ObjectiveTo review the outcome of intravitreous anti-vascular endothelial growth factor (VEGF) treatment in patients with X-linked retinoschisis (XLRS) complicated with vitreous hemorrhage (VH). MethodsA retrospective clinical study. From March 1, 2016 to April 1, 2022, 18 patients (19 eyes) diagnosed with XLRS complicated with vitreous hemorrhage in Beijing Tongren Hospital, Capital Medical University of Eye Center were included. All the patients were male, with a median age of 7.05±3.8 years. Best corrected visual acuity (BCVA) and wide-angle fundus photography were performed in all the patients. BCVA was carried out using international standard visual acuity chart, and converted into logarithm of minimum resolution angle (logMAR) in statistics analysis. According to whether the patients received intravitreal injection of ranibizumab (IVR), the patients were divided into injection group and observation group, with 11 eyes in 10 cases and 8 eyes in 8 cases, respectively. In the injection group, 0.025 ml of 10 mg/ml ranibizumab (including 0.25 mg of ranibizumab) was injected into the vitreous cavity of the affected eye. Follow-up time after treatment was 24.82±20.77 months. The VH absorption time, visual acuity changes and complications were observed in the injection group after treatment. Paired sample t test was used to compare BCVA before and after VH and IVR treatment. Independent sample t test was used to compare the VH absorption time between the injection group and the observation group. ResultsLogMAR BCVA before and after VH were 0.73±0.32 and 1.80±0.77, respectively. BCVA decreased significantly after VH (t=－3.620, P=0.006). LogMAR BCVA after VH and IVR were 1.87±0.55 and 0.62±0.29, respectively. BCVA was significantly improved after IVR treatment (t=6.684, P＜0.001). BCVA records were available in 5 eyes before and after IVR, and the BCVA values after VH and IVR were 0.58±0.31 and 0.48±0.20, respectively, with no statistically significant difference (t=1.000, P=0.374). BCVA increased in 1 eye and remained unchanged in 4 eyes after treatment. BCVA records were available in 5 eyes before VH and after VH absorption in the 8 eyes of the observation group. LogMAR BCVA before VH and after VH absorption were 0.88±0.28 and 0.90±0.26, respectively, with no significant difference (t=－1.000, P=0.374). After VH absorption, BCVA remained unchanged in 4 eyes and decreased in 1 eye. The absorption time of VH in the injection group and the observation group were 1.80±1.06 and 7.25±5.04 months, respectively. The absorption time of VH was significantly shorter in the injection group than in the observation group, the difference was statistically significant (t=－3.005, P=0.018). Multivariate linear regression analysis showed that IVR treatment was significantly correlated with VH absorption time (B=－6.66, 95% confidence interval －10.93-－2.39, t=－3.40, P=0.005). In the injection group, VH recurrence occurred in 1 eye after IVR treatment. Vitrectomy (PPV) was performed in one eye. In the 8 eyes of the observation group, VH recurrence occurred in 2 eyes, subsequent PPV in 1 eye. The rate of VH recurrence and PPV was lower in the injection group, however, the difference was not statistically significant(P=0.576, 1.000). In terms of complications, minor subconjunctival hemorrhage occurred in 2 eyes and minor corneal epithelial injury occurred in 1 eye in the injection group, and all recovered spontaneously within a short time. In the injection group, 9 eyes had wide-angle fundus photography before and after IVR treatment. There was no significant change in the range of peripheral retinoschisis after treatment. No obvious proliferative vitreoretinopathy, infectious endophthalmitis, retinal detachment, macular hole, complicated cataract, secondary glaucoma or other serious complications were found in all the treated eyes, and there were no systemic complications. ConclusionIntravitreous anti-VEGF treatment may accelerate the absorption of vitreous hemorrhage in patients with XLRS. No impact is found regarding to the peripheral retinoschisis.
