Retinopathy of prematurity (ROP) is a disorder of the developing retina in which abnormal proliferation of retinal blood vessels may lead to severe visual compromise or retinal detachment in infants born preterm. Insulin-like growth factor-1 (IGF-1) promotes normal retinal vessel growth in utero; however, IGF-1 levels fall substantially following preterm birth. By returning IGF-1 to in utero levels, postnatal treatment with IGF-1 may interrupt ROP pathogenesis, preventing disease or reducing its severity. To compare treatment with IGF-1 to standard care or placebo for the prevention of retinopathy of prematurity or treatment of early retinopathy of prematurity. We used CENTRAL, MEDLINE, Embase, Cochrane Database of Systematic Reviews, Issue 3, 2025, in the Cochrane Library, CINAHL Plus with Full Text (EBSCOhost), Epistemonikos, clinical trials registries (US National Library of Medicine Clinicaltrials.gov, World Health Organization's International Trials Registry Platform, and ISRCTN Registry), together with reference checking and citation searching to identify studies that are included in this review. The latest search date was 10 March 2025. We considered all randomized controlled trials (RCTs), cluster-RCTs, and quasi-RCTs comparing IGF-1 with standard care or placebo for the prevention of ROP or treatment of early ROP in preterm infants. We planned to exclude cross-over randomized trials. Our outcomes of interest were: • Development of Type 1 ROP, defined as ROP requiring treatment at any time during the birth hospitalization or outpatient follow-up • Development of ROP ≥ stage 3 at any time during the birth hospitalization or outpatient follow-up • Development of ROP of any severity at any time during the birth hospitalization or outpatient follow-up • Occurrence of one or more serious adverse events (SAEs) at any time during the birth hospitalization • Mortality during the birth hospitalization • Hypoglycemia during the birth hospitalization RISK OF BIAS: We used the original Cochrane Risk of Bias 1 tool (RoB 1) to assess possible bias in the included studies. Dichotomous data were reported using risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Where possible, we synthesized results for each outcome using meta-analysis with fixed-effect models. We used GRADE to assess the certainty of evidence for each outcome. We included two studies totaling 140 participants. Both included studies were parallel-group RCTs performed between 2011 and 2016 enrolling extremely preterm infants in well-resourced settings in Europe and North America. The two published primary study references describe a two-center RCT (n = 19) and a 20-center RCT (n = 121) comparing treatment starting on the first day of life with intravenous IGF-1 (as mecasermin rinfabate) to standard care for prevention of ROP in newborn infants at 23 weeks' to 27 weeks plus six days' gestational age with follow-up through 40 weeks' postmenstrual age. Type 1 ROP/ROP requiring treatment Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of Type 1 ROP/ROP requiring treatment (RR 0.94, 95% CI 0.38 to 2.35; P = 0.90; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). ROP ≥ stage 3 Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of severe ROP (RR 1.27, 95% CI 0.61 to 2.65; P = 0.52; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). ROP of any severity Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo for preventing development of ROP of any severity (RR 1.30, 95% CI 0.94 to 1.80; P = 0.12; I2 = 0%; 2 RCTs, 116 infants; very low-certainty evidence). SAEs during the birth hospitalization Evidence is very uncertain regarding the safety of treatment with IGF-1 as compared to standard care/placebo as reflected by the occurrence of one or more SAEs during the birth hospitalization in preterm infants (RR 1.18, 95% CI 0.94 to 1.47; P = 0.15; I2 = 65%; 2 studies, 140 infants; very low-certainty evidence). Post-hoc sensitivity analysis including only the larger RCT demonstrated an increased risk of experiencing one or more SAEs with IGF-1 compared to controls (RR 1.28, 95% CI 1.01 to 1.62, P = 0.05; RD 0.17, 95% CI 0.01 to 0.33, P = 0.04; number needed to treat for an additional harmful outcome (NNTH) 5.9; I2 = not applicable; 1 RCT, 121 infants; very low-certainty evidence). All-cause mortality during the birth hospitalization Evidence is very uncertain regarding the effect of treatment with IGF-1 as compared to standard care/placebo on all-cause mortality during the birth hospitalization in preterm infants (RR 1.69, 95% CI 0.71 to 3.99; P = 0.23; I2 = not applicable; 1 RCT, 121 infants; very low-certainty evidence). Hypoglycemia during the birth hospitalization Evidence is very uncertain regarding the safety of treatment with IGF-1 as compared to standard care/placebo as reflected by the incidence of hypoglycemia in preterm infants during the birth hospitalization (RR 1.00, 95% CI 0.62 to 1.63; P = 0.99; I2 = 0%; 2 RCTs, 140 infants; very low-certainty evidence). We assessed all results to be of very low certainty due to small total enrollment and substantial risk of bias. Both included studies had a high risk of bias in two domains. In addition, both were funded by industry. The available data are of very low certainty, and so we are not able to draw conclusions about the effects of treatment with IGF-1 in preterm infants for preventing or treating ROP, or about its effects on risk of serious adverse events, mortality, or hypoglycemia in this population. This Cochrane review had no dedicated funding. Protocol available via DOI: 10.1002/14651858.CD013216.
