Background:Insulin resistance (IR) elevates the risk of coronary artery disease (CAD). The triglyceride-glucose (TyG) index is a reliable substitute indicator for IR. Computed tomography-derived fractional flow reserve (CT-FFR) and coronary flow reserve (CFR) effectively assess coronary vascular function. This study aimed to investigate the relationship between the TyG index and coronary vascular function assessed by CT-FFR and CFR in suspected CAD patients. Methods:We enrolled 293 patients who underwent single-photon emission computed tomography (SPECT) along with coronary computed tomography angiography (CCTA), and analyzed the relationships among the CT-FFR, myocardial blood flow (MBF), CFR, and the TyG index. Results:Among the patients, those with a higher TyG index exhibited a relatively lower CT-FFR (0.80 vs. 0.85; P=0.02), rest-MBF (0.80 vs. 0.83; P=0.01), stress-MBF (1.92 vs. 2.26; P=0.01), and CFR (2.49 vs. 2.72; P=0.42). The TyG index was weakly and negatively correlated with the left ventricular (LV) CFR (r=-0.153; P=0.009). Among the patients without obstructive CAD, those with a high TyG index had a significantly lower CFR than those with a low TyG index (2.54 vs. 2.95; P=0.01), but no such significant difference was found in relation to the CT-FFR (0.91 vs. 0.93; P=0.72). Of the 879 vessels examined, 448 (51%) exhibited a reduced CFR. Compared with the vessels with a normal CFR, those with a decreased CFR exhibited a significantly increased obstructive CAD rate (40% vs. 29%; P<0.001), a lower CT-FFR (0.90 vs. 0.93; P<0.001), and a higher TyG index (8.81 vs. 8.67; P<0.001). In the vessels without obstructive CAD, the TyG index was higher in those with a reduced CFR compared with those with a normal CFR (8.80 vs. 8.59; P<0.001). The patient-level analysis revealed that male sex, the TyG index, obstructive CAD, and the CT-FFR were independently associated with the LV-CFR. The TyG index remained associated with the LV-CFR after adjustment for conventional risk factors. The TyG index remained independently associated with a reduced CFR in the patients without obstructive CAD. Conclusions:The TyG index was independently associated with coronary vascular function, including both epicardial artery and microcirculatory function. The patients without obstructive CAD and those with a decreased CFR exhibited an increased TyG index, indicating a relationship between the TyG index and microcirculatory dysfunction. The TyG index, as a marker of metabolic health, was also related to microvascular injury. Our results provide insights into the association between the TyG index and coronary vascular function, which may inform clinical risk assessment.
Retinal and choroidal vascular diseases including age-related macular degeneration (AMD), branch and central retinal vein occlusion (BRVO, CRVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) are important causes of blindness. Their treatments by anti-VEGF agents imply heavy economic impact. The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies and medical costs of 15,266 patients in Tianjin (2021–2024), utility values, and transition probabilities derived from clinical trials. Costs and outcomes were calculated separately under societal and medical insurance perspectives. Incremental cost-effectiveness ratios (ICERs) were computed, and sensitivity analyses (one-way, two-way and probabilistic) were conducted to assess result robustness. From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with ICERs as -442,423.176, -2,429,628.701, -69,339.384, -410,661.276 as Chinese Yuan/quality-adjusted life year (RMB/QALY) under the societal perspective, and -370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept’s ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. Sensitivity analyses confirmed the robustness of these findings. Conbercept is a cost-effective alternative to ranibizumab in RVO, DME, and PM from societal and medical insurance perspectives. In AMD, ranibizumab remains more clinically effective option. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China.
