR23 in modulating M & uuml;ller cells' activation and injury to retinal ganglion cells (RGCs) in DR. Using 75 db/db and 16 wild-type mice divided into eight groups, we assessed ChemR23 expression and its interaction with phosphatase and tensin homolog (PTEN) through molecular docking and surface plasmon resonance. Immunofluorescence confirmed the co-localization of ChemR23 with glutamine synthetase (GS) and PTEN in M & uuml;ller cells. Histological evaluation revealed retinal thinning and RGCs in 18-week db/db mice, accompanied by reduced synaptic markers (SYN, PSD95) and PTEN, alongside elevated glial fibrillary acidic protein, inflammatory cytokines, and phosphorylated protein kinase B (AKT). Activation of ChemR23 with Resolvin E1 (RvE1) or Chemerin 9 (C9) ameliorated these pathological changes. However, the protective effects were abolished by the PTEN inhibitor SF1670. These findings demonstrate that ChemR23 may regulate AKT phosphorylation through its interaction with PTEN, thereby protecting the retinal neurons and suppressing inflammatory responses and M & uuml;ller cell activation in DR.
Dopamine (DA) modulates signaling within the retina. The biochemistry and distribution of dopaminergic neurons in the retina have been extensively characterized. However, little is known about the effect of a high dopamine concentration in the retina on the retino-collicular pathway. In this experiment, functional neural activity was recorded simultaneously in the retina by electroretinogram (ERG) and in the superior colliculus (SC) in rats. Recordings were made without interruption before, during, and after intravitreal injections of DA and its antagonist, haloperidol (HA). A 3-s flash of light allowed discrimination between responses to the onset and offset of the stimulus. We found that a high dose of intravitreal injection of DA altered the ERG waveform and significantly (similar to 50%) reduced the sustained response to light in the SC, whereas both transient onset and offset responses remained unchanged. Conversely, injection of the DA antagonist HA did not affect the ERG waveform but drastically (similar to 80%) reduced the offset response in the SC. Our results support the idea that DA contributes to enhancing contrast sensitivity. Furthermore, our data indicate that this effect may occur through a reduction in the sustained response while preserving transient responses to stimulus onset and offset.
Retinal vein occlusion (RVO) is a major retinal vascular disorder in which the progression of nonperfusion area (NPA) is closely linked to visual outcomes. This study evaluates a 3D radiomics and deep learning fusion framework (SS-OCTA-omics) derived from swept-source OCTA imaging for predicting nonperfusion area (NPA) progression (Delta NPA > 1 PD) in RVO. A retrospective internal cohort of 87 RVO patients (with 22,272 slices of 2D data and 87 volumes of 3D data) and an external validation cohort of 109 patients (with 27,904 slices of 2D data and 109 volumes of 3D data) underwent SS-OCTA imaging, from which 2D and 3D radiomics features reflecting retinal microstructure were extracted. A 3D ConvNeXt-tiny network was developed to integrate deep learning and radiomics features, and its predictive performance was compared with 2D models, traditional radiomics approaches (SVM, Adaboost, and Logistic Regression), and clinical biomarkers, including vessel density (VD) and fractal dimension (FD). The 3D fusion model achieved an AUC of 0.794 (95% CI: 0.612-0.975) and an accuracy of 82.1% (95% CI: 0.631-0.939), outperforming 2D architectures (AUC 0.645 [95% CI: 0.634-0.656]), conventional radiomics (AUC 0.610 [95% CI: 0.405-0.815]), and clinical biomarkers (AUC 0.570 [95% CI: 0.363-0.776]). These findings highlight the potential of the SS-OCTA-omics framework to enhance individualized risk assessment in RVO.
Myopia is associated with retinal detachment (RD), a sight-threatening condition. This study aimed to determine whether specific myopic photoreceptor (PR) thickness profiles are associated with RD. In total, 10,328 myopic participants from the UK Biobank who underwent baseline optical coherence tomography (OCT) imaging were included. Thickness measurements of the external limiting membrane (ELM) to the inner and outer photoreceptor segments (ISOS) and from the ISOS to the retinal pigment epithelium (RPE) were obtained via OCT to serve as indicators of the inner and outer photoreceptor segments. Latent profile analysis categorized participants into distinct photoreceptor thickness profiles, and Cox's proportional hazard models were used to estimate the hazard ratios (HRs) of RD between the profiles. Two distinct photoreceptor thickness profiles were identified; Profile 2 (including 142 high myopia participants and 862 low/moderate myopia participants) demonstrated thicker ELM-ISOS and thinner ISOS-RPE measurements than Profile 1 (including 612 high myopia participants and 8,712 low/moderate myopia participants). After adjustment for all covariates (including demographic factors [age, gender, and ethnicity], socioeconomic factors [education and Townsend deprivation index], systemic factors [body mass index, high blood pressure, and diabetes], lifestyle factors [physical activity, sleep duration, smoking status, and drinking status], and ocular factors [intraocular pressure and mean spherical equivalent]), Profile 2 was associated with a significantly increased RD risk compared with Profile 1 (HR, 1.79; 95% confidence interval [CI], 1.07-2.99; p = 0.027). These findings suggest that photoreceptor thickness patterns may serve as novel indicators for myopic RD risk assessment.
Neovascular glaucoma (NVG) is a severe secondary glaucoma characterized by neovascularization of the iris and angle, often leading to uncontrolled intraocular pressure (IOP). This retrospective study compared the clinical efficacy of ultrasound cycloplasty (UCP) alone vs UCP combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in NVG management. Eighty eyes were included, with 45 treated using UCP alone and 35 receiving combined therapy. IOP, visual acuity (VA), and the number of glaucoma medications were evaluated preoperatively and at 1 d, 1 week, 1 month, and 3 months postoperatively. Both groups demonstrated significant IOP reductions at all follow-up visits (all p < 0.05). However, the combined-treatment group achieved greater IOP reduction at 1 month (-19.28 +/- 11.82 vs -13.55 +/- 8.43 mmHg, p = 0.020), and 3 months (-18.42 +/- 13.57 vs -10.14 +/- 10.64 mmHg, p = 0.007). Visual acuity improvement was also more pronounced in the combined group at 1 week (p = 0.013) and 3 months (p = 0.037). Postoperative medication burden decreased in both groups, with no significant between-group difference. These findings suggest that combining UCP with intravitreal anti-VEGF therapy provides superior short-term IOP control and visual outcomes compared with UCP alone, likely due to the complementary mechanisms of reducing aqueous humor production and suppressing anterior segment neovascularization.