To report aggregate data from the United Kingdom AMD (age-related macular degeneration) Audit, focussing on baseline characteristics, treatment and one year acuity and safety outcomes for eyes starting treatment for neovascular AMD between April 2021 and March 2023. Anonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at participating centres providing NHS-funded treatment. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation. Analysis included 54,882 eyes of 48,371 patients from 78 participating treatment centres. Just over 60% were female and the median age at the start of treatment was 79.9 years for first treated eyes and 82.2 years for second treated eyes. Median baseline acuity was 60 ETDRS letters (interquartile range (IQR)= 44-70) and 28.1% of eyes had "good" acuity, defined as ≥ 70 ETDRS letters. The initial three injections, during the loading phase of monthly treatment, were given within 10 weeks in 64% of eyes and the median number of injections in the first 12 months was 6 (IQR 4-8). The median interval between injections at the end of the first year of treatment was 8 weeks (IQR 6-12 weeks). Trained non-medical healthcare professionals administered at least 72% of injections. Median acuity after 12 months was 65 ETDRS letters (IQR 48-75) and 43.1% had "good" visual acuity. The incidence of intra-ocular inflammation and presumed infectious endophthalmitis after each injection were 0.03% (1 in 3,176) and 0.014% (1 in 7,013) respectively. There was no difference in the incidence of either complication by profession of the injector. Aggregate data from the UK AMD Audit provides real-world evidence and a benchmark against which other countries and centres can compare local performance and outcomes. Almost 91% of eyes retained stable acuity and avoided moderate visual loss after 12 months of treatment. The best acuity outcomes were obtained in younger patients and in eyes treated second, with good baseline acuity, prompt completion of the loading phase of treatment and receiving more injections during the first 12 months of treatment.
Circadian rhythms affect cardiovascular function, and the timing and severity of stroke and myocardial infarction (commonly known as a heart attack). Afternoon cardiac surgery may improve outcomes by reducing ischaemia-reperfusion injury (i.e. reducing tissue damage caused when blood supply returns to tissue (reperfusion) after a period of oxygen deprivation (ischaemia)). However, the evidence is conflicting. This systematic review assessed the impact of surgical timing on clinical outcomes after cardiac surgery. To assess the effects of early versus late surgical start times for on-pump cardiac surgery on mortality, cardiac outcomes, and quality of life. We searched CENTRAL, MEDLINE, Embase, and Web of Science Conference Proceedings Citation Index - Science, along with ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform trials registers. We also conducted reference checking, citation searching, and contacted study authors to identify studies for inclusion. The latest search date was 26 January 2025. We included randomised controlled trials (RCTs) in adults undergoing cardiac surgery comparing late with early surgical start times. We excluded non-randomised studies and studies in children. Our critical outcomes were short-term mortality (≤ 30 days postoperative), long-term mortality (> 30 days postoperative), and perioperative myocardial infarction. Other important outcomes were perioperative myocardial injury, postoperative atrial fibrillation, left ventricular ejection fraction, lengths of intensive care unit (ICU) and hospital stays, and quality of life. We used the Cochrane Risk of Bias 2 tool to assess bias in the included RCTs. As only one study met the inclusion criteria, we did not perform meta-analysis. We synthesised results descriptively, and used GRADE to assess the certainty of the evidence for specified outcomes. We included one study with 88 participants. The included study was conducted in France, and reported on differences in outcomes between morning and afternoon on-pump elective aortic valve replacement in adults. Critical outcomes No study reported short-term or long-term mortality data for early versus late surgical start times for on-pump cardiac surgery. In the included study, there was no evidence of a difference regarding in-hospital mortality between groups, with no deaths in both groups (risk ratio (RR) and 95% confidence interval (CI) not estimable; 1 study, 88 participants). The evidence is very uncertain about the effect of early versus late surgery on perioperative myocardial infarction (RR 0.29, 95% CI 0.06 to 1.30; 1 study, 88 participants, very low-certainty evidence). Important outcomes There was evidence of lower perioperative myocardial injury as measured by cumulative troponin release over 72 hours in those undergoing late surgery compared to early surgery (MD -46 ng/L × 72 h, 95% CI -79 to -13; 1 study, 88 participants). In the included study, there was no evidence of a difference in new-onset postoperative atrial fibrillation during hospital stay between groups (RR 0.75, 95% CI 0.40 to 1.40; 1 study, 88 participants). No study reported differences in left ventricular ejection fraction at discharge as a continuous variable for early versus late surgical start times for on-pump cardiac surgery. In the included study, there was no evidence of a difference in left ventricular ejection fraction < 45% at discharge between groups (RR 0.40, 95% CI 0.08 to 1.95; 1 study, 88 participants). No study reported differences in length of ICU admission for early versus late surgical start times for on-pump cardiac surgery. There was no evidence of a difference in need for inotropic support between groups in the included study (RR 0.25, 95% CI 0.03 to 2.15; 1 study, 88 participants). The evidence is very uncertain about the effect of late surgery on length of hospital stay (MD 0.00, 95% CI -1.48 to 1.48; 1 study, 88 participants, very low-certainty evidence). No study reported on the outcome of quality of life. The evidence is very uncertain about the effects of early versus late surgical start time for the outcomes of perioperative myocardial infarction and length of hospital stay. We found no data for the outcomes of short-term or long-term mortality, left ventricular ejection fraction, length of ICU stay, or quality of life. Late surgical start time could reduce the risk of perioperative myocardial injury as estimated by cumulative troponin release over 72 hours. More research is needed to determine whether scheduling heart surgery later in the day improves patient outcomes. This Cochrane review had no dedicated funding. Protocol (2022) DOI: 10.1002/14651858.CD014901.