PURPOSE:To evaluate the structural impact of intravitreal faricimab on the neovascular network in treatment-resistant Type 1 macular neovascularization (MNV) using quantitative swept-source optical coherence tomography angiography (SS-OCTA). METHODS:A retrospective, single-center cohort study was conducted on 21 eyes with Type 1 MNV (including polypoidal choroidal vasculopathy) that were unresponsive to intensive intravitreal anti-VEGF therapy. Patients underwent switching therapy with a single faricimab injection and were evaluated at baseline and Day 14. Quantitative SS-OCTA analysis included perfusion indices, vascular component segmentation (trunk vs. capillary), and fractal analysis (fractal dimension [FD] and lacunarity) to quantify lesion complexity and pruning. RESULTS:Despite a heavy prior treatment burden (mean 11.8 ± 6.5 injections), significant functional and anatomical improvements were observed. BCVA improved (P = 0.0088), and maximum pigment epithelial detachment height decreased (P = 0.0008) with reductions in CFT and SFCT. Crucially, SS-OCTA revealed profound network regression with reduced perfusion area (P = 0.0002) and vessel density (P = 0.0019). Component analysis demonstrated the regression of both recalcitrant trunk and capillary vessels. This vascular remodeling was confirmed by decreased branching complexity (intersection points, P = 0.0017; FD, P = 0.001) and increase in lacunarity (P = 0.0102), quantitatively indicating the "pruning" of the neovascular tree. CONCLUSIONS:Intravitreal faricimab demonstrated rapid regression of neovascular architecture in refractory MNV. Quantitative SS-OCTA findings suggest that dual Ang-2/VEGF-A inhibition may contribute to vascular pruning of both trunk and capillary vessels, supporting a potential benefit in structural remodeling compared with anti-VEGF therapy.
To evaluate the 3-year efficacy and safety of capsular tension ring (CTR) implantation during phacoemulsification with intraocular lens implantation (PEI) combined with trabeculectomy (Trab) in patients with acute angle-closure crisis (AACC). Retrospective cohort study. Patients who underwent PEI+Trab were divided into two groups according to whether they received concurrent CTR implantation. Postoperative clinical indicators were collected at 1, 3, 12, 24, and 36 months and compared between the CTR and non-CTR groups. Uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BCDVA), refractive prediction error (PE), intraocular lens (IOL) tilt, intraocular pressure (IOP), anterior chamber depth (ACD), corneal endothelial cell density (ECD), and complication rates. Among 114 eyes of 114 patients with AACC, 54 received CTR implantation and 60 did not. Three-year follow-up was completed in 68.4% of patients. At 3 years, UDVA was significantly better in the CTR group than in the non-CTR group (median [IQR] 0.22 [0.10–0.30] vs. 0.30 [0.22–0.60]; P = 0.02) and remained stable throughout follow-up. In contrast, UDVA in the non-CTR group fluctuated markedly and did not stabilize until 2 years after surgery. BCDVA was comparable between groups (median [IQR] 0.10 [0.00–0.16] vs. 0.10 [0.00–0.26]; P = 0.41). PE was consistently lower in the CTR group (0.32 ± 0.73 D vs. 0.77 ± 0.88 D; P = 0.03), and IOL tilt was also significantly reduced (median [IQR] 0.16° [0.12–0.29] vs. 0.42° [0.31–0.61]; P < 0.001). ACD and ECD did not differ significantly between groups (ACD: 3.55 ± 2.86 mm vs. 3.54 ± 2.59 mm, P = 0.85; ECD: 1410.05 ± 470.19 vs. 1558.98 ± 405.97 cells/mm², P = 0.14). IOP remained similar between groups at all time points over the 3-year follow-up (all P > 0.05). The CTR group showed a significantly lower incidence of CCS (0% vs. 20.6%; P = 0.01). However, rates of IOL pupil capture (19.4% vs. 2.9%; P = 0.03) and YAG laser capsulotomy for PCO (40.7% vs. 23.3%; P = 0.046) were higher in the CTR group. One patient in each group required reoperation. The proportion of patients requiring long-term antiglaucoma medications did not differ significantly between groups (9.7% vs. 2.9%; P = 0.26). In AACC patients undergoing PEI+Trab, CTR implantation reduces IOL tilt and PE, improves long-term refractive stability, thereby optimizing long-term UDVA, and lowers CCS risk without compromising IOP control or ACD stability. However, the higher incidences of IOL capture and YAG laser capsulotomy for PCO in the CTR group warrant further clinical investigation.
Age-related macular degeneration (AMD) is a prevalent neuroinflammation condition and the leading cause of irreversible blindness among the elderly population. Smoking significantly increases AMD risk, yet the mechanisms remain unclear. Here, we investigate the role of Sema4D-PlexinB1 axis in the progression of AMD, in which Sema4D-PlexinB1 is highly activated by smoking. Using patient-derived samples and mouse models, we discover that smoking increases the presence of Sema4D on the surface of CD8+ T cells that migrate into the choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 axis and interact with its receptor PlexinB1 on choroidal pericytes. This leads to ROR2-mediated PlexinB1 phosphorylation and pericyte activation, thereby disrupting vascular homeostasis and promoting neovascularization. Inhibition of Sema4D reduces CNV and improves the benefit of anti-VEGF treatment. In conclusion, this study unveils the molecular mechanisms through which smoking exacerbates AMD pathology, and presents a potential therapeutic strategy by targeting Sema4D to augment current AMD treatments.
