Proliferative Retinopathy Research Articles

Diabetic foot ulcers risk prediction in patients with type 2 diabetes using classifier based on associations rule mining

Identifying diabetic patients at risk of developing foot ulcers, as one of the most significant complications of diabetes, is a crucial healthcare concern. This study aimed to develop an associative classification model (CBA) using the Apriori algorithm to predict diabetic foot ulcers (DFU). This retrospective cohort study included 666 patients with type 2 diabetes referred to Shahid Beheshti Hospital in Iran between April 2020 and August 2022, of which 279 (42%) had DFU. Data on 29 specific baseline features were collected, which were preprocessed by discretizing numerical variables based on medical cutoffs. The target variable was the occurrence of DFU, and the minimum support, confidence, and lift thresholds were set to 0.01, 0.7, and 1, respectively. After data preparation and cleaning, a CBA model was created using the Apriori algorithm, with 80% of the data used as a training set and 20% as a testing set. The accuracy and AUC (area under the roc curve) measure were used to evaluate the performance of the model. The CBA model discovered a total of 146 rules for two patient groups. Several factors, such as longer duration of diabetes over 10 years, insulin therapy, male sex, older age, smoking, addiction to other drugs, family history of diabetes, higher body mass index, physical inactivity, and diabetes complications such as proliferative and non-proliferative retinopathy and nephropathy, were identified as major risk factors contributing to the development of DFU. The CBA model achieved an overall accuracy of 96%. Also, the AUC value was 0.962 (95%CI 0.924, 1.000). The developed model has a high accuracy in predicting the risk of DFU in patients with type 2 diabetes. The creation of accurate predictive models for DFU has the potential to significantly reduce the burden of managing recurring ulcers and the need for amputation, which are significant health concerns associated with diabetes.

Особливості ультраструктурних змін у нейросенсорних елементах сітківки щурів при моделюванні діабетичної ретинопатії на тлі осьової міопії

The formation and development of diabetic retinopathy in conditions of myopization of the eyeball is accompanied by the features of the clinical picture of retinopathy. With myopia, the incidence of especially proliferative retinopathy, as well as the rate of progression of these diabetic changes in the retina, can be reduced. The aim of our work was a comparative study of the ultrastructure of the neurosensory elements of the retina in rats in the simulation of streptozotocin-induced diabetes and deprivation axial myopia. Experiments were performed on rats aged from 2 to 10 weeks, which were divided into 4 groups. The 1st control group included intact animals, the 2nd - with myopia, the 3rd - with diabetes; the 4th - with myopia and diabetes. Two-week-old rats were modeled with a high degree of axial myopia by blepharorrhaphy of both eyes and exposure to low light for another 2 weeks. In rats with axial myopia and intact rats, streptozotocin-induced diabetes was modeled by repeated intraperitoneal administration of subdiabetic doses of streptozotocin (15.0 mg/kg body weight) for 5 days. After 2 months, all animals were removed from the experiment under anesthesia and their eyes were enucleated. The tissue samples were photographed in a PEM-100-01 electron microscope and the ultrastructure of the neurosensory elements of the retina was studied. The obtained results of the study indicate that ultrastructural retinal neurosensory elements differed in different groups. When modeling diabetes against the background of axial myopia, some areas with signs of hydropic dystrophy with large fields of organelle destruction were observed in the cells of the inner layers of the retina, mainly in the inner nuclear layer, which is inherent in diabetes, but there were also areas whose ultrastructure was close to normal. This indicates that the process of myopization of the eyeball of rats with the lengthening of the anterior-posterior axis can mitigate the severity of ultrastructural changes of the retina in the simulation of diabetic retinopathy.

Blood Cadmium Affects the Association between Serum 25-Hydroxyvitamin D3 and Diabetic Retinopathy Severity in the U.S. Population with Type 2 Diabetes.

Serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with diabetic retinopathy (DR) severity. Blood cadmium has also been reported to be associated with the presence of DR. Besides, cadmium can decrease the formation of calcitriol (active vitamin D) in blood. However, the effect of blood cadmium on the association between 25(OH)D3 and DR severity has not been studied comprehensively. Therefore, we designed this cross-sectional study to assess the effect modification of blood cadmium on the association between 25(OH)D3 and DR severity in the U.S. population with type 2 diabetes (T2D). This study was conducted using NHANES from 2005 to 2008. By having stratified participants based on blood cadmium category (low blood cadmium<2.76 nmol/L; high blood cadmium≥2.76 nmol/L), we evaluated the difference (interaction test) between the relationship of 25(OH)D3 with the severity of DR among low blood cadmium and high blood cadmium participants using multivariable logistic regression. In this cross-sectional study, a total of 283 participants were included. In the high blood cadmium group, the odds ratio for severe non-proliferative retinopathy (NPDR)/proliferative retinopathy (PDR) of high 25(OH)D3 (≥50 nmol/L) group was 0.26 (95% CIs: 0.09-0.69, p=0.01) compared with the reference group (low 25(OH)D3 group). Furthermore, there was evidence of interaction between 25(OH)D3 and blood cadmium on decreasing the incidence of severe NPDR/PDR. Our study indicated that blood cadmium might affect the association of 25(OH)D3 with DR severity in participants with T2D. More randomized controlled trials are needed to provide more evidence of such a finding.