Rhegmatogenous retinal detachment (RRD) associated with giant retinal tears (GRTs) are treated with vitrectomy but choice of intraocular tamponade is difficult, and practice varies amongst vitreoretinal surgeons.We sought to investigate the variables that determine choice of tamponade and how these may affect anatomical and visual outcomes. Cohort study of routinely collected data from the European Society of Retina Specialists and British and Eire Association of Vitreoretinal Surgeons vitreoretinal surgery outcomes database between 2011 and 2024.Consecutive eyes with GRT and primary RRD surgery that had vitrectomy, and either gas or silicone oil (SO),were included. Revision surgery or secondary causes of GRT including trauma and inflammation were excluded.The type of tamponade used was analysed by a range of baseline variables including macular status,GRT extent and the lowest GRT extent.Multivariable logistic and linear regression were used to investigate the association between baseline variables and surgical technique,including tamponade choice,on primary anatomical success and postoperative visual acuity (VA). 215 eyes with GRT associated RRD were analysed.The mean age was 53 years,80% were male,7% had PVR Grade C.58% of the cases were macula on.Overall,50% of the eyes received SO tamponade and 50% gas.Silicone oil was used in more of the macula off cases and in eyes with larger GRTs.Overall,187 of the 215 (87%) eyes achieved primary anatomical success,with 88% of gas tamponade cases achieving primary success versus 86% of the oil cases.Data on visual outcomes were available on 196 eyes of the 215 eyes.Overall, 57% of these eyes achieved 0.3 logMAR postoperative VA or better,with higher percentages in the gas compared to the oil group (78% versus 36%).Multivariable analysis found that tamponade type was not associated with anatomical outcome.The only factor associated with a reduced anatomical success rate was PVR C (Odds Ratio 0.29(95% confidence interval (CI) 0.09-0.90) p=0.03) Multivariable analysis found that postoperative VA was significantly better with gas compared to SO with oil.Overall, the odds of achieving a VA of 0.3 logMAR or better were at least 2 times higher with gas as compared to oil (Odds ratio 4.65 (95% CI: 2.41, 8.99), p<0.001),rising to at least 5 times higher in the subgroup of patients with a VA of 0.3 logMAR or better at baseline, (OR 17.56 (95% CI 5.15, 59.89), p<0.001). Our results show that gas tamponade has a similar anatomical success rate to SO,but better visual outcomes in the repair of GRT associated RRD.Further studies are needed to confirm these findings and inform tamponade choice.
To evaluate the clinical presentation, nasal endoscopic findings, and surgical outcomes of probing surgery (PS) or bicanalicular silicone tube intubation (BCI) performed under nasal endoscopic guidance (NEG) in pediatric patients with congenital nasolacrimal duct obstruction (CNLDO), regardless of previous surgical history. This retrospective cross-sectional study included CNLDO patients with data on demographics, fluorescein dye disappearance test (FDDT) results, dacryoscintigraphy findings, prior surgeries, and outcomes of NEG-PS or NEG-BCI. NEG-BCI using Crawford stents was performed intraoperatively in complex cases. Intraoperative and postoperative complications were recorded. Surgical success was evaluated clinically and with FDDT at postoperative months 1 and 6. Stents were retained for a minimum of 12wk, with follow-up for at least 6mo after removal. Of the 67 pediatric patients (67 eyes, mean age 37.4±17.5mo), 44 (65.7%) were female. Preoperative FDDT was graded 3+ in 85.1% of cases, and dacryoscintigraphy confirmed obstruction in 92.5%. Nine patients (13.4%) had a history of PS. At 6mo, surgical success was achieved in 96.6% (28/29) of the NEG-PS group and 71.1% (27/38) of the NEG-BCI group (P=0.009). All cases with probe exit through the inferior meatus (IM) were successful, whereas exits through the inferior concha (IC) or submucosal IM (SM) were significantly associated with failure (P<0.001). NEG allows intraoperative classification of CNLDO and selection of surgical method based on real-time anatomical findings. Probe exit through the IM predicts a high likelihood of success, whereas IC or SM exits are risk factors for failure. Incorporating NEG into routine practice may improve surgical precision and reduce the need for repeated procedures.