Background : This study investigated the association between photoreceptor structural restoration and visual function outcomes in patients undergoing surgery for closed macular holes (MHs). Using adaptive optics scanning laser ophthalmoscopy (AOSLO) and microperimetry, we aimed to provide a more detailed understanding of photoreceptor recovery and visual improvement in closed MHs. Methods : We conducted a retrospective observational study of 31 eyes of 28 patients who underwent vitrectomy with internal limiting membrane (ILM) peeling to treat idiopathic MHs. Visual and structural outcomes were monitored 3 months to 2 years postoperatively: best-corrected visual acuity (BCVA), MH diameter and duration, optical coherence tomography (OCT) images, 4° retinal mean sensitivity (RMS), fixation rates, 68.2% BCEA (binary contour ellipse area) of microperimetry, and cone density as measured by AOSLO. Based on the OCT findings, the patients were categorized into two groups: type 1 (closed MH with no neurosensory defect at the fovea) and type 2 (closed MH with a foveal neurosensory defect). Results : The analysis revealed that type 1 closures resulted in significantly better photoreceptor recovery, with cone cells migrating toward the fovea and forming dense islets, consistent with the integrity of the inner segment/outer segment layer on OCT. These patients also had better postoperative BCVA and higher RMS rather than fixation improvement, aligning with the improved cone density. In contrast, type 2 closures exhibited sparse cone distribution and a prevalence of large, high-density cells, possibly indicating glial cell proliferation and exposed retinal pigment epithelium (RPE). MH size, rather than duration or preoperative BCVA, was a key determinant of type 1 closure outcomes. Conclusion : AOSLO is a valuable tool for evaluating microstructural healing in MHs and reveals that type 1 closure, characterized by cone migration, leads to greater neuroretinal repair and improved BCVA and retinal sensitivity. Meanwhile, type 2 closures, marked by less photoreceptor recovery and higher glial proliferation, correspond to poorer visual function outcomes. This study highlights the role of photoreceptor density and migration in achieving optimal visual function post-surgery for MH closure.
Optical coherence tomography angiography (OCTA) is a noninvasive imaging technology that has been widely used to reveal high-resolution blood vessels and provide detailed visualization of the vascular system. Maintaining the connectivity of vessels and recognizing thin vessels are significant challenges for the task of retinal vessel segmentation. However, existing deep learning-based methods pay more attention to extracting specific semantic representations of blood vessels, but disregard their physiological directional characteristics. In this article, we propose a direction-guided network for retinal vessel segmentation. Specifically, to extract the multi-directional features of vessels, we design a directional convolution that generates a set of convolutional kernels with various directions to adapt to the intricate vascular architecture. To enhance the feature representations for connecting broken vessels, we propose a direction guidance module that aggregates global features of similar directions to perceive the overall topological vascular structure. Experiments conducted on two publicly available datasets (OCTA-500 and ROSE-1) and the clinical dataset (OCTA-CLINIC) obtained from the hospital demonstrate that the proposed method achieves competitive performance in retinal vessel segmentation. The source code is publicly available at: https://github.com/tjut311/DGNet.