Assessment of Serum Protein Carbonyls and Glycemic Biomarkers in Patients with Type 2 Diabetic Proliferative Retinopathy

Assessment of Serum Protein Carbonyls and Glycemic Biomarkers in Patients with Type 2 Diabetic Proliferative Retinopathy

Screening for Multiple Organ Damage in Indian Sickle Cell Disease Cohort- a Step Towards Comprehensive Care

Introduction: Sickle cell disease (SCD) is the most common hereditary monogenic disorder and is a major health burden in India. Meagre information is available on multiple organ damage among Indian SCD population. The present study attempts to understand the spectrum of organ damage in a group of Indian SCD cohorts. Objectives: To investigate the spectrum of early organ dysfunction and chronic organ damage among SCD patients at different age groups. To study the association of haematological and biochemical parameters with organ dysfunction or chronic organ damage. To understand the implication of genetic modifies with clinical profiles of SCD patients. Methodology: Clinical investigations of SCD individuals such as MRI of brain, ultrasonography of abdomen, spirometry of lung, 2 D echo of heart and ophthalmology. Laboratory investigations of SCD individuals such as haematological parameters by cell counter (Sysmax XP100), HbF &amp; HbS fractionization by HPLC method (Biorad Variant 2), liver function test and kidney function test by automated biochemistry analyser (Roche Cobas C111). Co-inheritance of α-thalassemia and Xmn-1 polymorphism by multiplex PCR and PCR-RFLP respectively. 100 SCD individuals were recruited with informed consent by a consecutive sampling for the study at ICMR-Centre for Research Management and Control of Haemoglobinopathies (ICMR-CRMCH), Chandrapur. SCD individuals at non-crisis, steady state; with no blood transfusion history prior 3 months or not admitted in hospital for vaso-occlusive crisis prior 1 month were enrolled in the period Jan'2021-Jan'2022. Result: One hundred SCD individuals (44 males: 56 females) were enrolled. The median age of individuals was 18 years (Interquartile range (IQR): 13-29 years). Individuals were categorized into two groups based on their ages. Children and adolescents group (6-17 years): 46 individuals, and Adults (18-52 years): 54 individuals. Out of 100, 65 were drug hydroxyurea (HU) are on HU, while remaining 35 were not taking HU. The median dosage of at 11.9 mg/kg/day (IQR: 9.17-13.5 mg/kg/day). The current study reports the spectrum of organ damage involving onset of organ dysfunction to end organ damage such as ischemia/sclerosis/atrophy 12/58 (20.7%) to stroke 2/58 (3.4%), mild restriction/obstruction 55/96 (57.3%) to mixed blockage lung disease 6/96 (6.2%), cholelithiasis 24/100 (24%) to chronic cholecystitis/cholecystectomy 6/100 (6%), shrunken spleen 16/100 (16%) to autosplenoctomy 24/100 (24%). No pulmonary hypertension determined by tricuspid valve regurgitation (TRV) &amp;gt;2.5 m/s was observed among 100 SCD individuals. No case of proliferative sickle retinopathy was detected in the cohort. Laboratory investigations: The mean ± standard deviation (S.D.) hemoglobin and HbF% levels among 100 SCD individuals were found to be 9.7±1.6 gm/dl and 21.2±6.6% respectively. Hematological and biochemical parameters showed association with liver and splenic dysfunction. Four out of 76 (5.3%) individuals were tested positive for microalbuminuria. No individual showed higher levels of estimated glomerular filtration rate. Molecular investigations: Ninety three HbS homozygous and 7 HbS-β thalassemia compound heterozygous were identified by ARMS-PCR method. The co-inheritance of α-gene mutations was observed in 45/94 (47.9%) SCD individuals, while the remaining 49/94 (52.3%) were normal. The Xmn1 polymorphism present in the Gγ globin promoter region -158 C→T (HBG2 c.-211 C→T) position, showed 88 as homozygous for mutant allele [+/+], while 12 as heterozygous[ +/-]. No association of α-thalassemia and Xmn1 polymorphism with organ dysfunction was observed. Conclusion: Though, vaso-occlusive crisis is the main clinical manifestation in SCD, sickle related organ damage is an important determinant for clinical severity of the disease. The progression of organ dysfunction/damage is evident as the age progresses. The comprehensive check-up at regular interval is required for the identification of early organ dysfunction and to prevent the chronic organ damage in SCD individuals.