To systematically summarize the efficacy and safety of flavonoids in the treatment of dry eye disease (DED), and review their mechanisms of action, and provide a scientific foundation for clinical translation. To retrieve papers published from the establishment of the database through May 12, 2025, eight databases were searched: the Chinese National Knowledge Infrastructure (CNKI), the China Biomedical Literature Database (CBM), the Wanfang Database, the China Science, Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. Two independent researchers conducted the literature selection and information extraction processes, utilizing the SYRCLE tool to assess the risk of bias. The results of eligible studies were subjected to narrative analysis. A total of 11 animal studies were included in this review, encompassing research conducted in China, the United States, Republic of Korea, and Japan. These studies involved six flavonoid-rich substances, such as Buddleja officinalis and purple corn extract (PCE), as well as four individual flavonoids including quercetin and daidzin, etc. The findings indicated that flavonoids have the potential to enhance tear secretion. Following interventions with quercetin eye drops and PCE administered at varying doses and time intervals, a significant increase in tear secretion was observed, which approached normal levels. Additionally, these interventions demonstrated a capacity to mitigate damage to the corneal epithelium. For instance, maqui berry extract (MBE) were found to improve corneal fluorescein staining scores while reducing damage to the corneal surface. Flavonoids significantly alleviate dry eye symptoms in animal models by enhancing tear secretion and mitigating corneal epithelial damage. The observed efficacy is attributed to a range of mechanisms, including anti-inflammatory, antioxidant, hormonal regulation, and anti-apoptotic effects. The consistent therapeutic outcomes noted in both mouse and rat models further underscore the translational potential of these compounds. Consequently, flavonoids are regarded as highly promising natural agents for ocular health. However, additional pharmacokinetic studies and clinical trials are necessary to confirm their efficacy and safety in human subjects with dry eye syndrome.
To investigate the role of pyruvate kinase M2 (PKM2) in high glucose (HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis. Human retinal microvascular endothelial cells (HRMECs) were cultured and divided into the following groups: normal glucose (NG, 5.5 mmol/L), HG (30 mmol/L), HG with PKM2 knockdown (HG+shPKM2), and HG treated with the pharmacological activator TEPP-46 (HG+TEPP-46). Cellular viability, proliferation, migration, and tube-forming ability were assessed using CCK-8, EdU, wound healing/Transwell, and Matrigel assays, respectively. The expression levels of PKM2, phosphorylated PKM2 (p-PKM2, Y105), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) were detected by Western blotting. The oligomerization status of PKM2 was analyzed via native gel electrophoresis. The subcellular localization of PKM2 was examined by immunofluorescence and nuclear-cytoplasmic fractionation. Under HG stimulation, the expression level of PKM2 was significantly increased (P<0.05). Knockdown of PKM2 was found to markedly suppress cell viability, proliferation, migration, and tube formation in HRMECs (P<0.05). Mechanistic studies revealed that phosphorylation of PKM2 at the Y105 site was promoted by HG treatment, which induced its dissociation from a tetramer to a dimer, thereby driving its nuclear translocation. Upon entering the nucleus, PKM2 was shown to exert critical non-metabolic functions; it was physically bound to HIF-1α and acted as its co-activator, leading to significant upregulation of VEGFA expression (P<0.05). In contrast, the PKM2 activator TEPP-46 effectively prevented dimerization and nuclear translocation of PKM2 by promoting its tetramerization. Consequently, the PKM2/HIF-1α axis-mediated upregulation of VEGFA was blocked, ultimately resulting in the reversal of HG-induced angiogenesis. HG influences retinal endothelial cell function by inducing PKM2 phosphorylation, dimerization, and nuclear translocation. The shift in PKM2 phosphorylation and oligomerization status represents a key mechanism through which TEPP-46 reverses HG-induced angiogenesis.