BACKGROUND:Anti-VEGF therapies improve visual acuity and reduce central macular thickness (CMT) in neovascular age-related macular degeneration(nAMD) patients. However, In our study, 35.76 % patients do not respond adequately to the anti-VEGF treatment.. Therefore, this study aimed to investigate imaging biomarkers and forecast the influencing factors of anti-VEGF treatment response in nAMD, aiming to enhance clinical evaluation. METHODS:We retrospectively analyzed data from patients treated with anti-VEGF at Tianjin Medical University General Hospital from August 2018 to August 2023, including 165 patients with exudative AMD. We investigated their sex, age, best-corrected visual acuity (BCVA)(LogMAR), number of anti-VEGF treatments, optical coherence tomography angiography (OCTA) results. A deep learning model, the improved LUNet model was used to analyze OCTA images, focusing on retinal features including foveal avascular zone (FAZ), vessel density (VD), vessel diameter index (VDI), vessel dispersion (Vdisp) of retinal layers(deep vascular complex and deep vascular complex) to assess their relationship with treatment response. RESULTS:After 6 months of anti-VEGF treatment, the patients' BCVA improved from 0.84 ± 0.40 to 0.70 ± 0.40 (t = 2.85, P = 0.005) (corresponds to an improvement from 20/140 to 20/100 on the Snellen scale.), CMT decreased from 300.16 ± 118.92 μm to 249.53 ± 84.39 μm (t = 4.46, P < 0.001). FAZ perimeter increased from 2.68 mm (2.29, 3.50) to 3.04 mm (2.57, 3.59) (Z=-2.05, P = 0.040), VDI decreased from 6.09 ± 0.83 to 5.90 ± 0.71 (t = 2.33, P = 0.021), central VD decreased (t = 2.21, P = 0.028). Logistic regression showed the Vdisp of macular neovascularization (Vdisp-MNV) (P = 0.007, OR 1.41), Vdisp of deep vascular complex(DVC) (P = 0.006, OR 0.45), neovascular surface area (SA) (P = 0.002, OR 0.26), and pigment epithelial detachment(PED) (P = 0.009, OR 0.29) significantly affected the response to anti-VEGF treatment. There were statistical differences in the association between the base line Vdisp of DVC (b = 0.07, t = 2.50, P = 0.014), base line intraretinal fluid (IRF) (b = 0.17, t = 2.02, P = 0.045) and base line BCVA, shown with multiple linear regression analysis. CONCLUSION:This study analyzed factors affecting treatment response. Vdisp in MNV showed positive correlation with anti-VEGF treatment response; SA and PED showed negative correlation with anti-VEGF treatment response. It allowed for making personalized treatment strategy to tailor interventions based on individual risk profiles and vascular characteristics which can enhance patient outcomes.
Retinitis pigmentosa sine pigmento (RPSP) is a atypical variant of inherited retinal degeneration characterized by the absence of retinal pigment deposits observed in typical retinitis pigmentosa, which poses significant challenges to clinical diagnosis and genetic investigation. Although high-throughput sequencing technologies have revolutionized the identification of disease-causing genes, studies on RPSP are limited. Therefore, this study aimed to analyze the clinical manifestations and genetic profiles of two patients with RPSP. Two novel potential disease-causing mutations were identified. Patient 1 had a heterozygous missense mutation (c.45G > C, p.Glu15Asp) in the GUCA1B gene, whereas Patient 2 had a homozygous frameshift insertion mutation (c.134_137dupCGGC, p.Ala47Glyfs*4) in the ABHD12 gene. Multimodal imaging techniques, including optical coherence tomography, fundus autofluorescence, adaptive optics scanning laser ophthalmoscope, and fluorescein angiography, combined with visual electrophysiological assessments revealed the structural and functional retinal alterations associated with RPSP. Bioinformatics analysis revealed that these mutations can respectively contributed to disease development by affecting calcium ion regulation in photoreceptor cells and by influencing the hydrolyzing of lysophosphatidylserine (lyso-PS). This study is the first to link novel mutations in GUCA1B and ABHD12 to RPSP. The findings highlight the critical importance of integrating multimodal imaging with genetic profiling in enhancing early diagnostic accuracy and refining genetic counseling strategies for this understudied condition.
ObjectivesTo explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR).MethodsWe retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC.ResultsThe inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group.ConclusionsRetinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.
AIM: To describe the multimodal imaging features, treatment, and outcomes of patients diagnosed with adult-onset Coats disease. METHODS: This retrospective study included patients first diagnosed with Coats disease at ≥18 years of age between September 2017 and September 2021. Some patients received anti-vascular endothelial growth factor (VEGF) therapy (conbercept, 0.5 mg) as the initial treatment, which was combined with laser photocoagulation as needed. All the patients underwent best corrected visual acuity (BCVA) and intraocular pressure examinations, fundus color photography, spontaneous fluorescence tests, fundus fluorescein angiography, optical coherence tomography (OCT), OCT angiography, and other examinations. BCVA alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were analyzed. RESULTS: The study included 15 patients who were aged 24-72 (57.33±12.61)y at presentation. Systemic hypertension was the most common associated systemic condition, occurring in 13 (86.7%) patients. Baseline BCVA ranged from 2.0 to 5.0 (4.0±1.1), which showed improvement following treatment (4.2±1.0). Multimodal imaging revealed retinal telangiectasis in 13 patients (86.7%), patchy hemorrhage in 5 patients (33.3%), and stage 2B disease (Shield's staging criteria) in 11 patients (73.3%). OCT revealed that the baseline central macular thickness (CMT) ranged from 129 to 964 µm (473.0±230.1 µm), with 13 patients (86.7%) exhibiting a baseline CMT exceeding 250 µm. Furthermore, 8 patients (53.3%) presented with an epiretinal membrane at baseline or during follow-up. Hyper-reflective scars were observed on OCT in five patients (33.3%) with poor visual prognosis. Vision deteriorated in one patient who did not receive treatment. Final vision was stable in three patients who received laser treatment, whereas improvement was observed in one of two patients who received anti-VEGF therapy alone. In addition, 8 of 9 patients (88.9%) who received laser treatment and conbercept exhibited stable or improved BCVA. CONCLUSION: Multimodal imaging can help diagnose adult-onset Coats disease. Anti-VEGF treatment combined with laser therapy can be an option for improving or maintaining BCVA and resolving macular edema. The final visual outcome depends on macular involvement and the disease stage.