Objectives To assess the effects of alpha-glucosidase inhibitors in patients with type 2 diabetes mellitus. Method We searched The Cochrane Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, reference lists of reviews on the topic of alpha-glucosidase inhibitors and we contacted experts and manufacturers for additional trials. Date of most recent search: December 2003 (Current Contents) and April 2003 (other databases). Randomised controlled trials of at least 12 weeks duration comparing alpha-glucosidase inhibitor monotherapy in patients with type 2 diabetes with any other intervention and that included at least one of the following outcomes: mortality, morbidity, quality of life, glycemic control, lipids, insulin levels, body weight, adverse events. Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer. A statistician checked all extracted data entrance in the database. We attempted to contact all authors for data clarification. Results We included 41 trials (8130 participants), 30 investigated acarbose, seven miglitol, one trial voglibose and three trials compared different alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. We found only few data on mortality, morbidity and quality of life. Acarbose had a clear effect on glycemic control compared to placebo: glycated haemoglobin –0.77% (95% confidence interval –0.90 to –0.64), fasting blood glucose –1.1 mmol/L (95% confidence interval –1.4 to –0.9), post-load blood glucose –2.32 mmol/L (95% confidence interval –2.73 to –1.92). The effect on glycated haemoglobin by acarbose was not dose-dependent. We found a decreasing effect on post-load insulin and no clinically relevant effects on lipids or body weight. Adverse effects were mostly of gastro-intestinal origin and dose dependent. Compared to sulphonylurea, acarbose decreased fasting and post-load insulin levels by –24.8 pmol/L (95% confidence interval –43.3 to –6.3) and –133.2 pmol/L (95% confidence interval –184.5 to –81.8) respectively and acarbose caused more adverse effects. Conclusions It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated haemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.
ObjectiveTo observe the effect of complement receptor 1 (CR1) on barrier of cultured human retinal epithelial cells (hRPE) under complement-activated oxidative stress. MethodsThe third to fifth passage of hRPE cultured on Transwell insert were used to establish a stable hRPE monolayer barrier. The hRPE monolayer barrier was exposed to 500 μmol/L ten-butyl hydroperoxide and 10% normal human serum to establish the hRPE monolayer barrier model of complement-activated oxidative stress in vitro. hRPE monolayer barriers under complement-activated oxidative stress were divided into two groups including model group and CR1 treatment (1 μg/ml) group. Model group and CR1 treatment group were treated with 1 μl phosphate buffer solution (PBS) or CR1 for 4 hours. Normal hRPE monolayer barrier were used as control in transepithelial resistance (TER) measurement experiment. TER was measured to evaluate the barrier function of hRPE. The hRPE-secreted vascular endothelial growth factor (VEGF) and chemokine (C-C Motif) Ligand 2 (CCL2), together with complement bioactive fragments (C3a, C5a) and membrane-attack complex (MAC) in the supernatant were detected by enzyme-linked immune sorbent assay. ResultsStable hRPE monolayer barrier was established 3 weeks after hRPE seeded on Transwell insert. Complement-activated oxidative stress resulted in a sharp decrease of TER to 54.51% compared with normal hRPE barrier. CR1 treatment could significantly improve TER of barrier under complement-activated oxidative stress to 63.48% compared with normal hRPE barrier(t=21.60, P < 0.05). Compared with model group, CR1 treatment could significantly decrease the concentration of VEGF and CCL2 by 11.48% and 23.47% secreted by hRPE under complement-activated oxidative stress (t=3.26, 2.43; P < 0.05). Compared with model group, CR1 treatment could also decreased the concentration of C3a, C5a and MAC by 24.00%, 27.87%, 22.44%.The difference were statistically significant (t=9.86, 2.63, 6.94; P < 0.05). ConclusionsCR1 could protect the barrier function of hRPE cells against complement-activated oxidative stress. The underlying mechanism may involve inhibiting complement activation and down-regulating the expression of VEGF and CCL2.