Hydrogen peroxide enhances transforming growth factor beta-2 induced epithelial–mesenchymal transition of ARPE-19 cells

BackgroundIn the pathophysiology of the retina, the epithelial–mesenchymal transition and oxidative stress play key roles. To find a relationship between oxidative stress and diabetic retinopathy or proliferative retinopathy, we used an in-silico approach. We also used an in vitro investigation to examine the synergistic effect of transforming growth factors-β2 (TGFβ2) and hydrogen peroxide (H2O2) on the epithelial–mesenchymal transition (EMT) of ARPE-19 cells, analyzing cell survival, cell migration by wound healing, and expression epithelial–mesenchymal transition markers at the protein and mRNA levels.ResultsFor 24 h, human retinal pigment epithelial cells (ARPE-19) were cultured in standard conditions and subjected to various concentrations of TGFβ2, H2O2, and their combinations. According to a bioinformatics study, signaling pathways including hypoxia-inducible factor (HIF-1), forkhead box O (FoxO), phosphoinositide-3-kinase (PI3K-Akt), and transforming growth factors-β (TGFβ-signaling), both growth factors and oxidative stress-associated proteins play a significant role in the development of retinopathies. In vitro studies showed that oxidative stress induced by H2O2 and TGFβ2 enhances the epithelial–mesenchymal transition of ARPE-19 cells.ConclusionsHydrogen peroxide enhances the TGFβ2-mediated epithelial–mesenchymal transition of human retinal pigment epithelial cells, or at least in cell line ARPE-19 cells.Graphical abstract

Abstract 17639: Association of Retinal Microvascular Changes With Incidence and Progression of Coronary Artery Calcium Score in Individuals With vs Without Diabetes Mellitus; Data From the Multi-Ethnic Study of Atherosclerosis

Introduction: Retinopathy (RP) is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. Microvascular disease may play a prominent role in coronary heart disease (CHD) development. We performed this study to evaluate the association of grades of RP with incidence of CAC (Coronary Artery Calcium) among those with zero CAC at baseline. Hypothesis: We performed this study to evaluate the association of grades of RP with incidence of CAC among those with zero CAC at baseline and to Identify the association of grades of MA and RP with progression of CAC among those with positive CAC at baseline. Methods: We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis (MESA), who had retinal photos and CAC score available. We analyzed the association of grades of RP with incidence and progression of CAC among subjects with and without DM with zero CAC and positive CAC at baseline from robust regression models. The grades of RP were defined as: no retinopathy, minimal non-proliferative R (NPR) (level 14 -20), early to moderate NPR (level 31-41) and severe NPR or proliferative RP (level 51-80). Results: Among those with zero CAC, in the diabetic group, early to moderate (95% CI [1.2, 2]) and severe (95% CI [1.3, 3]) NPR had significantly higher incident CAC risk than the non-retinopathy group. Among those with positive CAC at baseline, in the diabetic group, the early to moderate NPR group had higher CAC progression than the non-retinopathy group. (95% CI [-146, 228]). In the non-diabetic group, the minimal NPR group had significantly higher CAC progression than the non-retinopathy group (95% CI [1.8, 52.7]). Conclusions: In conclusion, after adjustment for major CHD risk factors, RP with any severity was associated with incident CAC in DM individuals, however only early to moderate NPDR was associated with CAC progression in them.

Evaluation of GBT021601 As a Therapeutic Agent to Restore Bone Marrow Health and Effective Erythropoiesis in a Sickle Mouse Model