Purpose To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. Methods A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. Results Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: β coefficient = -0.351, p = 0.023; perifovea: β coefficient = -0.338, p = 0.036). Perifoveal VLD (β coefficient = -0.343, p = 0.031) and FD (β coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (β coefficient = -0.396, p = 0.008), perifoveal VLD (β coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (β coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (β coefficient = -0.373, p = 0.023) and number of flow voids (β coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. Conclusions Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).
Introduction: This study aimed to investigate the relationship between age of myopia onset and high myopia and to explore if age of onset mediated the associations of high myopia with parental myopia and time spent on electronics. Methods: This cross-sectional study enrolled 1118 myopic patients aged 18 to 40. Information was obtained via a detailed questionnaire. Multivariable logistic regression and linear regression models were utilized to assess age of onset in relation to high myopia and spherical equivalent refractive error, respectively. Structural equation models examined the mediated effect of onset age on the association between parental myopia, time spent on electronics and high myopia. Results: An early age at myopia onset was negatively correlated with spherical equivalent refractive power. Subjects who developed myopia before the age of 12 were more likely to suffer from high myopia than those who developed myopia after the age of 15. Age of myopia onset was the strongest predictor of high myopia, with an area under the curve (AUC) in Receiver Operator Characteristic (ROC) analysis of 0.80. Additionally, age of myopia onset served as a mediator in the relationships between parental myopia, electronic device usage duration, and the onset of high myopia in adulthood. Conclusions: Age of myopia onset might be the single best predictor for high myopia, and age at onset appeared to mediate the associations of high myopia with parental myopia and time spent on electronics.
PURPOSE:To evaluate the relationship between the real-time changes of macular structure and visual function in rhegmatogenous retinal detachment (RRD) patients. METHODS:Forty-six patients were enrolled in this retrospective study. The best corrected visual acuity (BCVA) and macular structural changes were analyzed within 3 months after silicone oil tamponade. RESULTS:The mean final BCVA was significantly better than the preoperative BCVA (P = 0.002). The parafoveal thickness became thinner, the proportion of subretinal fluid (SRF) decreased, and the proportion of intact external limiting membrane (ELM) increased within 3 months postoperatively. The recovery stage and the integrity of ELM in the SRF (-) group were significantly faster than that in the SRF (+) group (all P < 0.05). The central foveal thickness (CFT), the inferior and temporal thickness of the parafovea, and the integrity of the ELM were significantly correlated with BCVA at each time point (all P < 0.05). Long duration of preoperative RRD, thinner CFT at 1 month postoperatively, and without integrity of ELM at 3 months postoperatively were associated with poor final BCVA recovery (R2 = 0.462). CONCLUSIONS:The macular microstructural tended to restore integrity within 3 months. The presence of SRF in macula delayed the recovery of RRD patients but did not affect the visual function.