ObjectiveTo evaluate the effectiveness and complications associated with the use of ranibizumab in the treatment of ZoneⅠand ZoneⅡretinopathy of prematurity (ROP). MethodsData from patients of ROP who had received intravitreal ranibizumab (IVR) injections in Peking University People's Hospital for the treatment of ROP from July 2012 to December 2013 were collected. In total, 151 eyes from 85 patients (56 male and 29 female) were analyzed. The mean birth weight was (1438.6±334.5) g (range:790-2280 g), mean gestational age was (30.1±2.0) weeks (range:25-37 weeks), mean age at the time of intervention was (37.0±6.2) gestational weeks (range:32-45 weeks), mean follow-up was (4.9±3.3) months (range:1.4-20.8 months). The main outcome measures were the regression of ROP and the complications that were associated with the IVR injections. ResultsAfter receiving IVR injections, 120 eyes (79.5%) exhibited ROP regression after single injection. Twenty-six eyes (17.2%) required additional laser treatment for ROP regression after the absence of a positive response to the IVR injections. Five eyes (3%) progressed to stage 4 ROP and required vitrectomy to reattach the retinas. Fifty of 120 eyes which were regressed after single IVR had recurrence of ROP and need additional laser or additional IVR. All of the eyes (100.0%) had attached retinas after the various treatments that they received. No notable systemic complications related to the IVR injections were observed. ConclusionsIVR injection seems to be an effective and well-tolerated method to treat ZoneⅠand ZoneⅡROP. Recurrence of ROP is common and long-term follow up may be needed.
ObjectiveTo investigate the prognosis and differences of visual function and fundus structure in retinopathy of prematurity (ROP) undergoing anti-vascular endothelial growth factor agents (VEGF) or laser photocoagulation treatment with long-term follow-up. MethodsRetrospective case control series. From January 2010 to December 2021, A total of 35 children (63 eyes) with ROP who were first diagnosed in Department of Ophthalmology, Peking University People's Hospital and followed up for as long as 5 years were included. Among them, 21 males (36 eyes) and 15 females (27 eyes) were enrolled. The average gestational age (GA) of the children at birth was 29.30±1.77 weeks. Among the included 12 aggressive ROP (A-ROP) eyes and 51 pre-threshold type 1 ROP eyes, no retinal detachment occurred. Each eye received only intravitreal injection of anti-VEGF agents or laser monotherapy after diagnosis, and divided into anti-VEGF group or laser group according to the treatment. Thirty-five eyes of 20 infants were included in the anti-VEGF group and 28 eyes of 15 infants were included in the laser group. GA, birth weight (BW) and postmenstrual age receiving first treatment were compared and no significant difference between the two groups was defined (P=0.844, 0.859, 0.694). The number of A-ROP, pre-threshold type 1 ROP eyes were also compared, and statistically significance can be defined (P=0.005). During the follow-up period, best corrected visual acuity (BCVA), refractive status, visual field, optical coherence tomography (OCT) and fluorescein fundus angiography (FFA) were performed. The BCVA examination was carried out using the international standard decimal visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. Refractive status was calculated as spherical equivalent (SE). Comparative observation of 5-year outcomes including BW, GA, fundus examination at the initial diagnosis, and BCVA, refractive status, visual field defect, central foveal thickness (CFT), subfoveal choroidal thickness (SFCT) and abnormality of peripheral retina in FFA were performed between the two groups. Differences between groups were compared using t test or nonparametric test for measurement data, and χ2 test was used for comparison between groups in enumeration data. ResultsFive years after treatment, retinal avascular areas were seen around the eyes in the anti-VEGF treatment group, with a size of 2.32±1.84 optic disc diameters, and 1 eye had fluorescein leakage at the junction of the peripheral avascular areas; eyes in the laser treatment group old photocoagulation spots were seen in the peripheral retina, and no fluorescein leakage was seen. The logMAR BCVA of the eyes in the anti-VEGF treatment group and laser treatment group were 0.15 (0.00, 0.20), 0.10 (0.00, 0.16), respectively; SE were 0.50 (－1.25, 1.31), 0.38 (－4.25, 1.75) D, respectively; mean defect (MD) values of visual field were 2.70 (1.20, 4.80), 4.25 (2.83, 6.98) dB; CFT, SFCT were 225.00±29.31, 287.18±68.56 μm and 237.17±32.81, 279.79±43.61 μm. There was no significant difference in logMAR BCVA, CFT and SFCT between the two groups (P=0.363, 0.147, 0.622); the lower quartile of SE and visual field MD value in the laser treatment group were significantly higher than those in the laser treatment group, but there was no significant difference in the median SE (P=0.109), and there was a statistically significant difference in the median MD value of the visual field (P=0.037). ConclusionsAnti-VEGF agents and laser therapy can achieve similar good visual prognosis for early ROP, and the peripheral visual field can be preserved to a greater extent, however, the peripheral visual field defect in the laser group is more significant than that in the anti-VEGF group. For ROP without retinal detachment, the thickness of the retina and choroid in the fovea is generally normal.
