Aims Oxidative stress and apoptosis are among the earliest lesions of diabetic retinopathy. This study sought to examine the anti-oxidative and anti-apoptotic effects of α-melanocyte-stimulating hormone (α-MSH) in early diabetic retinas and to explore the underlying mechanisms in retinal vascular endothelial cells. Methods Sprague-Dawley rats were injected intravenously with streptozocin to induce diabetes. The diabetic rats were injected intravitreally with α-MSH or saline. At week 5 after diabetes, the retinas were analyzed for reactive oxygen species (ROS) and gene expression. One week later, the retinas were processed for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and transmission electron microscopy. Retinal vascular endothelial cells were stimulated by high glucose (HG) with or without α-MSH. The expression of Forkhead box O genes (Foxos) was examined through real-time PCR. The Foxo4 gene was overexpressed in endothelial cells by transient transfection prior to α-MSH or HG treatment, and oxidative stress and apoptosis were analyzed through CM-H2DCFDA and annexin-V assays, respectively. Results In diabetic retinas, the levels of H2O2 and ROS and the total anti-oxidant capacity were normalized, the apoptotic cell number was reduced, and the ultrastructural injuries were ameliorated by α-MSH. Treatment with α-MSH also corrected the aberrant changes in eNOS, iNOS, ICAM-1, and TNF-α expression levels in diabetic retinas. Furthermore, α-MSH inhibited Foxo4 up-regulation in diabetic retinas and in endothelial cells exposed to HG, whereas Foxo4 overexpression abrogated the anti-oxidative and anti-apoptotic effects of α-MSH in HG-stimulated retinal vascular endothelial cells. Conclusions α-MSH normalized oxidative stress, reduced apoptosis and ultrastructural injuries, and corrected gene expression levels in early diabetic retinas. The protective effects of α-MSH in retinal vascular endothelial cells may be mediated through the inhibition of Foxo4 up-regulation induced by HG. This study suggests an α-MSH-mediated potential intervention approach to early diabetic retinopathy and a novel regulatory mechanism involving Foxo4.
Vogt-Koyanagi-Harada syndrome is common autoimmune uveitis that can cause blindness. Recent studies have shown that plasma exosomes carry disease-related proteins that may serve as biomarkers. Here, we aimed to find candidate biomarkers of Vogt-Koyanagi-Harada disease using proteomic analysis of plasma exosomes.Exosomes were isolated from the plasma of normal controls and Vogt- Koyanagi-Harada patients in the following groups: a) initial inflammatory attack (active stage), b) remission after one month of treatment (unstable stage), and c) stationary phase after three months of treatment (stable stage). Groups were analyzed by mass spectrometry using isobaric tags for relative and absolute quantitation. After functional analysis, proteins of interest were verified by ELISA.463 proteins were identified in the exosomes. Forty-three were upregulated at the active inflammation stage, including inflammation-associated proteins. Thirty-one were downregulated. Gene ontology and pathway analyses revealed differential proteins related to cell adhesion, cell phagocytosis, cytoskeleton movement, leukocyte migration across endothelial cells, and platelet activation. By ELISA, Carbonic anhydrase 2 and Ras-related protein Rap-1b were verified as more plentiful at the active stage compared to the normal control and stationary phase in exosomes, but not, however, in microvesicles or plasma.Plasma exosomes of Vogt-Koyanagi-Harada patients contain many proteins related to the degree of inflammation. The levels of Carbonic anhydrase 2 and Ras-related protein Rap-1b in exosomes can be used as biomarkers for active inflammation in Vogt-Koyanagi-Harada disease. Further investigation could help study the pathogenesis of Vogt-Koyanagi-Harada disease and identify therapeutic targets.