·AIM:To observe the clinical and multimodal imaging features of retinopathy associated with novel coronavirus disease 2019(COVID-19)infection,investigate the related risk factors,and analyze the treatment and prognosis. ·METHODS:A total of 7 patients(7 eyes)with clinically confirmed COVID-19-associated retinopathy in Tianjin Medical University General Hospital from December 13,2022 to January 13,2023 were included in the study.All patients underwent color fundus photography,IR,spectral-domain optical coherence tomography(SD-OCT),fundus autofluorescein(FAF)and other ophthalmic examination and serological examination. ·RESULTS:Among the included patients,2 cases(2 eyes)of central retinal vein occlusion(CRVO)appeared differently from previous CRVO.The hemorrhagic features of CRVO were round or fusiform shape hemorrhagic spots with white centers.One of them,the von Willebrand factor antigen(vWF:Ag)level was increased to 161.8%.The other case was positive in serologic test for lupus anticoagulant.In 2 cases(2 eyes)of multiple evanescent white dot syndrome(MEWDS),FAF showed that dots of high spontaneous fluorescence were scattered in the posterior pole.The prognosis of 2 MEWDS were good after the treatment of glucocorticoids.The 3 cases(3 eyes)of acute macular neuroretinopathy(AMN)showed reddened brown lesions in the macular area,hyporeflective lesions with clear boundaries on IR,and high signal intensity in the ONL and ELM,EZ/IZ signal fracture on SD-OCT. ·CONCLUSION:COVID-19 may cause inflammatory storm,involving all layers of retinal tissues and blood vessels,leading to the occurrence of various retinal lesions.Hormone therapy may be effective and the prognosis is good in most cases.Roth spot can be seen in fundus hemorrhage of CRVO,lupus anticoagulant and increased vWF:Ag may be risk factors for CRVO after COVID-19.
Neovascular age-related macular degeneration AMD (nAMD) is characterized by choroidal neovascularization (CNV) and could lead to irreversible blindness. However, anti-vascular endothelial growth factor (VEGF) therapy has limited efficacy. Therefore, we generated a chimpanzee adenoviral vector (AdC68-PFC) containing three genes, pigment endothelial-derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble forms of CD59 (sCD59), to treat nAMD. The results showed that AdC68-PFC mediated a strong onset of PEDF, sFlt-1, and sCD59 expression both in vivo and in vitro. AdC68-PFC showed preventive and therapeutic effects following intravitreal (IVT) injection in the laser-induced CNV model and very low-density lipoprotein receptor-deficient (Vldlr(-/-)) mouse model. In vitro assessment indicated that AdC68-PFC had a strong inhibitory effect on endothelial cells. Importantly, the safety test showed no evidence of in vivo toxicity of adenovirus in murine eyes. Our findings suggest that AdC68-PFC may be a long-acting and safe gene therapy vector for future nAMD treatments.
The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1β and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1β as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy.
Purpose:To identify the biomarkers in the critical period of development in diabetic retinopathy (DR) in Chinese with type 2 diabetes using targeted and untargeted metabolomics, and to explore the feasibility of their clinical application.Methods:This case-control study described the differential metabolites between 83 Chinese type 2 diabetes mellitus (T2DM) samples with disease duration ≥ 10 years and 27 controls matched cases. Targeted metabolomics using high-resolution mass spectrometry with liquid chromatography was performed on plasma samples of subjects. The results were compared to our previous untargeted metabolomics study and ELISA was performed to validate the mutual differential metabolites of targeted and untargeted metabolomics on plasma. Multiple linear regression analyses were performed to adjust for the significance of different metabolites between groups.Result:Mean age of the subjects was 66.3 years and mean T2DM duration was 16.5 years. By cross-validating with results from previous untargeted metabolomic assays, we found that L-Citrulline (Cit), indoleacetic acid (IAA), 1-methylhistidine (1-MH), phosphatidylcholines (PCs), hexanoylcarnitine, chenodeoxycholic acid (CDCA) and eicosapentaenoic acid (EPA) were the most distinctive metabolites biomarkers to distinguish the severity of DR for two different metabolomic approaches in our study. We mainly found that samples in the DR stage showed lower serum level of Cit and higher serum level of IAA compared with samples in the T2DM stage, while during the progression of diabetic retinopathy, the serum levels of CDCA and EPA in PDR stage were significantly lower than NPDR stage. Among them, 4 differential key metabolites including Cit, IAA, CDCA and EPA were confirmed with ELISA.Conclusion:This is the first study to compare the results of targeted and untargeted metabolomics via liquid chromatography-mass spectrometry to find the serum biomarkers which could reflect the metabolic variations among different stages of DR in Chinese. The progression of DR in Chinese at different critical stages was related to the serum levels of specific differential metabolites, of which there is a significant correlation between DR progression and increased IAA and decreased Cit, hexanoylcarnitine, CDCA, and EPA. However, larger studies are needed to confirm our results. Based on this study, it could be inferred that the accuracy of targeted metabolomics for metabolite expression in serum is to some extent higher than that of untargeted metabolomics.