Introduction: Hypoxia-mediated damage resulting from vaso-occlusion in sickle cell disease (SCD) leads to abnormal angiogenesis, such as occurs with moyamoya disease and proliferative retinopathy. Abnormal angiogenesis in mouse models of SCD has been observed to impact the bone marrow niche, resulting in a structurally abnormal vascular network. A dysfunctional bone marrow environment results in ineffective erythropoiesis and can damage hematopoietic stem cells (HSCs). Healthy HSCs are essential to the maintenance of hemoglobin (Hb) levels regardless of the rapid turnover of red cells and because of their potential as material for gene therapy. Recently, red cell transfusions were shown to reverse pathogenic angiogenesis in a sickle cell mouse model. However, chronic red cell transfusions are difficult to sustain in individuals with SCD due to complications including iron overload, risk of alloimmunization, and the time and cost involved. GBT021601 is a potent sickle Hb polymerization inhibitor that improves the rheology of red blood cells (RBCs) and has been shown to increase total Hb by as much as 3 g/dL. Here, we explore the effectiveness of GBT021601 for restoring bone marrow health and decreasing proangiogenic factors while maintaining the stemness of marrow cells to preserve erythrocyte maturation. Understanding the impact of GBT021601 on aberrant angiogenesis and the function of HSCs will indicate if it has a role in improving the bone marrow niche and HSC fitness in an era of expanded cell-based therapies for SCD. Methods: Nine-week-old, humanized Townes HbSS SCD mice were split into 3 cohorts (n=8 per group: 4 male, 4 female) and for 12 weeks were fed either standard chow (control) or chow containing 0.1% or 0.2% of GBT021601. After 12 weeks, the mice were phlebotomized and euthanized. Spleens were collected and weighed. Whole bone marrow was collected via centrifugation from both tibias and one femur; the other femur was saved for subsequent 3D confocal microscopy. Bone marrow was analyzed using flow cytometry to measure erythroid cell maturation (Annexin V, TER119, and CD44) and HSC markers (Lin, Sca-1, c-kit). Immunoblot analysis was performed on peripheral plasma to measure hypoxia-induced signaling and markers of angiogenesis (VCAM-1, VEGF-A, ANG-1, and -2). Results: Hb increased by 3 g/dL on average with administration of GBT021601, and spleen weights were significantly reduced ( P=0.0023 and P=0.0015 for control vs 0.1% and 0.2%, respectively). Flow cytometry of the extracted bone marrow revealed a significant increase in mature RBCs and a decrease in erythroid progenitors at all stages ( P&amp;lt;0.001 for RBCs and basophils; P=0.04, P=0.002, and P=0.001 for pro-, poly-, and ortho-chromatic erythroblasts, respectively) (Figure 1). HSCs, defined as Lin-Sca-1 +c-kit +, were not significantly different between groups (control vs 0.1%, control vs 0.2%, and for 0.1% vs 0.2%). Immunoblot analysis revealed a reduction in VCAM-1 and ANG-1 markers with administration of GBT021601 relative to control. However, no difference between ANG-2 and VEGF-A markers was observed between treated and control mice (Figure 2). Conclusions: Treatment with GBT021601 was effective at reducing extramedullary hematopoiesis as determined by the reduction in spleen size compared with control mice. VCAM-1 and ANG-1 are increased in HbSS compared with HbAA mice; treatment with GBT021601 reduced factors that contribute to pathogenic angiogenesis. Treatment with GBT021601 did not change ANG-2 and VEGF-A expression; notably, VEGF-A levels are similar between HbSS and HbAA mice. Our findings support GBT021601 as a sustainable treatment to reduce ineffective erythropoiesis and abnormal angiogenesis-which can otherwise damage the bone marrow niche-thereby suggesting a potential benefit for individuals with SCD participating in future cell-based therapies with curative intent and improved outcomes. More work is planned to examine the ability of GBT021601 to normalize the bone marrow environment and reduce the risk of deleterious effects on allogenic or autologous edited HSCs.

THE SIGNIFICANCE OF ARGON LASER IN PATIENTS WITH PERIPHERAL RETINAL BREAKS IN PREVENTING RETINAL DETACHMENT

&lt;p&gt;&lt;span&gt;Retinal detachment is a risk to one's vision that occurs about 1 in 10,000 times. Prior to the 1920s, this disease was completely blinding. Restoration of retinal detachments has been much simpler over the past 50 years thanks to procedures like scleral buckling, pneumatic retinopexy, and vitrectomy. Rhegmatogenous, tractional, and exudative retinal detachments are the three types. When subretinal fluid accumulates between the retinal pigment epithelium and the neurosensory retina, retinal detachment occurs. During this phase, three things might occur. Breaking the retina is one way to let vitreous directly enter the subretinal region. This retinal detachment is rhegmatogenous. Rhegmatogenous retinal detachments are frequently brought on by trauma- or posterior vitreous-separated-induced retinal tears. The growth of membranes on the vitreous or retinal surface is a second mechanism.These membranes have the capacity to physically divide the retinal pigment epithelium from the neurosensory retina. A tractional retinal detachment is what this is. Proliferative retinopathy caused by sickle cell anemia, diabetes, or other conditions that neovascularize the retina can cause tractional retinal detachment. Proliferative vitreoretinopathy following trauma or surgery may also contribute to tractional retinal detachments. Fluid exuding from a mass lesion or an accumulation of subretinal fluid caused by inflammatory mediators are the third causes of retinal detachment. Serous or exudative retinal detachment is the term used to describe this mechanism. Sarcoidosis and choroidal neoplasms are two examples of inflammatory or exudative retinal disease processes that can cause serous detachments. Patients with aggressively spreading cancers, such as testicular cancer, may also have serous retinal detachments. A case study of a retinal detachment without a profilactive argon laser and a known peripheral retinal break is presented. The patient arrived at our clinic with symptoms of retinal detachment that had been present for two to three weeks, as well as peripheral retinal breaks that had been photographed eight months prior.&lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;&lt;strong&gt;&lt;span&gt;Keywords: &lt;/span&gt;&lt;/strong&gt;&lt;span&gt;Retinal detachment; peripheral retinal breaks; rhegmatogenous; tractional; exudative; profilactive argon laser.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;