We aimed to evaluate the clinical characteristics and long-term prognosis of brain arteriovenous malformations (bAVMs) treated with multimodality management of one-staged hybrid operation.We identified bAVM patients treated with one-staged hybrid operation from a multicenter prospective cohort study (NCT03774017) between January 2016 and June 2020. Patients were divided into unruptured and ruptured groups by the hemorrhagic presentation. Long-term (>12 months) neurological disability, postoperative complications of stroke, and nidus obliteration were evaluated and compared between groups. Prognostic predictors associated with outcomes were analyzed.A total of 130 patients were identified in the study receiving one-staged hybrid operations, including 61 unruptured cases and 69 ruptured cases. Mean age was 29.1 years old, with 78 (60.0%) being male. Patients included in the study were followed up for a mean period of 37.4 (11.07) months. The annual hemorrhagic risk was 4.2% per year. Thirteen postoperative stroke events were detected in 11 patients (8.5%). Long-term disability occurred in 6.9% of cases, and 86.2% of patients experienced an unchanged or improved neurological status at the last follow-up. All patients achieved complete obliteration on follow-up angiographies. Increased AVM volume was associated with a higher risk of postoperative stroke (odds ratio (OR) 1.021, 95% confidence interval (CI) 1.006-1.037, and P = 0.006). Poor neurological status (OR 6.461, 95% CI 1.309-31.889, and P = 0.022) and infratentorial location (OR 5.618, 95% CI 1.158-27.246, and P = 0.032) were independent predictors for long-term disability.One-staged hybrid operation of embolization combined microsurgical resection can be performed as a safe and effective strategy for bAVM treatments. Long-term prognosis of complete obliteration with low rates of morbidity and mortality can be achieved. Unruptured and ruptured bAVMs acquired similar favorable outcomes after the multimodality treatment.
Objective: To compare the difference and agreement of corneal refractive power and astigmatism measured by the new swept-source anterior segment optical coherence tomography (SS-AS-OCT) device (CASIA2) and Scheimpflug imaging device (Pentacam) in age-related cataract patients. Methods: In this cross-sectional study, 112 eyes of 112 patients with age-related cataract were examined before phacoemulsification in the Tianjin Medical University Eye Hospital from April to May 2020. The steep keratometry (Ks), flat keratometry (Kf), mean keratometry (Km), degree and axis of astigmatism of the corneal anterior and posterior surfaces and the total cornea were recorded. The difference in astigmatism was analyzed by the arithmetic method and the vector method. The difference of data was evaluated using Paired t test or Wilcoxon test. The agreement of data was evaluated using Bland-Altman plots. Results: The patients were 44 males and 68 females with an average age of (67±10) years. There were no statistically differences in the Ks and Km values of the corneal anterior surface between the Pentacam and the CASIA2 (both P>0.05). There was significant difference in the Kf values of the corneal anterior surface between the Pentacam and the CASIA2 [(44.24±1.73) D vs. (44.14±1.64) D; t=2.278; P 0.05). Vector operation results showed that the astigmatism difference vector (DV) of the Pentacam and the CASIA2 on the anterior surface of the cornea was 0.06 D@57°±0.64 D,>0.50 D in 47 eyes (41.96%). The astigmatism DV on the posterior surface of the cornea was 0.07 D@174°±0.21 D, >0.50 D in 2 eyes (1.79%). The astigmatism DV on the total cornea was 0.13 D@3°±0.69 D,>0.50 D in 59 eyes (52.68%). The results of the two devices were positively correlated (r values of the Ks, Kf, Km, and astigmatism degree on the anterior surface of the cornea were 0.970, 0.968, 0.976, and 0.697, respectively, on the posterior surface of the cornea were 0.918, 0.875, 0.925, and 0.517, respectively, and on the total cornea were 0.951, 0.955, 0.959, and 0.622, respectively; all P<0.01). Bland-Altman analysis showed that the Ks, Kf, Km, and astigmatism degree of the corneal anterior and posterior surfaces measured by the two devices were consistent, with 2.68% to 8.04% of the measured values outside 95% limits of agreement (95%LoA). The 95%LoA of the total corneal Ks, Kf, and Km between the two devices was 0.01 to 2.28 D, 0.06 to 2.27 D, and 0.10 to 2.20 D, respectively, with a wide 95%LoA range and poor consistency. Conclusions: The corneal refractive power and astigmatism measured by the CASIA2 and the Pentacam shows little difference on the anterior surface of the cornea, with good agreement. However, the refractive power results of the posterior surface of the cornea and the total cornea show great difference, suggesting that these two instruments cannot be used interchangeably in clinical practice. (Chin J Ophthalmol, 2021, 57: 48-55).
