EDI-OCT as an auxiliary examination for the differential diagnosis of bullous CSC and Vogt-Koyanagi-Harada: A case report.

A 46-year-old male patient visited our clinic with a complaint of blurred vision in the right eye accompanied by headache and insomnia. The fundus examination showed three bullous retinal detachments in the right eye. Considering the prodromal symptoms and other fundus characteristics such as vitreous cells in the posterior pole and multifocal fluorescence leakages on fundus fluorescein angiography (FFA), initial diagnosis was considered as Vogt-Koyanagi-Harada (VKH). However, oral glucocorticoids didn't improve patient's vision. Further enhanced depth imaging (EDI)-optical coherence tomography (OCT) scan displayed hyper-reflective lesions at the choroidal layer. We proposed that hyper-reflective lesions at the choroidal layer on EDI-OCT may characterize the bullous variant of central serous chorioretinopathy (CSC). After fundus photocoagulation treatment, the patient's vision improved.

Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.

Alterations of the intestinal microbiota in age-related macular degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50. Recently, intestinal microbiota has been reported to be involved in the pathogenesis of ocular diseases. The purpose of this study was to discover more about the involvement of the intestinal microbiota in AMD patients. Methods: Fecal samples from 30 patients with AMD (AMD group) and 17 age- and sex-matched healthy controls (control group) without any fundus disease were collected. DNA extraction, PCR amplification, and 16S rRNA gene sequencing of the samples were performed to identify intestinal microbial alterations. Further, we used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction. Results: The intestinal microbiota was found to be significantly altered in the AMD group. The AMD group had a significantly lower level of Firmicutes and relatively higher levels of Proteobacteria and Bacteroidota compared to those in the control group. At the genus level, the AMD patient group showed a considerably higher proportion of Escherichia-Shigella and lower proportions of Blautia and Anaerostipes compared with those in the control group. Phenotypic prediction revealed obvious differences in the four phenotypes between the two groups. PICRUSt2 analysis revealed KOs and pathways associated with altered intestinal microbiota. The abundance of the top eight KOs in the AMD group was higher than that in the control group. These KOs were mainly involved in lipopolysaccharide biosynthesis. Conclusion: The findings of this study indicated that AMD patients had different gut microbiota compared with healthy controls, and that AMD pathophysiology might be linked to changes in gut-related metabolic pathways. Therefore, intestinal microbiota might serve as non-invasive indicators for AMD clinical diagnosis and possibly also as AMD treatment targets.

Accuracy and feasibility with AI-assisted OCT in retinal disorder community screening.

Objective: To evaluate the accuracy and feasibility of the auto-detection of 15 retinal disorders with artificial intelligence (AI)-assisted optical coherence tomography (OCT) in community screening. Methods: A total of 954 eyes of 477 subjects from four local communities were enrolled in this study from September to December 2021. They received OCT scans covering an area of 12 mm × 9 mm at the posterior pole retina involving the macular and optic disc, as well as other ophthalmic examinations performed using their demographic information recorded. The OCT images were analyzed using integrated software with the previously established algorithm based on the deep-learning method and trained to detect 15 kinds of retinal disorders, namely, pigment epithelial detachment (PED), posterior vitreous detachment (PVD), epiretinal membranes (ERMs), sub-retinal fluid (SRF), choroidal neovascularization (CNV), drusen, retinoschisis, cystoid macular edema (CME), exudation, macular hole (MH), retinal detachment (RD), ellipsoid zone disruption, focal choroidal excavation (FCE), choroid atrophy, and retinal hemorrhage. Meanwhile, the diagnosis was also generated from three groups of individual ophthalmologists (group of retina specialists, senior ophthalmologists, and junior ophthalmologists) and compared with those by the AI. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated, and kappa statistics were performed. Results: A total of 878 eyes were finally enrolled, with 76 excluded due to poor image quality. In the detection of 15 retinal disorders, the ROC curve comparison between AI and professors' presented relatively large AUC (0.891-0.997), high sensitivity (87.65-100%), and high specificity (80.12-99.41%). Among the ROC curve comparisons with those by the retina specialists, AI was the closest one to the professors' compared to senior and junior ophthalmologists (p < 0.05). Conclusion: AI-assisted OCT is highly accurate, sensitive, and specific in auto-detection of 15 kinds of retinal disorders, certifying its feasibility and effectiveness in community ophthalmic screening.

Association of cognitive function with Neurofilament light chain in the aqueous humor of human eye.