Clinical indicators for diabetic eyecare delivered by optometrists in Australia: a Delphi study

ABSTRACT Clinical relevance Valid and updated clinical indicators can serve as important tools in assessing and improving eyecare delivery. Background Indicators for diabetic eyecare in Australia were previously developed from guidelines published before 2013 and then used to assess the appropriateness of care delivery through a nationwide patient record card audit (the iCareTrack study). To reflect emerging evidence and contemporary practice, this study aimed to update clinical indicators for optometric care for people with type 2 diabetes in Australia. Methods Forty-five candidate indicators, including existing iCareTrack and new indicators derived from nine high-quality evidence-based guidelines, were generated. A two-round modified Delphi process where expert panel members rated the impact, acceptability, and feasibility of the indicators on a 9-point scale and voted for inclusion or exclusion of the candidate indicators was used. Consensus on inclusion was reached when the median scores for impact, acceptability, and feasibility were ≥7 and >75% of experts voted for inclusion. Results Thirty-two clinical indicators with high acceptability, impact and feasibility ratings (all median scores: 9) were developed. The final indicators were related to history taking (n = 12), physical examination (n = 8), recall period (n = 5), referral (n = 5), and patient education/communication (n = 2). Most (14 of 15) iCareTrack indicators were retained either in the original format or with modifications. New indicators included documenting the type of diabetes, serum lipid level, pregnancy, systemic medications, nephropathy, Indigenous status, general practitioner details, pupil examination, intraocular pressure, optical coherence tomography, diabetic retinopathy grading, recall period for high-risk diabetic patients without retinopathy, referral of high-risk proliferative retinopathy, communication with the general practitioner, and patient education. Conclusion A set of 32 updated diabetic eyecare clinical indicators was developed based on contemporary evidence and expert consensus. These updated indicators inform the development of programs to assess and enhance the eyecare delivery for people with diabetes in Australia.

Limited Hyperoxia-Induced Proliferative Retinopathy (LHIPR) as a Model of Retinal Fibrosis, Angiogenesis, and Inflammation.

The progression to fibrosis and traction in retinopathy of prematurity (ROP) and other ischemic retinopathies remains an important clinical and surgical challenge, necessitating a comprehensive understanding of its pathogenesis. Fibrosis is an unbalanced deposition of extracellular matrix components responsible for scar tissue formation with consequent tissue and organ impairment. Together with retinal traction, it is among the main causes of retinal detachment and vision loss. We capitalize on the Limited Hyperoxia Induced Retinopathy (LHIPR) model, as it reflects the more advanced pathological phenotypes seen in ROP and other ischemic retinopathies. To model LHIPR, we exposed wild-type C57Bl/6J mouse pups to 65% oxygen from P0 to P7. Then, the pups were returned to room air to recover until later endpoints. We performed histological and molecular analysis to evaluate fibrosis progression, angiogenesis, and inflammation at several time points, from 1.5 months to 9 months. In addition, we performed in vivo retinal imaging by optical coherence tomography (OCT) or OCT Angiography (OCTA) to follow the fibrovascular progression in vivo. Although the retinal morphology was relatively preserved, we found a progressive increase in preretinal fibrogenesis over time, up to 9 months of age. We also detected blood vessels in the preretinal space as well as an active inflammatory process, altogether mimicking advanced preretinal fibrovascular disease in humans.

Proliferative diabetic retinopathy as the initial presenting feature of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m2. The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease. The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial. The development of complications is seen at least a few years following the diagnosis. Occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important to prevent the progression of the disease.

Senescent Cells: Dual Implications on the Retinal Vascular System.

