Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 􀁐g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀁐g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Safety and efficacy of endovascular recanalization in patients with mild anterior stroke due to large-vessel occlusion exceeding 24 hours.

BACKGROUND: Endovascular recanalization (ER) has demonstrated efficacy as a treatment modality for patients presenting with acute ischemic stroke (AIS) caused by large-vessel occlusion (LVO) within a 24-hour timeframe. Nevertheless, the safety and effectiveness of ER in patients with a time of onset exceeding 24 h remain uncertain. OBJECTIVE: To evaluate the safety and efficacy of ER treatment for mild ischemic stroke beyond 24-h from symptom onset. METHODS: A retrospectively maintained database of mild AIS due to LVO from March2018 to September 2022 at a comprehensive stroke center was screened.Patients received ER or standard medical therapies (SMT) for anterior circulation AIS due to LVO > 24-h were selected. RESULTS: We included 47 LVO patients with mild AIS beyond 24-h who suffered neurological deterioration (ND). 34 of these patients underwent ER, the other 13 received SMT. The technical success rate of recanalization was 82.4% (28/34). Patients received ER had significantly lower NIHSS score at discharge and 90-day mRS score (p = 0.028, p = 0.037, respectively) compared to SMT. In addition, they had significantly lower 90-day recurrence of ischemic stroke and lower incidence of moderate-severe stroke (with a NIHSS score at least 5) (p = 0.037, p = 0.033). There were 4 patients (11.7%) had perioperative complications, and no symptomatic intracranial hemorrhage occurred. CONCLUSION: ER treatment for mild AIS due to LVO encountered ND was generally safe and effective, even beyond 24-h, and resulted in a good prognosis and lower 90-day recurrence compared to SMT.

ER for mild anterior stroke might be safe and feasible, even exceeding 24-h;The proposed protocol could be used for individualized treatment decision making;Modelling for heterogeneity of treatment effect.

Therapeutic effect of bone marrow mesenchymal stem cells on laser-induced retinal injury in mice.

Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment.

Comparative Accuracy of Barrett Integrated Keratometry Toric Calculator With Predicted Versus Measured Posterior Corneal Astigmatism.

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.].

Practical Nomograms and Risk Stratification System for Predicting the Overall and Cancer-specific Survival in Patients with Anaplastic Astrocytoma.

OBJECTIVE: Anaplastic astrocytoma (AA) is an uncommon primary brain tumor with highly variable clinical outcomes. Our study aimed to develop practical tools for clinical decision-making in a population-based cohort study. METHODS: Data from 2997 patients diagnosed with AA between 2004 and 2015 were retrospectively extracted from the Surveillance, Epidemiology, and End Results database. The Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses were applied to select factors and establish prognostic nomograms. The discriminatory ability of these nomogram models was evaluated using the concordance index and receiver operating characteristic curve. Risk stratifications were established based on the nomograms. RESULTS: Selected 2997 AA patients were distributed into the training cohort (70%, 2097) and the validation cohort (30%, 900). Age, household income, tumor site, extension, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors for both overall survival (OS) and cancer-specific survival (CSS). In the training cohort, our nomograms for OS and CSS exhibited good predictive accuracy with concordance index values of 0.752 (95% CI: 0.741-0.764) and 0.753 (95% CI: 0.741-0.765), respectively. Calibration and decision curve analyses curves showed that the nomograms demonstrated considerable consistency and satisfactory clinical utilities. With the establishment of nomograms, we stratified AA patients into high- and low-risk groups, and constructed risk stratification systems for OS and CSS. CONCLUSIONS: We constructed two predictive nomograms and risk classification systems to effectively predict the OS and CSS rates in AA patients. These models were internally validated with considerable accuracy and reliability and might be helpful in future clinical practices.

Effectiveness of toric intraocular lens implantation for correcting irregular corneal astigmatism in cataract eyes.