To study the characteristics of cataract extraction and surgical techniques in cases following vitrectomy.Extra-capsular extraction/phacoemulsification of cataract and intra-ocular lens implantation were performed under vitreous irrigation.Of 37 cases (40 eyes), 31 eyes (77.5%) had obtained post-operative visual acuity > or = 0.1, 12 eyes (30.0%) > or = 0.3. The complications included nuclear dislocation into vitreous cavity (1 eye) and vitreous hemorrhage (1 eye) in the operation, and rubeosis iridis (1 eye) and pupillary capture (1 eye) after the operation.Anti-hypotony must be emphasized in the operation of cataract extraction after vitrectomy, and the vitreous irrigation is a good way against hypotony, extra-capsular extraction is more suitable than phacoemulsification in cases with hard nucleus.
Purpose: To compare the prediction accuracy of the Barrett toric calculator using standard or integrated keratometry (IK) mode in combination with predicted or measured posterior corneal astigmatism (PCA) in a group of patients with cataract implanted with non-toric IOLs. Methods: In this retrospective clinical cohort study, the medical records of patients with age-related cataract who underwent phacoemulsification with the implantation of an aspheric monofocal IOL were reviewed. Four methods, including standard keratometry with predicted PCA (PPCA), IK combined with predicted PCA (IK-PPCA), and IK combined with measured PCA derived from IOLMaster 700 (Carl Zeiss Meditec AG) or CASIA2 (Tomey) (IK-MMPCA or IK-CMPCA), were applied to the Barrett toric calculator to calculate the predicted residual astigmatism. The mean absolute prediction error (MAPE), centroid of the prediction error, and proportion of eyes within the prediction error of ±0.50, ±0.75, and ±1.00 diopters (D) were all ciphered out from the four methods, respectively. Results: Data from 129 eyes of 129 patients were included in this study. The MAPE of the IK-PPCA method (0.57 ± 0.36 D) was significantly smaller than that of the PPCA (0.62 ± 0.38 D) and IK-CMPCA (0.63 ± 0.46 D) methods ( P = .048 and .014, respectively). There were no significant differences in the centroid vectors of prediction errors and predictability rates among the four methods (all P > .05). Conclusions: In the current version of the Barrett toric calculator, the predictive accuracy of the IK mode incorporating PPCA was slightly superior to using the standard keratometry mode or incorporating MPCA. [ J Refract Surg . 2024;40(7):e453–e459.]
To evaluate and compare the accuracy of iTrace and CASIA2 in measuring the postoperative orientation of toric intraocular lens (IOL) without mydriasis.Tianjin Medical University Eye Hospital, Tianjin, China.Prospective cohort study.Patients with SN6AT toric IOLs implanted after cataract surgery were enrolled. 1 month after surgery, the toric IOL orientation were measured by iTrace and CASIA2 in non-mydriatic, semi-dark conditions. Then, the toric axis was directly reviewed using the slit-lamp under full mydriasis. Axis measurement differences between each of the 2 devices and the slit-lamp, described as their relative differences (RDs), were calculated and compared. The percentage of RDs within 5 degrees, within 10 degrees and greater than 30 degrees were analyzed.77 eyes of 70 patients were included. Generally, the mean toric axis measurement RDs of CASIA2 and iTrace were 9.24 ± 10.53 degrees and 13.89 ± 15.47 degrees respectively ( P = .04). For CASIA2 (72 eyes), 54.17% (39), 72.22% (52), and 4.17% (3) of eyes had RDs within 5 degrees, within 10 degrees and greater than 30 degrees, compared with 40.00% (28), 61.43% (43) and 12.86% (9) for iTrace (70 eyes). The 95% limits of agreements of CASIA2 with slit-lamp was narrower than that of iTrace with slit-lamp. The median RD of CASIA2 was significantly smaller in eyes with pupil ≥4 mm under dark condition compared with eyes with pupil <4 mm ( P = .03).CASIA2 demonstrates greater precision in measuring toric IOL orientation under non-mydriatic conditions compared with iTrace. Moreover, the accuracy of CASIA2 is enhanced in cases of pupil >4 mm.