To investigate efficacy and ocular surface safety of 3 kinds of different correction methods for correction of high myopia in adolescents. A prospective, randomized, controlled clinical trial was conducted. From January 2022 to December 2022, 62 adolescents with high myopia (124 eyes) were recruited, with spherical refractive errors ranging from -6.00 to -7.50 diopters (D) and refractive astigmatism ≤1.50 D. All participants were randomly assigned to three groups: the orthokeratology combined with single-vision spectacle lenses (OK+SVLs) group (20 cases, 40 eyes), the peripheral defocus rigid gas permeable contact lenses (Defocus RGPCL) group (22 cases, 44 eyes), and the single-vision spectacle lenses (SVLs) group (20 cases, 40 eyes). All of them were followed up for 1.5y. The observation indicators included refractive error, axial length (AL), tear break-up time (BUT), percentage of hexagonal corneal endothelial cells (CEC), CEC density, and ocular surface adverse reactions. The three groups had mean age of 14.84±1.87y, 14.57±1.91y, and 14.80±1.52y, respectively. No statistically significant differences were found in age, gender, corneal curvature, AL, and spherical equivalent among the groups (all P>0.05). At the 6mo, 1, and 1.5y follow-ups after spectacle lens wear, the improvements in refractive error in the OK+SVLs and Defocus RGPCL groups were significantly superior to those in the SVLs group (F=4.221, P=0.017; F=7.226, P=0.001; F=16.140, P<0.001), while no significant difference was observed between the OK+SVLs and Defocus RGPCL groups (all P>0.05). Intergroup comparisons of AL changes revealed statistically significant differences at all follow-up time points (F=3.493, P=0.034; F=9.930, P<0.001; F=20.570, P<0.001), with no notable difference between the OK+SVLs and Defocus RGPCL groups (all P>0.05). After 1.5y of lens wear, the intergroup comparison of BUT showed a statistically significant difference (F=5.783, P=0.004), whereas no significant differences were found in the percentage of hexagonal CEC and CEC density among the three groups (all P>0.05). No severe complications were observed in the two contact lens groups; only 5 eyes presented with grade 1 or 2 bulbar conjunctival hyperemia and corneal epithelial staining. All adverse reactions were well controlled by temporary lens discontinuation or medication, and resumed lens wear subsequently, with no statistically significant difference in the incidence of adverse reactions between the two contact lens groups (P>0.05). Orthokeratology lenses and peripheral defocus RGPCL yield better visual acuity correction and superior image quality, which can minimize retinal image aberrations induced by high refractive errors. Both interventions achieve satisfactory corrective vision and effective myopia control effects in adolescents with high myopia, with no significant adverse reactions observed during the follow-up period, indicating a high level of wearing safety for clinical application.
To describe novel variants in the G protein-coupled receptor kinase 1 (GRK1) gene associated with Oguchi disease and to analyze the different multimodal imaging results. Five members of a single family were enrolled, including two confirmed cases of Oguchi disease and three carriers with novel variants in the GRK1 gene. All subjects underwent a comprehensive ophthalmological examination, including color vision testing, visual field testing, wide-field retinography, fundus autofluorescence, macular optical coherence tomography (OCT), and full-field electroretinography (ERG). The study found that both cases of Oguchi disease showed positive Mizuo-Nakamura phenomenon, moderate retinal thickening and packing of the three outermost hyper-reflective bands in the parafoveal region. After establishing a clinical diagnosis of Oguchi disease in patients IV-II and IV-III, molecular analysis revealed a similar genotype in the patients, both carrying two heterozygous variants in the GRK1 gene, the variants c.1055_1056delAC, p.(Tyr352CysfsTer32) and c.699+2T>C. Genetic testing also revealed that individual III-I was a heterozygous carrier of the novel variant c.1055_1056delAC in the GRK1 gene. In addition, the novel intronic variant c.699+2T>C was detected in the same gene in the heterozygous state in individuals III-II and IV-I. Family segregation showed that Oguchi disease was transmitted in an autosomal recessive pattern in this family. Two novel variants in the GRK1 gene are reported that are linked to Oguchi disease in a naïve Algerian family. The common findings observed on the OCT scans of our affected patients include packing of the three outer hyper-reflective bands, and thickening of the retina in the parafoveal region. These features are present not only in the affected patients but also in the carriers of the disease.
To investigate the levels of the triglyceride-glucose (TyG) index and sex hormone-binding globulin (SHBG) in patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy (DR), and to explore their correlations with biochemical parameters and the homeostasis model assessment of insulin resistance (HOMA-IR) in DR patients. Patients with T2DM and healthy individuals were enrolled. Age and body mass index (BMI) of the participants were collected, TyG of the subjects was calculated using the formula, SHBG level of the subjects was detected, and blood biochemical indexes were measured at the same time. The changes of each index among the groups were statistically analyzed, and the relationship between TyG, SHBG, DR and each index was analyzed. A total of 150 patients with T2DM and 64 healthy individuals as normal controls (NC, 28 males and 36 females, mean age 54.49±10.10y) were enrolled following ophthalmic evaluation. Patients were categorized into non-DR group (42 males and 36 females, mean age 56.68±8.02y) and DR group (35 males and 37 females, mean age, 53.83±11.10y). TyG levels were significantly elevated in both non-DR (7.25±0.62) and DR groups (8.02±0.82) compared to controls (6.85±0.48), with the DR group demonstrating higher TyG values than the non-DR group (P<0.05). The level of SHBG (nmol/L) in DR group (25.05±14.06) was lower than that in control group (41.90±22.6) and non-DR group (36.27±20.00; P<0.05). TyG exhibited significant inverse correlations with SHBG (r=-0.455) and high density lipoprotein (HDL; r=-0.430) levels (P<0.05). It was positively correlated with BMI, fasting blood glucose (FBG), 2h postprandial blood glucose (PBG), fasting C-peptide (FCP), glycated hemoglobin A1c (HbA1c), HOMA-IR, total cholesterol (TC) and triglycerides (TG) (r=0.406, 0.768, 0.386, 0.393, 0.475, 0.250, 0.242, 0.888, respectively, P<0.05). SHBG was negatively correlated with BMI, FBG, FCP, HbA1c and TyG (r=-0.440, -0.304, -0.407, -0.209, -0.455, respectively, P<0.05), and positively correlated with age, TG and HDL (r=0.238, 0.034, 0.227, respectively, P<0.05). Further multiple regression analysis showed that SHBG was negatively correlated with TyG (P=0.006). Elevated TyG index, reduces SHBG levels, and their negative correlation in the DR group suggest potential roles of TyG and SHBG in the pathogenesis and progression of DR. Combined assessment of SHBG and TyG may provide valuable insights for DR prediction and diagnosis.