A retrospective cohort study was conducted to observe the correction effect of Toric intraocular lens (IOL) implantation in cataract eyes with specific types of irregular corneal astigmatism. Thirty-four eyes with either the "asymmetric bow-tie" pattern (Type I) or the "angled bow-tie" pattern (Type II) were included. Corneal topography was assessed using Pentacam HR, and changes in preoperative corneal astigmatism, visual acuity, manifest refraction, and objective visual quality were measured and compared. The average uncorrected distance visual acuity improved significantly from 0.86 ± 0.40 logMAR to 0.22 ± 0.15 logMAR (P < 0.001). Preoperative corneal astigmatism of 2.05 ± 0.90 D was corrected to a postoperative residual astigmatism of 0.78 ± 0.57 D (P < 0.001), with 32% of eyes within 0.50 D. The residual astigmatism prediction errors in Type I and Type II cases were (0.97 ± 0.68 D) and (0.66 ± 0.37 D), respectively (P = 0.100). The mean spherical equivalent prediction error in Type II cases (0.07 ± 0.36 D) was significantly smaller than that in Type I cases (- 0.29 ± 0.52 D) (P = 0.030). This study concludes that Toric IOL implantation effectively corrects specific types of irregular corneal astigmatism in cataract surgery. Eyes with the "angled bow-tie" pattern show higher accuracy in refractive predictions compared to eyes with the "asymmetric bow-tie" pattern.

The predictive accuracy of Barrett toric calculator using measured posterior corneal astigmatism derived from swept source-OCT and Scheimpflug camera.

PURPOSE: To compare the performance of Barrett toric calculator incorporated with measured posterior corneal astigmatism (PCA) derived from IOL Master 700 and Pentacam HR versus predicted PCA. METHODS: The predicted residual astigmatism using Barrett toric IOL calculator with predicted PCA, measured PCA from IOL Master 700 and measured PCA from Pentacam were calculated with the preoperative keratometry and intended IOL axis with modification. The vector analysis was performed to calculate the mean absolute prediction error (MAE), the centroid of the prediction error and the percentage of eyes with a prediction error within ±0.50 D, ±0.75 D, and ±1.00 D. RESULTS: In 57 eyes of 57 patients with mean age of 70.42 ± 10.75 years, the MAE among the three calculation methods were 0.59 ± 0.38 D (Predicted PCA), 0.60 ± 0.38 D (Measured PCA from IOL Master 700) and 0.60 ± 0.36 D (Measured PCA from Pentacam) with no significant difference, either in the whole sample, the WTR eyes and the ATR eyes (F = 0.078, 0.306 and 0.083, p = 0.925, 0.739 and 0.920, respectively). Measured PCA obtained from IOL Master 700 resulted in one level reduction (from Tn to Tn-1) in 49.12% eyes in cylindrical model selection, while measured PCA obtained from Pentacam resulted in one level reduction of toric model selection in 18.18% eyes. CONCLUSION: The present study suggested that the incorporation of measured PCA values derived from IOL Master 700 and Pentacam produce comparable clinical outcome with the predicted PCA mode in Barrett toric calculator.

[Pathogenic mechanisms and therapeutic strategies of myopic traction maculopathy].

Myopic traction maculopathy is a group of ocular fundus diseases related to high myopia, which can severely impact on patients' visual function. It is well recognized that the abnormal of macular structure and function in the disease are resulted from various traction mechanisms, including the forces from posterior vitreous detachment, posterior vitreous cortex, and macular epiretinal membrane which acting on the inner retina, the force from posterior staphyloma which acting on the outer retina, and retinal intrinsic features such as the changes of inner limiting membrane and arterioles. The treatments are mainly based on surgery, including vitrectomy and scleral reinforcement surgery in order to relieve the retinal traction. The options of specific surgery procedures are still under debated. In this article, we reviewed the pathogenic mechanisms and therapeutic strategies of myopic traction maculopathy.

The impact of posterior corneal astigmatism on the surgical planning of toric multifocal intraocular lens implantation.