Vogt-Koyanagi-Harada syndrome (VKH) is an autoimmune disorder primarily characterized by bilateral granulomatous uveitis, which can lead to severe visual impairment and related complications. Traditional treatment typically involves glucocorticoid combined with immunosuppressants, but these therapies are associated with significant side effects, limited efficacy, and poor long-term prognosis. In recent years, biologic agents have emerged as a promising treatment for refractory VKH due to their targeted action, high efficacy, and low toxicity. Tumor necrosis factor-alpha (TNF-α) inhibitors, such as infliximab and adalimumab, have shown significant benefits in controlling inflammation, improving vision, and reducing steroid dependence, making them a key option for difficult-to-treat VKH. Among interleukin (IL) blockers, tocilizumab has demonstrated potential in patients who do not respond to traditional treatments. Rituximab, a B-cell targeting agent, has shown good efficacy and safety in patients resistant to TNF-α inhibitors. Additionally, research into novel biologics targeting the IL-23/IL-17 axis and IL-33 offers new directions for VKH therapy. While biologics provide clear advantages in VKH treatment, further research is needed to explore their long-term safety, cost-effectiveness, and optimal treatment regimens. Large-scale randomized controlled trials are required to validate their efficacy and identify personalized treatment strategies to improve long-term patient outcomes.
Objective To investigate the effects of knocking down Rac1 gene (ras-related C3 botulinum toxin substrate 1) by small hairpin RNA (shRNA) on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Methods One hundred and eight 7-day-old C57BL/6J mice were divided into three groups randomly.The OIR was induced by Smith protocol in 2 groups. OIR mice received an intravitreal injection of Rac1-shRNA plasmid or the nonsense plasmid in the geneintervention group and control group respectively at the age of postnatal day 11 (P11). Non-OIR mice also received an intravitreal injection of Rac1-shRNA plasmid at P11 as the blankintervention group which lived in the normoxic environment.Retinal neovascularization was investigated on flat-mounts after fluorescence angiography at P15 and P17. Endothelial cell nuclei breaking through the internal limiting membrane were counted on pathological section at P17.The expression of Rac1 and NF-kappa;B p65 subunit was measured by immuohistochemistry, Western blot, real-time polymerase chain reaction (RT-PCR) and in situ hybridization. Results Compared with the blank-control group,the level of Rac1 mRNA in the gene-intervention group decreased obviously（t=4.500，P=0.001）;the retinal non-perfusion areas,fluorescence leakage, neovascularization and the number of endothelial cell nuclei breaking through the internal limiting membrane were reduced significantly（t=6.521,P＜0.001）; the level of NF-kappa;B p65 nuclear translocation decreased（t=16.008,P＜0.001）while the expression of NF-kappa;B p65 mRNA was reduced obviously（t=3.354,P=0.006）, which was positively correlated with the expression of Rac1-mRNA (P=0.012).Conclusion Intravitreal injection of Rac1-shRNA with liposome in mice can effectively inhibit the expression of Rac1,and inhibit the retinal neovascularization under relative hypoxia via blocking the ROS-NF-kappa;B pathway.