Diabetic retinopathy (DR) is a common comorbidity of diabetes involving the formation of abnormal vascular structures in the retina. Tissue inhibitor of metalloproteinases 2 (TIMP2), initially identified as a key mediator of extracellular matrix turnover, is pivotal for inflammatory processes and tissue homeostasis. The current study examined the influence of TIMP2 gene variations on the risk for DR. We investigated the association of TIMP2 gene variations with DR by analyzing four single-nucleotide polymorphisms (SNPs) of the TIMP2 gene (rs16971783, rs2889529, rs7220980, and rs8068674) in a cohort of 672 patients with DR and 919 diabetic controls with normal ophthalmoscopic findings. Our results showed that rs16971783 of TIMP2 gene was associated with a higher risk for DR (TA vs. TT, AOR=1.445, p=0.028; TA+AA vs. TT, AOR=1.179, p=0.046). We further demonstrated that the association of rs16971783 with DR was exclusively observed in diabetic individuals with proliferative DR (TA vs. TT, AOR=1.827, p=0.035; TA+AA vs. TT, AOR=1.351, p=0.027), whereas not detected among those who suffered from non-proliferative DR. In addition, preliminary exploration of gene expression data from public resources reveald that rs16971783 regulated TIMP2 gene expression in various human tissues. Allele-specific expression of TIMP2 gene might contribute to the progression of DR.
To investigate the anti-inflammatory and neurorestorative effects of neuroprotectin D1 (NPD1) in Aspergillus fumigatus (A. fumigatus) keratitis in C57BL/6 mice. The left corneas of C57BL/6 mice were infected with A. fumigatus. Each mouse was injected intraperitoneally with 2 µg NPD1 at 1, 3, and 5d post infection (p.i.) and injected subconjunctivally with 5 µL NPD1 once a day. The severity of keratitis was observed by slit lamp and classified by clinical score at 1, 3, and 5d p.i. Hematoxylin and eosin (HE) staining was used to evaluate the histological changes and inflammatory cell infiltration of corneas at 3 and 5d p.i. Polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot were performed to detect the expression of IL-1β, MIP-2, CGRP, p-p38/p38 MAPK, Nrf-2, and HO-1. Immunofluorescence staining was utilized to assess the neutrophil infiltration and neural innervation. Flow cytometry assay was performed to test the number of total, M1 and M2 macrophages. In A. fumigatus infected C57BL/6 mice, NPD1 treatment ameliorated the severity of keratitis. Compared with the phosphate-buffered saline (PBS) control group, NPD1 treatment inhibited the infiltration of neutrophils and macrophages, increased the ratio of CD206+/CD86+ macrophages, reduced the phosphorylation level of p38 MAPK, and enhanced the expression of Nrf-2/HO-1 at 3d p.i. The number of corneal nerves and the mechanical sensitivity threshold of the NPD1 treatment group were significantly higher than the PBS group at 3 and 5d p.i. Meanwhile, the expression of IL-1β and MIP-2 in the NPD1 treatment group was significantly lower at 3 and 5d p.i. NPD1 improves the prognosis of A. fumigatus keratitis in mice by inhibiting the recruitment of neutrophils and macrophages, promoting M2 macrophage polarization and corneal nerve regeneration.
Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses. GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs). Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023. Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum. St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.
In China, the high incidence rate of myopia has become an important factor affecting children's visual health. In the contemporary social environment, prolonged use of electronic products and reduced outdoor activities have become important causes of the development of myopia in children, which reflects the significant influence of light on myopia. This review was performed by searching PubMed data sets including research articles and reviews utilizing the terms "light", "myopia", and "hyperopia reserve", and the review was concluded in October 2024. This article analyzes the impact of light on myopia, including light intensity, light wavelength, light frequency, light distribution, light rhythm, exposure time, and the impact of light exposure on hyperopia reserve, in order to provide new ideas for the prevention, control, and treatment of myopia, and to provide theoretical support for the development of more scientific and effective intervention measures.