Purpose: To investigate the influence of posterior corneal astigmatism on the prediction accuracy of toric multifocal intraocular lens (IOL) calculation. Methods: The keratometric astigmatism measured by Lenstar LS 900 (KCAL), keratometric astigmatism (KCAP) and total corneal astigmatism (TCA) measured by Scheimpflug camera (Pentacam HR) were documented and analyzed accordingly. Three deduction models using different parameters were compared. Model 1: KCAL â€‹+ â€‹keratometric corneal surgically induced astigmatism (KCSIA, 0.30 D @ 50°); Model 2: KCAP â€‹+ â€‹KCSIA); Model 3: TCA â€‹+ â€‹total CSIA (TCSIA, 0.23 D @ 50°). The prediction errors of each model as the difference vector between the actual and the intended residual astigmatism were compared. Results: Seventy-six eyes implanted with toric multifocal IOLs were included in this study. The vector differences of the actual KCSIA and TCSIA were statistically significant in the total sample and against-the-rule (ATR) subgroup (both P â€‹< â€‹0.05). Model 1 deduced the smallest mean values of prediction error, while that of Model 3 were smaller than that of Model 2, both in the total sample and the ATR subgroups (all P â€‹< â€‹0.05). Meanwhile, in the total sample and ATR subgroups, the centroid vector magnitudes of Model 3 were smaller than that of Model 1 (0.31 â€‹± â€‹0.76 D and 0.39 â€‹± â€‹0.76 D). Conclusions: The calculation of toric multifocal IOL should be individualized especially in the ATR eyes for the impact of PCA on the estimation of the preoperative corneal astigmatism and the CSIA.

Comparison of two objective methods for measuring postoperative toric intraocular lens orientation under the natural pupil.

PURPOSE: To evaluate and compare the accuracy of iTrace and CASIA2 in measuring the postoperative orientation of toric intraocular lens (IOL) without mydriasis. SETTING: Tianjin Medical University Eye Hospital, Tianjin, China. DESIGN: Prospective cohort study. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Plasmin-Induced Lens Epithelial Cells Detachment for the Reduction of Posterior Capsular Opacification.

Purpose: We sought to evaluate the efficacy and safety of plasmin injection in the capsular bag during the cataract operation for the prevention of posterior capsule opacification. Methods: Thirty-seven anterior capsular flaps taken from phacoemulsification surgery were immersed in either 1 µg/mL plasmin (plasmin group, n = 27) or phosphate-buffered saline (control group, n = 10) for 2 minutes and photographed after fixation and nuclear staining to compare the numbers of residual lens epithelial cells. In the animal experiments, the plasmin solution was injected into the capsular bag and remained for 5 minutes during hydrodissection or after lens extraction. The degree of posterior capsular opacity of the rabbits at 2 months were photographed by slit lamp biomicroscopy. In HLE-B3 cell culture, the cell detachment rate, proliferation, and apoptosis after the plasmin digestion were analyzed. Results: The residual lens epithelial cell numbers on the capsule after plasmin treatment were 168 ± 190.7/mm2 in the 1 µg/mL plasmin group, which was significantly lower than that of the control (1012 ± 798.8/mm2; P < 0.0001). In a rabbit model, the treatment of plasmin resulted in a significantly clearer posterior capsule compared with that of the control group at 2 months postoperatively. Conclusions: This study suggested that plasmin injection can induce effective lens epithelial cell detachment, which could be a promising adjunctive treatment to further improve the success rate in posterior capsule opacification prevention. Translational Relevance: Plasmin injection for lens epithelial cell detachment could significantly decrease the number of residual lens epithelial cells. This approach could be a promising treatment incorporating the current treatment approach to further improve the success rate in posterior capsule opacification prevention.

Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases.