ObjectiveTo observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD). MethodsA retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 (IL-8), complement C3 gene (C3), complement factor H (CFH), liver lipase (LIPC), cholesterol ester transfer protein (CETP), ATP binding cassette subfamily a member 1 (ABCA1), lipoprotein lipase (LPL), fatty acid desaturation gene cluster (FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. ResultsThere were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio (OR)=0.310, 95% confidence interval (CI) 0.106-0.910, P＜0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders (OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) (OR=3.031, 95% CI 1.036-8.867, P＜0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant (t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment (IL-8 rs4073: Z=－0.198, －1.651; P=0.843, 0.099; LIPC rs2043085: Z=－0.532, －0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.
ObjectiveTo observe the optical coherence tomography angiography (OCTA) image characteristics of polypoid choroidal vascular disease (PCV) after intravitreal injection of anti-vascular endothelial growth factor drugs, and to discuss its significance in the diagnosis and follow-up of PCV.MethodsA retrospective case study. From August 2018 to January 2020, 22 eyes of 22 patients with PCV diagnosed in the ophthalmological examination of Affiliated Hospital of Weifang Medical University were included in the study. Among them, there were 10 males with 10 eyes and 12 females with 12 eyes; the average age was 67.75±9.53 years. Best corrected visual acuity (BCVA), OCTA, and indocyanine green angiography (ICGA) were performed. All the affected eyes were injected vitreously with 10 mg/ml Conbercept 0.05 ml (including Conbercept 0.5 mg) once a month for 3 consecutive months.Tthe macular area of 3 mm×3 mm and 6 mm×6 mm with an OCTA instrument was scanned, and the foveal retinal thickness (CRT) was measured, the area of abnormal branch blood vessels (BVN). pigment epithelial detachment before and 12 months after treatment (PED) height, foveal choroid thickness (SFCT) were performed. The diagnosis rate of PCV by OCTA was observed, as well as the changes of various indicators of BCVA and OCTA. Before and after treatment, BCVA and CRT were compared by paired t test; BVN area, PED height, and SFCT were compared by variance analysis. The changes in imaging characteristics of OCTA before and after treatment were analyzed.ResultsAmong the 22 eyes, 8 eyes were BVN; 5 eyes were polypoid lesions (polyps); 5 eyes were BVN combined with polyps; 3 eyes were not found with BVN and polyps; 1 eye with small vascular network structure, this eye was ICGA Appears as strong nodular fluorescence (polyps). The detection rate of PCV by OCTA was 86.36% (19/22). Twelve months after treatment, BVN was significantly reduced or disappeared in 16 eyes (72.72%, 16/22); polyps disappeared in 17 eyes (77.27%, 17/22). Compared with before treatment, 12 months after treatment, BCVA increased (t=3.071), CRT decreased (t=2.440), the difference was statistically significant (P＜0.05); the average BVN area, PED height, and SFCT decreased. The difference in average BVN area and PED height was statistically significant (F=2.805, 3.916; P＜0.05), and the difference in SFCT was not statistically significant (F=0.047, P＞0.05).ConclusionsThe detection rate of PCV by OCTA is 86.36%. After PCV anti-vascular endothelial growth factor drug treatment, BVN area decrease and polyps subside. OCTA is an effective means for PCV diagnosis and follow-up after anti-VEGF drug treatment.
According to the best corrected visual acuity and the morphological changes of the macular fovea, responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability, including poor and non-responders. Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy, such as the related susceptibility genes, factors related with the development of choroidal neovascularization and morphologic parameters, pharmacokinetics and tachyphylaxis. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.