Objectives: To evaluate the predictive clinical role of neurofilament light chain (NfL), amyloid-ß (Aß), glial fibrillary acidic protein (GFAP), and phosphorylated tau at threonine 181 (p-tau181) proteins in human aqueous humor (AH) and quantify the retinal macular microvascular parameters by optical coherence tomography angiography (OCTA) as early diagnostic markers of Alzheimer's disease (AD). Methods: This prospective, single-site, cross-sectional, cohort study enrolled 55 participants, including 38 patients with neovascular age-related macular degeneration (nAMD) and 17 individuals with senile cataracts. The single-molecule array platform was used to quantitatively measure the levels of AH NfL, Aß40, Aß42, GFAP, and p-tau181 proteins in AH. The mini-mental state examination (MMSE) score was used to assess the global cognitive function. OCTA scan with 6 × 6 mm macular area was used to quantify the retinal thickness and microvascular densities of superficial retinal capillary plexuses and deep retinal capillary plexuses. Results: NfL, Aß40, Aß42, GFAP, and p-tau181 were detected in all AH samples by Simoa platform. Individuals with cataract had higher concentrations of NfL and p-tau181 but lower Aß40 and Aß42 and similar GFAP compared to those with nAMD. Lower MMSE scores showed a negative correlation with NfL concentration of AH not only in the nAMD group (p = 0.043), but also in the cataract group (p = 0.032). However, the MMSE scores were not associated with the levels of Aß40, Aß42, GFAP, or p-Tau181. Further analysis found that the Aß40 and Aß42 concentrations showed a strong positive correlation (p < 0.0001). In addition, the NfL concentration showed a mild positive correlation with that of GFAP in the cataract group (p = 0.021). Although it has not reached statistical significance, there was a correlation between the levels of NfL and Aß42 in the nAMD group (p = 0.051). Moreover, the macular superficial vessel density values had a negative correlation with the concentration of NfL (p = 0.004) but a positive correlation with MMSE scores (p = 0.045). The macular deep vessel density values were negatively correlated with the concentration of p-tau181 (p = 0.031) and positively correlated with MMSE scores (p = 0.020). Conclusion: The examination of AD-related biomarkers in human AH and OCTA may improve the ocular-based AD detection methods and contribute to forestalling the progression of preclinical AD.

Composition and diversity of gut microbiota in diabetic retinopathy.

Objective: Diabetic retinopathy (DR) is one of the most common complications of type 2 diabetes mellitus. The current study investigates the composition, structure, and function of gut microbiota in DR patients and explores the correlation between gut microbiota and clinical characteristics of DR. Methods: A total of 50 stool samples were collected from 50 participants, including 25 DR patients and 25 healthy controls (HCs). 16S ribosomal RNA gene sequencing was used to analyze the gut microbial composition in these two groups. DNA was extracted from the fecal samples using the MiSeq platform. Results: The microbial structure and composition of DR patients were different from that of HCs. The microbial richness of gut microbiota in DR was higher than that of normal individuals. The alterations of microbiome of DR patients were associated with disrupted Firmicutes, Bacteroidetes, Synergistota, and Desulfobacterota phyla. In addition, increased levels of Bacteroides, Megamonas, Ruminococcus_torques_group, Lachnoclostridium, and Alistipes, and decreased levels of Blautia, Eubacterium_ hallii_group, Collinsella, Dorea, Romboutsia, Anaerostipes, and Fusicatenibacter genera were observed in the DR groups. Additionally, a stochastic forest model was developed to identify a set of biomarkers with seven bacterial genera that can differentiate patients with DR from those HC. The microbial communities exhibited varied functions in these two groups because of the alterations of the above-mentioned bacterial genera. Conclusion: The altered composition and function of gut microbiota in DR patients indicated that gut microbiome could be used as non-invasive biomarkers, improve clinical diagnostic methods, and identify putative therapeutic targets for DR.

Association between risk factors and retinal nerve fiber layer loss in early stages of diabetic retinopathy.

AIM: To investigate the changes of retinal nerve fiber layer (RNFL) among normal individuals, diabetic patients without diabetic retinopathy (NDR) and non-proliferative diabetic retinopathy (NPDR), and explore the possible risk factors of early diabetic retinopathy (DR). METHODS: In this cross-sectional study, 107 participants were divided in three groups. Totally 31 normal individuals (control group), 40 diabetic patients without DR (NDR group) and 36 patients with NPDR (NPDR group) were included. Optical coherence tomography (OCT) was used to detect RNFL thickness and other optic disc parameters among different groups. The potential association between RNFL loss and systemic risk factors were assessed for DR, including diabetes duration, body mass index (BMI), hemoglobin A1c (HbA1c), serum lipids, and blood pressure. RESULTS: The average and each quadrant RNFL thickness were thinner in NPDR group compared to control group of the right (P=0.00, P=0.01, P=0.01, P=0.02, P=0.04) and left eyes (P=0.00, P=0.00, P=0.00, P=0.03, P=0.04). The average, superior and inferior RNFL thickness were thinner in NDR group compared to the NPDR group of the right (P=0.00, P=0.02, P=0.03) and left eyes (P=0.00, P=0.00, P=0.01). Diabetic duration was negatively correlated with the superior, inferior, and average RNFL thickness of the right (r=-0.385, P=0.001; r=-0.366, P=0.001; r=-0.503, P=0.000) and left eyes (r=-0.271, P=0.018; r=0.278, P=0.015; r=-0.260, P=0.023). HbA1c was negatively correlated with the superior, inferior, and average RNFL thickness of the right (r=-0.316 P=0.005; r=-0.414, P=0.000; r=-0.418, P=0.000) and left eyes (r=-0.367, P=0.001; r=-0.250, P=0.030; r=-0.393, P=0.000). Systolic pressure was negatively correlated with the inferior and average RNFL thickness of the right eye (r=-0.402, P=0.000; r=-0.371, P=0.001) and was negatively correlated with the superior and average RNFL thickness of the left eye (r=-0.264, P=0.021; r=-0.233, P=0.043). CONCLUSION: RNFL loss, especially in the superior and inferior quadrants, may be the earliest structural change of the retina in diabetic patients, and is also associated with diabetic duration, HbA1c, and systolic pressure.