Cellular senescence, a state of permanent cell cycle arrest in response to endogenous and exogenous stimuli, triggers a series of gradual alterations in structure, metabolism, and function, as well as inflammatory gene expression that nurtures a low-grade proinflammatory milieu in human tissue. A growing body of evidence indicates an accumulation of senescent neurons and blood vessels in response to stress and aging in the retina. Prolonged accumulation of senescent cells and long-term activation of stress signaling responses may lead to multiple chronic diseases, tissue dysfunction, and age-related pathologies by exposing neighboring cells to the heightened pathological senescence-associated secretory phenotype (SASP). However, the ultimate impacts of cellular senescence on the retinal vasculopathies and retinal vascular development remain ill-defined. In this review, we first summarize the molecular players and fundamental mechanisms driving cellular senescence, as well as the beneficial implications of senescent cells in driving vital physiological processes such as embryogenesis, wound healing, and tissue regeneration. Then, the dual implications of senescent cells on the growth, hemostasis, and remodeling of retinal blood vessels are described to document how senescent cells contribute to both retinal vascular development and the severity of proliferative retinopathies. Finally, we discuss the two main senotherapeutic strategies-senolytics and senomorphics-that are being considered to safely interfere with the detrimental effects of cellular senescence.

Visual outcome of treating proliferative sickle cell retinopathy in 108 eyes.

To report treatment methods and visual outcome of treating proliferative sickle cell retinopathy (PSCR). Retrospective interventional. Review of PSCR eyes treated between 2017 to 2022. Patient demographics, fundus findings at presentation, genotype, PSCR stage, treatment used, and visual outcome were assessed. 108 eyes of 88 consecutive patients were studied. Male: Female 48:40. Mean age: 38.91 (SD:12.52) years. Genotype: sickle cell haemoglobin C (SC) 83 eyes (76.9%), sickle cell haemoglobin S (SS) 19 eyes (17.6%), and sickle cell trait (AS) 6 eyes (5.5%). PSCR stages: 3: 15 eyes (11.0%), 4: 74 eyes (67.0%), and 5: 19 eyes (22.0%). Treatment methods: Intravitreal Injection (IVI) of anti-vascular endothelial growth factor (VEGF) only (27 eyes,25%), scatter retinal laser photocoagulation (SRLP) only (7 eyes, 6.5%), Vitrectomy + SRLP (29 eyes, 26.9%), IVI + SRLP (25 eyes, 23.1%), and Vitrectomy + IVI + SRLP (20 eyes, 18.5%). The treatment used correlated with PSCR stage (p = 0.000). IVI only was mostly used to treat stage 4 (81.4%), and SRLP only was used for stages 3 (42.9%) and 5 (57.1%). IVI + SRLP treated eyes had the best pre- and post-treatment vision. Vitrectomy + SRLP treated eyes had the most improved vision. SRLP only had least visual improvement. Fundus findings correlated with visual outcome (p = 0.003); but stage of PSCR, genotype and treatment used had no correlation (P > 0.05). Several options effectively treat PSCR. Visual outcome improved or remained same in 90.7% of treated eyes. Randomized controlled trials will determine the optimum treatment for each distinct presentation of PSCR. Treatment guidelines and a disease classification system of prognostic value are unmet needs.

Technique and Outcomes of Vitreoretinal Surgery for Complications of Proliferative Sickle Cell Retinopathy

Objective: To report the technique as well as the anatomic and visual outcomes of vitrectomy for vitreoretinal complications of proliferative sickle cell retinopathy (PSR). Methods: This was a retrospective review of case files of patients who had vitrectomy for complications of PSR at Goldberg’s stage 4 and 5 between January 2017 and June 2022 at Eye Foundation Hospital, Ikeja Lagos, Nigeria. Results: Within the period of the study, a total of 22 eyes (6 right eyes and 16 left eyes) of 21 patients diagnosed with either persistent vitreous hemorrhage (Goldberg PSR stage 4) or retinal detachment (RD) (Goldberg PSR stage 5) met the inclusion criteria. All eyes had three port pars plana vitrectomy. Eleven eyes (50%) had only vitrectomy, six eyes (27.3%) underwent combined vitrectomy with scleral buckling and vitrectomy combined with phacoemulsification was done in five eyes (22.7%). There was a statistically significant (P = 0.026) improvement in the postoperative best corrected mean logMAR visual acuity (0.88 ± 0.79) at the last follow-up visit compared to the presenting visual acuity (1.4 ± 1.0). All eyes (100%) achieved surgical success defined as clearing of vitreous hemorrhage and retinal reattachment at 1-week, 6, and 12 weeks postoperative review. Conclusion: Good anatomic success and improvement in visual acuity are achievable with surgery for advanced PSR at Goldberg stages 4 and 5.