Descemet's membrane detachment (DMD) is defined as the detachment of Descemet's membrane that occurs spontaneously or secondary to intraocular surgery. This review focuses on the characteristics and incidence of DMD following phacoemulsification and glaucoma surgery, and aims to compare DMD cases after phacoemulsification (PCE) and different types of glaucoma surgery in terms of incidence, risk factors, clinical manifestations, diagnosis and management strategies. The reported incidence of DMD after PCE ranges from 0 to 5%, and the complication is less frequently observed following glaucoma surgery. Patients with DMD may be asymptomatic or present with severe visual impairment caused by corneal edema, which is associated with the size and location of the detachment. The management of DMD varies according to the primary surgical procedure (PCE or glaucoma surgery), as well as case-specific factors including visual acuity, corneal clarity, and the size and location of the detachment. Longitudinal observational studies are warranted to investigate the underlying cellular mechanisms of DMD. Retrospective studies can be conducted to clarify the incidence and identify all potential risk factors for DMD following glaucoma surgery. In addition, it is crucial to explore all possible risk factors to reduce and prevent this complication.
To analyze the etiologies, disease course, clinical characteristics, and surgical management patterns of non-traumatic corneal perforation in China. This multicenter, retrospective study reviewed medical records from patients with non-traumatic corneal perforation treated at 16 tertiary hospitals in China from 2019 to 2021. Data collected included demographics, etiology, disease duration, perforation location, visual acuity on admission, and surgical procedures. A total of 796 eyes from 791 patients were included, comprising 271 women (34.2%) and 520 men (65.7%), with a mean age of 58.4±15.6y (range, 0.38-92y). Infectious keratitis was the leading cause (62.6%), followed by postoperative complications (12.8%) and autoimmune diseases (8.7%). Fungal infections were more prevalent in rural areas, while autoimmune-related perforations were more common in females. Autoimmune cases more frequently presented with a chronic disease course and better visual acuity at admission compared to infectious causes (P<0.001). Among infectious causes, viral keratitis exhibited the highest proportion of chronic cases (65.7%). Perforation location varied significantly by etiology, with infectious cases predominantly central and autoimmune cases more often peripheral or limbal (P<0.001). Overall, 88.3% of eyes presented with poor visual acuity on admission. Most eyes (90.0%) required surgical intervention. Penetrating keratoplasty was the most common procedure, especially for central perforations, while lamellar keratoplasty was preferred for peripheral and autoimmune-related cases. This nationwide, multicenter study provides a comprehensive epidemiologic characterization of non-traumatic corneal perforation. Infectious keratitis was identified as the predominant etiology. Distinct patterns in disease progression, perforation location, and surgical intervention were observed across etiologic subgroups. These findings underscore the relevance of etiology-stratified assessment and support the need for tailored clinical management strategies.
To compare the effect of orthokeratology (OK) and defocus incorporated multiple segment (DIMS) lenses on axial length (AL) elongation in bilateral myopic anisometropic children. This retrospective study enrolled bilateral myopic anisometropic children categorized into two groups: OK lenses and DIMS lenses. The eyes with more myopia (MM) were divided into MM eyes and the fellow eyes with less myopia (LM) into LM eyes. According to the myopia degree in MM eyes, the subjects were further assigned to -0.50 to -3.00 D subgroup and -3.25 to -6.00 D subgroup. The t-test was used to analyze the changes in AL elongation between groups and AL differences in both eyes, and the relationship between AL changes and baseline data was evaluated by Pearson linear correlation analysis. Totally 202 children (8-14y) were divided into OK group with mean age 10.97±1.91y (46 males and 50 females) and DIMS group with mean age 11.05±2.06y (58 males and 48 females). After 1y, the changes of AL in OK-MM eyes (0.14±0.18 mm) were significantly slower than that in OK-LM eyes (0.20±0.19 mm) and DIMS-MM eyes (0.19±0.18; P<0.001, P=0.037). The OK-LM eyes and DIMS-LM eyes, DIMS-MM eyes and DIMS-LM eyes showed no statistically significant difference in AL changes (P=0.337, 0.381). In the -0.50 to -3.00 D subgroups, DIMS-LM eyes had better effect of AL control than OK-LM eyes, the changes of AL in OK-MM eyes and DIMS-MM eyes were no statistically significant. In the -3.25 to -6.00 D subgroups, the results were similar in total group. The change of AL in four subgroups was negatively correlated with age (P<0.05). OK lens can reduce binocular anisometropia; DIMS lens has similar effect on the control of binocular myopia in children with myopic anisometropia. The OK lenses are more effective than DIMS lenses with higher degrees of myopia, while DIMS lens retard AL elongation more effectively than OK lens when the spherical equivalent refraction of MM eyes is lower than -3.00 D.