Retinal diseases are major causes of irreversible vision loss and blindness. Despite extensive research into their pathophysiology and etiology, pharmacotherapy effectiveness and surgical outcomes remain poor. Based largely on numerous preclinical studies, administration of mesenchymal stem cells (MSCs) as a therapeutic strategy for retinal diseases holds great promise, and various approaches have been applied to the therapies. However, hindered by the retinal barriers, the initial vision for the stem cell replacement strategy fails to achieve the anticipated effect and has now been questioned. Accumulating evidence now suggests that the paracrine effect may play a dominant role in MSC-based treatment, and MSC-derived extracellular vesicles emerge as a novel compelling alternative for cell-free therapy. This review summarizes the therapeutic potential and current strategies of this fascinating class of cells in retinal degeneration and other retinal dysfunctions.

Multimodality Treatment of Brain Arteriovenous Malformations with One-Staged Hybrid Operation: Clinical Characteristics and Long-Term Prognosis.

Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

Distribution and internal correlations of corneal astigmatism in cataract patients.

The aim of the study is to explore the distribution patterns and internal correlations of the morphological parameters of the cornea in patients with age-related cataract. The Pentacam HR was used to measure anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), total corneal astigmatism (TCA) and keratometric corneal astigmatism (KCA). With age, the proportion of with-the-rule (WTR) ACA decreased from 65.31% to 23.63%, while the against-the-rule (ATR) ACA increased from 26.53% to 56.20%. PCA exceeded 0.50 D in 9.14% of eyes, while 76.35% of them were ATR. The magnitude of ACA was positively correlated with PCA in the whole sample, with a more significant correlation in WTR eyes (sr = 0.349, P < 0.001). The vector summation effect of PCA to ACA changed from compensation to augmentation with aging. In 57.53% of WTR eyes, KCA was overestimated by an average of 0.21 ± 0.17 D, while it was underestimated by 0.38 ± 0.27 D in 87.62% of ATR eyes. In conclusion, among age-related cataract patients, ACA and TCA gradually shifted from WTR to ATR with aging, while most PCA remained as ATR. Ignoring the age-related changes and real PCA might cause overestimation of WTR astigmatism and underestimation of ATR astigmatism.

Proteomics Profiling of Plasma Exosomes in VKH Patients.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Human umbilical cord-derived mesenchymal stem cells treatment for refractory uveitis: a case series.

AIM: To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) treatment in patients with refractory uveitis. METHODS: A retrospective and noncomparative review was performed on four patients with refractory uveitis from December 2013 to December 2017. HUC-MSCs were administered intravenously at a dose of 1×106 cells/kg. Clinical response, relapse rate, change of visual acuity, and other metrics were evaluated. RESULTS: All four patients presented with responses to HUC-MSCs treatment, with three males and one female. The numbers of uveitis attacks per year after the HUC-MSCs treatment (0, 2, 0, 0 respectively) all decreased compared with the numbers before the treatment (3, 6, 4, 4 respectively). The oral steroid and immunosuppressive agents were tapered in all patients without recrudescence of ocular inflammation, and three patients discontinued their oral medicine at the last visit. The best corrected visual acuity (BCVA) of 3 patients was improved to varying degrees, and the BCVA of 1 patient remained at 20/20 (Snellen chart) from the first to the last consultation. CONCLUSION: The study provides an effective therapy of HUC-MSCs in maintaining remission in patients affected by uveitis refractory to previous immunosuppressant treatments.

Safety and efficacy of intravitreal conbercept injection after vitrectomy for the treatment of proliferative diabetic retinopathy.

BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of intravitreal conbercept (a recombinant fusion protein that primarily targets vascular endothelial growth factors) after vitrectomy for the management of proliferative diabetic retinopathy without tractional retinal detachment (TRD). SUBJECTS/METHODS: Fifty patients with non-clearing vitreous haemorrhage (VH) due to proliferative diabetic retinopathy without TRD were enroled. They were randomly divided into control and treatment groups (25 eyes to each group) after they provided informed consent. The treatment group received intravitreal conbercept (10 mg/mL, 0.5 mg) immediately after surgery, while the control group did not. The best corrected visual acuity (BCVA) and the central retinal thickness were measured. RESULTS: There were no significant between-group differences in baseline characteristics (P > 0.05), except in age (P = 0.003). Improvement in BCVA was significantly greater at 1, 4, 12, and 24 weeks post surgery in the treatment group than it was in the control group (P < 0.001). There were more cases in the control group who developed recurrent VH, but the recurrence rate of VH was not significantly different between the two groups at 12 and 24 weeks post surgery (P = 0.192 and 0.103). Central retinal thickness was lower in the treatment group than in the control group at 1 week (P = 0.012), 4 weeks (P = 0.01), 12 weeks (P = 0.001), and 24 weeks (P = 0.004) post surgery, which were statistically significant. CONCLUSIONS: An intravitreal injection of conbercept after vitrectomy improved visual acuity and seemed to reduce the recurrence of VH resulting in prompt visual recovery in the PDR patients.

Long-Term Clinical Outcomes after Mix and Match Implantation of Two Multifocal Intraocular Lenses with Different Adds.

PURPOSE: To compare long-term clinical outcomes between patients with bilateral implantation of +3.0 diopter (D) multifocal intraocular lenses (IOLs) and mix and match implantation of +2.5 D and +3.0 D multifocal IOLs. MATERIAL AND METHODS: This retrospective observer-masked cohort study comprised 66 eyes of 33 patients with two different strategies of binocular multifocal IOLs implantation: bilateral +3.0 D (17 patients) (bilateral group) and mix and match +2.5 D and +3.0 D (16 patients) (blended group). Patients were recruited 1 year (±3 months) after second-eye surgery. The primary effectiveness endpoint was binocular uncorrected intermediate visual acuity (UCIVA) at 70 cm. The secondary assessments included binocular visual quality tests and quality-of-vision questionnaire. RESULTS: The blended group showed clinically better UCIVA (0.10 ± 0.07 logMAR) at 70 cm than the bilateral group (0.26 ± 0.09 logMAR) with a difference of 0.16 ± 0.08 logMAR (P < 0.001). Similar binocular visual acuities were achieved between the two groups at the near and far distance. The binocular defocus curves showed better performance in the blended group from 50 cm to 1 m. The mean binocular contrast sensitivities under the photopic conditions with or without glare and mesopic condition without glare were clinically better in the blended group. Both the groups reported low rate of visual phenomena, high rate of spectacle independence, and satisfaction. CONCLUSIONS: Comparing with bilateral implantation of +3.0 D multifocal IOLs during the cataract surgery, mix and match implantation of +2.5 D and +3.0 D multifocal IOLs provides a wider depth of binocular focus, especially for intermediate distances, and better binocular visual quality.

Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1.

Although accumulated evidence supports the notion that mesenchymal stem cells (MSCs) act in a paracrine manner, the mechanisms are still not fully understood. Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from MSCs, were thought to carry functional proteins and RNAs to recipient cells and play therapeutic roles. In the present study, we intravitreally injected MSCs derived from either mouse adipose tissue or human umbilical cord, and their exosomes to observe and compare their functions in a mouse model of laser-induced retinal injury. We found that both MSCs and their exosomes reduced damage, inhibited apoptosis, and suppressed inflammatory responses to obtain better visual function to nearly the same extent in vivo. Obvious down-regulation of monocyte chemotactic protein (MCP)-1 in the retina was found after MSC-Exos injection. In vitro, MSC-Exos also down-regulated MCP-1 mRNA expression in primarily cultured retinal cells after thermal injury. It was further demonstrated that intravitreal injection of an MCP-1-neutralizing antibody promoted the recovery of retinal laser injury, whereas the therapeutic effect of exosomes was abolished when MSC-Exos and MCP-1 were administrated simultaneously. Collectively, these results suggest that MSC-Exos ameliorate laser-induced retinal injury partially through down-regulation of MCP-1.

α-Melanocyte-stimulating hormone protects retinal vascular endothelial cells from oxidative stress and apoptosis in a rat model of diabetes.

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.