Terminology for Retinal Findings in Sickle Cell Disease Research: A Scoping Review

To review the current sickle cell disease (SCD) literature to assess how "retinopathy" has been defined and to identify ocular outcomes that have been measured and described. A systematic scoping review of SCD literature was completed regarding ocular manifestations of SCD and vision outcomes across all medical specialties. Participants with SCD and control patients were included in our data extraction. We reviewed English-language literature from 2000 to 2021 for eligible studies by searching PubMed, Google Scholar, Embase, and the Cochrane library using terms to encompass SCD and ocular findings. Data collection included study information, patient characteristics, vision-related findings (inclusion criteria and/or study outcomes), and retinopathy characteristics (definition, when, how and by whom diagnosed). We identified 4006 unique citations and 111 were included in the analysis. Ophthalmologists were senior authors of about half (59/111; 53.2%) of the articles; most articles were published between 2016 and 2021 (71/111; 70.0%). The studies had been conducted primarily in North America (54/111; 48.6%) or Europe (23/111; 20.7%); designs were cross-sectional (51/111; 45.9%), prospective cohort (28/111; 25.2%), retrospective cohort (27/111; 24.3%), and case-control (4/111; 3.6%). Among studies reporting any retinopathy, it was commonly defined as a combination of nonproliferative sickle cell retinopathy and proliferative sickle cell retinopathy (PSR;52/87; 59.8%), infrequently as PSR only (6/87; 6.9%), or not defined at all (23/87; 26.4%). The Goldberg classification was used to grade retinopathy in almost half of the studies (41/87; 47.1%). Investigators reporting diagnostic methods used clinical fundus examination (56/111; 50.4%), OCT (24/111; 21.6%), fluorescein angiography (20/111; 18.0%), ultrawidefield fundus photographs (15/111; 13.5%), and OCT angiography (10/111; 9.0%), or did not report methods (28/111; 25.2%). There are inconsistencies in documentation of methods and outcomes in studies of SCD ophthalmic findings. Particularly concerning is the lack of documentation of ophthalmic examination methods, qualifications of examiners, and clarity and specificity of sickle cell retinopathy definitions. With the increase in SCD treatment research and novel systemic therapies available, it is important to adopt clear and consistent descriptions and rigorous data collection and reporting of ophthalmic outcomes in SCD studies. The authors have no proprietary or commercial interest in any materials discussed in this article.

Association of retinopathy with risk of all-cause and specific-cause mortality in the National Health and Nutrition Examination Survey, 2005 to 2008.

This study aimed to elucidate the relationship between retinopathy status or severity and the all-cause and specific-cause mortality risk based on the updated National Health and Nutrition Examination Survey (NHANES) database and 2019 Public Access Link mortality file. In this prospective cohort study, a total of 6,797 participants aged over 40 years based on NHANES 2005-2008 were analyzed. The severity of retinopathy was classified into 4 grades-no retinopathy, mild non-proliferative retinopathy (NPR), moderate to severe NPR, and proliferative retinopathy (PR). Multiple covariate-adjusted Cox proportional hazards regression models and Fine and Gray competing risk regression models were used to assess the all-cause and cause-specific mortality risks, respectively. The propensity score matching (PSM) approach was also applied additionally to adequately balance between-group covariates to validate our findings. A final total of 4,808 participants representing 18,282,772 United States (US) non-hospitalized participants were included for analysis, 50.27% were male (n = 2,417), 55.32% were non-hispanic white (n = 2,660), and mean [SE] age, 56.10 [0.40] years. After a median follow-up of 12.24 years (interquartile range, 11.16-13.49 years), 1,164 participants died of all-cause mortality, of which 941 (80.84%) died without retinopathy and 223 (19.16%) died with retinopathy at baseline. The presence of retinopathy was associated with increased all-cause mortality, cardiovascular disease (CVD), and diabetes mellitus (DM)-specific mortality, and the results remain consistent after PSM. Severity analysis showed that only mild NPR was associated with an increased all-cause mortality risk (hazard ratio (HR) = 2.01; 95% confidence interval (CI), 1.00-4.03), while increased CVD and DM-specific mortality risk were associated with all grades of retinopathy and were exponentially greater with increasing retinopathy severity, and the trend test was also significant (P for trend 0.004 and 0.04, respectively). Our findings suggest that the diagnosis of retinopathy is an independent risk factor for all-cause mortality in people over 40 years old. Retinopathy grading is significantly associated with the survival risk of patients with CVD or DM, it can be a valuable predictor in the stratified management and risk warning of CVD or DM patients, as well as in the monitoring of systemic vasculopathy status.

Diabetes and pregnancy study (DAPSY): a 10-year single-center cohort study of pregnancies affected by diabetes.