To develop an automated diagnostic system for early detection of diabetic retinopathy (DR) using fundus images by identifying exudates, hemorrhages, and microaneurysms with advanced image processing and machine learning techniques. Fundus images from the IDRiD dataset and additional Kaggle datasets were used. A wavelet-based band-pass filter was applied for edge enhancement of retinal features. Gaussian mixture model (GMM) clustering was used to segment and extract texture features. These extracted features were classified using machine learning algorithms, including a random forest classifier and a multilayer perceptron neural network. Performance metrics such as sensitivity, specificity, and accuracy were computed to evaluate the proposed model's diagnostic effectiveness. The random forest-based classification system achieved a sensitivity of 95.08%, specificity of 86.67%, and overall accuracy of 95.20% in detecting DR lesions. The combination of wavelet-based edge enhancement, GMM clustering, and neural network-based feature classification demonstrated high reliability in lesion identification. The proposed method effectively detects early signs of DR from fundus images, offering a high-accuracy, automated, and scalable solution for assisting ophthalmologists. Its application can support large-scale screening programs, particularly in regions with limited access to specialized eye care.
To investigate the effect of intravitreal injection of dexamethasone (DEX) implants on the corneal morphology of young adults with central retinal vein occlusion (CRVO). This was a retrospective study. The information of all patients was collected from the hospital information system. Patients diagnosed with CRVO were included. Corneal morphometric analysis was performed 1, 3, 6, and 12mo after the intravitreal injection of DEX. Corneal endothelial cell density (ECD), hexagonal cell ratio (HEX), and coefficient of variation (CV), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber angle (ACA), and anterior chamber volume (ACV) were evaluated. The mean age of the 80 patients (80 eyes) with CRVO was 33.10±3.26y. The mean disease duration was 4.94±2.12mo. The ECDs before and 1, 3, 6, and 12mo after DEX injection were 2718.22±333.14, 2692.74±324.84, 2577.55±365.27, 2624.30±345.53 cells/mm², and 2604.00±321.19 cells/mm², respectively. No difference was found in ECD at 1, 6, and 12mo after the injection compared with baselines. The ECD of patients was lower than baseline at three months (P<0.05), whereas the HEX and CV were not statistically significant compared with baseline (P>0.05). At the 12-month follow-up, a trend toward a decrease was observed in the CCT compared with baselines among the enrolled patients, but without significant difference (P>0.05). The parameters of the anterior chamber (ACD, ACA, and ACV) did not change significantly compared with baselines (P>0.05). No significant difference was found in corneal morphology between single and repeated DEX implant injections. In young adults with CRVO, intravitreal injection of DEX can temporarily decrease ECD. However, the remaining corneal endothelial morphological characteristics and anterior chamber parameters are unaffected.
To establish and validate a multidimensional predictive model of postoperative visual recovery after idiopathic macular hole (IMH) surgery. Retrospective cohort study. Examinations within a three-month period, both pre- and postoperative, included assessments of best corrected visual acuity (BCVA), intraocular pressure (IOP), and morphological parameters of IMH with optical coherence tomography (OCT). Then, a series of indices were derived, including the IMH index (MHI), diameter hole index (DHI), macular hole closure index (MHCI), hole form factor (HFF), and tractional hole index (THI). Subfoveal anatomical damage (macular hole inferior volume, Vi) was calculated based on the basal diameter (BD), minimum diameter (MD), and height at the narrowest point (HMD) of IMH. Pearson correlation analysis was utilized to discern significant correlations between postoperative BCVA and the multiple indices examined. A subsequent linear correlation analysis was performed. The study involved 51 eyes from 51 patients (mean age 66.90±6.07y) diagnosed with IMH. Preoperative BCVA was 1.22±0.76 logMAR and improved to 0.88±0.38 logMAR after surgery (P<0.001). The correlation analysis results showed significant correlations between postoperative BCVA and preoperative BCVA (P<0.001), BD (P=0.042), MD (P=0.001), MHI (P=0.047), THI (P=0.004), and Vi (P=0.007). The multidimensional model integrating THI, Vi, and preoperative BCVA significantly outperformed traditional predictors (MD, BD, and height) in terms of postoperative visual recovery prediction. THI, reflecting posterior vitreous traction mechanics, independently predicted anatomical reset potential (β=-0.06, P=0.022), while Vi, quantifying subfoveal photoreceptor disruption, was correlated with structural-functional recovery (β=0.01, P=0.046). Preoperative visual acuity served as a critical surrogate for retinal functional reserve (β=0.15, P=0.020). Redundant morphometric parameters (MHI, DHI, MHCI, HFF) were excluded, as their predictive contributions were subsumed by THI/Vi or mediated by preoperative vision. The combination of biomechanical traction (THI), subfoveal anatomical damage (Vi), and preoperative BCVA represents a clinically applicable framework for predicting postoperative visual recovery after IMH surgery. This model can be used as a practical tool to guide surgical planning, facilitating the identification of high-risk patients who may benefit from additional techniques (such as an internal limiting membrane flap) while optimizing resource allocation for standard cases.