Hidden Hunger of Vitamin E among Healthy College Students: A Cross- Sectional Study.

BACKGROUND: College students may have a risk of fat-soluble vitamin deficiencies due to unhealthy dietary habits, especially for vitamin A and E. They are important members of the human antioxidant network; deficiencies of these vitamins may increase the risk of many critical diseases. OBJECTIVE: The current study was undertaken to determine the status of vitamin A and E in college students. METHODS: Healthy college students were recruited, and fasting blood samples of them were collected and used for determining serum levels of retinol and α-tocopherol by the HPLC method. RESULTS: We found that there was no vitamin A deficiency in college students. However, vitamin E deficiency existed in 34.5% of college students, especially in males. All the students had no vitamin E adequacy. In addition, our findings showed that BMI was inversely associated with serum α-- tocopherol, but not serum retinol. CONCLUSION: These results suggest that vitamin E deficiency in college students should be given more attention, and it is necessary to consider using vitamin E supplements.

Cytokine and chemokine profile changes in patients after intravitreal conbercept injection for center macular edema due to branch retinal vein occlusion.

PURPOSE: This study aimed to ascertain cytokine concentrations in patients with center macular edema (CME) due to branch retinal vein occlusion (BRVO) before and during the period of treatment with intravitreal injection of conbercept (IVC) and to determine the relationship between these concentrations and disease activity. MATERIALS AND METHODS: The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine concentrations in aqueous humour. Experimental aqueous humour samples were collected from 22 patients with CME due to BRVO when IVC was administered at baseline and at 1 month, and control aqueous samples were collected by limbal paracentesis from 16 patients undergoing routine cataract surgery. RESULTS: Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the BRVO group than in the control group. In the BRVO group, VEGF levels were significantly lower one month after IVC than at baseline. However, the other cytokines did not significantly change during IVC treatment. The decreases in VEGF levels were closely related to the decreases in central macular thickness (CMT) and the increases in best-corrected visual acuity (BCVA). CONCLUSIONS: Many factors, such as angiogenic, inflammatory and growth factors, contribute to the pathogenesis of CME due to BRVO. IVC had no significant effect on cytokines other than VEGF in patients with CME due to BRVO. The changes in BCVA and CMT were associated with VEGF levels after IVC treatment.

A patient misdiagnosed with central serous chorioretinopathy: A case report.

BACKGROUND: Due to some similarities in the manifestations between central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV), PCV may be misdiagnosed as CSC. More attention should be paid to distinguishing these two disorders. CASE SUMMARY: A 52-year-old woman presented to our hospital with blurred vision in her left eye for approximately 1 wk. Anterior segment and intraocular pressure findings were normal in both eyes. Fundus photography of the left eye showed a seemingly normal adult oculus fundus without any obvious hard exudate or hemorrhage. Optical coherence tomography exhibited a hypo-reflective space beneath both the neurosensory retina and the pigment epithelium layer. The late phase of fluorescein angiography revealed increased leakage. The patient was initially diagnosed with CSC. At follow-up, however, the final diagnosis turned out to be PCV. CONCLUSION: CSC and PCV are two different retinal entities. Lipid deposition and hemorrhage are the most important elements that lead to confusion between these two entities. Indocyanine green angiography should be performed to make a definitive diagnosis, especially in cases with suspected PCV.

Cytokine and Chemokine Profile Changes in Patients After Intravitreal Conbercept Injection for Diabetic Macular Edema.

PURPOSE: This study aimed to investigate the concentrations of cytokines and chemokines in diabetic macular edema (DME) eyes before and during therapy with the intravitreal injection of conbercept (IVC) and to identify associations with disease activity. METHODS: The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine levels in aqueous humour. Experimental aqueous humour samples were collected from 18 patients with DME at the same time that IVC was performed at baseline and at 1 month. Control aqueous humour samples were collected from 16 patients undergoing cataract surgery. RESULTS: Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, eotaxin, granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DME patients than cataract patients. One month after IVC, the intraocular concentrations of VEGF were significantly lower in the eyes of DME patients than at baseline. No other cytokines were significantly altered by conbercept therapy. Best-corrected visual acuity (BCVA) slightly improved following IVC compared with that at baseline, although this difference was not significant, and central macular thickness (CMT) significantly decreased 1 month after IVC treatment. CONCLUSION: Angiogenic, inflammatory and growth factors are involved in the development of DME. With the exception of VEGF, IVC did not cause significant differences in any inflammatory cytokines or growth factors in DME patients. CMT is related to VEGF levels in aqueous humour.