The aim of our study was to investigate to what degree clinical characteristics can contribute to incidence and structure of pregnancy and childbirth complications in women with diabetes, and to reveal key risk factors for adverse outcomes. We conducted a retrospective single-center cohort study from January 2008 through December 2017, including 3069 singleton pregnancies, affected by type 1 diabetes (T1D, n = 498), type 2 diabetes (T2D, n = 214), and gestational diabetes mellitus (GDM, n = 2357). More than 10years duration of T1D associated with increased risk for preterm birth (RR 2.03, 95% CI 1.28-3.20) and preeclampsia (RR 1.57, 95% CI 1.09-2.26). Diabetic nephropathy, same as diabetic proliferative retinopathy, was associated with increased risk of C-section, preeclampsia development, SGA delivery. In patients with T1D who received CSII (12%), we do not report superior outcomes compared to MDI. Pre-pregnancy HbA1c level less than 6.5% reduced the risk of preeclampsia for T1D (RR 0.28, 95% CI 0.19-0.67) and risk of LGA birth for T2D (RR 0.43, 95% CI 0.19-0.92). Achieving glycemic target values by full-term pregnancy reduced the risk of excessive fetal adiposity (RR 0.81 for T1D, RR 0.39 for T2D). For T2D and GDM, the leading risk factors were obesity and chronic hypertension. For patients with GDM, insulin administration and early diagnosis of GDM were the significant risk factors for adverse outcomes. Diabetes during pregnancy is challenging for the clinician, but optimizing glycemic control, treatment regimens, and close attention to comorbidities can help to reduce the risks and ensure appropriate quality diabetes management.

SYVN1 Promotes STAT3 Protein Ubiquitination and Exerts Antiangiogenesis Effects in Retinopathy of Prematurity Development.

SYVN1, a gene involved in endoplasmic reticulum-associated degradation, has been found to exert a protective effect by inhibiting inflammation in retinopathy. This study aimed to clarify whether SYVN1 is involved in the pathogenesis of retinopathy of prematurity (ROP) and its potential as a candidate for target therapy. Human retinal microvascular endothelial cells (hRMECs) and a mouse model of oxygen-induced retinopathy (OIR) were used to reveal the retinopathy development-associated protein expression and molecular mechanism. An adenovirus overexpressing SYVN1 or vehicle control was injected intravitreally at postnatal day 12 (P12), and the neovascular lesions were evaluated in retinal flatmounts with immunofluorescence staining, and hematoxylin and eosin staining at P17. Visual function was assessed by using electroretinogram (ERG). Endogenous SYVN1 expression dramatically decreased in hRMECs under hypoxia and in ROP mouse retinas. SYVN1 regulated the signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) axis. SYVN1 overexpression promoted ubiquitination and degradation of STAT3, decreased the levels of phospho-STAT3, secretion of VEGF, and formation of neovascularization in hRMECs, which could be rescued by STAT3 activator treatment. In addition, SYVN1 overexpression prevented neovascularization and extended physiologic retinal vascular development in the retinal tissues of OIR mice without affecting retinal function. SYVN1 has a protective effect against OIR, and the molecular mechanisms are partly through SYVN1-mediated ubiquitination of STAT3 and the subsequent downregulation of VEGF. These findings strongly support our assumption that SYVN1 confers ROP resistance and may be a potentially novel pharmaceutical target against proliferative retinopathy.

Identifying Clinical Predictors of Proliferative Sickle Cell Retinopathy

Purpose To identify systemic and/or ophthalmologic predictors of proliferative sickle retinopathy. Methods Cross-sectional study comparing clinical, laboratory, and structural choriorretinal aspects between sickle cell disease patients with and without proliferative retinopathy. Patients underwent complete systemic and ophthalmologic evaluation. Enhanced depth spectral domain optical coherence tomography with choroidal binarization and optic coherence tomography angiography were performed and choriorretinal vascular components were compared. Results Forty-five eyes from 45 sickle cell patients were included. Ninety-one percent of patients were diagnosed with sickle cell retinopathy, 29% with proliferative retinopathy. Mean corpuscular volume, lactate dehydrogenase, and percentage of fetal hemoglobin were reduced in the subgroup of patients with proliferative retinopathy when compared with patients without proliferative retinopathy (p ≤ 0.001; p = 0.04; p ≤ 0.001, respectively). The best predictor of proliferative retinopathy was mean corpuscular volume (AUC = 0.842; p = 0.001), followed by the percentage of fetal hemoglobin (AUC = 0.763, p = 0.009) and lactate dehydrogenase (AUC curve = 0.706; p = 0.039). No differences were found between groups in the quantitative analysis of retinal vascularization using OCTA and choroidal vascularization using OCT (p ≥ 0.05). Conclusion Fetal hemoglobin and mean corpuscular volume may be good predictors of proliferative sickle retinopathy. The association between proliferative retinopathy and reduced levels of lactate dehydrogenase and mean corpuscular volume points to hypoxia and not hemolysis as a possible driving force in its pathophysiology.